Bombesin staining in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILD).

AIMS: We have analysed levels of bombesin-positive neuroendocrine cells (NECs) in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILDs) in order to validate proposed histological criteria for NEHI and investigate its aetiology. METHODS AND RESULTS: The extent of bombesin-positive cells within airway epithelium was analysed in lung biopsies from seven patients diagnosed with NEHI, including two classified previously as non-diagnostic, and other chILDs (n = 64) with age ranges of 1 month-18 years. NECs were counted and calculated as a percentage of airways containing NECs, average percentage of NECs per airway, percentage of airways with >10% NECs and number of neuroendocrine bodies (NEBs). Correlation with age and gender was also undertaken. Patients with NEHI had the highest average percentage of bombesin-positive NECs per airway compared to other chILDs. However, NEH was also seen in many other chILDs, and appears to be most prominent in disorders associated with lung immaturity such as histological patterns associated with surfactant protein-related disorders and pulmonary interstitial glycogenosis. CONCLUSIONS: NEH may, to a degree, be a marker of airway immaturity rather than the direct cause of NEHI. This possibility is supported by the fact that the number of bombesin-positive NECs decreased with age in this cohort, independent of disease type. The average percentage of bombesin-positive NECs per airway appears to be the best histological criterion for assessing the extent of NECs in the context of NEHI.

An integrated single-cell reference atlas of the human endometrium.

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors and lacked consensus in defining cell types. We introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas (313,527 cells) combining published and new endometrial single-cell transcriptomics datasets of 63 women with and without endometriosis. HECA assigns consensus and identifies previously unreported cell types, mapped in situ using spatial transcriptomics and validated using a new independent single-nuclei dataset (312,246 nuclei, 63 donors). In the functionalis, we identify intricate stromal-epithelial cell coordination via transforming growth factor beta (TGFß) signaling. In the basalis, we define signaling between fibroblasts and an epithelial population expressing progenitor markers. Integration of HECA with large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells and macrophages as most likely dysregulated in endometriosis. The HECA is a valuable resource for studying endometrial physiology and disorders, and for guiding microphysiological in vitro systems development.

Emergency hysterectomy following iatrogenic injury to the descending branch of the uterine artery during colposcopy.

Large loop excision of the transformation zone is an extremely common procedure routinely carried out in a gynaecology or colposcopy outpatient setting under local anaesthetic. Here, we present a rare case resulting in emergency hysterectomy. A healthy para 3, who had been diagnosed with microscopic cancer of the cervix, attended colposcopy for repeat excision. The colposcopy revealed a normal cervix, and diathermy loop excision was performed. During the procedure, heavy bleeding from the anterior cutting edge was noted. Despite the best attempts to manage the haemorrhage conservatively in outpatients, the bleeding persisted, and the patient was transferred to theatres. Examination under anaesthesia revealed an injury to the descending branch of the uterine artery, and emergency hysterectomy was performed. Immediate recognition of an extremely rare complication, fast decision-making and a cross-disciplinary approach led to a satisfactory outcome.

Ectopic thoracic meningioma: a diagnostically challenging case.

Whilst meningiomas are common neoplasms of the central nervous system; ectopic meningiomas are very rare. When they do occur, they are typically in the head and neck. Due to their rarity, they propose a diagnostic challenge with interesting pathological findings. To date, only seven ectopic meningiomas arising in the mediastinum have been reported in the literature. We aim to shift the focus on the diagnostic journey of this rare entity which involved various imaging and histopathological techniques. Our patient was successfully treated with no complications after four years through input from specialists and the multidisciplinary team.

A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

INTRODUCTION: Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives. METHODS: Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification. RESULTS: All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene. CONCLUSIONS: IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein.