Smeeta Gajendra

Chronic neutrophilic leukemia with V617F JAK2 mutation

Chronic neutrophilic leukemia (CNL) is a rare disease grouped under World health organization classification as chronic myeloproliferative disease. It is a diagnosis of exclusion in patients with sustained mature neutrophilia and splenomegaly with no evidence of other myeloproliferative disease or reactive neutrophilia. V617F JAK 2 mutation has been described in classical myeloproliferative diseases, but its association with CNL has been reported in a few cases. Here in, we describe three cases of CNL with presence of V617F JAK 2 mutation. To distinguish CNL from secondary neutrophilia can be difficult. Detection of the V617F JAK 2 mutation in such scenario can provide a useful diagnostic test to establish the neoplastic nature of the neutrophilia.

Prognostic and Predictive Significance of Smudge Cell Percentage on Routine Blood Smear in Chronic Lymphocytic Leukemia

INTRODUCTION/BACKGROUND Smudge cells are ruptured lymphocytes present on routine blood smears of chronic lymphocytic leukemia (CLL) patients. We evaluated prognostic and predictive significance of smudge cell percentage on a blood smear in CLL patients. MATERIALS AND METHODS We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears of 222 untreated CLL patients registered at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi over the past 12 years. RESULTS The male:female ratio was 3:1, and median age 60 (range, 28-90) years. Median absolute lymphocyte count was 42 × 10(9)/L. The median smudge cell percentage was 29.6% (range, 4%-79%). We found no correlation of proportion of smudge cells with age, sex, lymphocyte count, organomegaly, or response to therapy, although there was a significant correlation with the Rai stage at diagnosis. Median smudge cell percentage in stage 0 and I was 33% (range, 12%-79%), in stage II 31% (range, 12%-61%), and stage III and IV 21% (range, 4%-51%) (P < .001). Patients with ≤ 30% smudge cells had a shorter median progression-free period (PFP) of 30 months compared with patients who had more than 30% smudge cells (PFP, 45 months; P = .01). The 5-year survival rate was 51% for patients with 30% or fewer smudge cells, and it was 81% for patients with more than 30% smudge cells (P < .001) at a median follow-up of 3.5 years. CONCLUSION Simple and inexpensive detection of smudge cells on routine blood smears seems useful in predicting progression-free and overall survival in CLL patients and might be beneficial in countries with limited resources.

Immunophenotypic analysis of T‐acute lymphoblastic leukemia. A CD5‐based ETP‐ALL perspective of non‐ETP T‐ALL

T‐cell antigens [CD5,CD1a,CD8] define early T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL). To understand immature T‐ALL of which ETP‐ALL is part, we used these antigens to subcategorize non‐ETP T‐ALL for examining expression of myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/−) to start categorization, we studied 69 routinely immunophenotyped patients with T‐ALL. CD5− was a homogenous (CD8,CD1a)− M/S+ ETP‐ALL group (n = 9). CD5+ cases were (CD8,CD1a)− pre‐T‐ALL (n = 22) or (CD8,CD1a)+ (n = 38) thymic/cortical T‐ALL; M/S+ 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007). ETP‐ and pre‐T‐ALL together (CD1a−,CD5−/+ immature T‐ALL group) were nearly always M/S+ (29/31; 93.55%). In multivariate analysis, only ETP‐ALL predicted poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T‐ALL almost always means ETP‐ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity in T‐ALL, and the CD5+/−/CD1a−/CD8− immature T‐ALL group needs further study to understand the biology of the T‐ALL–myeloid interface. (ii) ETP‐ALL patients may be pre‐T‐ALL if CD2+; CD2+, conversely, CD5−/CD1a−/CD8− pre‐T ALL patients are ETP‐ALL. (iii) Immunophenotypic workup of T‐ALL must not omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be defined as recommended for ETP‐ALL, so that this entity can be better evaluated in future studies of immature T‐ALL, a group to which ETP‐ALL belongs. (iv) ETP‐ALL has poor prognosis.

Adrenal Histoplasmosis in Immunocompetent Patients Presenting as Adrenal Insufficiency.

Abstract Objective: Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, endemic in central and eastern states of United States, South America and Africa. India is considered to be non-endemic area for histoplasmosis. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients; whereas isolated adrenal involvement with adrenal insufficiency as the presenting manifestation of the disease is rare. Material and Method: Twelve patients from a non-endemic area with adrenal histoplasmosis, who were immunocompetent and diagnosed as adrenal histoplasmosis by cytology/histopathology between January 2012 to December 2014 were studied. 18F-FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) was used to assess the extent of involvement. Results: There were a total of 12 immunocompetent males (mean age: 56.9 years). Ten patients had bilateral adrenal involvement and two had a unilateral left adrenal mass. All the patients had histopathologically/cytologically proven adrenal histoplasmosis. Two patients had simultaneous histoplasmosis of other sites, one in the epiglottis and the other in the alveolus. 18F-FDG PET/CT was performed in 10 patients showing high FDG uptake in the adrenals. All these patients received Amphotericin B and/or Itraconazole treatment that led to symptomatic improvement. Conclusion: A diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients who present with nonspecific symptoms, clinical signs, laboratory and radiological features that can resemble adrenal neoplasms. Clinical specimens must be sent for cytopathology/histopathology together with fungal culture for a definite diagnosis and appropriate management.

Metastatic Renal Cell Carcinoma: An Unusual Cause of Bleeding Pancreatic Mass.

Renal Cell Carcinoma metastasizing to pancreas is uncommon, occurring in 1-2% of cases; lung being the most common site. It is usually asymptomatic, or may present as abdominal pain, weight loss, pancreatitis or gastrointestinal bleeding. Herein, we present a case of 75-year-old male presented as intraabdominal bleeding to the Emergency Department. Contrast enhanced computed tomography with angiography of abdomen showed lobulated soft tissue mass in the uncinate process region, infiltrating into the distal third and proximal fourth part of duodenum. A clinico-radiological diagnosis of carcinoma head of pancreas infiltrating into duodenum was made and the patient underwent Whipples operation. With past history of nephrectomy 3 years back, microscopy and the immunoprofile; a final diagnosis of clear cell renal cell carcinoma metastasizing to pancreas was given on histopathology. A high index of suspicion is required for patients with a history of RCC and they should be monitored lifelong for early detection of metastases and to improve survival.

Downgraded Lymphoma: B-Chronic Lymphocytic Leukemia in a Known Case of Diffuse Large B-Cell Lymphoma--De Novo Occurrence or Transformation.

Low-grade indolent lymphomas can be transformed into high-grade aggressive lymphomas [1,2,3,4]. Very few cases of transformation of high/intermediate-grade lymphoma to low-grade lymphoma have been reported in the literature [5,6]. This may arise through transformation of the original clone or may represent a new neoplasm resulting from additional genetic mutations that alter the growth rate, growth pattern, and sensitivity to treatment. A 57-year-old male diagnosed with diffuse large B-cell lymphoma (DLBCL) (non-germinal center B-cell type) in 2002 completed 6 cycles of CHOP followed by radiotherapy. In 2006, 18Ffluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed no active disease. In 2007 there was recurrence in the left obturator and external iliac nodes. Lymph node biopsy done outside our facility showed CD20+ B-cell lymphoma. The patient was advised to undergo intensive chemotherapy, but was lost to follow-up. In 2010, the patient came to our hospital with bilateral firm non-tender inguinal and right axillary lymphadenopathy without any organomegaly. 18F PET/CT revealed heterogeneous uptake in the left paraaortic, retrocaval, precaval, and bilateral internal iliac nodes. A previous diagnostic lymph node biopsy was reviewed, showing diffuse infiltration of large atypical cells, positive for CD20, CD30, MUM1, and Bcl2 with a Ki67 index of 80% and negative for CD3, CD5, and CD10, which was consistent with DLBCL (Figure 1A). Biopsy of the paraaortic mass revealed sheets of small lymphoid cells, which were positive for CD20, CD5, and CD23 and negative for CD3 and cyclin D1 with a low Ki67 index, suggestive of small-cell lymphoma (Figure 1B). 18F PETCT was repeated after 1 year, showing multiple FDG-avid cervical, supraclavicular, mediastinal, axillary, abdominal, and pelvic lymphadenopathies (Figure 1C). After 10 months, hemoglobin was 90 g/L, total leukocyte count was 21.1x109/L, and platelet count was 40x109/L. Peripheral blood smear showed 84% abnormal lymphoid cells, which were immunopositive for CD19, CD5, CD23, CD22 (dim), CD200, and CD20 with lambda light chain restriction and negative for CD10, FMC7, CD38, IgM, and CD103, confirming the diagnosis of chronic lymphocytic leukemia (CLL) (Figure 1D). The patient was started on a fludarabine, cyclophosphamide, and rituximab (FCR) regimen. After 6 cycles of FCR, he was in complete remission and was started on rituximab maintenance therapy. Letters to the Editor

Disseminated Histoplasmosis in an Immunocompetent Host Presenting as Pancytopenia with Bilateral Adrenal Masses

A 44-year-old male presented with fever, progressive weight loss, and anorexia for 6 months. The laboratory results showed deranged renal function tests. Serum adrenocorticotropic hormone was high at 252 pg/mL (normal limit: <46 pg/mL), suggestive of primary adrenal insufficiency. Serum free light chains were elevated, kappa at 87.97 mg/L (reference range: 3.30-19.40 mg/L) and lambda at 91.77 mg/L (reference range: 5.71-26.30). Ultrasonography of the abdomen showed hepatosplenomegaly with space-occupying lesions in bilateral suprarenal regions, while endoscopy ultrasound-guided fine-needle aspiration showed necrotizing granulomatous inflammation. Work-up for tuberculosis and human immunodeficiency virus was negative. The hematological parameters showed pancytopenia. The bone marrow aspiration revealed round to oval organisms with crescent-shaped eccentric nuclei both extracellularly and intracellularly, inside the macrophages and osteoclastic giant cells (Figure 1A). Bone marrow biopsy showed the presence of intracellular and extracellular oval capsulated globose organisms spread throughout the marrow spaces (Figure 1B). Periodic acid-Schiff (PAS) staining showed these organisms as bright eosinophilic structures with clear halos around them (Figure 1C). Gomori methenamine silver (GMS) staining showed clusters of fungal yeasts, morphologically compatible with Histoplasma capsulatum (Figure 1D). The patient was started with intravenous amphotericin B followed by oral itraconazole. His condition improved with recovery of counts and improvement of renal function; he is currently doing well. Informed consent was obtained. Figure 1 A) Bone marrow aspirate showing numerous Histoplasma capsulatum inside the osteoclastic giant cell and macrophage (inset) (Giemsa, 100x), B) bone marrow biopsy showing Histoplasma (H&E, 100x), C) PAS staining showed yeast-like cells with bright ... Histoplasmosis is a fungal infectious disease caused by inhalation of spores of Histoplasma capsulatum. It may present as a self-limiting form or progressive disseminated disease. Disseminated histoplasmosis may affect almost all systems, including the reticuloendothelial system, lungs, gastrointestinal tract, renal tract, central nervous system, visual system, bone marrow, and adrenal glands [1]. Histoplasmosis presenting as a bilateral adrenal mass in an immunocompetent patient is rare. A high index of suspicion is required for the diagnosis of disseminated histoplasmosis in a patient with unexplained fever, as it may mimic other chronic illnesses or a neoplasm. The differential diagnoses that should be considered are tuberculosis, sarcoidosis, adrenal hemorrhage, metastatic carcinoma, and lymphoma. Despite extensive imaging, positron emission tomography scanning, and fine-needle aspiration biopsy, a definite diagnosis may not be reached [2]. Bone marrow examination is a useful diagnostic test to establish a diagnosis of disseminated histoplasmosis. In our case, a middle-aged immunocompetent patient presented with nonspecific symptoms and bilateral adrenal mass with insufficiency, the diagnosis of which was only possible with bone marrow examination. Conflict of Interest Statement The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

Persistent Monotypic Plasma Cells with Absence of Neoplastic B Cell Component in a Treated Case of Waldenström Macroglobulinemia: A Sign of Residual Disease?

Waldenström macroglobulinemia (WM) is a rare indolent variant of non- Hodgkins lymphoma characterised by lymphoplasmacytic infiltration of bone marrow (BM) associated with a serum IgM paraprotein. The WHO classification states that the neoplastic cells of WM usually are positive for monotypic surface immunoglobulin light chain, IgM, CD19, and CD20 and are negative for CD5, CD10, and CD23. Serum monoclonal protein detection by serum protein electrophoresis and bone marrow aspirate and biopsy are required for WM diagnosis, monitoring and response assessment. Pathologist must dissuade themselves from making a hasty decision on calling a complete response in WM when neoplastic B cell component is absent. Evaluation of clonality of any residual plasma cells must be done in all cases of WM to evaluate the presence and extent of residual or persistent disease. Role of additional therapy targeted at these residual plasma cells in WM can be evaluated as tools for achieving complete remission. Herein, we present a case of WM with residual monotypic plasmacytosis in BM, without B lymphocytes after therapy.

Coexistence of scleroderma with multiple myeloma: a rare association

Coexistence of scleroderma with multiple myeloma (MM) is an unusual finding with unclear significance. Only 13 cases of MM with scleroderma have been reported until now. We report a case of a 24-year-old man with 8-year history of progressive thickening of skin all over the body. Histopathology of skin lesion was consistent with scleroderma. Bone marrow biopsy showed interstitial and focal increase in plasma cells and increased bone marrow fibrosis. Skeletal survey showed osteopenia, but no osteolytic lesion or fracture. The patient was diagnosed as scleroderma with coexistence of immunoglobulin A, κMM. The patient recovered with improvement of skin lesions after 9 months of therapy with thalidomide and dexamethasone.

Gastrointestinal Histoplasmosis: A Case Series

Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.