Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.

This review article - which is devoted to a wide range of physicians, e.g., pathologists, clinicians, radiologists, and general practitioners - is an up-to-date clinico-pathological description of cardiac tumours. Although rare, cardiac tumours are key components in oncology practice since both their early diagnosis and appropriate management denote urgent needs. Primary cardiac tumours (PCTs) are categorized in recent WHO classifications as well as in other scientific contributions. Their incidence is around 0.02 % while their prevalence is between 0.001 % and 0.03 %. Among PCTs, benign lesions account for 85 % of cases, while malignant neoplasms for 15 %. Compared to PCTs, secondary cardiac tumours are 20-30-fold more common. The most frequent PCTs in adulthood are papillary fibroelastoma and cardiac myxoma, while, in childhood, cardiac rhabdomyoma. Heart metastases may occur through direct extension, or, indirectly, via bloodstream, lymphatics or intracavitary diffusion. Thoracic cancers (e.g. from pleura, lung, breast) are the most frequent cause of cardiac metastasis followed by oesophageal and haematological malignancies. Symptoms of PCTs (e.g. arrhythmias, dyspnoea, chest discomfort, syncope) are usually the result of both their regional involvement and location. Non-invasive imaging techniques (e.g. echocardiography, MRI, CT) and biopsy are key means in delineating tumour characteristics, size, and adjacent structure involvement. Most PCTs require surgery, which is recommended to prevent life-threatening complications. While many benign cardiac neoplasms may be completely resected, the treatment of choice for malignant PCTs and metastases is a combination of surgery, radio- and/or chemotherapy, as well as new alternative treatments, which may prolong survival in a small patient subset.

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR). BRCA1/2 loss-of-function is linked to hereditary PCs and homologous recombination DNA-repair system deficiency: poly-ADP-ribose-polymerase inhibitors can be administered to BRCA-mutated PC patients. Recently, docetaxel-refractory metastatic castration-resistant PC patients with BRCA1/2 or ATM somatic mutations had higher response rates to pembrolizumab. PTEN regulates cell cycle/proliferation/apoptosis through pathways including the AKT/mTOR, which upregulates PD-L1 expression in PC. Our systematic literature review (PRISMA guidelines) investigated the potential correlations between PD-L1 and MMR/MSI/BRCA/PTEN statuses in PC, discussing few other relevant genes. Excluding selection biases, 74/677 (11%) PCs showed dMMR/MSI; 8/67 (12%) of dMMR/MSI cases were PD-L1+. dMMR-PCs included ductal (3%) and acinar (14%) PCs (all cases tested for MSI were acinar-PCs). In total, 15/39 (39%) PCs harbored BRCA1/2 aberrations: limited data are available for PD-L1 expression in these patients. 13/137 (10%) PTEN- PCs were PD-L1+; 10/29 (35%) PD-L1+ PCs showed PTEN negativity. SPOP mutations may increase PD-L1 levels, while the potential correlation between PD-L1 and ERG expression in PC should be clarified. Further research should verify how the efficacy of PD-1 inhibitors in metastatic castration-resistant PCs is related to dMMR/MSI, DNA-damage repair genes defects, or PD-L1 expression.

Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm.

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic–pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.

Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.