RESUMO
Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.
Assuntos
Adenocarcinoma , Carcinoma Ductal , Carcinoma Intraductal não Infiltrante , Neoplasias das Glândulas Salivares , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Fusão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases , Fatores de TranscriçãoRESUMO
The nature of the lymphoid stromal component in Warthin tumor and lymphadenoma of the parotid gland has been a controversial topic in salivary gland pathology for decades. Two theories exist: first, that these tumors arise from salivary gland inclusions within intraparotid lymph nodes; and second, that they arise within salivary gland parenchyma and induce tumor-associated lymphoid proliferation (TALP). A recent study demonstrated that low molecular weight cytokeratin is effective in distinguishing salivary gland tumors within lymph nodes from those inducing TALP via identification of extrafollicular reticulum cells, which are only found in true lymph nodes. Twenty-one Warthin tumors and 4 lymphadenomas were retrieved from the archives of the Department of Pathology at University of Texas Southwestern Medical Center. Cam5.2 immunohistochemistry was performed on each case and independently evaluated by two pathologists. Extrafollicular reticulum cells were identified by Cam5.2 immunostaining in 21 of 21 Warthin tumors (100%), and 3 of 4 lymphadenomas (75%). Extrafollicular reticulum cells were consistently localized to the perisinusoidal and paracortical areas of the lesions studied. Extrafollicular reticulum cells were identified via low molecular weight cytokeratin Cam5.2 immunohistochemistry in all of the Warthin tumors and most of the lymphadenomas evaluated. This finding strongly supports the notion that these most if not all of these tumors arise within intraparotid lymph nodes, presumably from salivary gland inclusions entrapped during embryonic development.
Assuntos
Adenolinfoma/patologia , Biomarcadores Tumorais/análise , Biomarcadores/metabolismo , Queratinas/metabolismo , Linfonodos/patologia , Neoplasias Parotídeas/patologia , Biomarcadores/análise , Biomarcadores Tumorais/metabolismo , Humanos , Imuno-Histoquímica , Queratinas/análise , Neoplasias das Glândulas Salivares/patologiaRESUMO
Nuclear protein in testis (NUT) carcinoma is a rare and highly aggressive epithelial malignancy defined by rearrangement of the NUTM1 gene on chromosome 15q14. Histologically, NUT carcinoma is an undifferentiated carcinoma formed by sheets and nests of primitive and monotonous "round blue cells" with foci of abrupt keratinization in a subset. NUT carcinoma runs a fulminant clinical course and is almost always quickly lethal, with a median overall survival of only 6.7 months. There is no consensus regarding treatment for this disease, and most patients respond poorly to conventional chemotherapy and radiation. We report a case of NUT carcinoma in an African-American man who initially presented in 2009 with a tracheal mass at age 28. Although fluorescence in situ hybridization (FISH) assays for NUTM1 and BRD4 rearrangements were negative, he was diagnosed based on diffusely positive NUT immunostaining and BRD4-NUTM1 on RNA sequencing. Since his initial presentation, he has undergone multiple surgical procedures and radiation therapy. His tumor has recurred twice, but he has survived for 129 months and is currently alive without disease. Long-term survival of patients with NUT carcinoma is incredibly unusual, especially in patients with tumors that exhibit a BRD4 rearrangement. False negative FISH is a pitfall in diagnosing NUT carcinoma; NUT immunostaining and RNA sequencing are more sensitive diagnostic methods.
Assuntos
Carcinoma/diagnóstico , Carcinoma/patologia , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias da Traqueia/diagnóstico , Neoplasias da Traqueia/patologia , Adulto , Carcinoma/genética , Reações Falso-Negativas , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteínas Nucleares/análise , Proteínas de Fusão Oncogênica/análise , Neoplasias da Traqueia/genéticaRESUMO
Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. While salivary gland neoplasia is rare in children, MEC is much more likely to occur in the pediatric population than Warthin tumor, a common benign salivary gland neoplasm associated with smoking and older age. The recently-reported Warthin-like variant of MEC bears a striking histologic resemblance to Warthin tumor, representing a potential diagnostic pitfall. Therefore, low-power observation of Warthin-like features in pediatric salivary gland tumors should prompt careful diagnostic consideration of Warthin-like MEC. Two cases of Warthin-like MEC in the parotid glands of teenaged patients were identified in the archives of the Department of Pathology at Children's Medical Center in Dallas, Texas. Surgical material for each case was reviewed and both diagnoses were verified. Fluorescence in situ hybridization (FISH) for CRTC1-MAML2 fusion was performed in both cases. Histologically, neither tumor exhibited the classic bilayer of oncocytic epithelial cells characteristic of Warthin tumor. Instead, the neoplastic epithelial cells exhibited architectural and cytologic atypia, with mucous cells interspersed. CRTC1-MAML2 gene fusions were identified via FISH and confirmed the diagnosis of MEC in both cases. Of note is that the second patient's tumor recurred with features of conventional MEC, indicating the potential for Warthin-like MEC to undergo this morphologic change. The present cases illustrate that Warthin-like MEC, like conventional MEC, may occur in the pediatric population. Pediatric and head and neck pathologists must be aware of this variant's existence and diagnostic criteria to avoid misdiagnosis as benign Warthin tumor.
Assuntos
Adenolinfoma/patologia , Carcinoma Mucoepidermoide/patologia , Neoplasias Parotídeas/patologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/patologiaRESUMO
Ameloblastic carcinoma is a rare odontogenic neoplasm that demonstrates the histologic characteristics of ameloblastoma, accompanied by the cytologic features of malignancy. The spindle-cell variant of ameloblastic carcinoma (SCAC) is exceptionally rare, with a total of 10 cases having been reported in the literature to date. Histologically, a prominent sarcomatoid cell population appears to originate from the epithelial (ameloblastic) component. Like conventional ameloblastic carcinoma, most cases of SCAC occur in individuals older than 40 years of age. Here, 3 additional cases of SCAC are reported, 2 of which occurred in young individuals. Diagnostic criteria to aid in the identification of SCAC are proposed. Finally, histologic and immunohistochemical evidence supporting the occurrence of epithelial-mesenchymal transition in SCAC is presented.