Dipesh Uprety

Renal failure secondary to leukemic infiltration of kidneys in CLL--a case report and review of literature.

Dear Editor, Although leukemic cell infiltration of the renal parenchyma commonly occurs in chronic lymphocytic leukemia (CLL), it is unlikely to cause renal failure. This article reports a rare case of undiagnosed CLL presenting with acute renal failure. A 70-year-old Caucasian gentleman presented with 18 months history of cervical adenopathy and 2 months history of generalized weakness, fatigue, anorexia, nausea, and vomiting. He had previously been fit and had no medical problems. The physical examination revealed multiple enlarged non-tender cervical and axillary lymph nodes bilaterally (size 2–4 cm). Systemic examination was unremarkable. Investigations revealed hemoglobin of 13.4 g/dl, platelets of 198,000/μL, white cells of 16,200/μL, absolute lymphocyte count of 9,136/μL, red cells of 3.64 million/μL, urea of 127 mg/dl, and creatinine of 15.2 mg/dl, Calcium level 9 mg/dl and albumin 4 gm/dl. CT scan of chest, abdomen, and pelvis revealed extensive adenopathy of the mediastinum, hilar, axillary, and abdominal and pelvis including the inguinal regions. Pathology examination of right axillary lymph node biopsy was indicative of CLL/SLL with tumor cells positive for CD20, CD5, and bcl-2 and negative for CD3, CD10, bcl-6, and cyclin D1. The axillary node biopsy (Fig. 1) showed effacement of nodal architecture by a monotonous population of small mature lymphocytes with irregular chromatin, scattered indented nuclei, and scant pale cytoplasms. A bone marrow aspiration biopsy was positive for involvement by CLL. A renal biopsy showed extensive involvement by atypical monomorphous lymphoid population with infiltration of the cortical interstitium by lymphocytes expressing CD20 and CD5. The photomicrograph (Fig. 2) has CD20+ lymphocytes encompassing a glomerulus (right) and renal tubule (left). There was no light chain deposition or evidence of amyloidosis. Immunofluorescence and electron microscopy were both negative for immune complexes. FISH panel for cytogenetics for CLL was negative for any abnormalities. The patient underwent dialysis for renal failure and received three cycles of fludarabine, rituxan, and cyclophosphamide. He responded well to chemotherapy and is currently in partial remission. Repeat bone marrow examination was negative for involvement by leukemia. Unfortunately, his renal function did not improve and he remains dialysis dependent.

Idelalisib- a PI3Kδ targeting agent for B-cell malignancies

Idelalisib, the first in-class phosphotidlyinositol 3-kinase delta (PI3Kδ) inhibitor, was approved by the US Food and Drug Administration in July 2014. It simultaneously received breakthrough therapy designation in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia (CLL) as well as accelerated approval as monotherapy for the treatment of relapsed follicular lymphoma and relapsed small lymphocytic lymphoma. In a pivotal phase III study of 220 patients with relapsed CLL, the overall response rate of patients who received rituximab plus idelalisib was 81%. The median progression-free survival (PFS) was 5 months with rituximab plus placebo group, but was not reached in the idelalisib arm. At 24 weeks, the PFS in patients receiving idelalisib was 93%. In a phase II trial of 125 patients with relapsed or refractory indolent non-Hodgkin lymphoma who received idelalisib 150 mg twice daily, the response rate was 57%. Complete response was seen in 6% of patients. The median duration of response was 12.5 months, and median PFS was 11 months. Idelalisib is a promising new therapy for relapsed indolent B-cell malignancies.

Occult gastric cancer presenting as hypoxia from pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) causing fatal pulmonary hypertension is a rare presentation of malignancy. In general, patients with PTTM rapidly succumb to death due to severe hypoxia. To date, very few cases of PTTM have been reported in the literature; and most of these cases were from gastric cancer and were diagnosed on post mortem autopsy, as it is extremely challenging to make an ante mortem diagnosis. We here report on a case of undiagnosed diffuse gastric cancer, presenting as worsening hypoxia. The clinical, radiographic, and echocardiographic features, and laboratory and pathological results were consistent with PTTM from gastric cancer. The patient was started on anticoagulation therapy, corticosteroids, and high-flow oxygen. However, her hypoxia worsened to the extent that she required ventilator support, and she died soon after intubation due to cardiac arrest. Since diffuse gastric cancer is associated with hereditary diffuse gastric cancer syndrome, cadherin 1 gene mutation analysis was performed to estimate the risk to her daughters. The test came back negative.

Precursor B-Cell Lymphoblastic Primary Cardiac Lymphoma â Case Report andReview of Literature

Primary cardiac lymphoma (PCL) is an extremely rare malignancy and an uncommon presentation of Non-Hodgkin’s Lymphoma. We report the first case of Precursor B-cell lymphoblastic PCL. A 44 year old Caucasian woman presented to our institution with one week history of worsening dyspnea, leg swelling and a weight gain of 12 pounds. Urgent echocardiography revealed pericardial effusion with tamponade physiology. Subsequent imaging showed a mass in the right atrio-ventricular groove. Pericardiocentesis was performed and cytopathology showed malignant appearing immature lymphocytes. Immunophenotypic analysis revealed 85% of the cells to be CD19 and CD10 positive. The cells were negative for CD20, surface light chains, CD3 and CD5 consistent with immature B-cells. Terminal deoxynucleotidyl Transferase (TDT) was strongly positive confirming Precursor B-cell Lymphoblastic Lymphoma. Clinical presentation of PCL can be varied and can mimic non-neoplastic primary cardiac problems. When PCL is suspected and a pericardial effusion is present, pericardial fluid analysis can be a reasonable first step. If diagnostic, it can avoid further invasive procedures. Chemotherapy remains the standard treatment and should be initiated early given the aggressive nature of these high grade lymphomas. Surgery is needed only in selected cases with obstructive features.

Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study

In 2011, ipilimumab was approved by the US Food and Drug Administration (FDA) for metastatic melanoma. Since its approval, numerous targeted therapies have been approved by the FDA. Population-based studies assessing the survival benefit from these agents are lacking. We therefore carried out this study to compare the 1-year, 2-year, and median overall survival (OS) among metastatic melanoma patients in pretargeted and post-targeted eras. This is a retrospective study that utilized the Surveillance, Epidemiology, and End Results (SEER-18) database, version 8.3.4 (22 March 2017). The patient groups were defined as the pretargeted era (2004–2010) and the post-targeted era (2011–2014) as ipilimumab was approved by the FDA in 2011. The database comprised of 5471 patients (3314 in the pretargeted era and 2157 in the post-targeted era). OS in the post-targeted era was found to be significantly better compared with the pretargeted era by Kaplan–Meier curve (1-year OS: 38.9 vs. 36.8%, 2-year OS: 28.3 vs. 23.5%, and median survival: 8 vs. 7 months, P=0.001 by the log-rank test). The survival was significantly better in the post-targeted era compared with the pretargeted era on multivariate analysis using a Cox proportional hazard model after adjusting for age, sex, race, and metasectomy status (adjusted hazard ratio of 0.889, 95% CI: of 0.832–0.951, P=0.001). There is significant survival benefit in metastatic melanoma patients since the introduction of immune checkpoint-blocking agents.

Racial Differences in Survival of Elderly Adults with Chronic Myeloid Leukemia Before and After the Introduction of Imatinib in the United States.

in activities outside the home. The one exception to this finding was the result that ADL improvements resulted in higher odds of loneliness. This may be due to decline in the number of persons that are helping the individual if less daily assistance is required, or it maybe a statistical anomaly, because few (n = 68, 2%) individuals had ADL improvements. Despite mounting evidence that loneliness is a risk factor for a wide range of problems, it receives little attention in health care. Identifying groups at particular risk of loneliness should become part of the preventative routine for elderly adults. All of the variables in the model can easily be determined in one healthcare visit. Recent research on interventions to combat loneliness provides evidence that the prevalence of loneliness can be reduced, but interventions can be implemented only once appropriate at-risk individuals have been identified.

The risk of secondary primary malignancy in early stage differentiated thyroid cancer: a US population-based study

protein function, encoding for an altered and non-functional isoform [12,13]. Interestingly from a clinical point of view, bsandwich mutations, such as p.V143A c.428T>C, are considered very promising targets for functional p53 rescue by generic small molecule drugs, able to restore wild-type-like activity [13]. When both alleles encode for a non-functional protein, p53 loses its function of ‘guardian of the genome’, causing high genomic instability and resistance to anticancer drugs [12]. In our case, homozygosity for p.V143A (c.428T>C) mutation could have caused tumor resistance after a prolonged response to trastuzumab. Due to the small size of the liver lesion and the ethical problem of performing a ‘clinically not required’ liver biopsy, it has not been possible to analyze the liver metastasis upfront treatment with trastuzumab. Missing this initial analysis, another hypothesis for the acquired resistance to trastuzumab could be that the mutation already existed when the metastasis first appeared, representing a more malignant subclone from the primary tumor. As regards to the expression of p53, IHC staining is usually used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites, a strong and diffuse pattern of p53 expression (greater than 60% of cells) being associated with a mutated TP53 gene in the most of cases [14]. In our case, IHC was not able to discriminate the heterozygous mutation of TP53 in the primary tumor and the homozygous mutation in the metastatic lesion, both appearing intensely positive. In conclusion, in our case, homozygosity for p.V143A c.428T>C mutation in exon5 of TP53 gene could be the cause of the acquired resistance in the course of trastuzumab therapy. Considering the difficulty to find suitable metastatic tissue specimens for molecular assessments and the uncommon presence of this mutation in gastric cancer, it could be hard to clinically verify this hypothesis, which, in our opinion, could be otherwise tested in vitro on HER2 overexpressing gastric cancer cell lines transfected with the p.V143A c.428T>C mutation.

Acquired Vitamin K Deficiency Presenting as a Catastrophic GI Bleed in a Hospitalized Patient

Acquired coagulopathy presenting as unexplained bleeding has been described in many critically ill hospitalized patients. The most common causes are DIC (Disseminated intravascular coagulation), renal or hepatic failure, Sepsis induced thrombocytopenia, HIT (Heparin induced thrombocytopenia), malignancy, acquired antibodies to clotting factors, drugs (anticoagulants, antibiotics), severe Vitamin K deficiency. We report a rare case of GI Bleed secondary to acquired Vitamin K deficiency.

Multiple Myeloma Presenting with Autoimmune Hemolytic Anemia

Autoimmune hemolysis is rare in multiple myeloma. We describe a rare case of multiple myeloma who presented with autoimmune hemolytic anemia at initial presentation.

HIV and Indolent Lymphoma

The incidence of non-Hodgkin’s lymphoma (NHL) is at least 100 times higher in the human immunodeficiency virus (HIV)-infected population as compared with the general population. Approximately 3 % of HIV/AIDS patients develop NHL. Among them, the risk increases with older age, duration of infection, and with a history of AIDS-defining events. Data supporting a decline in NHL in the post-HAART era are inconsistent. A prolonged immunocompromised state, with reduced immune surveillance, and chronic antigen stimulation, in the setting of infection with HIV, are contributors to the pathogenesis of NHL. Studies suggest that there are increased p53 gene abnormalities in HIV-1-related NHL. In this chapter, we will focus on the indolent subset of NHL in the HIV-infected population. Of the AIDS-defining illnesses, there are two subtypes of aggressive NHL including Burkitt lymphoma and DLBCL, which are disproportionately more prevalent among HIV lymphoma subtypes. There is a contradistinction in the prevalence of indolent subtypes of NHL in the HIV population, with the incidence rates of these lymphomas being lower as compared with the indolent subtypes in the general population, as described in SEER database analysis of patients from 1992 to 2009, suggesting less of an association with HIV.