Undifferentiated Endometrial Sarcoma of the Ovary: A Case Report with Review of Recent Literature and Discussion of Lacking Specificity of CD10 Immunoreactivity

Undifferentiated endometrial sarcomas (UESs) of the ovary are very rare tumors. This paper presents a case of a 56-year-old patient with a history of hysterectomy and bilateral salpingectomy seven years ago for uterine leiomyomata. Intraoperatively, a tumor originating from the left ovary, adherent to the sigmoid colon, with infiltration of the small intestine and the vaginal apex was found. Histologically, the tumor was composed of pleomorphic round and oval to spindled cells with polymorphous vesicular nuclei with coarse chromatin and large nucleoli. Mitotic activity was brisk. There were large necrotic areas. Adjacent to the tumor tissue endometrium-like glands surrounded by fibrous stroma with macrophages corresponding to ovarian endometriosis were noted. Tumor cells showed diffuse strong immunoreactivity for vimentin and patchy strong staining for CD10; no reactivities were found for AE1/AE3, desmin, S-100, LCA, CD20, c-kit, and CD31. The patient died of her neoplastic disease four months postoperatively. CD10 is frequently expressed in different gynecopathological as well as other lesions, and, thus, nonspecific without relevance to the classification of this case. Morphological features, extensive sampling, and appropriate immunohistochemistry including markers for cytokeratins and myogenic differentiation are mandatory to arrive at the correct diagnosis

DPP8/DPP9 inhibition elicits canonical Nlrp1b inflammasome hallmarks in murine macrophages

Activating germline mutations in the human inflammasome sensor NLRP1 causes palmoplantar dyskeratosis and susceptibility to Mendelian autoinflammatory diseases. Recent studies have shown that the cytosolic serine dipeptidyl peptidases DPP8 and DPP9 suppress inflammasome activation upstream of NLRP1 and CARD8 in human keratinocytes and peripheral blood mononuclear cells. Moreover, pharmacological inhibition of DPP8/DPP9 protease activity was shown to induce pyroptosis in murine C57BL/6 macrophages without eliciting other inflammasome hallmark responses. Here, we show that DPP8/DPP9 inhibition in macrophages that express a Bacillus anthracis lethal toxin (LeTx)–sensitive Nlrp1b allele triggered significantly accelerated pyroptosis concomitant with caspase-1 maturation, ASC speck assembly, and secretion of mature IL-1β and IL-18. Genetic ablation of ASC prevented DPP8/DPP9 inhibition-induced caspase-1 maturation and partially hampered pyroptosis and inflammasome-dependent cytokine release, whereas deletion of caspase-1 or gasdermin D triggered apoptosis in the absence of IL-1β and IL-18 secretion. In conclusion, blockade of DPP8/DPP9 protease activity triggers rapid pyroptosis and canonical inflammasome hallmarks in primary macrophages that express a LeTx-responsive Nlrp1b allele