Multiple myeloma with massive proliferation of signet ring cell like plasma cells: a case report

Vascular endothelial growth factor receptor 3 is a novel marker differing CD138-positive and CD138-negative multiple myeloma cells.

HIF-2α Upregulates CCR1 to Promote Dissemination of Plasma Cells in Multiple Myeloma

Plasma cell neoplasms (multiple myeloma, solitary plasmocytoma of bone and extra medullar plasmocytoma) are characterized by a monoclonal neoplastic proliferation of plasma cells. Multiple myeloma is a monoclonal malignant proliferation of plasma cells that causes osteolytic lesions in the vertebrae, ribs, pelvic bone, skull and jaw. We report a case of a 69-year-old male patient who presented with a tumefaction in the body of mandible, which had evolved over the previous two months. In the radiographic examination, an extensive osteolytic lesion was observed in the body of mandible. An incisional biopsy was performed and histopathological study revealed a malignant hematopoietic neoplasm formed by plasmacytoid cells. Knowledge about the maxillofacial manifestations of multiple myeloma is important for the early diagnosis of the disease, since its primary form can manifest itself in the jaw. Key words: Multiple myeloma, plasmacytoma, mandibular lesion.

Mer receptor expression promotes multiple myeloma disease development via a cell-extrinsic mechanism.

CD147 Is a Novel Regulator of Progression and Proliferation of Multiple Myeloma Plasma Cells

Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs' survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called "osteoblastic and vascular niches", thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs-BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs' proliferation and survival, PCs-BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.

Angioimmunoblastic T-cell lymphoma (AITL) is recognized as a distinct clinicopathological subtype of peripheral T-cell lymphomas. Its clinical features include generalized lymphadenopathy, constitutional symptoms, and autoimmune-related findings, such as hemolytic anemia. Pathologically, AITL is characterized by a polymorphous infiltrate in lymph nodes with prominent proliferation of high endothelial venules and follicular dendritic cells. We present an 80-year-old Chinese man with generalized lymphadenopathy and pulmonary infection, diagnosed as AITL based on the distinctive pathological findings and T-cell receptor gamma (TCR-γ) gene rearrangement analysis of lymph nodes. Importantly, the patient suffered from a coexisting plasma cell myeloma, as judged by monoclonal immunoglobulin in the serum, immature plasma cells, and rearrangement of the immunoglobulin heavy-chain (IgH) gene in the bone marrow. The patient received two courses of the chemotherapy but died of pneumonia 6 months after diagnosis. AITL can be accompanied by polyclonal or clonal proliferation of B lymphocytes; however, AITL are rarely associated with plasma cell proliferation. In fact, 14 AITL cases with plasma cell proliferation have been reported in the literature, but none of them manifested the infiltration of monoclonal immature plasma cells in the bone marrow. To the best of our knowledge, this is the first report of newly diagnosed, concurrent AITL and plasma cell myeloma, providing the evidence for the interplay between malignant T cells and plasma cell proliferation. A review of the literature has also supported a relationship between AITL and plasma cell proliferation. Awareness of this relationship is important for correct diagnosis and appropriate treatment of AITL.

A FAM46C-Dependent Molecular Circuit Modulates Antibody Synthesis and Proliferation in Plasma Cell Dyscrasias

Bone disease in multiple myeloma.

Plasma cell myeloma (PCM) is a lymphoproliferative disorder characterized by the malignant growth of monoclonal plasma cells within the bone marrow. Although risk factors for the development of PCM have been identified, the etiology on the majority of patients with PCM remains unclear. Cigarette smoking has been postulated as a potential risk factor for lymphoid malignancies; however, the association with PCM is inconclusive. We have carried out a meta-analysis of observational studies to assess the relationship, if any, between cigarette smoking and PCM. A literature search through December 2011 rendered 4 prospective cohort and 13 case–control studies evaluating such association. Our categorical meta-analysis showed that there is no association between ever, current, and former smokers and PCM.This lack of association was maintained when analyzing by study design, study quality, and geographical area of report. Similarly, meta regression analysis showed no association with the number of cigarettes smoked per day. In conclusion, our meta-analysis shows that there is no relationship between cigarette smoking and an increased incidence of PCM. Future studies should focus on other potential risk factors for PCM.

Introduction: Plasma cell neoplasms are characterized by the clonal proliferation of plasma cells. They include monoclonal gammopathy of undetermined significance, multiple myeloma, and solitary osseous or non-osseous plasmacytoma. Multiple myeloma is characterized by the proliferation of plasma cells in the bone marrow and can result in extensive skeletal destruction, whereas plasmacytoma is characterized by the proliferation of plasma cells restricted to one area of the body. Case Report: A 65-year-old female presented for workup of incidental mass noted on computed tomography (CT) of the chest. She was noted to have posterior mediastinal plasmacytoma with elevated IgA and free lambda light chains on serum electrophoresis. She subsequently underwent the bone marrow biopsy which revealed multiple myeloma. The patient was diagnosed with IgA lambda multiple myeloma with a posterior mediastinal plasmacytoma with multiple bony lesions. She underwent radiotherapy with interval resolution of posterior mediastinal mass and currently on chemotherapy for multiple myeloma. Conclusion: Once plasmacytoma is diagnosed, a further workup for multiple myeloma is needed as treatment is entirely different for both types of plasma cell neoplasms.

Phenotypic Analysis of Plasma Cells in Monoclonal Gammopathy and Multiple Myeloma Subjects.

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.

Keywords: Dutcher bodies; intranuclear pseudoinclusions; multiple myeloma; t(4;14); immature morphology

Introduction: Ascites is a rare complication of multiple myeloma (MM). Most reported cases have been associated with IgA type of myeloma. Here, we describe a case of IgG type MM. Case Report: A 58-year-old male nonalcoholic with hx coronary heart disease, hyperlipidemia was hospitalized for increasing abdominal distension associated with dyspnea. Examination revealed grossly distended abdomen with shifting dullness. Labs: Hb 8.5g/dL, Hct 25.8%, WBC 36.2K/mm3 (granulocytes 47%, lymphocytes 13%, monocytes 38%); platelets 281K/mm3, BUN 34mg/dL, Cr 1.7mg/dL, Ca 8.1mg/dL, PO4 3.6mg/dL, serum albumin 2.7g/dL, total protein 6.9g/dL, and other liver chemistry is normal. Ascitic fluid - orange, bloody appearance, rare mesothelial cells and lymphocytes with numerous highly atypical cells positive for CD 138, CD 117 and CD 45; WBC 175/mm3,RBC 15,500/mm3, ascitic fluid albumin 2.5g/dL and total protein 5.4g/dL. SPEP showed IgG level 4620mg/dL (normal 8-16) and IgA 31mg/dL (normal 68-423). CXR were normal, and skeletal survey showed lucent lesions in the lumbar spine. Flow cytometry revealed 37% abnormal lambda restricted plasma cells expressing CD 38 and 138. Bone marrow aspirate showed hypercellular marrow (100%) with marked plasmacytosis (90%) consistent with plasma cell myeloma. A diagnosis of multiple myeloma (MM) with plasma cell ascites was made, and the patient was started on treatment with dexamethasone, bortezomib, cisplantin, doxorubicin, cyclophosphamide, and etoposide with a good response. Discussion: MM is a neoplastic proliferation of malignant monoclonal plasma cells. Extramedullary incidence rate is rare, 4%. The most common sites for extra medullary plasmacytoma (EMP) are the upper respiratory tract, reticuloendothelial system, kidneys, and gastrointestinal (GI) tract. The GI tract is the site of origin in about 10% of the cases. The small bowel is the most common site of involvement, followed by colon, stomach, esophagus, and peritoneum. Plasma cell ascites is usually associated with extensive liver infiltration with plasma cells and myelomatous peritoneal infiltration. Peritoneal myeloma cell infiltrates proven by biopsy are extremely infrequent. These patients usually have IgA monoclonal spike. The GI involvement at the time of initial diagnosis of MM is much rarer than later in the course of the disease, and often develops in patients with relapsing disease after stem cell transplantation. Extramedullary progression of MM and monosomy 13 are associated with worse prognosis. This case is unique, as the patient was diagnosed with plasma cell ascites with IgG monoclonal spike.