No abstract

As the number of cancer survivors grows, so does the number of co-occurring primary malignancies and secondary malignancies. In rare cases, single driver mutations can be responsible for concomitant primary malignancies. By understanding the mechanisms that drive multiple primary malignancies (MPM), clinicians are capable of targeting molecular pathways that drive oncogenesis resulting in the successful treatment of many malignancies while also reducing the side effects of conventional chemotherapy.Herein, we report a case of co-occurring hairy cell leukemia (HCL) and malignant melanoma in a 69-year-old male. This patient tested positive for the BRAF V600E mutation and was initiated on a single agent, vemurafenib. He, unfortunately, succumbed to his illness before completion of his planned therapy course. This case report is intended to highlight the rare co-occurrence of BRAF-positive HCL and melanoma and to encourage driver mutation evaluation when a patient presents with MPM and the possibility of a unifying driver mutation. To the best of our knowledge, this is the first case of a co-occurring BRAF positive melanoma and HCL to be reported in a chemotherapy-naïve patient.

e20715 Background: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. 5-year survival rate for metastatic non-small cell lung cancer (NSCLC) is estimated at 4%. For patients who lack a driver mutation, platinum based chemotherapy had been the cornerstone treatment, but the addition of immunotherapy has altered the treatment landscape for many advanced NSCLC patients. Immunotherapy, with or without chemotherapy, has been demonstrated in many clinical trials to extend survival in both the first-line setting as well as subsequent lines of therapy. While the clinical trial data over the past several years has been robust, less is known about how these agents have fared in routine clinical practice. To understand this better, we utilized the National Cancer Data Base (NCDB) to examine the survival of patients who received immunotherapy for stage IV NSCLC. Methods: We queried the NCDB from 2004-2015 for patients with stage IV NSCLC treated with chemotherapy and at least 3 months of follow-up. Multivariable logistic regression was used to determine predictors of immunotherapy use. Multivariable cox regression was used to determine predictors of overall survival. A propensity score was calculated and used to mitigate indication bias. Results: Of 203,069 eligible patients, 5,877 received immunotherapy. The median age was 65 years (40-90). The median follow up was 10.6 months (3-154). Patients were more likely to receive immunotherapy if they were younger, had a lower comorbidity score, received treatment at an academic facility, had adenocarcinoma histology, private insurance, Caucasian race, and a more recent treatment year. The use of immunotherapy rose steadily across the dataset years, rising from 1% to 12%. Predictors of survival were younger age, lower comorbidity score, lower grade tumor, treatment at an academic facility, higher education, higher income, private insurance, metropolitan location, immunotherapy use, adenocarcinoma histology, and more recent year of treatment. On propensity-matched Kaplan-Meier analysis patients treated with immunotherapy in addition to chemotherapy had improved survival, 13.7 months compared to 11.8 months, p < 0.0001. Conclusions: This analysis demonstrates improved overall survival in stage IV NSCLC patients who received immunotherapy. There are inherent limitations of retrospective analyses of data from large databases, however the survival improvement noted in this study is concordant with the more robust prospective clinical research published to date.

Evans syndrome (ES) is a rare hematologic disorder characterized by the presence of Direct Antiglobulin test (DAT) positive autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and/or immune neutropenia. The risk of thrombosis has been well established in retrospective studies for ITP and AIHA; however, the risk of thrombosis in ES has been limited to case reports and individual case series. Whether the risk of thrombosis in ITP and AIHA is additive has not been well established, but preliminary observation suggests the rate of thrombosis is higher than the rate observed in ITP or AIHA individually. Furthermore, ES appears to be an underappreciated diagnosis. Anemia in the presence of ITP is often considered to be secondary to acute blood loss and a proper workup for hemolysis is often missed. Appropriate risk stratification of these patients is hindered by this lack of workup and many patients are unfortunately not treated appropriately and/or not offered appropriate prophylaxis for their level of thrombotic risk. The purpose of this case report is to not only increase the level of awareness among clinicians to initiate an appropriate diagnostic workup in patients presenting with anemia in the setting of ITP, but also to a heightened thrombotic risk warranting an appropriate thromboprophylaxis. This case also adds to the body of evidence that a "second-hit" phenomenon is often a precipitating cause for a thrombotic event.

Skin lesions are frequently encountered in clinical practice which can be a presentation of systemic diseases not excluding an occult malignancy. Commonly reported paraneoplastic dermatologic manifestations include acanthosis nigricans, dermatomyositis, erythroderma, hypertrophic osteoarthropathy, Sweet syndrome, and paraneoplastic pemphigus (PNP). PNP is a rare autoimmune mucocutaneous disease characterized by severe stomatitis, polymorphic skin eruptions, and associated underlying neoplasms most commonly non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and Castleman disease. PNP is characterized on histopathology as dyskeratotic epithelial cells with acantholysis with a typical immunofluorescence staining pattern of direct and/or indirect staining of intercellular, basement membrane, and dermoepidermal junction with immunoglobulin-G and C3. PNP has been described to have poor prognosis with a mortality range of 75-90% and a mean survival of less than 1year. We describe a previously unreported case of PNP associated with acute myeloid leukemia (AML) where the patient presented with a nonhealing ulcer and hemorrhagic crusting on the face that did not respond to antimicrobials and steroids. Investigations revealed leukocytosis with peripherally circulating blasts. Skin biopsy revealed an evolving PNP and bone marrow biopsy confirmed evidence of AML. The patient underwent induction, consolidation, and then successful allogenic bone marrow transplantation with complete remission. The skin lesion, which was initially refractory to treatments, surprisingly resolved within 7days of starting induction chemotherapy. In this case, the skin lesion was a key factor in early diagnosis and instituting treatment for the underlying AML. Early intervention gave our patient a better outcome with an ongoing survival of 18months since diagnosis, maintaining complete remission.