Polyclonal Plasmacytosis Research Articles

Recent Advances in the Treatment and Supportive Care of POEMS Syndrome

POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always straight forward and often the diagnosis is delayed. It is based on fulfilling mandatory criteria of polyradiculoneuropathy and monoclonal protein and the presence of one major criterion (Castleman disease, sclerotic bone lesions, or elevated VEGF), and at least one minor criterion. Due to the presence of neuropathy, it can be confused with chronic inflammatory demyelinating polyradiculopathy (CIDP), and if thrombocytosis and splenomegaly are present, it can be confused with myeloproliferative neoplasms. Due to the rarity of the syndrome, clear guidelines for treatment are still lacking. Immediate treatment targeting the underlying plasma cell proliferation results in a dramatic response in most patients. The key is early diagnosis and immediate anti-plasma cell directed therapy for the best clinical outcomes. For patients with disseminated disease as defined by bone marrow involvement or more than three osteosclerotic bone lesions, high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT) yields durable responses and is the preferred treatment in eligible patients. For patients with localized bony disease, radiotherapy has proven to be very effective. Lenalidomide and dexamethasone is a proven therapy in patients ineligible for ASCT. In this review article, we tackle the diagnostic approach and discuss the latest treatment modalities of this rare debilitating disease.

26362 Cutaneous polyclonal plasmacytosis presenting with rhinophymatous change in an adult caucasian male treated with carbon dioxide laser

A 69-year-old male with a history of nonmelanoma skin cancer and follicular occlusion tetrad presented to the dermatology clinic with a 4-year history of slow-growing rhinophymatous-like changes on his nose. Physical examination demonstrated multiple indurated, red-brown nodules varying in size from 6 to 10 mm on his right nasal ala, sidewall and bilateral medial cheeks. A shave biopsy was performed and showed a dense dermal infiltrate of plasma cells without cytologic atypia and few lymphocytes.

Idiopathic Polyclonal Plasmacytosis Presenting as Fever of Unknown Origin

An elderly male, after being flagged to have fever of unknown origin, was found to have plasmacytosis on bone marrow examination. On immunophenotyping, the proliferation was confirmed as polyclonal. No associated underlying condition such as infection or connective tissue disease was found. The importance of polyclonal plasmacytosis is discussed vis-a-vis the usual knee jerk reaction to diagnose multiple myeloma.

Idiopathic multicentric Castleman’s disease, infrequent cause of Lupus-like. Case Report.

Castleman’s disease (CD) or angiofollicular lymph node hyperplasia includes a heterogeneous mix of reactive lymphoproliferative processes with well-defined histological features. However, they differ in their localization patterns, clinical expression and etiopathogenesis. There are 4 types, one of them is the multicentric CD that is not associated with any viruses and has recently been called idiopathic MCD (iMCD). iMCD is a lymphoproliferative disorder with specific histopathological characteristics, more than one region of affected lymph nodes and absence of infection associated to human herpesvirus 8 and human immunodeficiency virus (HIV). iMCD covers multiple differential diagnoses and might simulate autoimmune diseases such as systemic lupus erythematosus. The aim of this article is to report the case of a patient with Castleman’s disease and lupus-like presentation. We present the case of a 38-year-old man without morbid history, who presented lumbago, fever, diaphoresis and asthenia with two months of evolution, associated to bilateral cervical adenopathies. General examinations result negative, antinuclear antibodies at a dilution of 1/640 were positive, and extractable nuclear antigens were positive suggesting moderate Systemic Lupus Erythematosus (SLE) plus secondary Sjögren’s. Methylprednisolone and Hydroxycloroquine boli were thus initiated. The patient evolved with anasarca, severe anemia, acidosis, polyserositis and multiple mediastinal adenopathies. Immunoglobulin and cyclophosphamide were thus initiated. He later presented fever, thrombocytopenia and nephrotic syndrome. Biopsy of cervical lymph node reported lymphadenitis with polyclonal plasmacytosis and concentric lymphoid hyperplasia, in agreement with iMCD. Treatment with Rituximab was initiated, which led to the favorable evolution of the patient. iMCD is a systemic inflammatory disease, its presentation corresponds to a constitutional syndrome resulting in a wide differential diagnosis. Every time suspicious adenopathies appear, they must be biopsied since this might lead to a definitive diagnosis.

Angioimmunoblastic T-cell Lymphoma Associated with Marked Polyclonal Plasmacytosis

Angioimmunoblastic T-cell Lymphoma Associated with Marked Polyclonal Plasmacytosis

REACTIVE PLASMACYTOSIS AT THE ONSET OF ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA. CASE REPORT

Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoproliferative disease with generalized lymphadenopathy, hepatosplenomegaly, intoxication and polyclonal hypergammaglobulinemia. The persistence of plasma cells in peripheral blood can be a manifestation of both tumor and reactive processes. In our article, we described the case of angioimmunoblastic T-cell lymphoma with an increase in the number of peripheral blood plasma cells to 28 %, and in bone marrow to 9 %. The complex diagnostics, including plasma cells immunophenotyping, morphology of the lymph node biopsy and bone marrow samples, made it possible to verify the diagnosis of angioimmunoblastic T-cell lymphoma with polyclonal plasmacytosis.

Immunophenotypic Evidence for Reactive Polyclonal Marrow Plasmacytosis in Multiple Myeloma Patients Receiving Long-Term Lenalidomide Therapy

Introduction: Maintenance therapy with lenalidomide (LEN) is considered standard of care in the US, supported by meta analysis showing that LEN maintenance is associated with significantly longer progression free survival (PFS) and overall survival (OS). In a previously reported study of MM patients (pts) treated with extended courses of LEN, we have described a polyclonal Ig and FLC elevation exceeding the upper limit of normal (up to 3-4 X the ULN) and associated with striking polyclonal bone marrow (BM) plasmacytosis (up to 20% of plasma cells (PCs)), occurring with a relatively high frequency (20% of pts) and associated with better outcome (Zamarin, Leukemia, 2013). Importantly, we cautioned about the risk of misinterpretation of this polyclonal Ig response and plasmacytosis. Since Immuno-histochemical staining (IHS) may often be an unreliable tool to distinguish between a reactive polyclonal plasmacytosis from monoclonal disease, especially when the percentage of PCs in the BM is relatively low (5 -15%), we aimed at confirming the polyclonal nature of this often unrecognized and paradoxical response to prolonged LEN exposure, and at validating the important role of BM assessment by flow cytometry (FACS) in this setting. Methods: Pts analyzed in this study were enrolled at MSKCC on three randomized, first line therapy, clinical trials (NCT01109004, NCT01208662, and NCT00807599). All pts were kept on LEN maintenance until POD, toxicity, or major event. BM aspirate and biopsy with IHS were performed as per standard of care. Eight-fluorochrome FACS method (minimum of 1 x 106 cells) was used for 2014 samples employing a surface marker cocktail (CD117 PC5.5, CD19 BV421, CD138 APC, CD56 PC7, CD45 APC-H7, CD38 BV510) and cytoplasmic Kappa FITC/Lambda PE staining. Ten-fluorochrome (minimum of 5 x 106 WBCs) method was used in 2015 and performed employing a surface marker cocktail (CD117 PC5.5, CD19 PC7, CD138 APC, CD56 APC-R700, CD45 APC-H7, CD81 Pacific Blue, CD38 BV510, CD27 BV605) and cytoplasmic Kappa FITC/Lambda PE staining. Results: Among 147 pts enrolled in the three trials, 55 achieved serologic CR after first line therapy. Of those, 46 had a BM biopsy with FACS analysis available. Among these 46 patients, bone marrow plasmacytosis as assessed by light microscopy of BM aspirate and biopsy ranged from 2% to 15% (32 pts had PCs ≤ 5%, 14 PCs > 5%). Among the 14 pts with > 5% PCs, 2 had PCs = 15%, 9 had PCs = 10%, and 3 between 6% and 9%. By FACS, 9 of 14 pts showed no clonal or phenotypically aberrant PCs. The percentage of aberrant PCs among all PCs in the other 5 pts remained low (≤7.3%). Among the 2 pts with PC = 15%, the percentage of aberrant PCs among all PCs was 0% and 7.3%. In pts with PC = 10%, the percentage of aberrant PCs among all PCs was 0% (6 pts), or ranged from 0.17% to 5.1% (3 pts). Figure 1 depicts representative pt cases with BM plasmacytosis estimated at 15% by light microscopy. PCs were gated based on CD38 and CD138 expression as well as forward and side scatter (not shown). Blue dots represent kappa LC expression; Red lambda LC. Proportion of aberrant PCs among total PCs in the sample is quantitated and shown using high sensitivity MRD detection with 10-color panel with 6-million event acquisitions. Panel A shows a pt with 15% PC in the BM with no residual disease confirming the polyclonal nature of the plasmacytosis. Panel B shows a pt with 15% PC exhibiting a low proportion of aberrant PCs (green) among a predominant background of normal polytypic PCs. In contrast, Panel C shows a pt with early relapsed disease with 15% PCs exhibiting a high proportion of aberrant PCs (99% of all PCs). Conclusions: These results confirm the common and striking polyclonal plasmacytosis (up to 15% PCs in this cohort) associated with prolonged LEN exposure, and the importance of FACS in the assessment of BM plasmacytosis in these MM pts. In the setting of current MM response criteria established by the IMWG and NCCN guidelines, mandating a BM plasmacytosis Disclosures Hassoun:Novartis: Consultancy; Binding Site: Research Funding; Celgene: Research Funding; Takeda: Consultancy, Research Funding. Roshal:BD Biosciences: Consultancy. Landau:Prothena: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Janssen: Consultancy; Spectrum Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Korde:Medscape: Honoraria. Landgren:Merck: Honoraria; BMS: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Medscape Myeloma Program: Honoraria.

Quantification of Marrow Plasmacytosis in HIV Patients

Introduction:A reactive, polyclonal increase in marrow plasma cells in pts with HIV is relatively common, reported to occur in 25% of cases in one series (1) and recently noted to be "usually seen" (2). However, quantification of the degree of marrow plasmacytosis has not been well described.Methods:Pts with a diagnosis of HIV and who had a bone marrow aspirate and biopsy performed at our institution over a 10 year period (2/2004-9/2014) were reviewed. Pts with a diagnosis of myeloma were excluded. A 500 cell count was performed on each marrow aspirate and plasma cell percentage determined.Results:65 pts were identified; 9 were excluded due to dry taps, so there were 56 evaluable marrow aspirates. Reasons for performing the aspirate and biopsy included: lymphoma staging (NHL in 11/65, HL in 4/65); abnormal SPEP (2/65); abnormal MRI (1/65); FUO (14/65), Kaposi's sarcoma/fevers (3/65), pancytopenia (15/65), thrombocytopenia (6/65), neutropenia (2/65) and anemia (10/65). The average marrow plasma cell percentage was 4.6%, with a range from 0- 21% (median 4%). Only 7/56 (12.5%) had >10% plasma cells. Of these 7 cases, only one had an identifiable cause (multicentric Castleman's) for the plasmacytosis. The 6 others had no neoplastic or infectious etiology, except for HIV itself (including one with 21% plasma cells). All had polyclonal plasmacytosis.Conclusions:In this small series of HIV marrows the degree of plasmacytosis was generally mild (average of 4.6%, which is barely above the upper limit of normal range of 3.5%). However, there were a minority of cases which exhibited significant plasmacytosis (as high as 21%) without any cause other than HIV. This suggests that, while significant marrow polyclonal plasmacytosis is usually not seen in HIV, it may occur as a result of HIV itself without any other identifiable cause.1) Karchen DS and Frost AR. The bone marrow in HIV-related disease: Morphology and clinical correlation. Am J Clin Path. 1991; 95(1): 63-71.2) Leibman HA and Tulpule A. "Hematologic manifestations of HIV/AIDS". Chapter 159. Hematology: Basic Principles and Practice, 6th edition. 2013. DisclosuresNo relevant conflicts of interest to declare.

Systemic polyclonal immunoblastic proliferation: a diagnostic review and differential diagnosis

Systemic polyclonal immunoblastic proliferation (SPIP) is a very rare, atypical expansion of plasma cells and lymphoblasts associated with an aggressive clinical presentation. The pathogenesis of SPIP is unknown and it is unclear whether these proliferations represent a clinicopathologic entity or rather a pattern of cellular proliferation. Some evidence of infection as an initiating event has been proposed. SPIP is often difficult to differentiate from other disorders, particularly in the context of an obscuring inflammatory response. Untreated or even treated cases can be fatal. The morphologic features are characterized by a pronounced proliferation of B immunoblasts and plasma cells that typically involve the blood, bone marrow, lymph nodes, spleen, thymus, liver, kidneys, thyroid, adrenal glands, and lungs. A subset of reported cases has responded well to treatment with corticosteroids alone or in combination with cytotoxic agents, showing complete remission and resolution of lymphadenopathy and normalization of peripheral blood findings. Here, we present a case of SPIP in a 58-year-old male with polyclonal plasmacytosis, hypergammaglobulinemia, diffuse lymphadenopathy, splenomegaly, and a diffuse maculopapular rash; SPIP with skin involvement is very unusual. Fortunately, our patient showed a striking response to steroids. This article provides a brief overview of the clinicopathologic features associated with this atypical lymphoplasmacytic proliferation and a review of the literature highlighting the differential diagnosis of lymphoplasmacytic disorders.

Whipple's in the valleys: a case of Whipple's with thrombocytopenia and endocarditis

IntroductionThis case report details the second described case of Whipple's disease-related thrombocytopenia in the medical literature. Whipple's disease is a rare multisystem infection caused by the actinomycete Tropheryma whipplei, first...

Role Of Tumor Necrosis Factor α In Bone Marrow Niche Dysfunction Of Patients With Systemic Lupus Erythematosus (SLE)

Objectives and backgroundSLE is a chronic systemic autoimmune disorder associated with autoantibodies and cytopenias. There are few studies of the pathogenesis of anemia of chronic inflammation in lupus. This study addresses the pathogenesis of the hematological manifestations of lupus. We have shown that SLE bone marrow (BM) exhibits striking death of niche and hematopoietic cells associated with tumor necrosis factor-α (TNFα) over-production. Here, we further examined the pathogenesis of hematological BM niche dysfunction. MethodsPathology records over the past 10 years from the University of Florida were reviewed and BM aspirates/core biopsies from 6 SLE patients were identified for further study. Wright-Giemsa stained BM aspirate smears and cytospin preparations, hematoxylin and eosin (H&E)-stained and reticulin stained BM core biopsies were reviewed. Immunohistochemistry (IHC) for TNFα, cleaved caspase-3, and CD71 was performed on core biopsies and expression levels were quantified morphometrically. BM specimens from individuals undergoing staging for lymphoma were selected as controls. ResultsFive of 6 SLE patients had nephritis and 3 were direct Coombs+ (one with hemolytic anemia). Mean hemoglobin was 9.1g/dL in SLE patients and 11.9g/dL in controls. Mean WBC was 3800/mm3 in patients and 8200/mm3 in controls, and mean platelet counts were 133,000/mm3 and 258,000/mm3, respectively. BM aspirates exhibited numerous apoptotic cells, erythroid dyspoiesis, plasmacytosis, hemophagocytosis, and phagocytosis of nuclear material by mature neutrophils (LE cells). Numerous LE cells were seen in 5/6 SLE BM aspirates. Compared to normal BM biopsies, SLE BM biopsies exhibited hypocellularity, erythroid dyspoiesis, polyclonal plasmacytosis, mild reticulin fibrosis, BM stromal damage/disorganization and 3 out of 6 with interstitial lymphoid aggregates. IHC with anti-cleaved caspase-3 antibodies, a specific marker of cell death, revealed numerous caspase-3+ cells in a range of 20-40% of total BM cells in contrast to control BMs of <5%. Interestingly, a large majority of osteoblasts or lining cells in BM osteal niches were caspase-3+ in SLE BM, whereas caspase-3+ cells were rare in control BM biopsies. Using double IHC (TUNEL assay plus anti-CD71 or myeloperoxidase antibodies), prominent apoptotic erythroid precursors with less extensive cell death of the myeloid and megakaryocytic lineages was found in SLE BM core biopsies. In SLE, caspase-3+ cells occupied 9-12% of the total BM area vs. 1-2% in control BM (p<0.001). As TNFα promotes Fas-mediated apoptosis and may damage hematopoietic precursors and/or stromal cells, we examined its production in SLE BM. IHC with anti-TNFα antibodies revealed intense intra- and extracellular staining surrounding neutrophils and monocytes, and the extent of TNFα staining was dramatically higher in SLE patients' BM biopsies than in controls. Staining was particularly intense adjacent to presumptive osteoblasts lining the surface of bone trabeculae, though there also was staining in interstitial regions. There was little TNFα staining of control BM. Morphometric analysis revealed 10-18% of the area in SLE BM intensely stained with anti-TNFα vs. 1-3.5% in controls (P < 0.001, Student t-test), suggesting that TNFα overproduction may cause BM niche dysfunction. ConclusionBM TNFα-mediated niche cell apoptosis is likely to be involved in the pathogenesis of SLE-associated hematological abnormalities. Disclosures:No relevant conflicts of interest to declare.

Cytogenetic Features Of Patients With Monoclonal Gammopathy Of Undetermined Significance (MGUS) and Asymptomatic Multiple Myeloma (AMM)

Cytogenetic Features Of Patients With Monoclonal Gammopathy Of Undetermined Significance (MGUS) and Asymptomatic Multiple Myeloma (AMM)

Clinical manifestation of angioimmunoblastic T-cell lymphoma with exuberant plasmacytosis

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma characterized by aggressive symptoms and various abnormal laboratory test results. One of the rare immunologic abnormalities in AITL is exuberant polyclonal plasmacytosis, but its clinical significance has not been evaluated. This report concerns three AITL cases with exuberant polyclonal plasmacytosis and investigates its clinical impact by comparison with 12 patients without plasmacytosis. Our study found that the performance status (PS) of the former was significantly worse and their serum immunoglobulin levels were significantly higher. All other parameters, including B symptoms, various prognostic scores, blood cell counts other than plasmacyte, and serum levels of lactate dehydrogenase, C-reactive protein and soluble interleukin-2 receptor, showed no significant differences. More importantly, although the diagnosis of AITL with plasmacytosis was not straightforward in our series, outcomes of treatment with conventional chemotherapy or immunosuppressive therapy with cyclosporine A were favorable. To conclude, AITL should be considered a candidate underlying disease of exuberant polyclonal plasmacytosis. Provided a correct diagnosis is made early and is followed by adequate treatment, the prognosis for AITL with plasmacytosis may not be worse than that for those without plasmacytosis despite the severe exhaustion at first presentation.

Successful tocilizumab treatment in a patient with human herpesvirus 8‐positive and human immunodeficiency virus‐negative multicentric Castleman's disease of plasma cell type nonresponsive to rituximab‐CVP therapy

We present and discuss the case of a HIV-negative female finally diagnosed upon histopathologic and molecular biologic evaluations with human herpesvirus 8 (HHV8)-positive multicentric Castleman's disease (MCD) of plasma cell type, but with no detectable HHV8-DNA in peripheral blood. She failed to respond to combination immunosuppressive therapeutic trials of corticosteroids and azathioprine, and neither an immunochemotherapy of rituximab-CVP (R-CVP) induced disease resolution. However, monoclonal anti-IL-6R antibody (tocilizumab) immunotherapy resulted in beneficial disease stabilization. A control lymph node biopsy indicated mild polyclonal plasmacytosis, and a negative HHV8 determination. The patient is still receiving tocilizumab. This case emphasizes the individual nature of MCD requiering more personalized disease management.

Reactive Polyclonal Gammopathy Associated with Polyclonal Plasmacytosis Is Common in Patients with Multiple Myeloma Receiving Prolonged Lenalidomide Therapy: A Retrospective Study of 104 Patients

Abstract 4033 BACKGROUND:Prolonged lenalidomide treatment is frequently used in patients with multiple myeloma (MM), both in the upfront and relapsed settings. We have previously reported a small series of 6 patients receiving prolonged lenalidomide treatment who presented with a polyclonal IgA gammopathy characterized by a marked elevation in the serum IgA level, polyclonal plasmacytosis in the bone marrow, and without any evidence of clinical disease progression. Although the immunologic mechanism underlying this observation is currently under investigation, it is important to recognize and characterize its incidence, clinical features, and prognostic significance. For these purposes, we have undertaken a retrospective analysis of all patients treated at MSKCC with prolonged course of lenalidomide. METHODS AND RESULTS:We retrospectively identified 104 patients with MM who received a prolonged course of lenalidomide (>6 months). Among these patients, 21 (20%) were noted to have polyclonal immunoglobulin (Ig) elevation above the upper limit of normal during lenalidomide therapy, affecting IgA in 13, IgG in 6, and both IgA and IgG in 2 patients. All 21 patients were without evidence of relapse or progression (R/POD) by serologic or clinical criteria at the time of polyclonal Ig elevation. In 15 patients the polyclonal Ig did not involve the initial monoclonal isotype. The median time from lenalidomide initiation to polyclonal elevation of Ig level was 10.9 months (range 2 to 38.6 months), with the median peak IgA level of 587 mg/dl (range 374 to 1190 mg/dl), and the median peak IgG level of 1800 mg/dl (range 1575 to 2650 mg/dl). Bone marrow aspirates and biopsies were available in 12 patients during the period of Ig elevation and the median plasmacytosis was 12% (range 5 to 20%) on the aspirate. Immunohistochemical (IHC) studies of the bone marrow biopsy showed moderate increase in CD138+ cells without light chain restriction. IHC using IgA and IgG antibody staining in the patients with IgA elevation confirmed that most plasma cells were IgA-producing and were not consistent with the original myeloma clone. To evaluate for the association of polyclonal gammopathy with progression free survival, we performed a landmark analysis on all 104 patients based on the magnitude of the absolute Ig elevation measured at 6 months after initiation of lenalidomide. The patients were divided into 2 groups on the basis of the median absolute elevation in the levels of IgA (40 mg/dl) or IgG (150 mg/dl) from the baseline prior to therapy initiation to 6 months after starting the treatment. Statistical comparison was limited by the small number of patients who had R/POD in the sample (n=16), but there was a trend toward improved PFS in the patients who achieved absolute IgA elevation >40mg/dl, though any difference was attenuated by 36 months following the 6-month landmark (logrank p-value: 0.54). Interestingly, when focusing exclusively on the 16 patients with R/POD during the followup, the median time to progression was 27.5 months and 13.1 months in patients with absolute IgA elevation >40mg/dl (n=10), and those with absolute IgA elevation <40mg/dl (n=6) at the 6 month landmark, respectively. CONCLUSIONS:Polyclonal gammopathy with Ig levels exceeding the normal range associated with polyclonal plasmacytosis occurs with a relatively high frequency (20%) in patients treated with prolonged courses of lenalidomide. Awareness of this effect is important especially in view of the associated significant bone marrow plasmacytosis, which may mistakenly be construed as R/POD in patients who are actually responding to treatment. In addition, the absolute elevation in the IgA level measured at 6 months post initiation of treatment may be a prognostic indicator of progression, with high elevations potentially indicating an extended benefit from lenalidomide treatment. Further studies are needed to validate these observations and to elucidate their mechanism. Disclosures:Giralt:Celgene: Honoraria, Research Funding. Landau:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding. Hassoun:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding.

Bartonella henselae infection in a man with hypergammaglobulinaemia, splenomegaly and polyclonal plasmacytosis

Bartonella henselae is an infrequently reported cause of polyclonal plasmacytosis and hypergammaglobulinaemia. We herein document B. henselae infection in a 66-year-old patient who presented with hypergammaglobulinaemia, splenomegaly with polyclonal plasmacytosis, stroke, and suspected prosthetic aortic arch infection. Clinicians should remain cognizant of the heterogeneous clinical presentations associated with bartonellosis.

Atypical angioimmunoblastic T-cell lymphomas masquerading as systemic polyclonal B-immunoblastic proliferation

Angioimmunoblastic T cell lymphoma (AITL) is a relatively rare peripheral T cell lymphoma derived from follicular T helper cells. AITL has a varied presentation, both clinically and morphologically. AITL can pose a diagnostic challenge as it may be difficult to identify and characterize the neoplastic cells among the polymorphous infiltrates composed of polyclonal B immunoblasts and plasma cells. In AITL, the reactive B cell and plasma cell proliferation is secondary to dysregulated secretion of cytokines such as interleukin-6 by the neoplastic follicular T helper cells. SPBIP is a condition of unknown etiopathogenesis characterized by systemic involvement by polyclonal B immunoblasts and plasma cells. We report two cases of AITL, which are presented with atypical findings making it difficult to diagnose. The cases had features similar to SPBIP. Our cases highlight the importance of screening cases of polyclonal plasmacytosis and SPBIP like cases for underlying AITL.

Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

Retinoic acid related orphan receptor gamma-t (RORγt) is known to be a master regulator of Th17-cell development. In this study, we generated RORγt-overexpressing transgenic (RORγt Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORγt Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORγt Tg mice developed massive polyclonal plasma-cytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, anti-erythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1 RORγt Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORγt Tg mice appeared to be due to the induction of excessive IL-6 production by IL-17. We detected increased numbers of CD11b(+) cells that produced IL-6. We also generatedIL-6-deficient RORγt Tg BALB/F1 background mice, which displayed high levels of serum IL-17, but did not develop severe hyperglobulinemia. Excessive IL-6 production by several cell types, including macrophages, in BALB/F1 RORγt Tg mice, might effect the development of plasma-cytosis. These results suggest that RORγt plays important roles in the development of plasmacytosis and autoantibody production.

54-Year-Old Man With Severe Prostatism, Palatal Mass, and History of Pancreatitis

54-year-old man with a history of benign prostatic hypertrophy, hypothyroidism, and well-controlled insulin-dependent diabetes mellitus secondary to idiopathic pancreatitis presented to our internal medicine consultation clinic. He complained of a lump in the hard palate, dry mouth present for 2 years, and bilateral submandibular gland swelling for which he had been evaluated by an otolaryngologist. A previous biopsy of the hard palate mass had demonstrated florid reactive lymphoid hyperplasia with fibrosis, polyclonal plasmacytosis and increased IgG4-positive plasma cells. He also complained of obstructive urinary symptoms and was found to have a very large and nodular prostate on digital rectal examination. The prostate-specific antigen level was 0.13 ng/mL (reference range, 0-3.2 ng/ mL), and results of urinalysis were unremarkable. A computed tomographic scan of the chest from an outside facility showed a mass in the right middle lobe in addition to bilateral renal lesions. Suspicion for a common link among his current symptoms and previous diagnoses was raised. 1. Which of the following is the most likely unifying diagnosis? a. Multiple myeloma b. Amyloidosis c. Metastatic prostate cancer d. IgG4-related sclerosing disease (IgG4RSD)

Polyclonal IgA Gammopathy Associated with Polyclonal Plasmacytosis in Patients Receiving Lenalidomide Maintenance Therapy

Abstract 5130 INTRODUCTION:Lenalidomide is commonly used in the treatment of multiple myeloma both in the upfront and relapsed settings and appears to also yield promising results as maintenance therapy after autologous stem cell transplantation. The immunomodulatory mechanisms of action of lenalidomide are complex and the side effects of long-term therapy are still not fully known. Here we report a series of patients on lenalidomide maintenance therapy who demonstrated significant elevation of serum polyclonal immunoglobulin A (IgA) levels with associated polyclonal plasmacytosis in the absence of disease progression. METHODS AND RESULTS:We identified 6 patients who, in the course of lenalidomide maintenance therapy, were noted to have asymptomatic elevation of serum IgA levels above normal limits without evidence of monoclonality by immunofixation of serum protein electrophoresis. The original myeloma-associated monoclonal protein was IgG kappa in 5 patients and IgG lambda in 1 patient. Two patients received lenalidomide as part of their induction regimen prior to autologous stem cell transplantation, and transient elevation of IgA level was noted at that time. None of the patients had evidence of IgA gammopathy prior to initiation of lenalidomide. Mean time from initiation of lenalidomide maintenance therapy to elevation of IgA level was 9.8 months (range 2 to 22 months). The mean highest IgA level reached for the 6 patients was 534 mg/dl (range 520 to 1190 mg/dl). Bone marrow aspirate and biopsy were available in 3 patients during the period of IgA elevation. The plasma cell population accounted for 9%, 12% and 20% of the bone marrow nucleated cells on the aspirate. Immunohistochemical staining (HIS) of the bone marrow biopsy showed a moderate increase in the number of CD138 positive plasma cells without light chain restriction. HIS using IgA antibody revealed that the plasma cells were mostly IgA producing. None of the 6 patients had any evidence of progression of their original myeloma-associated paraprotein in the setting of polyclonal IgA elevation. Five patients continue to receive lenalidomide maintenance to date (treatment time length ranging between 17.3 and 43.4 months) with no evidence of serologic or clinical disease progression and with persistently elevated IgA levels. One patient discontinued lenalidomide therapy secondary to development of neuropathy with subsequent normalization of IgA level 21 months later. CONCLUSIONS:Polyclonal IgA gammopathy associated with polyclonal IgA-producing plasmacytosis can occur with lenalidomide maintenance and perhaps lenalidomide treatment. The immunologic basis and implication of this observation is unknown. Awareness of this effect is important especially in view of the associated significant bone marrow plasmacytosis, which may mistakenly be construed as disease relapse or progression in patients who are actually responding to treatment. Disclosures:No relevant conflicts of interest to declare.