Unveiling Multiple Myeloma: Actively Bleeding Extramedullary Gastric Myelomas Lead to Diagnosis.

Multiple myeloma (MM) is a disease of plasma cell replication, leading to a disruption of hematopoiesis, which commonly presents clinically with anemia and fatigue. Extramedullary myelomas are plasma cell collections in bone or soft tissue associated with MM and most often occur later in the disease process. We present a case of a patient with symptomatic anemia with actively bleeding gastric nodules, which were later found to be extramedullary gastric myelomas when pathology demonstrated kappa-restricted plasma cell neoplasms. To confirm the overall diagnosis, a bone marrow biopsy verified the patient had MM.

Efficacy of Bendamustine, Pomalidomide, and Dexamethasone (BPD) Regimen in Relapsed/Refractory Extramedullary Myeloma: A Retrospective Single-Centre Study, Real-Life Experience.

BACKGROUND AND OBJECTIVES: Relapsed/refractory extramedullary myeloma (RREMM) is an uncommon and aggressive subtype of multiple myeloma defined by plasma cell proliferation outside the bone marrow. Therapeutic options for RREMM are limited, and the prognosis is generally unfavorable. This research aimed to assess the effectiveness of the bendamustine, pomalidomide, and dexamethasone (BPD) regimen in patients with RREMM. MATERIAL AND METHODS: We carried out a retrospective investigation of 11 RREMM patients who underwent BPD treatment. The primary endpoint was progression-free survival. The secondary endpoints of the study were two-year survival and overall response rate (ORR). We analyzed the sociodemographic and clinical features of the patients. RESULTS: The average age of the patients was 62 years. They had a median of four prior treatment lines, and eight patients had previously received autologous stem-cell transplantation. After eight BPD treatment cycles, the ORR stood at 54%, with one very good partial response (VGPR), five partial responses (PR), three progressive diseases (PD), and two stable diseases (SD). The median follow-up was 15 months, with a two-year PFS rate of 71.3% and a two-year survival rate of 81.8%. CONCLUSIONS: The BPD regimen demonstrated promising effectiveness in RREMM patients, yielding favorable ORR and survival rates. To corroborate these findings and explore additional treatment alternatives for this patient group, larger prospective studies are required.

Genetic Abnormalities in Extramedullary Multiple Myeloma.

Extramedullary multiple myeloma (or extramedullary disease, EMD) is an aggressive form of multiple myeloma (MM) that occurs when malignant plasma cells become independent of the bone marrow microenvironment. This may occur alongside MM diagnosis or in later stages of relapse and confers an extremely poor prognosis. In the era of novel agents and anti-myeloma therapies, the incidence of EMD is increasing, making this a more prevalent and challenging cohort of patients. Therefore, understanding the underlying mechanisms of bone marrow escape and EMD driver events is increasingly urgent. The role of genomics in MM has been studied extensively; however, much less is known about the genetic background of EMD. Recently there has been an increased focus on driver events for the establishment of distant EMD sites. Generally, high-risk cytogenetic abnormalities and gene signatures are associated with EMD, alongside mutations in RAS signalling pathways. More recently, changes in epigenetic regulation have also been documented, specifically the hypermethylation of DNA promoter regions. Therefore, the focus of this review is to summarize and discuss what is currently known about the genetic background of EMD in MM.

Extramedullary Multiple Myeloma: A Patient-Focused Review of the Pathogenesis of Bone Marrow Escape.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells, predominantly in the bone marrow. The presentation of MM in extramedullary tissue, particularly the liver, is uncommon with only a few reported cases in literature. We report a rare and unusual presentation of kappa light chain restricted MM with progression of disease to involve the liver. MM was initially diagnosed on bone marrow biopsy, initially treated with carfilzomib, lenalidomide and dexamethasone, later changed to bortezomib, daratumumab and dexamethasone. There was subsequent progression with a new biopsy-proven myelomatous liver lesion. The patient could not receive high-dose chemotherapy due to multiple co-morbidities and extent of disease and eventually succumbed to her disease rapidly. This article emphasizes the poor prognosis of extramedullary involvement in MM and the pathogenic mechanisms by which it develops. Based on a review of the literature of other cases and case series of solitary or diffuse myeloma involvement in the liver, high-dose chemotherapy in combination with proteasome inhibitors and immunomodulators has the best success rate with less relapse and progressive disease in extramedullary myeloma. Our analysis concluded that the gain of CD44, loss of CD56, loss of very late antigen-4 (VLA-4), imbalance of the chemokine receptor-4-chemokine ligand-12 (CXCR4-CXCL12) axis, metastasis-associated lung adenocarcinoma 1 (MALAT1) upregulation, RAS pathway activation as well as 13q and 17p deletions show an increased propensity of malignant plasma cells to leave the bone marrow and hone in extramedullary sites giving rise to more aggressive extramedullary diseases. Targeted therapeutics such as CD44v-directed therapy and reactivation of p53 to wild-type conformation could potentially be evaluated as treatment options in the future to improve outcomes in this aggressive form of MM, especially in patients with advanced disease and limited treatment options.

Secondary Extramedullary Myeloma of the Gallbladder: A Case Report.

Extramedullary myeloma (EMM) is an infrequent but well-established manifestation of multiple myeloma (MM), defined as a soft tissue plasma cell neoplasm without bone marrow involvement. Gallbladder involvement in EMM, however, is a very rare occurrence, with only 8 cases found in the English medical literature. Here, we present a case of an older adult male with a gallbladder mass in the presence of increasing serum kappa light chains after a normal bone marrow biopsy confirmed the complete remission of a previous MM diagnosis. Histopathologic evaluation of a biopsied sample confirmed the mass as an atypical plasma cell neoplasm. Later in his treatment, he developed several firm, smooth, violaceous skin nodules on the torso, which histopathology confirmed as also being atypical plasma cell neoplasms. We aim to contribute to the medical literature by expanding the pool of information regarding EMM of the gallbladder to support future diagnostic and treatment recommendations.

Gastrointestinal, hepatic, and pancreatobiliary involvement by plasma cell neoplasms: clinicopathologic correlations in a retrospective cohort of 116 cases.

AIMS: Plasma cell neoplasms (PCNs) may involve the gastrointestinal (GI) tract in two forms: plasmacytoma (PC), an isolated lesion that lacks marrow involvement, and extramedullary myeloma (EMM). However, previous literature on PCNs involving the GI tract, liver, and pancreas is limited. We evaluated the clinicopathologic features of the largest series of GI PCNs to date. METHODS AND RESULTS: Six institutional archives were searched for GI, liver, and pancreas cases involved with PCNs. Medical records were reviewed for clinical and imaging features. Histopathologic features evaluated included involved organ, tumor grade, and marrow involvement. Overall, 116 cases from 102 patients were identified. The tumors most presented as incidental findings (29%). The liver was most involved (47%), and masses/polyps (29%) or ulcers (21%) were the most common findings. Most cases had high-grade morphology (55%). The majority (74%) of GI PCNs were classified as EMM due to the presence of marrow involvement at some point during the disease course, occurring within a year of marrow diagnosis in 46% of patients. PC was classified in 26% of patients due to the lack of marrow involvement. Most (70%) patients died from disease within 10 years (median 14.1) of diagnosis and more than half (58%) died within 6 months. CONCLUSION: PC and EMM involving the GI tract, liver, and pancreas have a wide range of clinicopathologic presentations. Tumors may occur virtually anywhere in the GI tract or abdomen and may precede the diagnosis of marrow involvement. Both GI PC and EMM are associated with a poor prognosis.

Atypical Presentation of Plasma Cell Neoplasm of the Sternum.

Multiple myeloma (MM) is a rare plasma cell neoplasm characterized by monoclonal cell infiltration in the bone marrow, which can cause anemia, bone pain, and recurrent infections. Extramedullary myeloma (EM) is a rare clinical presentation with a poor prognosis. It involves the accumulation of clonal plasma cells in soft tissues with a tumor-like appearance, either presenting as a primary (initial) or secondary (relapse) malignancy. We present a case of a 65-year-old male who experienced an abrupt onset of chest pain associated with a localized sternal mass while exercising the day prior to arrival. Chest computed tomography (CT) scan with contrast revealed an expansile lytic lesion around the sternal area. Due to high suspicion for malignancy, a CT-guided core needle biopsy was done, which showed plasma cells with rare Dutcher bodies consistent with MM. Bone marrow smear showed the presence of 70% plasma cells confirming a diagnosis of MM. Early detection of this devastating disease may help improve survival. Therefore, physicians should have a high index of suspicion for MM in older patients with similar clinical presentations.

[Pomalidomide/cyclophosphamide/dexamethasone combination therapy for relapsed/refractory multiple myeloma accompanied by extramedullary lesions].

We retrospectively evaluated the efficacy of pomalidomide/cyclophosphamide/dexamethasone (PCd) treatment in seven patients with extramedullary disease (EMD). Three of the seven patients achieved VGPR (very good partial response) with PCd therapy. We handled a patient complicated with secondary plasma cell leukemia, which was completely cured with PCd regimen and succeeded to autologous stem cell transplantation. In addition, there were no severe infections during the treatment period. This is the first report demonstrating the efficiency and tolerability of PCd treatment for EMD.

A Rare Case of Extramedullary Plasmacytoma Presenting as Massive Upper Gastrointestinal Bleeding.

Gastrointestinal (GI) involvement by multiple myeloma is a rare entity. Clinical manifestations depend on the site and extent of involvement. GI bleeding, obstruction, and perforation can complicate the disease course. We report a rare case of an extramedullary plasmacytoma ulcerating through the gastric mucosa and presenting as a massive upper GI bleed, which was controlled surgically with en-bloc resection of the mass infiltrating the stomach, distal pancreas, and spleen. To our knowledge, this is the first case of immunoglobulin A (IgA) myeloma with multiple GI organ involvement presenting with massive upper GI bleeding.

Durable treatment response of relapsing CNS plasmacytoma using intrathecal chemotherapy, radiotherapy, and Daratumumab.

CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

Long non-coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma.

Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression-free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non-coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.

Primary laryngeal localization of multiple myeloma: A case report.

Multiple myeloma is a lymphoproliferative disease that may involve the bone marrow as well as extramedullary soft tissues. However, laryngeal localization of multiple myeloma is extremely rare. We herein present the case of a 68-year-old male patient with a history of dyspnea, dysphonia and dysphagia. Laryngoscopic examination revealed a lesion involving the right glottis and right vestibular (false) vocal fold, with absence of ipsilateral laryngeal motility and constriction of the airway. Computed tomography and magnetic resonance imaging revealed a gross swelling infiltrating the right glottis and right false vocal fold, sized 33×19×33 mm, with sub-centimeter laterocervical lymph nodes bilaterally. Careful integration of the clinical manifestations with the radiological and pathological data led to the diagnosis of multiple myeloma. Given the rarity of this localization, the purpose of this study was to increase knowledge of this disease among ear, nose and throat specialists, in order to enable a more timely diagnosis.

Extra-skeletal plasmablastic myeloma presenting as palatal growth - An unusual entity.

INTRODUCTION: Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells, monoclonal bone marrow plasmacytosis, the presence of M-protein in serum and/or in urine and osteolytic bone lesions. PRESENTATION OF CASE: We report a case of a 28-years old female, who was diagnosed to have relapsing extra-skeletal and extra-nodal plasmablastic myeloma, an atypical variant of MM with a poor prognosis. In addition to bone marrow plasmacytosis and the presence of M protein in the serum, the patient had an extramedullary lesion affecting the hard palate. DISCUSSION: There is a strong correlation with age. The peak incidence is seen in 6th-7th decade. The clinical course in adolescents and young individuals is generally indolent and the survival is longer. Extramedullary myelomas are rare tumors accounting for 0.4% of all head and neck malignancies. CONCLUSION: A case of extraskeletal plasmablastic myeloma presenting as a hard palate growth and that too in young female patient is an extremely rare and requires a multidisciplinary approach for management.

PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma.

Multiple myeloma patients may develop extraosseous involvement in the course of the disease making prognosis very poor and new drugs clearly needed. The PD-1/PD-L1 axis has emerged as a master immune checkpoint in antitumor responses and recent studies investigated the role of PD-L1 in multiple myeloma cells; no data however are still available about PD-L1 expression in extramedullary localizations. We demonstrate PD-L1 expression in 4/12 cases of extraosseous myeloma suggesting that these lesions represent a specialized microenvironment. We found presence of PD-1+ infiltrating lymphocytes in all observed cases supporting the relevance of PD-1/PD-L1 checkpoint in extramedullary myeloma. We also investigated the correlation in PD1/PD-L1 staining between marrow staining and EMP lesions.

Role of dynamic contrast-enhanced sonography for characterization and monitoring of extramedullary myeloma: comparison with serologic data.

OBJECTIVE: To measure blood perfusion in extramedullary myeloma by contrast-enhanced sonography, correlate it with specific hematologic parameters, and determine their utility for local and systemic response monitoring. METHODS: Twenty-five consecutive patients (14 male and 11 female; median age, 68 years) with extramedullary myeloma were included. After intravenous administration of 2.4 mL of sulfur hexafluoride, extramedullary myeloma masses were examined for 60 seconds. All patients underwent contrast-enhanced sonography at baseline, and 15 were monitored additionally (3 weeks during therapy). Average peak perfusion, regional blood flow (RBF), and regional blood volume (RBV) were calculated. Baseline perfusion parameters were compared with short-term follow-up sonographic data and serologic biomarkers (M gradient). For validation of extramedullary myeloma and systemic myeloma, patients underwent midterm (<3 months) imaging and serologic diagnosis. RESULTS: Patients with baseline ß2-microglobulin (B2M) greater than 3.5 mg/L (n = 17) showed higher perfusion parameters compared with baseline B2M less than 3.5 mg/L (n = 8). At short-term follow-up, patients were classified by serologic criteria as responders (n = 9) and nonresponders (n = 6) and by sonographic criteria as responders (n = 10) and nonresponders (n = 5). In sonographic responders, mean peak, RBV, and RBF dropped from 59.13, 1446.09, and 71.52 (artificial units) at baseline to 29.30, 364.19, and 34.64 at follow-up (P < .05), whereas in nonresponders, perfusion parameters increased from 33.18, 789.82, and 36.92 at baseline to 51.14, 1491.06, and 65.34 at follow-up (P > .05). Prediction of a midterm course of systemic myeloma using serologic data yielded sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.66, 0.77, 0.66, and 0.77, whereas sonographic results (judged by RBV) yielded values of 0.66, 0.55, 0.5, and 0.71. Separate prediction of a local (extramedullary myeloma) response by sonography yielded sensitivity, specificity, PPV, and NPV of 0.8, 1.0, 1.0, and 0.71. CONCLUSIONS: Contrast-enhanced sonography is a valuable tool for short-term monitoring of the treatment response in extramedullary myeloma.