Faculty Bibliography

Radiologic studies indicate that placental calcifications seen at 28-32 weeks' gestation are associated with adverse fetal outcome. One type of placental calcification is typically located at the basement membrane of chorionic villi. It has a fine particulate appearance and can only be seen microscopically. We have designated these calcifications as Intravillous and Intrafibrinous Particulate MicroCalcification (IPMC). In this study we examined the distribution and potential significance of IPMC. Placentas from 14 groups of fetal and maternal outcomes are examined histologically for IPMC. These groups were preterm birth, post term birth, intrauterine fetal demise, fetuses with non-reassuring heart rates, intrauterine growth restriction, fetal anomalies, mothers with gestational hypertension, gestational diabetes, placental abruption, pre-eclampsia and placentas of normal spontaneous vaginal births and placentas with chorioamnionitis, chronic villitis and infarcts. We observed fine dust-like particulates deposited in continuous and discrete patches. The particulates were predominantly located in the basement membranes of fibrotic chorionic villi and in perivillous fibrin. Compared to placentas without adverse outcomes, a higher incidence of IPMC was seen in intrauterine fetal demise cases and in cases with infarcts which suggests that hypoxia played a role in the etiology of IPMC.

A variety of chemotherapeutic agents have been used for treating recurrent or advanced stage uterine leiomyosarcoma (ULMS). The response rates of these current agents are disappointing, with partial response rates varying from 0% to 33%, and complete response rates varying from 0% to 8%. Recent studies have documented many molecular changes in ULMSs. Prominent amongst these are gains of growth factors C-MYC, Bcl-2, K-ras, and Ki-67, and losses in tumor suppressors p16, p53, Rb1, ING2 and D14S267. Various techniques that have been used to target these molecules are presented. Targeting specific therapies at these underlying molecular changes could potentially yield better response rates with fewer side effects.

Occult endometrial cancer is occasionally discovered in women with Lynch syndrome undergoing risk-reducing hysterectomy. The case presented here demonstrates that preoperative endometrial sampling can help detect these occult cancers; however, there are currently no recommendations for this preoperative intervention. A 50-year-old woman with Lynch syndrome underwent endometrial sampling prior to planned risk-reducing hysterectomy and bilateral salpingo-oophorectomy. The endometrial biopsy demonstrated a serous endometrial cancer. The patient was counselled regarding the diagnosis and revised operative plan, which now included staging, prior to surgery. Although the prevalence of occult endometrial cancer at the time of risk-reducing surgery in women with Lynch syndrome remains unknown, preoperative endometrial sampling may allow for improved patient counselling and surgical planning in this population, and can help avoid a subsequent surgery for staging.

Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the basement membrane, PMNs impeded early-stage tumor growth and retarded malignant progression. Unexpectedly, PMN recruitment and tumor growth control occurred independently of lymphocytes and cellular senescence and instead ensued as part of the tumor's intrinsic inflammatory response to hypoxia. In humans, a PMN gene signature correlated with improved survival in several cancer subtypes, including PTEN-deficient uterine cancer. These findings provide insight into tumor-associated PMNs and reveal a context-specific capacity for PMNs to directly combat tumorigenesis.

Endometriosis is a common disorder that causes significant morbidity from dysmenorrhea, pelvic pain, and subfertility. Establishment of a definitive diagnosis has important therapeutic implications; however, only approximately 50% of biopsies of laparoscopically suspicious areas provide a diagnosis of endometriosis. Histologic criteria for diagnosis require the presence of endometrial glands or endometrial-type stroma. We hypothesize that other frequently present, but nondiagnostic, histologic features of endometriosis suggest its presence in patients with nondiagnostic peritoneal biopsies. We performed a retrospective clinicopathologic study of morphologic and immunohistochemical features that may improve the histologic diagnosis of endometriosis on laparoscopic peritoneal biopsies. We compared diagnostic (n=88) and nondiagnostic (n=54) peritoneal biopsies from pathologically confirmed endometriosis cases with negative peritoneal biopsies (n=84) from early-stage gynecologic cancer cases. Statistical analysis utilized the Fisher exact test. Multiple morphologic features were significantly increased in nondiagnostic biopsies from patients with endometriosis in comparison with those from negative controls, including foamy macrophages (P=0.0001) and submesothelial stromal clusters (SSCs) (P=0.0008). SSCs ranged from subtle aggregates of spindle cells to nodules of whorled spindle cells with small vessels and extravasated red blood cells resembling stromal endometriosis. Immunohistochemical studies confirmed that ER and CD10-positive SSCs were present in a greater proportion of both nondiagnostic and diagnostic peritoneal biopsies and at a greater number of lesions per biopsy. The overall histologic detection rate of peritoneal biopsies for endometriosis was 62.0%, and inclusion of SSCs with or without foamy macrophages in the diagnostic criteria appreciably increased this rate to between 72.5% and 76.8%. We describe SSCs, which appear to be an early or less developed form of stromal endometriosis, and, when included in the diagnostic criteria, improve the histologic detection rate of endometriosis in peritoneal biopsies.