OBJECTIVE: Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis.
METHODS: We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period.
RESULTS: Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable.
CONCLUSIONS: Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses.

Hyalinizing clear cell carcinoma is an uncommon neoplasm arising in minor salivary glands. We present a rare case of hyalinizing clear cell carcinoma in the base of the tongue. We report a case of a 38-year-old female presented with a progressive history of hemoptysis and dysphagia over the course of 4 years. Examination revealed a mass originating from the base of the tongue with a biopsy confirmed as hyalinizing clear cell carcinoma . An Ovid MEDLINE and PubMed literature review was conducted due to the rarity of this type of tumor. The patient underwent surgical excision with immediate reconstruction with radial forearm free flap followed with adjuvant radiotherapy and was disease free at her most recent follow-up (12 months). Our review included a total of 13 new cases, including our case. The majority of the cases presented with dysphagia. Surgical excision is the mainstay of treatment, and overall these patients have a good prognosis. Our case highlights a rare presentation of hyalinizing clear cell carcinoma of the base of the tongue, successfully treated with surgical excision, free tissue reconstruction and adjuvant radiotherapy.

BACKGROUND: Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland-type carcinoma. Until now, 23 cases of pulmonary HCCC have been reported.
METHODS: Here, we present a patient with primary pulmonary HCCC along with vocal-cord squamous cell carcinoma (SCC) revealed by biopsy examination. The patient underwent radiotherapy for vocal-cord SCC, followed by right upper lobectomy and lymph node dissection 10 months later. Histology revealed polygonal cells with eosinophilic or clear cytoplasm in the myxoid matrix together with hyaline degeneration. The tumor involved the whole layer of the segmental bronchus and regionally involved the alveolar tissue along with one intrapulmonary lymph node. Targeted RNA sequencing revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1)- activating transcription factor 1 (ATF1) fusion. We analyzed the data on pulmonary malignant tumors between 2000 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database and reviewed all cases of pulmonary HCCC with EWSR1 fusion by searching PubMed. The results showed that head and neck (HN) adenoid cystic carcinoma (ACC) (47.89%) and HNSCC (22.54%) were the most common carcinomas occurring with pulmonary salivary gland-type malignant tumors. Screening of 24 cases of pulmonary HCCC with EWSR1 fusion revealed that five cases demonstrated lymph node metastases and only two had documented tumor recurrences. HCCC is rare and easily misdiagnosed as SCC, but the treatment regimen differs between pulmonary HCCC and SCC.
CONCLUSIONS: Hence, pulmonary tumors with clear cells must be diagnosed with caution. Next-generation sequencing (NGS) may be useful for diagnosis, especially in cases with a history of squamous cell carcinoma (SCC).

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes-a case of \"high-grade transformation\" and 1 \"possessing a novel partner gene for EWSR1.\" We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the \"high-grade transformation,\" harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4-fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1-fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the \"whole-genome doubling\" and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with \"high-grade transformation.\" Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, \"high-grade transformation\" and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland-type tumor newly recognized in recent years, with approximately 21 cases reported to date in the English literature, which constitutes a challenge in pathology diagnosis, particularly in small biopsy specimens. Here, we present a case of pulmonary HCCC diagnosed by computed tomography-guided percutaneous lung biopsy in a 70-year-old man\'s right lower lung. Although the morphology and immunophenotype of the tumor suggested the diagnosis of mucoepidermoid carcinoma, fluorescence in situ hybridization failed to reveal the rearrangement of MAML2 gene, which is characteristic of mucoepidermoid carcinoma. Instead, further molecular genetic testing showed that the tumor harbored a rare EWSR1::CREM fusion combined with a previously unreported IRF2::NTRK3 fusion. Pulmonary HCCC is commonly regarded as a low-grade malignant tumor with an indolent course, but this case has a different biological behavior, presenting extensive dissemination and metastases at the time of diagnosis, which expands our understanding of the prognosis of this tumor. The patient has had five cycles of combination chemotherapy and has been alive with the tumor for eight months.

暂无摘要。

Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland carcinoma with a generally indolent behavior, characterized by recurrent chromosomal translocation involving EWSR1 (22q12.2) leading to two fusion genes EWSR1::ATF1 or EWSR1::CREM. We report one case of HCCC with a novel SMARCA2::CREM fusion, identified by targeted RNA next generation sequencing by LD-RT-PCR, which has until now never been described in salivary glands. The exon 4 of SMARCA2 is fused to exon 5 of CREM. This fusion has been described previously in only one tumor, a central nervous system tumor (intracranial mesenchymal tumor) but not in other FET::CREB fused tumors. This fusion was confirmed by CREM break-apart FISH and reverse transcriptase polymerase chain reaction (RT-PCR). The tumor cells showed retained expression of INI1, SMARCA2, and SMARCA4 by immunohistochemistry. We compare its clinical, histopathological, immunophenotypic, genetic features with those previously described in HCCC, FET::CREB fusion-positive. Our results added data suggesting that different histomolecular tumor subtypes seem to be included within the terminology \"HCCC, FET::CREB fusion-positive,\" and that further series of cases are needed to better characterize them.

Pulmonary hyalinizing clear cell carcinoma (HCCC) is a new and rare form of lung salivary gland tumor. Only twenty-two cases have been reported in the literature to date. Furthermore, their clinicopathological features have not been fully characterized. In this paper, we describe the clinicopathological characteristics, immunohistochemical features, and molecular genetic changes in two HCCC cases. We also simultaneously reviewed related literature on similar cases reported. Of the two cases, one was of a 58-year-old man with a 4.3 cm lung tumor, which was the largest among all previously reported cases. The tumor showed an infiltrative growth pattern and perineural and vascular invasion microscopically. Moreover, nuclear grooves, high mitotic figures, and comedo necrosis were observed in addition to classic morphological features. More importantly, rare pseudopapillary structures were observed. The second case was of a 60-year-old woman in whom the tumor was mainly composed of multiple cysts filled with mucus. The remaining focal solid areas of the tumor comprised clear and acidophilic cells embedded in the hyalinizing stroma. Immunohistochemical analysis revealed that the tumor cells of both cases were positive for CK5/6, p40, and p63 expression, but negative for napsin A, TTF-1, and SOX10 expression. The HCCC diagnosis in both cases was validated by fluorescence in-situ hybridization (FISH) examination, which showed Ewing sarcoma breakpoint region 1-activating transcription factor 1 (EWSR1-ATF1) gene fusion. Primary pulmonary HCCC is a rare lung tumor originating from the bronchial mucosa, and its histological features may vary, such as rare pseudopapillary structures and abundant cysts. Thus, the diagnosis should be a combined analysis of histopathological characteristics with immunophenotype and molecular examination, including EWSR1-ATF1 gene fusion detection.

Minor salivary gland malignancies are a rare entity among head and neck tumors. As in major gland neoplasms, adenoid cystic carcinoma and mucoepidermoid carcinoma are the most common histological subtypes. Malignant tumors affecting minor salivary glands include a wide range of histopathologic types. Localization in the epipharynx and hyalinizing clear cell carcinoma subtype are exceedingly rare. A 47 year-old male presented to our clinic with a complaint of slowly progressing left-sided nasal obstruction. Endoscopy revealed a well-defined nodular epipharyngeal mass. Radiographic evaluation discovered a nonvascularized tumor of the tubal protuberance. The tumor was treated with wide local excision. Staging at the time found no evidence of regional lymph node metastases. Histologic examination revealed a hyalinizing clear cell salivary gland carcinoma demonstrating an EWSR1-ATF1 gene fusion. Restaging endoscopy and radiographic imaging 3 months after initial therapy did not reveal any signs of tumor persistence. The patient is currently in follow-up.

BACKGROUND: Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors. They most commonly involve the minor salivary glands of the head and neck. HCCC that occurs in uncommon locations and examining samples from small biopsy pose a diagnostic challenge for most pathologists.
METHODS: We herein report a primary pulmonary HCCC diagnosed by small biopsy and summarize its histologic, immunophenotypic, and molecular features along with a review of 11 previously reported cases to emphasize the potential diagnostic pitfalls.
CONCLUSIONS: Small biopsy diagnosis of primary pulmonary HCCC is challenging. A collection of mimics needed to be ruled out. Awareness of the key morphologic features of pulmonary HCCC combined with essential immunohistochemistry and molecular tests contributes to the correct diagnosis.