Larynx, hypopharynx & trachea

Contributed by Jamie Brown, M.D. and Ruta Gupta, M.D.

• In situ lesions (noninvasive) can be keratinizing or nonkeratinizing

Squamous cell carcinoma

• Conventional SCC
  • Histologically, similar to conventional squamous cell carcinoma at other head and neck sites
  • Typically consists of nests of squamous cells with or without keratin pearls and intercellular bridges
• Evidence of stromal invasion is required for diagnosis: desmoplastic stromal reaction is usually present
• Tumor grading is based on resemblance to normal squamous epithelium
• WHO diagnostic criteria
  • Essential: a malignant epithelial neoplasm with evidence of squamous differentiation and stromal invasion
  • Evidence for squamous differentiation: keratinization with keratin pearls or the presence of intercellular bridges; immunohistochemistry may be required for poorly differentiated tumors

Verrucous (Head Neck Pathol 2011;5:23)

• Infoldings of well differentiated squamous epithelium with abundant surface keratinization
• Densely eosinophilic cytoplasm
• Low mitotic rate
• Pushing borders and generally absent desmoplastic stromal reaction
• Prominent lymphoplasmacytic infiltrate usually present
• Presence of any high grade dysplasia or a minor component of conventional SCC warrants a diagnosis of hybrid verrucous SCC or invasive well differentiated SCC with verrucous features (ICD-O: 8070/3)
• WHO diagnostic criteria
  • Essential: acanthotic, hyperkeratotic and undulating squamous epithelium; bulbous keratotic crypts (elephant feet)
  • Smooth interface with the stroma with pushing invasion below the level of the surrounding normal epithelium
  • Cytologically bland squamous epithelium
  • Mitoses limited to basal / parabasal layers

Papillary SCC

• Papillary architecture composed of branching fibrovascular cores lined by stratified squamous epithelium with or without keratinization
• Epithelium lining papillae show marked dysplasia, with little or no maturation and a high N:C ratio (Head Neck Pathol 2011;5:23)
• WHO diagnostic criteria
  • Essential: exophytic growth composed predominantly of papillary fronds with fibrovascular cores covered by a nonkeratinizing malignant stratified squamous epithelium or in the keratinizing type, by high grade atypia
  • Desirable: stromal infiltration

Basaloid

• Lesional cells resemble the basal layer of stratified squamous epithelium; tumor cells have basophilic chromatin and a high N:C ratio and are usually arranged in nests with peripheral palisading (Head Neck Pathol 2011;5:23)
• Solid and cribriform growth patterns are also common
• Tumors usually have a high mitotic rate and necrosis is frequently seen
• WHO diagnostic criteria
  • Essential
    • Tumor with prominent basaloid morphology
    • Presence of squamous differentiation
    • Absence of neuroendocrine or myoepithelial differentiation by histology or immunohistochemistry
  • Desirable
    • High grade histological features
    • Myxoid to hyaline stromal alterations

Adenosquamous

• Conventional SCC component and adenocarcinoma; may be juxtaposed or admixed
• Conventional SCC component may show keratinization
• Adenocarcinoma component composed of glands arranged in a tubular of cribriform configuration
• Necrosis is common
• Perineural and lymphovascular space invasion is frequently seen
• Special stains (e.g., PAS, Alcian blue) will highlight mucin in the adenocarcinoma component
• WHO diagnostic criteria
  • Essential: biphasic tumor with squamous and glandular components that are distinctly recognized adjacent to each other on H&E examination
  • Desirable
    • Evidence of origin from surface epithelium (e.g., squamous dysplasia)
    • Mucin production

Spindle cell

• Spindle cells with overt features of malignancy such as pleomorphism, high mitotic rate, atypical mitoses
• May contain a conventional SCC component or intraepithelial dysplasia
• Heterologous differentiation may be present
• WHO diagnostic criteria
  • Essential: a mucosa based carcinoma with a malignant spindle cell component
  • Desirable
    • Polypoid tumor
    • Intraepithelial dysplasia
    • Invasive conventional SCC
    • Immunoreactivity for cytokeratin or p63 / p40 (in selected cases)

Lymphoepithelial

• Syncytial growth with a prominent lymphoplasmacytic infiltrate: may obscure tumor cells
• Solid or nested growth pattern
• Tumor cells usually have prominent nucleoli and a high mitotic rate
• Conventional SCC component may be present
• WHO diagnostic criteria
  • Essential
    • Tumor with syncytial growth
    • Inflammatory infiltrate
    • Vesicular chromatin
    • Prominent nucleoli
  • Desirable
    • Positivity for pankeratin and squamous markers (e.g., p40, CK5/6)
    • Exclusion of direct extension or metastasis

• References: Goldblum: Rosai and Ackerman's Surgical Pathology, 11th Edition, 2017, Longacre: Mills and Sternberg's Diagnostic Surgical Pathology, 7th Edition, 2022

Contributed by Jamie Brown, M.D. and Ruta Gupta, M.D.

Well to moderately differentiated conventional SCC

• Pseudoepitheliomatous hyperplasia:
  • Overlying necrotizing sialometaplasia, granular cell tumor or infection
  • Generally seen in the setting of inflammation; granulomas or giant cells may be present
  • Identification of underlying causes
• Verrucous SCC:
  • Broad tongues of invasion below the adjacent normal epithelium
  • Prominent keratinization
  • Lacks significant atypia
• Papillary SCC:
  • Exophytic growth of papillary fronds with fibrovascular cores

Poorly differentiated conventional SCC

• Malignant melanoma:
  • S100 and other melanoma IHC markers positive
  • Negative p40 / p63 negative
• Lymphomas, particularly diffuse large B cell lymphoma:
  • CD45 positive
  • Cytokeratin and p40 / p63 negative
• Neuroendocrine neoplasms:
  • Chromogranin, synaptophysin and INSM1 positive
  • p40 / p63 negative

Papillary

• Verrucous SCC:
  • Lacks significant cytological atypia and prominent keratinization
• Laryngeal papilloma:
  • Lacks cytological atypia; lack of stromal infiltration (not required for papillary SCC diagnosis)

Verrucous SCC

• Verrucous hyperplasia:
  • Histologically identical but lacks invasion
• Well differentiated conventional SCC:
  • Irregular, infiltrative growth and more cytological atypia

Basaloid SCC

• Adenoid cystic carcinoma:
  • No significant pleomorphism, no mitotic activity and no squamous differentiation
• Small cell carcinoma:
  • Positive neuroendocrine markers

Adenosquamous

• Conventional SCC or basaloid SCC with entrapped nonneoplastic glands
  • Lobular architecture and bland morphology of entrapped of glands
• Mucoepidermoid carcinoma (MEC):
  • Lack of in situ component
  • Lacks true squamous differentiation (instead has intermediate cells)
  • Lacks MAML2 translocation (FISH)

Spindle SCC

• Stromal reaction in conventional SCC, especially following radiotherapy:
  • p63 / p40 negative
• Other sarcomas (e.g., chondrosarcoma):
  • Lack of cytokeratin / p40 / p63 expression
  • Lack of in situ or conventional component
• Inflammatory myofibroblastic tumor:
  • SMA positive, ALK positive (50 - 60%)
  • May have focal keratin staining
  • p63 / p40 negative

Lymphoepithelial carcinoma

• Large cell lymphomas (e.g., diffuse large B cell lymphoma):
  • Lack of cytokeratin reactivity
  • Positive for lymphoid markers (e.g., CD45)
• Metastatic / locally advanced nasopharyngeal carcinoma:
  • Clinical correlation
  • EBV positive

The image above shows an invasive lesion present on the larynx of a 52 year old man. Which of the following is true?

1. The patient is likely to be a past or current smoker
2. The patient is likely to have a family history of laryngeal cancer
3. The patient is likely to have had a high risk HPV infection in the past
4. The patient is likely to have had an EBV infection in the past
5. The patient is likely to have poorly controlled diabetes

A. The patient is likely to be a past or current smoker. Laryngeal squamous cell carcinoma (SCC) is strongly associated with smoking. Answer C is incorrect because unlike mucosal SCC at other head and neck sites, laryngeal SCC is not generally associated with HPV infection. Answer D is incorrect because laryngeal SCC is not associated with EBV infection. Answer E is incorrect because laryngeal SCC is not associated with diabetes. Answer B is incorrect because most laryngeal SCC cases are sporadic.

Comment Here

Reference: Squamous cell carcinoma of larynx

The image above shows an incisional biopsy of a suspicious lesion from a false vocal cord in a 62 year old man. The lesion is centered in the glottis and extends superiorly. Which of the following is true about regional node involvement in this case?

1. Can be excluded due to the glottic location of the tumor
2. Less likely as the micrograph shows HPV associated SCC
3. Less likely due to the involvement of supraglottic structures
4. More likely due to the involvement of supraglottic structures
5. Unlikely as the micrograph shows the verrucous subtype

D. More likely due to the involvement of supraglottic structures. The micrograph shows conventional invasive squamous cell carcinoma. We are told that the lesion is centered on the glottis, which has a poor lymphatic supply. Supraglottic structures, such as the false vocal cords, have better lymphatic supply and their involvement increases the risk of regional node involvement. Answer B is incorrect because HPV status has not been shown to affect the risk of regional node involvement in laryngeal squamous cell carcinoma. Answer C is incorrect because supraglottic structures have a better lymphatic supply than the glottis (on which the tumor is centered) and therefore increase the risk of regional node involvement. Answer E is incorrect because the micrograph shows conventional SCC with irregular infiltrative nests as opposed to the broad invasive front of verrucous SCC. Answer A is incorrect because regional lymph node involvement cannot be excluded on the basis of an incisional biopsy, regardless of the location.

Comment Here

Reference: Squamous cell carcinoma of larynx