Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.

PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥ 5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.