Nasal cavity, paranasal sinuses, nasopharynx
Last revised 29 August 2011
Copyright (c) 2004-2010, PathologyOutlines.com, Inc.
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Primary references, normal anatomy, normal histology
Inflammatory/infectious lesions: allergic fungal sinusitis, allergic rhinitis, Aspergillus, chronic rhinitis, cholesterol granuloma, Churg-Strauss syndrome, eosinophilic angiocentric fibrosis, fungal ball, fungal disease, granulomatous lesions, idiopathic midline destructive disease, infectious rhinitis, Kartagener syndrome, leprosy, mucocele, Mucor, myospherulosis, nasal polyps, necrotizing sialometaplasia, pertussis, pharyngitis, rhinoscleroma, rhinosporidiosis, sinusitis, sarcoidosis, steroid injections, tuberculosis, Wegener’s granulomatosis
Nasopharyngeal carcinoma: general, keratinizing squamous cell, nonkeratinizing-differentiated, undifferentiated, papillary adenocarcinoma
Sinonasal carcinoma: general, adenocarcinoma-general, low grade adenocarcinoma, intestinal adenocarcinoma, cylindrical (transitional), small cell, squamous cell, undifferentiated (anaplastic)
Hematologic conditions: lymphoma-general, angiotropic lymphoma, diffuse large B cell lymphoma, follicular lymphoma, lymphoid hyperplasia, lymphomatoid granulomatosis, mantle cell lymphoma, NK/T cell lymphoma, peripheral T cell lymphoma, plasmacytoma
Other tumors: ameloblastoma, aneurysmal bone cyst, angioleiomyoma, angiomyolipoma, angiosarcoma, astrocytoma, carcinoid, chondrosarcoma, chordoma, cocaine related, craniopharyngioma, dermoid cyst, desmoplastic small round cell tumor, fibroinflammatory proliferation, fibroma, fibromatosis, fibroosseous lesions, fibrosarcoma, follicular dendritic cell, gangliocytic paraganglioma, giant cell reparative granuloma, giant cell tumor, glial heterotopia, glomus, hemangiopericytoma-sinonasal type, leiomyoma, lobular capillary hemangioma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, Masson’s tumor, melanoma, meningioma, myxoma, nasal chondromesenchymal hamartoma, nasopharyngeal angiofibroma, neurofibroma, nodular fasciitis, nonsecretory cyst, olfactory neuroblastoma, osteochondromyxoma, osteoma, papilloma, paraganglioma, pituitary adenoma, pleomorphic adenoma, psammomatoid ossifying fibroma, respiratory epithelial adenomatoid hamartoma, rhabdomyoma, rhabdomyosarcoma, Rosai-Dorfman disease, salivary gland anlage tumor, salivary gland tumors-general, schwannoma, seromucinous hamartoma, solitary fibrous tumor, teratoid carcinosarcoma, teratoma, Warthin’s
Miscellaneous: staging-nasal cavity & sinuses, staging-nasopharynx, staging-mucosal melanoma, post-chemotherapy atypia, grossing, features to report
AJCC Cancer Staging Manual (7th ed)
American Journal of Surgical Pathology (AJSP), Jan 1998 to Aug 2004
Archives of Pathology and Laboratory Medicine (Archives), Jan 1998 to Aug 2004
Human Pathology (Hum Path), Jan 1998 to July 2004
Modern Pathology (Mod Path), Jan 1998 to July 2004
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby-Year Book, Inc., 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Journal search terms: nose, nasal, paranasal, sinus, nasopharynx
Please refer to these primary references for more detailed discussions and photographs
Nasal cavity, paranasal sinuses and nasopharynx form functional unit
Nasal cavity
Divided into olfactory region (superior nasal turbinates and opposed septum) and respiratory region (rest of cavity)
Nasal chambers are on either side of median plane formed by nasal septum
Bounded above by cribriform plate; bounded laterally by turbinates
Bulla ethmoidalis: elevation on lateral wall of middle meatus, site of opening of middle ethmoid meatus
Choanae: posterior opening of nasal cavity, communicates with nasopharynx
Columella: anterior extreme nasal septum
Nares: anterior openings of nasal cavity
Vestibule: slight dilation inside anterior aperture of nostril, bounded laterally by ala and lateral crus of greater alar cartilage and medially by medial crus of greater alar cartilage; lined by skin containing hair and sebaceous glands
Lateral wall: contains superior, middle and inferior nasal turbinates (conchae); below each is corresponding nasal passage or meatus
Sphenoethmoidal recess: above superior turbinate, site of opening of sphenoidal sinus
Turbinates (concha): comprise lateral walls of each nasal cavity
Superior meatus: along upper border of middle turbinate, site of opening of posterior ethmoid meatus
Middle meatus: below and lateral to middle turbinate
Drawings: lateral wall of nasal cavity #1, #2 after removal of conchae, cartilages of nose-side view, from below, bone and cartilage of septum
Nasopharynx
Respiratory passage above and behind the soft palate
Part of pharynx, which also includes oropharynx and hypopharynx
Begins anteriorly at posterior turbinates and extends along plane of airway to the level of the free border of the soft palate
Anterior wall is perforated by posterior nares (choanae)
Posterior wall is also its roof, as well as the posterior base of skull; extends inferiorly to level of free border of soft palate where oropharynx begins
Lateral wall contains ostium of eustachian tube, surrounded by mucosa covered cartilaginous prominence; ostium is anterior to pharyngeal recess (fossa of Rosenmuller)
Paranasal sinuses
Diverticula of nasal cavity that extend into neighboring bones
Ethmoid sinuses: between the orbits; well developed at birth
Frontal sinuses: most anterior, above the orbits; small/rudimentary at birth; develop through puberty
Maxillary sinuses: under the cheeks; small/rudimentary at birth; develop rapidly during childhood until permanent teeth develop
Sphenoid sinuses: most posterior at base of brain; small/rudimentary at birth; develop rapidly during childhood until permanent teeth develop
Ohngren’s line: connects medial canthus of eye to angle of mandible; used to divide maxillary sinus into anteroinferior portion (infrastructure), associated with good prognosis for carcinomas, and superoposterior portion (suprastructure), with a poor prognosis for carcinomas
Nasal cavity
Lined by stratified squamous and respiratory type pseudostratified columnar epithelium, separated by transitional epithelium in some places
Respiratory mucosa (also called Schneiderian membrane) may contain goblet cells; may undergo squamous metaplasia
Superior third of nasal septum, superior turbinate and cribriform plate are covered with thinner olfactory mucosa, usually patchy in adults, which has neuroendocrine features
Seromucinous glands (resembling salivary glands) are present in submucosa, numerous near eustachian tube opening of nasopharynx, may undergo oncocytic metaplasia with increasing age
Normally no lymphoid tissue
Nasopharynx
Lined by stratified squamous epithelium (inferior anterior and posterior walls and anterior lateral walls) and respiratory type epithelium (around nasal choanae and roof of posterior wall); remaining areas have mixtures of squamous and respiratory or intermediate epithelium (also called transitional although it does not resemble urothelium ultrastructurally)
Intermediate epithelium is usually concentrated as a wavy ring at junction of nasopharynx and oropharynx
Seromucinous glands may undergo oncocytic metaplasia, and rarely form a mass or obstruct eustachian tube
Abundant lymphoid tissue present, particularly at rim of eustachian tube opening (Gerlach’s tonsil); functionally equivalent to that of GI tract or mucosal-associated lymphoid tissue (MALT)
Paranasal sinuses
Mucosa is continuous with nasal cavity and identical (respiratory type epithelium), but thinner and with fewer goblet cells and seromucinous glands
Normally no lymphoid tissue
Inflammatory/infectious lesions
Due to Aspergillus, Curvularia lunata or Fontana-Masson positive dematiaceous fungi (Drechslera, Bipolaris, Exoserohilium)
Produces “allergic mucin” (lamellated collection of inspissated inflammatory debris with numerous eosinophils and Charcot-Leyden crystals) and fungal hyphae
Mucin may require curettage to remove, may recur
May cause bony erosion due to pressure remodeling, but usually not invasive
Affects immunocompetent patients ages 20-49 years with chronic allergy, asthma, nasal polyps or sinusitis
May be due to tenacious mucin that traps normally nonpathogenic, low-virulence fungal organisms
Diagnosis initially missed in half of cases
Treatment: surgical removal, low-dose corticosteroids, possibly immunotherapy for underlying allergy
Gross: green, brown or black mucin with consistency of clay; gray-brown, laminated, gelatinous or translucent cut surface
Micro: mucosal edema, marked eosinophilic infiltrate, allergic mucin in 92%, eosinophils may have degenerative changes of smudged, elongated or basophilic nuclei; also plasma cells and lymphocytes; rare noninvasive fungal hyphae (often found only with GMS stain), rare neutrophils
Micro images: 1-allergic mucin (arrows) with fungus; 2-allergic mucin (arrows) without fungus; 3-fungi with sparse and fractured hyphae
References: Hum Path 2004;35:474
Also called hay fever
Due to exposure to plant pollens, fungi, dust mites, animal allergens
Affects 20% of US population
IgE mediated
Endoscopic images: swollen pale turbinates with thick secretions
Micro: mucous secretions have neutrophils and prominent eosinophils
Causes fungus balls (see below) in nasal antrum of immunocompetent patients with minimal inflammatory response, microabscesses or multinucleated giant cells
Also causes invasive aspergillosis, regardless of immune status, with extension into retroorbital region, cranium or parapharyngeal space; often fatal
Also causes allergic fungal sinusitis (see above)
Micro: septate hyphae that branch at 45 degrees
DD of invasive fungal infections: Zygomycetes, Pseudallescheria boydii, Paecilomyces, Alternaria, Cladosporium trichoides, Fusarium
Sequel to acute rhinitis (symptoms lasting 6 weeks or less), with development of secondary bacterial infection
Associated with deviated septum or nasal polyps; also ulceration and infection extending into sinuses
Endoscopic images: pale turbinates and dry secretions in smoker
Rare in nasal cavity or sinuses; usually associated with chronic middle ear disease
May be a reaction to hemorrhage
Treatment: excision
Case reports: maxillary sinus lesion of 38 year old man (Archives 2002;126:217)
Micro: foreign body giant cells surrounding empty, needle shaped spaces (cholesterol clefts representing cholesterol crystals that have dissolved due to alcohol in staining process), chronic inflammatory infiltrate, hemosiderin laden macrophages, dilated lymphatics
2/3 have nasal polyps or mucosal crusting
Micro: discrete necrotizing granulomas with numerous eosinophils, often forming microabscesses
DD: Wegener’s granulomatosis
Eosinophilic angiocentric fibrosis
Very rare; unknown cause
May be mucosal counterpart of granuloma faciale
Involves any portion of upper respiratory tract, often nasal septum and sinus mucosa
Usually women, mean age 44 years
Case reports: 45 year old man with no history of allergic disease (Archives 2004;128:90)
Treatment: corticosteroids, resection
Micro: thick collagen bundles, perivascular onion-skin fibrosis with eosinophil-rich inflammatory infiltrate; no granulomas, no necrosis, no vasculitis
DD: granuloma faciale (inflammatory vascular reaction with facial papules, neutrophilic and eosinophilic infiltrate, vasculitis with fibrinoid material in vessel walls)
Also called mycetoma, chronic noninvasive fungal sinusitis
Usually immunocompetent patients, often prior history of sinus disease, trauma or foreign body
Gross: grumous, friable, gray-brown-black material, often with clotted blood
Micro: tightly packed extramucosal hyphae, usually in maxillary antrum; no/minimal host response, no allergic mucin or tissue invasion; usually due to Aspergillus (hyphae with septation and branching at 45 degree angles, no spores)
Includes sinusitis (acute fulminant, chronic invasive), mycetoma, saprophytic infestation (fungal spores on mucous crusts of respiratory passages) and allergic fungal sinusitis
May develop post-steroid injection with amorphous foreign material
Cholesterol granulomas in paranasal sinuses are rare
Also due to fungal infections, myospherulosis, tuberculosis, Wegener’s granulomatosis
Idiopathic midline destructive disease
Diagnosis of exclusion
Gross: usually perforated nasal septum, perforated palate, erosion of antral bone or ulceration of skin overlying nose or antrum
Micro: acute and chronic inflammatory cells with variable necrosis; may have multinucleated giant cells or granulomas; no atypical lymphocytes, no fibrinoid necrosis of vessels, no prominent eosinophils
DD: Wegener’s granulomatosis (different clinical findings)
Also called “common cold”
Due to adenovirus, echovirus and rhinoviruses
Symptoms: catarrhal discharge, thick, edematous, erythematous nasal mucosa; enlarged turbinates
May cause pharyngotonsillitis; may have secondary bacterial infection
Situs inversus, bronchiectasis and sinusitis, due to defective ciliary action
Affects nasal mucosa in 95% of patients; may be initial manifestation of disease
Usually affects nasal septum and inferior turbinate
Micro: early - plasma cells with lesser numbers of histiocytes and lymphocytes; later - broad sheets of histiocytes with foam cells; well formed granulomas of tuberculous type are uncommon
Positive stains: acid fast stains
Also called pseudocyst
Complication of chronic sinusitis due to outflow obstruction
May destroy contiguous bones and resemble a neoplasm
2/3 in frontal sinus; also anterior ethmoid sinus
Micro: inflammatory cells and mucin lift epithelium of sinus and periosteum away from underlying bone; epithelium may undergo squamous metaplasia; extravasation of mucin into lamina propria with muciphages
Relatively common life-threatening fungal infection, associated with diabetic ketoacidosis, poor glycemic control or immunosuppression
Spreads rapidly across nerves and tissue planes to blood vessels of orbit and brain, causes thrombosis, hemorrhage and infarction
Member of phylum Zygomycota, class Zygomycetes, order Mucorales; found in high-organic matter and soil
Mortality rate of 48%
Case reports: 29 year old man post bone marrow transplant with psychosis and gingival lesion (Archives 2000;124:883)
Micro: broad nonseptate hyphae branching at 90 degrees, accompanied by numerous neutrophils and histiocytes within granulation tissue
Micro images: fungal hyphae in vessel lumen that infiltrate vessel wall; asexual structures (very rare in tissue)
Iatrogenic lipogranuloma after hemostatic packing of nasal cavity or paranasal sinuses with petrolatum based ointment and gauze
Resembles subcutaneous disease of East Africa
Micro: large tissue spaces with saclike structures containing brown spherules resembling Prototheca but actually clumped red blood
cells
Negative stains: GMS
Common; not neoplastic, but may fill entire nasal cavity or extend into cranial cavity or orbit
In children, must rule out cystic fibrosis
Often recur due to persistence of causative factors
Endoscopic images: gelatinous polyp #1; #2; #3; large polyp extending into oropharynx
Micro: edematous lamina propria with variable inflammatory infiltrate including eosinophils; subtypes include angiectatic (angiomatous), cystic, edematous, fibrous, glandular
Angiectatic polyps
Extensive vascular proliferation and ectasia with pseudoamyloid deposition that simulates malignancy
Due to marked reactive and reparative changes
May cause life threatening epistaxis, facial deformity or bone erosion and remodeling
Gross: gelatinous, semitranslucent masses with smooth, blue-gray glistening surface
Micro: dilated thin walled vessels in pools of eosinophilic material, associated with patchy necrosis and atypical spindle cells; associated with choanal polyps arising in paranasal sinuses and protruding into nasopharynx
Micro images: (1) proliferation of thin walled vascular channels; (2) thin walled vessels embedded in amorphous material (asterisks) or surrounded by amorphous material (arrows); (3) atypical stromal cells (arrows) and fibrin thrombi (right side-asterisk); (4) vascular channels lined by large hyperchromatic endothelial cells; also atypical stromal cells
DD: angiofibroma, hemangioma
References: Archives 2000;124:406
Antrochoanal polyp
4-6% of nasal polyps
Frequently occur in childhood
90% solitary
Arise from wall of maxillary antrum, extending through large primary or secondary maxillary ostium into nasal cavity
May pass into choanae or nasopharynx
Gross: long narrow stalk with firm, fibrous body
Micro: thin surface mucosa with no thickened basement membrane; stroma with stellate cells, less edema and fewer glands than inflammatory polyp; may have prominent dilated vessels with thrombosis or infarct; prominent eosinophils in only 20%
Atypical stromal cells
Common; have prominent cytoplasm, enlarged hyperchromatic nuclei resembling “radiation fibroblasts” or sarcoma
More common in younger patients or those with prominent fibrous stroma
No increased cellularity, no prominent vasculature, no mitotic figures
Resemble polyp on low power
Cystic fibrosis polyp
Must rule out cystic fibrosis in any child with nasal polyps
Present in 20% with cystic fibrosis
May arise up to 12 years before clinical diagnosis; rarely is initial manifestation of disease in adults
Micro: similar to inflammatory polyps, but no basement membrane thickening, no submucosal hyalinization, no/rare stromal eosinophils; may have large cystic glands with inspissated mucin in lumina; mucous glands, cysts and mucous contain predominantly acid mucin
Positive stains: purple-blue mucin with combined Alcian blue PAS stain (vs. red for inflammatory polyp)
Inflammatory polyp
Most common type of nasal polyp
Due to recurrent attacks of rhinitis (allergic, inflammatory)
Most people with polyps are NOT atopic; only 0.5% with atopy develop polyps
Usually ages 30 years or older (rarely < age 20 years)
Often recurs after surgery
Often associated with asthma, chronic rhinitis, aspirin intolerance (14%)
Gross: usually multiple and bilateral and involve nasal cavity and paranasal sinuses; have translucent, moist or edematous cut surface (opaque areas may represent papilloma); broad base of attachment is present; usually not destructive
Gross images: inflammatory polyps
Micro: respiratory epithelium, often with squamous metaplasia, edematous and loose stroma with hyperplastic mucous glands, inflammatory infiltrate (lymphocytes, plasma cells, eosinophils, neutrophils, mast cells); mucosa may be ulcerated or infected; basal membrane may be thickened; may have “bizarre” stromal cells (large and pleomorphic) due to reactive changes; may have prominent glandular component
Micro images: respiratory mucosa with edematous stroma with numerous eosinophils and plasma cells
Virtual slides: respiratory epithelium overlying edematous stroma with eosinophils and plasma cells
DD: papilloma
Benign process that resembles squamous cell carcinoma or mucoepidermoid carcinoma
Occurs after surgery on nose or sinuses
Micro: necrosis of seromucinous glands with secondary squamous metaplasia and reactive atypia
Micro images: Various
images
Contributed by Dr. Semir Vranic: #1; #2; top
Possibly life-threatening nasopharyngeal infection caused by Bordetella pertussis
Causes progressive, repetitive paroxysmal coughing, mild systemic complaints and lymphocytosis
Worldwide causes 60 million severe cases and 1 million deaths annually
In US, 5000-7000 annual cases, deaths usually only in infants younger than 1 year
Outbreak in Wisconsin (USA) in 1993 with attack rates of 23% (ages 30-49 years) and 33% (ages 50+)
Vaccination widely given, but efficacy may wane 4 years after last dose
Diagnosis: culture requires 5-7 days, also PCR
Treatment: erythromycin (but some cases are resistant)
References: Archives 2002;126:173
Often secondary bacterial infection by Streptococcus pneumonia or Staphylococcus aureus
Severe infections occur in infants or adults with neutropenia, HIV, diabetes, antibiotics
Streptococcus pneumonia pharyngitis: treat with antibiotics to prevent subsequent glomerulonephritis or rheumatic fever
Viruses: rhinovirus, echovirus, adenovirus, respiratory syncytial virus, influenza
Also called scleroma
Rare; chronic granulomatous disease affecting nasal cavity (95-100%), nasopharynx (18-43%), larynx (15-40%), trachea (12%) or bronchi (2-7%) caused by Klebsiella rhinoscleromatis
Usually low socioeconomic environments of central/South America, Africa, Middle East, Philippines, India; rare in US (usually immigrants)
Most common in young adults
Initially nonspecific rhinitis, then purulent, fetid rhinorrhea with crusting; then granulomatous stage with blue-red granular nasal mucosa with intranasal rubbery nodules or polyps, epistaxis, anosmia, enlargement of uvula, anesthesia of soft palate, variable airway obstruction; finally sclerosis
Treatment: tetracycline or trim-sulfa, possibly steroids, surgery to correct scars or stenosis
Microbiology: MacConkey agar cultures are 50-60% sensitive; bacteria is gram negative, encapsulated, nonmotile diplobacillus, member of Enterobacteriaceae, not normal flora, infective via drops or contamination of material that is inhaled
Case reports: polypoid intranasal mass in 32 year old woman (Archives 2001;125:159)
Micro: initially inflamed granulation tissue; later hyperplastic mucosa with pseudoepitheliomatous squamous hyperplasia, granulomatous inflammation, foamy macrophages (Mikulicz cells containing bacteria) and plasma cells with Russell bodies; variable vasculitis and ulceration; late-fibrosis, lymphocytes and plasma cells but no Mikulicz cells
Positive stains: PAS, Giemsa, Steiner or Hotchkiss-McManus stains for gram negative bacteria
EM: large phagosomes containing bacilli and finely granular material (antibodies on bacterial surface and aggregates of bacterial mucopolysaccharides)
DD: Rosai-Dorfman disease, leprosy
Caused by Rhinosporidium seeberi, traditionally thought to be a fungus, but actually an aquatic protistan parasite (J Clin Microbiol 1999;37:2750, Emerg Infect Dis 2000;6:273, Indian J Med Microbiol 2002;20:119)
Endemic in southern India, Sri Lanka and emigrants from this region (Diagn Pathol 2006;1:25, Singapore Med J 2004;45:224); rare indigenous cases in US (South Med J 1996;89:65)
Natural aquatic habitat, transmitted through traumatized epithelium, most commonly in nose and eye, also skin, ear, genitals and rectum
Risk factors: bathing or working in stagnant water
Rarely presents with disseminated skin disease (Indian J Dermatol Venereol Leprol 2007;73:185, Indian J Dermatol Venereol Leprol 2001;67:332)
Not transmitted person to person.
Case reports: Case of the Week #97
Treatment: surgical excision, may recur; no effective medical treatment
Gross: hyperplastic, polypoid, red, granular masses of nasal cavity; yellow pinhead spots represent mature sporangia; superficial mucus is common
Micro: large (100 to 450 microns), thick walled sporangia with 1000+ endospores, each 6-10 microns, accompanied by a mixed inflammatory infiltrate; may not be present in all sections and may need additional sampling for diagnosis
Micro images: image #1; #2; #3
contributed by Professor Venna Maheshwar, Drs. Kiran Alam and Anshu Jain, J. N. Medical College, India - #1; #2
Positive stains: GMS, PAS
DD: myospherulosis (large tissue spaces with saclike structures containing brown spherules that resemble Prototheca but are actually clumped red blood cells, GMS negative), Coccidiodes immitis (smaller spherules: 30-60 microns, smaller endospores: 2-5 microns), often arthroconidia and hyphae
Acute sinusitis
Often preceded by acute or chronic rhinitis
Usually self limited or well controlled with supportive treatment
Acute invasive fungal sinusitis (fulminant invasive fungal sinusitis)
Often seen in immunocompromised or diabetic patients, often ocular involvement or intracranial extension, associated with progressive disease and death
Treatment: vigorous systemic antifungal therapy
Micro: vascular invasion by fungi is present and may cause thrombi; also neutrophils, eosinophils, tissue necrosis and hemorrhage
Chronic sinusitis
Mixed bacterial flora, develops after acute sinusitis
May produce osteomyelitis of orbit or thrombophlebitis of dural venous sinus
Most commonly in maxillary sinus, and preceded by periapical infection from floor of sinus
May need biopsy for accurate diagnosis
Noninvasive fungal disease is often Aspergillus
Treatment: surgery to control disease may be necessary
Gross: edematous mucosa which blocks drainage and may cause empyema of sinus
Micro: glandular hyperplasia, squamous metaplasia, basement membrane thickening, inflammatory cells including eosinophils, edema; bone may show thickening and remodeling with osteoblastic rimming and fibrosis of bone marrow spaces; presence of allergic mucin (lamellated collection of inspissated inflammatory debris) suggests fungal organisms
Chronic noninvasive fungal sinusitis
Also called indolent fungal sinusitis
Associated with diabetes, immunocompromise or endemic areas (Sudan, Saudi Arabia)
Micro: fungi with surrounding foreign body inflammatory response or granulomas and tissue invasion; no vascular invasion by definition
5% of patients have upper airway involvement, usually in nasal septum or inferior turbinate
Micro: granulomas without caseous necrosis
DD: tuberculosis
Micro: granulomas with amorphous area (residual injected substance) surrounded by palisading histiocytes
Rare; usually associated with cervical lymphadenopathy
Usually isolated infection and not secondary spread from pulmonary infection
Diagnosis: culture or PCR
Gross: ulcerated or polypoid lesion of nasal septum or inferior turbinate; variable septal perforation
Micro: poorly formed granulomas, usually no necrosis; organisms rare
Rapidly progressive condition involving nasal cavity, lungs and kidney
Biopsies of 5 mm or more improve diagnostic yield
Note: lymphocyte rich biopsies are unlikely to be Wegener’s and more likely represent lymphoma
Diagnostic for Wegener’s: granulomatous inflammation, necrosis and vasculitis, in addition to clinical involvement of lung or kidney; OR two of three microscopic features and lung and kidney involvement
Probable: two of three microscopic features and (lung or kidney involvement) but not both
Suggestive: one of three microscopic features and lung and kidney involvement
Suspicious: one of three microscopic features and (lung or kidney involvement) but not both
Nonspecific: no microscopic features, either lung or kidney involvement
Gross: early disease usually lacks destruction of cartilage or bone
Micro: leukocytoclastic vasculitis of arterioles, small arteries and veins with geographic necrosis surrounded by palisading histiocytes, variable poorly formed granulomas with minimal lymphocytes; variable giant cells; granulomas and giant cells are distant from vessels or adjacent/within vessel wall; also epithelial ulcers; vessel may be obliterated by inflammatory cells and thrombus and be difficult to identify without elastic stain; all stages of vasculitis are present (acute: neutrophils with fibrinoid necrosis; chronic/healed: narrowed or obliterated lumina with concentric rims of perivascular collagen); usually no significant lymphoid infiltrate
Positive stains: elastic stains to identify badly damaged vessels
Negative stains: EBV
DD: Churg-Strauss syndrome, NK/T cell lymphoma, idiopathic midline destructive disease, tuberculosis, lymphoma, eosinophilic angiocentric fibrosis, cocaine-related lesions, systemic lupus erythematosus, necrotizing vasculitis from other causes
Nasopharyngeal carcinoma
Nasopharyngeal carcinoma-general
Demographics vary greatly by region
USA: rare, incidence of 0.4 per 100K in whites
Africa: common; #1 childhood cancer; associated with EBV
South China: most common cancer in adults (18% of cancers in Hong Kong, 21.4 per 100K in Hong Kong, see table), rare in children
70% male
Strongly associated with EBV infection for undifferentiated and nonkeratinizing subtypes
Other risk factors: consumption of salt-preserved fish containing carcinogenic nitrosamines, family history, specific HLA class I genotypes, tobacco smoking, chronic respiratory tract conditions and low consumption of fresh fruits and vegetables (Cancer Epidemiol Biomarkers Prev 2006;15:1765)
Laboratory: IgG against early EBV antigen is suggestive, but has 30% false positives; IgA against viral capsid antigen has 9-18% false positives
Diagnosis: blind biopsies, particularly in fossa of Rosenmuller, are recommended if diagnosis is suspected (70% sensitive)
Tumors arising from fossa of Rosenmuller frequently extend to paranasopharyngeal space, then along trigeminal nerve
Often metastasizes to regional nodes; common presentation is unilateral cervical lymphadenopathy; 25% have bilateral nodal metastases
May have distant metastases to bones
After radiation therapy, risk of 0.4% of subsequent carcinoma in nasal cavity of nasopharynx; differentiate from recurrence based on > 5 year delay, different histology, EBV negative (Hum Path 2000;31:227)
Treatment: immunotherapy (interferon), radiation therapy, chemotherapy
Good prognostic factors: younger age, lower stage, ipsilateral metastases, metastases limited to upper neck, no involvement of cranial nerves, orbit or intracranial structures; nonkeratinizing subtypes
Gross: may not be identifiable tumor
Nasopharyngeal carcinoma-general (continued)
Micro: three histologic subtypes - keratinizing squamous cell carcinoma (WHO type 1), nonkeratinizing-differentiated (WHO type 2) and nonkeratinizing-undifferentiated (WHO type 3) - see below
Nodal metastases: resemble diffuse large cell lymphoma but are focal, have large vesicular nuclei with single prominent nucleoli; may have marked eosinophilia resembling Hodgkin’s lymphoma; may have marked cystic changes resembling bronchial cleft cysts, may have granulomatous reaction with necrosis
Positive stains: keratin, EMA, EBV, EBER; often p53, variable CEA, variable S100
EM: tonofilaments and complex desmosomes
References: Mod Path 2002;15:229, Orphanet J Rare Dis 2006;1:23
Keratinizing squamous cell carcinoma of nasopharynx
Also called WHO type 1
Minority of nasopharyngeal carcinomas
Often EBV negative, older age group
5 year survival is close to 0%
Treatment: don’t respond to radiotherapy, but tend to remain localized
Micro: squamous differentiation with intercellular bridges or keratinization in most of tumor; rarely adenoid or acantholytic forms that mimic adenocarcinoma
Nonkeratinizing nasopharyngeal carcinoma-differentiated
Also called WHO type 2
Rare in childhood
5 year survival 35-50%
Treatment: variably radiosensitive, may metastasize to regional lymph nodes
Micro: cells lack squamous differentiation but have variable levels of maturation; cells are stratified with well defined cell margins that interdigitate in a pavement stone pattern; no mucin or glandular differentiation; variable chronic inflammatory cells
Micro images: fig 18A-interconnecting cords of neoplastic cells; fig 18B-no keratinization
Positive stains: CK5/CK6, CK8, CK13, CK14, CK19
Negative stains: CK4, CK7
Nonkeratinizing nasopharyngeal carcinoma-undifferentiated
Also called WHO type 3
Very rare in US, common in Taiwan and China (EBV endemic areas)
Often called lymphoepithelioma, although lymphocytes are not neoplastic and some cases lack lymphocytes
Bimodal age distribution (teens, 50+); in Taiwan, median age is 58 years (range 36-75 years); 2/3 male
5 year survival after radiation therapy alone is based on stage--confined to nasopharynx (stage I): 50-60%; cervical node involvement (stage II): 20-30%; invasion of surrounding structures (stage III): 5-30%
Survival does not vary based on Regaud or Schminke patterns below
Tends to metastasize to regional lymph nodes
Treatment: supervoltage radiotherapy and cis-platinum based chemotherapy (70-90% 5 year survival overall)
Case reports: Case of the Week #100, 2 cases of undifferentiated carcinoma with focal glandular differentiation (Archives 2000;124:1369)
Micro: syncytial arrangement of relatively uniform cells with indistinct cell margins; cells have vesicular nuclei and prominent nucleoli; may have spindle cells and scattered effete (“worn out”) cells with shrunken, hyperchromatic nuclei that are more variable than sinonasal undifferentiated carcinoma; usually (but not always) non-neoplastic lymphocytic infiltrate (often T cells) with plasma cells, eosinophils and macrophages; patterns below may be mixed; no necrosis
Nonkeratinizing nasopharyngeal carcinoma-undifferentiated (continued)
Regaud pattern: neoplastic cells form well defined nests and cords separated by inflammation
Schminke pattern: diffuse inflammatory cells permeate cell nests causing isolation of carcinoma cells within lymphoid background, resembling lymphoma; tumor cells have thin chromatin rims and lack lacunae
Micro images: core biopsy; undifferentiated carcinoma with sheets of tumor cells; CK 5/6; EBER #1; EBER #2; EBV+ by ISH; fig A-cohesive growth with identifiable nests surrounding benign lymphocytes; fig B-cells have indistinct cell borders, enlarged nuclei with vesicular chromatin and prominent eosinophilic nucleoli; left-diffuse growth resembling lymphoma; right-keratin+; top-tumor cells not evident; bottom left-tumor cells identifiable at high power; bottom right-epithelial cells easily identified with keratin stain; fig 1a-undifferentiated nasopharyngeal carcinoma with focal glandular elements; fig 1b-papillary focus; fig 1c-pagetoid spread; fig 1d-undifferentiated nasopharyngeal carcinoma; fig 2a-mucicarmine staining of glandular component; fig 2b-EMA (brown) and EBER ISH (blue nuclear) double staining
Cytology images: pap stain; cell block
Positive stains: keratin (particularly helpful for Schminke pattern, CK 5/6, CK8, CK13, CK19), EBER1 by in situ hybridization
Negative stains: CK4, CK7, CK14
DD: sinonasal undifferentiated carcinoma (arises in nasal cavity and paranasal sinuses only, hyperchromatic tumor cells with coarse chromatin, individual cell necrosis and necrosis of cell nests, EBER-1 negative, AJSP 2002;26:371), nonkeratinizing squamous cell carcinoma (cells are arranged in pavement stone pattern with more abundant eosinophilic cytoplasm and distinct cell borders), Hodgkin’s lymphoma (Reed-Sternberg cells are binucleated with no thin chromatin rims or have lacunar pattern), melanoma, metastatic carcinoma
Papillary adenocarcinoma of nasopharynx
Rare if exclude those of minor salivary gland origin
Arise from mucosa
60% males; median age 33 years (range 11-64 years); not associated with wood dust exposure or other known factors
Typically confined to nasopharynx
Excellent prognosis; slow growing and indolent; rarely recurs; no metastases reported to date
Treatment: surgery (transpalatal approach)
Gross: exophytic or pedunculated mass; 0.3 to 4.0 cm
Micro: papillary with arborization and fibrovascular cores or glandular with cribriform or back to back glands; lined by cuboidal or columnar cells with pink cytoplasm and round/oval nuclei that are variably clear or hyperchromatic; mild to moderate nuclear pleomorphism, no/rare nucleoli or mitotic figures; occasionally psammoma bodies; “clean” background without hemorrhage or necrosis; no angiolymphatic invasion or perineural invasion; no goblet cells
Micro images: papillae and glands arising from nasopharyngeal mucosa
Positive stains: keratin (diffuse), EMA (diffuse), CEA (focal), PAS (intracytoplasmic granules), mucin (intracellular or luminal)
Negative stains: GFAP, S100, thyroglobulin
DD: papillary thyroid carcinoma (thyroglobulin+, no epithelial dysplasia), intestinal adenocarcinoma-papillary type (nasal cavity and paranasal sinuses, usually wood dust exposure, more papillary and less glandular, tall columnar and goblet cells, “dirty” background with hemorrhage and inflammation), low grade papillary adenocarcinoma of salivary gland origin (rare in nasopharynx, arises from minor salivary glands in submucosa, not surface epithelial, usually S100+, aggressive with local recurrence (27%) and nodal metastases (17%))
Sinonasal carcinoma-general
Unusual, <1% of cancer deaths in US
Risk factors: nickel refiners, woodworkers
Usually HPV and EBV negative
Sites: within nose - usually vestibule and lateral wall; rarely septum; sinus - usually ethmoid, rare in frontal sinus
Usually diagnosed late with extensive bony destruction
Often extends locally; nodal spread is uncommon; metastases to lungs and occasionally bone
5 year survival is 60%
Treatment: surgery and radiation therapy; relapse usually within 2 years
Prognostic factors: stage, extension to pterygomaxillary fossa, invasion of dura
Micro: papillary subtypes have well developed fibrovascular cores; resemble fungiform papilloma but with widespread, severe nuclear abnormalities with pleomorphic, hyperchromatic, disorganized squamous cells; may have suprabasilar squamous cells
10% of sinonasal malignancies
Usually middle turbinate or ethmoid sinus, extending laterally to orbit or superiorly into anterior cranial fossa
Appear to arise from sinus mucosal lining, not underlying glands
Locally aggressive; nodal metastases are rare
Tubulopapillary tumors with minimal atypia are usually indolent
Histologic types are salivary gland, low grade, intestinal type
Micro: well differentiated tubulopapillary patterns, often with goblet cells and resembling colorectal carcinoma; may resemble small intestinal mucosa with resorptive, goblet, Paneth and endocrine cells; rarely coexists with atypical carcinoid
References: AJSP 2004;28:1026 (immunostaining differences between subtypes), Hum Path 2003;34:1101 (CK7/CK20 staining)
Low grade (seromucinous) adenocarcinoma
Median age 54 years, but range of 9-75 years
No site or gender predilection
No known risk factors
Good prognosis, although 30% recur; 78% are disease free after 6 years; death from disease due to local invasion, not metastases
Micro: papillary or tubular architecture of back to back glands lined by columnar cells with uniform nuclei; intracellular and extracellular mucin; often no nuclear stratification and mild to moderate pleomorphism; usually rare mitotic figures; rarely has complex papillary pattern with psammoma bodies; few goblet cells, necrosis uncommon
Positive stains: CK7 (75%, stains respiratory type epithelium and submucosal seromucous glands)
Negative stains: CK20, CDX2, MUC2
DD: oncocytic papilloma (stratified epithelium, no true glandular lumina, more abundant myxomatous stroma); intestinal type adenocarcinoma (colonic-type epithelium, more atypia), papillary thyroid carcinoma (thyroglobulin+)
Intestinal type (enteric) adenocarcinoma
Strong association with chronic exposure to fine hardwood dusts from woodworking industry (relative risk of 70-500x), who historically constituted 20% of these patients after interval of mean 40 years; also exposure to leather dust
Occupational cases involve men (85-95%), ethmoid sinus
Sporadic cases have no gender preference
Mean age 58 years for occupational and sporadic cases
5 year survival is 20-50%, although may have protracted clinical course with local recurrences and ultimate invasion of orbit and cranial cavity
3 year cumulative survival by histologic type: papillary I: 82%; papillary II: 54%; papillary III: 36%; alveolar-goblet: 48%; signet ring: 0%, transitional: 71%
Regional nodal metastases in 8%, distant metastases in 13%; tumors may change histologic type over type
May have tumor necrosis with sepsis
Xray: important in determining extent of disease and operative approach; early-soft tissue mass; late-osteodestruction and invasion of orbit or cranial cavity
Treatment: surgical excision with lateral rhinotomy; possibly radiotherapy; neck dissection not indicated since cervical nodal metastases are rare
Gross: polypoid, papillary or nodular, variable color, usually friable; may be ulcerated, hemorrhagic or mucoid
Micro: often high grade; resemble normal or neoplastic colonic or small intestinal epithelium; papillary tumors may be intramucosal or invasive; usually resemble colonic adenocarcinoma with back to back glands of pleomorphic columnar cells with intracellular mucin, but no prominent goblet cells; may have sheets of tumor cells, colloid-type tumors, signet ring cells; rarely resembles normal intestinal mucosa or villous adenoma; may contain Paneth or enterochromaffin cells
Klenisasser and Schroeder classification (Arch Otorhinolaryngol 1988;245:1):
Papillary tubular cylinder cell (frequencies -- 18%-I, 36%-II, 20%-III), alveolar goblet cell (13%), signet ring cell (3%), transitional (11%)
Also well differentiated (I), moderately differentiated (II) and poorly differentiated (III)
Papillary tubular cylinder cell-I (well differentiated): also called papillary type; fibrovascular fronds and glands/tubules covered by tall ciliated columnar (cylinder) cells; may have polarization of columnar cells with long axes perpendicular to basement membrane; may be stratified and crowded; pink cytoplasm and round/oval nuclei, variable chromatin and nucleoli; may have goblet cells; variable mitotic figures; often hemorrhagic, necrotic or inflammatory background; either invasive or in situ over broad front; may have bland cytology and resemble a villous adenoma or normal intestinal mucosa, but are still locally aggressive and destructive; may have indolent disease that causes death 10 years later
Papillary tubular cylinder cell-II (moderately differentiated): also called colonic type; well to moderately differentiated glands; resembles colonic adenocarcinoma; may have cystic spaces with intracystic papillary projections
Papillary tubular cylinder cell-III (poorly differentiated): also called solid type; diffuse proliferation of small cuboidal cells with pink to amphophilic cytoplasm, round and vesicular nuclei, often nucleoli, often mucin droplets; minimal gland formation
Alveolar-goblet cell: also called mucinous; glands distended with mucus or pools of mucin containing individual glands or strips of epithelium with admixed goblet cells
Signet ring: also called mucinous (as is alveolar-goblet cell); composed of small groups or single signet ring cells in pools of mucin; no strips of epithelium
Transitional: also called mixed; mixture of two of above types
Micro images: (1) papillary tubular cylinder cell-well differentiated; (2) papillary tubular cylinder cell-moderately differentiated; (3) alveolar-goblet cell
Positive stains: CK7 or CK20, CDX2 (may be focal), MUC2 (44%), p53 (18%), chromogranin and NSE (diffuse and strong intensity)
Negative stains: CEA (may be weak/focal)
DD: metastatic adenocarcinoma (uncommon from GI tract, usually from kidney, also lung, breast, testis, but must exclude clinically; also usually weak/negative for chromogranin and NSE, strong CEA, CK7 negative; staining is opposite for sinonasal intestinal carcinoma), papillary rhinosinusitis (may be papillary, but papillae are short and blunt; has “clean” background, thick and hyalinized basement membrane, ciliated surface cells, no atypia, prominent eosinophils), papillary adenocarcinoma of nasopharynx (usually not in nasal cavity or paranasal sinuses, usually not associated with wood dust exposure, more glandular, less papillary, few columnar / goblet cells, “clean” background)
References: AJSP 2003;27:1390 (CDX2-letter)
Cylindrical (transitional) cell carcinoma
Micro: stromal infiltration and atypia are usually obvious; may have intracellular mucin; rarely yolk sac-like features
DD: papilloma (no stromal invasion), post-chemotherapy changes
Very rare; resembles pulmonary oat cell carcinoma
More common in paranasal sinuses than nasal cavity
Mean age 51 years (range 38-68 years) in small study
Usually localized aggressive disease without metastases
Micro: diffusely cellular or nests of monotonous epithelial-type tumor cells with minimal cytoplasm, hyperchromatic nuclei, frequent mitotic activity with abnormal mitotic figures, large areas of necrosis; no evidence of neural differentiation; may have components of adenocarcinoma or squamous cell carcinoma
Positive stains: AE1-AE3, CAM5.2, neuron-specific enolase, chromogranin, synaptophysin
Negative stains: TTF1 (AJSP 2000;24:1217), S100, EBV
DD: olfactory neuroblastoma, post-chemotherapy changes
References: Archives 2003;127:461 (flow cytometry); Hum Path 1998;29:826
2/3 male; usually age 50+ years; rare in patients < 40 years old
Associated with cigarette smoking, nickel ore exposure, Thorotrast; possibly job related exposure to chromium, isopropyl alcohol and radium
Most common histologic subtype
Recurrences are common; death usually due to local spread
Nasal cavity carcinoma associated with 6-28% second primary neoplasms (40% in head and neck, also lung, breast, GI)
Maxillary antrum carcinoma associated with 5% incidence of second primary carcinoma in contralateral antrum, but no increased incidence at other sites
Micro: usually high grade with variable keratinization; nonkeratinizing tumors may resemble intermediate cells of papilloma or urothelium, often grow as large cell nests and cords with mild atypia
Unusual variants are spindle cell (keratin+) and verrucous carcinoma
Positive stains: CK4 (30%), CK5/6, CK7 (60%), CK8, CK13, CK14, CK19
DD: post-chemotherapy changes
Undifferentiated (anaplastic) carcinoma
Rare; very aggressive, median survival 10-18 months
Young adults and elderly (mean age 58 years, range 20-81 years), 2/3 male
75% men, 85% smokers
May be associated with nickel exposure
Mass in nasal cavity, maxillary antrum, ethmoid sinuses, often with extension into sphenoid sinus, frontal sinus, orbit and cranial cavity
Associated with prior nasopharyngeal carcinoma treated with radiation 6-26 years earlier
Xray images: large tumor of nasal cavity and paranasal sinus extending intracranially
Treatment: none (surgical resection difficult, chemoradiation therapy not useful)
Micro: nests, cords and sheets of small to large polygonal cells with distinct cell borders, moderate eosinophilic cytoplasm, pleomorphic nuclei with diffuse to coarsely granular chromatin, prominent nucleoli, extensive necrosis and apoptosis, frequent mitotic figures, extensive angiolymphatic invasion; no evidence of neuroendocrine differentiation (i.e. no Homer Wright rosettes, no fibrillary background, no ganglion-like cells); no squamous or glandular differentiation, no dense lymphoplasmacytic infiltrate
Micro images: sheets of moderately sized cells with eosinophilic nucleoli and brisk mitotic activity
Positive stains: CK7 (50%), CK8 (100%) CK19 (50%], Ki-67 (most cells, variable intensity), NSE (18-50%), EMA (18%), CD99 (14%)
Negative stains: CK 5/6, CK13, EBV, PLAP, CEA, S100, EBER1 by in situ hybridization, chromogranin, synaptophysin
EM: rare dense core granules in individual cells
DD: olfactory neuroblastoma, nasopharyngeal undifferentiated carcinoma (syncytial growth of cells with uniform nuclei with vesicular chromatin in inflammatory stroma), small cell carcinoma, lymphoma, melanoma, rhabdomyosarcoma
References: AJSP 2002;26:371 (vs. nasopharyngeal carcinoma undifferentiated), AJSP 2001;25:156 (stains/EBV)
Hematologic conditions
May present as sinonasal or nasopharyngeal mass
Almost always non-Hodgkin’s lymphoma
Most patients are elderly but broad age range
Often bulky lesions affecting multiple sinuses and nasal cavity, with extension into nasopharynx
5 year survival is 55% for stage I/II
Most common: NK/T cell, diffuse large B cell, peripheral T cell; mantle cell lymphoma most common in nasopharynx
Also called intravascular lymphoma; different from angiocentric lymphoma
Most tumor cells are intravascular and don’t infiltrate vessel wall
Considered a subtype of diffuse large B cell lymphoma
Most common lymphomas of nasal cavity and paranasal sinuses in US and Western Europe; also most common type in children
More common in paranasal sinuses than nasal cavity; may invade orbit
Case reports: T cell rich variant in ethmoid sinus (Archives 2000;124:1213)
Positive stains: CD20, CD79a
References: AJSP 1999;23:1356
In children, 75% male, usually localized disease, no bone marrow involvement, often in nasopharynx, excellent prognosis
Micro: usually centroblast predominant (grade 3 of 3) with high mitotic rate; may have plasmacytoid differentiation
Positive stains: monoclonal light chain expression, bcl6
Negative stains: bcl2
Molecular: usually no bcl2 gene rearrangements, but monoclonal
DD: florid follicular hyperplasia
Common, although only rarely presents as a mass in nasopharynx or nasal cavity
Micro: germinal centers with tingible bodies (macrophages containing apoptotic bodies), mixed inflammatory infiltrate, polyclonal light chains, no atypia
In nasopharynx, lymphocytes may infiltrate overlying epithelium producing lymphoepithelial lesions, but this does NOT indicate lymphoma at this site
EBV positive B cell proliferation associated with exuberant T cell reaction
Associated with immunodeficiency, including HIV
Common sites are lung, kidney, CNS, skin, subcutaneous tissue; rare in nasal area
Among the more common lymphomas of nasopharynx
Micro: sheets of small blue cells with irregular nuclei; overlying mucosa often undisturbed
Positive stains: CD19, CD20, CD5, cyclin D1
Negative stains: CD23
Molecular: t(11;14)
NK / T cell lymphoma, nasal type
Formerly called angiocentric lymphoma, polymorphic reticulosis
Commonly presents as lethal midline granuloma (destructive nasal or midline facial tumor)
Common lymphoma subtype at this location in Asia (Ai Zheng 2007;26:1170, Hum Path 2004;35:86), Central and South America (Appl Immunohistochem Mol Morphol 2007;15:38)
Rare in US; patients are often of Asian or Hispanic descent (AJSP 2000;24:1511)
Highly associated with EBV
5 year survival of 50% (Cancer 2006;106:609); commonly relapses to skin or subcutaneous tissue
Case reports: Case of Week #101, 34 year old man whose post-radiotherapy lymphocytes were morphologically normal, but EBER1+ by ISH (Archives 2002;126:602); 50 year old HIV+ African man (Archives 2001;125:660)
Treatment: radiotherapy, chemotherapy
Gross: usually perforated nasal septum, perforated palate, erosion of antral bone or ulceration of skin overlying nose or antrum
Micro: polymorphic infiltrate of lymphocytes (small to large), plasma cells, neutrophils and scattered atypical lymphoid cells with perinuclear clearing; frequent angiolymphatic invasion and necrosis, although vessel is usually infiltrated by atypical lymphocytes with no neutrophils and no fibrinoid necrosis present; often epitheliotropism; frequent histiocytes with erythrophagocytosis
NK / T cell lymphoma, nasal type (continued)
Micro images: extensive necrosis; pleomorphic tumor cells with necrosis; tumor cells invade vessel walls without fibrinoid necrosis #1; #2; keratin negative, with positive internal control; CD20 negative; CD3+, CD56+ #1; #2; EBV+ (by ISH); TIA+; fig a: large areas of tumor necrosis, fig b: medium/large lymphoma cells, fig c: CD94+, fig d: EBER1+ by ISH; fig A: tumor in skin with vascular infiltration and prominent necrosis, fig B: tumor infiltrates epidermis and dermis of skin, fig C: cells in peripheral blood are large granular lymphocytes with abundant cytoplasm and coarse azurophilic granules
prior to radiotherapy - fig a: variably sized pleomorphic lymphoma cells, fig b: venous wall invasion (arrow, elastic stain), fig c: UCHL1+ (T cell marker), fig d: EBER1+ by ISH
post-radiotherapy cardiac involvement - fig a: diffuse myocardial infiltration by lymphoma cells with fibrosis, fig b: small lymphoma cells without atypia, fig c: EBER1+ by ISH
Positive stains: CD2, CD3 (cytoplasmic), EBER-ISH (100%), CD56 (65%); p53 (50%), CD45RO, CD43, TIA1, granzyme B, perforin (35-100%), CD8 (20%), EBV LMP1 (48%)
Negative stains: CD3 (nuclear), CD16 (positive on histiocytes but not tumor cells), CD57; CD79a (usually)
Molecular: no T cell receptor gene rearrangement, no immunoglobulin light or heavy chain rearrangements
Molecular images: monoclonal proliferation of EBV+ cells
DD: Wegener’s granulomatosis, idiopathic midline destructive disease, diffuse large B cell lymphoma (the infiltrating T cells may obscure the neoplastic B cells, AJSP 1999;23:1356), florid HSV infection (HSV+, EBV-, no angioinvasion or angiodestruction, polyclonal, Mod Path 2003;16:166)
References: AJSP 1999;23:1356 (US cases)
Micro: no necrosis, no marked angiolymphatic invasion; often intense squamous hyperplasia proliferating downward from overlying mucosa, but without atypia
Negative stains: CD56
Molecular: clonal rearrangement of T cell receptor gene
Nasal cavity and paranasal sinuses are common site of extramedullary plasmacytoma
May present as soft, bleeding mass
Usually age 40+ years; 80% male
Most patients, even with solitary tumors, develop myeloma up to 10 years later
Treatment: radiation therapy
Micro: monomorphic infiltrate of immature plasma cells; usually no other inflammatory cells
Virtual slide: plasmacytoma
Positive stains: light chain monoclonality, EMA, variable CD45
DD: diffuse large B cell lymphoma with immunoblastic features, lymphoplasmacytic lymphoma (usually disseminated with monoclonal IgM gammopathy, plasma cells and lymphocytes), granulocytic sarcoma (eosinophilic myelocytes, positive chloracetate esterase stain)
Other tumors
Resembles peripheral ameloblastoma of oral cavity
DD: sinonasal extension of craniopharyngioma
Similar to giant cell reparative granuloma, but also has involvement of contiguous bones
15-26% recur
May be associated with fibrous dysplasia
Micro: spindled, ovoid or round histiocytes-like cells in well vascularized fibrous stroma; cells have 1-3 nuclei and may form giant cells with 10-20 nuclei that aggregate in groups of 6-12 cells; giant cells tend to invade and line vascular channels; lesions contain metaplastic woven bone and lamellar bone lined by osteoblasts and occasionally osteoclasts; prominent extravasation of blood, numerous mitotic figures
Also called vascular leiomyoma
Benign tumor of smooth muscle and endothelium
Rare in head and neck, very rare in nasal cavity (J Laryngol Otol 1994;108:244)
Most head and neck cases occur in females (B-ENT 2008;4:105)
Subclassification as capillary, cavernous or venous has no clinical significance
Case reports: 51 year old man (Case of the Week #138)
Treatment: simple excision (Laryngoscope 2004;114:661)
Micro: spindle cells that resemble smooth muscle plus numerous vessels
Micro images: #1; #2; #3; actin; desmin
Positive stains: actin, desmin, variable PR (Acta Otolaryngol 2002;122:408, Chinese Medical Journal 2007;120:350)
Negative stains: ER
Very rare in nasal cavity
In contrast to renal tumors, not associated with tuberous sclerosis, usually affects older men, small (up to 4 cm), HMB45 negative Micro: smooth muscle cells, fat cells and blood vessels of various sizes; lymphoid aggregates are present
Positive stains: alpha smooth muscle actin, muscle specific actin, S100 (fat cells)
Negative stains: HMB45 (unlike liver and kidney cases)
References: Archives 1999;123:789
Rare
Usually bleeding and polypoid masses
DD: papillary endothelial hyperplasia
May extend into nasal cavity
Rarely presents as intranasal tumor
15% occur in craniofacial bones
Xray: tumor centered in bone
Micro: small round cells with minimal cytoplasm; often has hemangiopericytoma-like vascular pattern, osteoid or cartilaginous foci
DD: rhabdomyosarcoma (not centered in bone but may erode into bone)
May occur as mass in nasal cavity or sinus
Better survival if less than 40 years old
May recur as a high grade spindled sarcoma, with poor prognosis
Micro: physaliphorous cells with multiple cytoplasmic vacuoles within myxoid stroma; no glandular formation; chondroid variants contain cartilage
Positive stains: cytokeratin, EMA
DD: adenocarcinoma
Reactive vascular changes
Case reports: exuberant ulcerative angiomatoid lesion of nasal septum (Hum Path 2000;31:239)
Micro: lobular pattern of polymorphous endothelial cells with infiltrative-type areas and occasional mitotic figures; also thrombosis with recanalization
DD: idiopathic midline destructive disease, angiosarcoma
Rarely occurs as nasopharyngeal or sphenoid sinus lesion
Benign epithelial tumor of central nervous system, usually in sellar and suprasellar areas
Often recurs after excision, rarely undergoes malignant change
Either ages 0-20 or 60+ years
Slow growing, often large when detected
Case reports: malignant tumor in nasal cavity and sinuses after surgery and radiotherapy and multiple recurrences (Archives 2000;124:1356)
Midline lesion
Associated with bony lesions and sinus tracts
May extend intracranially and cause CNS infection
Desmoplastic small round cell tumor
Rare, aggressive tumor, usually in abdomen of adolescents and young adults; 80% men
Case reports: sinonasal tumor in 21 year old woman extending into skull base (AJSP 2002;26:799)
Micro: nests of cells with variable amphophilic cytoplasm and hyperchromatic nuclei surrounded by desmoplastic stroma; highly invasive with necrosis and bone destruction; scattered mitotic figures; no glandular differentiation; no rosettes
Positive stains: keratin, vimentin, desmin (perinuclear dot-like pattern), focal neuron specific enolase; also EMA and CD57 (Leu7)
Molecular: t(11;22)(p13;q12) by RT-PCR (Wilms’ tumor suppressor gene-Ewing sarcoma gene transcript)
DD: olfactory neuroblastoma (no desmoplastic stroma, strongly positive for neuron specific enolase and synaptophysin, S100+ around periphery of tumor nests, negative for desmin and EMA), Ewings/PNET (translocation involves similar region but different breakpoint)
Fibroinflammatory proliferation
Resembles sclerosing mediastinitis but in nasal cavity or sinuses
Micro: fibroblasts in collagenous background, with acute and chronic inflammatory infiltrate and infiltration of adjacent tissues
DD: fibromatosis (no inflammatory background)
Small localized nodule less than 1 cm
Usually in nasal septum or vestibule
Usually no symptoms
Treatment: excision is curative
Micro: mature fibrous tissue, hypocellular, no infiltration of surrounding tissue
12% of fibromatosis cases involve head and neck
All ages, no gender preference
Recurs locally, particularly after incomplete excision, which is common in this region
Doesn’t metastasize; rarely regresses in children with multiple fibromatosis
May be component of Gardner syndrome
Gross: firm fibrous mass with infiltrative margins
Micro: broad fascicles and bundles of well differentiated fibroblasts and myofibroblasts with collagenous fibrous tissue; may be storiform but no herringbone pattern; cells have uniform nuclei with sharply pointed ends in cross section, dense chromatin, no nucleoli, rare mitotic figures; infiltrates surrounding tissue
DD: nasal fibroma, fibrosarcoma, scar (finer parallel arrays of collagen), neurofibroma (more delicate cells, S100+), fibroosseous lesions or desmoplastic fibroma (contain bone), angiofibroma (more vascular)
Fibrous dysplasia, ossifying fibroma, cementoossifying fibroma (also called psammomatoid ossifying fibroma in extragnathic facial bones)
Above disorders represent parts of microscopic spectrum
Fibrous dysplasia: irregular shapes (“Chinese letters”) of woven bone without osteoblastic rimming; Xray usually shows ill defined borders and ground-glass or orange peel quality; 20% recur
Ossifying fibroma: trabeculae of lamellar bone with prominent osteoblastic rimming; Xray usually shows well circumscribed margins and punched out appearance; rarely recurs
Cementoossifying fibroma: sharply defined, irregular, calcified spherules in densely fibrotic stroma with nonlinear bony trabeculae
Rare, clinically resembles fibromatosis
Only 10% of head and neck tumors metastasize
Rarely arises after radiation therapy
Micro: herringbone pattern of hypercellular, atypical fibroblasts, numerous mitotic figures
DD: spindle cell carcinoma (no herringbone pattern, usually typical areas of carcinoma, EMA+, keratin+), amelanotic melanoma (S100+, HMB45+)
Follicular dendritic cell tumor
Positive stains: CD21, CD35
Negative stains: keratin
DD: nasopharyngeal carcinoma-nonkeratinizing-undifferentiated
Rare at any site, only a few cases described in nasal cavity or nasopharynx
Usually is a periampullary tumor, although also described in jejunum, appendix, stomach
Not related to true paragangliomas
Micro: triphasic with epithelioid, spindle cell (nerve sheath-like) and ganglion cell-like elements
References: Archives 2001;125:1098
Giant cell reparative granuloma
Similar to aneurysmal bone cyst
Rarely occurs after dental extraction
15-26% recur
Micro: spindled, ovoid or round histiocytes-like cells in well vascularized fibrous stroma; cells have 1-3 nuclei and may form giant cells with 10-20 nuclei that aggregate in groups of 6-12 cells; giant cells tend to invade and line vascular channels; lesions contain metaplastic woven bone and lamellar bone lined by osteoblasts and occasionally osteoclasts; prominent extravasation of blood, numerous mitotic figures
Extremely rare
Micro: mononuclear cell background with abundant giant cells; resembles tumor of long bones
DD: aneurysmal bone cyst, fibroosseous lesion, giant cell granuloma
Also called nasal glioma
Not a true neoplasm but a malformation that cause tumor-like conditions in newborns and older infants; considered a variant of encephalocele (encephalocele is associated with bony defects, glial heterotopia is not)
Usually present at birth or clinically evident within a few years of birth
60% occur in nasal subcutaneous tissue, 30% in nasal cavity, 10% mixed
20% have small fibrous or glial attachment to CNS
Case reports: 2 year old boy with subcutaneous mass on nose (Archives 2000;124:1849)
Treatment: excision
Micro: mature astrocytes, gliosis and variable stromal fibrosis; occasional multinucleated giant cells resembling neurons; variable gemistocytic or mildly atypical astrocytes; usually no neuronal cells
Positive stains: S100, GFAP
Very rare
Case reports: 2 cases presenting as nasal polyps (Hum Path 1999;30:1259)
Micro: sheets and nests of monomorphic round cells associated with capillary-sized blood vessels
Positive stains: vimentin, smooth muscle actin, muscle-specific actin, CD34, synaptophysin
Negative stains: desmin
Hemangiopericytoma-sinonasal type
Uncommon tumor of pericytic myoid differentiation (unlike soft tissue hemangiopericytoma)
WHO calls it glomangiopericytoma; also called myopericytoma (J Laryngol Otol 2007 Apr 10:1 [Epub ahead of print])
Mean age 63 years, usually ages 40+ but range of 5-86 years; slight female predominance
Usually presents with airway obstruction or epistaxis in nasal cavity or paranasal sinus
Recurs locally (18%), no metastases; death due to disease is rare
Case reports: Case of the Week #84
Treatment: excision plus follow up
Gross: resembles allergic polyp; unilateral, unencapsulated, mean 3 cm, red to gray-pink, soft, edematous, fleshy to friable, often hemorrhagic
Micro: diffuse growth with fascicular, solid or focally whorled pattern of spindled or round/oval tumor cells that arrange themselves around prominent, small, thin-walled submucosal blood vessels; cells have variable cytoplasm and nuclei, indistinct cell borders, occasionally are multinucleated; minimal atypia, no necrosis, no/rare mitotic activity; vessels are prominent with staghorn appearance and perivascular hyalinization; often mast cells and eosinophils; surface epithelium is intact and usually respiratory
Hemangiopericytoma-sinonasal type (continued)
Micro images: (1) various images #1; #2; (3) bland spindled and round/oval cells with prominent blood vessels; #2; #3; #4; (7) CD34 highlights vessels, but tumor cells are negative; (8) smooth muscle actin is diffusely positive
Positive stains: vimentin (98%), smooth muscle actin (92%), muscle specific actin (77%), factor XIIIa (78%), laminin (52%); also D2-40 (Virchows Arch 2006;448:459)
Negative stains: CD31, CD34 (usually), factor VIII, keratin
EM: basal lamina surrounds individual cells, tapered cytoplasmic extensions, orderly bundles of filaments
DD: lobular capillary hemangioma (lobular pattern at low power, has spindled fibroblasts and prominent vessels, but overall granulation tissue-like appearance with only small capillaries), solitary fibrous tumor (similar vascular pattern but tumor has patternless pattern, ropey keloidal collagen, thin walled vascular spaces, D2-40 negative, Virchows Arch 2006;448:459), glomus tumor (also a pericytic tumor with similar staining, but extremely rare in sinonasal region, composed of compact epithelioid cells)
References: AJSP 2003;27:737 (analysis of 104 cases), Archives 2001;125:686 (2 cases)
Very rare
Mean age 40 years, range 20-67 years
Good prognosis with complete surgical excision, even if uncertain malignant potential or low grade leiomyosarcoma
Gross: usually small (~ 2 cm)
Micro: low cellularity, no nuclear pleomorphism, no infiltrative growth, no mitotic activity
Negative stains: Ki-67 (<5%)
DD: leiomyosarcoma (> 4 mitotic figures/10 high power fields, moderate nuclear pleomorphism, moderate to high cellularity, focal infiltrative growth, occasional tumor necrosis), smooth muscle tumor of uncertain malignant potential (1-4 MF/10 HPF, mild to moderate pleomorphism)
References: Archives 2003;127:297
Common; occurs in nasal cavity, usually on septum
Patients < 18 years are usually male; older patients are usually women, often pregnant, with regression after delivery
Treatment: excision
Gross: may be very large
Micro: capillary lobules that often surround a large central vessel; may have marked cellularity and frequent mitotic figures
Positive stains: actin, CD31
DD: nasopharyngeal angiofibroma
Malignant fibrous histiocytoma
Often maxillary antrum or other paranasal sinuses
Probably very rare; historically has also included sarcomatoid carcinoma, fibrosarcoma and desmoplastic melanoma
Malignant peripheral nerve sheath tumor (MPNST)
May be most common primary fascicular spindle cell sarcoma of head and neck
Adults, often in sinonasal tract
DD: schwannoma, spindle cell carcinoma, spindle cell melanoma
Also called intravascular papillary endothelial hyperplasia
Benign; related to organizing thrombi, but resembles angiosarcoma
Very rare in nasal cavity or paranasal sinus; usually in dermis and subcutis of head, neck, fingers or trunk
Case reports: ethmoid sinus tumor extending into sphenoid sinus and sella (Archives 2000;124:1224)
Micro: exuberant intravascular endothelial proliferation
Micro images: (1) tumor within dilated vascular space; (2) irregular anastomosing vascular channels lined by plump endothelial cells with slight nuclear atypia; (3) thin and thick walled vessels
DD: angiosarcoma
1% of all melanomas occur in this region, usually in nasal cavity
Frequently misclassified
Mean age 64 years, range 13-93 years, no gender preference, may affect teenagers
Established risk factors for cutaneous melanoma of sun damage, family history and atypical nevi don’t apply to this region
Difficult to diagnose if no intraepithelial component and no pigment
Poor prognosis, usually recurs; median survival 3 years; 5 year survival is 35%
Proposed staging:
T1 - single anatomic site; T2 - two or more anatomic sites
N0 - no nodal metastases; N1 - nodal metastases
M0 - no distant metastases; M1 - distant metastases
Stage: I - T1N0M0; II - T2N0M0; III - any T, N1M0; IV - M1
Treatment: complete excision
Case reports: 79 year old woman with nasal mass extending into orbit (Archives 2002;126:493)
Gross: solid polypoid growth, often pigmented, mean 2 cm; often ulcerated and necrotic
Micro: small uniform cells, 70% with pigment; 1/3 have junctional component; often nesting growth pattern; other patterns are small blue cell, spindle cell, epithelioid, pleomorphic; frequent vascular and deep tissue invasion; occasionally myxoid or with metaplastic bone; may have minimal pleomorphism, prominent spindle cells; rarely has fibrillar background with Homer-Wright rosettes
Micro images: (1) spindled cells invading cranial bone; (2) A-gross of hard palate pigmented macular lesion; B-tumor presents as nasal septum polyp; C-hard palate in situ melanoma; D-maxillary antrum melanoma; E-epithelioid melanoma in maxillary mucosa with moderate cytoplasm, pleomorphic nuclei, prominent nucleoli; F-nasal cavity sarcomatoid melanoma with cells resembling vacuolated lipoblasts; (3) A-poorly differentiated/undifferentiated tumor; B-pseudopapillary pattern; C-S100+ only rarely (not typical); D-HMB45+; E-MelanA+; F-tyrosinase+; G-microphthalmia transcription factor+; (4) figure 1-MRI shows large nasal mass involving right maxillary sinus and extending into right orbit, temporal and pterygoid fossa; 2-polypoid fragments of respiratory mucosa with submucosal cellular tumor; 3-necrosis and angiocentric tumor cells; 4-cells have moderate cytoplasm, round nuclei, inconspicuous nucleoli, but high mitotic rate
Positive stains: S100 (95%), HMB45 (98%), MelanA/Mart1 (100%), tyrosinase (100%), microphthalmia transcription factor (91%); also vimentin
Negative stains: EMA, CD3, CD4, CD8, CD56
DD: olfactory neuroblastoma (S100+, but not diffuse and strong; HMB45 negative)
References: AJSP 2003;27:594 (review of 115 cases); AJSP 2001;25:782 (stains); Archives 2003;127:997 (comparison to oral melanomas)
Rare, frequently misclassified
Mean age 48 years, range 13-88 years; no gender preference
Usually primary intranasal or paranasal mass; may also be an intracranial tumor invading sphenoid or frontal sinuses
Primary extracranial tumors have a good prognosis; intracranial lesions invading into upper respiratory tract are difficult to excise
Micro: whorled growth pattern of meningothelial spindle cells with psammoma bodies; may have atypical features
Positive stains: EMA, vimentin
Negative stains: S100 (usually)
DD: cementoossifying fibroma (cellular with fibroblastic stromal cells, calcifications contain cells), schwannoma, paraganglioma, melanoma, angiofibroma
References: AJSP 2000;24:640
Almost always involves mandible and maxilla in head and neck
Maxillary lesions may encroach on nose or antrum
Treatment: excision, although 25% recur
Micro: uniform spindle cells in myxoid stroma with occasional blood vessels; may have cellular foci with collagenous stroma, large bizarre nuclei
DD: fibromatosis (collagen throughout the lesion), low grade fibrosarcoma (more cellular, more atypical nuclei)
Nasal chondromesenchymal hamartoma
Rare; intranasal and paranasal polypoid mass in infants and occasionally older children
2/3 male, mean age 14 months, range 1 day to 7 years
Benign, but fills nasal cavity and usually extends into ethmoid sinuses
May erode bone, including cribriform plate, and have an intracranial component
Xray images: tumor in nasal cavity with cystic component
Treatment: excision
Micro: well demarcated mature cartilage, myxoid stroma, focal osteoclast-like giant cells, aneurysmal bone cyst-like formations, spindle cells, collagen fibers
Micro images: (1) lobules of cartilage and spindle cells; (2) reactive bone in fibrous stroma resembling fibrous dysplasia
Positive stains: vimentin, S100
EM: fibroblastic and myofibroblastic differentiation
EM images: loose bundles of microfilaments with foci of condensation
References: AJSP 1998;22:425; Archives 2001;125:400
Rare tumor, usually adolescent males (10-25 years), rarely in older patients or women (may be misdiagnoses)
75% have androgen receptors, but not estrogen or progesterone receptors
Arises from erectile-like fibrovascular stroma in posterolateral wall of roof of nose
May grow into nasopharynx, orbit or cranial cavity
May regress after puberty, especially after incomplete surgical excision or radiation therapy
Benign but recurs in 40%, usually within 1 year, particularly if not completely removed
Rare sarcomatous transformation after radiation therapy
Treatment: surgery (difficult to excise), preoperative embolization or anti-androgen therapy; chemotherapy or radiation therapy if advanced or aggressive
Gross: well circumscribed but unencapsulated polypoid fibrous mass, bleeds severely on manipulation and biopsy, may occlude nares; spongy cut surface
Micro: intricate mixture of stellate and staghorn blood vessels with variable vessel wall thickness ranging from single layer of endothelium to variable smooth muscle coat; irregular fibrous stroma (loose, edematous to dense, acellular); stromal cells are stellate fibroblasts with small pyknotic to large vesicular nuclei; larger vessels at base of lesion, smaller vessels with plump endothelial cells at growing edge of tumor; multinucleated stromal cells are common; mitotic figures are rare; minimal inflammation
Positive stains: c-Kit/CD117, androgen receptor (75%)
EM: electron dense granules composed of tightly bound RNA-protein complexes; stromal cells are myofibroblasts
DD: capillary hemangioma (less fibrous tissue, vessels lack erectile tissue appearance)
References: Archives 2003;127:1480 (pathogenesis), Mod Path 1998;11:1122 (androgen receptors)
Usually nonplexiform
Micro: delicate, spindle shaped cells in loose, myxoid stroma
Positive stains: S100
Usually occurs as subcutaneous lesion
May affect orbit or nasopharynx
Antral cyst lined by fibroblasts
Also called esthesioneuroblastoma
Rare, malignant neuroectodermal tumor thought to arise from olfactory membrane or olfactory placode (“placode”: platelike thickening of embryonic ectoderm from which a nerve ganglion or sensory organ will develop), which extends from roof of nasal cavity in fetus to mid nasal septum and superior turbinate
Not related to neuroblastomas elsewhere in body
Median age 50 years, range 3-79 years; no gender preference
Usually upper nasal vault; rarely in nasopharynx, maxillary or ethmoid sinus
Locally invasive into paranasal sinuses, nasopharynx, palate, orbit, base of skull, brain
20% develop distant metastases, usually to cervical lymph nodes and lung; late recurrence (after 10 years) is common
Xray images: subtraction angiogram shows tumor with origin in cribriform plate and invasion intracranially
Staging (Kadish): A-confined to nasal cavity; B-confined to nasal cavity and paranasal sinuses; C-other
40-50% are Stage B
5 year survival by stage: A-75%; B-68%; C-41%
Treatment: complete surgical excision (may require craniofacial resection), with radiation therapy or chemotherapy
Gross: red-gray, highly vascular, polypoid mass of soft tissue
Micro: nests or sheets of uniform small cells with scant cytoplasm, round nuclei with indistinct nuclear membrane and punctuate chromatin, no/indistinct nucleoli; mild to moderate nuclear pleomorphism; prominent fibrillary or reticular background in 85% of cases; may have abundant fibrovascular stroma that obscures tumor; often crush artifact; variable mitotic figures; variable Homer Wright rosettes (cells surrounding central zones of fibrils), ganglion cells and tumor cell melanin; necrosis is poor prognostic factor
Micro images: (1) irregular but sharply demarcated nests of uniform cells with punctate chromatin, focal nuclear molding; (2) S100 staining at periphery of nests
Positive stains: keratin, neuron-specific enolase (strong), synaptophysin (strong), chromogranin, neurofilament, catecholamines, S100 in cells at periphery of cell nests; occasional GFAP and keratin
Negative stains: EWS-FL1, CD99, EMA, desmin
EM: dense core neurosecretory granules, microtubules, neuritic processes, neurofilaments
Molecular: no t(11;22)(q24;q12) of Ewing/PNET
DD: lymphoma, Ewing/PNET, plasmacytoma, rhabdomyosarcoma, small cell carcinoma
References: Hum Path 1999;30:1356 (no t(11;22) in these tumors)
Rare congenital bone tumor presenting as painless mass
Associated with Carney complex (familial lentiginous and multiorgan tumor syndrome, AJSP 2001;25:164)
Sites: nasal region, also tibia, radius
Treatment: resection; recurs if incompletely excised
Gross: gelatinous, cartilaginous, bony
Micro: sheets and lobules of bland cells in myxomatous, cartilaginous, osseous, and hyaline fibrous matrix; low to moderate cellularity; erodes bone and frequently extends into soft tissue
Usually in frontal sinus, also other sinuses
Multiple osteomas are associated with Gardner syndrome
Treatment: excise only if symptomatic obstruction of sinus
Micro: dense lamellar bone with sparse intervening fibrous tissue, sparse osteoblasts
Also called schneiderian; subtypes are inverted (47-78%), fungiform (6-50%) and oncocytic (2-26%)
Benign neoplasm of respiratory mucosa, 1-5% of sinonasal tumors
Usually adults, 2/3 men, with nasal obstruction, stuffiness or epistaxis; also children
Rarely extends into cranial cavity or causes proptosis (inverted papillomas eroding bone by pressure)
Usually unilateral
3% develop carcinoma after excision, which has only a 25% survival rate
3% (particularly inverted and oncocytic subtypes) have coexisting focal invasive carcinoma, which has an excellent prognosis
Some have invasive carcinoma resembling papilloma but with subtle features of malignancy and a 25% survival rate
Often HPV 6/11 positive (particularly fungiform subtypes); EBV negative
Nasal septum tumors: usually mushroom-shaped and exophytic with thin central core of connective tissue
Lateral wall of nose: usually inverted, with inward epithelial growth
Treatment: excision (lateral rhinotomy, en bloc excision of lateral nasal wall, removal of mucosa in ipsilateral paranasal sinuses)
50-70% recur if treated by local excision only, particularly inverted subtypes
Case reports: two patients with small cell carcinoma and sinonasal undifferentiated carcinoma arising in oncocytic schneiderian papillomas (Archives 2001;125:1365)
Gross: soft to moderately firm, with granular or finely clefted surface; should submit all tissue for microscopic examination to look for small foci of carcinoma
Gross images: squamous papilloma
Micro: columnar or squamous epithelium cells, with some mucin containing cells; numerous microcysts; may have oncocytic features, occasional mitotic figures in basal layer, mild/moderate atypia; may have neutrophils or microabscesses with reactive epithelial changes
See subtypes below
Micro images: (1) thickened nonkeratinizing squamous epithelium overlying fibrovascular core; (2) a/b-small cell carcinoma undermining epithelium of overlying papilloma; c/d-sinonasal undifferentiated carcinoma mixed with carcinoma in situ and dysplastic epithelium; (3) carcinoma arising in papilloma
DD: nonkeratinizing squamous cell carcinoma (diffuse, severe nuclear atypia; often clear cytoplasm), inflammatory polyp (no oncocytic cells, no mucous inclusions), rhinosporidiosis (organisms are in epithelium and stroma), adenocarcinoma (eosinophilic cytoplasm, nuclear atypia), verrucous hyperkeratotic squamous lesions arising from nasal vestibule
References: Mod Path 2002;15:279
Fungiform papilloma
More common in men, usually ages 20-50 years
Arise on nasal septum
May be related to HPV 6/11 (57% are HPV+)
Not associated with increased incidence of carcinoma
Treatment: complete surgical excision; recurrences (22-50%) probably due to inadequate resection
Gross: exophytic, papillary or warty; gray-pink-tan
Micro: exophytic connective tissue stalks, often with serpiginous configuration, with delicate fibrovascular cores, lined by benign squamous or intermediate epithelium; may contain respiratory, intermediate or mucus secreting cells; variable koilocytosis and residual goblet cells; usually no/scant surface keratinization; no/rare mitotic figures, minimal inflammatory cells
Micro images: exophytic growth without surface keratinization, scattered goblet cells
DD: verrucae vulgaris (extensive surface keratinization, no mucous cells, no ciliated epithelium, no minor salivary glands, no septal cartilage)
Inverted papilloma
Usually men ages 40-70 years
Usually arise from lateral wall of nose or paranasal sinuses; only 8% arise from nasal septum
Variable positivity for EBV and HPV
Malignant change in 2-27%; either small focus or carcinoma, carcinoma with small focus of inverted papilloma, or inverted papilloma with later carcinoma at same site (mean 5 years later); if both present, report % of specimen that represents carcinoma
Treatment: lateral rhinotomy and medial maxillectomy with meticulous removal of all mucosa in ipsilateral paranasal sinuses; with this approach, is 0-30% recurrence; can remove endoscopically if very small
Gross: pink-tan-gray, soft to moderately firm, polypoid growth with convoluted or wrinkled surface
Gross images: inverted papilloma
Micro: hyperplastic epithelium, 5-30 cells thick, enclosed by basement membrane, which grows endophytically into underlying stroma; epithelium is squamous or respiratory-type mixed with goblet cells; may have transitional-type epithelium; 10-20% have focal surface keratinization; 5-20% display dysplasia; no/few mitotic figures; variable stroma (dense/fibrous or loose/myxoid), variable inflammatory cells but usually no eosinophils; usually no/few minor salivary glands; often coexists with ordinary nasal polyps
With focal verrucoid hyperplasia: rare; focal papillary squamous hyperplasia with marked parakeratosis or keratosis, with koilocytes but HPV negative
Micro images: (1) endophytic growth with epithelial islands well demarcated from stroma; (2) glycogenated squamous cells, lined by thin and delicate basement membrane; (3) downward growth into preexisting mucosal glands
DD: polyps with squamous metaplasia (thickening and hyalinization of basement membrane, prominent minor salivary glands, eosinophils and other inflammatory cells, no multilayered epithelium), respiratory epithelial adenomatoid hyperplasia, inverted ductal papilloma of minor salivary glands (grows intraluminally and is confined by duct), invasive carcinoma (cellular pleomorphism, keratin pearls, loss of basement membrane, unequivocal invasion, desmoplastic stroma, atypical mitotic figures)
Oncocytic papilloma
Also called cylindrical cell or columnar cell papilloma
No gender preference; most patients 50+ years; youngest patient reported is 33 year old woman
Only on lateral nasal wall or in sinuses
HPV negative
4-17% have coexisting carcinoma, usually squamous cell; may arise within the papilloma
Treatment: similar to inverted papilloma (lateral rhinotomy and medial maxillectomy); 25-35% recur, usually due to inadequate excision; can excise small tumors endoscopically
Gross: fleshy polypoid growth of variable color
Micro: endophytic or exophytic; irregularly distributed tall columnar cells, 2-8 layers thick, with finely granular eosinophilic cytoplasm resembling oncocytes; nuclei are small, dark and uniform or slightly vesicular; indistinct nucleoli; intraepithelial mucin filled cysts with neutrophils; edematous to fibrous stroma; variable inflammatory infiltrate, but few eosinophils; no/rare minor salivary glands
Micro images: oncocytic cells with intraepithelial mucin filled cysts containing neutrophils
DD: rhinosporidiosis (organisms involve stroma and lack oncocytic epithelium); low grade papillary adenocarcinoma (invasive, nuclear pleomorphism, single layered non-oncocytic epithelium, mitotic activity, perineural invasion, extensive bone destruction on Xray)
Intranasal or nasopharyngeal mass, often near fossa of Rosenmuller
Due to paraganglia associated with vagus nerve
Slow growing
Biopsy may cause extensive hemorrhage
Micro: tight nesting pattern (Zellballen) of cells with prominent cytoplasm, no/rare mitotic figures, surrounded by S100+ sustentacular (Schwann) cells
2% present as primary lesion of nasopharynx or nasal cavity
Some may arise as Rathke pouch remnants
Usually chromophobe type
Difficult to distinguish benign and malignant tumors by histology; must depend on presence of metastases; tumors with high MIB1 but p53 negative have uncertain malignant potential; tumors with high MIB1 and p53 expression act like carcinomas
Case reports: ectopic pituitary adenoma in nasal cavity with malignant transformation (AJSP 2002;26:1078)
Micro: rosette or ribbon pattern of polygonal cells with prominent, delicate vascular stroma
DD: downward extension of pituitary adenoma from sella through sphenoid bone (occurs in 10%), paraganglioma (larger cells with uniform nuclei), olfactory neuroblastoma
Also called mixed tumor
Most common benign tumor of nasal cavity and sinuses
Rarely recurs at this site; rarely metastasizes
Micro: rarely contains adult skeletal muscle
Psammomatoid ossifying fibroma
Distinctive solitary fibro-osseous lesion of young persons that affects orbit and paranasal sinuses
Affects extragnathic craniofacial bones (periorbital, frontal and ethmoid)
Slowly progressive, may invade and destroy surrounding tissue and cause bony erosion
Tends to recur after excision
Xray: expansile well-circumscribed, partially radiolucent lesion surrounded by a thick bony wall
Treatment: complete surgical excision
Case report: 13 year old girl with sino-orbital mass (Archives 2003;127:e301)
Micro: numerous small, round ossicles (psammomatoid bodies) embedded in cellular fibrous stroma and within bony trabeculae; stroma may be loose and fibroblastic or intensely cellular without collagen; contains variably shaped cells with indistinct cytoplasmic borders and basophilic nuclei; variable giant cells, stroma with cystic degeneration; rare mitotic figures; no anaplasia, no necrosis
DD: central cementifying fibroma (benign odontogenic jaw lesion, usually ages 20-39 years, female, has cementicles [related to dental cementum] not ossicles)
Respiratory epithelial adenomatoid hamartoma
First described in 1995
Usually posterior nasal septum of men median 58 years (range 27-82 years)
Associated with chronic rhinosinusitis
Treatment: complete excision; usually doesn’t recur
Gross: polypoid or exophytic, rubbery, tan-brown, up to 4.9 cm, but without destructive growth
Micro: proliferation of glandular spaces lined by ciliated epithelium or goblet cells; glands have thick, eosinophilic basement membranes; background resembles inflammatory polyp due to vascularization, edema and chronic inflammatory cells
Micro images: (1) numerous
glands lined by ciliated respiratory epithelium (resembles inverted papilloma); (2) each
gland is surrounded by an eosinophilic, thick basement membrane
Contributed by Dr. Semir Vranic: #1; #2; CK7
DD: inflammatory polyp (has fewer glands), inverted papilloma (usually on lateral nasal wall not nasal septum, usually hyperplastic squamous epithelium with only few goblet cells, thin basement membrane, no/rare mucoserous glands), adenocarcinoma (back to back glands, occasional nuclear pleomorphism, prominent mitotic activity, perineural invasion, desmoplastic stroma)
Benign neoplasm of striated muscle with preference for head and neck
Divided into fetal and adult types based on histologic features, not patient age
Micro: fetal type – immature slender muscle fibers and primitive spindle shaped mesenchymal cells; no pleomorphism, no mitotic figures, maturation at periphery of tumor
adult type – rarely in nasopharynx; clear cytoplasm (glycogen), finely granular cytoplasm, sparse striations
Positive stains: muscle markers
EM: Z bands in adult type
Common nasopharyngeal tumor of children (also lymphoma and nasopharyngeal carcinoma-nonkeratinizing-undifferentiated)
Most commonly in orbit, nasopharynx, middle ear/mastoid, nose or paranasal sinuses
75% are age 12 or younger; rarely teenagers, adults or elderly
85% are embryonal subtype, including botyroides variant; remainder are alveolar subtype; spindle cell or pleomorphic subtypes are rare
Alveolar have high rates of treatment failure
Survival varies by site – orbit: 90%; nose, paranasal sinuses, nasopharynx: 45%, other head and neck: 75%
Case reports: sclerosing subtype in nasopharynx (AJSP 2002;26:1175)
Gross: small red mucosal nodule or polypoid mass
Micro: highly cellular spindle cell tumor with frequent mitotic activity
embryonal – alternating hypercellular and hypocellular fields with myxoid or sparsely collagenized stroma; tumor cells have scanty cytoplasm, small, round/oval nuclei; may have occasional larger cells with abundant, deeply eosinophilic cytoplasm and cross striations
alveolar – fibrous septa lined by single row of tumor cells with additional tumor cells between the septa; may have multinucleated tumor cells, solid areas at periphery; may have clear cell changes due to glycogen (PAS+)
anaplasia – defined as marked hyperchromatic nuclei at least 3x larger than adjacent cells with clearly abnormal mitotic figures
maturation – after chemotherapy or radiation therapy; cells have large amounts of deeply eosinophilic cytoplasm
Micro images: A-embryonal subtype with small nuclear size and pleomorphism; B-alveolar subtype with larger, more uniform nuclei
Positive stains: desmin, myosin, myoglobin, myogenin, myoD1 (must make sure that tumor cells are actually staining, not adjacent skeletal muscle or histiocytes containing necrotic muscle)
Molecular: t(2;13), t(1;13) in alveolar subtype
DD: fetal rhabdomyoma, PNET/Ewing sarcoma (more uniform cells with minimal cytoplasm, CD99+, t(11;22) present), lymphoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, myxoma (almost never occurs in children)
Also called sinus histiocytosis with massive lymphadenopathy
May cause nasal polyps or involve paranasal sinuses or nasopharynx
Variable cervical adenopathy
Polypoid lesion of nasopharynx, presents at/near birth with respiratory distress
Benign, but may be life threatening due to location
Micro: biphasic pattern of peripheral squamous nests and duct-like lesions that blend into solid nodules centrally with focal cysts
Minor salivary gland tumors uncommonly arise in nasal cavity and sinuses, usually in nasal septum, turbinates or ostial regions
Usually malignant
Adenoid cystic carcinoma is most common malignant tumor; then mucoepidermoid carcinoma
Pleomorphic adenoma (mixed tumor) is most common benign tumor
Polymorphous low grade adenocarcinoma is very uncommon
Very rare
May be very cellular
In one study, 3 of 5 cases were in ethmoid sinus
Treatment: conservative surgical resection; no recurrence or metastases
Gross: pedunculated or polypoid, white-yellow, 2-4 cm; no nerve identified
Micro: no encapsulation; elongated spindle cells in fascicles with poorly defined cytoplasm, oval nuclei with tapering ends, focal nuclear palisading; overlying epithelium may be ulcerated; abundant vasculature; variable Verocay bodies, Antoni A and B patterns; no cytologic atypia, low mitotic rate
Micro images: (1) cellular schwannoma; (2) unencapsulated tumor of maxillary sinus; (3) figure 1-fascicles of elongated spindle cells without atypia; 2-Verocay bodies; 3-poorly demarcated tumor borders with occasional epithelial ulceration; 4-S100+, 5-low Ki-67/MIB1 staining
Positive stains: S100
Negative stains: EMA, CD34, Ki-67/MIB1 (1-5%)
DD: malignant peripheral nerve sheath tumor (atypia, tumor necrosis, high proliferation rate with abnormal mitotic figure, reduced S100 expression), melanoma (atypia, high mitotic rate, HMB45+, MelanA+ except in pure spindle cell melanomas), sarcomatoid carcinoma (EMA+, keratin+), leiomyoma (eosinophilic cytoplasm, elongated nuclei, muscle markers+), solitary fibrous tumor (hemangiopericytoma-like pattern, CD34+), meningiomas (EMA+, psammoma bodies), monophasic synovial sarcoma
References: Archives 2003;127:1196
Case reports: 54 year old man with large posterior nasal septal mass (Case of Week #191)
Uncommon, resembles pleural tumor
Closely related to hemangiopericytoma of soft tissues
Intranasal extension and erosion of adjacent structures is common, but tumors don’t metastasize
Usually ages 40+ years, no gender preference
Case reports: 48 year old chronic cocaine user (Archives 2004;128:e1)
Gross: polypoid mass; yellow-tan with smooth surface; pink-tan homogenous cut surface
Micro: nonencapsulated; patternless proliferation of bland spindled fibroblasts in collagenous background (ropey keloidal collagen), prominent blood vessels resemble hemangiopericytoma but have thin walls; hyper- and hypocellular areas; rare mitotic figures
Positive stains: vimentin, bcl2, CD34, CD99
Negative stains: muscle specific actin, desmin, S100, factor VIII, neurofilament, keratin, HMB45, CD117/c-kit
DD: hemangiopericytoma (less prominent collagenization, more prominent vessels)
Features of carcinosarcoma and immature teratoma
Adults; poor prognosis with 3 year survival of 40% due to uncontrollable local growth
Micro: primitive neuroepithelial elements with well formed rosettes; well formed glands with atypical epithelium; myxoid tissue; rhabdomyosarcomatous differentiation; benign and malignant cartilage; cellular areas
Positive stains: CD99, NSE, vimentin, keratin, EMA, GFAP, chromogranin, synaptophysin
Negative stains: beta hCG, CD45/LCA
References: Hum Path 1998;29:718
Infants and children
Usually benign
Also called papillary cystadenoma lymphomatosum
Very rare in nasopharynx; almost exclusively found in the parotid salivary gland
Usually men, peak incidence in seventh decade of life
Associated with cigarette smoking
Reactive, not neoplastic
Case reports: tumor of nasopharynx (Case of the Week #112)
Treatment: excision is almost always curative, rarely recurs; may be associated with other benign or malignant tumors.
Micro: glandular and cystic tumor lined by an inner double layer of oncocytic epithelium with a lymphoid cuff
Molecular: not clonal (Hum Path 2000; 31:1377, Mod Path 2005;18:964), although cases with coexisting mucoepidermoid carcinoma are associated with t(11;19) and the CRTC1/MAML2 fusion transcript (Genes Chromosomes Cancer 2008;47:309)
DD: Warthin-like variant of papillary thyroid carcinoma (similar histology plus papillary nuclear features, see topic in Thyroid Chapter).
Miscellaneous
TNM staging – Nasal cavity and paranasal sinuses
Excludes nonepithelial tumors (lymphoma, soft tissue, bone, cartilage)
Pathologic staging is required for nodal (pN) assessment; for T assessment, pT supplements but does not replace clinical assessment
Ohngren’s line: connects medial canthus of eye to angle of mandible; used to divide maxillary sinus into anteroinferior portion (infrastructure), associated with good prognosis for carcinomas, and superoposterior portion (suprastructure), with a poor prognosis
Primary tumor (T) – nasal cavity & paranasal sinuses
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
Primary tumor (T) - maxillary sinus
T1: Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone
T2: Tumor causing bone erosion or destruction including extension into the hard palate or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates
T3: Tumor invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses
T4a: Moderately advanced local disease - tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses
T4b: Very advanced local disease - tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx or clivus
Primary tumor (T) - nasal cavity and ethmoid sinus
T1: Tumor restricted to any one subsite (see below), with or without bony invasion
T2: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion
T3: Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate or cribriform plate
T4a: Moderately advanced local disease - tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses
T4b: Very advanced local disease - tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx or clivus
Notes:
Subsites are left and right maxillary sinus; septum, floor, lateral wall and vestibule (edge of naris to mucocutaneous junction) of nasal cavity; left and right ethmoid sinus
Regional lymph nodes (N) – nasal cavity & paranasal sinuses
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3: Metastasis in a lymph node, more than 6 cm in greatest dimension
Notes:
● A selective neck dissection ordinarily includes 6 or more lymph nodes
● A radical or modified radical neck dissection ordinarily includes 10 or more lymph nodes
● Negative pathologic examination of fewer than the 6-10 nodes above still mandates a pN0 designation
● Survival is significantly worse when metastases involve lymph nodes beyond the first echelon of lymphatic drainage, particularly lymph nodes in levels IV and V; thus, the region of nodal involvement should also be reported
● Midline nodes are considered ipsilateral
Level I: submental, submandibular; contains the submental and submandibular triangles bounded by the anterior and posterior bellies of the digastric muscle, and by the hyoid bone inferiorly, and the body of the mandible superiorly
Level II: upper jugular; contains the upper jugular lymph nodes and extends from the level of the skull base superiorly to the hyoid bone inferiorly
Level III: mid-jugular; contains the middle jugular lymph nodes from the hyoid bone superiorly to the level of the lower border of the cricoid cartilage inferiorly
Level IV: lower jugular; contains the lower jugular lymph nodes from the level of the cricoid cartilage superiorly to the clavicle inferiorly
Level V: posterior triangle; contains the lymph nodes in the posterior triangle bounded by the anterior border of the trapezius muscle posteriorly, the posterior border of the sternocleidomastoid muscle anteriorly, and the clavicle inferiorly; for description purposes, Level V may be further subdivided into upper, middle and lower levels corresponding to the superior and inferior planes that define Levels II, III and IV
Level VI: prelaryngeal, pretracheal, paratracheal; contains the lymph nodes of the anterior central compartment from the hyoid bone superiorly to the suprasternal notch inferiorly; on each side, the lateral boundary is formed by the medial border of the carotid sheath
Level VII: upper mediastinal; contains the lymph nodes inferior to the suprasternal notch in the superior mediastinum
Distant metastasis (M) – nasal cavity & paranasal sinuses
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups– nasal cavity & paranasal sinuses
0 : Tis N0 M0
I : T1 N0 M0
II : T2 N0 M0
III : T3 N0 M0 or T1-3 N1 M0
IVA : T4a N0-1 M0 or T1-4a N2 M0
IVB : T4b Any N M0 or Any T N3 M0
IVC : Any T Any N M1
Primary tumor (T) - nasopharynx
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor extends to the nasopharynx, or tumor extends to oropharynx or nasal cavity without parapharyngeal extension (denotes posterolateral infiltration of tumor)
T2: Tumor with parapharyngeal extension
T3: Tumor involves bony structures of skull base or paranasal sinuses
T4: Tumor with intracranial extension or involvement of cranial nerves, hypopharynx, orbit or with extension to the infratemporal fossa / masticator space
Regional lymph nodes (N) - nasopharynx
The distribution and the prognostic impact of regional lymph node spread from nasopharynx cancer, particularly of the undifferentiated type, are different from those of other head and neck mucosal cancers and justify the use of a different N classification scheme.
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, or unilateral or bilateral retropharyngeal lymph nodes, 6 cm or less in greatest dimension
N2: Bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
N3: Metastasis in a lymph node(s), greater than 6 cm in greatest dimension, or to supraclavicular fossa
N3a: Greater than 6 cm in dimension
N3b: Extension to the supraclavicular fossa
Notes:
● Midline nodes are considered ipsilateral
● Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma, and is the triangular region originally described by Ho. It is defined by three points:
(1) the superior margin of the sternal end of the clavicle,
(2) the superior margin of the lateral end of the clavicle,
(3) the point where the neck meets the shoulder. Note that this would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) containing tumor in the fossa are considered N3b
Distant metastasis (M) – nasopharynx
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups – nasopharynx
0 : Tis N0 M0
I : T1 N0 M0
II : T1 N1 M0 or T2 N0-1 M0
III : T1-2 N2 M0 or T3 N0-2 M0
IVA : T4 N0-2 M0
IVB : Any T N3 M0
IVC : Any T Any N M1
Primary tumor (T) – mucosal melanoma
T3: Mucosal disease
T4a: Moderately advanced local disease – tumor involving deep soft tissue, cartilage, bone or overlying skin
T4b: Very advanced local disease - tumor involving brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space or mediastinal structures
Regional lymph nodes (N) – mucosal melanoma
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastases
N1: Regional lymph node metastases present
Distant metastasis (M) – mucosal melanoma
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups – mucosal melanoma
III : T3 N0 M0
IVA : T4a N0 M0 or T3-4a N1 M0
IVB : T4b Any N M0
IVC : Any T Any N M1
Micro: striking nuclear enlargement, nuclear hyperchromasia and pleomorphism; may be full thickness or associated with squamous metaplasia
DD: dysplasia
References: AJSP 2001;25:652
At least one section per 1 cm of tumor for large tumors, including tumor center and periphery
Submit entire tumor if can do so in 5 sections or less
Submit resection margins
Submit samples of tissue from other sites
Tumor histologic type and pattern
Tumor size and location
Tumor histologic grade
Tumor extension to adjacent structures
Status of resection margins
Vascular invasion
Perineural invasion
Lymph nodes: for each level, number obtained, number involved by tumor, size of nodal metastases, presence of extracapsular spread
End of Nasal cavity, paranasal sinuses and nasopharynx chapter