The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

Peripheral nerve sheath tumors encompass a wide spectrum of lesions with different biological behavior, including both benign and malignant neoplasms as well as the recent diagnostic category, i.e., “atypical neurofibromatous neoplasm with uncertain biologic potential” to be used only for NF1 patients. Neurofibromas and schwannomas are benign Schwann-cell-derived peripheral nerve sheath tumors arising as isolated lesions or within the context of classical neurofibromatosis or schwannomatoses. Multiple tumors are a hallmark of neurofibromatosis type 1(NF1) and related forms, NF2-related-schwannomatosis (formerly NF2) or SMARCB1/LZTR1-related schwannomatoses. Perineuriomas are benign, mostly sporadic, peripheral nerve sheath tumors that show morphological, immunohistochemical, and ultrastructural features reminiscent of perineurial differentiation. Hybrid tumors exist, with the most common lesions represented by a variable mixture of neurofibromas, schwannomas, and perineuriomas. Conversely, malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or a pre-existing neurofibroma, and in about 50% of cases, these tumors are associated with NF1. The present review emphasizes the main clinicopathologic features of each pathological entity, focusing on the diagnostic clues and unusual morphological variants.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0–10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting.

Ductal carcinoma in situ (DCIS) shows overlapping epidemiology with invasive ductal carcinoma of the breast, sharing similar risk factorssuch as age, mammographic density, family history, and hormonal therapy as well as genetic factors such as BRCA1/BRCA2, histotypes, and molecular subtypes such as luminal A and B, HER2 enriched, and basal-type, thus suggesting its potential precursor role. A small percentage of patients with a history of DCIS die without a documented intermediate diagnosis of invasive breast carcinoma (IBC). The increased risk of death is usually associated with ipsilateral recurrence such as IBC. The slightly variable incidence of DCIS in different countries is mainly due to a different diffusion of mammographic screening and variability of the risk factors. The majority of DCIS lesions are not palpable lesions, which can be only radiologically detected because of the association with microcalcifications. Mammography is a highly sensitive diagnostic procedure for detecting DCIS with microcalcifications, while magnetic resonance imaging (MRI) is considered more sensitive to detect DCIS without calcifications and/or multifocal lesions. The aim of the present overview was to focus on the clinical, radiological, and pathological features of DCIS of the breast, with an emphasis on the practical diagnostic approach, predictive prognostic factors, and therapeutic options.

Background: The category of the “stromal tumors of the lower female genital tract” encompasses a wide spectrum of lesions with variable heterogeneity, which can be nosologically classified on the basis of their morphologic and immunohistochemical profiles as deep (aggressive) angiomyxoma (DAM), cellular angiofibroma (CAF), angiomyofibroblastoma (AMFB) or myofibroblastoma (MFB). Despite the differential diagnosis between these entities being usually straightforward, their increasingly recognized unusual morphological variants, along with the overlapping morphological and immunohistochemical features among these tumours, may raise serious differential diagnostic problems. Methods and Results: The data presented in the present paper have been retrieved from the entire published literature on the PubMed website about DAM, CAF, AFMB and MFB from 1984 to 2021. The selected articles are mainly represented by small-series, and, more rarely, single-case reports with unusual clinicopathologic features. The present review focuses on the diagnostic clues of the stromal tumours of the lower female genital tract to achieve a correct classification. The main clinicopathologic features of each single entity, emphasizing their differential diagnostic clues, are discussed and summarized in tables. Representative illustrations, including the unusual morphological variants, of each single tumour are also provided. Conclusion: Awareness by pathologists of the wide morphological and immunohistochemical spectrum exhibited by these tumours is crucial to achieve correct diagnoses and to avoid confusion with reactive conditions or other benign or malignant entities.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.