Mandible & maxilla
Clear cell carcinoma of salivary gland
Last author update: 1 March 2016
Last staff update: 10 May 2021
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PubMed Search: Clear cell carcinoma [title] salivary gland
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Clinical images | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Martinez A. Clear cell carcinoma of salivary gland. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillaclearcellcarcinomasalivary.html. Accessed December 4th, 2024.
Definition / general
- Rare, malignant, translocation associated epithelial salivary gland tumor characterized by nests and cords of clear cells surrounded by hyalinizing stroma
- EWSR1 rearrangements in >80% of cases
Terminology
- AFIP uses terminology - clear cell adenocarcinoma
- WHO uses terminology - clear cell carcinoma, not otherwise specified (NOS)
- Also called hyalinizing clear cell carcinoma (HCCC)
Epidemiology
- Rare, < 1% of all salivary gland tumors
- Mean age: 6th decade
- Slightly more common in females (1.2:1)
Sites
- More common in minor salivary glands (~80%), particularly base of tongue, palate, floor of mouth, tongue and buccal mucosa in oral cavity / oropharynx (Head Neck 2016;38:426)
- Less common in major salivary glands; parotid more common than submandibular gland
Etiology
- As with many translocation tumors, lesion tends to pursue a line of differentiation rather than originate from a particular line of derivation
- Currently, there is evidence that HCCC pursues a squamous line of differentiation based on:
- Ultrastructurally, the tumors have tonofilaments, desmosomes and glycogen
- Frequent connection to the surface mucosal epithelium
- Electron microscopy findings including some basal lamina reduplication
Clinical features
- Clinically, patients present with swelling and mass lesion
Diagnosis
- Diagnosis dependent on clinical, radiologic and pathologic correlation
Prognostic factors
- Generally, has an indolent clinical course with a good prognosis
- Recurrence rate ~11%
- The presence of necrosis, local / regional disease or positive margins is associated with recurrence
- Some sources say ~25% have regional nodal metastases at presentation (Cancer 2009;115:75) but recent studies have challenged that (Genes Chromosomes Cancer 2011;50:559)
Case reports
- 36 year old woman with painless swelling of upper right back tooth region (J Oral Maxillofac Pathol 2011;15:335)
- 37 year old woman with painless swelling on ventral tongue (J Pathol Transl Med 2015;49:351)
- 52 year old woman with gradually growing and indolent mass in right buccal mucosa (Case Rep Otolaryngol 2015;2015:471693)
- 60 year old man with a swelling in the base of the tongue (Case of the Month #483)
Treatment
- Primary resection with negative margins
Clinical images
Images hosted on other servers:
Echo, CT, MRI
Local findings
Mass
Operative findings
Postoperative
Gross images
Microscopic (histologic) description
- Nests and cords of clear cells with distinct borders and round to oval nuclei
- As with many translocation tumors, many areas of the lesion have a monotonous appearance
- A minority of the cells can contain eosinophilic as opposed to clear cytoplasm
- The cells are surrounded by variably hyalinized stroma
Microscopic (histologic) images
Contributed by Dr. Pooja Navale:
Images hosted on other servers:
Stratified squamous epithelium
Mitotic figures
Islands of of epithelial cells
Hyalinized areas
Carmine stain
PAS
p63. CD10, PAS
P63+
Pancytokeratin+
AE1/AE3, S100, SMA
Mucicarmine-
SMA-
Calponin-
S100-
Positive stains
Molecular / cytogenetics description
- > 80% show EWSR1 rearrangement by FISH
Differential diagnosis
- Clear cell odontogenic carcinoma (CCOC)
- Malignant epithelial odontogenic neoplasm also composed primarily of clear cells, which usually occurs in anterior mandible
- Unlike HCCC, the nests or cords may show focal palisading of basal cells (“ameloblastic”)
- Both tumors have EWSR1 rearrangements
- May represent "odontogenic analogue"
- Clear cell variant of calcifying epithelial odontogenic tumor (CEOT)
- Benign epithelial odontogenic neoplasm, clear cell variant may be composed primarily of clear cells
- Occurs in posterior mandible, intra-osseous location
- Variably sized polyhedral eosinophilic epithelial cells with distinct cell borders are arranged in small clusters, trabeculae, islands or a sheet-like pattern
- Nuclear pleomorphism is expected, but without appreciable mitotic activity
- Eosinophilic amyloid-like matrix material is haphazardly deposited in association with the tumor islands and calcified concentric profiles (Liesegang rings) are often identified.
- Ancillary studies show the epithelial cells of CEOT highlight with cytokeratin AE1/3, CK5/6 and p63, and amyloid-like material exhibits apple green birefringence when stained with Congo red and viewed with polarized light
- Clear cell renal cell carcinoma (CCRCC)
- Usually a known history of renal cell carcinoma
- CCRCCs are positive for PAX8
- Epithelial-myoepithelial carcinoma
- Malignant bisphasic tumor with an inner duct-like epithelial component and an S100+ outer myoepithelial component
- Occurs more commonly in the major salivary glands
- Hyalinizing clear cell carcinoma has only the clear cell epithelial component, and is S100-
- Mucoepidermoid carcinoma, clear cell variant
- Malignant epithelial tumor with variable amounts of mucous, epidermoid and intermediate cells
- Parotid gland most common location
- Mucicarmine will be positive in mucocytes
- Can be associatied with MAML2 rearrangement and NOT EWSR1 like HCCC
- Sinonasal renal cell-like adenocarcinoma (SRCLA)
- May be difficult to differentiate, but clear cell tumors involving the maxillary or palatal structures require consideration of a sinonasal neoplasm with secondary involvement of the oral region (Int J Clin Exp Med 2014;7:5469)
- Rare tumor characterized by a clear cell glandular proliferation, most often involving the nasal cavity, associated with a favorable clinical course
- Has round cells with clear cytoplasm and a prominent nucleolus arranged in a follicular pattern
- A tubular arrangement and papillary architecture of the clear cell proliferation have also been described
- No mucinous or myoepithelial differentiation, no necrosis, no hyalinization of stroma
- SRCLA vs. HCCC: no stromal hyalinization, no stromal vascularity; often has larger clear cells than HCCC and CCOC; has robust CA-IX immunostaining vs. focal positive in HCCC; negative for EWSR1 rearrangement
Additional references
Board review style question #1
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
A. HTN3-MSANTD3
B. EWSR1-ATF1
C. ETV6-NTRK3
D. MYB-NFIB
Board review style answer #1
