Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by uncontrolled proliferation of anastomosing lymphatic channels in the lungs, pleura and mediastinum. Several palliative treatment options have been suggested for this condition, such as surgical interventions, radiotherapy and systemic medications. However, the existing treatment modalities yield inconsistent results, and their use is often limited by toxic side effects. The aim of this case report is to demonstrate the diagnostic challenges of a rare disease and improvement in the condition of a DPL patient treated with sirolimus. A 27-year-old man presented to the pulmonologist with exertional dyspnea, chronic cough and intermittent hemoptysis. Upon medical investigation, a chest computed tomography (CT) scan revealed soft tissue masses infiltrating the mediastinum and bilateral interlobular septal thickening. A surgical biopsy was performed, and pathological tissue analysis showed findings consistent with the diagnosis of DPL. Treatment with sirolimus was initiated, maintaining trough concentrations between 10 and 15 ng/ml. At 21 months of treatment, the patient reported reduced symptoms of cough and dyspnea. A CT scan showed decreased interstitial thickening and reduced infiltrations in the mediastinum. Moreover, pulmonary function tests revealed a significant increase in FEV1 and FVC. The authors believe this is the first article reporting pulmonary function improvement in an adult DPL patient treated with sirolimus. Therefore, sirolimus therapy should be considered for DPL patients as it may be effective in improving their condition and preventing disease progression.

The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes—desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer types. Here, we aimed to investigate, define, and validate the immune subtypes in melanoma by coupling transcriptional and histological assessments of the lymphocyte distribution in tumor parenchyma and stroma. We used the transcriptomic data from The Cancer Genome Atlas melanoma dataset to screen for the desert, excluded, and inflamed immune subtypes. We defined subtype-specific genes and used them to construct a subtype assignment algorithm. We validated the two-step algorithm in the qPCR data of real-world melanoma tumors with histologically defined immune subtypes. The accuracy of a classifier encompassing expression data of seven genes (immune response-related: CD2, CD53, IRF1, and CD8B; and stroma-related: COL5A2, TNFAIP6, and INHBA) in a validation cohort reached 79%. Our findings suggest that melanoma tumors can be classified into transcriptionally and histologically distinct desert, excluded, and inflamed subtypes. Gene expression-based algorithms can assist physicians and pathologists as biomarkers in the rapid assessment of a tumor immune microenvironment while serving as a tool for clinical decision making.

Ectopic parathyroid adenoma is a rare pathology. We present a clinical case of a giant ectopic parathyroid adenoma (PA) in an unusual location, which brought significant diagnostical and therapeutical challenges. The tumour in the mediastinum was found incidentally on chest computed tomography (CT). A biopsy was conducted, and histological examination revealed a well-differentiated neuroendocrine tumour. The tumour was excised via right thoracotomy. The final histological examination revealed a parathyroid adenoma, which was unexpected for our team. After three years of observation, there is no evidence of tumour recurrence.