Vijai Tilak

A study of clinico-haematological profiles of pancytopenia in children

We report on the clinico-haematological profile of pancytopenia in children from the Departments of Pediatrics and Pathology, Institute of Medical Sciences, Banaras Hindu University, India, over a period of 30 months. Pancytopenia was defined as: haemoglobin <10 g/dL, absolute neutrophil count 1.5 × 109/L and platelet count <100 × 109/L. A detailed history, clinical examination and haematological parameters were recorded. Bone marrow aspiration and trephine biopsy were carried out in all cases. One hundred and five cases aged 1.5–18 years, with a mean age of 8.6 years, were included in the study. Aplastic anaemia was the most common cause of pancytopenia (43%) followed by acute leukaemia (25%). Infections were the third most common cause of pancytopenia of which kala azar was the most common. Megaloblastic anaemia was seen in 6.7%.

A study of bone marrow failure syndrome in children.

BACKGROUND Bone marrow failure syndrome (BMFS), or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. AIM To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. SETTING AND DESIGN This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. MATERIALS AND METHODS Children with pancytopenia (Hb 9 /L, platelet count<100x10(9)/L) and bone marrow cellularity<25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. STATISTICAL ANALYSIS Relative risk was estimated by odds ratio (OR) with 95% confidence interval (CI) in matched cases and controls. RESULTS Of the 53 children studied, 6 (11.3%) were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8%) had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the fathers occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. CONCLUSION Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.

Cutaneous zygomycosis: a possible postoperative complication in immunocompetent individuals.

Fungi in the class of zygomycetes usually produce serious infections in diabetics and immunocompromised hosts. Cutaneous zygomycosis is a less common form, with an unpredictable extent of anatomical involvement and clinical course. Here, we report two cases of primary cutaneous zygomycosis as postoperative complications in otherwise healthy females. Zygomycosis was suspected and specimens from the surgical debridement were examined by microbiological and histopathological studies for confirming the clinical diagnosis. Rapid diagnosis, liposomal amphotericin B, and proper debridement of affected tissue are necessary to avoid a fatal outcome.

Paroxysmal nocturnal hemoglobinuria in childhood: An uncommon presentation

An eight year old boy presented with severe anemia and bleeding spots. Complete blood count showed pancytopenia. There was mild reticulocytosis. Bone marrow was hypocellular with normoblastic erythroid hyperplasia. Hams test (acidified serum test) was positive which confirmed the diagnosis of Paroxysmal nocturnal hemoglobinuria (PNH). Although PNH is rare in childhood, it should be considered as a diagnostic possibility in cases of aplastic anemia as the two conditions can coexist. The presence of PNH in association with aplastic anemia can influence the outcome of the latter.

Clinical, hematological, and cytogenetic profile of aplastic anemia

Background Aplastic anemia manifests as peripheral blood cytopenias due to inability of the hematopoietic bone marrow to produce blood cells. Aims and objective The aim of this study was to investigate the differences in the clinicohematological profile of pediatric and adult aplastic anemia patients, if any, to establish the necessity of bone marrow biopsy for its diagnosis and to detect any chromosomal abnormality in the patients. Setting and design This study was carried out in the Departments of Pathology, Paediatrics, and General Medicine, and Centre for Genetic Disorders, in a university teaching hospital over 24 months. Materials and methods A total of 42 patients were diagnosed combining the clinical features, peripheral blood counts, and bone marrow examination. Of them, 24 patients were evaluated for cytogenetic abnormality. Statistical analysis All the observations were evaluated using simple and basic statistical tools - for example, range, mean, and median. Results Occurrence of severe anemia and frequency of leukopenia and absolute neutropenia were more common in children. The degree of leukopenia and absolute neutropenia was more severe in children. Because of frequent occurrence of blood tap and dry tap, diagnosis in many cases depended solely on bone marrow biopsy findings. All the core biopsy specimens floated after proper decalcification. Lymphocyte culture failed in nine cases, and the remaining 15 cases showed no cytogenetic abnormality. Conclusion Bone marrow biopsy is mandatory for diagnosing aplastic anemia. The findings of core biopsy floatation and its correlation with marrow cellularity and absence of chromosomal abnormality in aplastic anemia need larger studies to give any statistically significant opinion.

Lymphoma without Lymphadenopathy

A seventy-five years old man was presented to our hospital with a complaint of gradually progressive heaviness in the left half of abdomen for past 10 months. History was negative for fever, weight loss, and night sweats. Physical examination was noteworthy for moderate pallor and massive splenomegaly [Figure 1a]. Figure 1 Splenic area marked (a); Peripheral blood film (b); Ultrasonography showing splenomegaly (c). There was no lymphadenopathy. Routine investigations showed: Hemoglobin 70 g/L, total leucocyte count: 98.4 × 109/L, neutrophils: 4%, lymphocytes: 93%, monocytes: 2%, and platelet count: 103 × 109/L. Peripheral blood smear showed markedly increased the number of leukocytes with a fair number of smudged cells. Red blood cells showed anisopoikilocytosis with the predominantly normocytic normochromic picture [Figure 1b]. Platelets were reduced in number to 103 × 109/L. Renal and liver function tests, serum lactate dehydrogenase (298 U/L), serum uric acid levels (6.5 mg/dl), chest X-ray, and electrocardiogram were within normal limits. Coombs test was negative, and stool analysis was negative for occult blood. The ultrasonography of abdomen showed gross splenomegaly [Figure 1c]. Contrast-enhanced computed tomography (CT) of chest and abdomen confirmed splenomegaly and did not reveal additional information. However, positron emission tomography-CT imaging was not performed. Conventional karyotyping was normal. The patient did not give consent for splenic aspiration. Bone marrow aspiration and biopsy revealed diffuse infiltrates of small lymphoid cells with nuclear round contour and scanty cytoplasm, suggestive of chronic lymphocytic leukemia (CLL) [Figure 2a]. Immunophenotyping by flow cytometry revealed: CD79b (77.1%) was strongly positive, CD5 (98.1% of gated lymphocytes), and CD23 (51.1%) were positive. FMC-7 was positive (51.1%), and surface immunoglobulin (1.7%) was negative. Immunophenotyping results were disfavoring CLL/small lymphocytic lymphoma (CLL/SLL) as according to the scoring system, a score of 4 or 5 is required for the diagnosis of CLL, whereas here the score was 3. Figure 2 Bone marrow trephine biopsy (a); Fluorescence in situ hybridization was done, and it was positive for IgH/CCND1 fusion signal (b) Typically, CLL cells express weak monotypic surface immunoglobulin, CD5, CD19, CD23 and weak or absent CD79B, CD22, and FMC7. Using a recommended panel of scoring system for the diagnosis of CLL.[1] Ninety-two percent of CLL cases score 4 or 5, 6% score 3, and 2% score 1 or 2. Most other chronic B-cell lymphomas and leukemias score 1 or 2, but a minority score 3. Scores in CLL are usually >3, in other B-cell malignancies the scores are usually <3. The scatter parameters and antigen expression profile as studied by flow cytometry of the sample were suggestive of atypical chronic lymphocytic leukemia, B-CLL. No single type of lymphoma/leukemia was matching with clinical and flow cytmetry parameters. In spite of the absence of lymphadenopathy, presence of massive splenomegaly and lack of “CD23 negativity” mantle cell lymphoma (MCL) was a possibility before labeling it as atypical B-cell CLL, as there are case reports of MCL without lymphadenopathy and with CD23 positivity, but the combination of all three parameters (absence of lymphadenopathy, presence of massive splenomegaly, and CD23 positivity) were making possibility of MCL dubious. But flow cytometry results prompted us to pursue the diagnosis of MCL as it was the only other plausibility apart from CLL, for which flow results were least unfavorable. Fluorescence in situ hybridization (FISH) was done, and it was positive for IgH/CCND1 fusion signal. IgH/CCND1 fusion signal was detected in 92% cells by FISH [Figure 2b]. MCL is one of the several subtypes of B-cell non-Hodgkin lymphoma. The distinction between SLL/CLL and MCL has important clinical implications. Typically, SLL/CLL is CD23+, whereas MCL is CD23−. The majority of MCL cases co-express CD20, CD5, BCL2, and cyclin D1. MCL is usually negative for CD10, BCL6 and CD23. Chromosomal translocation characteristic for MCL is t(11;14)(q13;q32), which results in overexpression of the cell cycle protein cyclin D1.[2] In reports that include CD23+ MCL cases, detected by flow cytometric or immunohistochemical analysis, the frequency of CD23 expression has ranged from 2% to 45%. MCL is an aggressive lymphoma with moderate chemosensitivity. Reliably curative treatments for MCL are lacking. An inexorable pattern of progression is characteristic, with a median time to treatment failure of <18 months.[3,4] The absence of lymphadenopathy and presence of CD23 positivity makes this case a rare one among all MCL cases. This patient was started on bendamustine rituximab chemoregimen for 6 cycles, and he showed partial remission after completion of the forth cycle. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.