Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
 Home | Pathology Group MembersOur Hospital  Search This Website:
ENT Neoplastic issues


  1. Salivary gland:
    • Benign vs. malig. odds: parotid, 5:1 benign; minor glands, 6:1 malignant; & submandibular, 1:12.
  2. Supraglottic, nasopharyngeal:



  1. Cutaneous: H&N cutaneous mets tend to go to superficial face & neck nodes whereas interior, mucosal-derived carcinomatous mets go to deep nodes.
  2. Ear: [HERE]
    • benign:
      1. cholesteotoma: usually results originally from unhealed ruptured eardrum with subsequent benign squamous proliferation tending to be infected & eroding into inner ear & temporal bone & rarely causing a potentially fatal brain abcess in juxtaposed brain [FA11-7].
      2. acoustic neuroma:
    • malignant:
  1. Thyroid [HERE].
  2. Salivary glands:
    • adenoma:
      • benign mixed tumor (pleomorphic adenoma): a tumor of stromal differentiation with myxocartilagenous being telltale; usually mostly GFAP positive2.
      • oxyphilic adenoma:
      • Warthin's tumor:
      • basal cell adenoma: low mitotic rate tumor2; uniphasic tumor2, negative for myxoid areas; unencapsulated2 & often cystic; often palisade at tumor group periphery in a "basal cell" fashion; tubular, trabecular or solid growth patterns & may produce abundant basal lamina material around & within nests remindful of cylindroma & being referred to as a "membranous basal cell adenoma" (dermal analogue tumor). If also contains some features suggestive of mixed tumor, it may be referred to as a "hybrid basal cell adenoma" [LMC-05-5535].
      • canalicular adenoma: possibly a variant of the basal cell adenoma & high tendency to arise in minor salivary glands
      • myoepithelioma:
    • carcinoma: (sclerosis in a salivary gland almost always means malignant2)
      • malignant mixed tumor: if not infiltrated through tumor capsule, it is like a CIS...most die if extends 8mm or more beyond capsule1; though 30% have short history, think of this cancer when there is a very long clinical history2; there can just be focal cancer in a mixed tumor or the prior mixed tumor can be over-run by malignancy2.
        • monophasic: adenocarcinoma only (usually NOS2); carcinoma ex pleomorphic adenoma.
        • biphasic: epithelial & stromal components look malignant; carcinosarcoma...often rapidly lethal1.
      • basal cell adenocarcinoma: infiltrative growth pattern & greater than 4 mitoses per 10 hpfs & greater than 5% Ki672;
      • adenoid cystic carcinoma (ACC): unencapsulated & think of ACC in palate tumors2; classic cribriform pattern (can have tubular or solid...when solid, its grade III) & high propensity for perineural space invasion.
      • polymorphous low grade adenocarcinoma (PLGA): is almost exclusively an oral cavity minor gland cancer2; bland cytology and diverse patterns but always find foci of intimately mixed ducts & small tubules lined by a single layer of cuboidal cells embedded in a mucohyaline or hyalinized stroma2; usually circumscribed but unencapsulated...but periphery will show infiltrative areas2; 75% of cases have prominent perineural space invasion2; usually not nucleoli & mitotic rate low; mixed tumor is key DDX & PLGA mostly GFAP negative, has tubules with a single layer & no squamous differentiation, does not have cartilage2.
      • salivary duct adenocarcinoma: a d-CIS-like (as if breast) component with comedo-necrosis helps identify this entity which has cribriform and papillary growth; ER & PR negative but GCDFP positive; mucicarmine negative; sometimes perineural space invasion positive; a purported low-grade variant may have been PLGA2.
      • myoepithelial carcinoma: varying proportions of spindled to plasmacytoid cells set in a mucoid to myxoid background, possibly with some clear-cell change; IHCs, vimentin, SMM-hc, and calponin positive; can develop in a mixed tumor, myoepithelioma, or de novo & very rare2.
      • Acinic cell carcinoma: clear & granular cytoplasm; encapsulation and negativity for vascular invasion are better-prognosis signs; there is a papulocystic variant.
      • epithelial-myoepithelial carcinoma (EMC): uncommon...most are in major salivary glands...& composed of variable proportions of ductal & clear cells...definitely biphasic; tumor seems circumscribed but focal infiltration at margin and some perineural space invasion; clear cells calponin and SMM-hc reactive; thought of as a low grade cancer & worse prognosis of greater than 20% of cells have atypical nuclei2.
      • clear cell carcinoma: though possibly having a few duct areas, clearly not biphasic & is a minor salivary gland lesion2.
      • anaplastic (undifferented) small cell neuroendocrine carcinoma3 :
        • pulmonary type: ck20 negative & worse prognosis.
        • Merkel cell type: ck20 Golgi-dot positive & better prognosis [LMC-09-9260].
      • malignant lymphoepithelioma-like carcinoma/tumor (LELC7): be sure not a metastatic nasopharyngeal carcinoma (LELC tend to be EBV positive in Eskimos/orientals & not often in Caucasions [L06-9058]); often of Eskimo ethnicity; has best prognosis among the undifferentiated carcinomas; both components could be malignant; high mitotic rate clue to malignancy in the epithelial component if not clearly a malignant invasive pattern with desmoplastic stroma...pos. K903 can indicate that a poorly differentiated carcinomatous component is SCC. Current consensus is said to be that LELC does not come about by transformation from benign lymphoepithelial lesion (BLEL).
  3. Oral cavity:
    • mucosal:
      • ranula
    • other:
      • odontogenic keratocyst: [L-05-7912]
  4. Upper aerodigestive tract neoplasmas (UADT): nasal & sinonasal membranes of ectodermal origin; from pharyngeal distally is entodermal.
    • epithelial:
      • Schneiderian (C. Victor Scneider 1614-?) paillomas2:
        1. fungiform: exophytic/everted; arises on nasal septum; no surface keratinization; papillary fronds with thin fibrovascular cores covered thickly by transitional-like cells that focally contain intra-epithelial mucous cysts or some ciliated cells or even goblet cells; HPV6/11 associated.
        2. inverted: lateral nasal wall & sinuses (especially maxillary); squamous; some regard as a mucosal polyp with squamous metaplasia; invaginations (inversions) of epithelial groups of nonkeratinizing squamous cells over a thick basement membrane; surface epithelium can be ciliated to transitional & commonly have mucous cells with mucous cysts.
        3. cylindrical cell: lateral nasal wall & sinuses; stratified oncocytic cell layers; not HPV-associated.
      • adenoma:
      • benign lymphoepithelial lesion (BLEL): this nodule of mixed lymphoid and epimyoepithelial islands lacks epithelial cell & island atypia & islands often contain overproduced basement membrane-like material & islands are consistently EBV negative in BLEL.
      • neuroendocrine tumors: well differentiated (carcinoids) & moderately differentiated (atypical carcinoids); poorly differentiated (see SNEC, below).
      • carcinoma:
        1. Adenocarcinoma:
            • low-grade adenocarcinoma2: practically no pleomorphism & rarely lethal & treated by non-radical surgery.
              • low grade sinonasal papillary adenocarcinoma: predominant papillary component & monolayered cells have eosinophilic cytoplasm & can be confused with cylindrical cell papilloma; when psammoma bodies, mimics pap. thyroid but TBG IHC neg.
              • low grade non-papillary: predominant acinar/microglandular in back-to-back pattern; mitoses rare.
            • intestinal-type sinonasal adenocarcinoma (ITAC)2: more aggressive than low-grade, above; 85% occupational-associated (hardwood woodworkers) in males & sporadic cases in females; from benign-looking intestinal-like mucosa, to adenoma-like, to frankly carcinomatous = they are all bad & can be papillary. No way to distinguish a primary from a metastatic colorectal; so, colonoscopy in all cases to r/o a CRC primary. Types2:
              • papillary-tubular types, grade I-III...better prognosis.
              • goblet cell type.
              • signet ring cell type.
              • mixed or transitional type.
          • Squamous cell carcinoma (SCC): in small biopsies, desmoplasia or foreign body reaction to keratin can alert to invasion5; paradoxical maturation (kerain pearls or notably keratotic foci at stromo-epithelial interafce rather than mucosal surface [L11-14718]) can alert to invasion (especially in FS); blunt invasive profiles imply less aggression & dyscohesive invasion implies greater aggression5; poorly differentiated can be a problem in DDX; is K903 positive (if worried sarcoma or MFH).
            • keratinizing SCC: not EBV-associated; invasion tends to generate a desmoplastic response; well differentiated, moderately differentiated, & poorly differentiated.
            • nonkeratinizing SCC: EBV-related & p53 over-expression correlates with EBV relationship1; invasion generates little or no desmoplastic response.
              • differentiated SCC: pavemented and cell borders seen; how does the only moderately to poorly differentiated differ from the cylindrical [transitional] cell, below?
              • undifferentiated...nasopharyngeal (large cell undifferentiated) SCC1 (synonyms are: TCC,lymphoepithelioma, transitional cell epidermoid carcinoma, anaplastic ca., embryonal cell ca., basocellularis ca., spinocellularis ca., SCC, and epidermoid ca.6): cytoplasmic syncytium; tends to have such a striking accompanying lymphocytic background that older term was "lymphoepithelioma" (Regaud pattern if lymphs relatively spare carcinoma islands & Schminke pattern if lymphs blurr the carcinomatous component to point of looking like a mixed large & small cell lymphoma5); " lymphoepithelioma" has a particularly favorable response to raduiation. Worse prognosis if marked anaplasia and/or pleomorphism, high proliferation rate, lack of lymphocytic infiltrate, and high density of S100 dendritic cells1.
            • papillary (exophytic) SCC: assoc. with HPV &, (1) when clinically visible growths & (2) have the malignant epithelium (as opposed to a papilloma), considered an invasive cancer...though you may not "see" invaion & surgery is the treatment5.
            • adenoid (acantholytic, angiosarcoma-like) SCC: acantholytic pattern makes pseudo-lumina; IHC vascular markers negative5.
            • verrucous SCC1: a highly differentiated SCC. DDX, progressing from benign to malignant (and within the old DDX spectrum of verrucous hyperplasia & "proliferative verrucous leukoplakia" [PVL]...both of which are irreversible5, typified by a long clinical history 4); white warty to fungating or exophytic firm to hard masses5; mandatory to get laryngoscopic gross description & extent to help "make" the diagnosis; surgery preferred treatment:
              1. clinical lekoplakia (with epithelial layer thickening which might be faintly undulating & or only mild dysplasia)...if more than mild dysplasia, probably not PVL; then,
              2. verrucous hyperplasia (with architectural or only mild dysplasia); then,
              3. verrucous carcinoma (if not histologically obviously invasive, with pathologist's opinion to consider the details of extent of gross pathology...such as laryngoscopic presence of questionable areas of "invasion", plus presence of architectural atypia of staggered [rather than even & orderly] heights & depths of the verrucoid epithelial component, plus possibly the added presence of a little squamous cyto-atypism/dysplasia).
            • spindle cell (sarcomatoid) SCC (SCSCC): at least squamous is K903 positive; synonyms carcinosarcoma & metaplastic carcinoma, pseudosarcoma and Lane tumor5 & often polypoid to fungating, & spindled component (usually dominant) & obvious SCC component both look malignant, & can include heterologous elements, the stomal sometimes being deceptively collagenized, & S100 & HMB45 negative, & surgery preferred treatment5.
            • basaloid SCC (BSCC)2: H&E DDX brings up SNEC; a very high grade cancer of basaloid small cells predominating & intimately associated with a minority squamous component (dysplasia, CIS, and/or invasive SCC)5, with apoptosis, comedonecrosis, high mitotic rate, sometimes some peripheral palisading, smooth contours or circumscription of tumor-cell groups, and often with hyaline basal lamina material; may see focal spindled or even rosettes; can be NSE positive but not chromogranin or synaptophysin positive2.
          • Cylindrical (transitional) cell carcinoma1: closely related to SCC (how does it differ from a moderately differentiated nonkeratinizing conventional SCC?).
          • Salivary Gland type carcinomas: adenoid cystic, mucoepidermoid, adenosquamous, etc.
          • Sinonasal undifferentiated carcinoma (SNUC)2: "anaplastic carcinoma"1 & you'll think of SNEC ; often organoid pattern with nests, trabeculae, and ribbons of medium-sized cells; usually has large nucleoli, lots mitoses, & extensive vascular invasion2; apoptosis & micronecrosis common; keratin pos. & S100 negative & about 50% are NSE positive. DDX also includes melanoma and embryonal rhabdomyosarcoma; SNEC has smaller cell size & more hyperchromatic nuclear staining than SNUC2.
          • Small cell neuroendocrine carcinoma (SNEC)2: small cells, apoptosis, lots mitotic, and no circumscription of tumor components...just as with SNEC lung cancer; keratin pos. & ck20 negative; consider SNUC and BSCC.
      • salivary gland tumors1 of sinonasal and nasopharyngeal origin.
      • salivary gland enlage tumor of the nasopharynx: presents in newborn & is biphasic with squamous nests & duct-like structures at the periphery that blend centrally into solid nodules...perhaps hamartomatous1.
      • neurogenous tumors:
        1. olfactory neuroblastoma (ONB) [esthesioneuroblastoma]2: S100 pos & keratin weak to negative.
        2. Ewing sarcoma/peripheral neuroectodermal tumor (ES/PNET)2: keratin neg. & S100 negative.
        3. encephaloceles & nasal gliomas (glial heterotopias)
        4. tumor extensions from intracranial tumors: meningiomas & glial/astrocytic tumors; chordoma.
        5. paraganglioma
        6. peripheral nerve tumors
      • melanoma
    • mesenchymal:
      • nasopharyngeal angiofibroma1: erectile-tissue-like
      • hemangiopericytoma-like tumor2: a "vascular swamp" & cells are CD99 pos. & CD13 pos.; usually benign, and the superficial and deep aspects look exactly the same.
      • intranasal lobular capillary hemangioma2: pyogenic-granuloma-like pattern & superficial and deep aspects are alike.
      • nasopharyngeal solitary fibrous tumor1: highly vascularized lesion with alternating cellular and hypocellular zones.
      • sinonasal tract ameloblastoma
      • rhabdomyosarcoma
      • teratoid carcinosarcoma
      • follicular dendritic cell tumor
      • soft tissue tumors: be alert to post-radiation MFH vs. spindled or sarcomatoid SCC (LMC-06-5043...MFH must be K903 negative & spindled SCC positive).
      • giant cell reparative granuloma
      • primary localized amyloidosis
    • lymphoma: adults with tonsillar complaints and enlargement (especially if symetrical) that are refractory to usual treatments should be carefully processed in search of evidence of frank or early lymphoma [S12-2471, 51 y/o refractory and had normal CBC & tonsillectomy showed small lymphocytic lymphoma and CBC flow cytometry positive for a small clone of CLL].
  5. Laryngeal:
    • benign epithelial lesions
    • malignant epithelial:
      1. squamous dysplasias, CIS, & invasive:
        • usual SCC
        • spindled cell or sarcomatoid SCC: may need positive K903 to prove it & be sure to differentiate from post-radiation or other MFH [L06-8409].
      2. glandular dusplasias, CIS, & invasive.
    • benign soft tissue lesions
    • malignant soft tissue: be alert to post-radiation MFH vs. spindled or sarcomatoid SCC (LMC-06-5043...MFH must be K903 negative & spindled SCC positive).


  1. Rosai & Ackerman's 9th Ed, vol 1, about pages 344-345.

  2. Andrew G. Huvos, MD, ENT Workshop, 9th Annual "Seminar in Pathology", Pittsburgh, May 2-5, 2002.

  3. Mayo Clinic series, AJSP 21(2):226-34 &28(6):762-70.
  4. Louis S. Hansen, chair Oral Pathology, "Proliferative Verrucous Leukoplakia", Oral Surgery 60(3):285-298, Sept. 1985.
  5. Wenig BW (Beth Israel Med Ctr), Modern Path., 15(3):229-254, March 2002.
  6. Batsakis JG, Tumors of the Head and Neck..., 2nd Ed., 1979, 573 pages.
  7. Fletcher CDM, Diagnostic Histopathology of Tumors, 3rd. Ed. 2007.
  8. Paul E. Wakeley, Jr., "Head & Neck Pathology Session 11/16", "Oncologic Pathology: A Review and Update of Current Diagnostic Problems", ASCP CME in Charleston, S. C. , 15-17 Nov. 2010.

     (posting began 25 June 2005; latest addition 3 April 2012)

© Copyright 1999 - 2006, all rights reserved, Pathology Associates Of Lexington, P.A.