Site-Specific Survival of Extra Nodal Diffuse Large B-Cell Lymphoma and Comparison With Gastrointestinal Diffuse Large B-Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) constitutes 30% of all non-Hodgkin's lymphomas. It can present as a nodal disease or as an extra nodal disease. Based on the site of origin, extra nodal DLBCL (EN-DLBCL) may have a distinct clinical outcome. Apart from the site of origin, factors including demographics, stage, and presence of any other primary malignancy also affect the outcome. The purpose of our study was to characterize prognostically distinct groups based on the site of presentation of EN-DLBCL. Methods: We used 18 registries in Surveillance, Epidemiology, and End Results database to identify the patients with EN-DLBCL for 2000 - 2015 with last follow-up till December 31, 2018. A total of 30,290 EN-DLBCL patients were selected and categorized based on 13 broad sites grouping. Demographic variables were summarized. We did overall survival analysis with univariate and multivariate Cox-proportional hazard modeling. Short-term survival trend was calculated as well. Results: The percentage of EN-DLBCL of all DLBCLs is 34.48%. EN-DLBCL was comparatively seen more in males (54.94%) and non-Hispanic whites (71.52%). In terms of clinical characteristics, patients with EN-DLBCL were mostly diagnosed at age ≥ 60 years (66.11%), early stage (69.33%), and presentation as first primary cancer (81.89%). A higher risk of mortality was seen in non-Hispanic black (hazard ratio (HR) 1.36), with late age of onset (HR 2.69), late stage at presentation (HR 1.42), and with history of other malignancy (HR 1.29). Compared to the intestinal tract, the risk of overall mortality was higher in individuals with involvement of nervous system (HR 1.85), pancreas and hepatobiliary system (HR 1.22), and respiratory system (HR 1.18) and the best outcomes were seen in heart and mediastinal site (HR 0.58) of DLBCL. Conclusion: Based upon our population-based study, we conclude that primary site of presentation of EN-DLBCL is an important prognostic factor with significant difference in survival based on histological and epidemiological characteristics.

Trends of Ordering Hypercoagulability Work-Up at an Academic Medical Center.

BACKGROUND: Venous thromboembolism is a significant clinical event, with an annual incidence of 1-2 per 1000 population. Risk factors include recent surgery, prolonged immobility, oral contraceptive use, and active cancer. Inherited risks include protein C and S deficiencies, antithrombin deficiency, factor V Leiden mutation and prothrombin. These factors can be tested to guide therapy, but current evidence suggests that testing for inherited thrombophilia is not recommended in most inpatient settings. In the era of high value care, hypercoagulable testing for VTE creates a financial burden for the hospital and patients. We performed a retrospective chart review of hypercoagulable orders on VTE patients at our institution. METHODS: Institutional Review Board approval was obtained. A total of 287 adult patients admitted over a 3-month period with the diagnosis of VTE were included. Patients were identified via ICD-10 codes and data were collected from electronic medical records. Patient characteristics, provoked versus unprovoked VTE, and relative contraindications for hypercoagulability work-up were analyzed. Our primary outcome was to assess the appropriateness of thrombophilia testing in VTE patients based on screening guidelines. Our secondary outcome was to analyze the cost burden of ordering these tests. RESULTS: A total of 287 patients were included in our data analysis. Patient risk factors for VTE were malignancy, previous DVT, immobilization, surgery 3 months prior, and central line placement. Fifty-seven of 287 patients had at least one hypercoagulable test ordered during hospitalization which did not adhere to guidelines. Misuse of testing occurred during active thrombosis, active anticoagulation, presence of risk factors, first episode of VTE, and malignancy. The cost of ordering these 5 thrombophilia tests totaled over $40,000. CONCLUSION: In our study, numerous patients were tested without compliance to standard recommendations, which created financial and value-based burdens on our health care system. Increased awareness among clinicians is thus warranted to ensure high value care.

Small Bowel Gastrointestinal Stromal Tumor as a Gateway for Streptococcus anginosus Causing Multiple Liver Abscesses.

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal neoplasm of the gastrointestinal tract but consist of only 1% of all primary gastrointestinal neoplasms. Differentiated from other spindle cell tumors, GISTs are uniquely positive for CD117 expression which allows for molecular targeting therapy with imatinib mesylate (Gleevec). Clinical presentations are variable, ranging from asymptomatic to vague symptoms of abdominal pain, early satiety, abdominal distention or gastrointestinal bleeding. Very rarely, patients can present with tumor-bowel fistula and intra-abdominal abscesses. In this article, we discuss a rare presentation of a middle-aged male with multiple liver abscesses found to have a primary small bowel GIST. This patient received prompt intravenous antibiotics; however, hepatic abscesses can be easily misinterpreted as cystic hepatic metastases which can delay appropriate therapy. Streptococcus anginosus was found to be responsible for the formation of the liver abscesses visualized on computed tomography (CT) scan. Similar to Streptococcus bovis, knowledge in the literature is arising about the association between S. anginosus and gastrointestinal malignancies. This case highlights the importance of identifying concomitant primary GISTs with intra-hepatic abscesses, as these lesions can be easily misconstrued as liver metastases and consequently mismanaged. We herein emphasize that hepatic abscesses are a potential sequela of GISTs and should thus prompt further investigation for potential malignancies, if warranted, so that there is no delay in treatment of these gastrointestinal tumors.

Acute Myeloid Leukemia Acquiring Promyelocytic Leukemia-Retinoic Acid Receptor Alpha at Relapse.

Acute promyelocytic leukemia (APL) is identified as the M3 subtype of acute myeloid leukemia (AML). APL is presently one of the most curable leukemias. We describe here a rare case of APL who presented as a relapsed disease after 1 year of chemotherapy for AML. The patient lacked t(15;17) at the initial presentation but was present later at the time of relapse. The patient attained a complete remission following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide-based therapy. We discuss the possible mechanism behind secondary acquisition of promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) at relapse of AML. We also briefly discuss the clinical features, diagnosis and treatment of APL.

Carcinoid tumor of lung and BRCA mutation: a case report.

BACKGROUND: A BRCA mutation is a mutation in either of the BRCA1 or BRCA2 genes, which are tumor suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, whereas others have no proven impact. BRCA mutations are well known to be associated with breast, uterine, and ovarian cancers along with some nongynecological malignancies involving the peritoneum, prostate, pancreas, skin, stomach, and rectum. However, there are no reported cases to date of an association between carcinoid tumors and a BRCA mutation. CASE PRESENTATION: Our patient was a 33-year-old White woman with BRCA2 mutation who presented to her primary care physician for evaluation of abdominal pain. She underwent computed tomography of her abdomen and pelvis, which showed an incidental finding of infrahilar mass along with renal stones. Further workup with bronchoscopy and biopsy of the mass confirmed it to be a carcinoid tumor of the lung. CONCLUSIONS: No literature thus far exists describing a connection between BRCA mutations and carcinoid tumors. Early diagnosis and prompt treatment of carcinoid tumors are proven to have impact on survival and prognosis of these patients.

Hypercalcemia in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: An Unusual Presentation of a Rare Disease and Literature Review.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an extremely rare morphologic subtype of diffuse large B-cell lymphoma (DLBCL), accounting for only 1-3% of total cases. It is considered an aggressive lymphoma with a poor prognosis. Hypercalcemia has been described as an uncommon presenting symptom of patients with DLBCL in several case reports. Here, we report an unusual case of severe hypercalcemia in a patient who was ultimately diagnosed with T-cell/histiocyte-rich B-cell lymphoma. A 69-year-old male patient presented to our hospital with nausea, vomiting, weakness and unintentional weight loss. His initial blood tests showed a serum calcium level of 16.1 mg/dL and serum creatinine level of 3.25 mg/dL. He had high intact parathyroid hormone (PTH, 6.8 pg/mL), mildly elevated 25-hydroxyvitamin D and serum PTH-related peptide (PTHrP). To exclude malignancy, computed tomography (CT) scans of the chest, abdomen and pelvis were performed which were unremarkable. A bone marrow biopsy was performed to detect any hidden hematologic malignancy which showed large mononuclear cells with prominent nucleoli and occasional Reed-Sternberg cells, consistent with the diagnosis of THRLBCL. Subsequent positron emission tomography demonstrated diffuse fluorodeoxyglucose (FDG) uptake. This case reports a unique presentation of a rare subtype of non-Hodgkin's lymphoma. We highlight the importance of pursuing a thorough workup for causes of hypercalcemia as well as understanding the underlying mechanisms of severe hypercalcemia in malignancy.

Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis.

BACKGROUND: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration. Differentiation and treatment can be complex, especially when features of both syndromes are present and the patient has taken both serotonergic and neuroleptic agents. METHOD: Case analysis of a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine) presenting with mixed SS/NMS features and whose clinical management suggests a practical algorithm for treatment of undifferentiated SS/NMS in critical care settings. RESULTS: The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders--cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when clinical presentation becomes consistent with NMS (SS can be prolonged if serotonergic agent has long half-life). CONCLUSIONS: Prompt and appropriate identification and intervention are essential for successful management of SS and NMS. The suggested treatment algorithm allows for specific treatment of both disorders and avoids potentially exacerbating either one. The algorithm derived from this case could serve as both a practical guideline and impetus for further investigation in light of increasing psychotropic co-administration.

A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer.

PURPOSE: To test the hypothesis that progression of androgen sensitive prostate cancer is dependent on growth factors, such as platelet derived growth factor (PDGF), and inhibition of PDGF receptor (PDGF-R) with imatinib will induce anti-tumor activity. PATIENTS AND METHODS: This phase II study evaluated imatinib in patients with androgen sensitive prostate cancer and prostate specific antigen (PSA) progression after local therapy. Patients received 400 mg of imatinib orally twice a day for 24 weeks (six cycles). Patients were monitored every 4 weeks for an effect on PSA and toxicity. Immunohistochemistry (IHC) for PDGF-R was performed in available tumor specimens. RESULTS: Twenty-one patients were enrolled on this trial with a median age of 64 years. A total of 72 cycles of therapy were administered. Sixteen patients were evaluable for a response. Nine of the 16 patients demonstrated a stable PSA. Seven patients demonstrated PSA progression. Grade 3 and 4 toxicity included rash (4.1%), hematuria (1.4%), diarrhea (1.4%), and neutropenia (2.7%). Testosterone levels did not change during therapy. Four patients with available tumor demonstrated PDGF-R alpha and beta by IHC. CONCLUSIONS: This first study evaluated the efficacy and safety of imatinib in patients with early androgen sensitive prostate cancer following local therapy. As a single agent at this dosing, imatinib had limited biochemical activity.