Rare but Potentially Fatal Presentations of Diffuse Large B-cell Lymphoma: Leukemic Phase or Hemophagocytic Syndrome in Bone Marrow

Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin Lymphoma commonly presenting as a solid tumor either by nodal or extra-nodal manifestations. Here we describe two atypical presentations of lymphoma, finally resulting in the diagnosis of DLBCL. Case 1: A 53-year-old man with a previous history of nasopharyngeal carcinoma presented with a two-week history of B-symptoms and hyperleukocytosis. Peripheral blood film showed 78% abnormal mononuclear cells. Immunohistochemical stain showing Ki-67 of 90%, negative c-myc, BCL2 and BCL6, and negative c-MYC with fluorescence in-situ hybridization studies on the trephine biopsy, concluded the diagnosis of CD5+ DLBCL of ABC subtype. He received intravenous cyclophosphamide and oral prednisolone for cytoreduction, followed by 6 cycles of chemo-immunotherapy. However, he succumbed due to severe sepsis after the completion of therapy. Case 2: A 56-year-old lady who was initially investigated for pyrexia of unknown origin was noted to have hemophagocytosis upon bone marrow aspirate examination. The bone marrow trephine biopsy revealed some atypical clusters of B-cells positive for CD20 which was inconclusive. PET-CT scan noted an enlarged hypermetabolic spleen without lymphadenopathy. Splenic biopsy with immunohistochemical studies revealed DLBCL of ABC subtype. The diagnosis was consistent with primary splenic DLBCL. She became unwell post splenic biopsy and was admitted to the intensive care unit where she passed away 2 weeks later from Candida and Sternotrophomonas septicemia. These cases highlight the atypical presentations of a common subtype of NHL in our center. Arriving at the definitive diagnosis can be difficult especially when patients are acutely ill, hampering the necessary invasive procedures for diagnosis. The outcomes of both cases are briefly discussed hoping to spread awareness among clinicians on the rare and acutely critical presentations of DLBCL.

A case of spontaneous hypoglycemia

We describe a case of systemic lupus erythematosus with POEMS syndrome presenting as spontaneous hypoglycemia. A 58-year-old female suffered repeated episodes of hypoglycemia. During thesehypoglycemic episodes, her postprandial insulin level was inappropriately high. Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies,low C4level.Altered albumin-globulin ratio,monoclonal gammopathy (IgG LAMBDA), polyneuropathy and organomegaly lead to suspicion of concurrent presence of POEMS syndrome.Bone marrow examination revealed plasma cell dyscrasia and plasmacytoma in trephine biopsy confirmed the diagnosis.Here, we emphasize on autoimmune cause of hypoglycemia. BIRDEM Med J 2022; 12(1): 70-73

Bone marrow aspiration versus trephine biopsy: diagnostic value of both modalities when done simultaneously.

Objective: To compare diagnostic value of bone marrow aspiration and bone marrow trephine in reaching to final diagnosis. Study Design: Cross Sectional Descriptive study. Setting: Pathology Department of Khyber Teaching Hospital, Peshawar. Period: December 2015 to September 2016. Material & Methods: About 199 bone marrow procedure were done during study period. Nine cases were excluded because their trephine biopsy specimen was not available. So, the remaining 190 cases, of both the sexes and age above 2 years were included. Bone marrow aspiration and trephine biopsy were obtained from all the patients, and examined. Qualitative data was determined by frequency and percentages. Quantitative data was shown by mean and standard deviation. Results: 190 cases were included in the study. The mean age of the sample was 40 ±11.5 SD years (range: 2 to 81 years). Bone marrow aspirate alone could diagnose 139 (72.8%) cases while trephine biopsy alone was sufficient to diagnose 12 (6.3%) cases. Both the modalities showed similar diagnosis in 39 (20.9%) cases. Conclusion: Leukemias, anemias, and idiopathic thrombocytopenic purpura can be diagnosed by marrow aspiration alone. Aplastic anemia and myelofibrosis need marrow trephine for diagnosis. Both these modalities are important lest any diagnoses should be missed.

A comparative study of bone marrow aspirate with trephine biopsy in pancytopenia disorders

Pancytopenia is commonly reported in clinical hematology practice. Due to its varied marrow pathology and underlying ailments, diagnosis is often misleading and delayed. Bone marrow examination would provide a comprehensive diagnosis of both blood and bone marrow, since aspirate investigates the cytological morphology and biopsy evaluates the cellularity, architecture, and compact marrows.To compare bone marrow aspiration and trephine biopsy results in the diagnosis of pancytopenia, and to determine the sensitivity and specificity of aspirate examination in pancytopenia diagnosis.This prospective study was conducted at a tertiary care hospital from July 2014 to June 2016. A total of 320 samples were received at the department of pathology for bone marrow examination (aspirate and biopsy). Romanowsky (Leishman) stain was used to investigate aspirate samples. All biopsy samples were processed into 3-5 μ blocks and stained using hematoxylin and eosin after decalcification with 5.5% EDTA. Data analysis was performed using SPSS19.Pancytopenia constituted 56 (18.7%) cases with the mean age of 41.79 years. Of the total pancytopenia cases, hematological disorders constituted 50 (89.3%) cases and 6 (10.7%) were non-hematological cases. Aspirate and biopsy diagnosis positively correlated in 76.79% of cases. A 100% sensitivity and specificity of aspirate diagnosis was observed in, acute myeloid leukemia, hypersplenism, myelodysplastic syndrome, megaloblastic anemia, hematological malignancy in remission and negative for lymphoma infiltrate. Aspirate had no role in diagnosis of uremic osteodystrophy and myelofibrosis, whereas leishmaniasis was diagnosed on aspirate alone.Pancytopenia includes multiple underlying ailments which requires a differential diagnosis approach. Combining both aspirate and biopsy for diagnosis would benefit the patient in prognosis as they are complementary to each other.

Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics

The diagnosis of a myeloid neoplasm relies on a combination of clinical, morphological, immunophenotypic and genetic features, and an integrated, multimodality approach is needed for precise classification. The basic diagnostics of myeloid neoplasms still rely on cell counts and morphology of peripheral blood and bone marrow aspirate, flow cytometry, cytogenetics and bone marrow trephine biopsy, but particularly in the setting of Ph− myeloproliferative neoplasms (MPN), the trephine biopsy has a crucial role. Nowadays, molecular studies are of great importance in confirming or refining a diagnosis and providing prognostic information. All myeloid neoplasms of chronic evolution included in this review, nowadays feature the presence or absence of specific genetic markers in their diagnostic criteria according to the current WHO classification, underlining the importance of molecular studies. Crucial differential diagnoses of Ph− MPN are the category of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This review focuses on morphological, immunophenotypical and molecular features of BCR-ABL1-negative MPN and their differential diagnoses. Furthermore, areas of difficulties and open questions in their classification are addressed, and the persistent role of morphology in the area of molecular medicine is discussed.

Comparative characteristics of bone marrow cell composition, stroma, and trabecular bone in allogenic hematopoietic stem cell transplantation in patients with primary myelofibrosis

Introduction. Primary myelofibrosis (PMF) is a clonal disease violating the cell composition, histological topography and stroma in bone marrow (BM). Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy in PMF.Aim — description of change in the haematopoietic tissue cell composition and stroma, as well as in trabecular bone in allo-HSCT patients with fibrotic PMF.Materials and methods. We studies 24 trephine biopsy samples from nine PMF patients with allo-HSCT at the intervals: I — 1 month prior to, II — past 1–3 months and III — past 4–6 months from allo-HSCT. BM trephine biopsy slides were prepared in a standard histological assay with haematoxylin—eosin and additional staining with Gomori’s silver and Masson’s trichrome. Morphological change was evaluated in reticulin and collagen stroma, bone trabeculae, cellularity and topography of haematopoietic tissue.Results. The BM trephine biopsies of interval I were morphologically distinguished in three types by haematopoietic cellularity, stromal and trabecular sclerotic change. Post-transplant intervals II and III (3–6 months after allo-HSCT) did not reveal these types but showed an evident myelofibrosis and osteosclerosis reduction and signs of a restoring bone remodelling cycle. Myelopoietic lineages recovered in stages: the erythroid germ restored in three, granulocytic — in six months, and megakaryocytic cellularity did not fully recover in six months. Myelopoietic cellularity recovery outpaced blood recovery, which may be due to induced myelodysplasia or disruption of stromal niches.Conclusion. Allo-HSCT leads to the disappearance of PMF-pathognomonic BM morphology reflecting a histological remission. The reduction of myelofibrosis and osteosclerosis and normalisation of the trabecular bone remodelling cycle in post-transplant periods indicates an impact of cell microenvironment on PMF pathogenesis and warrants research into the composition and histological topography of cell microenvironment in PMF.

Clinicohaematological & Aetiological Profile of Bicytopenic / Pancytopenic Children in Dehradun, India - A 5-Year Study

BACKGROUND Cytopenia (bicytopenia / pancytopenia) in paediatric age group patients presents with variable clinical features from pallor, fever to organomegaly. Causes vary from megaloblastic anaemia to fatal leukaemias. The purpose of the study was to evaluate the etiological and clinico-haematological profile in children with bicytopenia and pancytopenia. METHODS The present retrospective study was carried out in the section of haematology, Department of Pathology of Shri Guru Ram Rai Institute of Health and Medical Sciences, Dehradun. All paediatric cases (up to 18 yrs.) with bone marrow examination, that were presented as bicytopenia or pancytopenia by routine haematological investigations were included in the study. RESULTS A total of 126 cases were included in the study, out of which, bone marrow aspiration was done in all 126 cases and trephine biopsy was done in only 78 cases. In our study, bicytopenia and pancytopenia was seen in 57.9 % and 42.1 % cases respectively. Most cases were recorded in 2nd decade. Pallor and fever were frequently observed clinical features in both cytopenias. Splenomegaly, lymphadenopathy and hepatomegaly were observed more in bicytopenia (34.2 %, 28.8 % and 27.4 % respectively). Bleeding and petechial rash were more common in pancytopenia (30.2 % and 20.8 % respectively). Anaemia and thrombocytopenia (67.1 %) were commonest combinations of bicytopenia followed by anaemia and leucopenia (26.0 %) and thrombocytopenia and leucopenia (6.8 %). CONCLUSIONS Bone marrow aspiration and trephine biopsy are important diagnostic tools in evaluating the cases of cytopenia. Both procedures are complementary to each other. KEY WORDS Bicytopenia, Pancytopenia, Megaloblastic Anaemia, Leukemia, Children