Orrock, Jared M.

ABSTRACT Eccrine spiradenomas are benign sweat gland neoplasms that rarely undergo malignant transformation. Carcinosarcoma arising from an eccrine spiradenoma is exceptionally rare. A 41‐year‐old male presented with a rapidly growing neck/shoulder mass, progressive numbness, spasticity, and weakness. Further workup additionally revealed an epidural mass with spinal cord compression. Both masses were excised and predominantly showed morphologic features of high‐grade osteosarcoma, with overtly malignant spindled cells producing lace‐like osteoid. However, a single section from the upper back mass contained a roughly 2 mm focus of conventional eccrine spiradenoma, with an adjacent small focus having features of a poorly differentiated non‐small cell carcinoma. The final diagnosis was that of a high‐grade carcinosarcoma with heterologous osteosarcomatous differentiation, arising from a pre‐existing eccrine spiradenoma, with metastasis to the T4‐5 epidural region. The patient experienced rapid regrowth of the spinal mass and underwent radiotherapy but had unresectable metastatic disease at 2 months follow‐up. We describe what is to our knowledge only the 21st example of carcinosarcoma arising from eccrine spiradenoma, mimicking metastatic osteosarcoma. Awareness of this very rare entity, careful sampling, close microscopic examination, and, in selected cases, ancillary immunohistochemistry are the keys to making this challenging diagnosis.

460 Background: The immune response has emerged as a strong prognostic factor in colon cancer. Whereas CD8+ T cells mediate antitumor response, regulatory T cells expressing FoxP3+ can antagonize this effect, though prognostic data conflict. These markers have yet to be analyzed with MMR status, which is important since dMMR tumors show enhanced immune response. Methods: CD8+ and FoxP3+ density were analyzed by immunohistochemistry (IHC) in resected stage II and III colon carcinomas (N = 216) from participants in phase III adjuvant 5-fluorouracil-based trials. High vs low immune density was dichotomized at the median. MMR status, determined by IHC or analysis of microsatellite instability, was categorized as dMMR (12%) or proficient MMR (pMMR). Cox models, stratified by study, were adjusted for age, stage, grade and, where noted, MMR. Results: The association of FoxP3+ density with overall survival (OS) differed by CD8+ density (P for interaction = .040). By multivariable analysis, FoxP3+high was significantly associated with improved OS in CD8+low tumors (hazard ratio 0.43 [95% confidence interval 0.19 – 0.95]; P = .030], but not in CD8+high tumors (P = .91). Results were consistent after MMR adjustment. We then determined their prognostic impact in the larger pMMR subset (N = 119). Tumors with high FoxP3+ were associated with improved OS in cases with low, but not high, CD8+ density ( Table ). These patients (FoxP3+high, CD8+low) had similar 5-year OS rates as 107 dMMR cases from parent studies (89% vs 80%; P = .74), despite having distinct clinicopathologic features. Conclusions: The prognostic impact of FoxP3+ T cells depends on CD8+, indicating the importance of analyzing both in combination. High FoxP3+ exerts a paradoxically favorable survival impact, but only when CD8+ is low. Survival in pMMR tumors with high FoxP3+ and low CD8+ was similar to that of dMMR tumors, indicating that a favorable pMMR subset can be identified. [Table: see text]