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Yet, the description of a polymorphic cell infiltration in LN biopsy, the absence of clinical lymphadenopathy at presentation, the history of psoriatic arthritis as well as the preceded treatment with anti-tumor necrosis factor (TNF)- and cyclosporine raised diagnostic concerns. Although the patient could not finally avoid R-CHOP immunochemotherapy, this case highlights that a trial of NBA withdrawal under very close monitoring could be a rational therapeutic choice even in patients with aggressive ID-LPDs. Keywords: diffuse large B-cell lymphoma; psoriasis; infliximab; apremilast; novel biologic agent; anti-TNF EN diffuse large B-cell lymphoma psoriasis infliximab apremilast novel biologic agent anti-TNF 1695 1700 6 10/12/23 20231001 NES 231001 The association of psoriasis with cancer has been a matter of debate, especially in the era of the novel biologic agents (NBA). Lastly, taking into consideration our case with the re-appearance of the lymphoma despite the change of NBA as well as all the other cases described in Table 1, the appearance of LPDs in psoriatic patients is a more complex process influenced by clinical disease duration and extension, the time length of immunosuppression and the nature of the various treatments administered. [Extracted from the article]

Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial alliance/CALGB 50303. The latter do not carry concurrent c-myc/bcl-2 and/or bcl-6 rearrangements and usually have the morphology of HGBL with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (HGBL-DLBCL/BL). Dear Editor, In the 2016 WHO classification, HGBL was defined as a separate entity, classified into double/triple-hit lymphomas and HGBL not otherwise specified (HGBL-NOS). [Extracted from the article]

This study aims to identify and define the type and frequency of elastotic alterations of vessels and ducts in pancreatic ductal carcinoma (PDAC) and evaluate its diagnostic significance. Representative tissue from 36 Whipple specimens, stained with Verhoeff's Van-Gieson, was studied focusing on the density and distribution of elastic fibers in walls of vessels and ducts, in perivascular and periductal tissue and in tumor stroma. Vessels and ducts within the carcinoma, at tumor periphery and in non-tumoral pancreas were grouped and examined separately. Vimentin and α-SMA immunostains were used for the depiction of fibroblasts and myofibroblasts. Histochemistry revealed mild to severe elastotic changes of vessels and ducts in all examined cases. Vascular and ductal elastosis was more prominent within the tumor and diminished at tumor periphery. In tumor stroma and non-tumoral pancreatic tissue mild or no elastosis was identified. α-SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant α-SMA+ cells around elastotic and non-elastotic vessels. Conclusively, vascular and ductal elastosis is a tumor-associated phenomenon in PDAC. Its presence is indicative of benignity acquiring a possible diagnostic role. [ABSTRACT FROM AUTHOR]

The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43) and malignant (n=44) lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA) staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.). Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.). In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301). Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165), lymphatic (p=0.1989), and vascular invasion (p=0.0555), as well as in those with increased risk of recurrence rate (p=0.1165), at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary brain tumor in adults, and the most lethal form of glioma, characterized by variable histopathology, aggressiveness and poor clinical outcome and prognosis. GBMs constitute a challenge for oncologists because of their molecular heterogeneity, extensive invasion, and tendency to relapse. Glioma cells demonstrate a variety of deregulated genomic pathways and extensive interplay with epigenetic alterations. Epigenetic modifications have emerged as essential players in GBM research, with biomarker potential for tumor classification and prognosis and for drug targeting. Histone posttranslational modifications (PTMs) are crucial regulators of chromatin architecture and gene expression, playing a pivotal role in malignant transformation, tumor development and progression. Alteration in the expression of genes coding for lysine and arginine methyltransferases (G9a, SUV39H1 and SETDB1) and acetyltransferases and deacetylases (KAT6A, SIRT2, SIRT7, HDAC4, 6, 9) contribute to GBM pathogenesis. In addition, proteins of the sumoylation pathway are upregulated in GBM cell lines, including E1 (SAE1), E2 (Ubc9) components, and a SUMO-specific protease (SENP1). Preclinical and clinical studies are currently in progress targeting epigenetic enzymes in gliomas, including a new generation of histone deacetylase (HDAC), protein arginine methyltransferase (PRMT) and bromodomain (BRD) inhibitors. Herein, we provide an update on recent advances in glioma epigenetic research, focusing on the role of histone modifications and the use of epigenetic therapy as a valid treatment option for glioblastoma. [ABSTRACT FROM AUTHOR]

Cardiac tumors range from benign to high grade malignancies. The incidence of cardiac involvement either by primary, or secondary tumors during autopsy is reported to be extremely low. Extranodal NK/T-cell lymphoma (ENKTL), nasal type is an unusual type of lymphoma. The skin is the second most common site of involvement after the respiratory tract. We present a case of a 63-year-old male, who was recently diagnosed with ENKTL, nasal type, who received chemotherapy, and died without any evident cause. The corpse was referred for routine medicolegal examination. Macroscopical determination of the cause of death was not feasible and subsequent histopathological examination revealed heart infiltration by ENKTL that was found in vivo in cutaneous lesions. Similar infiltrations existed in the pancreatic tissue. To the best of our knowledge, myocardial infiltration of ENKTL, inducing severe myocardial lesions that eventually caused death, is rare, with limited cases reported in the literature. [ABSTRACT FROM AUTHOR]

This letter to the editor describes a rare case of TEMPI syndrome in a 67-year-old female patient. The patient presented with telangiectasias, erythrocytosis, monoclonal gammopathy, and ascites. Further investigation revealed the presence of a lymphoplasmacytic clone and the MYD88 gene L265P mutation. The patient was treated with a combination of rituximab, cyclophosphamide, dexamethasone, and bortezomib, resulting in a significant improvement in her condition. TEMPI syndrome is a newly described hematolymphoid entity with paraneoplastic manifestations, and clinicians should be aware of this syndrome to ensure timely diagnosis and treatment. [Extracted from the article]

Chronic myelogenous leukemia at blast crisis with a T-cell phenotype (T-ALL CML-BC) at diagnosis, without any prior history of CML is extremely rare. After the introduction of tyrosine kinase inhibitors (TKIs), CML patients have a median survival comparable to general population and accelerated/blast crisis are rarely encountered. Most CML patients (80%) transform into acute myeloid leukemia and the rest into B-ALL. Anecdotal cases of Ph+ T-ALL, either de novo or in the context of CML-BC have been reported. Left shift in the blood, the presence of splenomegaly/extramedullary infiltration and the occurrence of BCR::ABL1 rearrangement in both the blastic population, as well as in the myeloid cell compartment are key points in differentiating de novo Ph+ T-ALL from T-ALL CML-BC. The latter is a rare entity, characterized by extramedullary disease, p210 transcript and clonal evolution. Lack of preceding CML does not rule out the diagnosis of T-ALL CML-BC. Prompt TKI treatment with ALL-directed therapy followed by allogeneic stem cell transplantation may offer long-term survival in this otherwise poor prognosis entity. In this paper, we describe a patient with T-ALL CML-BC at presentation, still alive 51 months after diagnosis and we offer a review of the literature on this rare subject. All clinical and laboratory features are provided in order to distinguish de novo Ph+ T-ALL from T-ALL CML-BC, underscoring the prognostic and therapeutic significance of such a differentiation. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphoma's (NHL) incidence is rising over time, and B cell lymphomas comprise the majority of lymphomas. The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue 1 (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in a variety of cellular processes, such as cell proliferation and survival. Its role in lymphomagenesis is confirmed in many different types of B cell lymphomas. This review is mainly focused on the PI3K/v-akt/mTOR pathway-related oncogenic mechanisms in B cell NHLs with an emphasis on common B cell lymphoma types [diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)]. Furthermore, it summarizes the literature regarding the clinical applications of the mTOR inhibitors temsirolimus and everolimus in B cell NHLs, which have been tested in a range of clinical trials enrolling patients with B cell malignancies, either as monotherapy or in combination with other agents or regimens. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the most common primary bone-originating tumor, whereas extramedullary plasmacytoma (EMP) is a plasma cell tumor that arises outside the bone and is most commonly found in the head and neck area. Gastrointestinal and particularly gallbladder involvement is exceedingly rare, and symptoms, if any are present, are usually similar to those seen with cholelithiasis. Treatment options usually include surgical resection and/or chemotherapy. In this report, we present a rare case of a clinically unexpected plasmablastic extramedullary plasmacytoma that was found on abdominal ultrasound (US) and magnetic resonance imaging (MRI) in a 61-year-old asymptomatic patient and led him to undergo cholecystectomy. A fluorodeoxyglucose positron emission computed tomography (FDG PET-CT) that was performed due to the onset of left thigh pain also demonstrated concurrent bone plasmacytoma. The patient is currently receiving chemotherapy and is also being prepared for autologous stem cell transplantation. In this context, we further present the diagnostic, therapeutic and prognostic challenges of EMPs. Lastly, we point out the distinct features of the plasmablastic subtype and analyze its differences compared to other histologic subtypes in achieving a successful diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1‐MAML2, YAP1‐NUTM1, and infrequently WWTR1‐NUTM1; YAP1‐NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1‐translocated tumors. This study sought to investigate potential novel NUTM1‐fusion partners among NUT IHC‐positive poromas and porocarcinomas. Methods: Thirteen NUT IHC‐positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi‐institutional international cohort. Next‐generation sequencing (NGS) assessed for NUTM1 fusion partners. Results: NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1‐NUTM1 (11/12 cases) and WWTR1‐NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read‐spanning YAP1‐NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case. Conclusion: While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1‐NUTM1 fusion was detected in 11 cases (92%) and WWTR1‐NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1. [ABSTRACT FROM AUTHOR]

Case: Wepresent a case of a 35-year-old-man with a giant sclerosing epithelioid fibrosarcoma(SEF) of the thigh. The patient presented with a history of a painful thigh mass. Plain radiographs revealed a soft-tissuemass with extensive calcifications, whereas on magnetic resonance imaging, a lobulated mass between the adductors and the posterior muscles of the thigh was noted. A wide en block resection was undertaken, and the histopathology confirmed the diagnosis of SEF. Postoperative radiation therapy was followed. The patient had no signs of recurrence at the 4-year follow-up. Conclusion: The clinicopathological, imaging characteristics, and treatment options of this rare soft-tissue tumor are discussed. [ABSTRACT FROM AUTHOR]

Background: Polycythemia vera (PV) is characterized by red cell mass expansion in the peripheral blood and can be complicated with thrombosis, bleeding, evolution to acute myeloid leukemia (AML) or a fibrotic phase. Paroxysmal nocturnal hemoglobinuria (PNH) in an acquired clonal haematopoietic stem cell disorder associated with chronic intravascular hemolysis, venous thrombosis, defective hematopoiesis, frequent episodes of infection and, rarely, leukemic transformation. Herein, we report an interesting case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, with unusual thromboses without hemolysis. Case presentation: A 51-year-old woman presented with increased levels of hematocrit, multiple liver, spleen, and left kidney infarctions and ascites; further investigation revealed a JAK2V617F-positive polycythemia vera and the presence of a significant PNH population (more than 90% CD55– CD59– cells among both granulocytes and red blood cells). Interestingly, the patient has experienced severe thrombotic events without any signs or symptoms of hemolysis. Conclusions: This case raises questions over uncharted aspects of the PNH etiopathogenesis and its potential association with myeloproliferative neoplasms (MPN) and highlights the difficulty of diagnosing and managing patients with more than one potentially thrombophilic conditions, especially with established and severe thromboses. [ABSTRACT FROM AUTHOR]

Expression of thioredoxin-1 (TXN) and CXCL9 is not restricted to THRLBCL macrophages, but may be observed in histiocytes and neoplastic (HRS) cells of EBV + mixed cellularity (MC) classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant HL. We aimed to validate and extend the above observations in 174 cHL patients evaluating the immunohistochemical expression of TXN, CXCL9 and IFN-γ. HRS-cell CXCL9 expression was higher in latent membrane protein-1 (LMP1)+, MC and Stage IV. TXN and CXCL9 expression by cHL histiocytes was more frequent in LMP1+, MC and older patients (only for CXCL9). TXN expression by HRS cells (≥80%) was independently associated with better failure-free survival. In conclusion, markers of TCHRLBCL histiocytes (TXN, CXCL9), as well as IFN-γ are also expressed by histiocyte subsets and neoplastic cells of cHL. The expression of some of them is more prominent in EBV + MC, but not restricted to this subtype. The prognostic implication of TXN needs further evaluation. [ABSTRACT FROM AUTHOR]

A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter twomolecule expressions weremore pronounced in the PCs in ∼40%of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients. [ABSTRACT FROM AUTHOR]

Mastocytosis is amyeloproliferative neoplasmcharacterized by clonal expansion of abnormalmast cells, ranging fromthe cutaneous forms of the disease to mast cell leukemia. In a significant proportion of patients, systemic mastocytosis (SM) coexists with another hematologic malignancy, termed systemic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD). Despite the pronounced predominance of concomitant myeloid neoplasms, the much more unusual coexistence of lymphoproliferative diseases has also been reported. Imatinib mesylate (IM) has a role in the treatment of SM in the absence of the KITD816Vmutation. In the setting of SM-AHNMD, eradicating the nonmast cellmalignant clone greatly affects prognosis. We report a case of an adult patientwith SMassociatedwith B-lineage acute lymphoblastic leukemia (B-ALL).Three cases of concurrent adult ALL and mastocytosis have been reported in the literature, one concerning SM and two concerning cutaneous mastocytosis (CM), as well as six cases of concomitant CM and ALL in children. [ABSTRACT FROM AUTHOR]

• PMLBCL rarely extends to extranodal subdiaphragmatic (ES) sites at diagnosis. • Among 455 patients, 32 (7%) had such localization at baseline. • Kidney, liver, and adrenals were most frequently involved. • ES site involvement had not independent prognostic impact beyond that of stage IV. [ABSTRACT FROM AUTHOR]