J. Mol. Pathol., Volume 5, Issue 2 (June 2024) – 3 articles

Endometrial cancer (EC) represents one of the most newly diagnosed cancers across gynecological malignancies. In particular, a plethora of risk factors (both biological and lifestyle-related) drastically impact the incidence rate of novel diagnosis accounting for 8300 cases/year. In the recent era of precision medicine EC molecular classification, integrating ESGO/ESTRO/ESP guidelines, four distinct diagnostic groups have been established including POLE-mutant (POLE-pos); High-instability MSI (H-MSI)–MMR-deficient (MMR-d); p53-abnormal (p53abn); and non-specific molecular profile (NSMP), also known as p53-wild-type EC patients on the basis of clinically relevant emerging biomarkers. In addition, molecular testing also plays a pivotal role in defining the best therapeutical option. In this scenario, the European Society for Medical Oncology (ESMO) recommended d-MMR/MSI-H status evaluation in the diagnostic workflow of Lynch syndrome or selecting EC patients that could benefit from immune checkpoint inhibitors (ICIs). Although immunohistochemistry (IHC) is considered the gold standard approach for d-MMR profiling, a series of molecular PCR-based techniques have rapidly developed to integrate H-MSI status in routine practice. Here, we technically overviewed the most relevant commercially available diagnostic assays for the determination of the H-MSI/dMMR status in EC patients. Full article

The liver is a multi-potent organ with important metabolic, immunological and endocrine functions. Hepatic physiology is maintained at a balanced state via the delicate actions of different liver-resident cells. Among several factors that modulate hepatic physiology, the harmony between the activity of pro- and anti-inflammatory cytokines is a crucial determinant. However, initiation of inflammatory activity can be detrimental if it goes unresolved, leading to severe consequences such as hepatitis, hepatic fibrosis, cirrhosis or even hepatocellular carcinoma (HCC). Different physiological processes can modulate the hepatic microenvironment; one such factor is a cytosolic protein complex called the inflammasome. Inflammasome activation is a consequence of the cellular encounter with pathogens or products of cellular damage. Once activated, inflammasomes promote the maturation of interleukin-1 family cytokines such as IL-1β and IL-18 via activation of caspase-1. These cytokines have a very potent role in modulating hepatic physiology. Various lines of reports suggest that inflammasome activation and IL-1 cytokines play critical roles in liver diseases, including hepatitis, hepatic fibrosis and HCC. Conversely, inhibition of inflammasome activation and/or IL-1 signaling prevents such effects. This review summarizes the mechanisms leading to inflammasome activation and the role it plays in hepatic physiology. Full article

Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues. It is the most common skin cancer. It is fairly common in fair Caucasians and quite uncommon in dark-skinned populations. It contributes to 65–75% of cutaneous malignancies in whites and 20–30% in Asian Indians. The most important causal factors appear to be radiation exposure and genetic predisposition. It may present as a nonhealing lesion that occasionally bleeds or as a pruritic lesion with no symptoms. Tumours rarely spread to regional lymph nodes. The clinical appearances and morphology of BCC are diverse. Clinical types include nodular, cystic, superficial, pigmented, morphoeaform, (sclerosing), keratotic and fibroepithelioma of Pinkus. Most of the lesions appear on the head and neck, usually above the line joining the tragus and the angle of the mouth. A biopsy should be performed on all lesions suspected of BCC. The primary aim of treatment is the complete excision of the tumour tissue. Other treatment modalities include cryotherapy, immunomodulatory drugs, laser treatment or locally applicable chemotherapeutic agents. Prevention consists of lifestyle changes such as avoiding sunburn, tanning beds and prolonged direct sun exposure, shade seeking, sunscreen application on the skin, and physical barrier methods such as protective clothing, hats and sunglasses. Regular sunscreen use in childhood and adolescence seems more beneficial than in adulthood. Full article