Molecular investigation of some DNA viruses in mucosal melanoma: Case-control study.

The association between viral infections and both cutaneous and mucosal melanoma (MM) has not been fully investigated. Here, we assessed the prevalence of the DNA of a broad range of viruses in 31 MMs and 15 biopsies of healthy mucosa (HM) using molecular methods. The parvoviruses CuV and B19V, herpesviruses HSV1, HSV2, EBV, HHV6, and HHV8, polyomavirus MCPyV, and α-HPVs were not detected, or rarely found, in MMs, and in HM, of the digestive, respiratory, and female genital tract. The overall prevalence of ß-HPV in MMs was not significantly higher compared to that in HM (70.9% and 53.3% respectively; p = 0.514). However, the number of MMs positive for ß-HPV types belonging to Species 3 and 5 and for some viral types belonging to Species 1, 2, 3, and 5 were significantly higher compared with HM (p < 0.05). Moreover, compared to HM, the MM samples contained a significantly higher number of ß-HPV types, mainly belonging to Species 1, 3, and 5 (p < 0.05). Our data, although suggesting a role for certain ß-HPV types in MM oncogenesis, require additional investigation in larger populations to support this hypothesis.

Maxillofacial Bone Involvement in Fibro-Osseous Lesions: Emphasizing the Significance of Differential Diagnosis.

The World Health Organization's (WHO) 2022 update on the classification of odontogenic and maxillofacial bone tumors has revolutionized diagnostic and treatment paradigms by integrating novel molecular insights. Fibro-osseous lesions of the maxillo-facial bones constitute a heterogeneous group encompassing fibrous dysplasia, Psammomatoid Ossifying Fibroma (PSOF), Juvenile Trabecular Ossifying Fibroma (JTOF), and other variants. Despite histological similarities, their distinct clinical manifestations and prognostic implications mandate precise differentiation. The intricacies of diagnosing fibro-osseous lesions pose challenges for pathologists, maxillofacial surgeons, dentists and oral surgeons, underscoring the importance of a systematic approach to ensure optimal patient management. Herein, we present two cases, fibrous dysplasia and Cemento-Ossifying Fibroma, detailing their clinical encounters and management strategies. Both patients provided informed consent for publishing their data and images, adhering to ethical guidelines.

Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

Burkitt lymphoma (BL) is characterized by tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to a favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of EBV + BL with granulomatous reaction compared to 8 cases of EBV + BL and 8 EBV- BL, both with typical "starry sky" pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated by multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (Cluster 2), EBV - BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky", both EBV + and EBV -. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, while BLs with "starry sky" were characterized by up-regulation of M2- polarization and pro-tumor response. Moreover, the analysis of additional signatures revealed an up-regulation of Dark zone-signature and epigenetic-signature in BL with typical "starry sky". Tumor associated macrophages (TAM) and epigenetic regulators may be promising targets for additional therapies in BL lymphoma opening novel immunotherapeutic strategies.

KRAS Mutations Are Associated with Shortened Survival in Patients with Epithelioid Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural surface that includes three major histologic subtypes, epitheliod, sarcomatoid and biphasic. Epithelioid mesothelioma is usually associated with better prognosis. The genetic mechanisms driving MPM, the possible target mutations and the correlation with overall survival remain largely unsettled. We performed target exome sequencing in 29 cases of MPM aimed at identifying somatic mutations and, eventually, their correlation with phenotypic traits and prognostic significance. We found that KRAS mutations, occurring in 13.7% of cases, were associated with shortened median survival (7.6 versus 32.6 months in KRAS wild-type; p = 0.005), as it was the occurrence of any ≥3 mutations (7.6 versus 37.6 months; p = 0.049). Conversely, the presence of KDR single nucleotide polymorphism p.V297I (rs2305948) resulted in a favorable variable for survival (NR versus 23.4 months; p = 0.026). With the intrinsic limitations of a small number of cases and patient heterogeneity, results of this study contribute to the characterization of the mutation profile of MPM and the impact of selected somatic mutations, and possibly KDR polymorphism, on prognosis.

Morphea Profunda with Tertiary Lymphoid Follicles: Description of Two Cases and Review of the Literature.

Morphea profunda or subcutaneous (deep) morphea is a variant of localized morphea, characterized by one or more ill-defined, deep sclerotic plaque. Preferential sites are the abdomen, trunk, sacral area, or extremities. The presence of hyperplastic lymphoid follicles in the context of the sclerotic bands of morphea is rarely described. Localized scleroderma is sustained by a profibrotic inflammatory profile. Transforming growth factor-ß (TGF-ß), an imbalance between functional subclasses of T-lymphocytes (innate immune cells) has a role in activate collagen deposition. In this case report, we present two cases of morphea profunda with lymphoid follicular hyperplasia. A systematic review of the literature on the pathophysiology of localized scleroderma is also presented, with particular reference to the presence of lymphoid structures.

A rare case of epidermoid cyst of the cecum.

Epidermoid cysts of the gastrointestinal tract are very uncommon and the published literature on this subject is anecdotal. We report the case of a 51-year-old man who was diagnosed with a cystic neoplasm located close to the cecum and the appendix. Given the strong suspicion of an appendiceal mucocele, the patient underwent a laparoscopic exploration. During the operation, a semisolid mass appearing to originate from the cecal wall was identified and a laparoscopic ileo-cecal resection was performed. The pathological diagnosis was an epidermoid cyst of the cecum. An epidermoid cyst of the cecum is a rare entity that usually has a mild and aspecific clinical picture. However, it should be included in the differential diagnosis of an occasionally diagnosed peri-cecal cystic lesion.

The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma.

Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.

TFE3 Gene Rearrangement in Perivascular Epithelioid Cell Neoplasm (PEComa) of the Genitourinary Tract.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms with unpredictable behavior. They are characterized by epithelioid cells, which stain with melanocytic markers, associated with spindle cells reactive for smooth muscle markers. PEComas may be sporadic or associated with the tuberous sclerosis complex, with mutations affecting mostly tuberous sclerosis complex (TSC) 2 and less frequently TSC1 genes. More recently a subtype of PEComa harboring TFE3 gene rearrangement, mutually exclusive with TSC complex mutations, has been identified. The bladder and the other genitourinary tract organs are an infrequent site of origin; to date, only 3 cases of primitive bladder PEComas, 1 prostatic PEComa, and 2 epithelioid angiomyolipomas of the kidney with TFE3 rearrangement have been described in literature. We report a bladder PEComa case with Xp11 rearrangement in a patient who previously had undergone chemotherapy for chronic lymphatic leukemia. We assessed the meaning of the presence of TFE3 rearrangement in genitourinary tract PEComas and the possible correlation of these uncommon lesions with previous chemotherapy. A better understanding of this entity's genetics may help suggest appropriate targeted therapy, which is still lacking in genitourinary tract PEComas.

Magnetic resonance features of sinonasal melanotic mucosal melanoma.

A 67-year-old man presented to ear, nose and throat department complaining of nasal congestion and recurrent epistaxis for 5 months. Nasal endoscopy revealed a pigmented polyp obstructing the right nasal cavity. MRI with contrast agent showed a right nasal cavity polypoid mass with hyper signal intensity (SI) both in non-enhanced T1-w and diffusion imaging, marked hypo SI in T2-w sequences and avidly contrast enhancement characterised by rapid wash-in without significant wash-out on dynamic perfusion imaging. Histological specimen showed epithelioid and spindle cells with focal intense pigmentations and immunohistochemical features compatible with primary melanotic sinonasal mucosal melanoma (SNM). As melanotic SNM shows MRI pathognomonic high non-enhanced T1-w SI, this case underlines the crucial role of MRI not only in assessing the local tumour extension/recurrence but also in increasing the diagnostic confidence of detecting melanotic SNM. Thus, MRI should be always performed in case of clinical-endoscopic suspicion of SNM.

Lymphatic and blood vasculature in primary cutaneous melanomas of the scalp and neck.

BACKGROUND: Scalp/neck melanomas have a poor prognosis, possibly because of a rich vascular supply that prompts tumor cells' dissemination. METHODS: We compared the accuracy of immunohistochemical (IHC) staining with morphology for the identification of lymphovascular invasion in 156 scalp/neck melanomas. We then analyzed the association of vessel invasion and density with pathological features and survival. RESULTS: IHC-detected lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were identified in 34.6% and 13.5% of cases, respectively. IHC increased the LVI/BVI detection compared to morphology (40.4% vs 16.6%; p < .001). The degree of peritumoral and intratumoral blood vessel density (BVD) was greater than lymphatic vessel density (LVD). Ulceration was the only factor independently associated with intratumoral (p = .029) and peritumoral (p = .047) BVD. Tumor thickness was the only independent predictor of survival (p = .002). CONCLUSION: IHC allows accurate assessment of lymphovascular invasion in scalp/neck melanomas. In these tumors, we observed a high incidence of BVI, which deserves further investigations.