Larynx and hypopharynx

Last revised 20 September 2007

Copyright (c) 2004-2007, PathologyOutlines.com, Inc.

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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

 

 

Primary references

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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

 

Normal anatomy

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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 sectioncoronal section #1#2entrance viewed from abovelaryngoscopic viewlaryngeal cartilages #1#2vocal cords and musclesmusclesligaments #1#2

Gross images: true and false vocal cords

Endoscopic images: (1) larynx, (2) larynx-labeled

 

Normal histology

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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

Acute laryngoepiglottitis

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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

 

Amyloidosis

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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

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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

 

Contact ulcer

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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

 

Crohn’s disease

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May have ulcerative and granulomatous lesions in epiglottis or elsewhere in larynx

 

Eosinophilic angiocentric fibrosis

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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

 

Fungi

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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

 

Histoplasmosis

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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)

Micro images: 1-endoscopy; 2-sheets of eosinophilic histiocytes; 3-histiocytic intracellular inclusions with peripheral halos; 4-yeast forms; 5-PAS; 6-GMS

DD: laryngeal carcinoma (clinically)

 

Nonspecific granulomas

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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

 

Rhinosclerosis

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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

Micro images: 1-CT scan shows mucosal thickening of subglottic larynx; 2-nonkeratinizing squamous mucosa with dense subepithelial plasma cells and large foamy histiocytes; 3-large foamy histiocytes and plasma cells with Russell bodies; 4-Warthin-Starry stain highlights small rodlike bacteria

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

 

Tuberculosis

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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

Aneurysmal bone cyst

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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

Micro images: 1-mass attached to anterior mucosa (gross image); 2-cellular lesion with numerous osteoclast-like giant cells and mononuclear cells in angiomatoid pattern; 3A-mature osteoid, giant cells and mononuclear cells; 3B-giant cells and mitotic figure

DD: telangiectatic osteosarcoma (clearly malignant cells in vascular background), giant cell tumor (less cystic, more nuclei in giant cells)

 

Chondroma

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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

 

Chondrometaplasia of larynx

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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

 

Cysts

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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

 

Giant cell tumor

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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

 

Granular cell tumor

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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

 

Hemangioma

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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

 

Mucinosis

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Very rare in larynx

Case reports: 3 year old boy intubated at age 2 months with recurrent respiratory infections (Hum Path 1990;21:856)

 

Mucous membrane plasmacytosis

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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

 

Papilloma

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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

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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

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Usually men, solitary

Recurrences frequently exhibit dysplasia

DD: verrucous carcinoma

 

Plasmacytoma

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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)

 

Pleomorphic adenoma

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Case reports: 40 year old woman with tumor of false vocal cord with squamous metaplasia (Archives 1986;110:245)

 

Rhabdomyoma

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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

 

Teflonoma

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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

 

Verruca vulgaris

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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

 

Verruciform xanthoma

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Case reports: child with systemic lipid storage disorder (AJSP 1989;13:309)

 

Vocal cord polyp

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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

Hyperplasia

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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)

 

Verrucous hyperplasia

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Irreversible mucosal lesion of upper aerodigestive tract that tends to progress to verrucous carcinoma or conventional squamous cell carcinoma

 

Dysplasia

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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

General

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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#3microinvasive carcinoma - A: arising from carcinoma in situ; B-arising from non-dysplastic epithelium; C-invasive although no apparent violation of basement membraneinvasive carcinoma with desmoplastic response; A-nested growth pattern; B-discohesive growthkeratin 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

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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