Monotypic Plasma Cells Research Articles

Plasma Cell Leukemia with atypical CCND1/IGH fusion and Monocytoid morphology; A Rare Case Finding

Abstract Introduction/Objective Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia, often presenting as a variant of multiple myeloma (MM). It is characterized by the presence of ≥5% circulating plasma cells in peripheral blood, either as a primary or secondary manifestation of MM. Methods/Case Report Our case is of a 77-year-old male who presented with epigastric tenderness and bi-basilar crackles. Laboratory results showed severe hypercalcemia, elevated creatinine, leukocytosis, and elevated absolute neutrophil and lymphocyte counts. Imaging revealed widespread lytic lesions in the ribs, scapulae, thoracolumbar spine, and bony pelvis. Peripheral blood smear showed significant macrocytic anemia with rare polychromatophilic cells, numerous immature plasmacytoid cells (>20% of total cell count) and monocytoid morphology. Flow cytometry confirmed a population of monotypic plasma cells (28% of total cells). Bone marrow biopsy revealed a hypercellular plasma cell infiltrate with complex clonal karyotypic abnormalities, including the t(11;14)(q13;q32), rearrangements of 1p, and gain of 1q. FISH analysis showed an atypical CCND1/IGH fusion in 57% of cells, with one fusion, two orange (CCND1), and two green (IGH) signals. The case presented demonstrates a rare instance of an atypical CCND1/IGH fusion in plasma cell leukemia with monocytoid morphology, which poses diagnostic challenges. Prompt and accurate diagnosis is essential for managing the condition, given its consistently poor prognosis despite advancements in therapy over the past decade. Results (if a Case Study enter NA) NA Conclusion Our case highlights the importance of recognizing rare molecular abnormalities in PCL and suggests that further research into the molecular pathways involved in the disease is needed to improve diagnosis, treatment options and clinical outcomes.

Coexistence of HHV-8-Associated Plasmacytic Multicentric Castleman Disease, Kaposi's Sarcoma, and Multiple Myeloma in a HIV-Negative Patient.

Multicentric Castleman disease (MCD) is a rare, aggressive lymphoproliferative disorder. Human herpesvirus-8 (HHV-8) has an important role in the pathogenesis of the disease and its association with Kaposi's sarcoma has been reported, especially in people living with human immunodeficiency virus (HIV). In this report, we present the case of HHV-8 positive MCD accompanied by Kaposi's sarcoma and multiple myeloma in an HIV-negative patient. A 78-year-old man with Kaposi's sarcoma presented with B symptoms, pancytopenia, lymphadenopathy, and splenomegaly. The bone marrow biopsy demonstrated 70% lambda-restricted monotypic plasma cell infiltration consistent with plasma dyscrasia. Also, the patient was diagnosed with HHV-8 positive MCD as a result of inguinal lymph node excisional biopsy. Treatment was initiated including ganciclovir and methylprednisolone and followed by rituximab. The patient passed away at the 24th hour of rituximab infusion due to shock. MCD and associated malignancies are difficult to treat and have a poor prognosis. More studies and data are needed to manage these patients. Multicentric Castleman disease (MCD), often linked with human herpesvirus-8 (HHV-8) and Kaposi's sarcoma, is rare and aggressive condition, particularly in human immunodeficiency virus (HIV)-positive patients.The coexistence of MCD, Kaposi's sarcoma, and multiple myeloma is exceptionally rare in HIV-negative, immunocompetent patient.This case highlights the challenges in diagnosing and managing complex presentations of MCD and related malignancies, with poor outcomes despite treatment.

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL (TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD (TET2), 40% of PCTFHL (SOCS1 (20%), ARID1A (20%)) and 64% of cAITL (TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases.

From Castleman disease histopathological features to idiopathic multicentric Castleman disease: a multiparametric approach to exclude potential iMCD histopathological mimickers

AimsInternational consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) includes lymph node Castleman disease (CD) histopathological features as major criteria. Our aim was to apply those criteria in a...

Piddling and Moderate-Primary Cutaneous CD4+ Small/Medium T Cell Lymphoproliferative Disorder

Initially contemplated as a provisional subtype of cutaneous T cell lymphoma (CTCL), primary cutaneous CD4+ small / medium T cell lymphoproliferative disorder manifests as an indolent, solitary cutaneous lesion in the absence of accompanying cutaneous lymphoma as mycosis fungoides. Preponderantly, infiltration of upper dermis with miniature to intermediate, pleomorphic CD4+ T cells in the absence of preceding or concurrent patches and plaques with focal epidermotropism is encountered. Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder commonly appears in adults as a solitary plaque, tumour or nodule situated upon face, neck, upper trunk or thoracic region. Upon cytology, pleomorphic, miniature, intermediate or occasionally enlarged T lymphoid cells with irregular nuclear contours are variably intermixed with miniature, reactive CD8+ T cells, B cells, plasma cells, histiocytes and monotypic plasma cells. Morphologically, an intense dermal infiltrate of atypical lymphoid cells or small / medium pleomorphic CD4+ T cells extending into subcutaneous tissue appears to configure a diffuse or nodular configuration wherein the enlarged, pleomorphic cells articulate &lt; 30% of neoplastic cellular infiltrate. Neoplastic lymphocytes appear immune reactive to T cell markers as CD3, CD4, CD5 along with T follicular helper markers as CD279 (PD-1), ICOS and CXCL13. Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder necessitates segregation from mycosis fungoides, cutaneous involvement with systemic T cell lymphoma of T follicular helper immuno-phenotype, benign inflammatory infiltrate, extra-nodal marginal zone (MALT) lymphoma or adult T cell leukaemia /lymphoma. The disorder can be therapeutically managed with intralesional steroids, radiotherapy or surgical extermination of lesion.

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype: an integrative clinical, pathological and molecular case series study.

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype (pcTFH-PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T-cell lymphomas (AITL). We describe the clinicopathological features of pcTFH-PTCL in this original series of 23 patients, and also characterize these cases molecularly. Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next-generation sequencing. All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T-cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B-cell lymphoproliferative disorder (LPD) on biopsy, including Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (n = 3), EBV+ LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2-RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2-RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1). Patients with pcTFH-PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH-PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate. What is already known about this topic? There is a group of cutaneous lymphomas that express T-follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities. These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T-cell lymphomas (PTCL) with TFH phenotype. What does this study add? This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH-PTCL) to be molecularly characterized. pcTFH-PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T-cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma. This has an impact on the treatment and follow-up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management.

Lymphoplasmacytic lymphoma with IgG or IgA paraprotein: a study of 29 cases including cases that can mimic plasma cell neoplasms

Lymphoplasmacytic lymphoma (LPL) with IgG or IgA paraprotein is rare and a subset of cases can mimic a plasma cell neoplasm (PCN). We studied 29 such cases to explore their clinicopathological features and the best diagnostic approaches with a focus on bone marrow findings. The cohort included 18 men and 11 women with a median age of 68 years. The median M protein was 3.1g/dL, IgG in 19patients (66%), IgA in 9 (31%), and dual IgG/IgA in 1 (3%). All patients had bone marrow involvement with CD138+ plasma cells (PCs) ranging from 1 to 35% (median, 10%). Two patients also had amyloidosis. Immunoglobulin light chain concordant monotypic PCs and monotypic B cells were identified in 96% of cases assessed by flow cytometry. Notably, the neoplastic PCs were consistently positive for CD45 (dim, 100%), CD19 (96%), CD81 (89%), CD27 (83%), rarely and only weakly or partially express CD56 (16%), whereas CD117 was consistently negative. Eleven cases analyzed by fluorescence in situ hybridization were negative for CCND1::IGH and myeloma-related aberrations. MYD88 mutation was detected in 17 of 24cases (71%), and CXCR4 mutation was identified in 6 of 19cases (32%), of which 4 had concurrent MYD88 mutation. In conclusion, the results highlight a potential diagnostic pitfall of LPL associated with marked plasmacytic differentiation and an IgG or IgA paraprotein that can resemble a PCN. Useful features in favor of LPL against PCN include the characteristic immunophenotypic profile of the PCs in LPL, absence of CCND1::IGH, and the presence of MYD88 and/or CXCR4 mutations.

PB2318: ACQUIRED WILLEBRAND SYNDROME REVEALING ASYMPTOMATIC MULTIPLE MYELOMA: A CASE REPORT

Background: Acquired Willebrand syndrome (AvWS) is a rare hemorrhagic syndrome, clinically and biologically identical to constitutional Willebrand syndrome (vWS). It predominantly affects subjects with no personal or family history of hemorrhage, at an average age of 60. Its prevalence has been estimated by some authors at 0.04%, and over 300 cases have been reported since its discovery in 1968. The pathologies responsible for acquired Willebrand syndrome are diverse; including lymphoproliferative and myeloproliferative syndromes,autoimmune and cardiovascular diseases, solid tumors, and even certain medications. The physiopathology is complex and leads to an accelerated clearance of Willebrand factor. A Willebrand anti-factor antibody is preferentially found during lymphoid proliferation, while the mechanical destruction of high molecular weight multimers is observed during heart problems. Aims: To emphasize the pre-existing link between acquired Willebrand disease and multiple myeloma, as well as show the complexity of this relation. Methods: We report the case of a patient in whom the diagnosis of acquired Willebrand syndrome allowed to reveal an asymptomatic multiple myeloma. Results: A 50-year-old patient was admitted for the etiological assessment of an iron deficiency anemia due to a hemorrhagic symptomatology made up of rectal bleeding and epistaxis. There was no family or personal history of hemorrhage, especially during circumcision and dental extractions. On the biological report, we found microcytic anemia with iron deficiency. The hemostasis assessment revealed an elongated partial thromboplastin time at 2.94 with a correct prothrombine ratio at 100%. Factor XIII has collapsed to 5%. FWV antigen was at 9.4%, and its activity at 3%. This biological profile was in favor of Willebrand disease type 3. On the etiological assessment, protein electrophoresis objectified a monoclonal peak with the presence of an immunoglobulin G kappa at immunofixation. The diagnosis of multiple myeloma was retained due to the presence of 28% of monotypic plasma cells for kappa light chains. CRAB criteria were absent except for anemia which has been attributed to chronic bleeding. ISS score was at 1. FISH was not carried out. The diagnosis of an AVWS on multiple myeloma was retained. Despite the absence of myeloma treatment criteria, the indication for chemotherapy has been made. The patient received 2 courses of chemotherapy combining bortezomib, thalidomide and dexamethasone. The hematological reassessment after 2 cures has shown a partial response on the monoclonal gammopathy. However, the absence of response on Willebrand’s disease was noted: the FWV antigen was at 3% and its activity at 11.5%, which resulted on the interruption of the chemotherapy protocol. The patient was put on rituximab for his von Willebrand’s disease according to the following protocol: 1g on Day 1, and on Day15. The cessation of the hemorrhagic syndrome was noted during the reassessment. Summary/Conclusion: Acquired von Willebrand syndrome is a very heterogeneous hemorrhagic syndrome, usually characterized by mild to moderate hemorrhagic symptoms, which can be severe and life-threatening in some cases. During the investigation of a hemorrhagic syndrome in the elderly, it is crucial to think of the AWVS. We recommend screening for AvWS in patients followed for onco-haematological pathologies when unexplained abnormal bleeding occurs.the treatment of the monoclonal gammapathy can allow the regression of the hemorrhagic manifestations in some cases.

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Diffuse Large B-Cell Lymphoma, Epstein–Barr Virus -Positive Kappa Monotypic Plasma Cell Proliferation and Invasive Carcinoma, Developing in a Child With Defective Mismatch Repair

Constitutional mismatch repair deficiency (CMMRD) syndrome is characterized by biallelic mutations in a mismatch repair gene and is associated with development of childhood cancers and symptoms resembling neurofibromatosis type 1, like café-au-lait spots. We describe the extremely rare case of a 12-year-old male presenting with several light brown macular lesions on the skin, gastrointestinal diffuse large B-cell lymphoma, adenomatous polyposis throughout the gastrointestinal tract and an intra-abdominal invasive carcinoma derived from upper gastrointestinal system. All neoplasia, as well as normal tissues, showed loss of Msh6 expression with immunohistochemistry. Molecular studies showed pathogenic homozygous p.F1088Sfs*2 mutation in MSH6. Furthermore, signs consistent with immunodeficiency, namely decreased levels of IgG and IgA in the serum, nodular lymphoid hyperplasia and EBV-associated plasma cell proliferation with monotypic kappa light chain expression in the ileum, were also noted. Our case depicts the phenotypic diversity of CMMRD syndrome and emphasizes its association with immunodeficiency, raising awareness to a feature not widely recognized.

Plasmacytoma/multiple myeloma type posttransplant lymphoproliferative disorder.

A 38-year-old male with a history of lupus nephritis and kidney transplantation 3 years ago, presented with fever, night sweats, and lymphadenopathy while being treated with tacrolimus, mycophenolate mofetil, and prednisone. Evaluation with PET and CT scan showed generalized lymphadenopathy and splenomegaly. (Left-sided figure). Biopsy of an inguinal lymph node showed a monotypic plasma cell proliferation (CD138+, kappa+, CD20-), as part of a monomorphic variant of post-transplant lymphoproliferative disease (PTLD) (Right-sided figure). The specific type was determined as plasmacytoma/multiple myeloma type PTLD. However, a diagnosis of PTLD type plasma cell-rich marginal zone lymphoma was also possible, although no separate malignant lymphocytic B-cell component could be demonstrated. No Epstein–Barr virus (EBV) positivity was found. Bone-marrow showed a similar monomorphic PTLD with an increased amount of plasma cells. Laboratory testing showed only mild anemia and no kidney function decline or hypercalcemia. M-protein was identified as IgA-kappa, 24 g/L. There were no bone lesions. Cytogenetics of the bone marrow showed no abnormalities. A diagnosis of plasmacytoma/multiple myeloma type PTLD was made, and treatment was commenced with thalidomide, bortezomib, and dexamethasone. Multiple myeloma/plasmacytoma-like PTLD is a rare complication of solid organ transplant. It is characterized by plasmacytic histology with the presence of CD138 and lack of CD20. Only 3.5% of PTLD are of this subtype [1]. In a retrospective cohort and case series, the median time from organ transplant to disease was 3–10 years [1-4]. Bone lesions were only present in a minority of patients [2] and many patients presented with extranodal disease [1, 3, 4] Similar to our patient, no significant hypercalcemia or renal insufficiency was found, and only mild anemia [3, 4] Patients had both positive and negative EBV immunohistochemical staining [2-4]. Patients underwent a reduction in immunosuppression and treatment with proteasome inhibitor-based regimens with 20% also receiving autologous stem cell transplants. The median overall survival was 2.4 years and survival was decreased compared to regular multiple myeloma patients [1]. In conclusion, plasmacytoma/multiple myeloma type PTLD often presents without bone lesions, hypercalcemia, or renal insufficiency. Differentiation between this entity and other PTLD's with a prominent component of plasma cells (including marginal zone lymphoma) can be difficult, as both can produce monoclonal paraproteins. Treatment for plasmacytoma/multiple myeloma type PTLD is currently similar to conventional myeloma, however outcomes are inferior.

IgM Plasma Cell Myeloma.

Immunoglobulin M plasma cell myeloma (IgMPCM) is a rare entity that is difficult to distinguish from other IgM-related neoplasms. The study aims to characterize the clinicopathologic features of IgMPCM, including MYD88 L265P and CXCR4 mutations. From our institutional archives, bone marrow biopsy specimens from January 1, 2008, to December 1, 2018, with monotypic plasma cells (PCs) expressing IgM that met current International Myeloma Working Group/World Health Organization criteria for PCM were included. Sanger sequencing was used to test for MYD88 L265P and WHIM-like CXCR4 mutations. Nine cases of IgMPCM were identified. Serum IgM paraproteins were detected in eight cases. CD138-positive PC burden averaged 41.9% (5%-80%). In four cases, PCs had lymphoplasmacytic morphology with cyclin D1 expression by immunohistochemistry. Three of four tested cases were positive for t(11;14) by fluorescence in situ hybridization, one with monosomy 13. The remaining case was positive for del13q14. All were negative for MYD88 L265P and WHIM-like CXCR4 mutations. Eight patients received immunochemotherapy, with four receiving autologous hematopoietic stem cell transplant. Median follow-up was 61 months (range, 11-120). All patients were alive except one. Distinguishing IgMPCM from other IgM-related disorders requires correlation with clinical, laboratory, and radiologic findings. Exclusion of MYD88 L265P and WHIM-like CXCR4 mutations may be useful to diagnose IgMPCM.

Sellar Plasmacytoma: An Unusual Presentation of Anaplastic Multiple Myeloma

Abstract Background: Anaplastic multiple myeloma (AMM) is an extremely rare morphological subtype of multiple myeloma that has been reported only sporadically. Furthermore, pituitary involvement by multiple myeloma is rare and can be misdiagnosed as a nonfunctioning pituitary adenoma, due to its radiological and clinical similarities. Clinical Case: A 46-year-old man with no past medical history presented with a 3-month history of left shoulder pain. Initial physical exam revealed a large left neck mass, which prompted a left shoulder x-ray remarkable for left supraclavicular mass. Chest CT scan showed a bony mass (7 x 4 x 4 cm) in the left anterior second rib with extra osseous soft tissue involvement. CT also noted left supraclavicular/infraclavicular and left axillary adenopathy. Patient also reported lightheadedness and double vision for a few months and found to have diplopia with upward gaze on exam. Brain MRI revealed uniformly enhancing mass in right sphenoid sinus involving the sella measuring 2.3x2.6x3.2cm. With exception of low Hemoglobin (10.5, 13.5 - 17.7 g/dL) and mildly elevated prolactin (29.9, 2.0 - 20.0 ng/mL), laboratory testing was within normal limits including complete blood count, metabolic panel and pituitary hormone levels. Patient underwent fine needle aspiration of the supraclavicular node, which showed anaplastic plasma cell neoplasm. Further work up noted elevated M-spike, Kappa light chain 92.7 (0.3-2.0 mg/dl), kappa/lamda ratio 23 (0.3-1.6) and beta-2 microglobulin 4324 (600-2,200 ng/mL). Bone marrow biopsy confirmed 70% myeloma involvement with kappa monotypic plasma cell population expressing CD20, CD138, CD38, and CD117. Patient underwent endoscopic endonasal trans-sphenoidal biopsy of the mass. Frozen section pathology revealed a plasma cell neoplasm, and a subtotal resection was performed. Final surgical pathology confirmed anaplastic plasma cell neoplasm. He was started on systemic chemotherapy and external beam radiation. Conclusion: Sellar involvement by myeloma is very rare with less than 50 cases reported in the literature. While rare, these tumors should be considered in the differential diagnosis for lesions involving the sella as the therapeutic approach is different from other sellar masses. While the radiographic appearance can be similar, pituitary plasmacytomas typically present with headache and neurological signs such as cranial nerve palsies and visual changes, with preserved pituitary function. Close attention to physical exam and lab parameters can provide clues to this rare diagnosis.

Monotypic Plasma Cell Proliferation of Uncertain Clinical Significance Mimicking Interstitial Cystitis: An Early Lesion of MALT Lymphoma?

We prospectively studied our institutional experience of bladder extranodal marginal zone (mucosa-associated lymphoid tissue [MALT]) lymphoma including bladder biopsies in which the possibility of MALT lymphoma was considered. We identified a subset of cases primary to the urinary bladder, presenting with prominent plasma cell infiltrates and symptoms mimicking bladder pain syndrome/interstitial cystitis. These proliferations were designated for this study as "monotypic plasma cell proliferation of uncertain clinical significance" (MPCP-US), as the features were insufficient for diagnosis of MALT lymphoma. We identified 33 patients, consisting of 22 cases of MPCP-US (6 of which were associated with amyloid deposition) and 11 cases of MALT lymphoma. MPCP-US was more prevalent in men (73%), a mass lesion was not identified at cystoscopy, and only 1 case had an accompanying urinary tract infection (4.5%). Histologically, MPCP-US presented as monotypic plasma cells arranged in a superficial band-like distribution in the lamina propria, predominantly kappa restricted (68%) and IgA+ or IgM+ (64% and 23%, respectively) and without a histologic mass of atypical B cells or plasma cells, not diagnostic for established MALT lymphoma or plasmacytoma. Secondary involvement of the bladder by other lymphoproliferative disorders was excluded and there was no evidence of progressive disease. MALT lymphomas are presented for comparison and our analysis demonstrated that MPCP-US represent a different clinicopathologic entity compared with classic MALT lymphoma. We present the first series of cases of MPCP-US. The recognition of this entity is fundamental to the development of management protocols to relieve intractable symptoms mimicking bladder pain syndrome/interstitial cystitis in these patients.

EBV Negative Plasmablastic Transformation of Plasma Cell Myeloma with Aberrant Acquisition of T-Cell Associated Markers: An Aggressive Disease with Very Short Survival

Introduction: Plasma cell neoplasms can show aberrant expression of different lineages related antigens, but expression of T-cell associated markers, is exceedingly rare. Herein, we describe two patients with plasma cell Myeloma who relapsed with an aggressive disease with plasmablastic morphology, skin involvement, high Ki-67, complex karyotype (with abnormalities in chromosome 1) and interestingly both patients showed aberrant acquisition of single or multiple T-cell associated markers including CD4 and died shortly after last presentation. T-cell markers were not expressed at diagnosis. Multiple theories have been proposed to explain aberrant expression of T-cell markers on a terminally differentiated plasma cells. Due to rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated. An extensive literature review for patients with similar findings was conducted and the relevant pathological, clinical and prognostic characteristics were summarised. Methodology: Herein we describe two patients with emergent plasmablastic morphology and aberrant acquisition of multiple T-cell markers (confirmed by both flow cytometry (FCM) and immunohistochemistry), diagnosed in national Centre for Cancer Care and Research in Qatar. In addition, we conducted a systematic literature review using PubMed, google scholar and Scopus for patients with plasma cell myeloma (PCM) and aberrant T-cell expression, using pre-defined search terms and synonyms. Results: Patients diagnosed in our centre: Case 1: A 47-year-old male presented with multiple subcutaneous swellings, skin biopsy showed plasma cell neoplasm (PCN). Serum protein electrophoresis showed two bands; IgD lambda and free lambda. The patient started on VRD followed autologous SCT. Two months later, he developed new skin nodules in the upper chest wall and right renal mass. BM at relapse, showed many pleomorphic myeloma cells with plasmablastic/ anaplastic morphology. FCM showed a large population of monotypic plasma cells expressing CD10 with aberrant expression of CD33, CD4 and CD7 (partial). By IHC: the plasma cells were positive for cMYC with aberrant expression of CD4 and CD7 (partial) and CD3 (minority of cells) with Lambda light chain restriction and negative for CD20, CD56 and CD117. KI-67 &amp;gt;90%. Karyotype: 47,X, Y,i(1)(q10) ,t(1;3)(p32;p13),+der(3)t(1;3)(p32;p13) ,add(4)(q35),der(8)t(8;15)(q24;q11.2) add(8)(p23),add(13)(q34),+20[20]. The patient started on second line treatment for two days, unfortunately, he progressively deteriorated and passed away. Case 2: 56-year-old male presented with solitary spinal plasmacytoma and PCM. The patient underwent local radiotherapy followed by Lenalidomide and dexamethasone for 12 cycles and achieved complete remission. 5 years later, the disease progressed with multifocal spinal lesions and right chest wall mass which was treated with Pomalidomide and Daratumumab but he progressed and developed as scalp mass lesion. BM was infiltrated by many myeloma cells with plasmablastic morphology. FCM showed a monotypic plasma cell with aberrant expression of CD4 and complex karyotype. New line of therapy include Elotuzumab-Pomalidomide-dexamethasone started and unfortunately the patient shortly succumb. Upon literature review: A total of 19 cases of PCNs (table 1) showed aberrant expression of T-cell associated markers (including the two cases reported here). 11 case at relapse &amp; two at initial presentation. Anaplastic/plasmablastic morphology and extramedullary presentation were reported in 8/12 cases. 10/18 patients out showed aberrant expression of CD4. 9/11 cases had a very short survival. Conclusion: Here we discuss an interesting, yet a rare finding of aberrant acquisition of T-cell associated markers on PCM. This review emphasises the importance of recognising atypical and rare immunophenotypic aberrancies in PCN that could possibly lead to diagnostic pitfalls (particularly with extramedullary involvement) and provide important prognostic information. We conclude that there is an evident association between aberrant expression of T-cell associated markers on PCM and aggressive disease including plasmablastic morphology, high KI-67, extramedullary involvement and adverse outcome with short survival. Disclosures No relevant conflicts of interest to declare.

Hematopoietic Progenitor Cell Mobilization and Collection for Autologous Hematopoietic Cell Transplantation in AL Amyloidosis: A Single Center Experience

Hematopoietic Progenitor Cell Mobilization and Collection for Autologous Hematopoietic Cell Transplantation in AL Amyloidosis: A Single Center Experience

Pediatric post-transplant lymphoproliferative disorder identified on random gastrointestinal biopsies shows non-mass-forming PTLD with clonal plasma cells: report of 2 cases

EBV-related lymphoproliferations in post-transplant settings range from non-destructive hyperplasia to polymorphic post-transplant lymphoproliferative disorder (PTLD) to overt lymphoma. Here we present two unusual cases of pediatric non-mass-forming gastrointestinal (GI) PTLDs with mixed pathologic features of non-destructive and polymorphic categories. Both patients were EBV naive and presented within 1 year of transplant with non-specific gastrointestinal symptoms (diarrhea, abdominal pain, and food intolerance) with hypoalbuminemia, cytopenia, and EBV viremia. No mass lesions were found on imaging and endoscopy. Random GI biopsies showed a non-mass-forming, but polymorphic-appearing lymphoid infiltrate with EBV positivity, monotypic plasma cells, and clonal B cells. Cyclophosphamide, steroids, and rituximab treatment had good clinical response in all cases, including one case which had poor response initially with rituximab alone. Based on these cases, we conclude that GI PTLD in children can present with vague abdominal symptoms, cytopenia, and hypoalbuminemia, and can be non-mass-forming and non-destructive. A high level of suspicion with random GI biopsies and clinicopathologic and laboratory correlation are required. Since these patients have no mass lesions, evaluating symptomatic relief, EBV viral load, improvement in cytopenia(s), serum albumin levels, and/or resolution of other systemic symptoms may be needed to monitor response to therapy.

Circulating MicroRNAs in Multiple Myeloma: a Literature Review.

Multiple myeloma is a tumour of antibody-secreting plasma cells characterized by clonal expansion and accumulation of monotypic plasma cells in the bone marrow. It is an incurable malignant neoplasm accounting for 10% all hematological malignancies. Globally, the annual percentage of new cancer cases and deaths attributed to multiple myeloma is estimated at about 0.8% and 1%, respectively. Furthermore, its global incidence ranges from 0.5 - 12/100,000 population. It causes hypercalcemia, renal insufficiency, anemia, thrombocytopenia, leucopenia, bone lesions, bone fractures, spinal stenosis, and endorgan damages. This neoplasm occurs due to a complex cytogenetic and chromosomal aberrations. These aberrations affect the expression and functions of microRNAs. Abnormal expression of these microRNAs plays an important role in the pathogenesis and angiogenesis of multiple myeloma and could have a potential role in the diagnosis, prognostic stratification, and treatment of multiple myeloma. This review aimed at summarising the expression of microRNAs and the implication of their dysregulation in the pathogenesis, diagnosis, and treatment of multiple myeloma.

Identification of ST3GAL6-AS1 Interactive Protein in Multiple Myeloma

Introduction: Multiple myeloma (MM) is a malignancy of antibody-secreting plasma cells (PCs) characterized by the clonal expansion and accumulation of monotypic PCs in the bone marrow (BM). Despite the remarkable improvements have been done in knowledge on the pathobiology of MM, therapy and medical care, MM still remains an incurable disease. Therefore elucidation of regulatory circuits altered such as long non-coding RNAs (lncRNAs) will allow us to obtain a better understanding into the biology and targeted therapy of MM. Overwhelming evidence suggests that lncRNAs have huge impact on adjusting gene expression through the processes of transcription and post-transcription regulation, genomic imprinting, and chromatin modification. In our previous study, we validated one lncRNA named ST3 beta-galactoside alpha-2,3-sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) which was upregulated markedly in MM patients. Further research revealed that ST3GAL6-AS1 promote the adhesion, migration and invasion ability of MM cells. To determine the precise mechanism underlying ST3GAL6-AS1 biological function, we expound its interactive protein in this study. Methods: Comprehensive Identification of RNA binding Proteins by Mass Spectrometry (ChIRP-MS) was utilized to identify interactive protein of ST3GAL6-AS1. MM cell line MM.1S was reversibly crosslinked with UV/formaldehyde under native condition, with or without prior lysis, then hybridized with biotinylated DNA antisense and pulled down with streptavidin dynabeads. Peptides were identified by MS eventually. Raw MS files were processed with MaxQuant (Version 1.5.6.0). Both peptide and protein FDR should be less than 0.01. Gene Ontology (GO) analysis (http://david.abcc.ncifcrf.gov/summary.jsp) was used to analyze differentially expressed transcripts. Pathway analysis of differentially expressed transcripts was accomplished using Kyoto Encyclopedia of Genes and Genomes (KEGG) database (http://www.genome.jp/kegg). String online software (http://www.string-db.org/) was utilized to predict protein-protein interactions. Results: ChIRP-MS analysis identified a total of 599 proteins were interacted with ST3GAL6-AS1, among them, 177 proteins were identified to bind with ST3GAL6-AS1 specifically compared with control group (Figure 1A). GO and KEGG analysis were based on these 177 specific proteins. GO analysis showed that the top ten enriched biological process (BP) were mainly involved in mRNA catabolic process and splicing, while cellular component (CC) was cytosolic part and molecular function (MF) was structural constituent of ribosome (Figure 1B). KEGG pathway analysis of the top five enriched pathways included spliceosome and ribosome (Figure 1C). In the specific interaction proteins, we found multiple proteins belong to heterogeneous nuclear ribonucleoproteins (hnRNP) family, such as hnRNPA, hnRNPU. Further research showed that involved hnRNPs interacted with each other (Figure 1D) and mainly took important role in spliceosome by GO and KEGG analysis (FDR&lt;0.01). The results above suggested that ST3GAL6-AS1 might regulate target mRNA splice and catabolism through its interactive proteins, especially hnRNP family. Conclusions: We have identified a group of proteins in MM cells which were specifically interacted with lncRNA ST3GAL6-AS1. These proteins mainly participate in mRNA catabolism and spliceosome, which might was the mechanism of ST3GAL6-AS1 to regulate its target gene in MM. Further investigation will focus on the exact action of ST3GAL6-AS1 through its interacting proteins. Figure 1 Disclosures No relevant conflicts of interest to declare.

SUN-432 A Case of Sellar Plasmacytoma Masquerading as Pituitary Carcinoma with Hypopituitarism

Background: Sellar plasmacytomas are rare tumors arising from clonal plasma cells localized to the sellar/parasellar region. They may mimic other pituitary pathology such as pituitary adenomas, chordomas, meningiomas or metastatic carcinomas in both clinical manifestations and radiographic evidence. Certain features such as predominance of cranial nerve palsies and absence of hypopituitarism appear to be more common with sellar plasmacytomas. We present an interesting case of a sellar plasmacytoma, initially mistaken for pituitary carcinoma, with rapid development of hypopituitarism and systemic multiple myeloma. Case: A 75 year old healthy male presented with sudden onset left eye diplopia and retro-orbital pain. Left eye ptosis and diplopia with left lateral and upward gaze were noted on exam. Initial MRI brain revealed a 17mm soft tissue mass involving pituitary and clivus, extending into the left superior orbital fissure, concerning for pituitary carcinoma. With the exception of low LH (1.2) and testosterone (25), baseline pituitary hormone labs, complete blood count and metabolic panel were within normal limits. Within 1 month, he acutely presented with fever, confusion, weakness, and bony pains. Repeat pituitary labs showed low ACTH < 5, AM cortisol 4.3, TSH 0.07, FT4 0.5. New findings of acute renal injury, hypercalcemia, anemia with elevated Mspike, Kappa light chain 39.7 (0.3-2.0mg/dl), kappa/lamda ratio 66.2 (0.3-1.6) and beta2microglobulin 4484 were found. Repeat MRI brain noted multifocal osseous metastatic disease with left sellar and cavernous sinus lesion contiguous with clival osseous lesion displacing pituitary gland, concerning for plasmacytoma. PET/CT showed focal lytic lesions in clivus and posterior left iliac bone. Bone marrow biopsy confirmed 70% myeloma involvement with kappa monotypic plasma cell population. He was started on hydrocortisone, levothyroxine, chemotherapy and XRT. Conclusion: The rarity of plasmacytomas, combined with their clinical presentation and imaging characteristics similar to other sellar tumors, can often result in misdiagnosis. Accuracy of diagnosis is critical, as sellar plasmacytomas and underlying multiple myeloma (present in 50% of cases) require XRT and systemic chemotherapy respectively rather than surgery. Although pituitary function is usually preserved in plasmacytomas, our case shows that acute anterior pituitary dysfunction can be an early presenting sign.