Skin-tumor
Last revised 18 May 2008
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Benign (nonmelanotic) epidermal tumors or tumor-like lesions: clear cell papulosis, cutaneous horn, fibroepithelial polyp, large cell acanthoma, melanoacanthoma, pseudoepitheliomatous hyperplasia, seborrheic keratosis, verrucous hyperplasia
Cysts: apocrine cystadenoma, bronchogenic cyst, cystadenoma, dermoid cyst, hidrocystoma, keratinous cyst, pigmented follicular cyst, steatocystoma, vellous hair cyst
Adnexal tumors: general
Apocrine glands: general, apocrine tubular adenoma, hidradenoma papilliferum
Eccrine sweat glands: acrosyringeal adenomatosis, aggressive digital papillary adenoma, chondroid syringoma, clear cell acanthoma, cutaneous lymphadenoma, eccrine acrospiroma, eccrine cylindroma, eccrine poroma, eccrine spiradenoma, intraepidermal epithelioma, mucinous carcinoma, myoepithelioma, papillary eccrine adenoma, papillary syringadenoma, sclerosing sweat duct carcinoma, sweat gland carcinoma, syringoma
Hair follicles: folliculofibroma, inverted follicular keratosis, keratinous cyst, keratoacanthoma, pilar tumor, pilomatrixoma, trichilemmoma, trichoepithelioma, trichofolliculoma, warty dyskeratoma
Sebaceous glands: nevus sebaceous of Jadassohn, sebaceous adenoma, sebaceous carcinoma, senile sebaceous hyperplasia
Premalignant/in situ: carcinoma in situ-general, actinic keratosis, bowenoid papulosis, Bowen’s disease, Paget’s disease
Carcinoma (non adnexal): adenoid cystic carcinoma, adenoid squamous cell, adenosquamous, basal cell, lymphoepithelioma-like, Merkel cell, metastatic, mucoepidermoid, small cell, spindle squamous cell, squamous cell, verrucous carcinoma, staging
Nevi: general, active, balloon cell, Becker’s, blue, cockarde, combined, compound, congenital, dermal, dysplastic, halo, Ito’s, junctional, lentiginous, Mongolian spot, Ota’s, Spitz, Sun’s
Melanoma: general, desmoplastic, minimal deviation, pigmented epithelioid melanocytoma, sentinel node biopsy, Breslow, Clark’s levels, features to report, staging
Other melanocytic lesions: general, atypical melanocytic hyperplasia, café-au-lait spot, ephelis, hyperpigmentation, paraganglioma-like dermal melanocytic tumor, solar lentigo, vitiligo
Lymphoma and related disorders: general, acute lymphoblastic, anaplastic large cell, angiocentric, blastic NK leukemia / lymphoma, diffuse large B cell, follicular, Hodgkin’s, HTLV-1, intravascular, Jessner’s lymphocytic infiltration of skin, leukemia, lymphoid hyperplasia, lymphomatoid papulosis, mantle zone, mast cell disorders, mycosis fungoides, NK/T cell, peripheral T cell, primary cutaneous (general), Woringer-Kolopp disease
Vascular tumors: acquired angioma, angiosarcoma, bacillary angiomatosis, benign hemangioendothelioma, benign lymphangioendothelioma, glomus, hemangioma, hemangioendothelioma and subtypes, intravascular papillary endothelial hyperplasia, Kaposi’s sarcoma, Kimura’s disease, lymphangioma, pyogenic granuloma, reactive angioendotheliomatosis, vascular leiomyoma, verruga peruana
Other tumors of skin: angiofibroma, atypical fibroxanthoma, benign cystic teratoma, benign fibrous histiocytoma, collagenous fibroma, dermatofibrosarcoma protuberans, dermatomyofibroma, endometriosis, epithelial sheath neuroma, granular cell tumor, hamartoma of scalp, histiocytoma, inclusion body fibromatosis, inflammatory pseudotumor, keloid, Langerhans cell histiocytosis, leiomyoma, leiomyosarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, meningioma, meningioma-like tumor of skin, neurofibroma, neurothekeoma, palisaded encapsulated neuroma, perineurioma, pleomorphic fibroma, schwannoma, sclerosing fibroma, sinus histiocytosis with massive lymphadenopathy, striated muscle hamartoma, supernumerary digit, xanthoma, xanthogranuloma
Go to Skin-nontumor chapter
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), January 2003 to February 2005
Archives of Pathology and Laboratory Medicine (Archives), Jan 2005 to February 2005 (must do cutaneous)
Human Pathology (Hum Path), Feb 2004 to December 2004 (must do cutaneous)
Modern Pathology (Mod Path), Jan 2003 to January 2005 (must do cutaneous)
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Journal search terms: skin, epidermis, dermis, cutaneous
Benign nonmelanotic epidermal tumors / tumor-like lesions
Children 0-3 years
Gross: small white maculopapular lesions
Micro: large pale cells (Toker’s cells), single or in clusters
Positive stains: CEA, EMA, low molecular weight keratin
DD: Paget’s disease
Also called cornu cutaneum
Usually caused by actinic keratosis, also verruca, seborrheic keratosis, inverted follicular keratosis, squamous cell carcinoma
Gross: protruding skin lesion composed or keratin and resembling a horn
Micro: usually epidermal type keratin (with granular layer); occasionally has trichilemmoma-like features (no granular layer but deep red granules)
Also called acrochordon, squamous papilloma, skin tag, soft fibroma
Common, non-neoplastic, no clinical significance
Ages 40+ years; usually face, neck, trunk, intertriginous areas
Associated with diabetes, intestinal polyposis; increase during pregnancy
May be a common endpoint of various processes, including seborrheic keratosis or warts
Acquired (digital) fibrokeratoma: collagenous protrusions covered by hyperkeratotic epithelium, often at interphalangeal joints; dermis lacks adnexae
Gross: soft, flesh-colored, baglike tumor, attached to skin by slender stalk
Micro: papillary, fibrovascular cores covered by squamous epithelium; may have ischemic necrosis due to torsion
Sun exposed skin, usually cheek or forehead
Benign, although may be related to actinic keratosis
Gross: light-tan to dark brown macule
Micro: atrophic, acanthotic or verrucous epidermis; hyperpigmented basal layer with rounded contour of rete ridges; larger than usual keratinocytes (large nuclei and cytoplasm) compared to adjacent normal epidermis; no atypia
May be a pigmented variant of seborrheic keratosis
Benign
Micro: resembles seborrheic keratosis but with prominent, dendritic melanocytes with abundant melanin granules; melanocytes are scattered throughout the lesion; no atypia
Pseudoepitheliomatous hyperplasia
Due to reparative changes associated with ulcer, trauma, chronic irritation, North American blastomycosis, tuberculosis, syphilis, granular cell tumor, Spitz nevi, melanoma
Micro: deep tongues of epithelial cells that may appear invasive but are thin, elongated, anastomosing and surrounded by inflammatory cells (acute/subacute); also dermal fibrosis and vascular proliferation; no/rare atypia
DD: squamous cell carcinoma (thicker strands, atypia, usually no prominent inflammatory infiltrate)
Common; usually age 40+ years
Benign, although may coexist with malignancy
Usually affects trunk, head and neck, extremities; only hair bearing skin
Not HPV related, although HPV present in morphologically similar cases of epidermodysplasia verruciformis and bowenoid changes
Dermatosis papulosa nigra: in blacks
Leser-Trelat sign: sudden appearance or increase in number and size of seborrheic keratoses, associated with internal malignancy
Treatment: superficial curettage, freezing
Gross: exophytic, sharply demarcated, pigmented lesions that protrude above surface of skin, appear to be stuck to skin, single or multiple, soft, tan-black
Micro: basal keratinocyte proliferations
Patterns: acanthotic – most common, rounded verrucous surface; thick layer of basal cells mixed with horn cysts (contain keratin) and pseudohorn cysts (downgrowth of keratin into tumor mass); no prominent granular layer; some cells contain melanin due to transfer from neighboring melanocytes
irritated – pronounced squamous metaplasia with abundant eosinophilic cytoplasm and whorled squamous eddies; often atypia and mitotic figures; resembles carcinoma
inverted follicular keratosis – irritated seborrheic keratosis that grows downward and involves hair follicles
Also hyperkeratotic, adenoid, acantholytic and desmoplastic patterns
Positive stains: low molecular weight keratin
Negative stains: high molecular weight keratin (usually), HPV
DD: squamous cell carcinoma (particularly desmoplastic pattern)
Papillomatosis associated with hyperkeratosis
Benign
Nonspecific change, associated with various entities
Epidermal nevus: if present since birth or early childhood; higher risk for basal cell carcinoma or adnexal tumors
Nevus sebaceous of Jadassohn: associated with malformed adnexal structures (see below)
Verruca vulgaris: exophytic growth with marked hyperkeratosis, focal parakeratosis, papillomatosis resembling church spires, prominent granular layer, koilocytosis, dilated vessels within papillary dermis
Cysts
Usually face, solitary or multiple
Lined by sweat duct-like epithelium which may have apocrine features
Lesion of suprasternal notch, discovered shortly after birth
Probably derived from branchial clefts, not bronchi
Micro: lined by bronchial (pseudostratified, ciliated columnar) epithelium
Also called cutaneous ciliated cyst
Usually extremities of teenage girls
May have mullerian derivation, although rarely described in males
Micro: cylindrical cells with cilia
Resemble keratinous cysts of epidermal type, but also have hair adnexae
Usually face of children along embryonic closure lines
Usually face, solitary or multiple
Lined by two rows of sweat duct-like epithelium which may have apocrine features
Keratinous cyst
See below
Hyperpigmented lesion with epidermal-type keratinization, contains laminated keratin, pigmented hair shafts, some growing hair follicles
Solitary (simplex, often scrotal) or disseminated (steatocytoma multiplex, autosomal dominant, dermal nodules 1-3 mm of upper arms, axilla, scrotum and presternal skin)
Gross: cysts contain clear fluid
Micro: cyst with elaborate inner folding of cyst wall with undulations of thin layer of stratified squamous epithelium resembling ductal portion of sebaceous gland; also lobules of sebaceous glands and small hair follicles
Children and young adults
Small, multiple cysts over chest wall and extremities
Micro: cyst lined by flattened, follicular sheath epithelium; contains numerous vellous hairs and soft keratinous material in lumen
Adnexal tumors
Usually differentiate only along one adnexal line, but there may be divergent differentiation within 1 or more tumors within the same patient
Algorithms (from Sternberg)
Cystic lesions:
(a) glandular lesions are hidrocystoma (two rows of cells) or cutaneous ciliated cyst (cylindrical cells with cilia)
(b) lesions with squamous keratinization are trichilemmal cysts, pilomatricoma, steatocytoma (sebaceous lobules in wall), vellous hair cyst (hair shafts in lumen), epidermoid cyst (contains lamellated keratin), dermoid cyst (adnexal structures in wall), trichofolliculoma (radiating immature hairs) or warty dyskeratoma (acantholytic dyskeratosis)
Basaloid tumors:
Trichoepithelioma / trichoblastoma (ribbons of basaloid cells, cysts and fibroblastic stroma), trichofolliculoma (mature and immature hair follicles), cylindroma (jigsaw-puzzle appearance with thickened basement membrane), spiradenoma (basaloid cells with 2 cell types), sebaceous adenoma or carcinoma, eccrine poroma (large nodules connected to epidermis), eccrine acrospiroma (large dermal nodules), pilomatricoma (ghost cells)
Squamoid tumors:
(a) solid lobules of eosinophilic cells are pilar sheath acanthoma (connected to crater-like cavity) or acrospiroma (not connected to crater-like cavity)
(b) lobules with clear cells are acrospiroma (luminal differentiation), trichilemmoma (epidermal connection, peripheral palisading, thick basement membrane) or sebaceous tumors
(c) lobules of squamous cells with central keratinization are proliferative trichilemmal tumor
Glandular tumors:
(a) apocrine differentiation: papillary hydradenoma (papillary fronds, vulvar/perianal) or tubular apocrine adenoma (epidermal connection)
(b) syringoma: small ducts with 2 rows of cells
(c) papillary eccrine adenoma: cystic ducts and papillary fronds
(d) papillated ducts open to epidermis: papillary syringadenoma (scalp) or nipple adenomatosis (nipple)
(e) mixed tumor (chondroid syringoma): chondromyxoid stroma and tubular or anastomosing glands
(f) sebaceous hyperplasia (lobular arrangement around a central duct), adenoma or carcinoma
Adnexal tumors-apocrine glands
Adnexal tumors of apocrine glands - general
Eccrine sweat gland tumors may exhibit apocrine differentiation
Pure apocrine tumors are rare
Micro: lobular pattern of dermal and subcutaneous tubular apocrine structures with epidermal connection; resembles papillary syringadenoma
Also called papillary hydradenoma
Perianal or vulvar
Micro: papillary fronds, ducts lined by apocrine type cells which show decapitation secretion and fibrous stroma
Adnexal tumors-eccrine sweat glands
Also called eccrine syringofibroadenoma
Gradual and symmetric spread of papular lesions over large areas of body
Micro: diffuse proliferation of acrosyringium-related cells in epidermis and dermis
Aggressive digital papillary adenoma
Usually digits
Recurs locally
Malignant counterpart has poor glandular differentiation, necrosis, atypia, invasion; metastasizes to lung in many cases
Micro: tubuloalveolar and ductal structures, also areas of papillary projections protruding into lumina (may resemble breast carcinoma)
Also known as mixed tumor of skin
Usually benign
Face, head, neck, extremities, trunk or back
May have areas of apocrine, follicular and sebaceous differentiation
Gross: nodular, circumscribed, nonulcerated
Micro: myoepithelial and epithelial type cells, some with abundant hyaline cytoplasm, in chrondomyxoid stroma; may have eosinophilic globules with radiating fibrillary structures around their lumina, similar to mammary collagenous spherulosis
Positive stains: inner epithelial layer - keratin, EMA, CEA; outer myoepithelial layer – vimentin, S100, NSE; variable smooth muscle actin, GFAP
Apocrine mixed tumors
Epithelial component is branching tubular structures with two cell layers; inner layer is columnar with eosinophilic cytoplasm, “decapitation” type secretion, often squamous metaplasia and basal nuclei
Legs of females, may be multiple
Acanthoma: benign tumor of epidermal keratinocytes
Gross: moist flat plaque
Micro: intraepithelial tumor of clear keratinocytes with dermal inflammation and abrupt transition to normal epidermis; may have melanocytic proliferation, psoriasiform acanthosis, parakeratosis
Positive stains: glycogen
DD: seborrheic keratosis
May be related to eccrine spiradenoma
Micro: multiple rounded lobules of basaloid cells with some peripheral palisading, focal keratinization, occasional duct formation, mixed with small lymphocytes
Also called solid-cystic or nodular hidradenoma
Arises from sweat gland distal excretory duct
Gross: nodules with cystic foci high in dermis
Micro: nests/lobules of cells resembling eccrine poroma with either clear cytoplasm or prominent squamous metaplasia; may have marked vascularity
Positive stains: keratin, EMA, CEA, S100, vimentin
DD: glomus tumor (different staining pattern)
Also called turban tumor, particularly when a large, multicentric scalp tumor
Somewhat common; solitary, small, slow growing adenoma, 90% in head and neck
Usually ages 40+ years, 90% women
Rarely associated with similar tumors in major salivary glands
Familial form (turban tumor syndrome, Brooke-Spiegler syndrome): autosomal dominant, multiple tumors of children / teenagers that may also involve trunk and extremities, or in association with spiradenoma, trichoepithelioma, milia or membranous variant of basal cell adenoma of salivary glands; due to mutations in CYLD gene at #16q12-13
Rarely undergoes malignant transformation
Spiradenocylindromas: features of cylindroma and eccrine spiradenoma; usually painful
Gross: pink-red dome-shaped nodule with smooth surface
Micro: compact nests of basaloid cells that fit together like a jigsaw puzzle, surrounded by thick basement membrane
Molecular: mutation in CYLD gene in #16 associated with multiple cylindromas
EM: differentiation towards intradermal coiled duct region of eccrine sweat glands
Palms and soles, also other sites
Benign, although eccrine porocarcinomas also exist
May be a subtype of eccrine acrospiroma
Gross: “moat and hillock” pattern
Micro: cords and nests of small keratinocytes attached to the epidermis; nests are sharply delimited from adjacent epidermis; also ducts and sharply delimited islands of squamous epithelium; either intraepidermal (“hydroacanthoma simplex”), intradermal (“dermal duct tumor”) or mixed (most common); dermis has reactive vessels and inflammatory infiltrate; also heavily pigmented variants
Positive stains: EMA
EM: features of eccrine gland acrosyringium
DD: basal cell carcinoma, seborrheic keratosis, acrosyringeal adenomatosis
Malignant eccrine poroma
Also called porocarcinoma
Most common sweat gland carcinoma
Usually lower extremities, may be pedunculated
Recurs locally, also metastasizes to regional lymph nodes
Micro: malignant eosinophilic and clear cells in lobular masses or islands with cystic cavities due to extensive necrosis; eosinophilic cells are polyhedral or fusiform with variable cytoplasm, hyperchromatic nuclei, distinct nucleoli, indistinct cell boundaries; clear cells are large and polyhedral with abundant clear cytoplasm and distinct cell borders; resembles eccrine poroma, but with obvious atypia and frequent mitotic figures; also epidermotropism resembling Paget’s disease; variable squamous differentiation, clear cell change and pigmentation
Either horizontal pattern (intraepidermal, like superficial spreading melanoma) or nodular (into dermis, like nodular melanoma)
DD for horizontal pattern: intraepidermal poroma (no atypia), seborrheic keratosis (no atypia), Bowen’s disease (more atypical keratinocytes, more severe architectural abnormalities), Paget’s disease (large cells, clear cytoplasm, mucin+)
DD for nodular pattern: squamous cell carcinoma (prominent keratinization, keratin pearls, no cystic cavities), sebaceous carcinoma (clear cells with bubbly cytoplasm), proliferating trichilemmal tumors (solid and cystic, well demarcated with palisading of peripheral layer), metastatic renal cell or other clear cell tumors, balloon cell melanoma
Extremely painful lesions, anywhere in body
Rarely transforms to high grade malignancy
Micro: sharply circumscribed, lobular adenomas; very cellular; cells have scant cytoplasm; high vascularity; variable T cells
Micro images: contributed by Dr. Amy Lynn, Toledo, Ohio - image
EM: epithelial and myoepithelial cells
DD: synovial sarcoma, metastatic carcinoma, thymoma, cutaneous lymphadenoma
Intraepidermal epithelioma of Borst-Jadassohn
Heterogeneous group of disorders, including irritated seborrheic keratosis, eccrine poroma and other intraepidermal sweat gland tumors
Also called adenocystic carcinoma
Scalp of elderly patients
Micro: resembles mammary colloid carcinoma with lakes of mucin containing small tumor cell clusters; may also have an infiltrating ductal pattern
DD: metastatic carcinoma
Tumors with myoepithelial cells but no epithelial cells
Usually benign lesions of extremities, but should be completely excised
May recur locally, rarely metastasize
Usually male, mean age 22 years (range 10-63 years)
Part of a continuum with mixed tumors (ductal structures but few myoepithelial cells)
Mitotic activity may predict more aggressive tumor
Gross: mean 1 cm, range 0.5 to 2.5 cm
Micro: well circumscribed dermal lesions, not connected to epidermis, may extend into superficial subcutis; either composed of (a) solid proliferation of ovid, spindled, histiocytoid or epithelioid cells with abundant eosinophilic syncytial cytoplasm and little stroma; or (b) reticular architecture with epithelioid, plasmacytoid or spindle cells in myxoid or hyalinized stroma; cells have ovoid/spindled nuclei, mild pleomorphism, small necrotic areas, fatty metaplasia, minimal mitotic figures (0-6/10 HPF), no ductal differentiation
Positive stains: required for diagnosis by Fletcher - (a) EMA+ or keratin+ and (b) S100 and (c) GFAP (50%) or muscle markers calponin, smooth muscle actin (57%) or muscle specific actin (HHF)
DD: benign mixed tumor, epithelioid benign fibrous histiocytoma (lower limbs, circumscribed, polypoid, plump and often binucleate epithelioid cells, may entrap dermal collagen, keratin-, myogenic markers-, S100-), Spitz nevus (large epithelioid melanocytes with prominent nucleoli, junctional component, downward maturation, HMB45+, S100+, EMA-, keratin-, myogenic markers-), epithelioid sarcoma (distal extremities of young adults, infiltrates along fibrous septa and fascial planes, discontinuous growth, S100-, GFAP-), cellular neurothekeoma (nested architecture, sclerotic dermal collagen, NKI-C3+, S100-, EMA-, keratin-), leiomyoma
References: Hum Path 2004;35:14
Myoepithelial carcinoma
Severe cytologic atypia and high mitotic rate
Usually distal extremities of blacks
Recur locally, don’t metastasize
Micro: eccrine duct-like structures, often dilated and with intraluminal papillomatosis
EM: differentiation towards secretory epithelium of sweat glands
DD: low grade eccrine carcinoma
Warty tumor of scalp, neck and face
Any age
Slow growing or a recent change in an apparent birthmark
1/3 have adjacent nevus sebaceous, 10% have adjacent basal cell carcinoma
Eccrine syringofibroadenoma: with prominent fibrous stroma
Syringocystadenocarcinoma papilliferum: malignant counterpart
Micro: glandular papillary proliferation connected to skin surface, dense plasma cell infiltrate
Positive stains: plasma cells are IgA+, IgG+
Sclerosing sweat duct carcinoma
Also called microcystic adnexal carcinoma
Slow growing nodule or plaque, usually on upper lip or face
Commonly recurs, metastases very rare
Micro: cords and nests of bland keratinocytes, keratin cysts and ductal differentiation; dense collagenous stroma; is invasive, may extend into subcutis or perineurial spaces; resembles syringoma; rarely is sebaceous differentiation
Uncommon
Usually adults
Difficult to diagnose; may be life threatening
Low grade: microcystic carcinoma, adenoid cystic carcinoma, mucinous carcinoma, extramammary Paget’s disease, mucoepidermoid carcinoma
Intermediate grade: ductal adenocarcinoma, aggressive digital papillary adenocarcinoma, acrospirocarcinoma
High grade: porocarcinoma, clear cell acrospirocarcinoma
Unknown grade: signet ring cell carcinoma, papillary syringadenocarcinoma
Includes malignant eccrine poroma (most common), mucinous carcinoma, sclerosing sweat duct carcinoma; also malignant chondroid syringoma (malignant mixed tumor), malignant myoepithelioma, malignant dermal cylindroma, malignant syringoma (syringoid eccrine carcinoma), malignant acrospiroma, aggressive digital papillary adenocarcinoma, apocrine carcinoma, adenoid cystic carcinoma, mucinous syringometaplasia
Benign sweat gland tumors can also undergo malignant transformation to high grade carcinoma
Micro: may resemble breast carcinoma, renal cell carcinoma, basal cell carcinoma
Positive stains: GCDFP-15, estrogen receptor, keratin, EMA, CEA
Negative stains : actin
DD: metastatic breast carcinoma, renal cell carcinoma
Multiple, yellow, papulonodular lesions on lower eyelids of women
Also face and neck, vulva, dorsal proximal and middle phalanges of hand or eruptive forms (below)
Appears to derive from sweat duct ridge
Micro: upper dermal clusters of small ducts lined by two layer thick epithelium, occasionally with comma shaped extensions; may have clear cells (due to glycogen); not infiltrative, no atypia, no mitotic figures, no local destruction
EM: eccrine origin
DD: basal cell carcinoma
Eruptive syringoma
Neck, anterior trunk, axilla, shoulder, anterior surfaces of arms, abdomen or pubic areas of young men or women
May be reactive, not neoplastic
Syringomatous carcinoma
Infiltrative epithelial tumors resembling syringomas
Micro: tubules, keratinizing cystic structures, islands and cords within desmoplastic stroma; involve epidermis and diffusely infiltrates dermis
DD: syringoma (usually multiple, limited to upper dermis, not infiltrative, no atypia, no mitoses, no local destruction), syringomatous carcinoma of salivary glands (in oral mucosa not skin)
Adnexal tumors-hair follicles
See also cysts (above)
Associated with Birt-Hogg-Dube’ (BHD) syndrome (autosomal dominant, multiple folliculomas on head and neck, acrocordons and trichodiscomas; also renal cell carcinoma [various types], renal oncocytoma and oncocytic hybrid tumors, lung cysts and spontaneous pneumothorax)
Human gene at 17p11.2 encodes folliculin, normally expressed in skin and adnexae; frameshift mutations occur in BHD causing premature protein termination
Tumor considered a hamartoma of hair follicle
Gross: skin papules
Micro: thin epidermal strands originating from a central hair follicle with prominent connective tissue
References: Mod Path 2004;17:998 (mRNA expression of Birt-Hogg-Dube’ mRNA)
Eyelid or face of elderly
May be irritated seborrheic keratosis, irritated verruca vulgaris or keratotic lesion of infundibular region of hair follicle
Gross: single nodule or papule projecting above skin surface
Micro: well circumscribed with squamous eddies containing an inverted papillomatous and acanthotic component; no inflammation
Most probably arise from infundibular portion of hair follicles
Clinically called (incorrectly) sebaceous cyst
Lesions of palm, sole or other sites may contain HPV 57 or 60
Cysts contain keratin and lipid debris from sebaceous secretions
Cysts may be painful if ruptured
Epidermal (epidermoid) type: also called infundibular cyst; lined by keratinized epithelium with distinct granular layer, contain lamellated keratin but no calcification; may have seborrheic keratosis-like changes in cyst wall
Trichilemmal (pilar) type: also called isthmus-catagen cyst; often on scalp, has trichilemmal-type keratinization (sudden keratinization without a granular layer), uneven boundary between keratinized and non-keratinized cells; non-lamellated keratin within the cyst, often with nucleated cells, often calcified
May represent proliferation of infundibular portion of hair follicle (since keratinization occurs without a granular cell layer), or a subtype of well differentiated squamous cell carcinoma
80% males, usually sun exposed skin of face; younger age group than squamous cell carcinoma of skin
Familial cases may be multiple