Form Of Multiple Myeloma Research Articles

Angiogenesis and osteopontin expression in paraskeletal myeloma with plasmablastic morphology and aggressive clinical course: a report of two cases

Extramedullary disease (EMD) of multiple myeloma (MM) can present as paraskeletal (paraosseous) plasmocytoma (PP) that arise from skeletal focal lesions or extramedullary plasmacytomas (EMP) that derive from hematogenous spread. The pathogenetic mechanisms that distinguish classical MM, PP, and EMP are still insufficiently known, as are the therapies that would be effective in EMD. The aim of this study was to evaluate immunohistochemically the angiogenesis, determined as microvessel density (MVD) and osteopontin expression in PP, of two patients with MM of plasmablastic morphology and an aggressive course of disease. We found high levels of MVD and osteopontin expression in both cases of PP. The role of angiogenesis and osteopontin in EMD should be clarified in future investigations, especially since there are no satisfactory therapeutic protocols for this form of multiple myeloma, and both of these biological factors can be the potential targets of new therapies.

Acute Plasma Cell Leukemia Presenting as Primary Hyperammonemic Encephalopathy

Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma (MM) and is a rare aggressive disease with a median overall survival of 6 - 11 months. We present a case of acute hyperammonemic encephalopathy as the initial presentation of PPCL in a 78-year-old woman to highlight an atypical presentation of this disorder. J Med Cases. 2020;11(10):320-323 doi: https://doi.org/10.14740/jmc3559

Orbital and adnexal amyloidosis: Thirty years experience at a tertiary eye care center.

Purpose:The aim of this work was to study the clinical presentation, management and outcomes of orbital and adnexal amyloidosis.Methods:This retrospective analysis included all the patients diagnosed with orbital and adnexal amyloidosis between January 1990 and December 2019. Positive staining with Congo Red and apple-green birefringence on polarized light microscopy established the diagnosis. Data analyzed included demographic profile, varied presentations, management, and outcome.Results:Thirty-three eyes of 26 patients were included. The male:female ratio was 1:1. The mean age of the study population was 42.6 ± 16 years. The median duration of symptoms was two years. Unilateral involvement was seen in 19 eyes (right = 11, left = 8). The most common presenting feature was acquired ptosis. Eyelid was the most commonly affected site followed by orbit and conjunctiva. Two patients had systemic involvement in the form of multiple myeloma and lymphoplasmacytic lymphoma. Complete excision was done in seven (26.9%) cases while 19 (73.1%) cases underwent debulking. Three patients underwent ptosis surgery. The median duration of follow-up was 1.5 years. Three cases had recurrence and underwent repeat surgery.Conclusion:Orbit and adnexa is a rare site for amyloidosis. It is usually localized; however it can occur as a part of systemic amyloidosis. Eyelid is the most common site of involvement and patients usually present as eyelid mass or ptosis. Complete excision is difficult and most of the patients usually undergo debulking surgery. All patients should undergo screening for systemic amyloidosis

Symptom burden and health-related quality of life impacts of smoldering multiple myeloma: the patient perspective

BackgroundSmoldering multiple myeloma (SMM) is an early form of multiple myeloma (MM). SMM is typically considered asymptomatic, and research on how it affects health-related quality of life (HRQoL) is limited. This study assessed the symptoms and HRQoL of patients with SMM and those who progressed from SMM to MM and evaluated the content validity of two patient-reported outcome instruments (EORTC QLQ-C30 and nine items from the EORTC QLQ-MY20) for use in SMM clinical trials. To address these objectives, concept elicitation and cognitive interviews were conducted with SMM patients and recently diagnosed MM patients.ResultsFifteen adult SMM and six adult MM participants with a prior SMM diagnosis were interviewed. On average, SMM study participants were 61 years old (46.0–78.0), 11 (73%) were female, and diagnosed 2.6 (±2.0) years ago. Each participant had experienced at least one symptom, most commonly tiredness/fatigue, weakness, and pain. The most common HRQoL impacts were emotional and physical. SMM study participants demonstrated good understanding of both the EORTC QLQ-C30 and EORTC QLQ-MY20 subscales and found them relevant to their SMM health state. The average age of MM participants was 53 years old (39.0–62.0); 5 (83%) were female and diagnosed 1.9 years ago (±2.1). MM participants most commonly reported tiredness, weakness, constipation, shortness of breath, and dry mouth as occurring when they progressed from SMM to MM.ConclusionsAlthough previously described as asymptomatic, these SMM participants reported experiencing symptoms that affected their lives. Additionally, the EORTC subscales measured symptoms SMM patients experienced. The participants with MM reported that the symptom burden and HRQoL impacts increased when diagnosed with MM. These findings suggest the need for increased surveillance of symptoms within the SMM population and further suggest that the EORTC subscales can be used to assess symptoms and impacts in both the SMM and MM populations.

Utilizing Multiparametric Flow Cytometry to Identify Patients with Primary Plasma Cell Leukemia at Diagnosis

Utilizing Multiparametric Flow Cytometry to Identify Patients with Primary Plasma Cell Leukemia at Diagnosis

Clinical Outcomes and Cytogenetic Features of Primary Plasma Cell Leukemia (pPCL) in the Era of Novel Agent Induction Therapy

Clinical Outcomes and Cytogenetic Features of Primary Plasma Cell Leukemia (pPCL) in the Era of Novel Agent Induction Therapy

Non Secretory Multiple Myeloma With HCV Infection: A Rare Case Entity

Multiple Myeloma is a neoplasm of B cell lineage characterized by excessive proliferation of abnormal plasma cells. It is characterized by a clinical pentad of 1) anemia, 2) a monoclonal protein in the serum or the urine or both, 3) bone leisons and or bone pain, 4) hypercalcemia>11.5g/dl and 5) renal insufficiency. Non secretory multiple myeloma is a rare variant of the classic form of multiple myeloma and accounts for 1% to 5 % of all cases of multiple myeloma. The clinical presentation and radiographic findings of non-secretory multiple myeloma and multiple myeloma are the same. The diagnosis of multiple myeloma requires the demonstration of monoclonal gammopathy in the serum or urine. In non-secretory multiple myeloma, however no such gammopathy can be demonstrated, making the diagnosis more difficult. We describe a 60 year old woman who initially presented with back pain which when further investigated by complete blood count revealed hemoglobin of 13g/dl, Total Leukocyte Count of 10,890 and platelet count of 1.5 lac/cmm. Viral markers revealed HCV positive. Hypercalcemia with a serum calcium level of 12.5g/dl was also demonstrated. MRI revealed multiple lytic bony lesions. No monoclonal gammopathy was found in the serum or urine and bone marrow biopsy showed marked plasmacytosis of > 45%. We present a case of Non Secretory multiple myeloma because of its illusive nature and rare entity.

Extramedullary plasmacytoma nose operated by raveh’s approach: a case report

Plasmacytoma is a clonal proliferation of plasma cells. Plasmacytoma can be disseminated in the form of multiple myeloma or solitary disease. Most common site of involvement of solitary extramedullary plasmacytoma being the upper respiratory tract. We present a case report of 60-year-old male who presented with bilateral nasal obstruction, epistaxis and swelling on the root of nose. Biopsy proved out to be a plasmacytoma which was operated by Raveh’s approach. Raveh’s approach is a very useful approach for skull base tumors in the sphenoethmoidal plane with minimal morbidity, no frontal lobe retraction and watertight closure of dura and excellent postoperative recovery.

AGGRESSIVE FORM OF MULTIPLE MYELOMA DIAGNOSED AT THE STAGE OF SEVERE RENAL FAILURE

The work presents a clinical case of the aggressive form of multiple myeloma including predominant lesions of the kidneys, stomach, liver, and lymph nodes.

Non-secretory multiple myeloma with extramedulary plasmocytoma

Non-secretory multiple myeloma (NSMM) is an uncommon variation of the classic form of multiple myeloma (MM) that has au analogous clinical and radiologic presentation except for the absence of the M-protein in sernm and/or urine. NSMM may have or not detectable monoclonal free light chain in urine/serum. We describe here a case of a 46-year-old woman who presented with back pain and lower limb weakness. A tumour lesion at DI level and multiple osteolytic bone lesions were found. This woman had no other symptoms and her basic blood biochemistry were nonnal. She had normal serum and urine protein electrophoresis. Biopsy from the D1 vertebra showed plasmocytoma. In the bone marrow, 20% atypical plasma cell fow1d, all were being CD38+ and CD 138+ in flowcytometry, confirming the diagnosis of myeloma presenting as NSMM. A high index of suspicion is needed to diagnose cases like this, as the biology ofNSMM is not completely understood.

Rare Aggressive Form of Multiple Myeloma with Diffuse Osteosclerosis and Elevated CA 15-3 Levels

We report the case of a 56-year-old female who had recently been examined for back and epigastric pain, and was diagnosed in the internal medicine ward as having an aggressive rare form of multiple myeloma with diffuse osteoblastic bone lesions. She also had high levels of breast tumor marker (CA 15-3), severe tumor lysis syndrome, and pleural and central nervous system involvement. A few cases of multiple myeloma with diffuse osteosclerosis that are not part of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changeshave) have been described. None of these cases were as aggressive as our case. To our knowledge it is the first report describing an elevation in CA 15-3 in conjunction with multiple myeloma.

Plasma Cell Leukemia-Behind a Disguise

Plasma cell leukemia is a variant form of multiple myeloma with its own unique form of presentation. It may have a presentation resembling a lymphoproliferative disorder which if not investigated in detail can lead to misdiagnosis and thus completely different line of investigation. Our patient presented to us with disturbed dietary regimen, significant weight loss and was a known case of hypothyroidism since 2009 for which he was on medications. At the other centre, complete blood picture showed bicytopenia with hyperleucocytosis while bone marrow biopsy performed showed a diagnosis of lymphoproliferative disorder with a morphological diagnosis of Hairy cell leukemia. At our center, his complete blood count showed bicytopenia with leucocytosis as before but the morphological examination of his peripheral smear showed the presence of 80% plasma cells. The immunophenotyping showed CD23(+) and CD56(+) while the immunohistochemistry showed CD23(+), CD56(+) and CD138(+). Cytogenetics showed the presence of t(4;14) in 5% of the cells examined. Based on the above mentioned investigations, a diagnosis of Plasma cell leukemia was reached and the patient was placed on a treatment regimen including Lenalidomide, Bortezumib and Dexamenthasone. His blood counts came within the normal range within a week of starting the treatment. Bone marrow biopsy accounts for one of the many steps that should be taken to reach a correct diagnosis. Keeping in mind the variable presentation a disease can show, as many investigative tools should be undertaken as is clinically and economically possible for reaching at a correct diagnosis and thus the decision of the eventual treatment plan for the patient.

Value Research of T-Regs Cells in Peripheral Blood of Patients with Multiple Myeloma

In this study we have assessed FOXP3 and its isoforms expression by CD4+ T cells from peripheral blood of 37 patients with various forms of multiple myeloma (MM) and 15 healthy volunteers. Newly diagnosed MM was in 17 patients; resistant/relapsed MM was registered in 13 patients and 7 patients had remission after chemotherapy. Significant role of FOXP3 expression by CD4+ T lymphocytes in pathogenesis of MM was shown. Thus, increase of FOXP3-expressing cells percent among CD4+ T cells is registered in patients with newly diagnosed MM and in resistant/relapsed patients. The main contribution to this percent increment is made by FOXP3D2 isoform expressing cells. In addition to the percent increment the number of CD4+FOXP3+ T cells is also risen in patients with newly diagnosed MM. The level of FOXP3 expression by CD4+ T cells also reflects the effectiveness of antitumor therapy, considering normalization of CD4+FOXP3+ T cells number and percent in patients with disease remission. We also discuss the possible relationship between FOXP3 mRNA post-transcriptional modification, namely alternative splicing, with stable expression of FOXP3 in T-regs cells.The level of an expression of T-regs cells can will be applied as criterion of efficiency of antitumor therapy. DisclosuresNo relevant conflicts of interest to declare.

Patients with extramedullary manifestation of multiple myeloma: Prognostic factors and survival.

e18552 Background: Multiple myeloma is a plasma cell dyscrasia that primarily involves bone marrow but also occurs in the soft tissues. While observing striking differences in clinical courses of patients with extramedullary plasmacytoma (EMP), solitary bone plasmacytoma (SBP), multifocal form of multiple myeloma (MFM) and multiple myeloma (MM), we wanted to assess prognostic factors and outcomes in those groups. This retrospective analysis was performed to evaluate response rate and overall survival (OS) of patients with extramedullary manifestations. Methods: We evaluated the data from 54 patients with MM (n=17), MFM (n=19), EMP (n=12) and SBP (n=6) treated at our institution from 1994-2012 and initially selected based on provided tissue samples. The MM control cohort was matched with regard to age, gender and prior treatment regimens. In 3 of 19 cases of MFM extramedullary locations were found at initial diagnosis. Two patients with EMP converted into MFM during the treatment. All EMP lesions arised in the upper aerodigestive tract. However extramedullary involvement in MFM was found in the head and neck (37%), chest (53%), abdomen (21%) and extremities (31%). Results: The 5-year OS rate was 92% in the patients with EMP. Whereas, 5-year OS rates of MM patients achieved 70.6%. MFM patients reached only 58% 5-year OS. The 5-year probability of progression was significantly higher in the group with MFM than EMP (89.5% vs 33%, p=0.0076, log rank test). Median progression free survival was 34 months for MM and 20 months for MFM (p=0.18). Conclusions: The 5-year progression free survival could be reached in 10 out of 12 patients with EMP. Two of the patients with primary EMP developed MFM. Moreover, the secondary development of extramedullary manifestation was associated with worse prognosis. Since the differences in the disease development cannot be easily predicted, there is an need of additional predictors that take into account different genetically determined risk status. Our retrospective analysis of genetic variations in this cohort of patients indicates the need of additional predictors in future randomized studies in these rare subtypes of MM.

Multiple myeloma with D immunoglobulin

The immunoglobulin D multiple myeloma is a rare form of multiple myeloma and affects a young population. It is characterized by its clinical severity and poor prognosis. We report four cases of multiple myeloma immunoglobulin D diagnosed and supported in the university hospital Center of Sale and Rabat-Morocco. We propose to study the epidemiological, clinical and biological characteristics of this rare type of monoclonal gammopathy. Through the observations reported, the clinical aspect of myeloma is characterized by the high frequency of extra-bone manifestations including impaired kidney function. The immunoglobulin D multiple myeloma is mainly type λ, the IgD κ is rare, the predominance of λ light chains could be explained by rearrangements at the immunoglobulin genes. Bence-Jones proteinuria is almost constant in the multiple myeloma immunoglobulin D, it is mainly type λ, reflecting excess production of light chains by plasma cells. The marrow is invaded by plasma cells in very different proportions of up to 95%. It's a clinical entity, difficult to diagnose, particularly when low homogeneous band on electrophoresis goes unnoticed for an eye inexperienced or when immune serum anti-IgD was not used during the immunotyping.

Atypical imaging feature of Non-secretory multiple myeloma

Non-secretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma in which no monoclonal gammopathy can be demonstrated in the serum or urine. We describe a rare case of non-secretory multiple myeloma in a 23 year old female presenting with bilateral limb weakness of two years duration. Clinically she was diagnosed to have Pott's spine and was treated with category 1 anti tubercular drugs. Hematological investigations showed plasmacytosis and radiography showed osteolytic lesions. No monoclonal gammopathy was found in the serum or urine. MRI showed multiple compressions with sclerosis within vertebral bodies suggestive of osteomalacia/ diffuse infiltrative disorder. The free light chain (FLC) assay revealed increment in the free kappa light chain and an abnormal κ/λ ratio. Free Light Chain assay (FLC) when used in complement with Protein Electrophoresis (PEP) and Immunofixation Electrophoresis (IFE) were pivotal in diagnosis of non secretory multiple myeloma or light chain myelomas. FLC is a useful monitoring tool because it reflects therapy results due to short serum half life.

A rare case of plasma cell leukemia in a 35 year old

Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supportive care. Patient improved dramatically and he was discharged on regular follow-up.

Bortezomib appears to have substantial activity in patients with plasma cell leukaemia, a rare, aggressive form of multiple myeloma,

Bortezomib appears to have substantial activity in patients with plasma cell leukaemia, a rare, aggressive form of multiple myeloma,

Blauverfärbung der Hände, Taubheitsgefühl an den Füssen, indolente Lymphknotenschwellung zervikal bei einem 73-jährigen Mann

A 73-years old patient came to our outpatient clinic because of a blue discoloration of his hands. Furthermore there was a systemic inflammatory reaction, burning pain and numbness of his feet due to a polyneuropathy, and an indolent enlargement of the cervical lymph nodes. In 1996 and 2001 cervical lymph node resections were done because of localized angiofollicular lymphnode hyperplasia (Castleman's disease). The laboratory values confirmed a systemic inflammatory reaction, a hypothyreosis and a monoclonal gammopathy. A CT-scan showed enlarged cervical, intrathoracic and abdominal lymphnodes and a splenomegaly. So all the criterias for a POEMS syndrome (special form of multiple myeloma) were met with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. The generalized lymphadenopathy corresponded histologically to the prior mentioned Castleman's disease. The patient responded well to systemic glucocorticoid treatment and today he is asymptomatic.

PET/CT and MR imaging in myeloma

Myeloma is the most common primary bone malignancy. It accounts for 10% of all hematological malignancies and 1% of all cancers. In the United States, there are an estimated 16,000 new cases and over 11,000 deaths yearly due to myeloma. Plasma cell dyscrasias manifest themselves in a variety of forms that range from MGUS (monoclonal gammopathy of undetermined significance) and smoldering myeloma that require no therapy, to the "malignant" form of multiple myeloma. The role of imaging in the management of myeloma includes: an assessment of the extent of intramedullary bone disease, detection of any extramedullary foci, and severity of the disease at presentation; the identification and characterization of complications; subsequent assessment of disease status. This review will focus on the use of PET/CT and MR imaging for myeloma patients at the time of initial diagnosis and for follow-up management, based on current reports in the literature and our practice at the Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center in Baltimore, USA.