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Introduction: In most cases the diagnostic workup of pleural mesotheliomas (MPM) starts with cytological examination of pleural effusion, but histology is needed to confirm the diagnosis. The introduction of BAP1 and MTAP immunohistochemistry have become a powerful tool to confirm the malignant nature of mesothelial proliferations also in cytological specimens. The objective of this study is to determine the concordance of BAP1, MTAP and p16 expression between cytological and histological samples of patients with MPM. Methods: Immunohistochemistry of BAP1, MTAP and p16 was performed on cytological samples and compared with the corresponding histological specimen of 25 patients with MPM. Inflammatory and stromal cells served as positive internal control for all three markers. In addition, samples of 11 patients with reactive mesothelial proliferations served as an external control group. Results: Loss of BAP1, MTAP and p16 expression was found in 68%, 72% and 92% of MPM, respectively. Loss of MTAP was associated with loss of p16 expression in all cases. Concordance of BAP1 between cytological and corresponding histological samples was 100% (kappa coefficient 1; p = 0.008). For MTAP and p16 kappa coefficient was 0.9 (p = 0.01) and 0.8 (p = 0.7788), respectively. Conclusions: Concordant BAP1, MTAP and p16 expression is found between cytological and corresponding histological samples, indicating that a reliable diagnosis of MPM can be made on cytology only. Of the three markers BAP1 and MTAP are most reliable in distinguishing malignant from reactive mesothelial proliferations

Background Post-mortem imaging has been suggested as an alternative to conventional autopsy in the prenatal and postnatal periods. Noninvasive autopsies do not provide tissue for histological examination, which may limit their clinical value, especially when infection-related morbidity and mortality are suspected. Methods We performed a prospective, multicentre, cross-sectional study to compare the diagnostic performance of post-mortem magnetic resonance imaging with computed tomography-guided biopsy (Virtopsy®) with that of conventional autopsy in foetuses and infants. Cases referred for conventional autopsy were eligible for enrolment. After post-mortem imaging using a computed tomography scanner and a magnetic resonance imaging unit, computed tomography-guided tissue sampling was performed. Virtopsy results were compared with conventional autopsy in determining the likely final cause of death and major pathologies. The primary outcome was the proportion of cases for which the same cause of death was determined by both methods. Secondary outcomes included the proportion of false positive and false negative major pathological lesions detected by virtopsy and the proportion of computed tomography-guided biopsies that were adequate for histological examination. Results Overall, 101 cases (84 fetuses, 17 infants) were included. Virtopsy and autopsy identified the same cause of death in 91 cases (90.1%, 95% CI 82.7 to 94.5). The sensitivity and specificity of virtopsy for determining the cause of death were 96.6% (95% CI 90.6 to 98.8) and 41.7% (95% CI 19.3 to 68.0), respectively. In 32 cases (31.7%, 95% CI 23.4 to 41.3), major pathological findings remained undetected by virtopsy, and in 45 cases (44.6%, 95% CI 35.2 to 54.3), abnormalities were diagnosed by virtopsy but not confirmed by autopsy. Computed tomography-guided tissue sampling was adequate for pathological comments in 506 of 956 biopsies (52.7%) and added important diagnostic value in five of 30 cases (16.1%) with an unclear cause of death before autopsy compared with postmortem imaging alone. In 19 of 20 infective deaths (95%), biopsies revealed infection-related tissue changes. Infection was confirmed by placental examination in all fetal cases. Conclusions Virtopsy demonstrated a high concordance with conventional autopsy for the detection of cause of death but was less accurate for the evaluation of major pathologies. Computed tomography-guided biopsy had limited additional diagnostic value. Trial registration ClinicalTrials.gov (NCT01888380).

Personalized treatment of metastatic non-squamous non-small cell lung cancer (NSCLC) requires detailed molecular characterization of the tumour including detection of predictive driver mutations and programmed death ligand 1 (PD-L1) expression. Complete detection is influenced by the amount of tumour cells sampled as well as their quality. Different sampling techniques may be necessary to provide sufficient tumour material for comprehensive molecular characterization. Missing the detection of targetable molecular genetic aberrations would have a serious impact on the quality of life and prognosis of a patient. This case report highlights the importance of biopsy technique in a patient with NSCLC. Several procedures—pleural puncture, transthoracic lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)—could not provide sufficient tumour material for precise tumour characterization. Only the addition of EBUS-guided transbronchial lymph node cryobiopsy (EBUS-TBLNC) enabled complete immunohistochemical and genetic tumour characterization, demonstrating PD-L1 expression in 100% of the tumour cells in the absence of actionable genetic alterations. Based on these results, immunotherapy was initiated.

Overall, neonatal cancer is uncommon. Because of its rarity and heterogeneity, diagnosis can be challenging. We report a unique case of a myoepithelial carcinoma in a 7 week old girl. Molecular diagnostic workup revealed a EWSR1-KLF15 gene fusion which was previously described in only six cases of myoepithelial tumors so far. All cases occurred in children and adolescents. To our knowledge, this is the first report of a congenital EWSR1-KLF15 fusion positive myoepithelial tumor in an infant.

Purpose Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor, and currently, there are no published treatment recommendations. Methods We performed a systematic literature review and synthesized clinical presentation, clinicopathological factors associated with metastatic disease, treatment options, and outcomes in men with MTVT. Results We included 170 publications providing data on 275 patients. Metastatic disease occurred in 84/275 (31%) men with malignant MTVT: Most common sites included retroperitoneal lymph nodes (LNs) (40/84, 48%), lungs (30/84, 36%), and inguinal LNs (23/84, 27%). Invasion of the spermatic cord or scrotum was the only risk factor for local recurrence [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.36–7.57]. Metastatic disease was associated with age ≥ 42 years (OR 3.02, 95% CI 1.33–6.86), tumor size ≥ 49 mm (OR 6.17, 95% CI 1.84–20.74), presence of necrosis (OR 8.31, 95% CI 1.58–43.62), high mitotic index (OR 13.36, 95% CI 1.53–116.51) or angiolymphatic invasion (OR 3.75, 95% CI 1.02–13.80), and local recurrence (OR 4.35, 95% CI 2.00–9.44). Complete remission in the metastatic setting was observed in five patients, most of whom were treated with multimodal therapy. Median survival in patients with metastatic disease was 18 months (IQR 7–43). Conclusion Malignant MTVT is a rare but aggressive disease. Since local recurrence is a risk factor for metastatic progression, we recommend aggressive local treatment. Survival and response to any treatment in the metastatic setting are limited.

Purpose Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes. Methods We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level. Results From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission. Conclusion Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2–21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p