Salivary glands
Primary salivary gland neoplasms - malignant
Clear cell carcinoma

Senior Author: Tony Ng, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.
Tony Ng, M.D., Ph.D.

Topic Completed: 17 December 2018

Revised: 11 October 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Clear cell carcinoma salivary glands[TI]

See also: Mandible / maxilla: Clear cell carcinoma of salivary gland

Tony Ng, M.D., Ph.D.
Page views in 2018: 140
Page views in 2019 to date: 2,161
Cite this page: Chapman E, Ng T. Clear cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/salivaryglandsclearcellcarcinoma.html. Accessed December 13th, 2019.
Definition / general
  • Unusual salivary gland tumor arising primarily in minor salivary gland sites
  • Molecularly defined by expression of EWSR1-ATF1 fusion oncogene or related fusion variants
  • Clear cell odontogenic carcinoma is its counterpart in gnathic bones and shares morphologic, immunohistochemical and molecular characteristics
  • See also clear cell carcinoma in the Mandible / Maxilla chapter
Essential features
  • Unusual salivary gland tumor
  • Most common sites are minor salivary glands of oropharynx and oral cavity (> 80%)
  • At least focal clear cell morphology with or without hyalinizing background
  • Molecularly defined by presence of EWSR1 fusion (ATF1 most common partner)
  • Usually low grade but high grade transformation with aggressive behavior reported
  • Important to differentiate from other primary and metastatic tumors
Terminology
  • Also called hyalinizing clear cell carcinoma
  • Clear cell carcinoma, not otherwise specified (NOS) in WHO 2005 classification
  • Clear cell adenocarcinoma in AFIP classification
ICD coding
  • ICD-10: C00 - C14 - Malignant neoplasm of lip, oral cavity and pharynx
  • ICD-O: 8010 / 3 - Carcinoma, NOS epithelial tumor, malignant
  • ICD-O: 8005 / 3 - Malignant tumor, clear cell type
Epidemiology
Sites
  • > 80% arise in intraoral minor salivary glands (most commonly base of tongue and soft palate)
  • Also reported in major salivary gland (parotid > submandibular) and other sites with salivary / seromucinous glands (e.g. nasopharynx, hypopharynx, larynx, nasal cavity, lacrimal gland, endobronchial)
Etiology
Clinical features
  • Submucosal lump presents with swelling or dysphagia; may ulcerate, may be painful
Radiology description
  • Fairly well circumscribed, contrast enhancing, endophytic or exophytic lesion most often arising in oropharyngeal minor salivary gland sites
  • T1 isointense, T2 hyperintense in reported case (AJNR Am J Neuroradiol 2007;28:127)
Radiology images

Images hosted on PathOut server:

Contributed by Tony Ng, M.D., Ph.D.

CT scan



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Echo, CT, MRI

Prognostic factors
Case reports
Treatment
  • Complete resection ± lymph node dissection curative in most cases
  • Should have long term followup
  • Limited data for radiation or chemotherapy (Crit Rev Oncol Hematol 2016;102:55)
Clinical images

Images hosted on PathOut server:

Contributed by Pallavi Parashar, D.D.S.

Submucosal mass



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Buccal mass

Gross description
Gross images

Contributed by Pooja Navale, M.D.


Contributed by Erin Chapman, M.D.

Submucosal mass

Microscopic (histologic) description
  • Cells arranged in nests, cords, trabeculae and sheets
  • Clear to eosinophilic cells with distinct borders; all have at least focal clear cells
  • Monomorphic ovoid nuclei
  • With or without dense hyalinized stroma; some have myxoid areas
  • Almost half of cases show at least focal mucinous differentiation but not always visible without special stains (Head Neck Pathol 2013;7:28)
  • Often connects to surface, possibly with pagetoid pattern
  • Low mitotic rate
  • Infiltrative edges with desmoplastic stroma; perineural invasion is common
  • May have tumor associated lymphoid proliferation and overlying pseudoepitheliomatous hyperplasia
  • Rarely show ductal differentiation, cyst formation or keratinization / pearls
  • Not seen: features of myoepithelial differentiation
  • High grade transformation defined by presence of high grade nuclear atypia with nuclear anaplasia, brisk mitotic activity and tumor necrosis (Head Neck Pathol 2013;7:S37)
Microscopic (histologic) images

Contributed by Pooja Navale, M.D.


Contributed by Tony Ng, M.D., Ph.D.

Soft palate mass

Clear cell proliferation

p40

Base of tongue mass

Clear cell and columnar phenotype

PASD



Buccal mass

Nests and cords of clear cells

Submucosal tissue

Contributed by Erin Chapman, M.D.

Posterior maxilla submucosal tumor

Islands and cords of tumor cells


Images hosted on other servers:

Hyalinizing clear cell carcinoma


Hyalinizing clear cell carcinoma

Cytology description
  • Clear cells that have monomorphic nuclei with grooves and inclusions, naked nuclei and a tigroid background with metachromatic matrix described from a scrape preparation (Diagn Cytopathol 2016;44:338)
Positive stains
Electron microscopy description
Electron microscopy images

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Filopodia and desmosomes

Molecular / cytogenetics description
Differential diagnosis
Board review question #1
The differential diagnosis for clear cell carcinoma of minor salivary gland (pictured) does not include



  1. Metastatic renal cell carcinoma
  2. Mucoepidermoid carcinoma
  3. Myoepithelial carcinoma
  4. Salivary duct carcinoma
  5. Squamous cell carcinoma
Board review answer #1
D. Salivary duct carcinoma

Comment Here
Board review question #2
80% of cases of clear cell carcinoma of minor salivary gland have rearrangement of which gene, also seen in clear cell sarcoma of soft tissue?

  1. ETV6
  2. EWSR1
  3. FLI1
  4. FUS
  5. MAML2
Board review answer #2
B. EWSR1

Comment Here
Board review question #3
Clear cell carcinoma of salivary gland is most commonly associated with the following gene fusion:

A. HTN3-MSANTD3
B. EWSR1-ATF1
C. ETV6-NTRK3
D. MYB-NFIB
Board review answer #3
B. EWSR1-ATF1
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