Naseem Uddin

Bright CD38 expression is an indicator of MYC rearrangement

The MYC gene (at 8q24, previously referred to as C-MYC) rearrangement (R) with immunoglobulin heavy chain gene (IGH) [t(8;14)(q24;q32)] or light chain genes [t(2;8)(p12;q24) or t(8;22)(q24;q11.2)] is an essentially constant genetic feature of Burkitt lymphoma [1]. However, this rearrangement can also be observed occasionally in other high grade Bcell lymphomas [2–5], many of which likely belong to the newly proposed category of ‘B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma’ in the 2008 WHO classification scheme. The prompt diagnosis of Burkitt lymphoma and its histological mimics carrying MYC R is of great clinical importance because of the aggressiveness of these lymphomas and the requirement of different therapeutic strategies. Previous studies have largely focused on immunohistochemical markers, such as high proliferation fraction (MIB-1 or Ki-674 90%), typical immunophenotype of CD10þ/bcl-6þ/bcl-27, and CD38þ/ CD44/T-cell leukemia-1þ(TCL-1), to predict the presence of MYC R [2–6]. Recently, two groups reported that differential gene expression patterns could accurately distinguish between high grade B cell lymphoma with or without MYC R [7,8]. Although these markers have moderate to excellent predictive power, they are not available to make immediate management decisions. In contrast, multi-parameter flow cytometry (MFC) immunophenotyping can be available within hours of a primary diagnostic procedure, such as a biopsy or fine needle aspiration (FNA). In light of the differential expression of CD38 in high grade B-cell lymphoma with and without MYC R, we aimed at defining the predictive power of CD38 expression analysed by MFC for MYC R. We used the institutional MFC and cytogenetics databases to search for cases of CD10(þ) B-cell lymphoma of medium to large cell size (so-called high grade B-cell lymphoma) with available MYC R fluorescence in situ hybridisation (FISH) analysis and/or conventional cytogenetics diagnosed from 2002 to 2008. This yielded 106 cases that were divided according to MYC status into three groups: 54 cases with MYC R in group I [50 cases with t(8;14)(q24;q32), 3 with t(2;8)(p12;q24) and 1 with t(8;22)(q24;q11.2)], 13 cases with numerical abnormalities of MYC (extra MYC signal) in group II, and 39 cases with normal MYC in group III. Of note, about one fourth of cases had a conventional karyotype, none of which showed evidence for other recurrent translocations such as t(14;18). The remaining cases were subjected to FISH analysis for t(8;14) only. In the cases with MYC R, there were no additional aberrant signals involving chromosome 14 to suggest a concurrent translocation involving immunoglobulin heavy chain gene [such as t(14;18)]. The four 4-color combinations (FITC/PE/PerCP/ APC) used to characterise the B-cell populations were CD10/CD19/CD20/CD38, kappa/lambda/20/ 38, lambda/kappa/CD5/CD19 and FMC-7/CD23/ CD5/CD19. The level of CD38-APC expression (clone HB7 from BD Biosciences) was quantified as mean fluorescence intensity (MFI) and classified as

Cytogenetic and Molecular Characterization of a Partial Trisomy 2p Arising From Inverted Duplication of 2p With Terminal Deletion of 2pter

Partial trisomy 2p is typically associated with partial monosomy of another chromosomal segment and results from a balanced translocation in one of the parents. Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes. Several cases initially interpreted as terminal duplications have instead been documented to represent inverted duplications with terminal deletions. Inv dup del(2p) has been reported in patients who manifest the clinical findings of trisomy 2p syndrome. Here we report on a 2‐month‐old girl with inv dup del(2p) and clinical manifestations that overlap those found commonly in partial 2p trisomy, as previously reported in the literature. Her clinical picture helps delineate the phenotype of 2p duplication disorders.

Colonic perforations in enteric fever.

We report a case of multiple colonic perforations in a 5-year-old boy due to typhoid fever. The main objective is to present the occurrence of this complication and discuss the management. The patient was admitted with nine days history of high-grade fever and abdominal pain. On examination, he was very sick looking child with acute abdomen. After initial workup and resuscitation, laparotomy was performed which revealed multiple colonic perforations with feacal peritonitis. The case revealed that one must not forget to inspect entire intestine including colon, as there may be perforations present in the large bowel.

Congenital Infantile Fibrosarcoma mimicking a cutaneous vascular lesion: A Case Report and Review of the Literature

Congenital infantile fibrosarcoma (CIFS) is a rare neoplasm of infancy that occurs most frequently in the extremities, and when presenting in the skin, may sometimes resemble infantile hemangiomas or other vascular lesions. Clinically, these tumors differ from hemangiomas in the time of onset, morphology, and growth pattern and must be evaluated histologically for definitive diagnosis. We describe an infant with a neoplasm involving the distal left forearm initially presumed to be a vascular lesion after evaluation by two separate ultrasound studies. He presented at seven weeks of life with a multinodular lesion that had enlarged significantly since birth, and the skin biopsy revealed a fibrosarcoma. This case highlights an unusual cutaneous presentation of CIFS, which varies in appearance from the previous 12 cases reported in the literature. We review the clinical manifestations of these congenital masses and emphasize early diagnosis for conservative therapy and improved prognosis.

Constitutional trisomy 8 mosaicism in a healthy bone marrow donor: Confirmation of first reported donor origin trisomy 8†

Between 1981 and 2010, we have treated 40 patients requiring chronic transfusion with periodic manual erythrocyte exchange and autologous plasma rescue (MEEX). Here, we present retrospective, long-term (median 22, range 14–29 years) follow-up data for a subset of seven patients with sickle cell syndromes who did not respond to hydroxyurea (HU). Patient characteristics are listed in Supporting Information, Tables I and II. MEEX was accomplished by using a single venous access and infusing 500 ml of isotonic solution (for adults) and removing 500 ml blood (range 400–600 ml according to the patient’s weight and the physician’s discretion). The rescue process involves centrifugation of the collected blood product and reinfusion of autologous plasma. This is followed by another 500 ml phlebotomy and the infusion of 2–3 units of packed Rh-matched, leuko-filtered, plasma-depleted red cells, with the aim of lowering HbS levels to around 40%. For pediatric patients, the bleeding volume is smaller (5–10 cc/Kg) and the volumes of infused saline and packed Rhmatched, leuko-filtered, plasma-depleted red cells are equal to the phlebotomy volumes, without plasma rescue. The interval between each MEEX procedure for these seven patients ranged from 45 to 90 days to maintain at all times HbS concentrations below 60–70% and the median number of procedures was 133 (range 85–204). None of the seven patients experienced acute complications of sickle cell disease (SCD), such as acute chest syndrome, splenic sequestration, stroke, bone necrosis, or priapism, or long-term complications such as renal failure, cerebrovascular or retinal damage, or pseudoxanthoma-like manifestations. None of the seven patients experienced alloimmunization and all but one patient had normal liver iron concentrations [assessed by superconducting quantum interference device, magnetic iron detector, magnetic resonance imaging (MRI), or biopsy]. This patient, who started the program at the age of 26 years with iron overload due to previous transfusions, required regular iron chelation therapy. Cardiac function tests indicated that all subjects had a left ventricular ejection fraction of >60% and cardiac T2 * > 20 mms (measured by MRI). There was no evidence of pulmonary arterial hypertension on echocardiography. During the observation period, five patients required hospitalization (four with acute cholecystitis and one due to venous occlusive crisis). Only one patient requires chronic analgesia (to relieve pain caused by pre-existing femur head necrosis). Automated EEX (AEEX) ensures lower postprocedural HbS levels (30% HbS vs. 40% with our MEEX protocol) because it makes use of two distal ports to increase the volume of red cells removed. However, the larger number of transfused units in AEEX exposes the patient to a higher transfusional risk. In addition, the automated procedure is significantly more expensive than the manual one, as indicated in Table I. Previous studies have indicated that EEX is a safe and efficacious alternative to both HU and simple transfusions for preventing complications of SCD and improving patients’ quality of life [1,2]. Our results with MEEX confirm previous findings including that if MEEX is started before significant iron overload occurs, the need for chelation therapy may be obviated [3]. Given the relative simplicity and the lower cost, MEEX should be considered for chronic transfusion therapy in developing countries [4].

IKBKG Mutation With Incontinentia Pigmenti and Ring-Enhancing Encephalopathy.

IKBKG Mutation With Incontinentia Pigmenti and Ring-Enhancing Encephalopathy Incontinentia pigmenti (IP, Bloch-Sulzberger syndrome) is an X-linked dominant genodermatosis affecting skin and other organs, including the brain, with variable expressivity. Incontinentia pigmenti results from mutations in the inhibitor of κ-βkinase-γ gene (IKBKG), which is located on Xq28. Deletions in this gene result in loss of function, leading to a wide variety of manifestations.1 This mutation is often lethal in males, resulting in miscarriage of male fetuses. Previously proposed revised diagnostic criteria2 included as major criteria any of 4 types of IP skin lesions and several minor criteria including anomalies of the brain, eyes, oral cavity, breasts, nipples, hair, and nails in a typical context of multiple male miscarriages and characteristic skin histopathology findings.