Immunohistochemistry for INI1 (SMARCB1) was performed on a renal tumor tissue section. The scan shows complete loss of nuclear INI1 expression in the malignant rhabdoid cells, with intact INI1 staining in admixed stromal cells and in benign renal tubular epithelium serving as internal positive controls. The tumor cells display classic rhabdoid morphology, including large polygonal cells with abundant eosinophilic or amphophilic cytoplasm, vesicular nuclei, prominent nucleoli, and high mitotic activity embedded in a fibrous to myxoid stroma. Immunostaining pattern helps distinguish SMARCB1-deficient rhabdoid tumors from other renal neoplasms. This INI1 loss is characteristic of rhabdoid tumors and forms part of a broader SMARCB1-deficient tumor spectrum, which includes atypical teratoid/rhabdoid tumors (ATRT) and extrarenal rhabdoid/teratoid tumors; however, roughly twenty percent of INI1-deficient rhabdoid tumors lack detectable SMARCB1 gene alterations, implying alternative inactivation mechanisms. Clinically, INI1 deficiency portends aggressive behavior and necessitates integrated diagnostic workup, including molecular studies. The image demonstrates the diagnostic significance of INI1 immunostaining for accurate classification, prognostication, and management decisions in pediatric and adult renal tumors. This biomarker supports differential diagnosis when histology is ambiguous and guides genetic counseling and potential targeted therapeutic considerations in SMARCB1-related neoplasms. Correlation with patient age, tumor stage, and ancillary tests enhances utility.

Immunohistochemistry image of a renal rhabdoid tumor (RTK) demonstrating loss of nuclear INI1 (SMARCB1) staining in tumor cells with preserved INI1 in endothelial and inflammatory cells, providing an internal positive control. Morphologically, the lesion shows sheets of rhabdoid cells with large polygonal shapes, eccentrically placed nuclei, prominent nucleoli, and abundant cytoplasm; paranuclear inclusions may be present. The tumor exhibits an overlapping immunophenotype: vimentin positivity with pan-c cytokeratin and EMA expression, compatible with the dual mesenchymal-epithelial nature of RTKs. In contrast, the tumor cells are negative for smooth muscle actin (SMA), desmin, and S‑100 protein. Myogenin and neuroendocrine markers can be variably expressed in some cases, underscoring potential immunophenotypic overlap with other renal neoplasms. INI1 loss is a defining feature of SMARCB1-deficient tumors, though rare RTKs retain INI1 and SMARCA4 (BRG-1) inactivation can occur with BRG-1 loss. Clinically, INI1 deficiency strongly supports a diagnosis of RTK and carries prognostic implications due to aggressive behavior. The image also notes that renal medullary carcinoma can display INI1 loss, highlighting overlapping but distinct SWI/SNF-deficient entities. This IHC pattern aids in differential diagnosis from Wilms tumor and other renal neoplasms, informs molecular testing strategy, and guides research into targeted therapies targeting the SWI/SNF complex.

Histopathology slide of a rhabdoid tumor showing the classic INI1/SMARCB1-deficient rhabdoid phenotype on hematoxylin-eosin stained tissue. Bright-field microscopy reveals loosely cohesive sheets of monomorphic tumor cells with eccentrically placed vesicular nuclei, prominent nucleoli, and intracytoplasmic eosinophilic inclusions. Cells may adopt a plasmacytoid or rhabdomyosarcomatous appearance. The pattern is highly characteristic but not entirely specific, and SMARCB1/INI1 loss by immunohistochemistry supports the diagnosis. Rhabdoid tumors are aggressive neoplasms most common in infancy and childhood, typically arising in the kidney or central nervous system (atypical teratoid/rhabdoid tumor), but extrarenal and extra-CNS sites have been described. Clinically relevant associations include rapid progression and poor prognosis, requiring prompt multimodal therapy. In differential diagnosis, focal rhabdoid features can complicate other renal neoplasms such as Wilms tumor, mesoblastic nephroma, and renal cell carcinoma, making accurate IHC and molecular testing essential. Diagnostic significance centers on recognizing INI1-deficient rhabdoid morphology, which guides prognosis and informs genetic counseling. This image serves educational purposes for pathologists, clinicians, and trainees, enabling histologic-pathologic correlation, differential diagnosis, and study of SMARCB1-related tumorigenesis across pediatric and, occasionally, adult populations. Correlate with radiology and clinical data for comprehensive diagnosis and treatment planning; consider SMARCB1 sequencing in ambiguous cases. This enhances diagnostic accuracy and patient management.

Histopathology image of a pediatric renal rhabdoid tumor captured with light microscopy on an H&E-stained renal tumor biopsy. The section shows high cellularity with sheets and clusters of tumor cells embedded in scant, fibrous stroma. Tumor cells are oval to polygonal with markedly eosinophilic to amphophilic cytoplasm, and nuclei are large, round to elongated with prominent nucleoli. Occasional rhabdoid features include eccentric, vesicular nuclei and prominent, glassy cytoplasm; mitotic activity is brisk with frequent atypical mitoses. There may be necrotic foci. The overall pattern is highly infiltrative, sometimes with perivascular pseudo-rosettes described in some renal rhabdoid tumors. The image may reflect loss of INI1 (SMARCB1) expression on immunohistochemistry, a hallmark of rhabdoid tumor, though not visible on H&E alone. Clinically, renal rhabdoid tumors are aggressive and often present with advanced disease including lymph node, liver, and lung metastases; prognosis is poor with 5-year survival around 15-25%, and less than 20% presenting at stage I. Treatment typically involves multimodal therapy: surgery, chemotherapy, and radiotherapy; investigational SMARCB1-targeted epigenetic therapies are under clinical trial. This histology is essential for differential diagnosis against Wilms tumor with rhabdoid features, renal medullary carcinoma, and other renal sarcomas, guiding patient management and prognosis. Important educational tool for pathology.