• Male
• Humans
• Adult
• Sphenoid Sinus
• Fluorodeoxyglucose F18
• Positron Emission Tomography Computed Tomography
• Head and Neck Neoplasms
• Adenocarcinoma, Clear Cell/pathology
• Salivary Gland Neoplasms/pathology

• Adenocarcinoma
• Head and neck neoplasm
• Salivary gland

• Chimeric protein
• Gene fusion
• Neo-antigen
• Sinonasal malignancies
• Translocation

• Humans
• Transcription Factors/genetics
• Nuclear Proteins/genetics
• Neoplasms/genetics
• Translocation, Genetic
• Gene Fusion
• Oncogene Proteins, Fusion/genetics
• Poly-ADP-Ribose Binding Proteins/genetics
• Chromosomal Proteins, Non-Histone/genetics
• Oncogene Proteins/genetics
• Oncogene Proteins/metabolism
• Cell Cycle Proteins

• ZIA DC000092 Intramural NIH HHS

As 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.

Clinicopathological 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.

Histologically, 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).

CCCs 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.

• clear cell carcinoma
• clear cell sarcoma
• hyalinizing
• immunohistochemistry
• salivary gland

• EWSR-ATF1
• Head and neck
• Hyalinizing clear cell carcinoma
• Oral cavity

• Adenocarcinoma, Clear Cell/pathology
• Adult
• Female
• Head and Neck Neoplasms/pathology
• Humans
• Male
• Middle Aged

• Clear cell carcinoma
• EWSR1 fusion
• Hyalinizing clear cell carcinoma
• Nodal metastasis
• Salivary gland tumor

Hyalinizing clear cell carcinoma (HCCC), also known as clear cell carcinoma, not otherwise specified [CCC, (NOS)], is a rare minor salivary gland tumor characterized by proliferation of clear cells, organized in trabecular cords, or solid nests within loose to densely hyalinized stroma. It is considered a diagnosis of exclusion by the World Health Organization (WHO) because other salivary tumors may also have a clear cell component. Hence, there is a wide differential diagnosis. EWSR1-ATF1 gene rearrangements are fairly specific for this tumor, however, one of the recent studies have described its presence in clear cell odontogenic carcinoma (CCOC) one of its histologic mimickers. EWSR1 and CREM fusions have recently been described in these tumors but its importance is still not well described. Here we present a case of a 33-year-old woman who presented with a recurrent lesion of the soft palate. Her initial lesion was resected and diagnosed as low-grade myoepithelial tumor. Surgical margins at the time of initial resection were positive and the re-excision was recommended but the patient did not undergo surgery. Two years later, local recurrence at the same site was found and an excision was performed yielding negative margins. Histopathologic examination revealed features consistent with hyalinizing clear cell carcinoma. The patient remains disease free 1 year after the re-excision. The pathology, clinical characteristics, differential diagnosis and treatment of hyalinizing clear cell carcinoma are reviewed.

• Carcinoma
• EWSR1-ATF1 fusion protein
• Head and Neck Neoplasms
• Mucoepidermoid
• PTCH protein, human
• Salivary Gland Neoplasms

Hyalinizing clear cell carcinoma (HCCC) is an uncommon tumor that originates in the salivary glands. This neoplasia constitutes less than 1% of minor salivary gland tumors.

A 67-year-old female visited the maxillofacial surgery department owing to a smooth, slightly yellowish protruding mass on the left side of the floor of the mouth, at the level of the molars; the tumor mass had a soft consistency on palpation and did not adhere to deep planes. The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen. Normal glandular tissue was absent, periodic acid-Schiff with and without diastase stains, and immunohistochemical reactions were performed to confirm the diagnosis. This is the second case reported in the literature of HCCC arising in the floor of the mouth.

HCCC is a rare salivary gland tumor that has not been studied extensively. Its diagnosis is usually challenging, because clinically, it can be confused with a benign neoplasm.

• Hyalinizing clear cell carcinoma
• Salivary gland tumor
• Immunohistochemical reactions
• Case report

• EWSR1
• FISH
• Hyalinizing clear cell carcinoma
• Immunohistochemistry
• Morphology
• Salivary glands