Offiong Francis Ikpatt

Biased Use of the IGHV4 Family and Evidence for Antigen Selection in Chlamydophila psittaci-Negative Ocular Adnexal Extranodal Marginal Zone Lymphomas

Extranodal marginal zone lymphomas (EMZL) are the most common lymphomas in the ocular adnexa. The etiology and potential role for antigenic stimulation in these lymphomas are still controversial. We have examined IGHV gene usage and mutations in 67 Chlamydophila psittaci-negative ocular adnexal EMZL. Clonal IGHV gene sequences were identified in 43 tumors originating from the orbit (19), conjunctivae (18) and lacrimal gland (6). Forty four potentially functional clonal IGHV gene sequences were detected with overrepresentation of the IGHV4 family and IGHV4-34 gene. All but 3 sequences were mutated with the average percent homology to the germ line of 93.5±6.1. Multinomial model and Focused binomial test demonstrated evidence for positive and/or negative antigen selection in 59% of the potentially functional IGHV genes. Intraclonal variation was detected in 8 of 11 tumor specimens. Overall our findings demonstrate that C. psittaci-negative ocular adnexal EMZL exhibit biased usage of IGHV families and genes with evidence for intraclonal heterogeneity and antigen selection in multiple tumors, implicating B-cell receptor-mediated antigen stimulation in the pathogenesis of these lymphomas.

Molecular and genomic aberrations in Chlamydophila psittaci negative ocular adnexal marginal zone lymphomas.

The etiology and pathogenesis of ocular adnexal extranodal marginal zone lymphoma (OAEMZL) are still unknown and the association with Chlamydophila psittaci (C. psittaci) has been shown in only some geographic regions. Herein, we comprehensively examined the frequency of chromosomal translocations as well as CARD11, MYD88 (L265P), and A20 mutations/deletions in 45 C. psittaci negative OAEMZLs. t(14;18)(q32;q21) IGH‐MALT1 and t(11;18)(q21;q21) API2‐MALT1 were not detected in any of the analyzed tumors while three tumors harbored IGH translocations to an unidentified partner. CARD11 mutations were not found in all analyzed tumors, while the MYD88 L265P mutation was detected in three (6.7%) tumors. A20 mutations and deletions were each detected in seven (15.6%) and six (13.3%) tumors, respectively. Therefore, the observed genetic aberrations could account for the activation of the nuclear factor (NF)‐kB signaling pathway in only a minority of the cases. Further studies are needed to identify the molecular mechanisms underlying the pathogenesis of OAEMZL. Am. J. Hematol. 88:730–735, 2013.

Post-transplant lymphoproliferative disorder presented as small bowel intussusception in adult liver transplant patient.

Intestinal obstruction after liver transplant is a rare complication, with diverse clinical manifestations. Intestinal adhesion is the most common cause. However, internal hernia, abdominal wall hernia, and neoplasm are also reported. Intussusception is another rare cause of intestinal obstruction, which has been reported primarily in pediatric patients. Herein, we report a case of intestinal obstruction from intussusception in an adult liver transplant patient associated with post-transplant lymphoproliferative disorder.

Diffuse large B-cell lymphoma presenting as miller fisher syndrome

We report a patient with diffuse large B‐cell lymphoma (DLBCL) who initially presented as Miller Fisher syndrome (MFS) responsive to high‐dose immunoglobulin treatment. Detailed investigations for the recurrence of neurological symptoms revealed DLBCL that was responsive to chemotherapy. DLBCL should be considered in the differential diagnosis of patients with MFS who have worsening of their neurological condition after initial improvement with conventional therapy. Muscle Nerve 45: 138–143, 2011

GENETICS OF BREAST CANCER IN WOMEN OF AFRICAN DESCENT: AN OVERVIEW

In 2003, an estimated 20,000 new cases of breast cancer were diagnosed among black women in the United States, making it the most common malignancy in this population (1). The rates of breast cancer incidence in Caucasian women and African American women are 113.2 and 99.3 cases per 100,000, respectively (1). In West Africa, the founder population of most African Americans, breast cancer has been considered to be a rare virulent disease of young women. According to the International Agency of Research on Cancer, breast cancer incidence in seven African countries has doubled, going from an average of 15.3 cases per 100,000 in 1976 to 33.6 per 100,000 in 1998 (2) (also see the contribution of Max Parkin in this book). This could be due to an actual increase in incidence or may be the result of improved reporting of cases. Unfortunately, the large numbers of resource poor nations in Africa make it extremely difficult to have accurate estimates of the number of breast cancer cases diagnosed in those countries. Nevertheless, the incidence of cancer, in general, appears to have increased in Africa and may likely be related to the changes in social conditions, life-style, and emergence of the AIDS epidemic (3). Although the AIDS epidemic has resulted in a striking increase in the incidence of Kaposi’s sarcoma (now the most common cancer in Africa), there has not been an increase in incidence of AIDS-associated breast cancer (4, 5).

Acute spontaneous tumor lysis syndrome as the initial presentation of ALK-positive diffuse large B-cell lymphoma

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a recently described, uncommon form of DLBCL, which has been seen primarily in young men and which presents with advanced disease. The fact that ALK-positive DLBCL is an uncommon diagnosis is likely due to the combined effects of this being an uncommon disease coupled with the challenges in the pathologic identification of this neoplasm. Prompt and accurate identification of this tumor is becoming increasingly important, however, as we enter the era of therapeutic ALK inhibitors, which are currently undergoing study in several clinical trials. Here, we report a case of ALK-positive DLBCL in a 39-year-old male patient who presented with spontaneous tumor lysis syndrome. We review the clinical, morphologic, immunohistochemical, and molecular aspects of this case and of ALK-positive DLBCL in general, with the purpose of bringing to light the existence of this disease and its potential future therapy.

Anaphylactic reaction to platelet transfusion as the initial symptom of an undiagnosed systemic mastocytosis: a case report and review of the literature

IntroductionThe association between anaphylactic reactions and systemic mastocytosis is well documented. However, platelet transfusion has not previously been reported as a potential elicitor of anaphylaxis in the context of systemic mastocytosis.Case presentationWe describe the clinicopathological findings of a 59-year-old Latin American man who presented to the emergency room with fatigue, leukocytosis, thrombocytopenia and mild hepatosplenomegaly. He developed two separate, temporally associated and severe anaphylactic reactions after receiving platelet transfusions. The result of a laboratory investigation for clerical errors and Coombs test was negative. Pre- and post-transfusion urine samples were negative for hemolysis. Bone marrow biopsy and aspirate smears performed demonstrated involvement by systemic mastocytosis, which had been previously undiagnosed.ConclusionsWe posit the transfusion reaction to be an anaphylactic reaction to transfused products as a result of heightened allergic sensitivity due to the underlying systemic mastocytosis. To the best of our knowledge, this is the first reported case of a severe anaphylactic-type reaction to blood products occurring in the setting of a previously undiagnosed systemic mastocytosis. Furthermore, it seems there are no published studies closely examining the relationship between hematopoietic neoplasms and transfusion reactions in general.

Use of Web-based training for quality improvement between a field immunohistochemistry laboratory in Nigeria and its United States-based partner institution

The importance of hormone receptor status in assigning treatment and the potential use of human epidermal growth factor receptor 2 (HER2)-targeted therapy have made it beneficial for laboratories to improve detection techniques. Because interlaboratory variability in immunohistochemistry (IHC) tests may also affect studies of breast cancer subtypes in different countries, we undertook a Web-based quality improvement training and a comparative study of accuracy of immunohistochemical tests of breast cancer biomarkers between a well-established laboratory in the United States (University of Chicago) and a field laboratory in Ibadan, Nigeria. Two hundred and thirty-two breast tumor blocks were evaluated for estrogen receptors (ERs), progesterone receptors (PRs), and HER2 status at both laboratories using tissue microarray technique. Initially, concordance analysis revealed κ scores of 0.42 (moderate agreement) for ER, 0.41 (moderate agreement) for PR, and 0.39 (fair agreement) for HER2 between the 2 laboratories. Antigen retrieval techniques and scoring methods were identified as important reasons for discrepancy. Web-based conferences using Web conferencing tools such as Skype and WebEx were then held periodically to discuss IHC staining protocols and standard scoring systems and to resolve discrepant cases. After quality assurance and training, the agreement improved to 0.64 (substantial agreement) for ER, 0.60 (moderate agreement) for PR, and 0.75 (substantial agreement) for HER2. We found Web-based conferences and digital microscopy useful and cost-effective tools for quality assurance of IHC, consultation, and collaboration between distant laboratories. Quality improvement exercises in testing of tumor biomarkers will reduce misclassification in epidemiologic studies of breast cancer subtypes and provide much needed capacity building in resource-poor countries.

Bone Marrow-Liver-Spleen Type of Large B-Cell Lymphoma Associated with Hemophagocytic Syndrome: A Rare Aggressive Extranodal Lymphoma

Recently, an unusual subtype of large B-cell lymphoma (LBCL) with distinctive clinicopathologic features has been recognized; it is characterized by involvement of bone marrow with or without liver and/or spleen, but no lymph node or other extranodal sites, usually associated with fever, anemia, and hemophagocytic lymphohistiocytosis (HLH). Because of this distinctive clinical presentation, it has been designated “bone marrow-liver-spleen” (BLS) type of LBCL. To date there is only one series of 11 cases of BLS type of LBCL with detailed clinical, pathologic, and cytogenetic data. Herein, we describe a case of BLS type LBCL presenting with associated HLH in a 73-year-old female. The bone marrow core biopsy showed cytologically atypical large lymphoma cells present in a scattered interstitial distribution and hemophagocytosis and infrequent large lymphoma cells were seen in the bone marrow aspirate smears. Circulating lymphoma cells were not seen in the peripheral blood smears. The patient underwent treatment with chemotherapy (R-CHOP) but unfortunately passed away 2 months after initial presentation. BLS type of LBCL is a very rare and clinically aggressive lymphoma whose identification may be delayed by clinicians and hematopathologists due to its unusual clinical presentation and pathologic features.