Hydatidiform moles (HM) are members of gestational trophoblastic diseases (GTD) and, in some cases, might progress to gestational trophoblastic neoplasia (GTN). HMs are either partial (PHM) or complete (CHM). Some HMs are challenging in arriving at a precise histopathological diagnosis. This study aims to investigate the expression of BCL-2 by immunohistochemistry (IHC) in HMs as well as in normal trophoblastic tissues "products of conception (POC) and placentas" using Tissue MicroArray (TMA) technique. TMAs were constructed using the archival material of 237 HMs (95 PHM and 142 CHM) and 202 control normal trophoblastic tissues; POC and unremarkable placentas. Sections were immunohistochemically stained using antibodies against BCL-2. The staining was assessed semi-quantatively (intensity and percentage of the positive cells) in different cellular components (trophoblasts and stromal cells). BCL-2 showed cytoplasmic expression in more than 95% of trophoblasts of PHM, CHM and controls. The staining showed a significant reduction of the intensity from controls (73.7%), PHMs (76.3%) to CHM (26.9%). There was a statistically significant difference between PHM and CHM in the intensity (p-value 0.0005) and the overall scores (p-value 0.0005), but not the percentage score (p-value > 0.05). No significant difference was observed in the positivity of the villous stromal cells between the different groups. All cellular components were visible using the TMA model of two spots/case (3 mm diameter, each) in more than 90% of cases. Decreased BCL-2 expression in CHM compared to PHM and normal trophoblasts indicates increased apoptosis and uncontrolled trophoblastic proliferation. Construction of TMA in duplicates using cores of 3 mm diameter can overcome tissue heterogeneity of complex lesions.

Platinum-based chemotherapy is the standard chemotherapy for high grade serous ovarian cancer and primary peritoneal high-grade serous carcinoma. PARP inhibitors have changed the paradigm of the treatment in platinum-sensitive ovarian cancers and primary peritoneal high-grade serous carcinoma with BRCA1/2 mutation or homologous recombination deficiency (HRD). Platinum-resistant ovarian and primary peritoneal high-grade serous carcinoma have a lower chance to treat and have worse outcomes. We described a case of patient with a platinum resistant primary peritoneal high-grade serous carcinoma with a rare somatic BRCA2 amplification. There are no guidelines for the treatment of ovarian cancer or primary peritoneal high-grade serous carcinoma with BRCA2 amplification. BRCA2 amplification could result in extreme homologous recombination repair (HRR) pathway efficiency and in less platinum sensitivity, which could be a molecular signature for platinum resistance. Free platinum chemotherapy regimens could be more effective in cases with BRCA2 amplification. Further studies are necessary to establish better approaches and strategies for oncological management and treatment in BRCA2 amplification high grade ovarian cancer and primary peritoneal high-grade serous carcinoma.

Placental site trophoblastic tumor (PSTT), also known as atypical choriocarcinoma, syncytioma, chorioepitheliosis or trophoblastic pseudotumor, is a rare gestational trophoblastic disease (0.25-5% of all trophoblastic tumors) and it is composed by neoplastic proliferation of intermediate trophoblasts at placental implantation site. It consists of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells with a characteristic vascular and myometrial invasion. Main differential diagnoses are gestational choriocarcinoma (GC) and epitelioid trophoblastic tumor (ETT). We present a case of PSTT in a 25-year-old woman. Neoplastic cells showed moderate/high nuclear pleomorphism, abundant amphophilic, eosinophilic and clear cytoplasm, numerous mitotic figures (10 mitoses/10 HPF), and myometrial invasion. Other features are necrosis, vascular invasion with replacement of myometrial vessels by tumor cells and hemorrhage. The patient showed typical low serum β-hCG levels and high serum humane placental lactogen (hPL) levels.

The fifth edition of the World Health Organization (WHO) “Blue Book” on urinary and male genital tumours was published in 2022, but since when has the WHO been concerned about the classification of these neoplasms? It all began in 1952, when the WHO committee of Health Statistics established that, in order to statistically categorise tumours, they had to be classified according to anatomical site, histological type and degree of malignancy. In 1956 the WHO Executive Board proposed organising specific centres to fullfil this project. Following the establishment of these centres in 1958, microscope slides were sent to different pathologists with the purpose of reaching a consensus on classification criteria. The WHO centre for urinary and male genital tumours was the Armed Forces Institute of Pathology (AFIP) in Washington, under the direction of F.K. Mostofi, who was responsible for the first two editions, with separate books dedicated to each organ: Urinary bladder first edition in 1973 1, second edition in 1999 2; Testis first edition in 1977 3, second edition in 1998 4; Kidney first edition in 1981 5, second edition in 1998 6; and Prostate first edition in 1980 7. No publication covered tumours of the Penis. These volumes provided brief reviews accompanied by coloured illustrations of all recognised neoplasms and their variants. The third edition, printed in 2004, saw a considerable change 8. Firstly, tumours of the various organs of the urinary and male genital systems, including the penis, were gathered in a single book. Secondly, the editors, J.N. Eble, G. Sauter, J.I. Epstein and I.A. Sesterhenn, were from different institutions. Thirdly, the preliminary drafting of tumour types was accomplished by a large number of pathologists from different countries, and a consensus meeting was held at the International Agency for Research on Cancer (IARC) in Lyon, where the book was published. After a consensus meeting at the University Hospital in Zürich, the fourth edition, edited by H. Moch, P.A. Humphrey, T.M. Ulbright and V.E. Reuter, was released in 2016 and updated the contents following the guidelines set out in the third edition 9. The current edition, published in print as well as a website (htpp://tumourclassification. iarc.who.int) in 2022, can boast an extensive editorial board (M.B. Amin, D.M. Berney, E.M. Comperat, A. Hartmann, S. Menon, G.J. Netto, M.R. Raspollini, M.A. Rubin, S.K. Tickoo and S. Turajlic) that convened via video conference in January 2021, during the Covid-19 pandemic 10. Updates are provided with a uniform layout for each chapter and individual tumours are described on the basis of clinical features, epidemiology, etiology, pathogenesis, histopathology, diagnostic molecular pathology, staging and prognosis. Information on macroscopy and cytology as well as essential and desirable diagnostic criteria are also included. Another novelty of this edition is specific chapters comcerning genetic tumour syndromes, neuroendocrine neoplasms, mesenchymal and haematolymphoid tumours, most often found in the urinary and male genital tracts. The evolution of the WHO “Blue Books” is characterised not only by the updating of tumour classifications but also by full coverage of clinical, morphological and molecular genetic data. Without becoming comprehensive textbooks, they are essential tools conveying international standards for diagnosis and cancer research.

SummaryPrimary acinic cell carcinoma (ACC) of the lung is an extremely rare neoplasm that more often arises near to a right bronchus. It is characterized by two populations of clear and dark eosinophilic cells, arranged in a glandular acinar pattern. Mitosis are rare and tumor cells show small and eccentric nuclei. Positive stain for PAS, PAS-D, cytokeratin, A1AT and A1ACT is reported, while TTF1, p40, synaptophysin, SMA, and S100 are substantially negative. DOG-1 positive stain was observed in ACC of the salivary glands and its negativity was proposed to distinguish between primary and metastatic ACC of the lung. Here, we report the 30th case of primary ACC of the lung, describing the immunohistochemical positivity for DOG-1 and the molecular status of the neoplasm for the first time.

SummaryMelanoma is an important cause of skin cancer related death throughout the world, particularly in Europe, the United States, and Australia. Rarely melanoma undergoes divergent differentiation to simulate the full morphologic and immunohistochemical features of other malignancies, notably sarcoma. However, such cases retain the molecular signatures of melanoma, including BRAF gene mutations. Gene mutation analysis of tumour DNA, now standard practice for all melanomas of stage III or above, may establish the diagnosis of melanoma in some advanced malignancies of unknown lineage. A prior history of melanoma or risk factors for melanoma may be the first clue that an advanced malignancy represents metastatic melanoma. Recognition of this presentation of melanoma can allow a patient to access well-tolerated life-prolonging therapies such as targeted therapy, inhibiting the BRAF/MEK pathway, and immune checkpoint inhibitor therapy.

SummaryNeoadjuvant therapy (NAT) in breast cancer is administered to downstage the tumor, de-escalate surgery, and provide prognostic information that can be used to tailor subsequent adjuvant therapy. In this respect, the pathological evaluation of both pre-NAT biopsies and post-NAT surgical specimens is crucial to precisely assess the treatment response. With the increasing possibilities of NAT protocols and the rising number of eligible patients, it has become extremely important to standardize the pathological response assessment. Here, we provide an update on the recommendations of the Italian Group for the Study of Breast Pathology - the Italian Society of Pathology (GIPaM-SIAPeC) for the analysis of breast cancer samples before and after NAT.

SummarySubcutaneous parasitic infections are possible matches in routine pathology and can be detected not only in patients coming from or travelling in tropical countries, but also when the anamnesis does not suggest at first worm infestations.Here we report the case of a young man from the north-west of Italy, with a negative anamnesis for travels but the presence of dogs at home, who presented a subcutaneous nodule showing a nematode surrounded by a fibrous capsule; the morphology was suggestive for Dirofilaria repens. Dirofilariosis is a zoonosis caused by D. repens or D. immitis, which can be acquired by dogs and cats through mosquitos bites; the disease is widespread in developing countries, but it is also emerging in Western countries, becoming an important public health issue.