Clinicopathological and molecular study of 10 salivary gland clear cell carcinomas, with emphasis on rare cases with high grade transformation and occurring in uncommon sites

Lanlan Xuan,Suxia Wang,Jianwei Yuan,Honggang Liu,Jianguo Wei

doi:10.1186/s13000-022-01200-z

Abstract

BackgroundAs a rare salivary gland malignancy, clear cell carcinoma (CCC) is easily misdiagnosed. This study identified the features that allow better recognition of the clinicopathological and molecular characteristics and the prognosis of CCC, focusing on high-grade transformation (HGT) in this tumor and cases arising in uncommon sites.MethodsClinicopathological and follow-up data for 10 CCC samples were retrieved. Immunohistochemical (IHC) staining was performed, and fluorescence in situ hybridization (FISH) was used to detect EWSR1 gene rearrangements, EWSR1–ATF1 gene fusions, and MAML2 gene rearrangements.ResultsHistologically, typical CCCs comprised bland polygonal or round cells with clear cytoplasm. In contrast with typical CCCs, HGT tumor cells exhibited nuclear pleomorphism, high nuclear-to-cytoplasmic ratios, high mitotic activity, and necrosis. Rare morphologic features such as pseudopapillae, gland-like spaces, and entrapped ducts were also observed. Occasionally, tumors involving the oral cavity might arise from the overlying epithelium of the mucosal surface. Immunohistochemically, all the cases expressed p63, p40, and CK5/6, while myoepithelial-related markers were uniformly negative in all cases. HGT exhibited a wild type p53 expression pattern. FISH demonstrated EWSR1 rearrangement (10/10) and EWSR1–ATF1 fusion (4/5); however, MAML2 remained intact (0/3).ConclusionsCCCs with HGT or occurring in uncommon sites are extremely rare. Combining morphology based IHC and molecular detection provided reliable evidence that the HGT component represented a transformation of CCC rather than the coexistence of another tumor and helped differentiating CCCs in uncommon sites from their mimics, avoiding potential misdiagnosis and inappropriate therapy. The overall prognosis for CCCs is good, except for the HGT cases, which needed continued treatment.

Highlights

As a rare salivary gland malignancy, clear cell carcinoma (CCC) is misdiagnosed
CCC has the characteristic morphology of bland monomorphic tumor cells with clear cytoplasm, arranged in nests, islands, and sheets in a hyalinized stoma, which is why it was originally termed “hyalinizing clear cell carcinoma” (HCCC) [1]
Case selection We searched for a total of 1669 cases of salivary gland tumor (SGT) using the files of the SGT Registry at the Department of Pathology in Beijing Tongren Hospital, of which 10 cases pertained to CCC, accounting for 0.6%

Summary

Introduction

As a rare salivary gland malignancy, clear cell carcinoma (CCC) is misdiagnosed. This study identified the features that allow better recognition of the clinicopathological and molecular characteristics and the prognosis of CCC, focusing on high-grade transformation (HGT) in this tumor and cases arising in uncommon sites. Clear cell carcinoma (CCC) is a low-grade salivary gland tumor (SGT), first described by Milchgrub et al in 1994 from a series of 11 cases. CCC is typically present in the minor salivary glands of female patients aged 50–80 years; it is indolent and rarely involves lymph nodes or develops distant metastases [2]. It is difficult to definitively diagnose CCCs found in uncommon sites due to the lack of distinguishing characteristics; misdiagnosing CCCs in uncommon sites as other malignancies with clear cell morphologic changes is common

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Discussion

Conclusion