Diagnosis Of Plasma Cell Myeloma Research Articles

A case of multiple myeloma with AL amyloidosis showing giant Russel bodies.

A 67-year-old male patient presented to our hospital with streptococcus pneumonia and a neck phlegmon. As part of an initial workup, a review of an intravenous immunoglobulin order for a possible secondary hypogammaglobinaemia and pneumosepsis showed low IgA and IgM subsets but overall increased IgG class proteins (0.08, 0.3, and 22.8 g/L respectively). The IgG class subset analysis showed decreased IgG class 2–4 but elevated IgG class 1 levels (28.7 g/L). For lack of bona fide hypogammaglobinemia, intravenous immunoglobulin therapy was denied, and further workup including a bone marrow biopsy was undertaken. Patient also presented with secondary erythrocytosis (Haemoglobin 195, janus kinase 2 [Jak2] negative, with increasing erythropoietin [EPO] level), attributed to severe sleep apnea and asthma. A serum electrophoresis (SPEP) showed an IgG lambda monoclonal protein (19 g/L) with elevated serum lambda free light chain (588.5 mg/L) with a marked concomitnat background gamma globulin suppression. A bone marrow biopsy showed scanty background residual trilinear hematopoiesis with an increase in lambda clonal plasma cells (90% of cellularity). Specifically the bone marrow aspirate showed frequent inclusions overlaying the nucleus (Dutcher bodies) and cytoplasm (Russel bodies) of the plasma cells (Figure 1, panel A, white and black arrows respectively, stained by May-Grünwald- Giemsa x 40 objective). Many of the inclusions seen were smaller leaving the cellular morphology intact. Having said this, within the aspirate particles, large/giant inclusions were seen (panel B, aspirate granule x40 magnification). Moreover, a trephine biopsy showed many large spherical bodies which showed cytoplasmic ballooning and resulted in complete cellular effacement and displacement of the nucleus (Figure 1, panels C–E Hematoxylin and Eosin stain x40 (C) and x50 (D,E) magnification respectively; black arrows point to overstuffed plasma cells with eccentric nuclei). CD138/lambda stains confirmed that these were not cell-free but were inclusions within the plasma cell cytoplasm (Figure 1, panels F and G, CD138 and lambda stains respectively, x20 magnification). Lastly a Congo red stain for amyloid showed salmon pink deposits with apple green birefringence under polarized light (panels H&I showing a bone marrow blood vessel, Congo red ×20 magnification). With a confirmed diagnosis of plasma cell myeloma the patient was treated with cyclophosphamide, bortezomib and dexamethasone therapy, forgoing any intravenous immunoglobulin. The first description of intracytoplasmic inclusion in multiple myeloma were provided by Russel (1890) and subsequently termed Russel bodies. Mott cells refer to plasma cells with multiple inclusions such as Russel bodies. Dutcher bodies refer to cytoplasmic inclusions that overlay the nucleus. These cytoplasmic inclusions have been observed in both reactive and malignant plasma cells. They represent accumulations of mucopolysaccarides and immunoglobulin, which highlights the common nature of these inclusions. There is no established prognostic significance of such inclusions. One study by Jiang et al. reveals a correlation between the presence of Dutcher bodies and t(4;14), which is an adverse prognostic marker in multiple myeloma. Both authors were involved with taking photos, and writing and editing the manuscript. The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported The authors received no specific funding for this work. There are no patient identifiers in this study. Verbal consent has been obtained at the time of bone marrow biopsy. All data have been presented and are available for review.

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.

Simultaneous diagnosis of plasma cell myeloma and chronic lymphocytic leukemia on bone marrow trephine biopsy.

Simultaneous diagnosis of plasma cell myeloma and chronic lymphocytic leukemia on bone marrow trephine biopsy.

Case report: Thoracic and lumbar plasma cell myeloma mimicking hemangiomas on MRI and 18F-FDG PET/CT

Plasma cell myeloma (PCM) is a malignant clonal disease of abnormal proliferation of plasma cells, which is the second most common hematological malignancy after leukemia. PCM often diffuses and involves the bones of the whole body, especially the spinal column, ribs, skull, pelvis, and other axial bones and flat bones. Herein, we present a 55-year-old man who came to the hospital seeking medical help for low-back pain and numbness in his lower limbs. Computed tomography (CT) was performed because the clinician suspected that the patient had a herniated disc, and the results showed that the 7th thoracic vertebrae and the 3rd lumbar vertebrae showed a low density of bone destruction with “honeycombing” changes. Magnetic resonance imaging (MRI) showed that the corresponding lesions presented long T1 and long T2 signals, and the lesions were significantly enhanced in contrast-enhanced T1WI sequences, and fluoro18-labeled deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed mild radioactive uptake in the lesions. Based on these imaging findings, the patient was considered for a diagnosis of hemangiomas, and surgery was performed because the affected vertebra was pressing on the spinal cord. However, intraoperative frozen section examination showed that the patient had plasma cell myeloma. Our case study suggests that PCM involving a single thoracic and lumbar spine is rare and should be considered as one of the imaging differential diagnoses of hemangiomas. Moreover, the diagnosis of PCM is difficult when the number of lesions is small, especially when the plasma cell ratio is within the normal reference range in laboratory tests.

PB1962: COMPARISON OF EXPRESSION OF NSD2, CYCLIN D1 AND C-MAF BY PLASMA CELLS IN BONE MARROW AND BONE PLASMACYTOMA IN PATIENTS WITH PLASMA CELL MYELOMA

Background: Bone plasmacytomas forms as a result of destruction of bone structures by tumor proliferate and its escape out of the medullar cavity. According published data, the incidence of bone plasmacytomas at the time of plasma cell myeloma (PCM) diagnosis ranges from 7 to 32,5%, whereas rates are higher in a relapse. Bone plasmacytomas in most cases are composed of mature plasma cells, while immature morphology is mainly characteristic for extramedullary plasmacytomas. It is shown, that plasmacytoma cells are the descendants of bone marrow tumor plasma cells. Due to acquisition of new qualities as a downregulation of adhesion molecules, secretion of growth factors, activation of oncogenes and antiapoptotic factors, new subclones of tumor cells can survive without support from bone marrow microenvironment. Aims: to compare morphological consistency and immunohistochemical characteristics of PCM substrate in bone marrow trephines and bone plasmacytomas biopsy specimens. Methods: In retrospective study were included 13 patients with PCM aged from 36 to 67 years (median 55 years). At the time of diagnosis all patients underwent biopsy of bone plasmacytoma. The diagnosis of PCM verified according to IMWG criteria (2014). All patients have been examined with routine laboratory tests, immunochemical analysis of serum proteins and urine, cytologic examination of bone marrow smears, histologic and immunohistochemical examinations of bone marrow trephines and bone plasmacytomas biopsy specimens, instrumental examinations (CT, MRI). Immunohistochemical staining of bone marrow trephines and bone plasmacytomas biopsy specimens made with using a stainer Leica Bond-Max, reactions with antibodies to CCND1 (clone SPA4, Cell Marque), NSD2 (clone 29D1, Abcam), c-MAF (clone ERP16484, Abcam). The cut-off scores for determining positivity for markers have been taken 5% for CCND1, 10% for NSD2 and c-MAF (by T. Murase et al., 2019). Microscopic examination of histologic and immunohistochemical slides have been done on light microscope Leica 3000. Results: PCM substrate by histologic examination in bone marrow trepnines and bone plasmacytomas biopsy specimens were presented by mature plasma cells. In two patients (1 and 8) in bone plasmacytoma have been seen proplasmocytes between mature plasma cells, but in bone marrow have been seen only clusters of mature plasma cells. According to the results of immunohistochemical examination the expression of proteins-products of oncogenes have been revealed in most patients (12 of 13) in plasma cells of bone marrow and bone plasmacytomas, wherein in half of the patients (patients 7-12) the expression of proteins-products of oncogenes coincides in bone marrow and bone plasmacytoma. We have revealed a discordant expression in another patients (tabl. 1). We’ve paid a special attention to the patients 1-3, in whom in bone marrow have been revealed an expression of 1/3 protein, but in bone plasmacytoma – 2/3 (patients 2 and 3) or all of 3 studied proteins (patient 1). This phenomenon is possible to consider as a heterogeneity of clonal composition of bone plasmacytoma as a consequence of tumor evolution. Image:Summary/Conclusion: Discordant expression of proteins-products of oncogenes NSD2, cyclin D1 and c-Maf in tumor cells in bone marrow and bone plasmacytoma could be evidence of different tumor clones activation in PCM.

Artificial Intelligence in Plasma Cell Myeloma: Neural Networks and Support Vector Machines in the Classification of Plasma Cell Myeloma Data at Diagnosis

Background: Plasma cell neoplasm and/or plasma cell myeloma (PCM) is a mature B-cell lymphoproliferative neoplasm of plasma cells that secrete a single homogeneous immunoglobulin called paraprotein or M-protein. Plasma cells accumulate in the bone marrow (BM) leading to bone destruction and BM failure. Diagnosis of PCM is based on clinical, radiologic, and pathological characteristics. The percent of plasma cells by manual differential (bone marrow morphology), the white blood cell (WBC) count, cytogenetics, fluorescence in situ hybridization (FISH), microarray, and next-generation sequencing of BM are used in the risk stratification of newly diagnosed PCM patients. The genetics of PCM is highly complex and heterogeneous with several genetic subtypes that have different clinical outcomes. National Comprehensive Cancer Network guidelines recommend targeted FISH analysis of plasma cells with specific DNA probes to detect genetic abnormalities for the staging of PCM (4.2021). Recognition of risk categories through training software for classification of high-risk PCM and a novel way of addressing the current approaches through bioinformatics will be a significant step toward automation of PCM analysis. Methods: A new artificial neural network (ANN) classification model was developed and tested in Python programming language with a first data set of 301 cases and a second data set of 176 cases for a total of 477 cases of PCM at diagnosis. Classification model was also developed with support vector machines (SVM) algorithm in R studio and interactive data visuals using Tableau. Results: The resulting ANN algorithm had 94% accuracy for the first and second data sets with a classification summary of precision (PPV): 0.97, recall (sensitivity): 0.76, f1 score: 0.83, and accuracy of logistic regression of 1.0. SVM of plasma cells versus TP53 revealed a 95% accuracy level. Conclusion: A novel classification model based only on specific morphological and genetic variables was developed using a machine learning algorithm, the ANN. ANN identified an association of WBC and BM plasma cell percentage with two of the high-risk genetic categories in the diagnostic cases of PCM. With further training and testing of additional data sets that include morphologic and additional genetic rearrangements, the newly developed ANN model has the potential to develop an accurate classification of high-risk categories of PCM.

An Unusual Case Of Pernio (Chilblains) With Underlying Cryoglobulinemia – Case Study

Abstract Introduction/Objective Pernio or chilblains, is a rare condition associated with small pruritic swellings of the extremities triggered by low temperature. Generally, the patients experience a burning and itching sensation in the affected areas that increases with return to warm temperature. The underlying risk factors include autoimmune disorders and cryoglobulinemia. Herein we present an unusual and rare case of chilblains that evaded diagnosis for few years. The general concepts of analytical and clinical evaluations of this condition, with emphasis on accurate diagnosis of gammopathies, along with the importance of laboratory evaluations and accurate interpretation of laboratory results will be discussed. Methods Multiple laboratory investigations (CBC, electrolyte analysis, serum protein electrophoresis, free light chain analysis) were pursued together with skin biopsies. Additionally, CT scan under low radiation exposure and bone marrow biopsy were followed. Plasma sample viscosity at room temperature was evaluated. Results Skin biopsies from right anterior thigh and left arm revealed leucocytoclastic vasculitis with normal perivascular staining for C3 and fibrinogen. Serum sample at room temperature exhibited increased viscosity and protein electrophoresis identified a highly elevated IgG kappa monoclonal globulin peak whose concentration increased upon warming and dilution of the sample, suggesting that agglutinin precipitated at cold temperature (below body temperature). Analysis of free light chains revealed elevated concentration of kappa light chain whose concentration also increased upon warming the serum sample. Whole body CT scan and bone marrow biopsy analysis further identified lytic lesions. These investigations established the diagnosis of plasma cell myeloma (CD138 staining) with expression of monoclonal immunoglobulin precipitating at temperatures below that of the body. Conclusion Given the above findings this case of chilblains can be classified as cryoglobulinemia vasculitis. The importance of attention to details (e.g. characteristics of serum samples), accurate interpretation of laboratory findings and analysis clinical information are all very crucial to arrive at a differential diagnosis.

Oral Cavity: an Inception to Diagnose Plasma Cell Myeloma. Case Report and Literature Review

Plasma cell myeloma (PCM) is a malignant disease of monoclonal plasma cells which is multicentric in origin. The accurate diagnosis demands contemplation of conventional histopathology with meticulous correlation of medical history, clinical and imaging details; and adjunctive investigations. We report a case of 50 year old female who presented with chief complaint of diffuse swelling of jaw and close observation revealed walking difficulty attributed to bone pain. Imaging showed ill-defined punched out lesions in left mandible. Biopsy with adjuvant immunohistochemistry revealed features suggestive of plasmacytoma and work up for plasma cell myeloma was advised. Further investigations showed features of end organ damage (hypercalcemia, increase serum creatinine, anemia, and > 1 osteolytic lesions). Serum electrophoresis and bone marrow aspiration confirmed the diagnosis of plasma cell myeloma. Patient was referred to oncology department where thalidomide was prescribed and patient showed drastic improvement in symptoms within a month. However demise of patient occurred after 7 months which might be attributed to delay in diagnosis by the clinician. Thus, this case report highlights the need of awareness and knowledge on the part of dental professionals for even rare systemic diseases to emphasize early diagnosis and treatment.

Case Study: An Unusual Presentation of Smoldering Multiple Myeloma in a patient with End Stage Renal Disease

A 59-Year-Old Male patient presented to the benign hematology clinic with a chief complaint of persistent macrocytic anemia with mild thrombocytopenia of unclear etiology. The patient has an extensive medical history including end stage renal disease on hemodialysis post failed kidney transplant and recurrent gastrointestinal bleeds. Two colonoscopies have recently been unable to identify a bleeding source that would account for prolonged anemia. The degree of anemia that the patient was experiencing was disproportionate to clinical documentation of bleeding, and high MCV with normal TSH, Folate, B12 and no alcohol intake ruled out a deficiency as cause of anemia. Iron studies indicated that the cause was Anemia of Chronic disease. A Bone Marrow Biopsy was requested to rule out a Hematologic Malignancy. The Bone Marrow Biopsy came back with a reported diagnosis of Plasma Cell Myeloma as the core biopsy was fifty percent cellular and plasma cells made up fifteen to twenty percent of core biopsy cellularity. Paraprotein and radiologic studies were ordered to further differentiate between multiple myeloma, plasma cell leukemia and smoldering multiple myeloma. Radiologic studies were negative for pathogenic lesions, while paraprotein studies showed a monoclonal gammopathy of IgG Kappa and a bioclonal IgA region that couldn9t be further quantified. The patient was further refered to the malignant hematology Myeloma team. The patient hasn9t returned to make any further appointments with hematology, but has been admitted once for complications related to his end stage renal disease. Asymptomatic myeloma, also known as smoldering myeloma, is characterized by having a clonal plasma cell population in the bone marrow that is greater than 10 percent while having no organ damage. Some patients will start out asymptomatic before progressing to full blown disease. Treatment normally begins after symptoms evolve.

Case Study: An Unusual Presentation of Smoldering Multiple Myeloma in a Patient With End-Stage Renal Disease

<h3>ABSTRACT</h3> A 59-year-old male patient was presented to the benign hematology clinic with a chief complaint of persistent macrocytic anemia with mild thrombocytopenia of unclear etiology. The patient had an extensive medical history, including end-stage renal disease on hemodialysis after failed kidney transplant and recurrent gastrointestinal bleeds. Two colonoscopies had recently been unable to identify a bleeding source that would account for prolonged anemia. The degree of anemia that the patient was experiencing was disproportionate to clinical documentation of bleeding, and high mean corpuscular volume with normal <i>thyrotropin</i>, Folate, B12 and no alcohol intake ruled out a deficiency as cause of anemia. Iron studies indicated that the cause was anemia of chronic disease. A bone marrow biopsy was requested to rule out a hematologic malignancy. The bone marrow biopsy came back with a reported diagnosis of plasma cell myeloma, as the core biopsy was 50% cellular and plasma cells made up 15%–20% of core biopsy cellularity. Paraprotein and radiologic studies were ordered to further differentiate between multiple myeloma, plasma cell leukemia, and smoldering multiple myeloma. Radiologic studies were negative for pathogenic lesions, whereas paraprotein studies showed a monoclonal gammopathy of IgG Kappa and a bioclonal IgA region that could not be further quantified. The patient was further referred to the malignant hematology myeloma team. The patient has not returned to make any further appointments with hematology but has been admitted once for complications related to his end-stage renal disease. Asymptomatic myeloma, also known as smoldering myeloma, is characterized by having a clonal plasma cell population in the bone marrow that is greater than 10% while having no organ damage. Some patients will start out asymptomatic before progressing to full-blown disease. Treatment normally begins after symptoms evolve.

Classic features of primary systemic amyloidosis (AL amyloidosis) leading to diagnosis of plasma cell myeloma

The diagnosis of primary systemic amyloidosis, also known as AL (amyloid light-chain) amyloidosis, is often delayed owing to its nonspecific manifestations as well as its rarity. A 64-year-old woman presented with an eight-month history of significant weight loss, anemia, fatigue, and progressive painful cutaneous lesions on her hands, lips, back, perianal, and vulvar area that were originally treated unsuccessfully with antimalarials and systemic corticosteroids. Histopathological examination revealed an amorphous dermis with pale pink material that demonstrated positive birefringence with Congo red staining. Subsequently, the patient underwent a bone marrow biopsy, which uncovered a plasma cell myeloma, the source of her amyloidogenic protein production.

Prognostic Impact of Bone Marrow Erythropoiesis on Newly Diagnosed Plasma Cell Myeloma: A Single Institutional Analyses

Introduction: In plasma cell myeloma (PCM), tumor burden and activity plays an important role in diagnosis and prognosis (e.g. circulating plasma cells), however very little attention has been directed to the impact of the non-plasma cell component of the bone marrow. The presence of anemia has been used to distinguish PCM from smoldering myeloma; however this can be a non-specific finding as there are many potential causes of anemia besides PCM. We sought to determine if the level of erythropoiesis in bone marrow biopsies may be a more reliable prognostic factor. In the study herein, we assessed the level of bone marrow erythropoiesis in patients with newly diagnosed PCM, and compared those findings with cytogenetic results (CGs), other prognostic factors and overall clinical outcome. We hypothesized that patients with adequate erythropoiesis (AEp) are likely to have favorable cytogenetics and better outcome compared to those with decreased erythropoiesis (DEp).Methods: We retrospectively reviewed pathology database for bone marrow biopsies in patients with diagnosis of plasma cell myeloma (PCM) at Beaumont Hospital, an academic community center from 2012 and 2014. Biopsy cases without anemia were excluded. A total of 91 patients with plasma cell myeloma and anemia were identified. Each biopsy was re-examined to determine the level of erythropoiesis. The level of erythropoiesis was calculated by multiplying erythroid fraction (obtained from M:E ratio) with non-plasma cell bone marrow cellularity. Cases were separated into AEp and DEp using an erythroid compartment cut-off of 7.5% based on already established data. Kaplan-Meier analysis was used to compare survival between groups.Results: Demographic distribution of studied patients were 46 (50.1%) white, 39 (43%) African Americans and 6 (6.6%) others. Out of 91 cases analyzed, 38 (42%) had AEp whereas 53 (58%) had DEp. Among those with AEp, 23 (62%) had favorable CGs (defined as those without t (4, 14), t (14, 16), t (14, 20) or 17 p deletion); 15 (38%) had unfavorable CGs. Among those with DEp, 14 (26%) had favorable CGs whereas 39 (74%) had unfavorable cytogenetics. The vast majority of patients with favorable CGs were alive whether they had AEp (87%) or DEp (79%), thus CGs remained significant even after controlling for erythroid compartment (p = 0.03). Overall, those with AEp were noted to have significantly lower β-2 microglobulin (AEp median =2.42 mg/dL, DEp median = 4.50 mg/dL, p = 0.02). Kaplan-Meier analysis showed a significant difference in survival curves among the four groups (AEp with favorable CGs, AEp with unfavorable CGs, DEp with favorable CGs, DEp with unfavorable CGs, p<.0001). While the two groups with favorable CGs showed no significant difference (p=.6050), the two groups with unfavorable CGs did (p=.0027).Conclusion: Our findings suggest that patients with PCM and anemia are not a homogenous population. Assessment of the erythroid compartment in these patients reveals a population with AEp that has more favorable CGs and lower β-2 microglobulin than patients with DEp. Despite this finding, patients with favorable CGs had a favorable clinical outcome whether they had AEp or not, indicating that current therapies can overcome differences in erythropoiesis in that group. For patients with unfavorable CGs, however, those with AEp had superior survival outcome compared to those with DEp, indicating that there may be some prognostic or diagnostic utility to assessing erythropoiesis in patients who meet current criteria for PCM, and possibly, incorporating erythropoietic activity into diagnostic/prognostic schema. DisclosuresNo relevant conflicts of interest to declare.

Performance of Diagnostic Tests for Plasma Cell Myeloma

Introduction. In vitro laboratory tests to diagnose of plasma cell myeloma vary considerably in sensitivity, specificity and positive and negative predictive values. We compared the performance of quantification of free immunoglobulin light chains with other methods used to detect a monoclonal protein in serum and/or urine.Objective. Compare sensitivity, specificity and positive and negative predictive values of several in vitro laboratory tests to detect monoclonal proteins in serum and urine in persons with plasma cell myeloma.Methods. 70 subjects with plasma cell myeloma and 50 controls were studied. Diagnostic tests included: (1) quantification of free and total immunoglobulin light-chains by immune assays; (2) immune fixation of heavy-and light-chains in serum and urine after gel electrophoresis; and (3) serum protein capillary electrophoresis. Diagnosis of plasma cell myeloma was based on clinical and radiological criteria, bone marrow examination and flow cytometric immune phenotyping with monoclonal antibodies to CD56, CD19, CD138 (CD38) and CD45. Sensitivity, specificity and positive and negative predictive values for each tests were estimated from contingency tables.Results. Quantification of free immmunoglobulin light-chains had the highest sensitivity and specificity and best positive and negative predictive values. Immune fixation of serum immunoglobulins was next best. Quantification of total immunoglobulin light-chains was the least sensitive and specific with the worst positive and negative predictive values. Quantitation of free light-chains had the additional advantage of objectivity (independence from observer bias). The immune fixation test was the most subject to observer bias.Conclusion. Quantification of free immunoglobulin light-chains had the best sensitivity, specificity and positive and negative predictive values for diagnosing plasma cell myeloma. (Table 1) DisclosuresNo relevant conflicts of interest to declare.

Lower number of 5-hydroxymethylcytosine-expressing cells in plasma cell myeloma than in reactive plasma cell hyperplasia: a useful immunohistochemical approach for identification of neoplastic plasma cells

Plasma cell myeloma (PCM) is a haematological malignancy defined by aberrant proliferation of plasma cells in the bone marrow. For the diagnosis of PCM, immunostaining of light chains or surface marker analyses by flow cytometry is needed but sometimes difficult. Aberrant methylation at the carbon-5 position of cytosine results in 5-methylcytosine (5-mC), which is a well-known epigenetic hallmark of cancer in mammals. 5-mC is oxidised to 5-hydroxymethylcytosine (5-hmC), and low 5-hmC levels occur in several cancers and haematopoietic malignancies. We compared the expression of 5-hmC by immunohistochemistry (IHC) in neoplastic plasma cells in 31 PCM cases and in non-neoplastic plasma cells in 14 benign reactive lesions. The mean percentage of 5-hmC-positive cells was 7.8% and 81.5% in PCM and plasma cell hyperplasia, respectively. Thus, the frequency of 5-hmC-positive cells in PCM specimens was significantly lower than that in reactive plasma cell hyperplasia (p < 0.001 by Student's t-test). IHC of 5-hmC is a useful method for differentiating neoplastic plasma cells from non-neoplastic plasma cells in reactive lesions even in tiny tissue samples unsuitable for flow cytometric analyses or for immunoglobulin light chain IHC.

Intracranial hemorrhage as initial manifestation of plasma cell myeloma: A case report

This is the case of a previously healthy 48 year-old male whom presented with mild confusion, low-grade headache, and left sided weakness. Computed tomography of the head revealed a large acute right frontal lobe intracranial hemorrhage (ICH) and intraventricular extension, with normal vascular imaging. Initial laboratory testing was inconsequential. The patient required emergent evacuation, with pathology revealing only elements of a hematoma. Further laboratory testing and bone marrow biopsy results confirmed the diagnosis of plasma cell myeloma. Other systemic signs/symptoms of this disease were notably absent. This report provides the first description of an ICH as the presenting manifestation of plasma cell myeloma (PCM; multiple myeloma).

Significant cytogenomic evolution identified by SNP chromosome microarray analysis accompanies plasmablastic transformation of a hyperdiploid plasma cell myeloma

Plasma cell myeloma (PCM) is a hematological malignancy involving clonal proliferation of plasma cells in bone marrow. It is the third most common hematolymphoid malignancy in the USA and primarily affects elderly people with a median onset age of 69 years and a survival duration ranging from a few months to more than 10 years. This variation is due largely to the fact that PCM is a genetically complex and heterogeneous disease. The tumor cells demonstrate a wide range of morphological features, from mature and recognizable plasma cells to pleomorphic forms. In a subset of cases, however, the tumor cells demonstrate plasmablastic morphology which predicts a poor prognosis. We present a patient with an initial diagnosis of plasma cell myeloma with typical morphology and a hyperdiploid karyotype predictive of a favorable outcome. The patient’s disease was unresponsive to chemotherapy and evolved over the course of 43 months into a myeloma with plasmablastic features characterized by a highly complex abnormal karyotype demonstrating previously unidentified poor cytogenetic markers including CKS1B gene duplication and p53 gene deletion by fluorescence in situ hybridization (FISH). Post-mortem evaluation by single nucleotide polymorphism (SNP array) chromosome microarray analysis revealed additional structural abnormalities in the diagnostic specimen as well as significant genomic evolution in the plasmablastic myeloma.

A Herald of Plasma Cell Myeloma: A Report of Malignant Plasma Cells Identified in Parathyroid Adenoma and a Review of Non-parathyroid Malignancies in Parathyroid Glands

Involvement of the parathyroid glands by non-parathyroid neoplasia is an infrequent event. Rare cases of metastases to the parathyroid gland have been reported in parathyroidectomies and autopsies of patients with known solid or hematopoietic malignancies. Here, we present a case of atypical clonal plasma cells incidentally identified within a parathyroid adenoma resected for hyperparathyroidism and hypercalcemia, which served as the sentinel event for a subsequent diagnosis of plasma cell myeloma. To our knowledge, this is the only reported case of a hematopoietic malignancy involving a parathyroid adenoma and the only reported case of malignant hematopoietic cells initially detected in parathyroidectomy.

The value of bone marrow imprint in diagnosis of plasma cell myeloma and monitoring the remission after chemotherapy

Objective To investigate the value of bone marrow imprint in the diagnosis of plasma cell myeloma and the remission rate after chemotherapy. Methods Bone marrow aspiration, bone marrow imprint, and bone marrow biopsy of plasma cell myeloma with 128 patients were collected. The bone marrow biopsy was used as the standard. Bone marrow imprint was compared to bone marrow aspiration in bone marrow nucleated cells quantity, infiltration degree, and diagnostic coincidence rate. Sensitivity, specificity, positive predictive value, and Youden index were evaluated. Results The results of bone marrow imprint showed that the number of nucleated cells was better than that of bone marrow aspiration (P 0.05). Bone marrow biopsy combined with CD38 (+ ) showed the degree of infiltration of bone marrow as the standard, and the bone marrow imprint was better than that of bone marrow aspiration (P 0.05). To evaluate the compliance rate of bone marrow infiltration in bone marrow imprint: In phase I, the compliance rate of bone marrow aspiration was 95.83% (23/24) and bone marrow imprint of 91.67% (22/24), the difference was not statistically significant (P>0.05); In phase II, bone marrow imprint coincidence rate was 92.86% (65/70), which was significantly higher than that of bone marrow aspiration in 65.71% (46/70) (P<0.05); In phase III, bone marrow imprint coincidence rate was 79.41% (27/34), which was significantly higher than that of bone marrow aspiration in 44.12% (15/34) (P<0.05). The other parameters, such as sensitivity, specificity, positive predictive value, and Youden index were better than those of bone marrow aspiration. Conclusions Bone marrow imprint has characteristics that both bone marrow aspiration and bone marrow biopsy have. It has obvious advantages in diagnosis of plasma cell myeloma and monitoring the remission after chemotherapy. Key words: Bone marrow examination; Biopsy; Microtomy; Multiple myeloma/DI/DT

Współistnienie dyskrazji komórek plazmatycznych i zespołu mielodysplastycznego — opisy przypadków i przegląd piśmiennictwa

The improvement in plasma cell myeloma (PCM) treatment and much longer overall survival of the patients led to the observation of long-term complications of the therapy. These include secondary malignancies, such as myelodysplastic syndromes (MDS) and acute myeloid leukemia. Definitely less common is the co-occurrence of MDS at the point of diagnosis of PCM or MDS evolving during the observation of untreated patients with monoclonal gammapathy of undetermined significance. In the article we describe 5 patients: one with a therapy-related MDS, the co-occurrence of both diseases from the diagnosis and MDS preceding PCM for several years.

Clonal heterogeneity in plasma cell myeloma

A 52-year-old man presented to the emergency department with fevers and chills in December, 2014, and was admitted with a diagnosis of pneumonia. CT to exclude pulmonary embolus showed diff use osseous lytic lesions, and he was also found to have anaemia and an IgG kappa monoclonal protein of 55·8 g/L on protein electrophoresis (a single band). After a bone marrow biopsy he was given a diagnosis of plasma cell myeloma and was treated with four cycles of CyBorD chemotherapy (cyclophosphamide, bortezomib, and dexamethasone) in preparation for an autologous stem cell transplantation. The aspirate from the bone marrow sampling showed a substantial increase in plasma cells (fi gure). The bone marrow core biopsy sample showed a hypercellular marrow with increased plasma cells, estimated to occupy 80% of marrow cellularity by CD138 immunohistochemistry. We saw that the neoplastic plasma cells had two distinct immunophenotypes: one population expressed CD138, kappa, and CD56; the other expressed CD138, kappa, CD20, and CD79a. Morphological diff erences were visible on routine haematoxylin and eosin staining, with prominent nucleoli in the CD56 area (fi gure). We could not create a more extensive immunophenotype because of tissue limitations, and too few events were captured by fl ow cytometry to allow characterisation using this technique. This case shows clear phenotypic heterogeneity in plasma cell myeloma, which might be due to multiple neoplastic clones (clonal heterogeneity). Immunophenotyping is routinely used in haematology to infer clonality, although variation is not defi nitive proof of clonality. Clonal heterogeneity in plasma cell myeloma is the foundation of work in the area of clonal tiding. Clonal tiding has been described in plasma cell myeloma with diff erent clones competing for dominance dependent on variable resistance to chemotherapy. These diff erent clones are typically shown using molecular techniques, but our image provides a practical illustration of this concept. Whether intratumoural phenotypic variation correlates to true clonal heterogeneity, and whether there is a role for identifi cation of this easily assessed entity in routine clinical practice, is unclear.