Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma

Combined Intrathoracic and Subcutaneous Splenosis Discovered 51 Years after Abdominal Trauma

Splenosis is a rare condition that results from the autotransplantation of splenic parenchyma into unexpected locations such as the abdomen or subcutaneous tissue. In the presence of coexisting injury to the diaphragm intrathoracic transplantation can occur emerging as single or multiple pleural-based masses. This occurs after traumatic rupture of the spleen and is usually asymptomatic, only to be discovered incidentally on routine thoracic or abdominal imaging. To our knowledge this is the third documented case of combined intrathoracic and subcutaneous splenosis found in English literature. This occurred in a 71-year-old male involved in a motor vehicle accident at age 19 requiring urgent splenectomy. He has a significant cigarette smoking history and was referred to our hospital for further evaluation of an abnormality seen on shoulder X-ray

Pneumocystis Pneumonia Presenting as an Enlarging Solitary Pulmonary Nodule

Pneumocystis pneumonia is a life threatening infection that usually presents with diffuse bilateral ground-glass infiltrates in immunocompromised patients. We report a case of a single nodular granulomatous Pneumocystis pneumonia in a male with diffuse large B-cell lymphoma after R-CHOP therapy. He presented with symptoms of productive cough, dyspnea, and right-sided pleuritic chest pain that failed to resolve despite treatment with multiple antibiotics. Chest X-ray revealed right lower lobe atelectasis and CT of chest showed development of 2 cm nodular opacity with ground-glass opacities. Patient underwent bronchoscopy and biopsy that revealed granulomatous inflammation in a background of organizing pneumonia pattern with negative cultures. Respiratory symptoms resolved but the solitary nodular opacity increased in size prompting a surgical wedge resection which revealed granulomatous Pneumocystis pneumonia infection. This case is the third documented report of Pneumocystis pneumonia infection within a solitary pulmonary nodule in an individual with hematologic neoplasm. Although Pneumocystis pneumonia most commonly occurs in patients with HIV/acquired immunodeficiency syndrome and with diffuse infiltrates, the diagnosis should not be overlooked when only a solitary nodule is present

Pneumocystis Pneumonia Presenting as an Enlarging Solitary Pulmonary Nodule

Pneumocystis pneumonia is a life threatening infection that usually presents with diffuse bilateral ground-glass infiltrates in immunocompromised patients. We report a case of a single nodular granulomatous Pneumocystis pneumonia in a male with diffuse large B-cell lymphoma after R-CHOP therapy. He presented with symptoms of productive cough, dyspnea, and right-sided pleuritic chest pain that failed to resolve despite treatment with multiple antibiotics. Chest X-ray revealed right lower lobe atelectasis and CT of chest showed development of 2 cm nodular opacity with ground-glass opacities. Patient underwent bronchoscopy and biopsy that revealed granulomatous inflammation in a background of organizing pneumonia pattern with negative cultures. Respiratory symptoms resolved but the solitary nodular opacity increased in size prompting a surgical wedge resection which revealed granulomatous Pneumocystis pneumonia infection. This case is the third documented report of Pneumocystis pneumonia infection within a solitary pulmonary nodule in an individual with hematologic neoplasm. Although Pneumocystis pneumonia most commonly occurs in patients with HIV/acquired immunodeficiency syndrome and with diffuse infiltrates, the diagnosis should not be overlooked when only a solitary nodule is present

Palmitoylation controls trafficking of GAD65 from Golgi membranes to axon-specific endosomes and a Rab5a-dependent pathway to presynaptic clusters

The GABA-synthesizing enzyme GAD65 is synthesized as a soluble cytosolic protein but undergoes post-translational modification(s) to become anchored to the cytosolic face of Golgi membranes before targeting to synaptic vesicle membranes in neuroendocrine cells. Palmitoylation of cysteines 30 and 45 in GAD65 is not required for targeting to Golgi membranes but is crucial for post-Golgi trafficking to presynaptic clusters in neurons. Here, we show that palmitoylated GAD65 colocalizes with the small GTP- binding protein Rab5a in Golgi membranes and in axons but not in dendrites. In the presence of the constitutively positive mutant Rab5(Q79L) palmitoylation resulted in polarized targeting of GAD65 to giant Rab5a-positive axonal endosomes, characterized by the absence of the Rab5a-effector molecule EEA1 and the transferrin receptor. By contrast, Rab5a-positive/EEA1-positive somatodendritic giant endosomes containing the transferrin receptor were devoid of GAD65. Palmitoylation-deficient GAD65 was excluded from endosomal compartments. A dominant negative mutant of Rab5a, Rab5a(S34N), specifically blocked axonal trafficking and presynaptic clustering of palmitoylated GAD65, but did not affect axonal trafficking of mutants of GAD65 that fail to traffic to giant axonal endosomes containing Rab5a(Q79L). Two transmembrane synaptic vesicle proteins, VAMP2 and VGAT also localized to the axonal giant endosomes, and their axonal trafficking and presynaptic clustering was blocked by Rab5a(S34N). The results suggest that palmitoylation of GAD65 regulates the trafficking of the protein from Golgi membranes to an endosomal trafficking pathway in axons that is dependent on Rab5a and is required for the targeting of several synaptic vesicle proteins to presynaptic clusters

Liver failure due to relapsed myeloma and hepatic iron overload

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myeloma. We present a case of a 49-year-old female with relapsed/refractory multiple myeloma who presented with rapid onset liver failure, due to both iron deposition and malignant plasma cell infiltration of the liver as a terminal event. A review of the literature on hepatic complications in multiple myeloma patients is presented

Management of Primary Plasma Cell Leukemia Remains Challenging Even in the Era of Novel Agents

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm 3 distinguishes it from MM. After initial stabilization and diagnosis confirmation, treatment of PCL in a fit patient typically includes induction combination chemotherapy containing novel agents typically, with proteasome inhibitors (such as bortezomib) and immunomodulatory drugs (eg, lenalidomide), followed by autologous hematopoietic stem cell transplant (HSCT) and multidrug maintenance therapy using novel agents post-HSCT. Long-term outcomes have improved employing this strategy but the prognosis for non-HSCT candidates remains poor and new approaches are needed for such PCL patients not eligible for HSCT. Here, we report a case of primary PCL, and a comprehensive and up to date review of the literature for diagnosis and management of PCL. We also present the findings of Positron Emission Tomography (PET) scan. Since PCL is often associated with extra-medulary disease, including PET scan at the time of staging and restaging may be a novel approach particularly to evaluate the extra-medullary disease sites