Kamilia Rizkalla

Modulation of T cell activation by stomatin-like protein 2.

T cell activation through the Ag receptor (TCR) requires sustained signaling from signalosomes within lipid raft microdomains in the plasma membrane. In a proteomic analysis of lipid rafts from human T cells, we identified stomatin-like protein (SLP)-2 as a candidate molecule involved in T cell activation through the Ag receptor. In this study, we show that SLP-2 expression in human primary lymphocytes is up-regulated following in vivo and ex vivo activation. In activated T cells, SLP-2 interacts with components of TCR signalosomes and with polymerized actin. More importantly, up-regulation of SLP-2 expression in human T cell lines and primary peripheral blood T cells increases effector responses, whereas down-regulation of SLP-2 expression correlates with loss of sustained TCR signaling and decreased T cell activation. Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation.

Interstitial Deletion of 8(q13q22) in Diffuse Large B-Cell Gastric Lymphoma

An interstitial deletion in the long arm of chromosome 8 as the sole structural anomaly was detected in a primary gastric diffuse large B-cell lymphoma, high-grade mucosa-associated lymphoid tissue (MALT) type, from a 74-year-old man. Low-grade MALT lymphoma was not seen in the sections submitted for examination. Helicobactor pylori organisms were found in a biopsy performed prior to resection of the tumor. The karyotype was described as 45, X,-Y,del(8)(q13q22). No rearrangement between chromosome 8 and others was detected with fluorescence in situ hybridization using a whole chromosome 8 painting probe. Fluorescence in situ hybridization with the C-MYC gene showed its normal location at 8q24 on both chromosomes 8 without rearrangement. Amplification of C-MYC was not detected in interphase cells. Deletion of 8q may represent a unique genomic alteration in this particular subtype of primary gastric lymphoma.

Extensive Bone Marrow Necrosis in a Case of Acute Myeloid Leukemia Transformed from a Myeloproliferative Neoplasm.

Extensive necrosis affecting more than 50% of the bone marrow is an extremely rare histopathological finding. Relatively little is known about its clinical significance because it is most commonly identified at autopsy - whether it is an independent prognostic marker or whether it is a surrogate marker of underlying disease burden remains unclear. We describe herein a case of a 66-year-old patient with acute myeloid leukemia who presented with acute bone marrow failure and was found to have extensive necrosis. We include presenting clinical features, pathology attained at biopsy, and the challenge of treatment. Bone marrow necrosis is a rare but important clinicopathological entity whose recognition may herald the way for more effective prognostication of underlying disease.

Mediastinal Choriocarcinoma Masquerading as Relapsed Hodgkin Lymphoma

Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL). A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) alternating with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). He achieved a complete remission after 6 cycles. Ten years after treatment, the patient presented with a persistent cough, haemoptysis, right supraclavicular lymphadenopathy, and weight loss. His chest X-ray showed opacification of the lower right hemithorax with a widened mediastinum. Given unresponsiveness to several antibiotics and lack of evidence for lung volume loss, there were concerns over lung infiltration with relapsed lymphoma. Transbronchial fine needle aspiration biopsy suggested recurrence of his HL. MOPP alternating with ABVD was again given. Due to disease progression, brachytherapy as well as a cocktail of dexamethasone, cytarabine, and cisplatin were also tried. However, on a subsequent excisional lymph node biopsy, it turned out that the tumour was in fact choriocarcinoma and not relapsed HL. Unfortunately, despite aggressive therapy, the patient’s disease rapidly progressed, and he died within 2 weeks.

Leishmaniasis involving the bone marrow of a patient with multiple myeloma

Dear Editor, A 64-year-old man with multiple myeloma was treated with high-dose dexamethasone followed by autologous stem cell transplant and, subsequently, lenalidomide plus dexamethasone for relapsed disease with a very good partial response. After 2 years of therapy, he developed progressive pancytopenia with total white blood cell count 1.5×10/L, hemoglobin 93 g/L, platelet count 81×10/L, and neutrophil count 0.7×10/L. Despite holding lenalidomide and dexamethasone, there was no improvement in his pancytopenia. The serum protein electrophoresis showed a marked polyclonal gammopathy (total IgG 57.6 g/L), and a bone marrow aspirate showed a polyclonal plasma cell population representing about 10 % of the total nucleated cell count. Importantly, the aspirate showedmany intraand extracellular microorganisms (Fig. 1). CTscan of the abdomen showed hepatosplenomegaly without any focal definitive lesions. Further history revealed that he had spent a week in Texas on a farm that housed imported exotic animals (including zebras and deer from Africa and South America) several months prior to developing this pancytopenia. Extensive serological tests for infectious causes of his presentation including toxoplasmosis, histoplasmosis, coccidioidomycosis, Q fever, and cat scratch disease were negative. Fungal culture was done from the aspirate and was negative. Due to clinical concern about the possibility of visceral leishmaniasis, leishmaniasis serology was evaluated and found to be positive. Subsequent polymerase chain reaction (PCR) test confirmed the diagnosis of visceral leishmaniasis. Initial treatment with liposomal amphotericin was started, but due to an immediate rise in serum creatinine, this therapy was discontinued and the patient received miltefosine. Within 2 weeks, all blood counts were back to normal. Miltefosine was given for 28 days followed by secondary prophylaxis with amphotericin every 3 weeks for 9 months. Currently, the patient has been off all medications for 6 months without signs of leishmaniasis recurrence. His blood counts remain normal, his polyclonal gammopathy resolved, and his multiple myeloma remains in complete remission. Leishmaniasis is a vector-borne disease that is caused by an obligate intra-macrophage protozoa. It is endemic in large areas of the tropics, subtropics, and the Mediterranean basin. This disease is characterized by both diversity and