Stromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcome.

Androgen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.

Oestrogen hormone receptors in focal nodular hyperplasia.

BACKGROUND: The role of hormones in focal nodular hyperplasia (FNH) has been investigated with conflicting results. OBJECTIVE: The aim of this study was to evaluate oestrogen and progesterone receptor immunohistochemical expression in FNH and surrounding normal liver (control material). METHODS: Biopsy materials from FNH and control tissue were investigated using an immunostainer. Receptor expression was graded as the proportion score (percentage of nuclear staining) and oestrogen receptor intensity score. RESULTS: Study material included tissue from 11 resected FNH lesions and two core biopsies in 13 patients (two male). Twelve samples showed oestrogen receptor expression. The percentage of nuclear oestrogen receptor staining was <33% in eight FNH biopsies, 34-66% in two FNH biopsies, and >67% in both core biopsies. The better staining in core biopsies relates to limitations of the staining technique imposed by the fibrous nature of larger resected FNH. Control samples from surrounding tissue were available for nine of the resected specimens and all showed oestrogen receptor expression. Progesterone receptor expression was negligible in FNH and control samples. CONCLUSIONS: By contrast with previous studies, the majority of FNH and surrounding liver in this cohort demonstrated oestrogen receptor nuclear staining. The implications of this for continued oral contraceptive use in women of reproductive age with FNH remain uncertain given the lack of consistent reported growth response to oestrogen stimulation or withdrawal.

Forensic features of pharmacobezoars.

Three cases of pharmacobezoars are reported to demonstrate typical autopsy findings and potential lethal mechanisms: (i) A 32-year-old woman died following an overdose of prescription medications. A gelatinous pharmacobezoar was found forming a cast of her bronchial tree. (ii) A 24-year-old woman also died following an overdose of prescription medications. At autopsy, two pharmacobezoars were present, one within the larynx and another occluding the right main bronchus. Deaths in both cases were attributed to airway occlusion by pharmacobezoars complicating mixed drug toxicity. (iii) A 79-year-old man was found dead in a car. Death was attributed to the combined effects of carbon monoxide and drug toxicity with a large pharmacobezoar lodged within the esophagus. Pharmacobezoars are specific types of bezoars that occur when pharmaceutical materials, such as tablets, suspensions, and/or drug delivery devices, aggregate and contribute to death by occluding airways with tenacious material or by eluting drugs.

Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar: benign lymphoepithelial cyst, head of pancreas.

Pancreatic lymphoepithelial cysts are more common in men, can occur anywhere in the pancreas, are sharply demarcated from surrounding tissues, and range in size from 1.2 to 17 cm. Patients are usually middle aged, presenting symptoms include abdominal pain, nausea, vomiting, and diarrhea, although many tumors are asymptomatic and are discovered incidentally on organ imaging or at autopsy. An elevated serum carbohydrate-associated antigen 19-9 may wrongly suggest a mucinous neoplasm. The diagnosis can be made preoperatively with a combination of organ imaging, fine needle aspiration biopsy, or ultrasound-guided Trucut biopsies. Cysts can be unilocular, bilocular, or multilocular, have walls up to 0.6 cm thick which are lined by squamous epithelium, occasional columnar mucinous cells, and small foci of sebaceous cells. The epithelium is surrounded by a dense rim of lymphoid tissue with scattered lymphoid follicles. Invaginations of the epithelium into the lymphoid tissue, reminiscent of a Warthin tumor, are occasionally observed. The pathogenesis is unknown. Pancreatic lymphoepithelial cysts are cured by conservative resection but if they are asymptomatic and are diagnosed before surgery, no treatment is necessary.