Fine needle aspiration cytology of metastatic SMARCA4‐deficient sinonasal teratocarcinosarcoma: First report in literature

Abstract

Inactivating mutations of SMARCA4 and accompanying loss of BRG1 immunoexpression were recently identified in majority of sinonasal teratocarcinosarcomas (TCS). These rare and aggressive neoplasms have potential for nodal metastasis, presenting opportunities for diagnosis on fine needle aspiration cytology (FNAC). However, their cytological features have not been described till date. A 22‐year‐old male was diagnosed to have SMARCA4‐deficient TCS on a nasal mass biopsy, and was started on neoadjuvant chemotherapy. Four months later, FNAC from cervical lymph nodes showed predominantly discohesive tumor cells with moderate to abundant cytoplasm and enlarged vesicular nuclei with prominent nucleoli. Occasional cohesive fragments showed ovoid to spindled tumor cells attached to fibrovascular cores. Few loosely cohesive cells with scant cytoplasm and nuclei having stippled chromatin, and rhabdoid cells were also seen. Frequent mitoses, apoptosis and nuclear streaking were evident. Overt squamous or glandular differentiation was absent. Tumor cells showed loss of BRG1 immunostaining and β‐catenin immunopositivity on a cell block, consistent with metastatic SMARCA4‐deficient TCS. The diversity of cell types in SMARCA4‐deficient TCS can result in a broad spectrum of cytological features that overlap with that of other regional metastatic tumors including neuroendocrine carcinoma, olfactory neuroblastoma and melanoma. Further, all components of TCS as seen in the primary tumor may not be present in nodal metastases. Thus, SMARCA4‐deficient TCS should be considered in the differential diagnosis of metastatic poorly/undifferentiated malignancies in cervical lymph node aspirates, and appropriate ancillary tests viz. BRG1 immunostaining employed for accurate diagnosis.

Three shades of an unusual mediastinal tumour

“…14 In the thoracic cavity, SMARCA4-deficient non-small cell lung carcinoma (SMARCA4d-NSCLC) is a pertinent differential to consider. In this and BRM favours thoracic SMARCA4-UT) 4,15 ; however these were not available in our institution at the time of writing. A recent case-control study has also identified additional cytomorphological features that favour thoracic SMARCA4-UT over SMARCA4d-NSCLC: tumour necrosis, dominant single-cell pattern, nuclear moulding, indistinct cell borders and rhabdoid cells.…”

“…Alterations of SWI-SNF complexes occur in a diverse and expanding group of mesenchymal and epithelial malignancies, including poorly differentiated, undifferentiated and dedifferentiated carcinomas of the thoracic cavity, gastrointestinal system, genitourinary tract, and sinonasal tract. 4,5 SWI-SNF deficient tumours not only defy ontological classification schemes, but also present in a wide range of ages and locations, as well as demonstrate a diverse range of morphologies, including round cell, rhabdoid cell, epithelioid cell and myxoid/chordoid pattern. 5 Nomenclature for the thoracic tumour has evolved from "SMARCA4-deficient thoracic sarcomas" 6 to "SMARCA4-deficient thoracic sarcomatoid tumours", in recognition of studies that suggest these tumours likely represent undifferentiated/dedifferentiated carcinomas in smokers based on similar mutation profiles (high tumour mutation burden, mutations of KRAS, STK11 and KEAP1), which are uncommon in other sarcomas.…”

“…Alterations of SWI‐SNF complexes occur in a diverse and expanding group of mesenchymal and epithelial malignancies, including poorly differentiated, undifferentiated and dedifferentiated carcinomas of the thoracic cavity, gastrointestinal system, genitourinary tract, and sinonasal tract 4,5 . SWI‐SNF deficient tumours not only defy ontological classification schemes, but also present in a wide range of ages and locations, as well as demonstrate a diverse range of morphologies, including round cell, rhabdoid cell, epithelioid cell and myxoid/chordoid pattern 5 …”

The roles of the SWI/SNF complex in cancer

“…In conclusion, perturbations of the SWI/SNF complex are identified in a significant subset of human cancers, including a wide range of mesenchymal and nonmesenchymal neoplasms affecting both children and adults. Because most patients with SW1/SNF‐deficient tumors pursue an aggressive clinical course and present at advanced stages, recognizing these tumors on small biopsies, including fine‐needle aspiration and cytology specimens, is crucial for establishing a refined diagnosis for these patients 7,48,49 . These tumors share common undifferentiated “rhabdoid” appearances, which represent a helpful clue in their diagnostic workup.…”

“…Because most patients with SW1/SNF-deficient tumors pursue an aggressive clinical course and present at advanced stages, recognizing these tumors on small biopsies, including fineneedle aspiration and cytology specimens, is crucial for establishing a refined diagnosis for these patients. 7,48,49 These tumors share common undifferentiated "rhabdoid" appearances, which represent a helpful clue in their diagnostic workup. Novel therapeutic approaches are being developed for a variety of malignancies unified by SWI/SNF deficiency, and ongoing translational research efforts are expected to further expand mechanistic insights into the complex biology of the SWI/SNF complex and its key roles in human cancer.…”