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.

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.

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-β (TGF-β), 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.

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.

Background/Objectives: B-cell receptor (BCR) signalling is implicated in Burkitt lymphoma (BL) lymphomagenesis, although its activation may differ across biological and epidemiological settings. While surface IgM is the predominant immunoglobulin isotype of BCR in BL, cases expressing IgA transcripts or lacking detectable surface immunoglobulin (sIg) expression have been reported, suggesting a more complex pattern of sIg expression than previously recognized. This study aimed to evaluate sIg heavy-chain expression by immunohistochemistry in a relatively large series of BL cases from endemic and sporadic settings and to investigate the mutational landscape of surface immunoglobulin-undetectable (sIg-UND) cases. Methods: sIg heavy-chain expression was assessed by immunohistochemistry in 55 formalin-fixed paraffin-embedded BL samples. Targeted next-generation sequencing was performed on four sIg-UND cases using an Illumina capture-based custom panel covering 74 lymphoma-related genes. KRAS and NRAS hotspot mutations were additionally assessed by real-time PCR. Results: Overall, 41/55 cases showed IgM expression, including 31 IgM-positive and 10 IgM+/UND cases, whereas 8/55 cases showed IgA expression (IgA+/UND). IgA-expressing cases were significantly enriched at mucosal sites, particularly the oral cavity and gastrointestinal tract, consistent with the relevance of these anatomical sites to mucosal IgA production. Six cases lacked detectable sIg expression, showing negativity for all tested immunoglobulin heavy chains in more than 90% of neoplastic cells. Four sIg-UND cases were available for sequencing. These cases harbored mutations affecting genes commonly altered in BL, together with alterations in genes less commonly represented in recurrent BL series, such as MEF2B, CREBBP, PRDM1, PIM1, ARID3A, HIST1H1B, and HIST1H1C. Conclusions: Our study provides a systematic immunohistochemical characterization of surface immunoglobulin heavy-chain expression in a relatively large series of endemic and sporadic BL. We identified a subset of IgA-expressing BL cases enriched at mucosal sites, whereas rarer cases lacked detectable surface immunoglobulin expression. The mutational profile of sIg-UND cases highlights alterations affecting genes involved in epigenetic regulation, chromatin organization, and B-cell differentiation, which may contribute to the biological heterogeneity of these cases. No KRAS or NRAS hotspot mutations were detected in the four sequenced sIg-UND cases, as assessed by targeted NGS and real-time PCR. Further functional studies are needed to clarify the biological and clinical significance of sIg-UND BL cases and to determine the functional relevance of the identified alterations.