Sarcomatoid Renal Cell Carcinoma With Unusual Metastasis to the Small Intestine Manifesting as Perforated Appendicitis.

BACKGROUND: Sarcomatoid renal cell carcinoma is a rare form of dedifferentiated carcinoma with a high metastatic rate and adverse prognosis. Common sites of metastasis include lymph nodes, lung, liver and bone. We report a case of sarcomatoid renal cell carcinoma with unusual metastasis to the small intestine in a 65-year-old female with a history of clear-cell renal cell carcinoma with focal sarcomatoid transformation. CASE REPORT: The patient presented to the Emergency Department with worsening abdominal pain. Imaging showed perforated acute appendicitis, however, diagnostic laparoscopy found no evidence of appendicitis, but a small punctate perforation in the small intestine. Gross examination of the small intestine showed a 2 cm tan-white lobular firm lesion at the perforation site involving the full thickness of the wall. Histological examination revealed a high-grade spindle-cell neoplasm with hyperchromatic and pleomorphic nuclei, frequent mitotic figures, and necrosis. Immunohistochemically, the tumor cells were positive for CD10 and carbonic anhydrase 9, but negative for pan-cytokeratin, epithelial membrane antigen, paired box gene 8, renal cell carcinoma, desmin, smooth-muscle actin, c-KIT, discovered on gastrointestinal stromal tumor protein 1, CD34, and S100. Molecular studies showed that the tumor cells were microsatellite stable but harbored mutations in polybromo-1, telomerase reverse transcriptase, and von Hippel-Lindau genes, supporting renal cell carcinoma in nature. The patient received radiation therapy but unfortunately died after one month due to rapid disease progression. CONCLUSION: This was a rare and challenging case of sarcomatoid renal cell carcinoma metastasis to the small intestine with loss of some renal cell carcinoma markers, reinforcing the aggressive nature of this entity and the importance of correlating findings with the prior history for reaching correct diagnosis.

Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

BACKGROUND: Platinum (Pt)-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC). However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC) in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC) specimens would correlate with improved pathologic response to Pt-based NAC in MIBC. METHODS: A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR), N = 4; ≤ypT1N0M0 (pathologic partial response, pPR), N = 6; ≥ypT2 (minimal pathologic response/progression), N = 9)]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry. RESULTS: Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011). Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095) or no response/progression (P = 0.020). There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively). CONCLUSIONS: Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.