Last revised 20 September 2007
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Table of contents
Primary references, normal anatomy, normal histology
Inflammatory/infectious lesions: acute laryngoepiglottitis, amyloidosis, chronic laryngitis, contact ulcer, Crohn’s disease, eosinophilic angiocentric fibrosis, fungi, histoplasmosis, nonspecific granulomas, rhinosclerosis, tuberculosis
Benign tumors: aneurysmal bone cyst, chondroma, chondrometaplasia, cysts, giant cell tumor, granular cell tumor, hemangioma, mucinosis, mucous membrane plasmacytosis, papilloma, plasmacytoma, pleomorphic adenoma, rhabdomyoma, teflonoma, verruca vulgaris, verruciform xanthoma, vocal cord polyp
Premalignant lesions: hyperplasia, verrucous hyperplasia, dysplasia
Squamous cell carcinoma: general, basaloid, glottic, hypopharynx, papillary, pyriform sinus, spindle cell, subglottic, supraglottic, transglottic, verrucous
Other carcinoma: adenoid cystic, adenocarcinoma, lymphoepithelioma-like, metastases, mucoepidermoid, neuroendocrine, small cell
Other malignancies: angiosarcoma, chondrosarcoma, liposarcoma, lymphoma, melanoma, paraganglioma, rhabdomyosarcoma
Miscellaneous: TNM staging, grossing, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), March 1977 to Oct 2004
Archives of Pathology and Laboratory Medicine (Archives), Jan 1976 to Oct 2004
Human Pathology (Hum Path), Mar 1970 to Sept 2004
Modern Pathology (Mod Path), Jan 1988 to Oct 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: larynx, vocal cord, glottic, hypopharynx, epiglottis
Please refer to these primary references for more detailed discussions and photographs
Tubular structure between pharynx/root of tongue and trachea at level of cervical vertebrae C4-C6 in males, somewhat higher in females and during childhood
Composed of cartilaginous tissue that undergoes ossification and may completely replace cartilage by age 20
At puberty, increases in size in males due to enlargement of cartilages
Cartilages are connected by ligaments and moved by numerous muscles
Staging anatomy:
Anterior limit is anterior or lingual surface of suprahyoid epiglottis, thyrohyoid membrane, anterior commissure and anterior wall of subglottic region (composed of thyroid cartilage, cricothyroid membrane and anterior arch of cricoid cartilage)
Posterior and lateral limits include laryngeal aspect of aryepiglottic folds, arytenoids region, interarytenoid space and posterior surface of subglottic space (mucous membrane covering surface of cricoid cartilage)
Superolateral limits are tip and lateral borders of epiglottis
Inferior limit is plane passing through inferior edge of cricoid cartilage
Supraglottic portion: epiglottis (lingual and laryngeal aspects), false vocal cords (ventricular bands), aryepiglottic folds (laryngeal aspect), arytenoid cartilages, ventricles; derived from third and fourth branchial pouches; inferior boundary is horizontal plane passing through lateral margin of ventricle at its junction with superior surface of vocal cord
Glottic portion: true vocal cords (superior and inferior surfaces) and anterior and posterior commissures; derived from sixth branchial pouch
Subglottic portion: between lower border of true vocal cords and first tracheal cartilage (or lower margin of cricoid cartilage); derived from sixth branchial pouch
Anterior commissure: convergence of thyroepiglottic, vestibular and vocal ligaments and conus elasticus; tendon provides anterior attachment for true vocal cords; tendon also separates glottic and supraglottic parts of larynx
Arytenoid cartilage: two hyaline cartilages at upper border of cricoid cartilage at back of larynx that support the vocal cords; each is pyramidal; apex is surmounted by small, conical, corniculate cartilage
Conus elasticus: extends from superior border of cricoid cartilage to free edge of vocal cord, then thickens to form vocal ligament, which runs length of true vocal cord close to mucosal surface, then continues along floor of ventricle as thyroglottic ligament
Diagrams: conus elasticus from above
Cricoid cartilage: hyaline cartilage that is smaller but thicker and stronger than thyroid cartilage; upper edge is 1 cm below true vocal cords at mid larynx; forms the only complete trachiobronchial ring with posterior quadrate lamina (deep and broad, 2-3 cm high) and anterior arch that is narrow and convex; articulates with inferior horns of thyroid cartilage
Cuneiform cartilages: two small, elongated pieces of cartilage on either side of aryepiglottic fold
Epiglottis: thin, bicycle saddle-like, elastic fibrocartilage
Apex is attached to inner thyroid cartilage just above anterior commissure by thyroepiglottic ligament
Projects up behind tongue and body of hyoid bone, partly covers laryngeal entrance
Sides are attached to arytenoid cartilages by aryepiglottic folds
Upper and anterior surface is free, covered by mucous membrane reflected onto pharyngeal tongue and lateral wall of pharynx to form median and lateral glossoepiglottic folds
Median glossoepiglottic fold divides area between base of tongue and epiglottis into two valleculae
Not essential for respiration, phonation or deglutition
Hyoid bone: supports thyrohyoid and hyoepiglottic ligaments; not strictly part of larynx
Hypopharynx: comprises posterolateral pharyngeal wall (from level of floor of valleculae to level of inferior border of cricoid cartilage), postcricoid esophagus (has anterior wall and extends from level of arytenoids cartilages superiorly to inferior border of cricoid cartilage) and pyriform sinuses (lie lateral to and below opening of larynx, each bounded laterally by medial aspect of thyroid lamina and medially by aryepiglottic fold)
Pre-epiglottic space: bounded posteriorly by epiglottic cartilage and thyroepiglottic ligament, anteriorly by thyroid cartilage and thyrohyoid membrane, superiorly by hypoepiglottic ligament; space communicates laterally with paraglottic space above ventricle
Pyriform sinus: not strictly part of larynx; inverted 3 sided pyramid with apex inferiorly at level of cricopharyngeus muscle, bounded superiorly by glossoepiglottic folds, medially by aryepiglottic folds, laterally by pharyngeal wall
Thyroid cartilage: largest cartilage of larynx; shield shaped forming anterior surface of larynx and acute angle in midline of neck (laryngeal prominence, Adam’s apple); originally only hyaline cartilage, but ossifies at age 25 at sites of muscle origin or insertion; lower edge is 1 cm below anterior commissure
Lymphatics: separate systems exist above and below ventricle; are also subdivided as superficial (mucosal) and deep; few lymphatics are present in true vocal cord
Pyriform sinus drains laterally into deep cervical nodes, occasionally to paratracheal nodes
Supraglottic lymphatics drain through thyrohyoid membrane into upper cervical and anterosuperior nodes
Subglottic lymphatics drain into prelaryngeal (Delphian) node on cricothyroid membrane, then into pretracheal, paratracheal and supraclavicular nodes
Diagrams: sagittal section, coronal section #1, #2, entrance viewed from above, laryngoscopic view, laryngeal cartilages #1, #2, vocal cords and muscles, muscles, ligaments #1, #2
Gross images: true and false vocal cords
Endoscopic images: (1) larynx, (2) larynx-labeled
Junction between epithelial types may be abrupt or separated by transitional area; patches of squamous epithelium in respiratory epithelium are common, particularly in smokers
Dendritic melanocytes may be present in basal layer, particularly in blacks
Epiglottis: stratified squamous epithelium similar to oral cavity, with modified salivary glands that secrete thick mucous; laryngeal surface also has pits containing mucous glands
Cartilage has full thickness fenestrae that communicate with preepiglottic “space”, which contains fat and areolar tissue
Micro images: epiglottis #1, #2, #3
False vocal cords and other supraglottic larynx: ciliated, columnar epithelium extending into ventricle of Morgagni, with submucosal modified salivary gland epithelium
Micro images: false vocal cord
Glottis: space between two vocal cords
Hypopharynx: covered by non-keratinizing stratified squamous epithelium; contains mucosal glands, scattered lymphoid aggregates, rich lymphatic plexus
Reinke’s space: lamina propria of true vocal cord, between base of squamous epithelium and vocal ligament
True vocal cords: stratified squamous epithelium with no/rare submucosal glands
Gross images: normal vocal cords
Micro images: true vocal cord, true and false vocal cords
Virtual slides: normal vocal cords
Subglottic larynx: epithelium resembles trachea/major bronchi – ciliated columnar epithelium with submucosal glands
Inflammatory/infectious lesions
Also called acute supraglottitis
Rare; due to Haemophilus influenza type B or Streptococcus pyogenes; reduced incidence due to childhood vaccine for H. influenza
May produce sudden lethal swelling of epiglottis and vocal cords
Gross: red and edematous epiglottis
Micro: acute inflammatory infiltrate with edema, extending to adjacent soft tissues
Micro images: H. influenza (gram stain)
Virtual slides: H. influenza laryngitis
Croup: laryngotracheobronchitis in children; inflammatory narrowing produces inspiratory stridor
1% of laryngeal tumors; usually asymptomatic
Mean age 38 years, more common in men
Usually localized but may be associated with multifocal disease
Does not develop into myeloma but may recur locally and occasionally cause death after a prolonged period
May be due to immunocyte dyscrasias or MALT tumor (since lymphocytes are monoclonal)
Laboratory: usually negative for monoclonal proteins by serum or urine electrophoresis
Treatment: surgical excision
Gross: polypoid or granular lesions, mean 1.6 cm
Micro: acellular amorphous eosinophilic infiltrate in stroma, often accentuated around vessels and seromucous glands; sparse lymphoplasmacytic infiltrate
Micro images: apolipoprotein AI and transthyretin amyloidosis of larynx
Additional images: (1) amyloid deposition in lamina propria; (2) perivascular (A) and periglandular (B) amyloid deposition; (3) lymphoplasmacytic infiltrates near amyloid deposition; (4) apple-green birefringence with Congo red stain and polarized light; (5) kappa light chain restriction (left-kappa, right-lambda)
Positive stains: Congo red; light chain restriction
References: Mod Path 2000;13:528, Am J Path 2000;156:1911 (apolipoprotein AI amyloidosis)
Chronic (nonspecific) laryngitis
Commonly due to upper respiratory tract infection, overuse of voice, heavy exposure to tobacco smoke or alcohol
Case reports: CMV laryngitis and probable lymphoma in AIDS patient (Archives 1992;116:539)
Micro: lymphocytic infiltrate with variable plasma cells and histiocytes; variable epithelial hyperplasia
Also called granulomatous ulcer, posterior commissure ulcer
At level of posterior commissure, near vocal process of arytenoid cartilage
May recur after local excision, but eventually subsides
Treatment: conservative (don’t excise), because surgical trauma may cause recurrence
Micro: ulcerated or hyperplastic epithelium (occasionally pseudoepitheliomatous hyperplasia), overlying exuberant granulation tissue
References: Archives 1990;114:825
May have ulcerative and granulomatous lesions in epiglottis or elsewhere in larynx
Eosinophilic angiocentric fibrosis
Rare upper respiratory tract inflammatory lesion
May be variant of granuloma faciale that occurs more commonly in nasal cavity
Case report with Wegener’s granulomatosis (J Clin Path 2001;54:640)
Micro images: perivascular fibrosis with obliteration of vascular lumina, adjacent eosinophils, lymphocytes and plasma cells
DD: Wegener’s granulomatosis
May need special stains to diagnose when inflammation or hyperkeratosis is also present (Archives 1986;110:141)
Local excision may be curative
See also Histoplasmosis, below
Case reports: Aspergillus infection with pseudoepitheliomatous hyperplasia, resembling carcinoma (Hum Path 1983;14:184)
Micro images: A: Candida infection with marked pseudoepitheliomatous hyperplasia; B: PAS+ fungi
Common cause of fungal laryngitis in US (also blastomycosis)
Early lesions are in vocal cords and epiglottis
Granulomatous lesion involving anterior larynx is likely to be histoplasmosis
Case reports: epiglottic mass in 78 year old retired soil science professor in nonendemic region (Archives 2004;128:574)
DD: laryngeal carcinoma (clinically)
Usually men, unilateral, symptomatic
Often at vocal process of arytenoid cartilage
50% post-traumatic, often post-intubation or after laryngeal biopsy
Foreign body granulomas may occur after injection of Teflon into paralyzed vocal cords
Micro: ulceration and highly cellular granulation tissue with granulomas
DD: sarcoidosis, tuberculosis, histoplasmosis
Rare; chronic granulomatous disease of 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
Slowly progressive with remission and relapse; not fatal unless it obstructs the airway
Treatment: antibiotics for months to years; possibly steroids, surgery to treat airway compromise and tissue deformity
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: supraglottic granulomas in 27 year old man from Central America (Archives 2001;125:159)
Micro: catarrhal/atrophic, granulomatous and sclerotic stages; initially squamous metaplasia and inflamed granulation tissue; later pseudoepitheliomatous squamous hyperplasia with foamy macrophages (Mikulicz cells containing bacteria), plasma cells with Russell bodies, granulomatous inflammation; 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, other granulomatous processes
May simulate carcinoma clinically
Begins with edema of posterior interarytenoid space, then spreads to epiglottis, aryepiglottic fold and vocal cords
Micro: granulomas with variable caseation necrosis
Positive stains: acid-fast
Benign tumors
Rare; <10 cases reported
Comparable to bony disease
Case reports: 22 year old man with subglottic mass (Archives 2001;125:673)
Treatment: conservative surgery; don’t recur
Micro: mononuclear and multinucleated giant cells surround cavernous spaces filled with blood; also spindle cells and mature osteoid; non-atypical mitotic figures present
DD: telangiectatic osteosarcoma (clearly malignant cells in vascular background), giant cell tumor (less cystic, more nuclei in giant cells)
Present in <1% of laryngectomies
Usually arise posteriorly from cricoid cartilage and project anteriorly, causing partial obstruction; rarely present in thyroid cartilage
Children and adults, usually 2 cm or less
Highly associated with chondrosarcoma
Some advocate treatment as chondrosarcoma due to high association
Micro: resemble normal cartilage but with lobular architecture and slightly larger nuclei, only rarely multiple nuclei; no atypia, no mitotic figures, no necrosis
DD: low grade chondrosarcoma
2% of laryngeal specimens
Gross: nodules < 1 cm, usually on vocal cords; may be multifocal
Micro: elastic rich cartilage nodules, composed of small, uniform, eosinophilic chondrocytes without nuclear abnormalities; usually no lobular pattern of hyaline cartilage; margins are indistinct with peripheral zone of transition between cartilage and surrounding tissue
Ductal (75%) or saccular (24%); lined by squamous or respiratory mucosa or both
Ductal cyst: due to dilation of mucous glands; small, superficial, usually in true vocal cord or epiglottis
Laryngocele: air containing dilation of tip of ventricle that communicates with ventricle via a narrow stalk; either internal or external or both; may become infected and accumulate pus (laryngopyocele)
Micro images: three types of laryngocele
Oncocytic cyst: type of ductal cyst lined partially or completely by oncocytes; often has papillary infoldings; may recur; rarely is diffuse within the larynx
Saccular cyst: due to distention of laryngeal saccule; large, deep, often within ventricle; may cause neonatal airway obstruction; contains mucus
Tonsillar cyst: squamous lined crypt-like structure with abundant lymphoid follicles in cyst wall
Rare; < 50 cases reported
Benign but can invade into vital structures or cause airway obstruction
Usually involves thyroid cartilage in areas of enchondral ossification, with extension into adjacent structures
Case reports: 23 year old man with 4 cm mass arising in thyroid cartilage (Archives 1994;118:834)
Treatment: excision; no recurrences reported
Micro: numerous multinucleated osteoclast-like giant cells within cellular and vascular stroma containing plump, oval mononuclear cells with nuclei similar to giant cells; expansile and infiltrative growth; frequent mitotic figures; often secondary cystic degeneration, reactive bone formation; no cytologic atypia
Micro images: (1) submucosal polypoid tumor without surface involvement; (2) reactive bone formation (left) and cystic degeneration (lower right); (3) giant cells and mononuclear cells (inset: mitotic figure); (4) osteoclast-like giant cells have nuclei similar to mononuclear cells
DD: giant cell reparative granuloma (aggregated cells, often near areas of hemorrhage, no giant cells with 20+ nuclei; more fibrotic stroma), brown tumor of hyperparathyroidism, osteoblastoma (fewer giant cells, broad sheets of mineralized osteoid), aneurysmal bone cyst, nonossifying fibroma, foreign body reaction, fibrous histiocytoma
References: Mod Path 2001;14:1209
Also called myoblastoma
May occur in children
Gross: small, yellow, covered by epithelium
Micro: nests of cells with granular and eosinophilic cytoplasm, bland small round/oval nuclei; may have overlying pseudoepitheliomatous hyperplasia
Micro images: A/B: marked pseudoepitheliomatous hyperplasia simulating invasive squamous cell carcinoma; C: S100+
Positive stains: S100, PAS
DD: invasive squamous cell carcinoma
Usually cavernous with thick walled vessels
Infants: sessile, poorly circumscribed subglottic mass, often with obstructive symptoms, and with massive hemorrhage after biopsy; 50% have skin hemangiomas
Adults: much less common, usually supraglottic
Treatment: laser therapy, systemic steroids, interferon, intralesional steroid injection
Very rare in larynx
Case reports: 3 year old boy intubated at age 2 months with recurrent respiratory infections (Hum Path 1990;21:856)
For upper aerodigestive tract cases, 2/3 were men, mean age 54 years, range 40-67 years
Affects larynx, pharynx, palate, lips, mouth, tongue and trachea
Treatment: none successful although apparently a benign process
Gross: cobblestone or warty appearance of mucosa
Micro: psoriasiform epithelial hyperplasia with dyskeratosis and dense subepithelial plasmacytosis; plasma cells are mature but diffuse and expansive
Stains: polyclonal light chains
References: AJSP 1994;18:1048
Warty outgrowths of laryngeal surface epithelium
Micro: proliferative well-differentiated squamous epithelium overlying fibrovascular cores with koilocytotic change (enlarged, often multiple, wrinkled nuclei); may have mild to moderate dysplasia (increased cellularity, loss of regularity of basal layer, hyperchromatic nuclei extending from basal to intermediate layers), mitotic activity is common; tumors in respiratory mucosa have less apparent maturation
Micro images: papilloma, inverted papilloma #1, #2
Children
Usually multiple
Occur on true vocal cords, false cords, epiglottis, subglottic area, rarely tracheobronchial tree
Recurs commonly, possibly years after excision or destruction; recurrences often cease at puberty; recurrences may be massive and rapid, leading to airway compromise and tracheostomy or laryngectomy
Associated with HPV 6 and 11 in most cases
Rarely extends into tracheostomy stoma or laryngeal soft tissue (invasive papillomatosis), rarely develops squamous cell carcinoma after radiation therapy or spreads/progresses to lower respiratory tract as papillomas or squamous cell carcinoma
Treatment: excision, electrodesiccation, laser surgery, cryosurgery; treatment may destroy vocal cords; laryngectomy if extensive involvement
Adults
Usually men, solitary
Recurrences frequently exhibit dysplasia
DD: verrucous carcinoma
Head and neck plasmacytomas uncommon in children; in adults are associated with long survival
Case reports: 12 year old girl with plasmacytoma and localized amyloidosis of larynx (Hum Path 2001;32:132)
Case reports: 40 year old woman with tumor of false vocal cord with squamous metaplasia (Archives 1986;110:245)
Has predilection for head and neck, including larynx
Treatment: local excision; usually no recurrence
Micro: cells often have cross striations, also intracytoplasmic crystal-like particles
Subtypes include adult, fetal cellular and fetal myxoid types
Teflon used to correct unilateral laryngeal paralysis; rarely infiltrates into soft tissues of neck and larynx
Micro: foreign body granulomatous reaction with birefringent material
References: Hum Path 1990;21:617
Uncommon
Case reports: 37 year old woman with HPV 6/11 in true vocal cord lesion (Archives 1991;115:895)
Micro: superficial, keratotic vocal cord lesion; has prominent keratohyaline granular layer, parakeratosis, sharp acanthotic pegs
Positive stains: HPV
DD: verrucous carcinoma
References: AJSP 1982;6:357
Case reports: child with systemic lipid storage disorder (AJSP 1989;13:309)
Also called laryngeal nodule or singer’s nodule
Noninflammatory response to injury causing hoarseness
More common in heavy smokers or singers due to inflammation, allergic or immunologic causes, possibly secondary to hemorrhage
Almost never transforms to malignancy
Treatment: excision or vocal rest
Gross: smooth, round, 1-3 mm growths on true vocal cords, often on anterior third
Gross images: laryngeal polyp
Endoscopic images: vocal cord polyp #1, #2
Micro: (a) telangiectatic polyps with stratified squamous epithelium overlying numerous thin-walled dilated vessels and fibrinous exudates in edematous mucosa, variable chronic inflammatory infiltrate, or (b) gelatinous polyps with stratified squamous epithelium, edematous submucosa containing fibrin and proliferating fibroblasts, thin walled vessels present but less than telangiectatic subtype; vessels may resemble thrombosed varices
DD: angioma (usually supraglottic, vessel walls are thicker, doesn’t respond to vocal rest)
Premalignant lesions
Also called keratosis
Usually involves true vocal cords and interarytenoid area
Associated with smokers, singers and others who use voices excessively
Gross: white thickening of involved areas; verrucous keratosis if undulating warty configuration; pachyderma larynges if extensive keratinization
Micro: when in respiratory (ciliated columnar) epithelium (false cord, ventricle, subglottic region), initially hyperplasia of reserve cells under epithelium, then replacement of epithelium by full thickness reserve cells, then complete squamous metaplasia; may have hyperkeratotic epithelium
No nuclear abnormalities are present, but underlying submucosal glands persist
Pseudoepitheliomatous hyperplasia: exuberant reactive overgrowth of squamous epithelium without atypia; may resemble invasive squamous cell carcinoma
DD: dysplasia (nuclear atypia)
Irreversible mucosal lesion of upper aerodigestive tract that tends to progress to verrucous carcinoma or conventional squamous cell carcinoma
For columnar epithelium, resembles cervical dysplasia
Associated with HPV 16 and p53 expression
Leukoplakia: clinical term describing any white lesion on a mucous membrane; usually associated with mucosal thickening and not dysplasia
Erythroplakia: clinical term describing red lesion on a mucous membrane; usually associated with dysplasia or malignancy
In smokers, for squamous epithelium, features of nuclear pleomorphism, mitotic activity, abnormal mitotic figures and stromal inflammation are associated with progression to invasive carcinoma
Keratosis: increase in surface keratin, often with prominent granular cell layer and orthokeratin (cells without nuclei) mixed with parakeratin (flat keratotic cells with pyknotic nuclei); not related to dysplasia
Dyskeratosis: abnormal keratinization of epithelial cells
Dysplasia: spectrum of abnormal epithelial maturation and cellular atypia that may or may not precede invasive carcinoma
Carcinoma in situ: full thickness dysplasia of mucosa without violation of basement membrane; same as severe dysplasia
Overall, low risk of development of invasive squamous cell carcinoma after dysplasia; for mild dysplasia, 7% develop in situ or invasive carcinoma vs. 24% with moderate dysplasia vs 25% with severe dysplasia
High risk of progression to invasive carcinoma for severe keratinizing dysplasia vs. non-keratinizing dysplasia
Treatment: mild/moderate dysplasia may be reversible; severe dysplasia requires intervention (vocal cord stripping, surgery, radiation therapy, endoscopic laser resection), as well as surveillance of entire upper aerodigestive tract
Gross: erythema of involved areas
Mild dysplasia: normal or mildly disordered basal layer with retained maturation and stratification of upper layers; mild nuclear atypia and possibly mitotic figures in basal third of epithelium; no abnormal mitotic figures; variable keratosis and chronic inflammatory infiltrate
Moderate dysplasia: moderate nuclear atypia, usually with prominent nucleoli and mitotic figures, most pronounced in lower two thirds of epithelium; cell maturation and stratification are present in upper layer; no abnormal mitotic figures; variable keratosis
Severe/high grade: marked nuclear abnormalities and loss of maturation greater than two thirds of epithelium; large atypical nuclei, some bizarre; nuclear pleomorphism is common; may have prominent nucleoli; mitotic figures high in epithelium, often abnormal
Keratinizing dysplasia: defined as lesions in which epithelial alterations are so severe that there is a high probability of progression to invasive carcinoma; includes dyskeratotic cells and mitotic figures, with variable atypical forms above basal zone, variable surface keratinization
Carcinoma in situ: full thickness nuclear abnormalities without stromal invasion; cells are usually keratinized, but may be basal-like; often lumped together with severe dysplasia; may represent peripheral portion of invasive carcinoma
Papillary carcinoma in situ: papillary fronds with a fibrovascular core covered by squamous epithelium with marked atypia
Note: invasion may occur by dysplastic cells without full thickness epithelial involvement
Micro images: (1) nonkeratinizing dysplasia: A-mild; B-moderate; C-severe/carcinoma in situ; (2) severe dysplasia-keratinizing; (3) carcinoma in situ extending into seromucous glands
References: Mod Path 2002;15:229
Squamous cell carcinoma
9,000 new cases annually in US; 40% mortality
Represents 90% of all laryngeal cancers
96% male; usually ages 40+ (but can occur in younger patients)
Major risk factors are smoking, enhanced by heavy alcohol consumption
HPV is not an early factor, but positive in 20%, usually HPV 16
EBV a factor in 40% of hypopharyngeal carcinomas (Hum Path 1999;30:1071)
Site influences histology and clinical behavior – either glottic, supraglottic or transglottic
Spread is limited by tough membranes / ligaments
Recurrence rate of 3% per year, second primary rate is 5% per year, usually in lung
Metastases to regional lymph nodes and lungs; direct extension to thyroid gland and jugular vein
Prognostic features: TNM; also tumor grade, tumor size, mitotic count, vascular invasion, margins
5 year survival by site: glottic – I: 90%; II: 85%; III: 60%; IV: <5%; supraglottic – I: 85%; II: 75%; III: 45%; IV: <5%; transglottic: 50%; subglottic: 40%
Case reports: nodal metastasis occurring post-radiation therapy with mixture of squamous cell carcinoma and rhabdomyosarcoma (AJSP 1993;17:415)
Gross: pink to gray ulcerated mass; vocal cord lesions often keratotic
Micro: invasion indicated by desmoplasia around malignant squamous cells, often with keratinization at periphery; progression of columnar epithelium areas is similar to squamous cell carcinoma of cervical or lung; progression of vocal cord tumors is similar to squamous cell carcinoma of skin or esophagus
Well, moderate or poorly differentiated, based on degree of keratinization, pearl formation, intercellular bridges, mitotic activity
Smaller tumors are usually better differentiated
Micro images: squamous cell carcinoma #1, #2, #3; microinvasive carcinoma - A: arising from carcinoma in situ; B-arising from non-dysplastic epithelium; C-invasive although no apparent violation of basement membrane; invasive carcinoma with desmoplastic response; A-nested growth pattern; B-discohesive growth; keratin granuloma associated with invasive carcinoma (B: cytokeratin stain)
Positive stains: AE1, AE3, p53 (50%, usually wild type)
References: Hum Path 1999;30:274 (HPV), Mod Path 2002;15:229
Basaloid squamous cell carcinoma
Highly malignant, median survival 18 months (for all sites in head and neck)
Heavy smokers or drinkers, often with advanced disease at diagnosis and other primary tumors in the area
Usually men, ages 50+ years
Usually base of tongue, hypopharynx or supraglottic larynx