Deniz Peker

Acute myeloid leukemia, version 3.2017: Clinical practice guidelines in oncology

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.

Diffuse Large B‐Cell Lymphoma with Primary Treatment Failure: Ultra‐high Risk Features and Benchmarking for Experimental Therapies

The outcomes of patients with DLBCL and primary treatment failure (PTF) in the rituximab era are unclear. We analyzed 331 patients with PTF, defined as primary progression while on upfront chemoimmunotherapy (PP), residual disease at the end of upfront therapy (RD) or relapse < 6 months from end of therapy (early relapse; ER). Median age was 58 years and response to salvage was 41.7%. Two‐year OS was 18.5% in PP, 30.6% in RD and 45.5% in ER. The presence of PP, intermediate‐high/high NCCN‐IPI at time of PTF or MYC translocation predicted 2‐year OS of 13.6% constituting ultra‐high risk (UHR) features. Among the 132 patients who underwent autologous hematopoietic cell transplantation, 2‐year OS was 74.3%, 59.6% and 10.7% for patients with 0,1 and 2–3 UHR features respectively. Patients with PTF and UHR features should be prioritized for clinical trials with newer agents and innovative cellular therapy.

Myeloma cell–derived Runx2 promotes myeloma progression in bone

The progression of multiple myeloma (MM) is governed by a network of molecular signals, the majority of which remain to be identified. Recent studies suggest that Runt-related transcription factor 2 (Runx2), a well-known bone-specific transcription factor, is also expressed in solid tumors, where expression promotes both bone metastasis and osteolysis. However, the function of Runx2 in MM remains unknown. The current study demonstrated that (1) Runx2 expression in primary human MM cells is significantly greater than in plasma cells from healthy donors and patients with monoclonal gammopathy of undetermined significance; (2) high levels of Runx2 expression in MM cells are associated with a high-risk population of MM patients; and (3) overexpression of Runx2 in MM cells enhanced tumor growth and disease progression in vivo. Additional studies demonstrated that MM cell-derived Runx2 promotes tumor progression through a mechanism involving the upregulation of Akt/β-catenin/Survivin signaling and enhanced expression of multiple metastatic genes/proteins, as well as the induction of a bone-resident cell-like phenotype in MM cells. Thus, Runx2 expression supports the aggressive phenotype of MM and is correlated with poor prognosis. These data implicate Runx2 expression as a major regulator of MM progression in bone and myeloma bone disease.

A Close Association of Autoimmune-Mediated Processes and Autoimmune Disorders with Chronic Myelomonocytic Leukemia: Observation from a Single Institution

Chronic myelomonocytic leukemia (CMML), a clonal hematopoietic stem cell disease, may be linked to immune-mediated processes and/or autoimmune disorders (AID), although the exact pathogens are still elusive. We retrospectively analyzed 123 CMML patients in our institution. Twenty-four CMML patients (19.5%) had at least one immune-mediated disorder, most commonly idiopathic thrombocytopenic purpura, gout and psoriasis. Four of these 24 patients (15%) had more than one AID. We found that, in contrast to the general population with a prevalence rate of 3.2-5.2%, newly diagnosed CMML patients demonstrated a high prevalence and variety of immune-mediated processes and/or AID. When we compared the results with those of myelodysplastic syndromes published in the literature, the prevalence of AID in these two groups of patients is similar. Our results also showed that the presence of cytogenetic abnormalities was less in CMML patients with AID (6 of 21; 28.6%) than in those without AID (37 of 94; 39.4%), although there was no statistical significance (p = 0.334). A multicenter large cohort study of CMML with AID is recommended to illustrate the molecular relationship between the two distinct groups.

Unique presentation of blastic plasmacytoid dendritic cell neoplasm: a single-center experience and literature review

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. Very few cases of BPDCN have been described with lack of skin manifestations at the time of diagnosis. Here we report two rare non‐cutaneous presentations of BPDCN without obvious skin lesions at our institution and also the literature review. Our first patient had a unique presentation of BPDCN confined to the sinonasal region with central nervous system involvement. The second patient we report is also atypical with regard to widespread disease that uncharacteristically spared the skin and bone marrow. BPDCN is a rare hematological malignancy involving immature plasmacytoid dendritic cells. It poses a diagnostic challenge requiring multidisciplinary approach to manage this disease. It is important to identify effective therapies for both cutaneous and non‐cutaneous presentations of BPDCN, since most cases are uniformly fatal with conventional chemotherapy alone. High‐dose induction therapy based on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) regimens, to achieve complete remission followed by allo‐hematopoietic stem cell transplantation from related or unrelated donors is recommended to improve long‐term survival in these patients. Larger scale studies are warranted to understand the pathophysiology of the disease and the important prognostic indicators for optimal management. Copyright

Azathioprine induced Epstein Barr virus-positive mucocutaneous ulcer arising in perianal fistula and abscess associated with Crohn's disease

Dear Editor, Epstein Barr virus-positive (EBV +) mucocutaneous ulcer is a recently recognized entity associated with immunosuppression 1,2. We report a case of azathioprine induced EBV + lymphoproliferative disease (LPD) presenting at a site associated with long standing Crohns associated complex perianal fistulas and recurrent perianal abscess. A 63 year old man was diagnosed with Crohns disease (CD) approximately 30 years back after he presented with small bowel obstruction and was subsequently managed with ileocolic resection. He was medically treated by long term immunosuppression with azathioprine (150 mg per day) and then he recently underwent seton placement for the management of …

Extramedullary Involvement by Chronic Myelogeneous Leukemia in Five Patients With Unusual Clinicopathologic Features: A Review of the Effectiveness of Tyrosine Kinase Inhibitors

Chronic myelogeneous leukemia (CML) is associated with BCR-ABL1 fusion gene leading to an abnormal tyrosine kinase molecule. The accepted first-line treatment is imatinib mesylate (IM). CML uncommonly occurs in the extramedullary sites at initial presentation or relapse. Here we report five adult patients with CML who developed myeloid sarcoma (MS) while on treatment with IM. A retrospective medical chart analysis was performed to identify CML patients with MS who were diagnosed and treated at the University of Alabama at Birmingham. The age ranged between 21 and 36 years (median: 28.5) with a male to female ratio of 4:1. All of the patients were diagnosed with CML in chronic phase with initial treatment including IM. The median interval period between the initial diagnosis of CML and MS was 27 months (range 7 - 60 months). The sites of extramedullary involvement included lymph nodes (n = 2), central nervous system (n = 2) and hepatobiliary organs (n = 1). All patients were treated with either induction therapy or stem cell transplant (SCT) following the diagnosis of MS. The median survival was 16 months (range 1 - 72 months). The longest survival was observed in a patient who successfully received SCT therapy. IM is frequently used as the first therapeutic choice in new diagnosed CML; however, its penetration and effectiveness in extramedullary tissue is still unclear. The current report also supports the literature with less favorable prognosis of CML in younger individuals.

Malignant Transformation in Von-Meyenburg Complexes: Histologic and Immunohistochemical Clues With Illustrative Cases.

Benign developmental defects known as Von-Meyenburg complexes (VMCs) have been postulated to progress to cholangiocarcinoma (CC) in rare instances. Although a gradual, sequential histologic transition from VMCs to CC has been described in some of these cases, the underlying genetic mechanism is yet to be elucidated. Here, we review the literature to put together a report on the clinicopathologic features and immunohistochemical changes associated with such transformation. We also review the documented association between CC and p16INK4a inactivation, and discuss a possible role for this mechanism to contribute in VMCs to CC progression. In addition, using 2 illustrative cases encountered at our institute, we provide morphologic and immunohistochemical clues that can be used to detect such progression from hamartoma to malignancy. These cases and the accompanying review of literature further solidify the association between VMCs and CC.

Burkitt Lymphoma Arising From Lymphoplasmacytic Lymphoma Following Acquisition of MYC Translocation and Loss of the ETV6 Tumor Suppressor Gene

Lymphoplasmacytic lymphoma is a mature B-cell lymphoma with variable plasmacytic differentiation that displays an indolent clinical course. Its transformation to a high-grade B-cell lymphoma may occur uncommonly. Although acquisition of a MYC translocation could result in transformation of a low-grade lymphoma into diffuse large B-cell lymphoma, Burkitt lymphoma, or B-lymphoblastic leukemia, to our knowledge the latter 2 transformations have not been well documented in lymphoplasmacytic lymphoma. We report the case of a 70-year-old woman with a 9-year history of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia who presented with rapid enlargement of a left neck mass and pancytopenia, which was diagnosed as Burkitt lymphoma with extensive bone marrow involvement. A series of histopathologic, molecular, and cytogenetic evaluations proved a cytogenetic evolution including t(8;14)(q24;q32)/MYC-IgH and identical clonal B-cell gene rearrangements from the 2 distinct lymphomas, confirming stage 4 aggressive Burkitt lymphoma arising from lymphoplasmacytic lymphoma.

Plasmablastic microlymphoma arising in human herpesvirus-8-associated multicentric Castleman disease in a human immunodeficiency virus-seronegative patient with clinical response to anti-interleukin-6 therapy.

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