No abstract

Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms, which arise in anatomical locations other than gonads. The pathogenesis of these neoplasms is still poorly understood and it is a matter of debate if they really represent extragondal primary neoplasms or rather extragondal metastasis from occult gonadal neoplasms. The actual observations suggest that EGGCTs represent a unique entity, so their biology and behavior are substantially different from gonadal counterparts. The diagnosis of EGGCTs is often challenging, and differential diagnosis is particularly wide. Nevertheless, a correct diagnosis is essential for the correct management of the patient. We summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.

Rationale About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. Objective To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. Methods and results We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. Conclusions The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.

Primary cutaneous B-cell lymphomas (PCBCLs) comprise a group of extranodal B-cell non-Hodgkin lymphomas B-cell derived, which primarily involve the skin without evidence of extracutaneous disease at the time of diagnosis. They include ∼25% of all cutaneous lymphomas and are classified in three major subgroups (World Health Organization (WHO) 2017): primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center cell lymphoma (PCFCL), and diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). This classification also includes some less common entities such as intravascular large B-cell lymphoma. Recently, WHO-EORTC added Epstein-Barr virus positive (EBV+) mucocutaneous ulcer, as a new provisional distinct entity, to cutaneous B-cell lymphomas. PCBCLs are classically characterized by patches, plaques, or nodules showing great variability for color, shape, and location. Diagnosis requires histological examination with immunohistochemical staining. In general, therapeutic options depend on the exact histological and immunohistochemical classification, disease presentation, and risk assessment. PCMZL and PCFCL are considered indolent lymphomas with a good prognosis and are associated with 5-year disease-specific survival ≥ 95%. In contrast, PCDLBCL, LT is considered an aggressive lymphoma with a survival rate in 5 years of lower than 60%. Patients with a solitary lesion or limited lesions in a single anatomical site require different treatments as compared to patients with generalized lesions or refractory disease or extracutaneous involvement. Therapeutic choice includes observation, local, or systemic therapy based on histology and disease extension. Patient management is multidisciplinary, including dermatologists, pathologists, hemato-oncologists, and radiation oncologists.

No abstract

Molecular heterogeneity is a frequent event in cancer responsible of several critical issues in diagnosis and treatment of oncologic patients. Lung tumours are characterized by high degree of molecular heterogeneity associated to different mechanisms of origin including genetic, epigenetic and non-genetic source. In this review, we provide an overview of recognized mechanisms underlying molecular heterogeneity in lung cancer, including epigenetic mechanisms, mutant allele specific imbalance, genomic instability, chromosomal aberrations, tumor mutational burden, somatic mutations. We focus on the role of spatial and temporal molecular heterogeneity involved in therapeutic implications in lung cancer patients.

Background: Cutaneous melanoma is one of the most severe skin diseases. Nodular melanoma is the second melanoma subtype in order of frequency. The prognosis of skin melanoma depends on the vertical growth of the tumor (Breslow index). For this measurement, excisional biopsy is strongly recommended. This is, however, an invasive procedure and may cause damage to the lymphatic drainage system. The HFUS system, , can be extremely useful for determining tumor thickness in the preoperative phase, given its high resolution capacity. The aim of this preliminary study is to define the role of HFUS for the nodular skin melanoma Breslow thickness in adults before surgery by making a comparison with histological features. Methods: In this study, 14 melanocytic lesions (8 male and 6 female) were evaluated with dermatoscopic clinical features strongly indicative of nodular melanoma. Out of these, excisional biopsy of 7 lesions was requested. The ultrasounds were performed preoperatively. The images were acquired through the first ultrasound scanner with ultra-high frequency probes (range from 50MHz to 70 MHz) available on the market under the EEC mark (Vevo "MD, FUJIFILM Visual Sonics, Amsterdam, the Netherlands) equipped with a linear probe of 50-70 MHz. Results: From the ultrasonographic analysis of 14 nodular melanoma thickness was determined for the presence of two hyperechogenic laminae, separated by a hypo / anechoic space. The twelve lesions were in situ while the other two lesions showed ultrasonography for example; the satellite lesions (less than two centimeters from the primary lesion) and in transit (localizable to more than two centimeters from the primary lesion). Four of these lesions were ulcerated. A comparsion was made the 7 lesions on between the thickness calculated with this method, and that obtained on the bioptic piece. The presence of a positive concordance has been evident in all of the cases. Conclusions: If further studies are needed to support its widespread clinical use, its is believed that, in expert hands and with an interdisciplinary team, HFUS is already capable to reliably calculate a Breslow index in a large majority of patients with cutaneous melanoma.

BackgroundSolitary fibrous tumor is an uncommon soft tissue neoplasm with intermediate biological behavior, which rarely metastasizes. Malignant solitary fibrous tumor, although not clearly defined, is rarely described in the prostate. The present case is characterized by some peculiarities if compared with previously reported cases of prostatic malignant solitary fibrous tumor. Firstly, it does not show a homogeneous morphology: part of the neoplasm (about 50%) showed the features of a conventional solitary fibrous tumor, while the remaining part showed the features of a malignant solitary fibrous tumor. In addition, the case is the first malignant solitary fibrous tumor reaching a huge diameter of 20 cm and replacing all prostatic parenchyma. Interestingly, normal prostatic parenchyma was observed on left-lobe trans-rectal needle-core biopsies, but was totally absent in surgical specimen. Since radical prostatectomy was carried out about 4 months after the biopsies, such discordant data may suggest exceedingly rapid growth of the neoplasm.Case presentationWe report a case of a 62-year-old male, presented at medical observation for urinary retention, constipation and an enlarged prostate gland. A trans-rectal prostatic biopsy showed a low-grade spindle cell neoplasm. Histopathological examination of the prostatectomy specimen showed patternless architecture with hypocellular and hypercellular areas and hemangiopericytoma-like vessels. In some fields the neoplasm was characterized by a high mitotic index and evident cellular atypia. Immunohistochemically, neoplastic cells were positive for CD34, bcl2, CD99, STAT6 and partially for PgR. The neoplasm was diagnosed as a malignant solitary fibrous tumor.ConclusionsThe differential diagnosis of spindle cells tumors arising in the prostrate is broad and includes lesions of epithelial and mesenchymal origin, primary prostatic lesions such as stromal tumors of uncertain malignant potential and stromal sarcoma, as well as anatomically ubiquitous soft tissue neoplasms. Solitary fibrous tumors should be considered in cases of prostatic tumors with a spindled morphology, but malignancy in such tumors is extremely rare in the prostate. A review of literature showed only four additional cases. Because of the unpredictable biological behavior and the possibility of recurrence, a long-term clinical and instrumental follow-up is recommended.