Reactive Plasmacytosis Research Articles

Systematic literature review of published cases of reactive plasmacytosis in peripheral blood and bone marrow

AimsThis study aims to summarise published cases of reactive plasmacytosis to provide a resource to aid haematopathologists and clinicians in the diagnostic workup of reactive plasmacytosis.MethodsWe searched published articles on...

Correlation between Morphological Typing and Monoclonality of Bone Marrow Plasma Cells and Its Diagnostic Value for High-Risk Smoldering Multiple Myeloma

To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells, and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM). The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital. The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain (sFLC) ratio, next-generation sequencing (NGS) detection results, and its correlation with monoclonal plasma cells detected by flow cytometry (FCM) were further verified. The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected, and the distribution of plasma cell clusters in patients with different disease was observed. The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis (RP) group, monoclonal gammopathy of undetermined significance (MGUS) group, smoldering multiple myeloma (SMM) group, HR-SMM group and multiple myeloma (MM) group; while the mean percentage of immature, primitive, reticular and flaming plasma cells were increased successively in the order of RP group, MGUS group, SMM group, and HR-SMM group, and the difference between any two groups was statistically significant (P < 0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2% of the total plasma cells. The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients (kappa=0.879 and kappa=0.891, both >0.75)，and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-( γ=0.825). The levels of non-involved immunoglobulin in IgG, IgA and IgM type HR-SMM patients were all decreased by more than 25% compared with the normal reference range, and the differences were statistically significant (P < 0.05). There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups (P >0.05). In HR-SMM patients, the immature, primitive, reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells, and they are correlated with monoclonal plasma cells. The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

Reactive plasmacytosis in HIV infection

Reactive plasmacytosis in HIV infection

Morphological Spectrum of Bone Marrow Aspirates in Infections: A Clinico-Hematological Analysis.

Bone marrow examination (BME) is an invaluable tool for cases with pyrexia of unknown origin and pancytopenia. However, it is under-utilized for diagnosing infectious etiology and there is a paucity of literature regarding its role in infective pathology. This study aims to bring to light the role of BME in diagnosing infectious pathology. A retrospective study was carried out on bone marrow aspirates (BMAs) sent to the hematology department over the past 4 years. Clinical details, peripheral smears and BMA were retrieved from the records and analyzed. Leishman-stained peripheral smears and BMA were studied along with bone marrow biopsy wherever feasible. A total of 52 cases were studied. The most common clinical presentation was fever, clinical finding was splenomegaly and hematological finding was anemia. Based on the morphological findings in combination with clinical history, cases were categorized into-parasitic (26.9%), viral (23.1%), tubercular (11.5%), and nonspecific infections (38.5%). Parasites such as Leishmania donovani, microfilaria, plasmodium falciparum, and vivax were reported in 14/52 (27%) cases. Associated BMA findings were plasmacytosis, eosinophilia, reactive lymphocytosis, or dyserythopoiesis. In 38% (20/52) cases, no specific cause of infection was found in the bone marrow. These patients showed histiocytosis, hemophagocytosis, maturation arrest in myeloid lineage, relative myeloid hyperplasia, dysmyelopoiesis, toxic granulation/vacuolation in myeloid cells, lymphocytosis, increased plasma cells or monocytosis in marrow. Increased histiocytes, hemophagocytosis, dysplastic changes, maturation arrest, relative myeloid hyperplasia or reactive plasmacytosis, lymphocytosis, and monocytosis are BMA features which must alert the pathologist towards an infectious disease process, a knowledge of these changes can help extend the scope of BME beyond hemato-lymphoid malignancies.

Hairy Cell Leukemia with Marrow Reactive Plasmacytosis and Mast Cell Hyperplasia: A Case Report and Brief Review of the Literature

Hairy cell leukemia (HCL) and HCL-like disorders, including HCL-variant, are disorders of heterogeneous mature lymphoid B-cells known for their hairy cell infiltration accompanied by a specific genetic profile, various clinical presentations, and, as they are uncommon hematological malignancies characterized by pancytopenia, the need for appropriate therapy. Sometimes HCL creates diagnostic challenges for clinicians, and its coincidence or association with mast cell and plasma cell infiltration is a rare condition. Herein, we report a case of HCL with confusing manifestations. A 44-year-old man was referred to the hospital for weakness, fatigue, and watery, non-bloody diarrhea. The laboratory tests showed pancytopenia, leading to a referral for bone marrow aspiration and biopsy. Medium to large cells exhibiting widespread cytoplasm, oval nuclei similar to monocyte nuclei (kidney-shaped) accompanied by an increased number of mast cells, and plasma cells were observed in the biopsy sample. In flow cytometry, the neoplastic cells were positive for CD19, FMC7, and the co-expression of the CD20/CD25, CD11C/CD22, and CD103 markers. In immunohistochemical staining, the mast cells were positive for CD117, the plasma cells were positive for CD138, and the hairy cells were positive for CD20. Overall, hematopathologists must be aware of various morphologic confounding factors such as lack of typical cell morphological features and increased plasma cell and mast cell infiltration in the diagnosis of patients with HCL.

Diving in the big blue: Atypical Mott cells in rapidly fatal primary amyloidosis.

A 75-year-old man with no previous medical history presented at the emergency unit with asthenia, anorexia, weight loss, and progressively increasing dyspnea revealing acute heart failure (N-terminal pro b-type natriuretic peptide:16 667 ng/L; troponemia: 47 ng/L). Echocardiography showed a granular appearance of the myocardium and interventricular septal hypertrophy, suggestive of amyloidosis. Chemistry disclosed high levels of immunoglobulin kappa light chains at 1240 mg/L (lambda light chains 14 mg/L; κ/λ ratio 86) and a detectable but unquantifiable IgA κ peak. Myocardial biopsies pathology showed an endocardium thickened by fibrosis. Within the myocardium, the presence of interstitial fibrillary deposits stained by Congo red and birefringent in polarized light confirmed the diagnosis of cardiac amyloid light-chain (AL) amyloidosis. The search for other organ damage disclosed vegetative involvement with orthostatic hypotension, icteric cholestasis (bilirubin 51.8 mg/L), undocumented digestive involvement (diarrhea with evocative endoscopic lesions), and glomerulonephritis (urinary proteinuria 4 g/24 h with 3 g/24 h albumin and 1 g/24 h immunoglobulin light chains). A bone marrow aspirate displayed 17% of plasma cells. Interestingly, a particular pattern of huge atypical Mott cells was identified (Figure 1A,B). The latter had so many cytoplasmic inclusions that the cytoplasm, and the nucleus could not be discriminated. These atypical cells are however plasma cells with an endoplasmic reticulum loaded with immunoglobulins and should be integrated as such in cell counts. Classical plasma cells and typical Mott cells with a few Russel bodies were also present (Figure 1C) indicating a continuum in the shape of the diseased plasma cells. Treatment with cyclophosphamide–bortezomib–dexamethasone-daratumumab was initiated in emergency. Unfortunately, the patient died 3 days later, of multiple organ failure. No additional septic or toxic causes could be identified. Mott cells are activated plasma cells containing intracytoplasmic inclusions with a “bunch of grapes” appearance. These inclusions, called Russell bodies, are dilated cisternae of the endoplasmic reticulum containing condensed immunoglobulins. They were identified in 1901 by the surgeon F.W Mott in the brains of monkeys with trypanosomiasis. Mott cells have been described in various pathological conditions: reactive plasmacytosis, monoclonal gammopathies, high grade B-cell lymphomas, Wiskott-Aldrich syndrome, and von Recklinghausen neurofibromatosis. AL amyloidosis is caused by clonal expansion of plasma cells producing misfolded immunoglobulin light chains responsible for the deposition of insoluble fibrillar proteins in many organs. Those most frequently affected are the kidneys, heart, liver, and peripheral nervous system. AL amyloidosis is a rare disease, and its diagnosis is often delayed. Although associated with a poor prognosis, AL amyloidosis presents a heterogeneous clinical expression and evolution. To our knowledge, the presence of Mott cells has rarely been described in this pathology. KR, ME, and BLC wrote the manuscript. KR, ME, and BLC performed biological analyses. CS treated the patient. All authors critically reviewed the manuscript. The authors have no conflict of interest to disclose. The authors received no specific funding for this work. The research was conducted in accordance with the principles embodied in the Declaration of Helsinki and in accordance with local statutory requirements.

BONE MARROW PLASMACYTOSIS- REACTIVE OR MALIGNANT? A DIAGNOSTIC CHALLENGE TO A NOVICE PATHOLOGIST

Plasmacytosis can be due to both reactive causes as well as monoclonal proliferation. Reactive plasmacytosis is seen in infections, malignancy, iron deciency, megaloblastic anemia, hemolytic anemia , liver cirrhosis, Castleman's disease and streptokinase treatment. Plasmacytosis in elderly patient can be a diagnostic confusion especially in absence of one or more of hypercalcemia, Renal insufciency, anemia and bone lesions (CRAB). We encountered a similar case of elderly person whose nal diagnosis was made after thorough radiological and pathological evaluation.

Perianal Plasmoacanthoma After BCG-Immunotherapy: Case Report and Review of Literature

Plasmoacanthoma is a rare verrucous tumor classified as a form of reactive plasmacytosis. We present the first reported case of plasmoacanthoma following exposure to bacillus Calmette-Guérin (BCG) and a comprehensive review of the literature to better illustrate the patients’ characteristics and proposed risk factors, clinical features, diagnosis, treatment, and outcome of current reports. A 64-year-old female presented with a perianal hyperkeratotic plaque and diffused inflammatory macerated erosions in the intergluteal cleft and adjacent to the plaque after intravesical BCG immunotherapy. Laboratory studies disclosed systemic abnormalities and local infection or malignancies. Biopsy showed intradermal polyclonal plasma cell infiltration with acanthosis. The lesions were successfully treated with carbon dioxide laser ablation followed by the combination of pulsed dye laser and intralesional corticosteroid. Diagnosis of cutaneous reactive plasmacytosis should be confirmed by excluding the systemic causes of plasmacytosis and malignancies. It responds well to intralesional corticosteroids; however, in severe cases and large sizes, other treatments such as carbon dioxide laser ablation and pulsed dye laser should be considered as a combined therapy. Identification of causative factors is impractical while skin irritants with subsequent inflammation seem to be involved; as in the current report, BCG contact with skin initialized the pathologic process.

Reactive bone marrow plasmacytosis: A common denominator with diverse etiology

Background and Aims: Reactive plasmacytosis (RP) is characterised by the diffuse distribution of mature polyclonal plasma cells in the bone marrow (BM) and it is known to occur in various disorders. These need to be differentiated from the clonal plasma cell dyscrasias (PCD). We aim to study the morphological features of RP and to help differentiate them better from PCD. Materials and Methods: We analysed 1409 consecutive BM aspirates for the percentage of plasma cells along with the associated clinical findings. The study group included cases with BM RP and the polyclonality being supported by serum protein electrophoresis or by kappa/lambda immunohistochemistry on BM biopsy. The clinical records, haemogram and BM aspiration findings were retrieved and reviewed in all cases. Morphological features of RP cases were analysed in detail. Further, these cases were compared with 10 confirmed cases of PCD in an attempt to distinguish between the two on morphology. Results: A total of 210 BM aspirates showed increased plasma cells (>3.5%). Clonality could be proven in 135 cases, of which 98 cases were polyclonal and 37 were PCD. Majority of RP cases were >40 years with male predominance. The plasma cell concentration in RP ranged from 4% to 25%. The associated diseases included infections followed by autoimmune diseases. On the morphology, RP unveiled scattered, non-aggregated mature plasma cells while in PCDs, there was a mixture of both immature and mature forms including plasmablasts with frequent clustering. Conclusion: A number of diseases show increased percentage of plasma cells in BM raising suspicion of PCD. It may be difficult to distinguish reactive from neoplastic conditions as there is an overlap both in cell counts and morphology. Assessment of subtle morphological features along with associated clinical and laboratory findings are cardinal for making a correct diagnosis.

Tissue-Specific Immunopathology in Fatal COVID-19.

Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.

Association of Multiple Myeloma and Giant Cell Arteritis - A Case Report.

Autoimmune diseases (AID) have been associated with a variety of lymphoproliferative disorders. Multiple myeloma (MM), one of the most common haematologic malignancies characterized by clonal proliferation of bone marrow plasma cells, has been associated with a range of autoimmune disorders. In this report, we described a case study of a patient admitted to our Internal Medicine Department for a bone marrow biopsy and myelogram due to a monoclonal peak observed by his general practitioner. However, at admission he presented typical giant cell arteritis (GCA) complaints, suggesting the coexistence of both diseases. The possible pathogenesis, as found in the literature, explaining the association will be discussed.LEARNING POINTSA relationship between AID and lymphoproliferative diseases, although rare, may occur and some studies suggest that the diagnosis of autoimmune disease has a negative impact on survival in MM patients.Bone marrow plasmacytosis can present a diagnostic dilemma, since it may be due to neoplastic or non-neoplastic conditions (that is, reactive plasmacytosis associated with AID, chronic infection, metastatic carcinoma, liver diseases and acquired immunodeficiency).Immunophenotyping in a myelogram or immunohistochemistry in bone marrow studies are useful in confirming a monoclonal plasma cell proliferation.

Патоморфологическая и иммуногистохимическая характеристика изменений лимфатических узлов у умерших от COVID-19 по данным аутопсий

Introduction. The pathogenesis of the novel coronavirus infection COVID-19 is being actively studied. Nevertheless, our up-to-date knowledge of lymphoid tissue response in the secondary immune organs dur-ing severe COVID-19 remains extremely limited. The aim of the study was to evaluate patterns of immu-nomorphological alterations in lymph nodes in patients with severe COVID-19 and to assess lymphocytes functional activity in them. Materials and methods. Lymph node tissue (autopsy material) from 17 deceased patients with severe COVID-19 was examined by histological and immunohistochemical methods using antibodies to CD4, CD8, CD20, CD30, CD123, CD138, PD-1. Results. Examined lymph nodes demonstrated lymphoid follicles reduction and paracortex expansion with reactive plasmacytosis and extrafollicular B-cell activation as well as sinus histiocytosis, variable hemophago-cytic cells, and blood vessel congestion. Red thrombi were observed in some lymph nodes. Hemorrhages in the stroma were frequent, and massive hemorrhages were found in individual nodes. Immunohistochemical study revealed CD4+ T-helpers predominance in the paracortex andcytotoxic CD8+ lymphocytes depletion together with an increase in the expression of both the PD-1 suppressor protein and the CD30 activation anti-gen on the lymphocyte surface. CD123-positive plasmacytoid dendritic cells resided in sinuses in abundance. Conclusion. Demonstrated B-associated zone reduction and cytotoxic T-lymphocytes depletion with an up-regulation of PD-1 expression in the lymph nodes in patients with severe COVID-19 indicate immune response exhaustion. At the same time, observed significant reactive plasmacytosis with the presence of numerous T-helper cells constitutes a morphological substrate of the humoral immunity. These findings might indicate the ineffec-tiveness of the humoral response at late stages of COVID-19 infection in context of cytotoxic immunity failure. Keywords: novel coronavirus infection, SARS-CoV-2, COVID-19, B- and T- immune response, lymph node

The cut-offs for kappa/lambda ratio in bone marrow immunohistochemistry for the diagnosis of multiple myeloma

ABSTRACT Objective: The previously reported kappa/lambda ratio cut-offs for plasma cell clonality by immunohistochemistry were in different values. This study aimed to identify the cut-offs with the highest accuracy for the diagnosis of multiple myeloma. Methods: Bone marrow specimens consecutively recruited between January 2011 and March 2019. The patients were at least 18 years old with clinical suspicion of multiple myeloma and had bone marrow plasma cell ≥10% by CD138 immunohistochemistry. The index test was immunohistochemical stains for plasma cell kappa/lambda ratio. The reference standard to classify as multiple myeloma required meeting any of the following (1) kappa/lambda ratio ≤1/16 or ≥16, (2) abnormal plasma cell morphology, and (3) monoclonal immunoglobulin. Results: From 147 specimens (70 multiple myelomas and 77 reactive plasmacytosis), our cut-offs kappa/lambda ratio for light chain restriction at ≤1/7 or ≥9 yielded an area under the receiver operating characteristic curve of 1.0000 while ≤1/16 or ≥16 yielded 0.9643 (p-value 0.0212). Conclusion: The cut-offs for kappa/lambda ratio at ≤1/7 or ≥9 for diagnosis of multiple myeloma yielded the highest diagnostic accuracy. The suggested cut-offs could be of potential value in resource-limited laboratories.

A RARE CASE OF EPSTEIN BARR VIRAL MYOCARDITIS-INDUCED CARDIOGENIC SHOCK

SESSION TITLE: Case Report Semifinalists 8 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Epstein barr virus (EBV) is a ubiquitous virus whose clinical association ranges from infectious mononucleosis to lymphomas and nasopharyngeal carcinomas. We present a case of EBV associated myocarditis, hepatitis, disseminated intravascular coagulation (DIC) and multiple system organ failure (MSOF). CASE PRESENTATION: 63-year-old man presented with 1 week of chest pain and dyspnea to our Emergency Room. On initial examination, the patient was alert and oriented, with mild respiratory distress. EKG showed low voltage QRS and diffuse ST depression. CXR showed mild interstitial edema. Serum chemistries showed Hemoglobin 4, White count 0.92, platelet count of 72,000 , Creatinine 2.4, BUN 56, high sensitivity troponin 2665 ng/L, proBNP 29,766 pg/ml, AST 1435, ALT 738, Total bilirubin 17.3, GGTP 26. Hepatobiliary imaging was without evidence of cirrhosis, it did show cholelithiasis, however the patient did not have clinical evidence of acute biliary pathology. He rapidly deteriorated and developed acute hypoxic respiratory failure and encephalopathy requiring admission to the ICU. He was intubated and mechanically ventilated. Point of Care Ultrasound showed diffuse biventricular hypokinesis. His CXR showed worsening pulmonary edema. He was initiated on dobutamine and Lasix infusions. He was also noted to be oozing from all IV sites and his work up was consistent with DIC. He received blood products for correction of coagulopathy. The clinical suspicion for an acute coronary syndrome was low, and he was considered a poor candidate for cardiac catheterization given DIC and renal failure. High dose steroids were initiated for suspicion for myocarditis. Complete infectious workup revealed EBV DNA by PCR. Given profound pancytopenia a bone marrow biopsy was performed which showed reactive plasmacytosis, no blast cells and few histiocytes engulfing red cells. While Hemophagocytic lymphohistiocytosis was considered based on his bone marrow biopsy results, further cytological studies revealed 20q chromosomal deletion consistent with myelodysplastic syndrome (MDS). The patient responded to therapy and was successfully extubated, dobutamine infusion was weaned off and renal function recovered. Unfortunately the patient developed multiple embolic infarcts. Patient and his family opted for discharge to hospice where he died one week later. DISCUSSION: EBV related myocarditis and MSOF represents a rare, potentially fatal complication of a usually benign, self-limiting disease. In our patient, acute EBV infection may have been reactivated in the setting of immunocompromise, however the possibility that chronic EBV infection played a role in the development of MDS cannot be excluded. CONCLUSIONS: EBV is a rare cause of myocarditis and MSOF. Appreciation of the potential virulence of the pathogen, prompt diagnosis and better therapeutics are necessary for management of this fatal presentation of EBV. Reference #1: Angelini, A., Calzolari, V., Boffa, G., Maddalena, F., Chioin, R., & Thiene, G. (2000). Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis. Heart (84), 245-250. Reference #2: Miller, R., Ward, C., Amsterdam, E., Mason, D., & Zelis, R. (1973). Focal mononucleosis myopericarditis simulating myocardial infarction. . Chest (63), 102-105. Reference #3: Sabbatini, S., Manfredi, R., Ortolani, P., Trapani, F., & Viale, P. (2012). Myopericarditis during a primary Epstein-Barr virus infection in an otherwise healthy young adult. An unusual and insidious complication. Case report and a 60 year literature review. Le Infezioni in Medicina (2), 75-81. DISCLOSURES: No relevant relationships by Shaeesta Khan, source=Web Response No relevant relationships by Ritika Paul, source=Web Response

The diagnostic value of kappa/lambda ratios determined by immunohistochemistry in the differentiation of plasma cell myeloma from reactive plasmacytosis

Context: Plasma cell myeloma (PCM) is the second-most common B-cell malignancy in western countries. In this disease, the bone marrow is infiltrated by monoclonal plasma cells, which may secrete immunoglobulin light chains. In this line, reactive plasma cells may infiltrate into the bone marrow that can lead to misdiagnosis of the disease. Aims: The purpose of this study was to determine monoclonality using immunohistochemistry (IHC) for kappa and lambda light chains in bone marrow biopsy (BMB) specimens. These findings may be useful in the differentiation of PCM from reactive plasmacytosis. Materials and Methods: In this study, BMB paraffin blocks from 90 patients including 45 cases of PCM and 45 patients with reactive plasmacytosis were collected at the pathology center of Imam Reza Hospital from 2006 to 2014. IHC staining for CD138 and Kappa-Lambda light chains were performed. Relative frequencies of Kappa to Lambda light chain positive cells were calculated. Statistical Analysis Used: The results were analyzed with spss16 and Rx64 3.1.2 software. Results: Strong Kappa staining was found in 37 of 45 PCM cases (82.2%), with the ratio of Kappa/Lambda>3 and eight other cases (17.8%) expressed Kappa/Lambda

Role of CD138, CD56, and light chain immunohistochemistry in suspected and diagnosed plasma cell myeloma: A prospective study

Introduction:Plasma cells (PCs) have conventionally been counted on the bone marrow aspirate, and small focal involvement may be missed even on bone marrow biopsy sections.Material and Methods:We aimed to study the role of CD138, CD56, anti-κ, and anti-λ immunohistochemistry (IHC) to separate PC myeloma from reactive plasmacytosis and to study the utility of these in cases suspected as myelomas and lacking >10% PCs on bone marrow aspirate. The study comprised 35 diagnosed myelomas, 20 reactive plasmacytosis, and 19 M-band positive suspected myelomas. CD138 IHC was performed on all cases along with CD56, anti-κ, and anti-λ IHC. PCs were counted on CD138-immunostained sections by manual count and by image analysis. In addition, CD56 expression was correlated with clinical features in diagnosed myeloma group.Results:In all cases, both manual counts and image analysis, PC counts were significantly higher on the CD138 stained sections than bone marrow aspirates. It was seen that the manual PC counts and image analysis counts were equivalent in diagnosed myeloma cases. CD56 expression was seen in ~62.85% diagnosed myeloma cases while it was negative in cases of reactive plasmacytosis. CD56 expression was significantly higher in patients with lytic lesions (78.26% vs. 21.74%). CD138, anti-κ, and anti-λ IHC also helped classify 11/19 (57.8%) cases correctly.Conclusion:The use of CD138 along with the light chain and CD56 IHC adds a high diagnostic value in myeloma patients and suspected myeloma cases. The PCs can be counted manually on the CD138-immunostained sections and correlate well with the counts obtained by image analysis.

Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple Myeloma

Introduction:HIV infection and the resulting immunodeficiency predispose individuals to various plasma cell disorders including reactive plasmacytosis, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plamacytomas. Studies have demonstrated nearly 4.5-fold increased risk of MM in HIV-infected (HIV+) individuals. Limited evidence from case reports/small series of MM in HIV+ patients have suggested a younger age at presentation, more disseminated disease, an aggressive clinical course and inferior outcomes as compared to uninfected counterparts. However, these studies included small numbers of patients, and often lacked appropriate comparison groups. We aim to compare clinical characteristics and outcomes of HIV+ and uninfected subjects with MM, with the hypothesis that significant differences will be detected between the two groups.Methods:We analyzed all patients with histologically proven MM in the Veterans Aging Cohort Study (VACS). VACS is a prospective, observational cohort, beginning in 1996, of > 40,000 HIV+ and > 80,000 age-, race/ethnicity-, sex-, and clinical site- matched (1:2) uninfected patients under care in the Veterans Health Administration. Clinical variable were obtained via chart review. The variables studied included stage at diagnosis (Durie-Salmon and International Staging System- ISS), bone marrow plasma cell involvement at diagnosis, presence of asymptomatic vs clinical MM, involvement with bone lesions at diagnosis, and presence of extramedullary (EM) involvement during the course of disease. Differences between the HIV+ and uninfected patients were compared using appropriate bivariate methods (chi-squared or Fisher's test, where applicable). All p values were two sided and the level of significance chosen was 0.05.Results:A total of 162 patients (62 HIV+, 100 uninfected) with MM were included in this study. Patients were predominantly male 99.4%; 57% were black, 28% white, 15% Hispanic or other ethnicity. Average age at the time of diagnosis was 59, and did not differ between the two groups. The distribution by Durie-Salmon stage was as follows: 28% stage 1, 18% stage 2 and 54% stage 3. By ISS, 43% had stage 1, 25% had stage 2 and 31% had stage 3 disease. 10% had asymptomatic disease. 54% had lytic lesions on skeletal survey. When HIV+ and uninfected patients were compared, based on the available data, there were no statistically significant differences in the distribution of MM by stage, presence of clinically symptomatic MM or presence of lytic lesions. However, we observed a significantly higher rate of the presence of extramedullary disease in the HIV+ as compared with uninfected group (>1 EM site 21% vs 19%, 1 EM site 21% vs 11%, none 57% vs 78%; p value 0.02). Comparison of overall survival between the two groups, and analysis of the impact of HAART on survival are ongoing.Conclusion:This is the largest published study to date to compare the clinical characteristics and outcomes of MM between HIV+ and uninfected individuals. We observed a significantly higher rate of EM disease in the HIV+ group, an important finding since EM disease is associated with poor prognosis. Ongoing analysis will provide additional data on treatment responses, including the role of HAART, and a comparison of clinical outcome data between these two groups. DisclosuresNo relevant conflicts of interest to declare.

Reactive plasmacytosis mimicking multiple myeloma associated with SFTS virus infection: a report of two cases and literature review

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV), which is classified into the genus Phlebovirus and family Phenuiviridae. Reactive plasmacytosis mimicking multiple myeloma is a very rare condition in association with SFTS. Here, we describe two SFTS cases who presented with hyperimmunoglobulinemia, as well as extensive bone marrow and peripheral blood plasmacytosis, which mimicked multiple myeloma (MM).Case presentationWe report two cases who presented with fever and blood routine abnormity which were conformed as SFTS eventually. They were performed bone marrow aspiration and were admitted to the department of hematology with a preliminary diagnosis of MM. They all had hyperimmunoglobulinemia, extensive bone marrow and peripheral blood plasma cells, prolonged activated partial thromboplastin time (APTT), elevated hepatic enzyme. The two patients recovered with treatment of doxycycline, human immunoglobulins, plasma transfusion, and other supporting treatments. But case 1 occurred lymphoma 8 months later and died.ConclusionSFTS might be one of differential diagnosis of MM in certain endemic area. We also conclude that SFTSV is a pantropic virus that could injure most tissues and cells of the human body.

Role of Immunohistochemistry in trephine biopsies of Bone Marrow: A 5-year Retrospective study from a tertiary care hospital

Background: Bone Marrow Biospy (BMB) often needs ancillary tests like Immunohistochemistry (IHC) to confirm the morphological diagnosis, to categorize malignant conditions. Methods: A retrospective study was done on BMB with IHC done on the sections are reviewed and analysed correlating the clinical, Bone marrow aspirate(BMA) and BMB interpretations. Result: A 5 year study on 934 BMB required IHC as an adjunct on 16.2% of the biopsies. It was done on 10.6% of cases. The distribution of cases was 43% of Acute leukemia(AL), 19% multiple myeloma, 8& lymphomas, 9% metastasis. 20 % of other cases which included chronic lymphocytic leukemia(CLL), myelodysplastic syndrome (MDS), megaloblastic anemias, infective conditions and reactive marrows. Conclusion: IHC is a reliable method to confirm and categorize AL, to differentiate reactive and neoplastic plasmacytosis, to confirm, categorize and stage lymphomas, to detect metastasis. DOI: 10.21276/APALM.1506

Laboratory investigation of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome

Objective To investigate the immunological characteristics and clinical significance of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome (SFTS). Methods Bunyavirus-infected patients who were diagnosed with SFTS were collected from March 2015 to October 2015 in Taizhou Hospital. Morphology analysis of bone marrow and peripheral blood (PB) smear, as well as flow cytometry analysis of plasma cell immune phenotype from peripheral blood were conducted. Serum immunoglobulin levels and helper T hymphocytes (Th)1/Th2 cytokine expressions were detected. Mann-Whitney U test was used. Results PB plasma cells from all of the SFTS patients increased in varying degrees, and the phenotype of the plasma cells was CD19+ CD38+ + CD45+ CD138+ , which indicated normal mature plasma cells. The ratio of PB plasma cells was >0.030 in 10/16 patients, and >0.300 in 2/16 patients. The ratios of PB plasma cells in the patients with severe and critical groups were significantly higher than that in the mild group (0.052 vs 0.016, P 0.05). The serum IgG, IgA and IgM levels did not increase in acute stage, with the median of 11.6 g/L, 2.56 g/L and 1.60 g/L (reference value 0.46 to 3.04 g/L), respectively. Conclusion The patients with SFTS show excessive humoral and cellular immunity, and the severity of disease is positively correlated with the ratio of peripheral plasma cells and the levels of cytokines IL-6 and IL-10. Key words: Novel bunyavirus; Severe fever with throbocytopenia syndrome; Reactive plasmacytosis; Lymphohistiocytosis, hemophagocytic; Cell morphology; Plasma cells; Cytokines