Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop.

The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session on cavity-based lymphomas included sixty-eight cases in seven sections. The disease entities discussed include primary effusion lymphomas (PEL), extracavitary primary effusion lymphomas and confounding entities (ECPEL), HHV8-negative B-lineage lymphomas-effusion based (EBV-negative, EBV-positive, and plasmablastic types), diffuse large B-cell lymphoma associated with chronic inflammation, fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL), breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and other lymphomas presenting as an effusion. All entities above are discussed; however, three are delved into greater detail given the challenges with classification: ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. Cases exemplifying the diagnostic difficulty in differentiating ECPEL from HHV8-positive diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder were discussed. The more recently recognized effusion-based HHV8-negative large B-cell lymphoma is explored, with several cases submitted raising the question if this subset should be carved out as a specific entity, and if so, what should be the refining diagnostic criteria. Case submissions to the FA-DLBCL section yielded one of the largest case series to date, including classic cases, cases furthering the discussion on disease sites and prognosis, as well as novel concepts to be considered in this entity. The 2022 EA4HP/SH workshop cases allowed for further confirmation of the characteristics of some of the more historically accepted cavity-based lymphomas, as well as further inquiry and debate on relatively new or evolving entities

Correction to: The many faces of nodal and splenic marginal zone lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.

Session 3 of the lymphoma workshop of the XXI joint meeting of the European Association for Haematopathology and the Society for Hematopathology took place in Florence, Italy, on September 22, 2022. The topics of this session were splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas and their differential diagnosis as well as related entities. Forty-two cases in these categories were submitted to the workshop, including splenic lymphomas (marginal zone and diffuse red pulp lymphomas), transformed marginal zone lymphomas (splenic and nodal), nodal marginal zone lymphomas with increased TFH-cells, and pediatric nodal marginal zone lymphomas. The case review highlighted some of the principal problems in the diagnosis of marginal zone lymphomas, including the difficulties in the distinction between splenic marginal zone lymphoma, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant/splenic B-cell lymphoma with prominent nucleoli which requires integration of clinical features, immunophenotype, and morphology in blood, bone marrow, and spleen; cases of marginal zone lymphoma with markedly increased TFH-cells, simulating a T-cell lymphoma, where molecular studies (clonality and mutation detection) can help to establish the final diagnosis; the criteria for transformation of marginal zone lymphomas, which are still unclear and might require the integration of morphological and molecular data; the concept of an overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma; and the distinction between pediatric nodal marginal zone lymphoma and “atypical” marginal zone hyperplasia, where molecular studies are mandatory to correctly classify cases

COMPREHENSIVE ANALYSIS OF BASELINE OUTCOME BIOPREDICTORS IN YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA: THE ANCILLARY BIOLOGICAL STUDIES OF FONDAZIONE ITALIANA LINFOMI (FIL) MCL0208 CLINICAL TRIAL

Despite the improvement in therapeutic schedules, a relevant fraction of mantle cell lymphoma (MCL) patients still experience primary treatment failure. This is due to a deep biological heterogeneity, not adequately dissected by the clinical predictors alone, as the MIPI (MCL International Prognostic Index). The Fondazione Italiana Linfomi (FIL) MCL0208 trial (NCT02354313) is a prospective, randomized phase III trial comparing lenalidomide maintenance vs observation after an intensive citarabine containing chemo-immunotherapy followed by autologous transplantation in frontline MCL patients <66 years.[Ladetto, ASH 2018] Several biological ancillary studies were planned upfront, prospectively investigating the prognostic impact of putative biomarkers. Here we present a comprehensive analysis of the clinical impact of all the identified biopredictors

Hairy cell leukemia in kidney transplantation: lesson from a rare disorder

We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer

ALK-positive anaplastic large cell lymphoma with PAX-5 expression: report of a case

ALK-positive anaplastic large cell lymphoma (ALCL) is a well-defined entity included in the 2008 WHO classification, comprising about 5% of non-Hodgkin lymphomas and 10 to 30% of childhood lymphomas. Although lacking several T-cell antigens, it is generally considered a T-cell derived neoplasm. Since both ALCL and Hodgkin lymphoma (HL) strongly express CD30, and they can show overlapping morphological features, the B-cell specific marker PAX5 is widely used for distinguishing the two entities. PAX5 is considered the most specific B-cell marker, and is defined as "the guardian of B-cell identity". We report an exceptional case of ALK-positive ALCL with PAX5 expression. A 38-years old patient presented with fever and generalized lymphadenopathy lasting for two months at the time of biopsy. A basic cytofluorimetric analysis was performed, showing the presence of a large cell population with dim CD5 and CD4 expression. Histopathological evaluation revealed an effaced lymph node architecture, due to the presence of a neoplastic infiltration by medium-sized cells in wide aggregates; occasionally larger cells with "hallmark" morphology were present; intrasinusoidal involvement was evident. These atypical cells showed a strong staining for CD30, as well as perforin, while granzyme B was only focally expressed. Other T-cell markers (CD2, CD3, CD5, CD7, ZAP70) and B-cell markers (CD20, CD79a) were negative, with the notable exception of PAX5, which showed a dim but specific staining, similar to that observed in HL. ALK was diffusely expressed in neoplastic cells, with a predominantly cytoplasmic granular staining. Double chromogenic stains and immunofluorescence were also performed to confirm the findings. ALK-positive diffuse large B-cell lymphoma was ruled out because this case didn't show the typical immunoblastic/plasmablastic morphology, didn't express plasma cell markers and was diffusely CD30-positive. The patient was unfortunately lost at follow-up. Four cases of PAX5-positive ALCL were recently described, of which only one was ALK-positive, diagnosed on a vertebral lesion. A previous study had identified three PAX5-positive ALK-negative ALCL, but no ALK-positive cases. To our knowledge, this case is the first description of lymph node involvement by PAX5-positive and ALK-positive ALCL. Our data show that the morphological presentation is totally overlapping with classical ALCL; we also confirm that PAX5 can be rarely expressed in ALCL and should not be taken as a final proof of the B-cell origin of a neoplastic population