An unusual cause of gynaecomastia in a male

Summary: Beta-human chorionic gonadotropin (βhCG) is normally produced by syncytiotrophoblasts of the placenta during pregnancy and aids embryo implantation. However, it is also secreted in varying amounts in non-pregnant conditions commonly heralding a neoplastic process. We present a case of 50-year-old man, who presented with bilateral gynaecomastia with elevated testosterone, oestradiol, suppressed gonadotropins with progressively increasing levels of human chorionic gonadotropin (hCG). Biochemical and radiological investigations including ultrasonography of testes, breast tissue, MRI pituitary and CT scan full body did not identify the source of hCG. FDG PET scan revealed a large mediastinal mass with lung metastasis. Immunostaining and histological analysis confirmed the diagnosis of primary choriocarcinoma of the mediastinum. It is highly aggressive and malignant tumor with poor prognosis. Early diagnosis and management are essential for the best outcome. Learning Points: High βhCG in a male patient or a non-pregnant female suggests a paraneoplastic syndrome. In the case of persistently positive serum hCG, exclude immunoassay interference by doing the urine hCG as heterophilic antibodies are not present in the urine. Non-gestational choriocarcinoma is an extremely rare trophoblastic tumor and should be considered in young men presenting with gynaecomastia and high concentration of hCG with normal gonads. A high index of suspicion and extensive investigations are required to establish an early diagnosis of extra-gonadal choriocarcinoma. Early diagnosis is crucial to formulate optimal management strategy and to minimize widespread metastasis for best clinical outcome

A rare solitary and endobronchial pulmonary hyalinising granuloma requiring bilobectomy.

Pulmonary hyalinising granuloma is a very rare disease often presenting as multiple smooth rounded nodules within the lung parenchyma and mimicking metastatic disease. Solitary pulmonary hyalinising granuloma is an even rarer subgroup, and to our knowledge, there have been no endoluminal pulmonary hyalinising granulomas reported. A 36-year-old female non-smoker with no significant past medical history presented with a persistent cough and was found to have a right lower lobe bronchial lesion causing lower lobe obstruction. After multiple failed attempts at tissue diagnosis from both percutaneous and endobronchial biopsies, and with worsening haemoptysis, the patient underwent a right thoracotomy and lower bilobectomy. The histopathology was reported as a solitary endobronchial pulmonary hyalinising granuloma. Although benign in nature, tissue diagnosis can be difficult in these lesions, especially when presenting as a solitary mass in a central location. This report demonstrates that these lesions can also be found endobronchially necessitating parenchymal resection for diagnosis and obstructive symptoms

Applicability of routine targeted next-generation sequencing to estimate Tumor Mutational Burden (TMB) in patients treated with immune checkpoint inhibitor therapy.

It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients' TMB but may aid identification of candidate somatic variants of predictive/prognostic significance

New liberalism, new language? The use of collectivist concepts in the budget speeches of 1893–95 and 1906–14

The article considers the Budget Speeches of Asquith and Lloyd George during the period of the Liberal social reforms of 1906–14. It examines how these Budget speeches conceptualised the debate surrounding these reforms and discusses the extent to which this conceptualisation can be seen as reflecting the discursive character of a New Liberalism. The focus is on key collectivist concepts—“the state”, “the community”, “the people” and “the nation”. These were concepts which were very far from being the preserve of the Liberals but it is argued they were unpacked and used in ways that constituted a different conceptual terrain from that which had characterised previous Liberal budget speeches. The article considers the frequency of their usage but, more importantly, their collocation and rhetorical context and argues that these do indeed suggest that in important respects these budgets displayed a rhetorical character reflective of the ideology of New Liberalism