An introduction to head and neck pathology

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Head and neck pathology is squamous cell carcinoma and weird stuff. The thyroid is dealt with in its own article, as is pathology of the salivary gland.

Cytopathology of the head and neck is dealt with in a separate article called head and neck cytopathology.

Clinical

Oral lesions

DDx:[1]

  • Leukoplakia.
    • Unidentified white lesion.
    • More worrisome than erythroplakia.
    • Often assoc. with epithelial thickening (hyperkeratosis, acanthosis).
  • Erythroplakia.
    • Unidentified red lesion.
    • Often erosion.

Benign cystic lesions

Cytology dealt with in Head and neck cytopathology.

DDx

Lateral:

  • Brachial cleft cyst.
  • Cystic hygroma.

Medial:

  • Thyroglossal duct cyst.

Both:

  • Epidermoid cyst.
  • Cystic squmaous cell carcinoma.

Rathke cleft cyst

Main article: Rathke cleft cyst
  • Arises from intermediate lobe - embryonic remnant.
  • Benign cystic lesion without calcification.
  • Related to craniopharyngioma.

Thyroglossal duct cyst

General

  • Congenital.
  • Midline.

Treatment:

  • Surgical excision (with piece of hyoid bone).

Microscopic

Features:

  • Cyst.
    • Lining:
      • Squamous or respiratory epithelium.
      • Cyst contents: debris.
  • +/-Thyroid gland.
  • +/-Granulomatous inflammation (phagocytosis of debris).

Images:

Branchial cleft cyst

  • AKA branchial cleft remnant.

General

  • Benign congenital thingy in the lateral neck.[3]
  • Treatment: excision.

Clinical image: Branchial cleft cyst (thefreedictionary.com).

Microscopic

Features:

  • Cystic space lined by squamous epithelium - usually.
  • Connective tissue:
    • +/-Adipose tissue.
    • +/-Cartilage.
    • +/-Bone.
    • +/-Muscle.

Image:

Benign lymphoepithelial lesion

  • AKA benign lymphoepithelial cyst

General

  • Usually parotid gland.
  • Associated with autoimmune disease, e.g. Sjoegren disease, may not remain benign.[5]

Microscopic

Features:

  • Lymphocytes.
  • Ductal epithelial cells.[6]

Note:

IHC

  • CD20, CD3 -- mixed population.
  • Kappa ~ lambda.

Other benign

Vocal cord nodule

General

  • Benign.
  • AKA singer's nodule.
  • Etiology: overuse, mechanical trauma (?).

Microscopic

Features:[7]

  • Early:
    1. Edema.
    2. Fibroblasts proliferation.
  • Late:
    1. Subepithelial hyaline / stromal hyaline.
    2. Blood vessels - dilated.

Notes:

  • No inflammation.

Images:

Pemphigus vulgaris

Main article: Pemphigus vulgaris

General

  • May lead to blindness.
  • Oral lesion is classically: first to show & last to go.
    • Oral lesions usually precede the skin lesions.

Etiology:

  • Autoimmune disease.
    • Antibodies against: desmoglein 1, desmoglein 3.

Microscopic

Features:[8]

  • Suprabasilar blistering.

DDx: Hailey-Hailey disease.

Pyogenic granuloma

  • AKA lobular capillary hemangioma.[9]

General

  • Sometimes pregnancy tumour.
  • Seen in children, young adults, pregnant women.

Clinical:

  • May grow quickly - clinically suspicious for a malignancy.

Notes:

  • Name of entity is a misnomer:
  • The WMSP advocates the name lobular capillary hemangioma.[10]

Gross

Features:[11]

  • Erythematous.
  • Hemorrhagic.

Usually location:[10]

Microscopic

Features:[12]

  • Polypoid or peduculated.
  • Vascular, i.e. many blood vessels, with plump endothelium.
  • Usu. thinned epithelium[13] or ulcerated.[10]
  • Lobular arrangement of vascular (seen at low power).[14]

DDx:

Why it is not...

Image:

IHC

Features - positive for vascular markers:[10]

  • CD34 +ve.
  • CD31 +ve.
  • Factor VIII +ve.

Hairy leukoplakia

General

Features:[15]

  • Oral lesion.
  • Thought to be caused by EBV.

Gross:

  • White confluent patches (icing sugar).

Microscopic

Features:[16]

  • Hyperkeratosis (thicker stratum corneum).[17]
  • Acanthosis (thicker stratum spinosum).[18]
  • "Balloon cells" in upper stratum spinosum - perinuclear clearing.

Plummer-Vinson syndrome

Triad:[11]

  • Iron-deficiency anemia.
  • Glossitis.
  • Esophageal dysphagia (usually related to webs).

Oral candidiasis

  • Fungus.
  • May be associated with immunodeficiency, e.g. AIDS, organ transplant/immunosuppression.

Forms:[15]

  • Pseudomembranous (thrush).
  • Erythematous.
  • Hyperplastic.

Rhinoscleroma

General

  • Caused by Klebsiella rhinoscleromatis.
  • Nose involved +95% of the time.[19]

Gross

  • Nasal mass - may be deforming.

Image:

Microscopic

Features:[20]

  • Macrophages - clear-to-foamy cytoplasm.
  • Lymphocytes.
  • Plasma cells.

DDx:

Images:

Stains

  • Warthin-Starry stain +ve (rod-shaped organisms).
  • Dieterle stain +ve (rod-shaped organisms).

Neoplasms

Odontogenic tumours and cysts

Main article: Odontogenic tumours and cysts

This is a rather large topic and dealt with in a separate article.

It includes:

Pharyngeal/nasopharyngeal specimens

  • Specimens may be challenging to interpret as there is normally an abundance of lymphoid cells.
  • Malignant tissue can look benign.[22]
  • May be difficult to differentiate from other malignancies.

Histology

  • Upper airway distant from areas with friction: respiratory type epithelium.

Work-up of negative H&E Bx differs by site:

Sinonasal undifferentiated carcinoma

  • Abbreviated SNUC

General

  • Very aggressive/poor prognosis - survival measured in months.[24]

Microscopic

Features:[25]

  • Architecture: nested, trabecular or lobular.
  • Distinct cellular borders.
  • Small-to-moderate cytoplasm.
  • +/-Distinct nucleoli.
  • Tumour cell size variable (small to large).

Note:

  • Glandular and squamous differentiation are absent by definition.[26]

Images:

IHC

Features:[25]

  • Pankeratin +ve.
  • EMA +ve.
  • CK7 +ve.
  • CK5/6 -ve.

Others:

  • NSE +ve/-ve.
  • Chromogranin A -ve.
  • Synaptophysin -ve.

Nasopharyngeal carcinoma

  • Abbreviated NPC.

General

  • "Nasopharyngeal carcinoma" is the name of an entity - it is not a descriptive term.
  • Strong association with Epstein-Barr virus (EBV).

Note:

Microscopic

Features:[27]

  • Prominent lymphoid component - key feature.
  • Features of squamous cell carcinoma:
    • Cohesive cells with:
      • Abundant dense eosinophilic cytoplasm.
      • Central nuclei +/- small/indistinct nucleoli.

Image(s):

Histologic subclassification

World Health Classification (2005) for NPC:[28]

Type Histology Description EBV Prevalence Prognosis
1 keratinizing SCC graded poorly-well-diff. -ve ? bad
2a nonkeratinizing carcinoma, differentiated well def. cell borders & tumour nest borders, mimics appearance of UCC +ve ? good
2b nonkeratinizing carcinoma, undifferentiated sheets/syncytial, vescicular nuclei, prominent nucleoli, pink cytoplasm ? most common ?
3 basaloid SCC mimics BCC - see basaloid SCC ? least common ?

IHC

  • EBER +ve.
  • p16 -ve.[29]

Notes:

  • HPV associated squamous cell carcinomas are p16 +ve.

Squamous lesions

  • Premalignant lesions
    • Mild dysplasia.
      • Low risk of progression to invasive lesions.
    • Moderate dysplasia.
    • Severe dysplasia/carcinoma in situ (CIS).
      • Histologically severe dysplasia and CIS cannot be differentiated reliably; ergo, there can be considered the same thing.
      • Severe dysplasia is not a necessary intermediate for cancer, i.e. invasive squamous cell carcinoma may be present with moderate dysplasia.
  • Invasive squamous cell carcinoma (SCC).
    • "Microinvasive" squamous cell carcinoma - term should be avoided as there is no concenus on what it means.
    • There are several subtypes of SCC.

Squamous cell carcinoma

Main article: Squamous cell carcinoma

General

  • Most common tumour of the head & neck.

Microscopic

Classification

SCC is subdivided by the WHO into:[30]

  • Keratinizing type (KT).
    • Worst prognosis.
  • Undifferentiated type (UT).
    • Intermediate prognosis.
    • EBV association.
  • Nonkeratinizing type (NT).
    • Good prognosis.
    • EBV association.

Features based on classification:[30]

  • KT subtype:
    • Keratinization & intercellular bridges through-out most of the malignant lesion.
  • UT:
    • Non-distinct borders/syncytial pattern.
    • Nucleoli.
  • NT:
    • Well-defined cell borders.

Invasion

Features:

  • Eosinophilia.
  • Extra large nuclei/bizarre nuclei.
  • Inflammation (lymphocytes, plasma cells).
  • Long rete ridges.
  • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.

Pitfalls:

  • Tangential cuts.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

Notes on invasion:

Image(s):

Overview of subtypes

There are several subtypes:[32]

  • Basaloid - poor prognosis, usu. diagnosed by recognition of typical SCC.
  • Warty (Condylomatous).
  • Verrucous - good prognosis, rare.
  • Papillary.
  • Lymphoepithelial, rare.
  • Spindle cell, a common spindle cell lesion of the H&N.

Verrucous squamous cell carcinoma

Features:

  • Exophytic growth.
  • Well-differentiated.
  • "Glassy" appearance.
  • Pushing border.

DDx: papilloma.

Spindle cell squamous carcinoma

  • Key to diagnosis is finding a component of conventional squamous cell carcinoma.

IHC:

  • Typically keratin -ve.
  • p63 +ve.

DDx:

  • Spindle cell melanoma.
  • Mesenchymal neoplasm.

Basaloid squamous cell carcinoma

Features:

  • Need keratinization. (???)

DDx:

  • Neuroendocrine tumour.

Lymphoepithelial (squamous cell) carcinoma

  • Rare.
  • +/-EBV.

Small cell anaplastic carcinoma

  • Rare.

DDx:

Granular cell tumour

Main article: Granular cell tumour

General

  • May mimic (well-differentiated) squamous cell carcinoma - histopathologically.
    • There is a well-described phenomenon called pseudoepitheliomatous hyperplasia.[34]
  • Usually a benign tumour.

Microscopic

Features:

  • Large polygonal cells with abundant (eosinophilic) granular cytoplasm.

Image:

Olfactory neuroblastoma

See also: neuroblastoma.
  • AKA esthesioneuroblastoma.

General

  • Prognosis: poor.

Microscopic

Features:

DDx:

Image:

IHC

  • S100:
    • Sustentacular cells +ve.
    • Small round cells -ve.
  • Neuroendocrine markers +ve (CD56, synaptophysin).

Others:

  • CD45 -ve (r/o lymphoma).
  • AE1/AE3 -ve (r/o carcinoma).

Craniopharyngioma

Main article: Craniopharyngioma
  • Cystic lesion +/- calcifications +/-squamous nests.
  • Related to Rathke cleft cyst.

Nasopharyngeal angiofibroma

See also: Angiofibroma.

General

  • AKA juvenile nasopharyngeal angiofibroma.
  • Classical adolescent males with recurrent nose bleeds.

Microscopic

Features:[36]

  • Fibroblastic cells with plump (near cuboidal) nuclei.
  • Fibrous stroma.
  • Abundant capillaries.

Images:

Nasal polyps

Overview

DDx (benign - multiple):[37]

  • Autoimmune/idiopathic:
    • Asthma.
    • Allergic rhinitis.
    • Churg-Strauss syndrome (AKA allergic granulomatous angiitis).
      • Features: asthma, eosinophilia, granulomatous inflammation, necrotizing systemic vasculitis, and necrotizing glomerulonephritis.[38]
    • Nonallergic rhinitis with eosinophilia syndrome (NARES).
  • Infectious:
    • Fungal infection (with allergic component - AFS = allergic fungal sinusitis).
    • Chronic rhinosinusitis.
  • Genetic
  • Associations:
    • Alcohol intolerance ~ 50%.
    • Aspirin intolerance - upto ~ 25%.

Tumours:

  • Juvenile nasopharyngeal angiofibroma (young males).
  • Nasopharyngeal carcinomas.
  • Sarcomas.
  • Hemangioma.
  • Papilloma.
  • Other.

Epidemiology

  • More commonly assoc. with nonallergic conditions.[37]

Treatment

  • Recurrent polyps: Functional endoscopic sinus surgery (FESS).

Inflammatory polyps with neutrophils

General

  • Histologic findings are non-specific; DDx includes:[39]

Microscopic

Features:

  • Neutrophil predominant.
  • Edema.
  • +/-Mucus-impaction (dilated glands with mucus).
    • Suggestive of cystic fibrosis.[40]

Allergic nasal polyp

General

  • People with allergies.

Gross

  • Polypoid mass - several millimetres to centimetres in size.

Microscopic

Features:[41]

  • Normal respiratory epithelium.
  • Stroma with:
    • Edema.
    • Eosinophils.
    • +/-Other inflammatory cells (plasma cells, lymphocytes, neutrophils).

Tonsillar lymphangiomatous polyp

Microscopic

Features:[42]

  • Polyp with lymph channels.

Schneiderian papilloma

  • AKA Schneiderian polyp.
  • AKA sinonasal papilloma.[43]

General

  • Lumpers vs. splitters debate about whether it is one entity or three.[44]

Subclassification:[44]

  • Inverted (Schneiderian) - most common ~60-65%.
  • Fungiform (Schneiderian) - less common ~30-35%.
  • Oncocytic (Schneiderian) - least common ~5%.

Inverted

Fungiform

  • AKA exophytic papilloma, AKA septal papilloma.[44]

Oncocytic

  • Lateral nasal wall.[44]

Microscopic

Inverted Schneiderian papilloma

Features:[44]

  • Well-demarcated epithelial islands in the stroma.
  • Squamous +/-surface keratinization or respiratory type epithelium (with cilia).
  • +/-Neutrophils.
  • +/-Goblet cells.

Notes:

  • May mimic invasive SCC.

Images:

Fungiform Schneiderian papilloma

Features:

  • Exophytic growth pattern - key feature.

Oncocytic Schneiderian papilloma

Features:

  • Oncocytes - key feature.
  • Exophytic or endophytic growth pattern.

See also

References

  1. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 780. ISBN 0-7216-0187-1.
  2. ↑ URL: http://150.59.224.157/pathology/index.php?now_position=1&first_category_id=2&second_category_id=19. Accessed on: 4 February 2011.
  3. ↑ URL: http://www.childrenshospital.org/az/Site663/mainpageS663P0.html. Accessed on: 15 March 2011.
  4. ↑ URL: http://www.pathology.med.ohio-state.edu/residents/InternalGate/Area51/ResidentSlideCollection/RSLdx.asp. Accessed on: 15 March 2011.
  5. ↑ Goto, TK.; Shimizu, M.; Kobayashi, I.; Chikui, T.; Kanda, S.; Toshitani, K.; Shiratsuchi, Y.; Yoshida, K. (May 2002). "Lymphoepithelial lesion of the parotid gland.". Dentomaxillofac Radiol 31 (3): 198-203. doi:10.1038/sj/dmfr/4600690. PMID 12058269.
  6. ↑ Metwaly, H.; Cheng, J.; Ida-Yonemochi, H.; Ohshiro, K.; Jen, KY.; Liu, AR.; Saku, T. (Jul 2003). "Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion).". Virchows Arch 443 (1): 17-27. doi:10.1007/s00428-003-0824-0. PMID 12761623.
  7. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970310-2. Accessed on: 4 February 2011.
  8. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1193. ISBN 978-1416031215.
  9. ↑ Baglin, AC. (Aug 2011). "[Vascular tumors and pseudotumors. Pyogenic granuloma (lobular capillary hemangioma)].". Ann Pathol 31 (4): 266-70. doi:10.1016/j.annpat.2011.05.014. PMID 21839350.
  10. ↑ 10.0 10.1 10.2 10.3 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 12. ISBN 978-0781765275.
  11. ↑ 11.0 11.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 776. ISBN 0-7216-0187-1.
  12. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 775. ISBN 0-7216-0187-1.
  13. ↑ URL: http://basicpathology-histopathology.blogspot.com/2009/10/head-and-neck-oral-cavity-reactive_3282.html. Accessed on: 2 February 2011.
  14. ↑ S. Sade. 8 September 2011.
  15. ↑ 15.0 15.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 777. ISBN 0-7216-0187-1.
  16. ↑ URL: http://www.pathologyoutlines.com/oralcavity.html#hairyleukoplakia.
  17. ↑ URL: http://www.emedicine.com/asp/dictionary.asp?keyword=hyperkeratosis.
  18. ↑ URL: http://www.emedicine.com/asp/dictionary.asp?keyword=acanthosis.
  19. ↑ Chan, TV.; Spiegel, JH. (Oct 2007). "Klebsiella rhinoscleromatis of the membranous nasal septum.". J Laryngol Otol 121 (10): 998-1002. doi:10.1017/S0022215107006421. PMID 17359555.
  20. ↑ URL: http://www.brown.edu/Courses/Digital_Path/systemic_path/hn/rhinoscleroma2.html. Accessed on: 18 January 2012.
  21. ↑ URL: http://www.jameswpattersonmd.com/case_studies/index.cfm?CFID=387434. Accessed on: 21 February 2012.
  22. ↑ S. Raphael. December 2008.
  23. ↑ S. Raphael. December 2008.
  24. ↑ Pitman, KT.; Costantino, PD.; Lassen, LF. (1995). "Sinonasal undifferentiated carcinoma: current trends in treatment.". Skull Base Surg 5 (4): 269-72. PMC 1656535. PMID 17170968. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1656535/.
  25. ↑ 25.0 25.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 38. ISBN 978-0781765275.
  26. ↑ 26.0 26.1 Mills, SE. (Mar 2002). "Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas.". Mod Pathol 15 (3): 264-78. doi:10.1038/modpathol.3880522. PMID 11904342.
  27. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 145. ISBN 978-1416002741.
  28. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 39. ISBN 978-0781765275.
  29. ↑ Gulley ML, Nicholls JM, Schneider BG, Amin MB, Ro JY, Geradts J (April 1998). "Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product". Am. J. Pathol. 152 (4): 865–9. PMC 1858242. PMID 9546345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858242/.
  30. ↑ 30.0 30.1 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 975. ISBN 978-0781740517.
  31. ↑ Wenig BM (March 2002). "Squamous cell carcinoma of the upper aerodigestive tract: precursors and problematic variants". Mod. Pathol. 15 (3): 229–54. doi:10.1038/modpathol.3880520. PMID 11904340. http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf.
  32. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2. Accessed on: March 9, 2010.
  33. ↑ URL: http://www.biomedcentral.com/1471-2407/6/146. Accessed on: March 9, 2010.
  34. ↑ Abu-Eid R, Landini G (March 2006). "Morphometrical differences between pseudo-epitheliomatous hyperplasia in granular cell tumours and squamous cell carcinomas". Histopathology 48 (4): 407–16. doi:10.1111/j.1365-2559.2006.02350.x. PMID 16487362.
  35. ↑ URL: http://path.upmc.edu/cases/case467.html. Accessed on: 21 January 2012.
  36. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 144. ISBN 978-1416002741.
  37. ↑ 37.0 37.1 URL: http://emedicine.medscape.com/article/994274-overview. Accessed on: 16 March 2011.
  38. ↑ http://emedicine.medscape.com/article/333492-overview
  39. ↑ URL: http://emedicine.medscape.com/article/994274-diagnosis. Accessed on: 16 March 2011.
  40. ↑ Beju D, Meek WD, Kramer JC (April 2004). "The ultrastructure of the nasal polyps in patients with and without cystic fibrosis". J. Submicrosc. Cytol. Pathol. 36 (2): 155–65. PMID 15554502.
  41. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 144. ISBN 978-1416002741.
  42. ↑ http://www.nature.com/modpathol/journal/v13/n10/full/3880208a.html
  43. ↑ URL: http://emedicine.medscape.com/article/862677-overview. Accessed on: 19 November 2011.
  44. ↑ 44.0 44.1 44.2 44.3 44.4 44.5 Barnes L (March 2002). "Schneiderian papillomas and nonsalivary glandular neoplasms of the head and neck". Mod. Pathol. 15 (3): 279–97. doi:10.1038/modpathol.3880524. PMID 11904343. http://www.nature.com/modpathol/journal/v15/n3/full/3880524a.html.
  45. ↑ Vrabec, DP. (May 1994). "The inverted Schneiderian papilloma: a 25-year study.". Laryngoscope 104 (5 Pt 1): 582-605. PMID 8189990.

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