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Chronic myeloid leukemia (CML) is characterized by increased and unregulated proliferation of granulocytic lineage in the bone marrow and presence of these immature myeloid cells in the peripheral blood with presence of Philadelphia (Ph) chromosome. Tyrosine kinase inhibitors are the most important drugs in the CML therapy and provide long disease-free survival. Due to the increased survival of CML patients with continual administration of these drugs, the chance of development of secondary malignancies may increase. The most common secondary malignancies are prostate, colorectal and lung cancer, non-Hodgkin lymphoma, malignant melanoma, non-melanoma skin tumors and breast cancer. Herein, we are describing a rare case of Hodgkin lymphoma in a patient of CML after ten year of primary disease presentation. Hodgkin lymphoma in a known case of CML is very rare and further studies are also needed to know the pathogenic relationship between the two entities and to assess the risk of secondary Hodgkin lymphoma in CML patients treated with tyrosine kinase inhibitors. CML itself is a risk factor for development of solid cancers and hematologic malignancies. In addition, patients on chemotherapy are immune-compromised and may be at greater risk of neoplasm driven by infectious agents such as Epstein-Barr virus.

The requirement for the mutation analysis for Kirsten rat sarcoma viral oncogene (KRAS) in colorectal cancer (CRC) is rapidly increasing as it is a predictive biomarker and also, its absence signifies response to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. The aim of our study was to investigate the pathological diagnosis and distribution of KRAS mutations in colorectal cancer with the use of next generation sequencing platform (Ion Torrent).A total of 56 CRC samples were tested to identify the genetic mutations, especially KRAS using the primers which included ~2800 COSMIC mutations of 50 oncogenes. Ion Torrent personal genome machine (semiconductor-based sequencing) was used for the sequencing and analysis. Along with KRAS, other 49 genes were also studied for COSMIC mutations.KRAS mutation 25 (44.6%) had the highest frequency, followed by TP53 10 (17.9%) and PIK3CA mutation 4 (7.1%). Of all the KRAS mutations identified, mutations in codon 12 were most frequent followed by mutations in codon 13 and 61. The most frequent substitution was glycine to aspartate mutation in codon 12 (p.Gly12Asp) followed by glycine to valine (p.Gly12Val). Combinations of mutations were also studied. Our study revealed that seven cases (12.5%) had both KRAS and TP53 mutations (highest of all the combinations).The analysis of KRAS mutation frequency and its mutational subtype analysis in human CRCs by using semiconductor-based platform in routine clinical practices have been performed in Indian population. The findings were similar to earlier published reports from the Western literature.

Erdheim–Chester disease (ECD) is a rare multi-system, non-Langerhans cell histiocytic disorder (NLCHD) with only a few hundred cases reported in the literature. Its diverse clinical manifestations require a high level of diagnostic suspicion. BRAFV600E mutation analysis is of critical significance, as it has implications for targeted therapy with BRAF inhibitors such as vemurafenib and dabrafenib. We report a case of symptomatic, central nervous system (CNS)-predominant ECD initially presenting with CNS mass lesions mimicking meningiomas on imaging and prominent periorbital xanthogranulomas. CNS presentation of ECD, although not infrequent, bears particular significance here from a therapeutic point of view, since only partial debulking was possible owing to anatomical complexities. Radiological evaluation following surgery showed no significant change in the size of the lesions. Targeted therapy was commenced following histopathology, immunohistochemistry (IHC), and molecular testing, resulting in marked improvement of clinical symptoms and tumor regression. Thus, diagnostic accuracy was imperative for symptomatic relief in this rare but aggressive neoplasm with a complex clinical presentation and misleading initial radiological impressions, bearing an otherwise grim prognosis.

A 15-year-old girl presented with complaints of low-grade fever associated with cough and weakness. This was associated with loss of weight and decreased appetite along with menstrual irregularitie...

Context: Secondary acute myeloid leukemia (sAML) may arise from a previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome, chronic myeloproliferative neoplasm, or as a complication in patients receiving chemotherapy or radiotherapy for a primary malignancy, including hematological and non-hematological/solid malignancies (therapy-related AML [t-AML]). Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. It is associated with specific clinical features with a uniformly poor prognosis. Objective: To study patients of t-AML with respect to clinical presentation, laboratory parameters (including flow cytometry immunophenotyping), cytogenetic and molecular studies, and clinical outcome. Design: This study was a retrospective analysis of patients of t-AML from January 2011 to December 2019. Patients: The patients underwent a detailed hematological work up: peripheral blood smear, bone marrow examination along with flow cytometric immunophenotyping, and karyotyping and molecular studies (NPM1, FLT3ITD/TKD, BCR/ABL, PML/RARA, INV16, AML-ETO). Outcomes of the patients were also reviewed. Results: A total of 20 cases of therapy-related AML were diagnosed in patients treated for various malignancies of the breast (9 cases), prostate (3 cases), and pancreas (2 cases), as well as lymphomas (NHL: 4 cases and HL: 2 cases). There were 7 males and 13 females (M:F: 1:1.85) with a median age of 63 years (range 35–82 years). Median latency period to t-AML was 3.5 years (range 0.5–11.0 years). Median haemoglobin was 72.5 g/L (61–151 g/L), WBC count 3.7× 109/L (1.02–169.1×109/L), platelet count 40 × 109/L (12–257 ×109/L, peripheral blood and bone marrow blast percentage 48% (5-98%) and 76% (20–98%), respectively. AML with monocytic differentiation was the most common morphological and flow cytometric subtype (50% cases). Complex karyotype was seen in 50% cases. Molecular studies for NPM, FLT3ITD/TKD, PML/RARA, AML-ETO, and INV16 showed 8 cases with NPM1 positivity and 4 case with FLT3ITD positivity. Only 4 patients (20%) achieved complete remission but relapsed within 1 year of duration. Ten patients succumbed to their disease, the majority within 1 year of t-AML diagnosis. Conclusion: The study highlights the development of therapy-related AML following chemotherapy and/or radiotherapy as an important therapy-related complication. The latency period and clinical manifestations may differ depending on the type of cytotoxic drug, cumulative dose, and dose intensity. A close hematological follow-up should always be done for an accurate and timely diagnosis.

Objective The aberrant expression of CD5 in both HCL and HCL-v is a very rare event. Although a number of CD5 positive HCL and HCL-v cases have been reported, but these are far and few in between. We aimed to review the reported cases of CD5 positive HCL and its variant. Method We hereby report a case of CD5 positive HCL, with variations in PIK3CA and PDGFRA gene, along with a brief review of literature of the cases of CD5 positive HCL and its variant. Results and Conclusion The current case was positive for CD103, CD11c, CD25, and CD123 which has led the diagnosis to be of typical HCL. With the extensive literature review we found that only 26 cases of hairy cell leukemia [HCL and HCL-v] bearing CD5 expression have been reported so far. The positivity of CD5 is more common in HCL-v as compared to HCL. Additional prospective studies of CD5+ HCL and its variants are required to show whether they are a clinically significant subgroup of lymphoid malignancies. © 2016 International Clinical Cytometry Society

Myelodysplastic syndromes (MDS) are fairly common hematological disorder of elderly. They are a group of clonal malignant hematopoietic stem cell disorders characterized by dysplastic morphology, variable cytopenia and a variable threat of transformation to AML. These dysplastic changes are a result of chromosomal abnormalities and somatic mutations. MDS is the most common myeloid neoplasm of the older adults with median age at diagnosis being 72 years and an average incidence rate of 0.2 per 100,000 people per year. MDS is diagnosed and classified according to the WHO 2008 classification system, which utilizes peripheral blood and bone marrow findings. Other essential investigations include flow cytometry, genetic profile and chromosomal analysis. Various prognostic scoring system have been developed which help guide the treatment. Treatment of complications associated with MDS also forms an essential component of the management of this disease.

BACKGROUND It is important to detect Latent Iron Deficiency (LID) to prevent development of an overt iron deficiency anemia. Early detection is difficult by using conventional hematological and biochemical parameters. Soluble transferrin receptor (sTfR) is presently the gold standard for diagnosing LID. We evaluated the utility of Reticulocyte Hemoglobin Equivalent (Ret-He), a newer hematological parameter, to predict LID in blood donors as compared to sTfR. METHODS This was a randomized prospective study performed on 501 donor samples over a period of three-months. All donors were included after administering medical history questionnaire and a brief physical examination in accordance with national guidelines (Hb ≥12.5). Additional samples were collected during donation according to the institutional standard operating procedure (SOP). All hemograms were performed on the Sysmex XE-2100 analyzer which included Ret-He. sTfR was measured in batch assays by ELISA (Biovendor, Czech Republic). Ret He

Inflammatory myofibroblastic tumor (IMT) of lung is a rare tumor, accounting for ~0.7% of all lung tumors with varied clinical and radiological presentations. The origin of this tumor is unknown but some studies suggest that it might be a true neoplasm as some mutations on chromosome 2p23 of anaplastic lymphoma kinase (ALK) have been found to be related to this tumor. The morphology of IMT is quite vague and the histopathological diagnosis is predominantly given on excision specimens; in fact, only 6.3% of cases are diagnosed based on analysis of biopsy specimens alone. We illustrate a case of IMT diagnosed in a young male on core biopsy, where the case presented with a large tumor in the lung with metastases to multiple sites that was hence unresectable. Post 3 months of treatment with Crizotinib, there was significant reduction in the tumor size. Another interesting finding was that the ALK immunostain, which helped immensely in the diagnosis, was appreciated better on the Ventana platform rather than on the Dako platform.

EBV-associated PTLD is increasingly recognized as an important cause of morbidity and mortality in both solid organ and hematopoietic stem cell transplant recipients. Mortality rates due to PTLD and virus-induced HLH are reported to be quite high. We report a case of EBV-associated PTLD and HLH in a child after liver transplantation who was successfully managed due to timely intervention. This case highlights that measurement of EBV load by quantitative polymerase chain reaction assays is an important aid in the surveillance and diagnosis of PTLD and early detection of EBV-induced PTLD, and aggressive treatment with rituximab is a key to survival in patients who have undergone liver transplantation.

Background Chronic lymphocytic leukemia (CLL) is one of the commonest leukemias that has been reported extensively throughout the literature. The characteristic phenotype includes co-expression of CD5 and CD23, along with dim expression of light chain and CD22/CD79b, with lack of FMC7. The immunophenotypic scoring system given by Matutes has been used to differentiate CLL from non-CLL chronic lymphoproliferative disorders. Various aberrancies have been described in CLL cases, including abnormal (dim or bright) expression of B cell markers and lineage infidel T cell, myelomonocytic, or rarely Natural killer (NK) cells markers. However, the aberrant co-expression of CD56 and CD57 has not yet been reported. Method and Results We hereby report a case of 62-year female with a typical CLL phenotype and Matutes score of 5, showing the expression of CD56 and CD57. Conclusion This entity may represent a rare subtype of CLL which needs to be studied more extensively for its prognostic implications. This is the first report of CLL with aberrant CD56 and CD57 expression. © 2015 International Clinical Cytometry Society

Haematogones are benign B lymphoid precursors which may mimic neoplastic lymphoblasts and pose diagnostic difficulty especially when the percentage of haematogones exceeds 10% in the bone marrow. Flow cytometric analysis with combination of CD19/CD10/ CD20/CD34/CD38/CD58 can be used to differentiate the two depending upon the difference in the fluorescence intensity between blasts and haematogones. We hereby present a case of Common Acute Lymphoblastic Leukaemia Associated Antigen (CALLA) positive Acute Lymphoblastic Leukaemia (ALL), in which patient presented with haematogone proliferation in bone marrow after 6 months of chemotherapy mimicking relapse. The distinction was made on flow cytometric immunophenotyping by using optimal antibody combination. Distinction of benign haematogones from neoplastic lymphoblasts is essential for disease management in cases of post chemotherapy or post marrow transplant, especially in patients of ALL. Flow cytometric immunophenotyping is reliable to distinguish haematogones from residual lymphoblasts in almost all cases when optimal antibody combinations are used.

Aims: This study aims to establish biological reference interval for novel platelet parameters. Settings and Design: A total of 945 healthy individuals, age ranges from 18 to 64 years (881 males and 64 females) coming for voluntary blood donation from June to August 2012 (3 months) were enrolled after exclusion of rejection criteria. Materials and Methods: The samples were assayed by running in complete blood count + reticulocyte mode on the Sysmex XE-2100 hematology analyzer and the reference interval for the population was calculated using Clinical and Laboratory Standards Institute guidelines. Statistical analysis used: Tests were performed using SPSS (Statistical Product and Service Solutions , developed by IBM corporation), version 13. Student t test and pearsons correlation analysis were also used. Results: The normal range for various parameters was platelet count: 150-520 × 10 3 /cu mm, immature platelet fraction (IPF): 0.3-8.7%, platelet distribution width (PDW): 8.3-25.0 fL, mean platelet volume (MPV): 8.6-15.5 fL, plateletcrit (PCT): 0.15-0.62%, high immature platelet fraction (H-IPF): 0.1-2.7%, platelet large cell ratio (P-LCR): 11.9-66.9% and platelet-X (PLT-X) (ch): 11.0-22.0. Negative correlation was observed between platelet count (r = −0.468 to r = −0.531; P < 0.001) and PCT (r = −0.080 to r = −0.235; P < 0.05 to P < 0.001) with IPF, PDW, MPV, H-IPF, P-LCR, and platelet-X. IPF/H-IPF showed a positive correlation among them and also with PDW, MPV, P-LCR, platelet-X (r = +0.662 to r = +0.925; P < 0.001). Conclusions: These novel platelet parameters offer newer avenues in research and clinical use. Establishing biological reference interval for different platelet parameters would help determine true high and low values and help guide treatment decisions.

Extrapulmonary tuberculosis coexistent with lymphomas in the same organ are rare and have been reported in the literature. The most common organs that are involved are small bowel, bronchus, kidney, and lymph nodes. Interestingly, the lymphoma that is commonly present with extrapulmonary tuberculosis is Hodgkin’s lymphoma followed by low-grade non-Hodgkin’s lymphoma. In the present study, we report a 60-year-old man with complaints of fever, loss of appetite, and generalized weakness. On investigation, generalized lymphadenopathy was noted, and the biopsy of cervical lymph node revealed coexistence of diffuse large B-cell lymphoma with extrapulmonary tuberculosis. This case is the second reported case of diffuse large B-cell lymphoma with extrapulmonary tuberculosis in the world and the first in India.