Clinically Undetected Hodgkin Lymphoma Diagnosed Initially on Bone Marrow Biopsy: A Large Retrospective Observational Study from a Tertiary Care Center

Introduction Hodgkin lymphoma (HL) involving the bone marrow (BM) is relatively rare with an incidence ranging from 4% to 18%. The incidence of primary HL of marrow is 0.25%. To the best of our knowledge, the present study is the largest study on HL diagnosed initially on marrow biopsy. Objective To establish diagnostic criteria based on clinicopathological and histological features in HL diagnosed first on the marrow. Materials and Methods This was a retrospective study done from January 2012 to December 2020 that included 36 cases of HL diagnosed initially on BM. Based on the presence of large mononuclear or binucleate Reed–Sternberg (RS)-like cells in a polymorphous inflammatory background, HL was suspected and immunohistochemistry (IHC) with CD15 and CD30 was done. Correlation with subsequent lymph node biopsies was done, wherever possible. Results Fever (94.4%) was the most common symptom, followed by loss of weight (66.7%). Twenty-one cases (58.4%) had uni/bicytopenia and 15 cases (41.6%) had pancytopenia. Only one case showed suspicious mononuclear RS cells on aspirates and the rest of the cases were diagnosed on trephine biopsy alone. Trephine imprints showed variable cellularity in 13 (36%) cases. Diffuse involvement was seen in 24 cases (66.7%), and focal nodular aggregates were seen in 12 cases (33.3%). Out of 36 cases, 26 cases (19 cases on marrow and 7 cases on lymph node) were confirmed as HL with IHC. Immunophenotype of the RS cells on the marrow was CD30+/CD15+ in (6/29) (20.7%) cases, CD30+/CD15− in (7/29) (24.1%) cases and CD30−/CD15+ in (6/29) (20.7%) cases. Seven cases (26.9%) were diagnosed on subsequent lymph node biopsy as mixed cellularity HL with IHC confirmation. Marrow fibrosis was seen in 16 cases (44.4%), and granulomas were seen in 8 cases (22.2%). Conclusion In cases presenting with long-standing fever and cytopenias, HL must always be suspected, even if there are no palpable lymph nodes. Bone marrow biopsy is preferable over aspiration in such cases and IHC plays a major role in diagnosing the cases.

Retrospective Analysis of Intra-Departmental Requests for Consultation To Hematology Department

Aim: To investigate how much information a specialist hematologist receives at the time of initial assessment of referred patients through a referral letter. Study design: Retrospective study Place and duration of study: Haematology department BVH, October 2020 to February 2021 (5 months) Methods & Results: Among the 96 referral letters received, Majority 45 (47%) was referred from medicine department. Most common reason for referring the patient was evaluation of Pancytopenia n=19 (19.8%), Request for bone marrow biopsy n=14 (14.6%), being the second most common. The reason for referral was not properly stated in n=9 (9.4%) of patients in our study. Majority of referred patients were above 46 years of age n=22 (22.9%). CBC was mentioned only in n=35 (36.5%). Conclusion: Our study concludes that quality of referral letter was well below the acceptable standards. A well-documented protocol for referral letter is the need of hour to improve the quality of a referral process. Keywords: referral letter, pancytopenia, bone marrow, hematology clinics

Indolent T-Lymphoblastic Proliferation in Idiopathic Multicentric Castleman Disease

Benign and polyclonal proliferation of immature T cells in a lymph node with preserved morphological architecture is called indolent T-lymphoblastic proliferation (iT-LBP). Although overall rare, they have been described in association with both benign and malignant disorders including Castleman disease. We report the first case of idiopathic multicentric Castleman disease associated with iT-LBP, all previous reports of iT-LBP in Castleman disease were unicentric. A 37-year-old-male presented with 3 months of fevers and B-symptoms and was found to have enlargement of multiple bilateral lymph node sites on both sides of diaphragm along with splenomegaly. Anemia, elevated C-reactive protein, hypoalbuminemia, and elevated interleukin-6 levels were present. Biopsy of a lymph node showed features suggestive of idiopathic multicentric Castleman disease and iT-LBP. Bone marrow biopsy was unremarkable. Siltuximab and steroids were used to treat the condition.

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

Introduction Acquired amegakaryocytic thrombocytopenia (AAT) is an extremely rare disease characterized by acquired megakaryocytic aplasia or hypoplasia with no other lineage abnormalities. Given limited evidence, the first aim of this study was to describe the characteristics, management and outcome of patients with AAT, the second aim was to examine the therapeutic response through a systematic review of published case reports. Patients and Methods We carried out a retrospective multicenter study through the French Reference Network for Adult Autoimmune Cytopenias, including patients aged > 18 years with acquired thrombocytopenia with a platelet count < 50 x 10 9/L, associated with a megakaryocytes / granulocytes ratio < 50 % on bone marrow, diagnosed from July 2007 to February 2020. Exclusion criteria were: abnormal granular lineage, evidence of dysplasia, bone marrow infiltration by tumor cells or hematologic malignancy, significant karyotype abnormality, and significant paroxysmal nocturnal hemoglobinuria clone. Bone marrow biopsy were centrally reviewed. Patients' medical charts were collected using the standardized form of the referral center for adult immune thrombocytopenia (ITP). Response to treatment was defined according to standardized international criteria for ITP: response (R) and complete response (CR) were respectively defined as platelet count of > 30 × 10 9/L with at least a doubling of the baseline value, and platelet count of > 100 × 10 9/L ; overall response as either R or CR. We performed a systematic review conducted through Medline and Scopus databases from 1970 to April 2021. Cases were included in the analysis if initial platelet count was < 50 x 10 9/L and bone marrow examination was available, demonstrating a megakaryocyte hypoplasia or aplasia with no alternate diagnosis. Results We screened 23 patients reported as thrombocytopenia with absence or decreased megakaryocytes. Eleven patients were excluded because of: presence of megakaryocytes on bone marrow biopsy despite megakaryocytic aplasia on bone marrow aspirate (n=2), absence of bone marrow biopsy (n=4), aplastic or hypoplastic bone marrow (n=3), moderate thrombocytopenia > 50 x 10 9/L (n=1), lack of data (n=1). Twelve patients were included in the analysis. AAT patients had a median age of 52.5 years, 5/12 (41.7%) were female, 6/12 (50%) had a preexisting autoimmune disease (Table 1). All bone marrow biopsies reviewed to date contained CD8+ T-cell infiltrates. Eight patients received a first line treatment with corticosteroids and/or intravenous immunoglobulins (IVIg), a single response was observed. Ten patients received cyclosporine in monotherapy resulting in 4CR, and 1R or in combination with diverse agents with heterogenous responses. Six had received a single therapy with thrombopoietin receptor agonists (TPO-RAs) inducing 4 CR. Eventually, 9 patients (75%) achieved a CR under therapy, obtained with ciclosporin alone in 3 cases, ciclosporin in association with TPO-RA or ATG in 2 cases, cyclophosphamide followed-up by mycophenolate mofetil in 1 case, and TPO-RAs alone in 4 patients (of whom 3 had previously received at least on immunosuppressive therapy). After a median follow up time of 4.0 years (range 1.2 - 11.9), 2 (16%) patients eventually developed an aplastic anemia, 7 and 41.5 months respectively after initial AAT diagnosis. The literature search yielded 108 articles, of which 75 articles reporting 85 cases were included in the final analysis. The pooled analysis of newly reported and historic cases included 97 cases. Overall response rates to corticosteroids and IVIg were respectively 22.4 % and 5.3 % (Table 2). Ciclosporin was used as single agent in 37.1 % of patients, with an overall response rate of 66.7 %. TPO-RAs were used in 9 cases, with a CR in 7 patients (77.8%). Overall, 9/97 patients (9.3 %) experienced an aplastic anemia during the follow-up. The presence of a thymoma was associated with a higher risk of aplastic anemia (OR 6.83 (95%CI 1.22-34.00, p=0.020)). Conclusion Distinguishing AAT from ITP is of significance as the outcome and response to therapy strongly differ. Aplastic anemia may occur in the follow-up but remain rare. Corticosteroids and IVIg are inefficient in most cases, ciclosporin appear to be very effective, TPO-RA could also be an option, as single therapy or in associations. Further data will be needed to define the respective place of these treatments. Figure 1 Figure 1. Disclosures Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenix: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Amgen: Honoraria; Sobi: Other: Attendance Grant; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding. Michel: Amgen,Novartis,UCB,Argenx,Rigel: Honoraria. Godeau: Amgen: Consultancy; Novartis: Consultancy; Grifols: Consultancy; Sobi: Consultancy. Mahevas: GSK: Research Funding; Amgen: Honoraria.