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Kumar V, Batool S, Misra S, Ahuja A, Marwah S, Baweja G, Kumar S. Reactive bone marrow plasmacytosis: A common denominator with diverse etiology. HAMDAN MEDICAL JOURNAL 2022. [DOI: 10.4103/hmj.hmj_52_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Successful Treatment for Solitary Bone Plasmacytoma of the Maxilla: A Rare Case Report. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2020. [DOI: 10.5812/ijcm.91352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Introduction: Plasma cell tumors are monoclonal neoplastic proliferation of plasma cells which are divided into three groups: solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) which are localized forms, and multiple myeloma (MM) which is the disseminated form. Skull, long bones, and vertebrae are common sites for SBP and its presence in maxillofacial area is rare. There is a possibility that SBP converts to MM and some authors believe that it can be the early stage of MM. Case Presentation: Here, we present a 59-year old male patient with a mass in maxillary bone enlarging after tooth extraction. Cone beam computed tomography (CBCT) confirmed the existence of a poorly defined lesion in the left maxilla. The microscopic evaluation and immunohistochemical studies confirmed the diffuse and monoclonal population of cells, indicating the diagnosis of plasma cell tumor. There was also no evidence of bone marrow involvement in the aspiration. Conclusions: Early and precise diagnosis of SBP is a crucial element to rule out the possibility of MM. It must be kept in mind that there is possibility of recurrence or progression to MM after treatment which can completely change the course of disease, and this emphasizes the importance of regular follow up.
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Iosif E, Rees C, Beeslaar S, Shamali A, Lauro R, Kyriakides C. Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature. World J Gastrointest Endosc 2019. [DOI: 10.4253/wjge.v11.i4.309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Iosif E, Rees C, Beeslaar S, Shamali A, Lauro R, Kyriakides C. Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature. World J Gastrointest Endosc 2019; 11:308-321. [PMID: 31040892 PMCID: PMC6475702 DOI: 10.4253/wjge.v11.i4.308] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 03/27/2019] [Accepted: 04/09/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.
CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search (PubMed database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma (EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males (67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach (41%), followed by the duodenum (15%). The most common presenting complaint was melena (44%). In the majority of cases, the EMPs were a secondary manifestation (63%) at the background of multiple myeloma (26%), plasmablastic myeloma (7%) or high-grade plasma cell myeloma (4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.
CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.
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Affiliation(s)
- Evangelia Iosif
- Department of Gastrointestinal Surgery, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
| | - Clare Rees
- Department of Haematology, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
| | - Salome Beeslaar
- Department of Histopathology, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
| | - Awad Shamali
- Department of Gastrointestinal Surgery, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
| | - Roberto Lauro
- Department of Gastrointestinal Surgery, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
| | - Charis Kyriakides
- Department of Gastrointestinal Surgery, Frimley Park Hospital, Frimley, Camberley GU16 7UJ, United Kingdom
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Abstract
Myeloma is characterized by the neoplastic proliferation of monoclonal plasma cells. A diagnosis of myeloma is based on the criteria proposed by the International Myeloma Working Group and the pathological findings.Myeloma cells are classified into four types: mature, immature, pleomorphic, and plasmablastic. There are three patterns in which myeloma infiltrates bone marrow - nodular, interstitial, and diffuse. Dutcher bodies are highly specific to neoplastic myeloma cells. On immunohistochemical staining, the specificity of CD138 is high for plasma cells. As a clear image is often not obtained from the immunohistochemical staining of the immunoglobulin light chain, in situ hybridization is recommended. Abnormal expression of CD56 is seen in 70-80% of cases by flow cytometry analysis. CD56 expression definitively indicates myeloma, suggesting its high diagnostic value. Evaluation of the infiltration pattern, monoclonality, and abnormal antigen expression of plasma cells is more important than the plasmocytic ratio to determine whether a case is reactive or neoplastic.Multiple gene abnormalities function in the onset and progression of myeloma. In our department, we analyze CCND1, FGFR3, MAF, and del (17p13) by FISH for all myeloma cases. None of the cases with genetic abnormalities were recognized by G-banding. Therefore, FISH is more effective than G-banding for the evaluation of genetic abnormalities in myeloma.
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Roshal M. Minimal Residual Disease Detection by Flow Cytometry in Multiple Myeloma: Why and How? Semin Hematol 2018; 55:4-12. [PMID: 29759152 DOI: 10.1053/j.seminhematol.2018.02.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 02/27/2018] [Indexed: 11/11/2022]
Abstract
The outlook for myeloma patients has steadily improved with the introduction of newer drug combinations in recent years. Unlike older therapies that largely achieved only modest levels of neoplastic clone reduction, the newer drug combinations have led to deeper suppression of myeloma clones in most patients. Frequently the neoplastic clones become undetectable with traditional disease evaluation approaches. Recent studies using ultrasensitive disease monitoring have demonstrated that patients with disease undetectable by traditional techniques show wide heterogeneity in disease levels varying by several orders of magnitude. Moreover, measurement of the depth of disease suppression even at very low level has emerged as the most powerful prognostication tool in myeloma. Minimal (or measurable) residual disease (MRD) evaluation has also been proposed as a relevant tool in assessment of drug efficacy and in selection of further therapeutic options. In the face of the robust MRD measurement utility data, it has become critical to develop widely applicable disease monitoring techniques that can be applied to more patients in a variety of clinical setting. Both DNA-based and flow cytometry-based approaches have been successfully developed for this purpose achieving sensitivity approaching 1 neoplastic cell in a million. This review article focuses on the theoretical and practical aspects and challenges of deep MRD monitoring in myeloma by flow cytometry. Challenges of flow cytometric disease monitoring in the era of antigen-directed therapy are also discussed.
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Affiliation(s)
- Mikhail Roshal
- Hematopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
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Alexandrakis MG, Passam FH, Pappa CA, Dambaki C, Sfakiotaki G, Alegakis AK, Kyriakou DS, Stathopoulos E. Expression of Proliferating Cell Nuclear Antigen (PCNA) in Multiple Myeloma: Its Relationship to Bone Marrow Microvessel Density and other Factors of Disease Activity. Int J Immunopathol Pharmacol 2016; 17:49-56. [PMID: 15000866 DOI: 10.1177/039463200401700107] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The expression of the proliferating cell nuclear antigen (PCNA) was studied in plasma cells in bone marrow biopsies from patients with multiple myeloma (MM) using a double immunostaining method. In the same samples, microvessel density (MVD), after staining with anti-CD34 antibodies, was determined before and after chemotherapy. The correlation of PCNA expression and MVD with other myeloma parameters (clinical stage, bone marrow plasma cell infiltration and serum interleukin –6 (IL-6)) was also investigated. The study population included 51 newly diagnosed MM patients, 12 patients in plateau phase after treatment and 15 normal controls. Pretreatment mean ± SE values of PCNA, MVD, plasma cell infiltration and serum IL-6 were significantly higher than post treatment values and controls. Pretreatment PCNA expression correlated significantly with bone marrow MVD (p<0.05) plasma cell infiltration (p<0.01) and IL-6 (p<0.01). These findings show that the proliferative activity of plasma cells is related to the angiogenic activity in the bone marrow of multiple myeloma patients. Both PCNA and MVD correlate with markers of disease activity thus may provide additional information when included in the initial evaluation of myeloma bone marrow biopsies.
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Affiliation(s)
- M G Alexandrakis
- Department of Hematology, University Hospital of Heraklion, Medical School of Crete, Greece.
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Igase M, Shimokawa Miyama T, Kambayashi S, Shimoyama Y, Hiraoka H, Hirata Y, Iwata M, Baba K, Mizuno T, Okuda M. Bimodal immunoglobulin A gammopathy in a cat with feline myeloma-related disorders. J Vet Med Sci 2015; 78:691-5. [PMID: 26638898 PMCID: PMC4873863 DOI: 10.1292/jvms.15-0156] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
A 10-year-old female spayed mixed breed cat with a subcutaneous mass on the right hind
limb was revealed with bimodal monoclonal gammopathy composed of IgA by
immunoelectrophoresis and immunofixation. Approximately 1 month after referral, the cat
died due to renal failure. Postmortem immunohistopathologic evaluation of the subcutaneous
mass revealed neoplastic cell proliferation of plasma cells and giant myeloma cells.
Neoplastic cells were also present in the liver and spleen. These results led to the
diagnosis of a rare case of feline myeloma-related disorders with extramedullary
plasmacytoma infiltrating in multiple locations. This report emphasizes the necessity to
accumulate cases with similar clinicopathologic findings in the future.
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Affiliation(s)
- Masaya Igase
- Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan
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Lee BD, Park MR, Kwon KH. Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features. Imaging Sci Dent 2015; 45:199-203. [PMID: 26389064 PMCID: PMC4574059 DOI: 10.5624/isd.2015.45.3.199] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2015] [Revised: 05/11/2015] [Accepted: 05/24/2015] [Indexed: 11/18/2022] Open
Abstract
A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.
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Affiliation(s)
- Byung-Do Lee
- Department of Oral and Maxillofacial Radiology and Wonkwang Dental Research Institute, College of Dentistry, Wonkwang University, Iksan, Korea
| | - Moo-Rim Park
- Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Korea
| | - Kyung-Hwan Kwon
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Wonkwang University, Iksan, Korea
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Rosado FG, Morice WG, He R, Howard MT, Timm M, McPhail ED. Immunophenotypic features by multiparameter flow cytometry can help distinguish low grade B-cell lymphomas with plasmacytic differentiation from plasma cell proliferative disorders with an unrelated clonal B-cell process. Br J Haematol 2015; 169:368-76. [PMID: 25644063 DOI: 10.1111/bjh.13303] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 11/27/2014] [Indexed: 11/30/2022]
Abstract
Highly sensitive flow cytometry studies may incidentally identify B cell clones when used to assess plasma cell clonality in bone marrows. Clinical history, which can help differentiate related clones (low grade B cell lymphoma with plasmacytic differentiation/LBCL-PD) from unrelated ones (plasma cell proliferative disorder (PCPD) with an unrelated B cell clone), is often unavailable in referred specimens. We sought to identify morphologic or phenotypic features that would help predict the significance of these clones in the absence of history. We included only cases with identical light chain B and plasma cell clones, as determined by 6-color flow cytometry with additional DNA ploidy analysis, in which the relationship between clones could be established by review of medical records. There were 26 cases; 18 were related (14 were Waldenstrom macroglobulinemia) and eight were unrelated (seven multiple myeloma). Features seen exclusively in LBCL-PD include CD19+/CD45+ clonal plasma cell phenotype (66·7%, P = 0·0022) and morphologic features such as paratrabecular bone marrow involvement, increased mast cells, and plasma cells surrounding B-cell nodules. Aneuploidy was identified exclusively in PCPD cases (75%, P = 0·000028). We conclude that CD19+/CD45+ clonal plasma cell phenotype and aneuploidy are useful in distinguishing related clones (LBCL-PD) from unrelated clones (PCPD).
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Affiliation(s)
- Flavia G Rosado
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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Variant morphology in multiple myeloma. Indian J Hematol Blood Transfus 2014; 30:86-7. [PMID: 25332545 DOI: 10.1007/s12288-013-0259-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 04/08/2013] [Indexed: 10/26/2022] Open
Abstract
A 45-year-old man presented to the clinic with the chief complaints of low back pain, marked weight loss, and pallor of 2 months duration. He was found to have severe normocytic anemia with leukoerythroblastosis. Bone marrow aspirate resulted in a dry tap. Marrow trephine biopsy showed findings initially interpreted as poorly differentiated carcinoma involving marrow. Immunohistochemistry and protein studies established a diagnosis of IgG Kappa multiple myeloma. Correlation of marrow biopsy findings with clinical, radiological and immunological data remain an essential part of the diagnostic evaluation of multiple myeloma.
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What We Mean When We Talk About MRD in Myeloma. A Review of Current Methods. Part 1 of a Two-Part Series. Curr Hematol Malig Rep 2014; 9:379-88. [DOI: 10.1007/s11899-014-0238-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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The value of FDG PET/CT in the initial staging and bone marrow involvement of patients with multiple myeloma. Skeletal Radiol 2011; 40:843-7. [PMID: 21229354 DOI: 10.1007/s00256-010-1088-9] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2010] [Revised: 10/30/2010] [Accepted: 12/16/2010] [Indexed: 02/02/2023]
Abstract
OBJECTIVE The aim of this study was to describe the role of positron emission tomography/computed tomography (PET/CT) with fluorine-18 fluorodeoxyglucose (FDG) in the detection of skeletal and visceral involvement in patients with MM (multiple myeloma) at the initial diagnosis and to evaluate the relation between maximum standardized uptake values (SUVmax) of FDG with bone marrow cellularity and plasma cell ratios. MATERIALS AND METHODS The study population consisted of 42 patients (15 F, 28 M; mean ± SD age; 47 ± 12 years). Thirty-two patients were referred for initial diagnosis and ten patients were referred for assessment of therapy response. PET/CT scan was obtained 60 min after the administration of 5.4 MBq/kg FDG. The SUVmax of FDG uptake was measured from the region of interest, which was placed at the site of most prominent lesion in bone marrow in PET/CT images. RESULTS Thirty patients were positive (29 of 32 initially diagnosed, one of ten previously treated) and 12 patients were negative on PET/CT scan. Conventional radiological methods were negative in three of 30 FDG PET/CT-positive patients and these methods did not show any pathological finding in 12 FDG PET/CT-negative patients. The sensitivity of FDG PET in detecting bone marrow involvement at initial diagnosis was 90%. There was a significant correlation between SUVmax values and bone marrow biopsy cellularity and plasma cell ratios, (r = 0.54 and r = 0.74, p < 0.01). CONCLUSIONS The results of this study demonstrated that FDG-PET is a useful technique for the assessment of MM and the correlation between SUVmax and plasma cell ratios in bone marrow biopsy may avoid repeated bone marrow biopsies in the follow-up period.
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Abstract
The plasma cell neoplasms are malignancies of the most terminally differentiated cells in B-cell ontogeny and are usually associated with the production of a monoclonal immunoglobulin molecule or M protein. These malignancies include tumors whose clinical manifestations are directly attributable to the end-organ damage induced by the dysregulated proliferation of neoplastic plasma cells. In contrast, disorders, such as primary amyloidosis, have a paradoxically low burden of neoplastic plasma cells, rendered highly pathogenic by the end-organ damage induced by deposition of the secreted paraprotein. In this article, discussion focuses on plasma cell myeloma. The molecular pathogenesis of plasma cell myeloma is reviewed and the diagnosis of the plasma cell neoplasms discussed.
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Affiliation(s)
- Robert B Lorsbach
- Department of Pathology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Mail Slot 517, Little Rock, AR 72205, USA.
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Tatsas AD, Jagasia MH, Chen H, McCurley TL. Monitoring residual myeloma: high-resolution serum/urine electrophoresis or marrow biopsy with immunohistochemical analysis? Am J Clin Pathol 2010; 134:139-44. [PMID: 20551278 DOI: 10.1309/ajcp69tcavdgscwi] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Numerous methods exist for monitoring residual disease in multiple myeloma using peripheral blood, urine, and bone marrow (BM) techniques. This study was conducted in a cohort of 83 patients to compare residual disease detection using serum protein electrophoresis (SPE) and urine protein electrophoresis (UPE) with immunofixation with immunoperoxidase staining of BM tissue sections. Of the 83 patients, 49 had a positive SPE and/or UPE result and all had BM involvement shown by immunohistochemical analysis. The results for SPE and UPE were negative in 17 patients, and all 17 had a negative immunohistochemical BM result for a negative predictive value for SPE/UPE of 100%. In addition, SPE and UPE detected residual disease in 17 patients with negative BM biopsy studies. SPE and UPE can be used to screen patients for residual disease, and negative results for both can obviate the need for BM biopsy for the detection of residual disease by immunohistochemical analysis.
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Stifter S, Babarović E, Valković T, Seili-Bekafigo I, Stemberger C, Nacinović A, Lucin K, Jonjić N. Combined evaluation of bone marrow aspirate and biopsy is superior in the prognosis of multiple myeloma. Diagn Pathol 2010; 5:30. [PMID: 20482792 PMCID: PMC2883968 DOI: 10.1186/1746-1596-5-30] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Accepted: 05/18/2010] [Indexed: 11/16/2022] Open
Abstract
Background Estimation of plasma cell infiltrates in bone marrow aspirates (BMA) and bone marrow biopsy (BMB) is a standard method in the diagnosis and monitoring of multiple myeloma (MM). Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of the study was to compare the percentage of plasma cells obtained by both methods with the patient clinical parameters and survival. Methods This retrospective study included BMA and BMB of 59 MM patients. The conventional differential count was determined in BMA to estimate the percentage and cytologic grade of plasma cells. The pattern of neoplastic infiltration and percentage of plasma cells were estimated on CD138 immunostained BMB slides microscopically and by computer-assisted image analysis (CIA). Results Significantly higher values of plasma cell infiltrates were observed in pathologist (47.7 ± 24.8) and CIA (44.1 ± 30.6) reports in comparison with cytologist analysis (30.6 ± 17.1; P < 0.001 and P < 0.0048, respectively). BMB assessment by pathologist counting and using CIA showed strongest correlation (r = 0.8; P < 0.0001). Correlation was also observed between the pathologist and cytologist counts (r = 0.321; P = 0.015) as well as comparing the percentage of plasma cells in BMA and CIA (r = 0.27; P = 0.05). Patients with clinical stage I/II had a significantly lower CIA plasma cell count than those with clinical stage III (P = 0.008). Overall survival was shorter in patients with more than 25% of atypical plasma cell morphology estimated in BMA (P = 0.05) and a higher percentage of tumor cell infiltrates estimated by the pathologist and CIA (P = 0.0341 and P = 0.013, respectively). Conclusion Study results suggested the combined analyses to be useful as a routine procedure to achieve more accurate and informative diagnostic data.
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Affiliation(s)
- Sanja Stifter
- Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia
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Paiva B, Vidriales MB, Pérez JJ, Mateo G, Montalbán MA, Mateos MV, Bladé J, Lahuerta JJ, Orfao A, San Miguel JF. Multiparameter flow cytometry quantification of bone marrow plasma cells at diagnosis provides more prognostic information than morphological assessment in myeloma patients. Haematologica 2010; 94:1599-602. [PMID: 19880781 DOI: 10.3324/haematol.2009.009100] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Quantification of bone marrow plasma cells in multiple myeloma patients using conventional morphology is of limited prognostic value, while the merit of multiparameter flow cytometry immunophenotyping is still considered unproven. Here we compare the bone marrow plasma cell counts obtained by morphology and multiparameter flow cytometry and explore the potential prognostic impact of both techniques in 765 newly diagnosed, uniformly treated multiple myeloma patients. Although multiparameter flow cytometry generally yields lower plasma cell counts (median percentage of 11% vs. 40%, respectively; p<0.001), there is a significant positive correlation between the two techniques (R =0.46, p<0.001). Regarding prognosis, multivariate analysis selected the bone marrow plasma cell counts obtained by multiparameter flow cytometry as an independent prognostic factor for overall survival (p=0.007), supporting the incorporation of multiparameter flow cytometry immunophenotyping into the routine diagnostic evaluation of multiple myeloma patients and validating the clinical utility of bone marrow plasma cell counting by multiparameter flow cytometry approaches. (clinicaltrials.gov identifier: NCT00560053).
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Affiliation(s)
- Bruno Paiva
- Hospital Universitario de Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain
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Junquera L, Gallego L, Torre A, Hernando J, Fresno MF. Synchronous oral squamous cell carcinoma and extramedullary plasmacytoma of the tonsil. ACTA ACUST UNITED AC 2009; 108:413-6. [DOI: 10.1016/j.tripleo.2009.03.048] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2009] [Revised: 03/20/2009] [Accepted: 03/31/2009] [Indexed: 10/20/2022]
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Ioannou MG, Stathakis E, Lazaris AC, Papathomas T, Tsiambas E, Koukoulis GK. Immunohistochemical evaluation of 95 bone marrow reactive plasmacytoses. Pathol Oncol Res 2008; 15:25-9. [PMID: 18553158 DOI: 10.1007/s12253-008-9069-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2008] [Accepted: 05/20/2008] [Indexed: 12/25/2022]
Abstract
We histologically and immunohistochemically studied 95 bone marrow (BM) reactive plasmacytoses. Ten biopsies from plasma cell myeloma (PCM) patients served as a control group. In addition, we studied 10 monoclonal gammopathy of undetermined significance (MGUS) cases. Histologically, plasmacytosis varied between 5% and 25% with an interstitial pattern of plasma cell (PC) distribution being characteristically displayed. Immunohistochemically, we did not find any CD56/NCAM nor cyclin D1 expression in all biopsies (95 of 95, 100%), not even a weak, doubtful one; PCs were all polyclonal and CD138 positive. On the contrary, myeloma-associated PCs showed monoclonality for kappa- or lambda- light chain and strong CD56/NCAM immunoreactivity (8 of 10, 80%); four of them were cyclin D1 positive. Osteoblasts exhibited similar CD56/NCAM expression in both groups. Our data confirm the diagnostic utility of CD56/NCAM in the phenotypic characterization of polyclonal plasma cells, suggesting an important role of this particular immunomarker in the BM trephine study of polyclonal versus neoplastic plasmacytic infiltrations.
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Affiliation(s)
- Maria G Ioannou
- Department of Pathology, Medical School, University of Thessaly, Larisa, Greece
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Mellor PJ, Haugland S, Smith KC, Powell RM, Archer J, Scase TJ, Villiers EJ, McNeil PE, Nixon C, Knott C, Fournier D, Murphy S, Polton GA, Belford C, Philbey AW, Argyle DJ, Herrtage ME, Day MJ. Histopathologic, Immunohistochemical, and Cytologic Analysis of Feline Myeloma-Related Disorders: Further Evidence for Primary Extramedullary Development in the Cat. Vet Pathol 2008; 45:159-73. [DOI: 10.1354/vp.45-2-159] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Feline myeloma-related disorders (MRD) are rare neoplasms of plasma cells. The multistep transformation model of myeloma in humans is based on the premise that plasma cells undergo neoplastic transformation primarily within the intramedullary compartment and that over time they become poorly differentiated and metastasize to extramedullary locations. Historically, diagnostic criteria used for human multiple myeloma have been applied to the cat, with the assumption that feline MRD commonly arises in the intramedullary compartment. Our objectives were to describe the features of feline MRD confirmed by cytology, histopathology, histochemistry, and immunohistochemistry and to categorize these tumors. A priori hypotheses were 1) tumor category predicts survival and 2) cats with well-differentiated tumors commonly have extramedullary involvement in contrast to human myeloma patients. This multicenter, retrospective study identified 26 MRD cases. There was good agreement between histopathologic and cytologic tumor categorization. Histochemistry and immunohistochemistry were shown to be valuable adjunct tests in the diagnosis of MRD. Cats with well-differentiated tumors had increased median survival relative to those with poorly differentiated tumors (254 versus 14 days). We have reported that marked extramedullary involvement at initial clinical presentation is significantly more common in the cat than in human MRD patients. In this study, we demonstrate that cats with well-differentiated tumors more commonly have extramedullary involvement than human myeloma patients with well-differentiated tumors (90% versus 20%, P < 0.0002). These results contrast strongly with the human myeloma model of primary intramedullary neoplastic transformation and suggest that primary extramedullary neoplastic transformation may be more common in feline MRD.
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Affiliation(s)
- P. J. Mellor
- Department of Veterinary Medicine, University of Cambridge, UK
| | - S. Haugland
- Department of Veterinary Medicine, University of Cambridge, UK
| | - K. C. Smith
- Royal Veterinary College, University of London, UK
| | - R. M. Powell
- Department of Veterinary Medicine, University of Cambridge, UK
| | - J. Archer
- Department of Veterinary Medicine, University of Cambridge, UK
| | - T. J. Scase
- Department of Veterinary Medicine, University of Cambridge, UK
| | - E. J. Villiers
- Department of Veterinary Medicine, University of Cambridge, UK
| | | | - C. Nixon
- Faculty of Veterinary Medicine, University of Glasgow, UK
| | | | | | | | - G. A. Polton
- Davies Veterinary Specialists, Higham Gobion, UK
| | | | - A. W. Philbey
- Faculty of Veterinary Medicine, University of Glasgow, UK
| | - D. J. Argyle
- Royal Dick School of Veterinary Studies, University of Edinburgh, UK
| | - M. E. Herrtage
- Department of Veterinary Medicine, University of Cambridge, UK
| | - M. J. Day
- School of Clinical Veterinary Science, University of Bristol, UK
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Abstract
AIMS The aim of the current study was to asses the frequency of increased fibrosis in myeloma and to find its correlation with other bone marrow parameters and survival. METHODS Forty-four multiple myeloma patients diagnosed between 2001 and 2005 were included in the present study. A detailed study of the bone marrow aspiration smears and trephine biopsy was done. Bone marrow fibrosis was graded and correlated with other parameters like plasma cell morphology, pattern of infiltration, mitotic activity and also with the survival of the patients. RESULTS Increased fibrosis was seen in nine cases (20.5%). It was observed that plasma cell burden in the marrow was under-estimated in the aspirate smears compared with the trephine biopsy in patients with increased fibrosis. Increased marrow fibrosis correlated significantly with poorly differentiated plasma cell morphology (p = 0.020) and mitotic activity (p = 0.003), which by themselves are established prognostic markers for survival in multiple myeloma. Patients with increased fibrosis of the marrow also had a median survival time of just 11 months. CONCLUSIONS A bone marrow trephine biopsy is essential in all cases of myeloma at diagnosis, as it helps identify a subset of myeloma patients with increased marrow fibrosis and poorer prognosis.
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Affiliation(s)
- Rajiv Subramanian
- Department of Pathology, JIPMER, Dhanvantari Nagar, Pondicherry 605006, India
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22
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Al-Quran SZ, Yang L, Magill JM, Braylan RC, Douglas-Nikitin VK. Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry. Hum Pathol 2007; 38:1779-87. [PMID: 17714757 PMCID: PMC3419754 DOI: 10.1016/j.humpath.2007.04.010] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2006] [Revised: 04/09/2007] [Accepted: 04/20/2007] [Indexed: 12/16/2022]
Abstract
Assessment of bone marrow involvement by malignant plasma cells is an important element in the diagnosis and follow-up of patients with multiple myeloma and other plasma cell dyscrasias. Microscope-based differential counts of bone marrow aspirates are used as the primary method to evaluate bone marrow plasma cell percentages. However, multiple myeloma is often a focal process, a fact that impacts the accuracy and reliability of the results of bone marrow plasma cell percentages obtained by differential counts of bone marrow aspirate smears. Moreover, the interobserver and intraobserver reproducibility of counting bone marrow plasma cells microscopically has not been adequately tested. CD138 allows excellent assessment of plasma cell numbers and distribution in bone marrow biopsies. We compared estimates of plasma cell percentages in bone marrow aspirates and in hematoxylin-eosin- and CD138-stained bone marrow biopsy sections (CD138 sections) in 79 bone marrows from patients with multiple myeloma. There was a notable discrepancy in bone marrow plasma cell percentages using the different methods of observation. In particular, there was a relatively poor concordance of plasma cell percentage estimation between aspirate smears and CD138 sections. Estimates of plasma cell percentage using CD138 sections demonstrated the highest interobserver concordance. This observation was supported by computer-assisted image analysis. In addition, CD138 expression highlighted patterns of plasma cell infiltration indicative of neoplasia even in the absence of plasmacytosis. We conclude that examination of CD138 sections should be considered for routine use in the estimation of plasma cell load in the bone marrow.
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Affiliation(s)
- Samer Z Al-Quran
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Box 100275, Gainesville, FL 32610-0275, USA.
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23
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Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, Larson DR, Plevak MF, Jelinek DF, Fonseca R, Melton LJ, Rajkumar SV. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356:2582-90. [PMID: 17582068 DOI: 10.1056/nejmoa070389] [Citation(s) in RCA: 610] [Impact Index Per Article: 33.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and outcome of this disease are unclear. METHODS We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of the International Myeloma Working Group for the diagnosis of smoldering multiple myeloma between 1970 and 1995. Bone marrow aspirate and biopsy specimens were studied, and patients were followed throughout the course of disease. RESULTS During the 26-year period, 276 patients fulfilled the criteria for smoldering multiple myeloma. During 2131 cumulative person-years of follow-up, symptomatic multiple myeloma or amyloidosis developed in 163 persons (59%). The overall risk of progression was 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% per year for the last 10 years; the cumulative probability of progression was 73% at 15 years. At diagnosis, significant risk factors for progression included the serum level and type of monoclonal protein, the presence of urinary light chain, the extent and pattern of bone marrow involvement, and the reduction in uninvolved immunoglobulins. The proportion of plasma cells in the bone marrow and the serum monoclonal protein level were combined to create a risk-stratification model with three distinct prognostic groups. CONCLUSIONS The risk of progression from smoldering multiple myeloma to symptomatic disease is related to the proportion of bone marrow plasma cells and the serum monoclonal protein level at diagnosis.
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Affiliation(s)
- Robert A Kyle
- Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
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24
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Smock KJ, Perkins SL, Bahler DW. Quantitation of Plasma Cells in Bone Marrow Aspirates by Flow Cytometric Analysis Compared With Morphologic Assessment. Arch Pathol Lab Med 2007; 131:951-5. [PMID: 17550325 DOI: 10.5858/2007-131-951-qopcib] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2006] [Indexed: 11/06/2022]
Abstract
Abstract
Context.—Accurate quantitation of bone marrow plasma cells is an important component in the diagnosis and posttreatment assessment of plasma cell dyscrasias. Although flow cytometry is sometimes used for this purpose and can rapidly evaluate many cells, the accuracy of flow-based plasma cell quantitation compared with morphologic assessment (currently the gold standard) is uncertain as direct comparison studies have not been previously reported.
Objective.—To determine how percentages of plasma cells in diagnostic aspirate smears quantitated by morphologic assessment relate to percentages of plasma cells quantified by flow cytometry.
Design.—Thirty bone marrow cases with 10% or more plasma cells and leukemia/lymphoma flow cytometry immunophenotyping studies were identified from our hematopathology database. The Wright-stained aspirate smears, marrow biopsy sections, and flow cytometry histograms were reviewed.
Results.—Morphologically determined plasma cell percentages from the diagnostic aspirate smears were consistently higher than those determined by flow cytometry. Much of this difference appeared to be related to differences in sample quality. However, the cellular processing involved in performing flow cytometry also appeared to reduce plasma cell percentages in many cases.
Conclusions.—This study helps define the limitations of flow cytometry for quantitating plasma cell loads in marrow aspirate specimens that may significantly affect the diagnosis or assessment of treatment response.
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Affiliation(s)
- Kristi J Smock
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
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26
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Owotade F, Ugboko V, Ajike S, Salawu L, Amusa Y, Omole M. Head and neck manifestations of myeloma in Nigerians. Int J Oral Maxillofac Surg 2005; 34:761-5. [PMID: 15979285 DOI: 10.1016/j.ijom.2005.02.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2004] [Revised: 12/30/2004] [Accepted: 02/07/2005] [Indexed: 10/25/2022]
Abstract
A study on the clinicopathologic features of myeloma as it manifests in the head and neck region was conducted over a 15-year period. A total of six patients were seen and they constituted 20% of all myeloma cases. The mean age was 41.5 years, three were males and three were females. Clinical presentation was varied and included swelling, epistaxis and gingival bleeding. The duration of symptom ranged from 3 months to 6 years. Definitive diagnosis was extramedullary myelomatosis in three patients, multiple myeloma in two patients while one patient had solitary plasmacytoma of bone. Chemotherapy alone was the treatment modality in two patients, one had surgery combined with chemotherapy and one patient had only supportive therapy. Two patients did not receive treatment, as they requested for discharge against medical advice. One patient followed up for a period of 1 year recovered with residual neurological deficits. This study confirms the rarity of myeloma in the head and neck region and where it occurs; it is most likely multiple myeloma or extramedullary myelomatosis. In this part of the world, mortality rate is aggravated by late presentation and inability to afford chemotherapy.
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Affiliation(s)
- F Owotade
- Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, Nigeria.
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27
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Monill J, Pernas J, Montserrat E, Pérez C, Clavero J, Martinez-Noguera A, Guerrero R, Torrubia S. CT features of abdominal plasma cell neoplasms. Eur Radiol 2005; 15:1705-12. [PMID: 16034641 DOI: 10.1007/s00330-005-2642-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2004] [Revised: 12/09/2004] [Accepted: 12/20/2004] [Indexed: 11/29/2022]
Abstract
The aim of this study was to describe the CT features of abdominal plasma cell neoplasms. We reviewed CT imaging findings in 11 patients (seven men, four women; mean age 62 years) with plasma cell neoplasms and abdominal involvement. Helical CT of the entire abdomen and pelvis was performed following intravenous administration of contrast material. Images were analyzed in consensus by two radiologists. Diagnoses were made from biopsy, surgery and/or clinical follow-up findings. Multiple myeloma was found in seven patients and extramedullary plasmacytoma in four patients. All patients with multiple myeloma had multifocal disease with involvement of perirenal space (4/7), retroperitoneal and pelvic lymph nodes (3/7), peritoneum (3/7), liver (2/7), subcutaneous tissues (2/7) and kidney (1/7). In three of the four patients with extramedullary plasmacytoma, a single site was involved, namely stomach, vagina and retroperitoneum. In the fourth patient, a double site of abdominal involvement was observed with rectal and jejunal masses. Plasma cell neoplasm should be considered in the differential diagnosis of single or multiple enhancing masses in the abdomen or pelvis. Abdominal plasma cell neoplasms were most frequently seen as well-defined enhancing masses (10/11).
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Affiliation(s)
- J Monill
- Hospital de Sant Pau, Universitat Autonoma de Barcelona, Avda. Sant Antoni M. Claret 167, 08025, Barcelona, Spain.
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28
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Abstract
Multiple myeloma is a systemic malignant disease and is associated with a poor prognosis. It is characterized by neoplastic proliferation of plasma cells involved in the production and secretion of monoclonal immunoglobulins (M proteins). It is generally a disseminated disease involving many bones. Systemic symptoms include bone pain, pathologic fracture, renal failure, hypercalcemia, weight loss, anemia, thrombocytopenia, and neutropenia. This condition may occur as a solitary lesion (solitary plasmacytoma), which in some patients eventually progresses to plasma cell myeloma. Extramedullary plasmacytoma is defined as neoplastic proliferation of plasma cells in the soft tissue. It usually occurs in the upper respiratory tract, such as the nasal cavity or posterior oropharynx. The authors present a rare plasmacytoma case with maxilla involvement.
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Affiliation(s)
- Ragip Ozdemir
- Ankara Training and Research Hospital, 1. Plastic and Reconstructive Surgery Clinic, Ankara, Turkey.
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29
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Wilson CS. The plasma cell dyscrasias. Cancer Treat Res 2004; 121:113-44. [PMID: 15217208 DOI: 10.1007/1-4020-7920-6_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Affiliation(s)
- Carla S Wilson
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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30
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Abstract
The application of immunohistology to the spectrum of plasma cell disorders has yet to be incorporated widely into routine haematology practice. This technique enables the direct visualisation of specific surface and cytoplasmic antigens in the context of the individual cell and the surrounding anatomical neighbourhood. This review outlines the role of bone marrow immunohistology in the laboratory evaluation of patients with suspected and established plasma cell neoplasms and its emerging role in understanding myeloma biology for possible future therapeutic application.
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Affiliation(s)
- A Wei
- Department of Haematology, The Royal Melbourne Hospital, Parkville, 3050, Victoria, Australia
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31
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Luque R, García-Trujillo JA, Cámara C, Moreno A, Eiras P, Roy G, Villar LM, Lombardía M, Brieva JA, Bootello A, Roldán E. CD106 and activated-CD29 are expressed on myelomatous bone marrow plasma cells and their downregulation is associated with tumour progression. Br J Haematol 2002; 119:70-8. [PMID: 12358905 DOI: 10.1046/j.1365-2141.2002.03792.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Malignant plasma cells (PC) from multiple myeloma (MM) patients characteristically home to the bone marrow (BM). High numbers of tumour cells are found in the peripheral blood (PB) only at end-stage disease (secondary plasma cell leukaemia, PCL) in a minority of patients. Using flow cytometric and fluorescence in situ hybridization (FISH) analysis, a high percentage of tumoral BM PC from untreated patients was found to express CD106. In addition, these cells also expressed an activated form of CD29, as determined using the CD29 activation reporter monoclonal antibody HUTS-21. Adhesion-binding experiments showed that CD106+-activated CD29+ BM PC from these patients adhered to fibronectin (FN) in a CD29/CD49d-dependent manner. In contrast, marrow PC from progressive patients and BM or circulating malignant cells from secondary PCL patients expressed lower levels or were negative for CD106 and activated CD29, respectively, with a decreased or zero ability to adhere to FN. The expression of constitutive CD29 and CD49d, however, was similar during disease progression. We conclude that BM myelomatous cells co-express CD106 and a functionally active form of CD29. Moreover, our results suggest that the loss of expression and/or function of these antigens are associated with the progression of MM and may explain the exit of tumoral cells from the BM.
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Affiliation(s)
- Rosario Luque
- Servicio de Inmunología, Hospital Ramón y Cajal, Madrid, Spain
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32
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Mukunyadzi P, Bardales RH, Wilson CS, Sawyer JR, Stanley MW. Soft tissue masses in patients with multiple myeloma: a fine-needle aspiration study of 30 cases with flow cytometry and clinical correlation. Cancer 2001; 93:257-62. [PMID: 11507699 DOI: 10.1002/cncr.9039] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND To the authors' knowledge, the prognostic significance of plasma cell cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and biopsies to assess plasma cell differentiation, tumor burden, and response to treatment. Monitoring of ST lesions by fine-needle aspiration (FNA) is not performed routinely. The objective of the current study was to examine ST masses in MM patients using FNA and to classify and determine the prognostic significance of MM in these lesions based on cytologic features. METHODS FNAs of 30 ST masses from 27 patients with a history of MM were examined for disease involvement. In the patients with MM, the cytologic features were evaluated and the lesions were graded as low grade, intermediate grade, or high grade based on the classification of Bartl et al. for MM in BM specimens. Concurrent BM samples as well as cytogenetic and flow cytometric results also were reviewed. RESULTS Twenty-seven of the FNA specimens (90%) were positive for MM, and three specimens (10%) were negative (one case each of lipoma, keratinous cyst, and aspergillosis). Among the MM cases, 5 (18.5%) were low grade, 15 (55.6%) were intermediate grade, and 7 (25.9%) were high grade (blastic MM). Simultaneous BM involvement was present in 23.5% of low-grade MM (4 of 17 cases), 35.3% of intermediate-grade MM (6 of 17 cases), and 71% of high-grade MM (5 of 7 cases). Clinically, 10 of 24 patients (42%) died within 9 months (median, 2 months). Patients with high-grade myeloma (blastic MM) in ST masses appeared to have worse survival; 43% (3 of 7 patients) died by a median time of 2 months, compared with 12% of patients with low-grade and intermediate-grade MM (2 of 17 patients). CONCLUSIONS FNA of ST masses appears to improve the management of MM patients by providing diagnostic material, samples for ancillary studies, and prognostic information. ST MM can be classified reliably into grades of prognostic significance utilizing the classification of Bartl et al. Intermediate-grade MM was the most frequent subtype present in ST masses.
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Affiliation(s)
- P Mukunyadzi
- Department of Pathology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
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Kato N, Kimura K, Yasukawa K, Aikawa K. Metastatic cutaneous plasmacytoma: a case report associated with IgA lambda multiple myeloma and a review of the literature of metastatic cutaneous plasmacytomas associated with multiple myeloma and primary cutaneous plasmacytomas. J Dermatol 1999; 26:587-94. [PMID: 10535253 DOI: 10.1111/j.1346-8138.1999.tb02053.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We present the case of a 67-year-old Japanese woman with immunoglobulin A lambda (IgA lambda) multiple myeloma (MM). She had firm nodular cutaneous lesions on the trunk and scalp without adjacent bone involvement. The patient was diagnosed as having IgA lambda MM of stage IIIA with 52% plasmacytosis in the bone marrow six months before the appearance of the cutaneous lesions. The abnormal plasma cells showed moderate to marked dysplasia in both the bone marrow and skin lesions. The abnormal plasma cells in the bone marrow exhibited abnormal karyotypes: 41, XX, der (1) t (1p; 1q), -4, -10, -14, -16, -17, 17p+, that differed from the "unfavorable" karyotype reported previously. We reviewed the cases of metastatic cutaneous plasmacytoma in MM and cases of primary cutaneous plasmacytoma that have been reported in English or Japanese and identified the Ig class. Among the 83 cases of metastatic cutaneous plasmacytomas in MM, IgG, IgA, IgD, and Bence-Jones protein were found in 52%, 23%, 16%, and 6%, respectively. A disproportionately high frequency of IgD lambda MM was found to have spread to the skin, compared with the frequency of IgD MM itself, which was present in only around 2% of the MM cases. Among the 18 primary cutaneous plasmacytomas, IgG, IgA, and Bence-Jones protein were found in 56%, 11%, and 17%, respectively, but no IgD was found.
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Affiliation(s)
- N Kato
- Department of Dermatology and Clinical Research Institute, National Sapporo Hospital, Japan
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34
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Campanacci M. Multiple Myeloma. BONE AND SOFT TISSUE TUMORS 1999:581-598. [DOI: 10.1007/978-3-7091-3846-5_35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Larson RS, Sukpanichnant S, Greer JP, Cousar JB, Collins RD. The spectrum of multiple myeloma: diagnostic and biological implications. Hum Pathol 1997; 28:1336-47. [PMID: 9416688 DOI: 10.1016/s0046-8177(97)90221-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Myeloma is a common and well-studied hematopoietic neoplasm with an impressive spectrum of clinical, laboratory, and histological findings. To enhance our understanding of the diversity of myeloma, including its earliest forms, the clinical and pathological findings in 145 cases of myeloma were documented and analyzed. Our analysis indicated that myeloma has at least two distinct subtypes: one presenting with bone lesions and a nodular growth pattern and the other presenting with anemia and an infiltrative growth pattern. The relationship of these two forms to plasma cell biology is not clear, although both types appear to arise in the marrow. The criteria used in this study identified 85% of cases overall, with a range of 70% to 100%, depending on clinical presentation. Immunoperoxidase studies are required to establish the diagnosis in patients with early marrow involvement. Myeloma in younger patients appears to be clinically and pathologically similar to myeloma in older patients. Factors such as dysplasia, immunoglobulin type, or leukemic phase were evenly distributed among clinical presentations and did not apparently identify clinicopathological subtypes of myeloma.
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Affiliation(s)
- R S Larson
- Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
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36
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37
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Affiliation(s)
- R Bataille
- Laboratory of Hematology, Institute of Biology, Nantes, France
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38
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Pich A, Chiusa L, Marmont F, Navone R. Risk groups of myeloma patients by histologic pattern and proliferative activity. Am J Surg Pathol 1997; 21:339-47. [PMID: 9060605 DOI: 10.1097/00000478-199703000-00011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
We investigated the histologic pattern and the cell proliferative activity of myeloma cells by the analysis of the nucleolar organizer regions (AgNORs) in bone marrow biopsy specimens from 150 multiple myelomas at diagnosis. The objective was an attempt to define risk groups of myeloma patients. On univariate analysis, the percentage of bone marrow plasma cells (BMPC%), the pattern of infiltration, the degree of plasma cell (PC) atypia, the marrow fibrosis, and the number of AgNOR/PC were correlated with survival time. On multivariate analysis, only AgNOR counts and pattern of infiltration retained independent prognostic significance. At 4-year followup, all patients with BMPC% < or = 20, interstitial pattern of invasion, and well-differentiated (G1) PC plus AgNOR/cell < or = 3.32 were alive, while no patient with BMPC% >50, diffuse pattern of infiltration, and poorly differentiated (G3) PC plus AgNOR/cell >5.15 survived (p < 0.0001). In conclusion, the histologic pattern and proliferative activity of myeloma cells, evaluated by AgNOR counts, are reliable predictors of survival in myeloma. Both parameters can be easily assessed in the same biopsy specimen, are reproducible, and permit identification of a group of patients with favourable outcome at 4-year followup. Thus, bone marrow biopsy should always be included in the diagnostic procedures for myeloma patients.
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Affiliation(s)
- A Pich
- Department of Biomedical Sciences and Human Oncology, University of Turin, Italy
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39
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Pisano JJ, Coupland R, Chen SY, Miller AS. Plasmacytoma of the oral cavity and jaws: a clinicopathologic study of 13 cases. ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY, ORAL RADIOLOGY, AND ENDODONTICS 1997; 83:265-71. [PMID: 9117760 DOI: 10.1016/s1079-2104(97)90015-9] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Plasmacytoma of the jaw bones and oral cavity, as in other anatomic sites, comprises three distinct entities: multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma. This article is a retrospective study of 13 cases; 9 occurred in the mandible and 4 in the maxilla. The most common radiographic finding was a radiolucency that many times was superimposed on the roots or apices of nearby teeth. The most common symptom was localized pain, and the most frequent clinical sign was a raised red lesion on the alveolar ridge. The disease affects older persons, and the posterior mandible is the most frequently reported location. The degree of dysplasia of tumor cells was evaluated as there is a reported correlation with survival rates.
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Affiliation(s)
- J J Pisano
- Conemaugh Valley Hospital, Johnstown, Pa., USA
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40
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Grignani G, Gobbi PG, Formisano R, Pieresca C, Ucci G, Brugnatelli S, Riccardi A, Ascari E. A prognostic index for multiple myeloma. Br J Cancer 1996; 73:1101-7. [PMID: 8624271 PMCID: PMC2074407 DOI: 10.1038/bjc.1996.212] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient.
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Affiliation(s)
- G Grignani
- Università di Pavia, IRCCS Policlinico S. Matteo, Italy
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41
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Pellegrini W, Facchetti F, Marocolo D, Salvi L, Capucci A, Tironi A, Rossi G. Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections. Histopathology 1995; 27:397-405. [PMID: 8575729 DOI: 10.1111/j.1365-2559.1995.tb00302.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.
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Affiliation(s)
- W Pellegrini
- Department of Pathology, University of Brescia, Italy
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Sailer M, Vykoupil KF, Peest D, Coldewey R, Deicher H, Georgii A. Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients. Eur J Haematol 1995; 54:137-46. [PMID: 7720832 DOI: 10.1111/j.1600-0609.1995.tb00204.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.
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Affiliation(s)
- M Sailer
- Pathologisches Institut der Medizinischen Hochschule Hannover, Germany
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