Clinicopathologic and Immunohistochemical Characterization of Sarcomatoid Chromophobe Renal Cell Carcinoma

Abstract

Sarcomatoid differentiation in chromophobe renal cell carcinoma (ChRCC) is a rare finding and a significant predictor of worse outcomes. When the sarcomatoid component overgrows the conventional component or is the only component on a biopsy, the differential diagnoses encompass a variety of entities. Therefore, we reviewed 22 sarcomatoid ChRCCs and characterized the immunophenotype. Given that renal carcinomas with sarcomatoid features may benefit from immune checkpoint inhibitor-based therapy we also assessed the programmed death-ligand 1 (PD-L1) (28-8) expression. DOG1, CD117, cytokeratin 7, and PAX8 were negative in 100%, 88%, 63%, and 44% of the sarcomatoid components, respectively. GATA3 was expressed in 31% of the conventional components and in 50% of the sarcomatoid components. One conventional and 3 sarcomatoid components expressed PD-L1. Sarcomatoid ChRCCs have a high propensity for metastases and cancer progression. Distant metastatic disease was seen in 73% of the cases and median survival in this cohort was <1 year. The sarcomatoid portion had increased expression of PD-L1 and frequent loss of expression of multiple immunohistochemical markers associated with ChRCC. Half of the sarcomatoid ChRCC exhibited GATA3 expression, 3 of which did not express PAX8.

Sarcomatoid and Rhabdoid Renal Cell Carcinoma

“…34 The male-to-female ratio ranges from 1.3:1 to 2.3:1. [2][3][4][10][11][12]34 The majority of patients with sarcomatoid RCC present with large primary tumors as well as synchronous metastases. The presentation is variable and depends on the stage of the disease at diagnosis.…”

“…90 Hypocellular sarcomatoid spindle cell proliferations have been reported. 10 The sarcomatoid element is most often fibrosarcoma-like with intersecting fascicles of malignant spindle cells, pleomorphic undifferentiated sarcoma-like, or of an unclassified morphology (Figs. 3A-F).…”

“…Markers characteristic of usual chromophobe renal cell carcinoma-keratin 7 and CD117-are detected significantly less often in sarcomatoid elements at 23% and 8% of cases, respectively. 10,11 Note that CAIX expression in a sarcomatoid RCC element is not specific for a clear cell sarcomatoid element since 100% (7 of 7 cases) of sarcomatoid components of chromophobe RCC are positive for CAIX. 10…”

“…In recent years substantial progress has been made in understanding molecular mechanisms involved in this progression. Sarcomatoid and rhabdoid proliferations are not recognized by the WHO 2022 classification as distinct histologic types of RCC but rather as transformational changes that may arise in a background of a number of distinct histologic types including clear cell RCC, papillary RCC, chromophobe RCC, collecting duct carcinoma, thyroid-like follicular carcinoma, acquired cystic disease-associated RCC, mucinous and tubular spindle cell carcinoma, ALK-rearranged RCC, succinate dehydrogenase (SDH)-deficient RCC and malignant mixed epithelial and stromal tumor 1–4,10–30 . Although they are not distinct types of renal cell carcinoma, the diagnosis of sarcomatoid and rhabdoid changes in renal cell carcinoma is vital due to prognostic and therapeutic considerations.…”

GATA3 in Renal Neoplasms: Increased Utility and Potential Pitfalls

“…An important pitfall in the use of GATA3 is that the renal neoplasms with high-grade features may express GATA3. Recent studies show consistent GATA3 expression in sarcomatoid chromophobe RCC (50%), 7 fumarate hydratase deficient RCC (Figure 2D, 48–63%), 8,9 and collecting duct carcinoma (33%), 8 which may cause challenging in distinguishing these tumors from urothelial carcinoma of the renal pelvis, the top differential diagnosis with consistent GATA3 expression. Of note, PAX8 is positive in a subset of (18%) upper urothelial carcinoma, 10 further complicating the differential work-up.…”