Al-Ola Abdallah

Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature

Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.

Successful Treatment of Bing-Neel Syndrome Using Intrathecal Chemotherapy and Systemic Combination Chemotherapy Followed by BEAM Auto-Transplant: A Case Report and Review of Literature

Neurological complications occur in approximately 25% ofpatients with WM. Although they are most often present as pe-ripheral neuropathy, hyperviscosity can produce central nervoussystem (CNS) changes that resolve promptly after plasma exchange.Rarely is the CNS directly involved as is the case in Bing-Neelsyndrome (BNS), which results from infiltration of pons, medulla,periventricular white matter, or leptomeningeal spaces by lympho-plasmacytoid cells.

Unilateral conjunctival AL kappa amyloidosis with trace evidence of systemic amyloidosis

Summary Background: Amyloidosis is a systemic disorder that results from the tissue deposition of various proteins with distinctive morphological characteristics. Conjunctival amyloidosis is a rare variant which is generally localized and not associated with systemic involvement. Case Report: We present here a case of 47-year-old female patient with right eyelid swelling that progressed over a 12 year period and eventually underwent surgery with pathology showing AL conjunctival amyloidosis. Unlike in most other reported cases of localized amyloidosis, she was noted to have amyloid deposition in the bone marrow and gastrointestinal tract upon extensive evaluation without any evidence of underlying plasma cell dyscrasia. She has been on observation without evidence of systemic progression or recurrence of conjunctival amyloid. Conclusions: Although it initially appeared that our case represented an isolated form of AL (kappa)-type conjunctival amyloidosis, systemic evaluation revealed trace amount of amyloid in the bone marrow and GI tract. It is feasible that upon very close scrutiny patients with seemingly localized AL amyloidosis may have trace amounts of amyloid involving other organs and based on experience from this single patient we believe that it is safe to observe such patients closely rather than pursue systemic therapy

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Multiple Myeloma in HIV-Positive Patients in the Highly Active Antiretroviral Therapy Era: The Myeloma Institute of Research and Therapy Experience

Introduction Non-Hodgkin lymphoma is the most common hematopoietic malignancy associated with acquired immune deficiency syndrome (AIDS). However multiple myeloma has also been reported a number f times in patients with human immunodeficiency virus (HIV) since 983 when the first case of a plasmacytoma was reported in a person with IV infection. Before the advent of highly active antiretroviral therapy (HAART) in 1996, the management of HIV-related hematopoietic malignancies was very difficult. High-dose chemotherapy and autologous stem cell transplantation (ASCT), which was standard therapy for he-

Pazopanib- and bevacizumab-induced reversible heart failure in a patient with metastatic renal cell carcinoma: A case report

Vascular endothelial growth factor receptor (VEGFR) antagonists are used in the treatment of metastatic renal cell carcinoma (mRCC) and other tumors. They are known to cause cardiovascular toxicities such as hypertension, left ventricular systolic dysfunction (LVSD), heart failure, thromboembolism, myocardial ischemia and infarction. Pazopanib is a tyrosine kinase inhibitor targeting (VEGFR)-1-2-3, plateletderived growth factor receptor (PDGFR)–a/-b and stem cell growth factor receptor, tyrosine protein kinase (c-kit). It is approved for the treatment of mRCC and soft tissue sarcoma. Severe LVSD is a rare but serious adverse effect of pazopanib with an incidence of less than 0.6% in patients with mRCC and 1% in patients with soft tissue sarcoma. We report a case of symptomatic reversible heart failure induced by pazopanib in a patient with mRCC, which recurred with subsequent bevacizumab treatment. To date, only five patients enrolled in various clinical trials developed severe LVSD after receiving pazopanib, and only two cases of pazopanib-associated heart failure are published. To our knowledge, this is the first case of recurrent heart failure caused from different vascular endothelial growth factor (VEGF) inhibitors which resolved after discontinuation of both agents.

Clinical Presentation and Gene Expression Profiling of Immunoglobulin M Multiple Myeloma Compared With Other Myeloma Subtypes and Waldenström Macroglobulinemia

Purpose Multiple myeloma (MM) is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated postgerminal B cells. It is a heterogeneous disease both at the genetic level and in terms of clinical outcome. Immunoglobulin M (IgM) MM is a rare subtype of myeloma. Similar to Waldenström macroglobulinemia (WM), patients with MM experience IgM monoclonal gammopathy; however, both diseases are distinct in terms of treatment and clinical behavior. Materials and Methods To shed light on the presentation of IgM MM, its prognosis, and its gene expression profiling, we identified and characterized 21 patients with IgM MM from our database. Results One of these patients presented with a rare IgM monoclonal gammopathy of undetermined significance that progressed to smoldering myeloma. The median survival of the 21 patients was 4.9 years, which was comparable to a matched group of patients with non-IgM MM with similar myeloma prognostic factors (age, gender, albumin, creatinine, anemia, lactate dehydrogenase, β2-microglobulin, cytogenetics abnormalities), but much less than the median survival reported for patients with WM (9 years). We identified a cluster of genes that differ in their expression profile between MM and WM and found that the patients with IgM MM displayed a gene expression profile most similar to patients with non-IgM MM, confirming that IgM MM is a subtype of MM that should be differentiated from WM. Conclusion Because the prognosis of IgM MM and WM differ significantly, an accurate diagnosis is essential. Our gene expression model can assist with the differential diagnosis in controversial cases.

Outcomes of VDPACE with Immunomodulator Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

27 mg/dL. Ibrutinib was held due to its common side effect, bleeding. The patient was referred to Urology to rule out bladder cancer with the concern of a prior history of cyclophosphamide treatment. Cystoscopy demonstrated mildly elevated bladder neck, otherwise normal for any acute pathology. Overall, it was thought that the benign bleeding could be from the prostatic urethra irritation and patient was started on tamsulosin. In the follow-up appointment patient had a bleeding for 20 minutes from the venipuncture site. The further evaluation for bleeding showed that patient had decreased vWF Ag (33%), vWF Activity (13%) and aVWFD was diagnosed. Meanwhile, patient’s IgM was 778 mg/dL. Ibrutinib was resumed considering that the IgM increased. In the next follow-up, patient’s bleeding symptoms were resolved and did not recur, his IgM decreased to 32 mg/dL and vWF Ag (229%), vWF Activity (204%) dramatically increased. Discussion: This case describes the challenge of diagnosing the etiology of bleeding in WM and highlights the importance of systematic approach. The incidence of hyperviscosity syndrome and related bleeding has decreased with early diagnosis of WM. Ibrutinib, a Bruton tyrosine kinase inhibitor used in WM has a main side effect of bleeding related to abnormalities in platelet aggregation. aVWFD can be associated with various mechanisms affecting vWF: autoantibodies, decreased synthesis, adsorption on cancer cells, damage. IgM autoantibodies against vWF in WM and associated aVWF disease is rarely observed. Although there are several mechanisms for bleeding in WM, the systematic approach to evaluate will be key to elucidate the underlying diverse mechanisms.

Image Diagnosis: Splenic Infarction Associated with Oral Contraceptive Pills in a Healthy Young Woman

CASE PRESENTATION A 23-year-old white woman with no significant medical history presented to the Emergency Department with 3 days of progressively worsening left upper quadrant abdominal pain. She described the pain as a constant, “pressure-like” pain, radiating to her back and associated with nausea. She denied any vomiting, constipation, diarrhea, fever, chills, rigors, night sweats, weight loss, loss of appetite, dysuria, hematuria, urinary frequency, history of trauma, or personal history or family history of thromboembolism. She had never smoked and denied any alcohol or illicit drug use. She had been taking oral contraceptive pills (OCP)—norgestimate and ethinyl estradiol—for several years. Physical examination revealed a normal body mass index and tenderness in the left upper quadrant of the abdomen. Laboratory work-up showed a white blood cell count of 13.5 K/μL, with an absolute neutrophils count of 10.8 K/μL, hemoglobin of 14.2 g/dL, platelet count of 249 K/μL, serum sodium of 136 mmol/L, serum potassium of 3.1 mmol/L, creatinine of 0.8 mg/dL, lipase of 15 U/L, and LDH of 175 IU/L. Urine analysis was unremarkable, and blood cultures were negative. Further laboratory work-up revealed a partial thromboplastin time of 21.2 seconds (23.0-36.9 s) and a prothrombin time of 13.5 seconds (12.0-14.7 s). Hypercoagulability work-up was negative for factor V Leiden or prothrombin gene mutations. Her antithrombin III activity was 106% (80%-120%), protein C activity was 175% (70%-160%), protein S activity was 91% (65%-140%), activated protein C resistance ratio was 2.53 (2.00-4.00 ratio), and fibrinogen was normal. Anticardiolipin IgG, anticardiolipin IgM, antibeta-2 glycoprotein IgM, anti-eta-2 glycoprotein IgG, and lupus anticoagulant were all negative. Paroxysmal nocturnal hemoglobinuria panel, hepatitis B and C panel, antinuclear antibody panel, and HIV-1 and HIV-2 Ab screens were also negative. High-performance liquid chromatography results were negative for sickle cell trait. Peripheral blood smear showed leukocytosis with neutrophilia, with no evidence of dysplastic changes or immature myeloid or lymphoid cells, including blasts. The red blood cells were normal in morphology without schistocytes or spherocytes. A computed tomography (CT) scan of the abdomen revealed a 5.7 cm x 3.0 cm x 3.3 cm wedge-shaped area of nonenhancement in the superior and medial aspect of the spleen, most consistent with an infarction (Figures 1 and 2). A CT scan of the chest was negative for pulmonary arteriovenous malformation, and venous Doppler ultrasound of the lower extremities was negative. The splenic artery and vein appeared normal with no evidence of arterial occlusion or venous thrombosis. An echocardiogram showed a normal ejection fraction, with no regional motion abnormalities and no vegetation, though there was a small physiologic right-to-left shunt. The patient was advised to discontinue the OCP. Because OCP use has been associated with increased risk of thromboembolic events,1-3 and because our patient was symptomatic because of her splenic infarct, she was started on anticoagulation therapy with a full dose of enoxaparin 1 mg/kg twice a day and warfarin 5 mg oral daily. Once her international normalized ratio

Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib.

INTRODUCTION Metastatic renal cell carcinoma (RCC) to the head and neck is rare. It is the third-most common cause of distant metastasis to the head and neck, after breast cancer and lung cancer. Several drugs are available to treat metastatic RCC including high-dose interleukin and targeted therapy. Immunotherapy with nivolumab was recently approved by the US Food and Drug Administration (FDA) as a second-line treatment for patients with metastatic RCC. CASE PRESENTATION We present a case of metastatic RCC in a 71-year-old man with a single complaint of a 1-year history of pain while chewing food. Positron emission tomography-computed tomography showed diffuse metastatic disease. Nivolumab, off-label use before its recent FDA approval, was combined with sunitinib and resulted in an excellent and ongoing response. DISCUSSION RCC is the third-most common cause of distant metastasis to the head and neck. The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease. The other important aspect of this case is the almost complete response of his metastatic disease to the combination of nivolumab and sunitinib that was used off label before the FDA issued the approval. Future clinical trials should look at combining immunotherapy with targeted therapy in metastatic RCC.

A unique presentation of unilateral pleural effusion in a patient with a high-grade plasma cell neoplasm

High-grade plasma cell neoplasms include multiple myeloma with plasmablastic morphology, primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL) [1]. Although these entities have specific diagnostic criteria in the World Health Organization (WHO) Classification [1], there may be some overlap in the clinical presentation of these diseases. Furthermore, occasional rare patients present with highgrade plasma cell neoplasms that do not fit well into any defined category. Here we describe a case of a high-grade plasma cell neoplasm in a HIV-negative, elderly patient with a unique presentation of unilateral pleural effusion preceding development of lymphadenopathy. This case illustrates the challenges that may occur in the diagnosis and treatment of an atypical high-grade plasma cell neoplasm. The patient was a 70-year-old man with a history of stage IV diffuse large B-cell lymphoma (DLBCL) diagnosed in July 2006 when he was 63 years old. Malignant B cells had centroblastic morphology, expressed CD20, BCL2 and BCL6 without CD138 expression, and had a hyperdiploid karyotype with multiple structural and numerical abnormalities. Fluorescence in situ hybridization (FISH) analysis revealed 3-6 non-rearranged MYC gene signals that were consistent with 3-6 copies of chromosome 8 seen in karyotype. The patient received eight cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy and remained in complete remission until February 2014, at which time the patient presented to the hospital with shortness of breath and left sided pleuritic chest pain. He denied hemoptysis, cough, fever, chills, rigors, night sweats, weight loss or loss of appetite. Chest X-ray (CXR) revealed interval development of a moderate left pleural effusion, and subsequent computed tomography (CT) scan of the chest and abdomen showed a large left pleural effusion with near complete atelectasis of the left lower and lingual lobes [Figure 1(A)]. There was no interval development of lymphadenopathy in the chest, abdomen or retroperitoneum and no lymphadenopathy in the supraclavicular and axillary regions. A therapeutic and diagnostic thoracentesis showed a heavily blood stained pleural effusion with lactate dehydrogenase (LDH) 3120 IU/L, white blood cells (WBC) 18 600/mm3 and red blood cells (RBC) 390 000/mm3. Bacterial culture of the fluid was negative. Cytologic smear of the fluid showed a large population of malignant cells with plasmacytic/plasmablastic features [Figure 1(B)]. Immunohistochemical staining showed that the malignant cells were positive for CD138, but negative for CD20, PAX-5, BCL2, BCL6, cytokeratin AE1/AE3, S-100, CK5/6 and TTF-1 (data not shown). The malignant cells were negative by immunohistochemistry for human herpesvirus 8 (HHV8) and negative by in situ hybridization for EBV-encoded RNA (EBER). Flow cytometry of the pleural fluid showed that the malignant cells were positive for CD38, CD56, CD138 and CD79b, but negative for CD3, CD5, CD10, CD19, CD20, CD22, CD30, CD34 and CD45. FISH analysis revealed that the malignant cells were positive for two different IGH rearrangements, FGFR3-IGH and MYC-IGH, with an extra chromosome 1q signal. Malignant cells were negative for CCND1–IGH or IGH–MAF fusions and negative for BCL2 gene rearrangement. Cytogenetic analysis of the pleural fluid revealed a complex hypodiploid clone in all cells analyzed [45,X,  Y, add (1)(p12), add (1)(q25), add (2)(p16), del (5)(q31),  7,  8, add (10) (q24),  13, del (13;14)(q10;q10), add (15)(q26), add (17) (q21),  18,  3mar] not clonally related to the DLBCL diagnosed in 2006. Laboratory values showed a normal complete blood count (CBC), normal serum creatinine, calcium and LDH. Serum protein electrophoresis (SPEP) showed a faint M spike identified by immunofixation electrophoresis (IFE) as immunoglobulin G (IgG) kappa, with a serum free kappa light chain of 41.8 mg/dL, serum free lambda light chain of Leukemia & Lymphoma, October 2015; 56(10): 2989–2991