Anaemia of chronic disease among pulmonary tuberculosis patients is associated with inflammatory marker at the start of intensive phase.

Background: Tuberculosis (TB) disrupts iron balance through systemic inflammation. Pulmonary tuberculosis (PTB) is linked to diverse anaemia types, necessitating intricate haematological and biochemical assessments for diagnosis. This study aims to describe the prevalence of anaemia of chronic disease (ACD), iron deficiency anaemia (IDA) among PTB patients and factors associated with these types of anaemia. Methods: A cross-sectional analysis was conducted from community-based cohort study involving sputum-positive PTB patients from 2018 to 2020 in urban Puducherry. Participants were enrolled from 10 primary health centres within 2 weeks of initiating anti-tubercular treatment (ATT). Blood samples were collected for assessing haematological and biochemical parameters. The sTfR/log ferritin ratio was used to distinguish between ACD and IDA. Data were captured using Epicollect5 and analysed using STATA V14. Result: Of the 176 PTB patients included, 63.07% (111/176) had anaemia, with ACD being the predominant type (84.6%, 94/111). The C-reactive protein (CRP) levels were higher among the anaemic group [40.77 (16.66-58.51) mg/dl vs 24.65 (14.23-47.26) mg/dl] and higher among the ACD as compared to IDA [46.9 (22.3-61.2) vs 20.8 (13.0-39.1) mg/dl]. Undernourished [adjusted prevalence ratio (APR) =3.43; confidence interval (CI): 1.21-9.69] and patients having low risk of dependence on tobacco [APR = 1.52; CI: 1.10-2.11] had higher risk of ACD. Female patients had higher risk of IDA [APR = 4.95, P < 0.01]. Conclusion: The largest proportion of the PTB participants with anaemia had ACD. Acute-phase reactant and inflammatory marker are increased among newly diagnosed new sputum smear-positive (NSP) PTB participants at the start of ATT. Addressing inflammation is needed for combating anaemia in PTB patients.

Myeloid sarcoma: Experience from a tertiary care center in southern India - A series of eight unusual cases.

BACKGROUND: Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm. MATERIALS AND METHODS: This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details. RESULTS: These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate. CONCLUSION: Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.

Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia.

Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.

A case series of therapy-related leukemias: A deadly ricochet.

Therapy-related leukemias(t-leukemia) are late complications arising from chemotherapy and radiotherapy. t-leukemia have a poor prognosis and are more difficult to treat compared to de novo leukemias. The authors present three cases of t-leukemia seen in our hospital in a three year period and discuss new updates concerning the treatment of t-leukemia.

Extramedullary early T-cell lymphoblastic crisis in a young pregnant chronic myeloid leukemia patient: Diagnosis with fine-needle aspiration cytology and flow cytometry.

Chronic myeloid leukemia (CML) most commonly presents in chronic phase. Blast crisis in CML is usually of myeloid phenotype, whereas among lymphoid lineage, B-cell lymphoblastic crisis is common. T lymphoblastic crisis is rare with near early T-cell precursor (ETP) immunophenotype being exceedingly rare and very little is known about its characteristics, treatment, and prognosis. Blast crisis can occur in extramedullary sites with lymph node being the most common site. CML is also less investigated and studied in pregnancy as it is considered a disease of older adults. We report a rare case of CML presenting in extramedullary site (lymph node) as extramedullary T-cell lymphoblastic crisis of near ETP immunophenotype in a young pregnant female, which was diagnosed on fine-needle aspiration cytology in combination with flow cytometry.

Clinicopathological Profile of Paraprotein-Associated Kidney Disease in Monoclonal Gammopathies: An Observational Study.

Background Renal involvement in monoclonal gammopathies presents with different clinico-morphological patterns and can manifest at the onset or the late phase of hematological disease, or after chemotherapy. The spectrum is ever-expanding with advancements in diagnostic methods. Renal biopsy is needed for accurate diagnosis, as each of these patterns carries therapeutic and prognostic implications. Methods A total of 41 cases of monoclonal gammopathies were included in the study. Clinical, biochemical, and hematological details were obtained, and pathological variables were observed. Patients were followed till the maximum possible period, and treatment history and follow-up creatinine details were collected. Results The spectrum of renal biopsy lesions observed included light chain cast nephropathy (LCCN) n=19, amyloidosis n=11, monoclonal immunoglobulin deposition disease (MIDD) n=6, and proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) n=5; 10 of these cases can be categorized as monoclonal gammopathy of renal significance (MGRS). Acute kidney injury (AKI) (41%) is the predominant clinical presentation in general whereas the majority of amyloidosis cases presented with nephrotic and sub-nephrotic proteinuria. LCCN cases had high serum creatinine and calcium, positivity for M-spike, as well as a high FLC ratio, compared to the other types. Around 100% of LCCN and MIDD patients had myeloma and 100% of PGNMID cases had normal marrow. Conclusion More than three-fourths of patients were diagnosed with monoclonal gammopathies with biochemical and hematological workups after an initial kidney biopsy. The clinicopathological profile of these patients had a broad spectrum but there were still some consistent findings within the different types. A subgroup of patients (MGRS) had undetectable serum paraproteins but had monoclonal immunoglobulin deposition in the kidney.

Myeloma Cast Nephropathy an Unusual Association with HIV Infection Presenting with Renal Dysfunction.

Human immunodeficiency virus (HIV)-associated renal disease is a pan-nephropathy, causing glomerular, tubular, and interstitial changes. The common lesion is the collapsing variant of focal segmental glomerulosclerosis. Multiple myeloma presenting as light chain cast nephropathy in an HIV-positive patient is very rare. A 45-year-old female retropositive patient presented with one episode of hematuria. Kidney biopsy was performed with a clinical diagnosis of acute interstitial nephritis (AIN). Biopsy showed unremarkable glomeruli. Tubules were dilated and showed a few periodic acid-Schiff (PAS) positive and many PAS-negative fractured casts surrounded by histiocytic reaction. Immunofluorescence and immunohistochemistry (IHC) showed lambda restriction by the casts. Bone marrow aspirate showed an increase in plasma cells, and the biopsy showed nodular aggregates of atypical plasma cells, which showed lambda restriction by IHC. PAS-negative fractured tubular casts are known to be associated with HIV-related nephropathy and need detailed hematological workup to rule out an associated plasma cell dyscrasia.

Clinico-Pathologic Profile and Treatment Outcomes of Patients with Diffuse Large B Cell Lymphoma Based on Cell of Origin Classification.

Diffuse large B cell lymphoma (DLBCLs) constitute 40% of all non-Hodgkin lymphoma and it represent a heterogeneous group of neoplasms rather than a single clinicopathological entity. We analysed the outcomes and clinical features based on the cell of origin in a series of patients with DLBCL from our institute. Medical case records of all newly diagnosed DLBCL treated in our institute from January 2015 to July 2017 were analysed for this study. Cell of origin classification was based on immunohistochemistry using Hans algorithm. Kaplan-Meier curves were used to determine survival. Ninety-five patients were diagnosed to have DLBCL subtype. Immunophenotypic subtyping was available for 71 patients. The median age at diagnosis was 56 years with no difference between Germinal centre B cell (GCB) and non-Germinal centre B cell (non-GCB) subtypes. Approximately 44% of patients had extra-nodal disease, stomach being the commonest site. Forty percent of patients had stage III/IV disease. Bulky disease and extra-nodal presentation was predominantly seen with non-GCB subtype (46% vs 20% and 36% vs 29% respectively). Rituximab was used in 75% of the patients with DLBCL. The 2-year disease-free survival was 70% versus 53% (p = 0.38) in GCB versus non-GCB subtype. This is one of the few data on DLBCL patients reported from India which has described outcomes based on the cell of origin. The disease-free survival in our country appears to be superior in GCB subtype which needs to be confirmed in a larger subset of patients.

Does negative pressure wound therapy with saline instillation improve wound healing compared to conventional negative pressure wound therapy? - A randomized controlled trial in patients with extremity ulcers.

BACKGROUND: Wounds are important health problems that cause significant financial burden and loss of time to work, more so in low and lower middle income countries. Negative pressure wound therapy (NPWT) is widely established in managing acute and chronic extremity wounds. We studied the effects of addition of normal saline instillation to NPWT in terms of changes in granulation tissue, bacterial-burden and overall wound healing using readily available means and materials including wall suction for negative pressure, sponge and adhesive transparent sheet for dressing and normal saline for irrigation. METHODS: All patients with extremity ulcers initially underwent surgical debridement. They were then allotted into two groups, group 1 (NPWT with normal saline instillation- NPWTi) including 25 patients and group 2 (NPWT) including 23 patients. Tissue-bit samples taken on day1 and day 10 were used for bacteriology and for assessing histology. The wound surface-area was measured using the software ImageJ on day 1 and day 10. RESULTS: Median log difference in colony-count between day1 and day10 was 0.6 (0.2-1.4) in group1 and 0.13 (0.04-0.6) in group 2 (p < 0.05). Mean percentage reduction in wound size was 28.82 and 19.80 in group 1 and group 2 respectively (p < 0.05). Histological parameters of wound healing assessed as surface epithelium, granulation, inflammatory cells, proliferative blood-vessels and fibroblasts were significantly better in group1. A drawback observed with NPWTi was skin maceration around the ulcer which was successfully managed. CONCLUSION: Our findings suggest that wound healing is significantly better when saline instillation is combined with NPWT. It can aid in complex extremity ulcers management by reducing the size of the wound with healthier looking granulation tissue.

Post-chemotherapy Changes in Bone Marrow in Acute Leukemia With Emphasis on Detection of Residual Disease by Immunohistochemistry.

Introduction In acute leukemia, the leading cause of treatment failure is disease relapse leading to a low level of complete remission and short overall survival. Post-chemotherapy marrow examination gives vital clues regarding treatment response and marrow regeneration. Aim We aimed to study the histomorphological changes in post-chemotherapy bone marrow in acute leukemias, monitor residual disease by immunohistochemistry (IHC) on trephine biopsy, and correlate survival status. Method This study was a prospective clinical study. A total of 155 post-induction cases (acute myeloid leukemia [AML] - 68 and acute lymphoblastic leukemia [ALL] - 87), from January 2014 to December 2015, were included with a follow-up of 4-28 months. A detailed histomorphology was studied in all cases. IHC was applied in 88 cases of post-induction marrow, which showed morphologic suspicion of an increase in blasts. Observations Post-induction marrow was hypercellular in 55.9% of AML and normocellular in 56.3% of ALL. Regenerative hematopoiesis was noted in 37.4% of AML and 88.5% of cases of ALL. Marrow serous atrophy and stromal edema were associated with delayed recovery of counts and their recovery duration ranged from one to five months. Twenty-seven bone marrow aspirates were unsatisfactory, and their trephine biopsies were showed remission in 20 cases and stromal changes in nine cases. In addition, trephine biopsy picked up residual leukemic blasts in four cases in which aspirate showed remission status. Post-induction marrow IHC with scattered positivity for blasts showed sustained remission in 96% cases, and in those with clustered positivity, 28.6% showed residual disease, and 7.2% showed relapse at the end of the study period. The median survival duration was 13, 3, and 12 months for cases with sustained remission, residual disease, and relapse, respectively. There was a statistically significant difference in median survival of patients in the three groups (sustained remission, residual disease, and relapse) (p=0.000). Conclusion We conclude that histomorphology augmented by IHC on trephine biopsy gives valuable information regarding post-chemotherapy changes and residual disease status. Bone marrow trephine biopsy is an important tool to assess the remission status of patients with acute leukemia.

An Unusual Presentation of Recurrent Childhood Kimura Disease: Ileocecal Involvement.

Kimura disease commonly presents as an isolated swelling over the head and neck region. Intestinal involvement by Kimura disease in children is uncommonly reported. We report a 10-year-old boy who had presented with an ileocaecal mass with peripheral blood eosinophilia and elevated immunoglobulin E levels. The histopathologic examination from the ileocaecal mass was suggestive of Kimura disease. He had 2 recurrences once in the left axillary region and once in the bilateral cervical region. Ileocaecal involvement in Kimura disease is an uncommon presentation in childhood. Careful evaluation of complete blood count is critical in making diagnosis and avoiding unnecessary invasive procedures.

Hemophagocytic Lymphohistiocytosis in Children: Clinical Profile and Outcome.

OBJECTIVES: The objectives of this study were to describe the clinical and etiologic profile and outcomes of children with hemophagocytic lymphohistiocytosis (HLH) in a tertiary care hospital in South India. METHODS: This is a combined 2-year prospective (2017 to 2018) and 5-year retrospective (2012 to 2016) descriptive study in which children from birth to 18 years who satisfied the HLH-2004 diagnostic criteria were included. Case details from patient records were analyzed. RESULTS: Fifty-three cases were enrolled of which 20 were prospective and 33 were retrospective. Fever, hepatomegaly, anemia, and hyperferritinemia were the common presentations. Infectious triggers were found in 33 (62%) cases. Five cases were secondary to rheumatic diseases, and 8 were primary HLH. Bacterial (14 cases) followed by viral infections (10 cases) were the leading triggers. Scrub typhus (6 cases) and dengue (4 cases) were the most common infectious agents. Major complications include febrile neutropenia (38%) and multiorgan dysfunction (26%). One child developed secondary malignancy. The most frequently used immunosuppressive drug for the treatment of HLH was steroid (70%), while 28% of cases recovered with only supportive therapy. The overall mortality was 41%. CONCLUSIONS: Infections were the most common triggers for HLH of which tropical infectious agents constituted the majority. Treatment with steroids alone or regimens without cytotoxic drugs may result in resolution of secondary HLH with mild to moderate disease activity. Without stem cell transplant, primary HLH has a high mortality rate.

Profile of anemia in acute lymphoblastic leukemia patients on maintenance therapy and the effect of micronutrient supplementation.

BACKGROUND: Anemia is a common finding and important cause of morbidity in patients with acute lymphoblastic leukemia (ALL) at diagnosis or during the course of its protracted treatment. We studied profile of anemia in ALL patients on maintenance therapy and evaluated specific micronutrients as cause of this anemia. PATIENTS AND METHODS: ALL patients who were on maintenance therapy and had grade ≥ 2 anemia were recruited for the study. Serum iron studies, folate, and vitamin B12 were done to identify micronutrient deficiency and to initiate supplementation with specific components if found to be deficient. Toxicities, improvement of anemia, micronutrient levels, and disease outcome were studied after 3 months. RESULTS: From March 2015 to September 2016, 105 ALL patients were found to be on maintenance fulfilling the inclusion criteria. Overall, the proportion of anemia was 80%(N = 84). Majority had normocytic normochromic anemia (71%). Macrocytic anemia was seen in 18% and microcytic hypochromic in 9.5%. In patients with anemia of grade ≥ 2 (N = 84), 38 patients (45%) had biochemical deficiency of serum folate, and 7 (8%) had vitamin B12 deficiency. No biochemical evidence of iron deficiency was found. Supplementation of deficient micronutrients improved anemia: mean hemoglobin significantly increased from 8.06 ± 1.63 to 10.78 ± 1.53 (p < 0.001) at 3 months; and reduced treatment toxicities, mean number of febrile neutropenia episodes (p = 0.007), and treatment interruptions of > 2 weeks (p = 0.002) were lowered. Patients with anemia had significantly more relapses (N = 14,64%) compared to patients without anemia (N = 8,36%), (p = 0.040). CONCLUSION: Timely identification and correction of micronutrient deficiencies causing anemia in ALL patients on maintenance can enhance treatment outcomes.

IgG4-related lymphadenopathy masquerading as Hodgkin lymphoma: lessons from a pathologist's desk.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder affecting multiple organ systems. The awareness of this disease has tremendously increased over the last decade leading to effective treatment and decreased morbidity to the patients. Histopathology plays an important role in the diagnosis of IgG4-RD, and definite histologic criteria are proposed in clinically suspected patients. We report a patient with multiple organ system involvements of the salivary gland, lymph node and kidney. IgG4-related lymphadenopathy (IgG4-RL) in this patient was misdiagnosed as nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). Refractoriness to treatment for NLPHL and subsequent manifestations of renal involvement lead us to the correct diagnosis of this potentially treatable condition. IgG4-RL can mimic reactive proliferation as well as lymphomas. We report the clinical presentation and discuss the problems faced by pathologists in diagnosing IgG4-RL. We believe that awareness of this rare presentation will enhance the knowledge in diagnosing IgG4-RD.