RESUMEN
Leydig cell hyperplasia (LCH) is a rare cause of hyperandrogenism that has been described only in case reports. The cases presented herein contrast the traditional presentation of LCH with an affected asymptomatic individual. The first case involves a 74-year-old woman presenting with symptomatic hyperandrogenism, whose symptoms resolved after bilateral salpingo-oophorectomy (BSO). The second patient presented with postmenopausal bleeding and an abdominal mass. Following total abdominal hysterectomy (TAH) and BSO, pathology showed ovarian LCH with concomitant endometrial cancer. The diagnosis of LCH is complex and requires careful investigation of many differential diagnoses. Incidentally discovered LCH may shed light on evolution and disease progression. Cases of LCH found in the setting of endometrial pathology may have implications on other states of testosterone excess.
RESUMEN
In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.
