Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality

Nada Shaker; Ruwaida Ben Musa; Zofia Tynski; Nuha Shaker; Omar P Sangueza; Brandon Boyd

doi:10.1177/10668969241260215

Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality

Int J Surg Pathol. 2024 Jun 20:10668969241260215. doi: 10.1177/10668969241260215. Online ahead of print.

Authors

Nada Shaker¹, Ruwaida Ben Musa², Zofia Tynski³, Nuha Shaker⁴, Omar P Sangueza⁵, Brandon Boyd⁶

Affiliations

¹ Department of Pathology and Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus, USA.
² Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, USA.
³ Department of Pathology, Hackensack Meridian Health, Montclair, USA.
⁴ Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, USA.
⁵ Departments of Dermatology and Dermatopathology, Wake Forest University School of Medicine, Winston-Salem, USA.
⁶ Department of Pathology, Fairfield Medical Center, Lancaster, USA.

PMID: 38899907
DOI: 10.1177/10668969241260215

Abstract

Background. SMARCA4-deficient undifferentiated tumors are rare and pose a diagnostic challenge. This study delves into the intricate diagnostic terrain of SMARCA4-deficient undifferentiated tumors, providing insights into their diverse clinical presentations and diagnostic approaches. Case Presentation. A 69-year-old heavy-smoker man with adalimumab-treated rheumatoid arthritis presented with multiple lesions. A CT scan revealed a spiculated lung mass, enlarged mediastinal lymph nodes, and hepatic lesions. A whole-body FDG-PET/CT scan revealed heterogeneous hypermetabolic lesions in the lung, liver, and bone. Initial two core needle liver biopsies and a left upper lobe lung wedge resection initially indicated steatohepatitis and granulomatous formation with no evidence of malignancy. Several months later, the patient returned with left-sided flank pain and significant weight loss. CT scan identified a thigh mass, adrenal lesion, and extensive multiple skeletal lesions. A biopsy of the thigh mass revealed an extensively necrotic, epithelioid-to-spindled cell neoplasm with positive staining for pan keratin, focal staining for CD56, and a loss of nuclear expression of SMARCA4. A final diagnosis of SMARCA4-deficient undifferentiated tumor was rendered. Unfortunately, the patient's condition deteriorated, and he died a few weeks after receiving the final diagnosis. Conclusion. SMARCA4-deficient undifferentiated tumors have emerged as recent subjects of medical study, distinguished by their unique morphology and SMARCA4-deficient immunohistochemistry. These tumors present diverse clinical manifestations, affecting multiple organ systems. This report underscores the diagnostic complexities associated with complex clinical presentation and highlights the importance of multidisciplinary collaboration in addressing challenging clinical scenarios, particularly among heavy smoker male patients and intricate radiological presentations.

Keywords: SMARCA4; SMARCA4-deficient; SMARCA4-deficient carcinomas; SMARCA4-deficient tumors; SMARCA4-deficient undifferentiated tumor; SMARCA4-deficient undifferentiated tumor of the lung; heavy smoking related sarcomas; poorly differentiated carcinoma.