Neoplastic Proliferation Of Plasma Cells Research Articles

A young patient with cord compression diagnosed as a solitary sacral plasmacytoma: a case report

Plasmacytoma is a subgroup of plasma cell neoplasms characterized by localized proliferation of neoplastic plasma cells. It is a rare disease that accounts for only less than 5% of all plasma cell tumours and can present alone or with multiple myeloma. Here, we report a clinical case of unusual presentation, in which solitary sacral plasmacytoma of a previously well young woman presented with bilateral lower limb numbness. She was found to have a sacral-originated tumour, which was later diagnosed as a solitary sacral plasmacytoma with the help of imaging and histological evaluation, along with the absence of the end organ damage.

Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells, which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell "boost" to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. There is currently a paucity of data on the response rates and outcomes of patients with relapsed MM who undergo cytotoxic chemotherapy followed by a stem cell boost; this study examines the outcomes of patients treated with this approach. We conducted a retrospective chart review from two oncologic treatment centers in the United States of adult patients who underwent a first ASCT between 1999 and 2021 and subsequently received cytotoxic chemotherapy followed by stem cell boost further on in their disease course. Survival analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to compare survival curves. We found that the majority (56.6%) of these patients responded to therapy and that 60.6% of these patients were able to receive at least one subsequent line of therapy post-boost. Furthermore, patients who responded to therapy had significantly longer median overall survival compared to those who did not respond (323 days vs 93 days, p=0.0045), and age did not affect response to therapy. This data allow clinicians to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of stem cell boost in patients with multiply relapsed/refractory MM.

Multiple Myeloma

The second most common hematologic malignancy is the clonal proliferation of neoplastic plasma cells within the bone marrow. There is the presence of monoclonal immunoglobulins in the serum and/or urine. This results in anemia, myelosuppression, bone destruction, and clinical consequences of para-proteinemia on kidney function and other organ systems. The disease manifests through the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Less frequent manifestations of multiple myeloma are of extramedullary localizations. Myeloma cells can become independent of the bone marrow microenvironment, circulate freely in the blood, and infiltrate organs. This results in a high-risk state characterized by increased proliferation, evasion of apoptosis, and treatment resistance. It can affect any area of tissue. Most commonly it involves the pleura, lymph nodes, chest wall, liver, skin/soft tissue, lungs, CNS, genitourinary system, breast and pancreas. In patients with confirmed multiple myeloma, the diagnosis of extramedullary involvement is typically established by the presence of pathological soft tissue masses using radiological methods such as computed tomography (CT) scan, positron emission tomography/CT (PET/CT), magnetic resonance imaging (MRI), or ultrasound, along with biopsy or physical examination. The molecular mechanisms underlying the development of extramedullary multiple myeloma (EMM) have not been fully defined. Various cytogenetic abnormalities are observed, and some studies have generated genomic sequencing profiles that distinguish EMM from classic multiple myeloma. While plasma cell leukemia (PCL) and central nervous system (CNS) EMM indicate a poor prognosis, outcomes for other manifestations can be highly heterogeneous. Sensitive imaging modalities including PET/CT and MRI (Fig.1) are integral components of diagnosis and response assessment. Patients with extramedullary multiple myeloma (EMM) have a clear survival disadvantage.

Solitary plasmacytoma: A case report

Plasmacytoma is a discrete, unifocal, and monoclonal neoplastic proliferation of plasma cells. It may present as one of the three distinct clinical entities: multiple myeloma (MM), solitary plasmacytoma of the bone, and extramedullary plasmacytoma. Solitary plasmacytoma of the bone accounts for 3% of all plasma cell neoplasms. About 50% of the cases of solitary plasmacytoma of the bone transform into MM. The most commonly involved sites are vertebrae and long bones. It is extremely rare in jaws. We are presenting a case of solitary plasmacytoma of the maxilla in a 59-year-old female patient with comprehensive clinical, radiological, histological, and immunohistochemical features.

Exploiting the Gut Microbiota to Boost Immunotherapy and Switch the Trajectory of Multiple Myeloma

Clonal proliferation of neoplastic plasma cells in the bone marrow (BM) and organ dysfunction characterizes multiple myeloma (MM), a treatable but incurable disease. Although asymptomatic smoldering MM (SMM) often precedes full blown MM, most patients affected by SMM are only offered active observation, which increases their frustration and anxiety. In transgenic Vk*MYC mice developing de novo MM, we found a direct link between gut microbiota composition and T helper 17 (Th17) lymphocytes, which migrated from the gut to the BM during asymptomatic MM (Early-MM), and favored the expansion of neoplastic plasma cells, thus fueling progression to symptomatic disease (Late-MM) [Calcinotto A. et al. Nat Commun (2018) 9(1):4832]. Similarly, in SMM patients, higher levels of BM Interleukin-17 (IL-17) predicted accelerated disease [Calcinotto A. et al. Nat Commun (2018) 9(1):4832]. Interestingly, Prevotella melaninogenica ( P.m.), a human commensal, limited MM aggressiveness in mice challenged with Vk*MYC-derived MM cells (t-Vk*MYC) by restraining Th17 cell expansion [Calcinotto et al. Nat Commun (2018) 9(1):4832]. Because the gut microbiota also contributes to the therapeutic efficacy of immune checkpoint blockade (ICB) and human neoplastic plasma cells express PD-L1, we hypothesized that modulation of the gut microbiota by P.m. could limit Th17 cell expansion in mice affected by Early-MM, thus fully exploiting the therapeutic potential of anti-PD-L1 against MM. Clinical trials combining anti-PD-1/PD-L1 antibodies, dexamethasone and immune modulatory drugs in MM were halted by US FDA because of unfavorable benefit-risk profile and life-threatening immune related adverse events (irAEs). Because IL-17 is involved in irAEs [Johnson et al. Cancer Immunol Res (2019) 7 (6): 860-865], we also hypothesized treatment with P.m. could restrain ICB-induced expansion of Th17 cells while unleashing CD8-mediated antitumor immunity. Early-MM Vk*MYC mice and t-Vk*MYC, the latter mimicking aggressive MM, were treated with P.m. and/or anti-PD-L1 and disease progression was monitored by paraprotein quantification in blood. Anemia provided clinical evidence of symptomatic disease. At sacrifice, gut, spleen and BM were analyzed by flow cytometry. In vitro assays were conducted to clarify the mechanism by which the gut microbiota influenced the induction of Th17 cells. To mimic cutaneous irAE, the skin of treated mice was exposed to imiquimod, which induces Th17-mediated inflammation [van der Fits et al. J Immunol (2009 )182(9): 5836-5845]. Body weight loss, skin inflammation, and inflammatory infiltrate into secondary lymphoid organs were taken as measure of imiquimod-induced toxicity. In Vk*MYC mice, all neoplastic plasma cells expressed PD-L1. Treatment of Early-MM Vk*MYC mice with anti-PD-L1 antibodies delayed progression to Late-MM, thus extending previous findings on the use of ICB in this model to anti-PD-L1 antibodies and Early-MM [Guillerey et al. J Clin Invest (2015 )125(5): 2077-2089]. Treatment with P.m. exerted a similar effect on disease progression, suggesting that a treatment as simple as taking a probiotic has an impact on MM evolution. When P.m. was combined with anti-PD-L1 antibodies, evolution to Late-MM was further delayed or even blocked. Single and combined treatments also reduced MM aggressiveness in t-Vk*MYC mice. Mechanistically, P.m. limited the expansion of gut-born Th17 cells and their accumulation in the BM of treated mice without dampening the antitumor cytotoxic response elicited by the ICB. Thus, only the combined treatment provided the most favorable CD8/Th17 and CD8/T regulatory cell ratios. Ex vivo, P.m.-conditioned BM DCs showed a limited propensity to produce Th17-polarizing cytokines. In vitro, stimulation of both human and mouse DCs with P.m. reduced polarization of naïve T cells toward a Th17 phenotype. Skin application of imiquimod in C57BL/6 mice induced psoriasis-like lesions and expansion of Th17 cells both in draining lymph nodes and spleen. The contextual administration of anti-PD-L1 antibodies worsened imiquimod-induced inflammation. An ongoing experiment will clarify if mice receiving P.m. and ICB experience reduced skin lesions. Taken together, our data support the development of microbiota-based strategies in combination with ICB to treat full-blown MM and to prevent progression of asymptomatic SMM to full-blown disease.

Single-cell analysis of the CD8+ T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69- subset suggesting potent cytotoxic effectors exist within the tumor bed.

Multiple myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of Granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T cells from patients with MM more closely resembles TCR-activated CD8+ T cells from age-matched controls than their resting counterparts.

Protein-Functionalized Microgel for Multiple Myeloma Cells' 3D Culture.

Multiple myeloma is a hematologic neoplasm caused by an uncontrolled clonal proliferation of neoplastic plasma cells (nPCs) in the bone marrow. The development and survival of this disease is tightly related to the bone marrow environment. Proliferation and viability of nPCs depend on their interaction with the stromal cells and the extracellular matrix components, which also influences the appearance of drug resistance. Recapitulating these interactions in an in vitro culture requires 3D environments that incorporate the biomolecules of interest. In this work, we studied the proliferation and viability of three multiple myeloma cell lines in a microgel consisting of biostable microspheres with fibronectin (FN) on their surfaces. We also showed that the interaction of the RPMI8226 cell line with FN induced cell arrest in the G0/G1 cell cycle phase. RPMI8226 cells developed a significant resistance to dexamethasone, which was reduced when they were treated with dexamethasone and bortezomib in combination.

MM-547 Multiple Myeloma Response to Therapeutic Protocols: An Iraqi Center Experience

Multiple myeloma (MM) is a clonal proliferation of neoplastic plasma cells producing a monoclonal paraprotein of light and/or heavy chain present in the serum and/or urine. Achieving complete response (CR) is the initial goal of myeloma therapy. The recent therapeutic protocols increase MM CR and survival age. This study aimed to determine the efficacy of the main protocols used in Iraq. A cross-sectional study consecutively included all MM patients between July 2015 and May 2022 at one of the main hematology hospitals in Iraq, the National Hematology Centre, to assess the overall response rate (ORR) which represents ≥very good partial response (VGPR). Of the 52 enrolled patients, the mean (±SD) age was 61.5±11.0 years with a 1.5:1.0 male to female ratio and 30.8% had comorbidities. Two participants (3.8%) died before the end of the study. The presenting features include bone pain and backache (67.3%), followed by a mass and lower limb weakness (1.9% each). The radiological changes were lytic lesions (34.6%) and vertebral wedging (15.4%). The main laboratory features were anemia (69.2%, 10.0±1.5g/dL), IgG kappa paraprotein (51.9 %), and high levels of creatinine (35.3%, 1.4±1.5mg/dL) and calcium (30.8%, 9.5±1.7mg/dL). The available drugs include bortezomib (V), lenalidomide (R), thalidomide (T), cyclophosphamide (C), and dexamethasone (D) were used in triple therapeutic regimens, VRD, VTD, and VCD, with or without autologous stem cell transplantation (ASCT). The outcomes were assessed for each protocol used. Results and Main Outcomes: Among 52 patients, 50 were evaluated at a median follow-up of 60.5 months. The median survival could not be calculated, since 2 patients died due to renal failure. ORR was achieved in 75% of the patients, and partial response (PR) in 11.5%. When outcomes were stratified by treatment regimens, there were statistically significant differences in ORR; the best was observed among VRD-group (p<000.1). Subsequently, 21 (40.4%) patients received ASCT with non-significant differences in ORR from those without transplants (P>0.05). VRD achieved the best antitumor activity in MM, followed by VTD, and VCD was the least. Triple therapeutic regimens effectiveness showed non-significant differences, whether used alone or with ASCT.

S2214 A Rare Case of Secondary Extramedullary Plasmacytoma With Ileocecal Involvement

Introduction: Extramedullary plasmacytomas (EMPs) are a rare type of plasma cell dyscrasia characterized by the neoplastic proliferation of plasma cells in soft tissue.EMPs share characteristics with multiple myeloma (MM) and can present as primary tumors or secondary to other plasma cell neoplasms.Herein we present an extremely rare case of a patient with established MM who was found to have an asymptomatic ileocecal mass with biopsy findings consistent with secondary EMP. Case Description/Methods: A 62-year-old female with a past medical history of MM and Ulcerative Colitis (UC) presented to the gastroenterology clinic for evaluation of her UC before consideration of an experimental therapy trial for her refractory MM.On presentation, she denied changes in her bowel habits or blood in her stool. Lab results 2 weeks prior to presentation were significant for leukopenia at 2.9k/uL, normocytic anemia with hemoglobin at 8.5gm/dL, Calcium 8.2 mg/dl, and total protein of 5.7g/dl. Colonoscopy showed nodular, ulcerated mucosa at the hepatic flexure as well as a large polypoid non-bleeding, non-obstructing, non-circumferential mass at the ileocecal valve. Histopathology of the mass returned positive for CD138 Kappa and negative for lambda AE1/AE3, CAM 5.2, GATA3, ER, consistent with a diagnosis of plasma cell myeloma. The patient continued on salvage chemotherapy but passed shortly thereafter (Figure). Discussion: Plasma cell neoplasms (PCNs) involving extra-osseous tissues are known as extramedullary plasmacytomas (EMPs).EMPs are further classified into primary EMPs, which are localized proliferation of clonal plasma cells in the absence of a systemic plasma cell dyscrasia, and secondary EMPs, where there is already a known primary PCN present. To the best of our knowledge, secondary EMP involving the small intestine and cecum is rare and only reported in a handful of case reports.Due to the indolent course of EMPs, nonspecific gastrointestinal manifestations may go undiagnosed in a subset of patients with MM. The prognosis of secondary EMP involving the gastrointestinal tract remains unclear, however, the limited data we have indicates a poor prognosis.On the other hand, novel treatments of MM continue to improve survival rates in patients with MM. As mortality in these patients decreases, the incidence of secondary EMPs is expected to proportionately rise as well. As such, more data is needed to understand how to monitor and treat this patient population for extramedullary involvement in order to generate good outcomes.Figure 1.: Large polypoid non-bleeding, non-obstructing, non-circumferential mass at the ileocecal valve before and after biopsy.

Light-Chain Multiple Myeloma Presenting as a Bone Tumor in the Right Knee Joint – a Case Report

Myeloma is the neoplastic proliferation of plasma cells. The peak age of onset of this disease is the seventh decade, and it is rare in young patients. Myeloma usually presents as lytic lesions in axial bones and rarely present as a joint disease. Usually, the tumor cells secrete monoclonal immunoglobulins. Non-secretory myeloma is a rare clinical entity. The incidence of light-chain myeloma is 16 – 20 % among all multiple myelomas, and the more common subtype is the lambda chain type. We present a case of kappa light chain-type myeloma in a 29-year-old male with the presenting lesion in the right knee joint. The case is presented for its rarity due to the age of patient, presentation, and type of myeloma.

Thymic plasmacytoma presenting as polyneuropathy and revealing multiple myeloma: a case report

BackgroundMultiple myeloma (MM) is the most frequent malignant plasma cell disorder with proliferation of neoplastic plasma cells in the bone marrow or other tissue, most commonly in the upper aerodigestive tract. The invasion of the thymus is exceptional. Neurological complications are usual, but represent exceptionally the revealing symptom.Case presentationWe report a case of polyneuropathy revealing a thymic plasmacytoma as a mediastinal invasion of MM in a 48-year-old woman. She was admitted after developing progressive ascending distal paresthesias and weakness in lower limbs. Examination showed symmetrical distal sensorimotor impairment with axillary and inguinal adenopathies. Electroneuromyography revealed a sensorimotor length-dependent neuropathy. Serum protein electrophoresis showed monoclonal protein peak in β-γ globulin region. Immunoelectrophoresis showed IgA lambda monoclonal gammapathy. Myelogram and bone marrow biopsy revealed plasmocytosis of 5%. Chest computed tomography showed a histologically confirmed thymic plasmacytoma associated with a lytic lesion of the 5th rib leading to the diagnosis of MM.ConclusionsThe association between a thymic plasmacytoma and peripheral neuropathy is rare and a workup for MM is necessary to guide therapeutic management.

Gastric involvement of multiple myeloma: A case report

Multiple Myeloma (MM) is a neoplastic proliferation of plasma cells involving mainly bone and bone marrow. However, extra-skeletal spread in the form of plasmacytomas is also very common, which usually manifests as localized extramedullary collection of malignant Plasma cells. This paper is a report on gastric involvement of plasma cell infiltration, also known as gastric plasmacytoma.

Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment.

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

PB2007: FACTORS ASSOCIATED WITH EARLY RELAPSE IN MYELOMA PATIENTS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

Background: Multiple myeloma (MM) is a clonal disease characterized by a neoplastic proliferation of plasma cells that make up approximately 10% of hematologic malignancies. Autologous hematopoietic stem cell transplantation (ASCT) after an induction regimen using combination of immunomodulatory drugs, proteasome inhibitors and dexamethasone is considered the standard treatment of newly diagnosed multiple myeloma in eligible patients. Aims: To demonstrate the pre-transplant factors associated with early relapse in MM patients undergoing ASCT. Methods: 27 adult MM patients who underwent ASCT at The Stem Cell Transplant Center of Dokuz Eylul University Hospital between October 2011 and August 2021 and who relapsed within 18 months of transplantation were included in this study. The data were compiled from the Dokuz Eylul Hematology archive and the Hospital Information Management System at Dokuz Eylul University Hospital and analyzed with SPSS v.24 (Statistical Package for Social Sciences). Mann-Whitney U test is used to compare kappa/lambda ratios, Kaplan Meier test is used to analyze survival and log-rank test is used to test significant difference between survival of two groups. Results: The median age at diagnosis is 57 (42-68) and 52% of patients were male (n=14). Patients received a median one line of treatment before ASCT (1-3). According to the ISS staging system, 9 patients were stage I, 9 patients were stage II and 9 patients were stage III. In 43% of patients (n=12), extramedullary (EM) disease involvement was present at the diagnosis. 33% had hypercalcemia (n=9), 19% had kidney involvement (n=5), 57% had anemia (n=16), and 75% had bone (n=21) at the time of diagnosis. Two patients achieved complete remission (CR) after 2 courses of induction therapy. But they lost this response pre-ASCT and they relapsed in 5th and 6th month after ASCT respectively. The median time to relapse post-ASCT was 6 (2-17) months. In 63% of these patients, clinical relapse was observed, treatment was started due to aggressive biochemical relapse in the rest. 25% (n=7) had EM disease involvement in relapse. In this patient group, the median survival after ASCT is 32 months (5-120). In 3 out of 10 patients with biochemical relapse, EM disease was not observed despite being present at the time of diagnosis. In 9 of the 17 patients with clinical relapse and EM disease at diagnosis, 7 patients relapsed with EM disease. Median Kappa/Lambda ratios at the time of diagnosis were 13.84 and 13.1 at the time of relapse. There was no statistically significant difference in kappa/lambda rates at the time of diagnosis and relapse of patients with biochemical and clinical relapse. Median progression-free survival (PFS) was 5 months in those with clinical relapse and 8 months in patients with biochemical relapse. Median overall survival (OS) was 19.2 months in those with clinical relapse and it was not reached in those with biochemical relapse (p=0.001) (Fig. 1). Image:Summary/Conclusion: It is known that in multiple myeloma, ASCT prolongs PFS. Early loss of response in patients who achieved CR after 2 courses of treatment may be a prognostic clue. OS and PFS are shorter in those with clinical relapses while biochemical relapses are more indolent. The fact that 43% of our patients have EM disease involvement in diagnosis indicates that this feature may be associated with early relapse. Outcomes of single and tandem ASCT in these patients should be examined in further studies.

Development of blood components samples collection as a source for new biomarkers search in multiple myeloma.

e15009 Background: Multiple myeloma (MM) is a B-cell malignancy resulting from the abnormal proliferation of neoplastic plasma cells that produce monoclonal immunoglobulin (Ig). The high variability of the course of this disease, its genetic clonal heterogeneity, is due to chromosomal deletions, chromosomal hyperploidy involving an odd number of chromosomes, as well as genetic aberrations, such as rearrangement of the Ig heavy chain gene loci. Since the available biomarkers do not take into account this feature of MM, there is a need to develop more advanced biomarkers that will more accurately predict the course of the disease and response to treatment. Methods: The collection of MM samples included biological samples obtained from patients over 18 years of age with a diagnosis of MM, who received treatment in the National Medical Research Center of Oncology since 2019. Only patients who signed an informed consent for the use of their biomaterial for scientific purposes were included in the project. The material was collected according to the developed algorithm of clinical information and biological material collection, sample preparation, quality control and storage in the cryostorage of the National Medical Research Centre for Oncology of the Ministry of Health of Russia (Rostov-on-Don). Results: As of December 23, 2021, collection consists of 387 samples of whole blood, serum, plasma and mononuclear cells obtained from 42 MM patients of both sexes, whose average age was 59.7 ± 1.49 (±SD) years. Each patient was assigned a unique identification number. Freezing of the obtained samples occurred in accordance with the low-temperature storage protocol. Registration, accounting and certification of the material were carried out in a specialized database for recording and storing information about biological samples. Conclusions: The identification of MM biomarkers is important for increasing the sensitivity of molecular monitoring, which makes it possible to stratify patients into risk groups for early relapses and treatment resistance development. Thanks to the accumulated experience, the Biobank of the National Medical Research Centre for Oncology of the Ministry of Health of Russia serves as a valuable resource for providing research in the development of new predictive molecular markers.

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches.

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.

Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene.

Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.

Multiple Myeloma as a rare cause of membranoproliferative glomerular nephritis

Multiple myeloma (MM) is a relatively uncommon cancer characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin(Ig). Renal failure in multiple myeloma is around 48% and it may be the presenting manifestation of MM.[1] Renal involvement is multifactorial including light chain cast nephropathy amyloidosis, monoclonal Ig deposition disease and less frequently cryoglobulinaemic glomerulonephritis and proliferative glomerulonephritis.[2-5] Hence membrano proliferative glomerulonephritis (MPGN) is a rare form in MM. Here we report a case of multiple myeloma with MPGN in a 60-year-old male who succumbed to death while on chemotherapy.

Extramedullary plasmacytoma of the tongue: A case report

Background: Tongue extramedullary plasmacytoma is a very rare pathology. Despite rare cases, extramedullary plasmacytoma should be considered as a differential diagnosis in case of a mass in the tongue. A total of 19 cases were reported with EMP in English literature along with the case we will address. It is characterized by a monoclonal neoplastic proliferation of plasma cells in the absence of multiple myeloma (MM). Histopathology and immunohistochemistry are very important for the diagnosis and differential diagnosis. Case presentation: The case we will describe is an 80-year-old lady from Albania who presents with a vegetative lesion in the form of a thick plate on the dorsal part of the tongue with dimensions 6 X 5 X 1.5 cm. A material of 0.5 cm diameter was taken from the lesion for the biopsy. After histopathological examination, immunohistochemical examinations, and after correlations with laboratory, clinical and imaging data, the diagnosis of extramedullary plasmacytoma of the tongue was reached. The patient underwent radiotherapy treatment. Conclusions: EMP is a rare tumor, accounting for 3% of plasma cell neoplasms and &lt;1% of all head and neck tumors. The diagnosis of EMP, in this case, was reached with biopsy, immunohistochemistry, and the correlation with laboratory and imaging data. We will show the importance of biopsy along with immunohistochemistry in the diagnosis and differential diagnosis of extramedullary plasmocytoma of the tongue. Keywords: plasmacytoma; immunohistochemistry; biopsy; plasma cell. Abbreviations: EMP: Extramedullary plasmacytoma; MM: Multiple myeloma; Cm: centimeter

SUCCESSFUL MANAGEMENT OF SPHENOID RELAPSE OF MULTIPLE MYELOMA WITH RADIATION THERAPY: A CASE REPORT

Multiple myeloma (MM) is typically characterized by neoplastic proliferation of plasma cells in the bone marrow and can result in extensive skeletal destruction. Involvement of skull base is extremely rare, especially sphenoid bone. We report in this work the case of a 62-year-old woman, who presented with a sphenoid relapse of multiple myeloma treated with radiation therapy, with signicant clinical improvement and almost complete disappearance of the sphenoid metastasis. We shed light, through this case, on the rarity of sphenoid metastases in multiple myeloma and on the role of radiotherapy in the management of this type of location.