Objectives: To describe the radiologic and clinicopathologic features of extranodal Rosai-Dorfman disease (RDD) in our patient population. Methods: Via a data mining engine, we evaluated 13 cases of extranodal RDD in 10 patients treated at our institution from 2000 to 2014. Results: There was a marked female predominance (90%) in our series. The most common clinical presentation was a palpable, painless mass, which often simulated a neoplasm. Only two cases occurred in children. Multicentric and recurrent disease were uncommon. Histologically, all cases showed large histiocytes with emperipolesis in a mixed inflammatory background, with areas of dense, storiform collagen fibrosis. Positive S-100 and CD68 with negative CD1a in histiocytes are characteristic. Conclusions: Extranodal RDD is rare and its manifestations varied. It may constitute a clinical and pathologic diagnostic challenge. Clinical suspicion and recognition of its histologic features are necessary for correct diagnosis and avoiding unnecessary treatment. Resection is curative in most cases.

Background Chondrosarcoma is one of the most common malignant bone tumors in adults. Conventional chondrosarcoma represents around 85% of all chondrosarcomas and is notoriously difficult to treat with chemotherapy. Case presentation We describe a 67-year-old man with metastatic conventional chondrosarcoma who was treated with nivolumab. Treatment was discontinued after restaging showed increased tumor burden, which later proved to be pseudoprogression. The patient restarted nivolumab and continues to have a near complete response. Conclusion Conventional chondrosarcoma may be sensitive to checkpoint inhibitors. Further, this case demonstrates clearly the phenomenon of pseudo-progression in this disease, a factor that must be considered in the design of clinical trials and clinical care. This case supports additional study of immunomodulatory agents in this deadly disease.

Purpose: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design. Experimental Design: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis. Results: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy. The most prevalent immune cells in the tumor before neoadjuvant therapy were myeloid cells (45% of all immune cells) and B cells (37%), with T (13%) and natural killer (NK) cells (5%) also present. Neoadjuvant therapy significantly increased the total immune cells infiltrating the tumors across all histologic subtypes for patients receiving neoadjuvant radiotherapy with or without chemotherapy. An increase in the percentage of monocytes and macrophages, particularly M2 macrophages, B cells, and CD4+ T cells was observed postneoadjuvant therapy. Upregulation of genes and cytokines associated with antigen presentation was also observed, and a favorable pathologic response (≥90% necrosis postneoadjuvant therapy) was associated with an increase in monocytic infiltrate. Upregulation of the T-cell checkpoint TIM3 and downregulation of OX40 were observed posttreatment. Conclusions: Standard neoadjuvant therapy induces both immunostimulatory and immunosuppressive effects within a complex sarcoma microenvironment dominated by myeloid and B cells. This work informs ongoing efforts to incorporate immune checkpoint inhibitors and novel immunotherapies into the neoadjuvant setting for STSs.