hyalinizing clear cell carcinoma

WP

Definition: Hyalinizing clear-cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with distinctive clear-cell morphology and pattern of hyalinization as well as focal mucinous differentiation. It is associated with a EWSR1 rearrangement.

However, histological overlap exists with other salivary gland tumors, such as epithelial-myoepithelial carcinoma (EMCa), salivary myoepithelial carcinoma, and mucoepidermoid carcinoma (MEC).

Images

 Primary paranasal sinus clear cell carcinoma with ATF1-EWSR1 fusion

• https://twitter.com/PathologyTweet/status/822082629398892544

 Hyalinizing clear-cell carcinoma (HCCC) of the salivary gland

• https://twitter.com/smlungpathguy/status/826544159204990978
• https://twitter.com/aakasharmand/status/1242103491021029376

Microscopy

HCCC consist of cells with abundant clear cytoplasm, arranged in cords, trabeculae or clusters in a hyalinized stroma.

Nuclear pleomorphism is usually minimal and mitoses are infrequently seen.

Owing to their glycogen content, which explains the "clear" appearance under the microscope, tumour cells stain with PAS.

Immunochemistry

 CK+
 p63+
 SMA-
 S100-
 p16+/- ( CDKN2A )

Immunostains for S100 and smooth muscle actin (SMA) are typically negative, but positive for cytokeratins and epithelial membrane antigen (EMA).

HCCCs typically have a recurrent chromosomal translocation, t(12;22), involving the genes EWSR1 and ATF1.[5] The same translocation is seen in clear cell sarcoma.

The histologic differential diagnosis includes mucoepidermoid carcinoma (clear cell variant), acinic cell carcinoma (clear cell variant), epithelial-myoepithelial carcinoma and metastatic clear cell carcinoma.

Molecular biology

 ATF1-EWSR1 gene fusion ( ATF1 and EWSR1 )

• EWSR1-ATF1 fusion gene in hyalinizing clear-cell carcinoma of salivary gland. (21484932)
• The presence of EWSR1-ATF1 fusion in most HCCCs reliably separates these tumors from its histological mimics.
• The distinction from mucoepidermoid carcinoma (MEC) is particularly important, as conventional MEC grading schemes overgrade these indolent HCCCs, potentially impacting on treatment.

See also

 sinonasal tumors
 salivary tumors
 clear cell tumors

• clear cell carcinomas

Open access references

 Hyalinizing clear cell carcinoma: report of eight cases and a review of literature. O’Sullivan-Mejia ED, Massey HD, Faquin WC, Powers CN. Head Neck Pathol. 2009 Sep;3(3):179-85. PMID: 20596970 [Free]

 Hyalinizing clear cell carcinoma: case series and comprehensive review of the literature. Solar AA, Schmidt BL, Jordan RC. Cancer. 2009 Jan 1;115(1):75-83. Review. PMID: 18980290 [Free]

A hyalinizing clear cell carcinoma (HCCC) is a rare low-grade tumor of the salivary glands made up of clear cells that form cords and nests in hyalinized stroma. Primary HCCCs of the paranasal sinus have been rarely described.

Paywall references

 Primary paranasal sinus clear cell carcinoma with EWSR1-ATF1 fusion: report of two molecularly confirmed cases exhibiting unique histopathology. Hum Pathol doi : 10.1016/j.humpath.2016.09.036

 EWSR1 Genetic Rearrangements in Salivary Gland Tumors: A Specific and Very Common Feature of Hyalinizing Clear Cell Carcinoma. Shah AA, Legallo RD, van Zante A, Frierson HF Jr, Mills SE, Berean KW, Mentrikoski MJ, Stelow EB. Am J Surg Pathol. 2013 Feb 15. PMID: 23426124

 EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordoñez B, Have C, Asa SL, Leong IT, Bradley G, Klieb H, Weinreb I. Genes Chromosomes Cancer. 2011 April PMID: 21484932