SMARCA4/BRG1-Deficient Sinonasal Carcinoma: Morphologic Spectrum of an Evolving Entity

Context.— Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS). Objective.— To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features. Design.— SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases. Results.— Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment had better outcome. Conclusions.— SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.

A Challenging and Rare Case of Metastatic Follicular Dendritic Cell Sarcoma Originating from a Tonsil

Introduction/Objective Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor of follicular dendritic cells. Most cases of FDCS are described in lymph nodes, but it can involve extra-nodal locations such as the tonsil. Methods/Case Report We report a case of a 55-year-old male with a 6-month history of a slow growing left neck mass. The patient had a poorly differentiated carcinoma of the left tonsil diagnosed based on morphologic features eight years ago, followed by chemoradiation, and subsequent left tonsillectomy without tumor identified. Imaging reported a 4.0 cm mass in the left neck level III lymph node location. Biopsy of the mass revealed a spindle cell neoplasm. It was difficult to reach a definitive diagnosis despite an extensive work-up. Review of the previous left tonsil biopsy showed a pleomorphic epithelioid cell proliferation. On the radical resection specimen of the left neck mass, a 4.5 cm, tan-gray, fleshy, necrotic mass was present. Microscopically, it demonstrated a neoplasm with spindle cell and epithelioid cell proliferation, with extensive necrosis. A wide panel of immunostains was performed; the tumor cells showed positivity for CD21, CD23, CD35, and focally weak positivity for cytokeratin OSCAR and Synaptophysin. Squamous cell markers were negative. These findings are consistent with FDCS. Further work-up on the original tonsil tumor displayed immunostaining profile of FDCS. This case was consulted with the National Institute of Health (NIH) for confirmation of the diagnosis. Results (if a Case Study enter NA) NA Conclusion Morphologically, FDCS can present with various histologic patterns, which can lead to diagnostic pitfalls, and common confusion with poorly differentiated carcinoma or soft tissue tumors, especially in needle biopsies. Generally, patients present with a prolonged clinical course, with a 50% and 25% chance of recurrence and metastasis respectively, hence the awareness and accurate diagnosis of this entity is important in biopsies of lymph nodes or of extranodal locations such as a tonsil.

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

BackgroundMelan-A/MART-1 is a melanocytic differentiation marker, which is recognized as an antigen on melanoma cells. It is relevant for pathologists as a useful diagnostic marker in the diagnosis of melanocytic tumors. However, the expressional pattern of Melan-A in poorly differentiated carcinoma of lung has never been reported so far.Case presentationHere, we report a 77-year-old female patient who presented with a large mass in the right lung and was subsequently diagnosed with a poorly differentiated carcinoma of lung. We unexpectedly found that the carcinoma in this patient exhibited diffuse Melan-A expression. ConclusionThis is the first case reported of a poorly differentiated carcinoma of lung with Melan-A expression. This report shows that Melan-A can express in poorly differentiated carcinoma, and highlights a potential diagnostic pitfall in the diagnosis of carcinoma, which urges pathologists to exercise caution in cases where Melan-A positivity and illustrates the need for further immunohistochemical or molecular examination to avoid misdiagnosis.

Challenging Diagnosis in NUT Carcinoma

Nuclear protein in testis (NUT) carcinoma represents a highly aggressive, poorly differentiated carcinoma that is genetically defined by rearrangement of NUT gene. The histomorphological appearance ranges from entirely undifferentiated carcinoma to carcinoma with prominent squamous differentiation. NUT carcinoma can display neuroendocrine features. Although it is typically distributed along the midline axis, it may manifest in nonmidline locations. The majority of patients develop rapidly disseminated disease. We illustrate 2 cases of NUT carcinoma, one located in the lung, which closely resembled a neuroendocrine carcinoma, and the other one with assumed lung origin demonstrating metastatic dissemination with diffuse bone involvement, which was clinically first suspected to be a hematological malignancy. Due to its undifferentiated nature, NUT carcinoma may be confused with many entities. NUT immunohistochemistry is considered to be sufficient for the diagnosis. Fluorescence in-situ hybridization analysis and next-generation sequencing are currently used to confirm the diagnosis.

NSD3-NUTM1-rearranged carcinoma of the median neck/thyroid bed developing after recent thyroidectomy for sclerosing mucoepidermoid carcinoma with eosinophilia: report of an extraordinary case

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an exceedingly rare low-grade thyroid malignancy of unknown histogenesis. NUT carcinoma is another rare, highly aggressive neoplasm with predilection for the midline, defined by recurrent NUTM1 fusions. The bromodomain family genes (BRD4 or BRD3) and rarely NSD3, ZNF532, or others are known fusion partners. We describe an extraordinary case of a 42-year-old female with a thyroid SMECE treated by thyroidectomy and neck dissection. She presented 6 months later with extensive midline recurrence encasing/compressing the trachea. Biopsy revealed poorly differentiated carcinoma with abrupt squamous differentiation, suggestive of NUT carcinoma. Immunohistochemistry confirmed expression of monoclonal NUT antibody. Targeted RNA sequencing revealed the NSD3-NUTM1 fusion in the NUT carcinoma, but not in the SMECE. This unique case highlights unusual sequential origin of two exceptionally rare entities at same anatomic site and underlines the necessity of sampling unexpectedly aggressive recurrences of otherwise indolent malignancies.

Incident of Thyroid Carcinomas and Other Pathologies with Age Correlation in Patients Presented with Palpable Thyroid Masses Undergoing Thyroidectomies

Background: Thyroid cancer is the leading cause of death both in developing and developed countries. Patients present with enlarged thyroid. Radiology shows hot and cold nodules. Thyroidectomy or lobectomy is done to rule out malignancy. Objective: To determine the incidence of thyroid carcinomas and other pathologies in thyroidectomy specimen of different age group patients presenting with clinically enlarged thyroid. Study Design: Cross-sectional study. Settings: Department of Histopathology, Foundation University Medical College (FUMC), Islamabad and Department of surgery, Fauji Foundation Hospital (FFH), Rawalpindi Pakistan. Duration: from Jan 2012 to March 2019. Methodology: All the thyroidectomies specimens send from Surgery department of FFH to Histopathology Department of FUMC during study period and fulfilling the pre-set criteria were included in the study. All the data and results were analyzed using SPSS version 17.0. Results: Out of 500 total patients, 89% (n=445) were diagnosed as having multinodular goiter, 2.6% (n=13) thyroiditis, 2.2% (n=11) follicular adenoma, 0.8% (n=4) Hurthle cell adenoma, 0.2%(n=1) hyalinizing trabacular adenoma and thyroid carcinomas. The carcinomas comprised 2.6%(n=13) papillary carcinoma, 0.8%(n=4) poorly differentiated carcinoma,0.8%(n=4) anaplastic carcinoma,0.6%(n=3) medullary carcinoma and 0.4%(n=2) follicular carcinoma. In 445 patients of multinodular goiter 158 patients were in the age range of 41-50 years, in 13 cases of thyroiditis 7 were in the age range of 31-40 years, in 11 cases of follicular adenoma 4 patients were in the age range of 31-40 years, in 4 cases of hurthle cell adenoma 3 patients were in the age range of 41-50 years, in 13 cases of papillary thyroid carcinoma 5 patients were in the age range of 31-40 years, in 4 cases of poorly differentiated carcinoma 2 patients were in the age range of 41-50 years and in 4 cases of anaplastic carcinoma 2 patients were in the age range of 61-70 years. Conclusion: The study concluded that thyroid carcinomas collectively constituted 5.20% of the study cases. Papillary carcinoma was the most frequent malignant neoplasm constituting 2.6 % and occurring mostly in the age range of 31-40 years, while anaplastic carcinoma comprised of 0.8% of malignant lesions occurring in the age range of 61-70 years. The most frequent cause of thyroid enlargement was multinodular goiter (89%) with majority of the patients in the age range of 41-50 years.

Massive Bone Marrow Carcinomatosis Presenting with Leukoerythroblastic Blood Reaction

We present a case of an extensive bone marrow infiltrate of poorly differentiated carcinoma, in a 19-year-old male with suspected progression of sinusal undifferentiated carcinoma, after several lines of treatment.