Myeloid Neoplasm with PDGFRA Rearrangement Manifesting as a Retromolar Pad Mass.

Myeloid neoplasms with PDGFRA rearrangement are rare, and most commonly present with features of chronic eosinophilic leukemia; however, they rarely manifest as acute myeloid or lymphoblastic leukemia. Patients typically present with symptoms of hypereosinophilia including cardiovascular and pulmonary symptoms. An increase in mast cells is also a common feature of this disease, and there may be elevated serum tryptase with significant clinical overlap with systemic mastocytosis. Here, we present an unusual case of a myeloid neoplasm with PDGFRA rearrangement manifesting as a retromolar pad mass in a patient with a prior diagnosis of systemic mastocytosis. This case highlights the possibility of soft tissue involvement by myeloid neoplasms with PDGFRA rearrangement in the oral cavity. The identification of this entity is of significant clinical importance because many patients can be effectively treated with tyrosine kinase inhibitors.

SOX10 Immunoexpression in Basaloid Squamous Cell Carcinomas: A Diagnostic Pitfall for Ruling out Salivary Differentiation.

SOX10 immunoexpression is increasingly recognized in salivary gland tumors, including but not limited to those with myoepithelial, serous acinar, and intercalated duct differentiation. However, SOX10 expression has not been extensively evaluated in other epithelial tumors that can mimic salivary origin. Basaloid squamous cell carcinoma (SCC) is a unique variant of SCC that shows morphologic overlap with several salivary tumors, including adenoid cystic carcinoma, basal cell adenocarcinoma, and myoepithelial carcinoma. We performed SOX10 immunohistochemistry on 22 basaloid SCCs and 280 non-basaloid SCCs. If tissue was available, we also performed immunohistochemistry for S100 and p16, and in-situ hybridization for high-risk HPV RNA. SOX10 was positive in 13/22 basaloid SCCs (59%), including 5/6 (83%) that were HPV-positive and 6/12 (50%) that were HPV-negative. Only 2/12 basaloid SCC (17%) demonstrated focal S100 expression. All non-basaloid SCCs were SOX10 negative. Frequent positivity for SOX10 in basaloid SCC presents a significant diagnostic pitfall for distinguishing these tumors from various basaloid salivary carcinomas. The preponderance of SOX10 expression in the basaloid variant of HPV-positive SCC also presents a diagnostic challenge in separating it from HPV-related multiphenotypic sinonasal carcinoma. SOX10 may be more broadly considered a marker of basal differentiation and should not be assumed to be specific for salivary origin in epithelial head and neck tumors.

Usefulness of NKX2.2 Immunohistochemistry for Distinguishing Ewing Sarcoma from Other Sinonasal Small Round Blue Cell Tumors.

NKX2.2 is a new immunohistochemical marker that has been reported to be sensitive and specific for Ewing sarcoma (ES). It has not, however, been investigated specifically in the sinonasal small round blue cell tumor (SRBCT) differential diagnosis which includes many tumors specific to that site. It has also not been investigated in the newly recognized "adamantinoma-like" variant of ES. Immunohistochemistry for NKX2.2 was performed on 170 poorly differentiated sinonasal neoplasms: 73 squamous cell carcinomas (67 poorly differentiated, non-keratinizing, or basaloid types and 6 nasopharyngeal carcinomas), 46 olfactory neuroblastomas, 8 sinonasal undifferentiated carcinomas (SNUCs), 6 melanomas, 7 Ewing sarcomas, 6 SMARCB1-deficient carcinomas, 6 teratocarcinosarcomas, 5 alveolar rhabdomyosarcomas, 4 solid adenoid cystic carcinomas, 4 NK/T cell lymphomas, 3 NUT carcinomas, and 2 small cell carcinomas. NKX2.2 was positive in 7 of 7 (100%) Ewing sarcomas, including 3 adamantinoma-like variant (all diffuse, 5 strong and 2 weak). It was also positive in 5 of 6 (83%) teratocarcinosarcomas (strong, but focal), 12 of 46 (26%) olfactory neuroblastomas (diffuse, 2 strong and 10 weak), 4 of 6 melanomas (2 diffuse, 2 focal, all weak), and 1 of 2 small cell carcinomas (diffuse and strong). All squamous cell carcinomas, NUT carcinomas, SMARCB1-deficient carcinomas, SNUCs, solid adenoid cystic carcinomas, NK/T cell lymphomas, and alveolar rhabdomyosarcomas were negative. In the sinonasal SRBCT differential diagnosis, NKX2.2 is a useful and very sensitive marker for Ewing sarcoma, including the treacherous adamantinoma-like variant. At the same time, it is not entirely specific, as it will be positive in a subset of other neuroendocrine/neuroectodermal tumors. As a result, NKX2.2 must be utilized as part of an immunohistochemical panel with other markers, especially cytokeratins, melanoma markers, and CD99.

Cystic major salivary gland lesions: Utilizing fine needle aspiration to optimize the clinical management of a broad and diverse differential diagnosis.

INTRODUCTION: The use of fine-needle aspiration (FNA) cytology for the preoperative evaluation of salivary gland lesions is an accepted but, currently, nonstandardized practice. More specifically, cystic major salivary gland lesions are relatively rare and can be very challenging to diagnose on FNA due to low cellularity and an incredibly broad differential diagnosis. The purpose of this study was to investigate the diagnostic utility of preoperative FNA cytology for cystic major salivary gland lesions. METHODS AND MATERIALS: The electronic pathology archives of The Johns Hopkins Hospital were searched to identify FNA specimens of cystic major salivary gland lesions over a 15 year period (January 1, 2000 to December 21, 2015). The age, race, sex, biopsy site, use of ultrasound guidance, cytopathologic diagnosis, and presence or absence of clinical follow-up were recorded for each patient. Cases were divided into those with and without follow-up. Diagnostic performance between FNA and follow-up data were recorded. RESULTS: A total of 145 cases met the inclusion criteria, while 123 (84.8%) patients had follow-up data available. Of these patients, 67.5% underwent FNA as the only pathologic diagnostic modality. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of cystic neoplasms were 41.6%, 99.0%, 90.9%, and 87.6%, respectively. For cases containing mucin, 100.0% sensitivity and specificity were achieved. CONCLUSION: FNA of cystic salivary gland lesions is a useful clinical decision-making tool that can reduce the number of patients ultimately requiring surgical excision. Although specificity is high, a relatively low overall sensitivity makes clinical and radiologic correlation imperative.

The presence of neuroendocrine features generates a broad differential diagnosis in the fine-needle aspiration of bone and soft tissue neoplasms.

INTRODUCTION: Biopsy of bone and soft tissue (BST) lesions occasionally yields neoplasms with neuroendocrine (NE) features. We identify a differential diagnosis for neoplasms containing NE features when encountered on fine-needle aspiration (FNA) of BST masses. MATERIALS AND METHODS: The cytopathology archives of the Johns Hopkins Hospital were searched for any BST FNA specimen diagnosed as a neoplasm with NE features or in which NE immunohistochemical (IHC) markers were ordered. Specimen diagnoses were reviewed and specimens were excluded if neuroendocrine features were not considered at the time of original diagnosis. RESULTS: A total of 179 specimens met the inclusion criteria. Of these, 64 (36%) and 115 (64%) neoplasms were primary and metastatic, respectively. A total of 29 distinct entities were identified. Sixteen were entities with established NE differentiation and 13 were entities not typically regarded as having an NE origin. The most commonly encountered neoplasms included small cell carcinoma of all primary locations (38), Ewing sarcoma (37), medullary thyroid carcinoma (24), Merkel cell carcinoma (23), and paraganglioma (10). NE IHC markers were ordered in 45% of cases; 86% were positive by at least one NE marker. Entities with established NE differentiation were more likely to be positive for NE IHC than those not typically regarded as having NE differentiation (100% and 59%, respectively). CONCLUSIONS: A variety of BST lesions-including neoplasms not typically thought to have neuroendocrine differentiation-can possess NE cytomorphologic features and/or NE IHC marker positivity. The patient's clinical presentation and history can help narrow the differential diagnosis.