Cytopathologic Features of Metastatic Malignant Mesothelioma With SMARCB1 (INI-1) Deficient Diagnosed by Ultrasound-Guided Fine-Needle Aspiration: A Case Report

Diagnostic Cytopathology 2025 December 29 [Link]

Jun Yang, Juandi Liu, Jing Jin, Deng Pan, Lei Shao

Abstract

Malignant mesothelioma (MM) is a rare yet aggressive neoplasm that arises from mesothelial cells lining the thoracic and abdominal cavities, the pericardium, and the tunica testis. Characterized by rapid progression, high invasiveness, and a poor prognosis, MM poses significant clinical challenges. SMARCB1, also referred to as INI-1, hSNF5, or BAF47, is located on chromosome 22q11.2 and serves as a critical subunit of the SWI/SNF chromatin remodeling complex. INI-1 functions as a tumor suppressor and plays a vital role in DNA damage repair and regulation of cell growth. Case Presentation: A 37-year-old Chinese male with no history of asbestos exposure but a 10-year smoking history (30 cigarettes per day) presented with a cough lasting one month and a fever persisting for one day. Computed tomography (CT) showed multiple enlarged supraclavicular lymph nodes measuring up to 30 × 15 mm bilaterally. An ultrasound-guided fine-needle aspiration (FNA) of the left supraclavicular lymph nodes was subsequently performed. The SurePath-prepared liquid-based cytopathology (LBC) using Papanicolaou-staining revealed tumor cells organized in clusters with indistinct borders. The cells exhibited abundant cytoplasm and pleomorphic round nuclei, which displayed prominent nucleoli and mitotic activity. Additionally, scattered lymphoid fragments were observed in the background. The FNA sample was formalin-fixed and paraffin-embedded for cell block; 4-μm thick sections were prepared. Histological examination using HE-stained cell block revealed a solid sheet-like tumor growth characterized by minimal stroma and the absence of fibrovascular cores. The neoplastic cells had well-defined borders, abundant eosinophilic (partially clear) cytoplasm, and round-to-oval nuclei displaying focal atypia, finely dispersed chromatin, and prominent nucleoli. Immunohistochemistry (IHC) demonstrated positive staining for CK(pan), calretinin, D2-40, and SMARCA4, whereas NapsinA, TTF-1, P40, NUT, and WT-1 yielded negative results. The confirmed loss of INI-1 expression ultimately led to the diagnosis of metastatic INI-1 deficient MM. Conclusion: This case highlights the cytomorphological features and immunophenotype of INI-1 deficient MM diagnosed through FNA. An accurate diagnosis requires a thorough clinicopathological correlation and a comprehensive IHC panel.