Morfología e inmunofenotipo de las células plasmáticas en el mieloma múltiple

  • Nataly J. Rincón-Vásquez Hospital General de Medellín
  • Patricia E. Jaramillo-Arbeláez Universidad de Antioquia
  • Carlos M. Llanos-Albornoz Desarrollo e Innovación INCA
Palabras clave: mieloma múltiple, inmunofenotipo, morfología, células plasmáticas, citometría de flujo, médula ósea.

Resumen

El avance en el conocimiento de la fisiopatología del mieloma múltiple ha permitido el acercamiento a la comprensión de su heterogeneidad, en términos del comportamiento clínico, citomorfológico, fenotípico, bioquímico, genético y molecular, lo que contribuye al desarrollo de nuevos tratamientos y al establecimiento de modelos que apuntan hacia una cronicidad de la enfermedad. Los cambios morfológicos de la célula plasmática en el mieloma múltiple indican, principalmente, alteraciones a nivel del núcleo, que orientan a la diferenciación de las células reactivas de aquellas clonales; además, que su inmadurez es de mal pronóstico. Igualmente, la expresión de ciertos marcadores monoclonales, y la ausencia de otros, detectados mediante citometría de flujo, clasifican inmunofenotípicamente a las células neoplásicas del mieloma múltiple, lo que permite considerar esta herramienta como una de las mejores en el diagnóstico y en el manejo de la enfermedad mínima residual. En esta revisión se pretende enfatizar en la importancia de identificar los cambios morfológicos que se dan en las células plasmáticas y su relación con las características inmunofenotípicas en las neoplasias, que tienen una asociación pronóstica importante en el desarrollo del mieloma múltiple.

Descargas

La descarga de datos todavía no está disponible.

Biografía del autor/a

Nataly J. Rincón-Vásquez, Hospital General de Medellín

Microbióloga y Bioanalista, estudiante de maestría en Microbiología y Bioanálisis, con énfasis en Hematología, Universidad de Antioquia. Bacterióloga, área de Hematología, Laboratorio Clínico, Hospital General de Medellín. Medellín, Colombia.

Patricia E. Jaramillo-Arbeláez, Universidad de Antioquia

Bacterióloga, especialista en Hematología, MSc en Microbiología con énfasis en Hematología y en Bioética. Docente de Hematología, Universidad de Antioquia. Medellín, Colombia.

Carlos M. Llanos-Albornoz , Desarrollo e Innovación INCA

Tecnólogo Médico. Director del Centro de Investigación, Desarrollo e Innovación INCA. Lima, Perú.

Referencias bibliográficas

Gorczyca W. Plasma cell neoplasms. Atlas of Differential Diagnosis in Neoplastic Hematopathology (ed 3a). Boca Ratón, Florida, Estados Unidos: CRC Press; 2014: 359-382.

https://doi.org/10.1201/b16685-16

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (ed 4a). Lyon, Francia: International Agency for Research on Cancer; 2008.

San Miguel JF, Gutierrez NC, Mateo G, Orfao A. Conventional diagnostics in multiple myeloma. Eur J Cancer 2006; 42: 1510-1519.

https://doi.org/10.1016/j.ejca.2005.11.039

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375-2390.

https://doi.org/10.1182/blood-2016-01-643569

Ramasamy K, Lonial S. Fast Facts: Multiple Myeloma and Plasma Cell Dyscrasias. Oxford, Reino Unido: Health Press Limited; 2015.

Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol 2016; 91: 719-734.

https://doi.org/10.1002/ajh.24402

Erikci AA, Ozturk A, Tekgunduz E, Sayan O. Acute myeloid leukemia complicating multiple myeloma: a case successfully treated with etoposide, thioguanine, and cytarabine. Clin Lymphoma Myeloma 2009; 9: E14-15.

https://doi.org/10.3816/CLM.2009.n.066

Luca DC, Almanaseer IY. Simultaneous presentation of multiple myeloma and acute monocytic leukemia. Arch Pathol Lab Med 2003; 127: 1506-1508.

Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR, et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011; 118: 4086-4092.

https://doi.org/10.1182/blood-2011-05-355743

Dincol G, Nalcaci M, Dogan O, Aktan M, Kucukkaya R, Agan M, et al. Coexistence of chronic neutrophilic leukemia with multiple myeloma. Leuk Lymphoma 2002; 43: 649-651.

https://doi.org/10.1080/10428190290012218

Cid Ruzafa J, Merinopoulou E, Baggaley RF, Leighton P, Werther W, Felici D, et al. Patient population with multiple myeloma and transitions across different lines of therapy in the USA: an epidemiologic model. Pharmacoepidemiol Drug Saf 2016; 25: 871-879.

https://doi.org/10.1002/pds.3927

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003; 53: 5-26.

https://doi.org/10.3322/canjclin.53.1.5

Blade J, Kyle RA, Greipp PR. Multiple myeloma in patients younger than 30 years. Report of 10 cases and review of the literature. Arch Intern Med 1996; 156: 1463-1468.

https://doi.org/10.1001/archinte.1996.00440120125014

El Mangad F EZ, El Bouchti I. Multiple Myeloma in Unusually Young Patient: A Case Report. Int J Clin Med 2014; 05: 890-893.

https://doi.org/10.4236/ijcm.2014.515119

Ramón Rodríguez LG, Agramonte Llanes O, Hernández Padrón C, Espinosa Martínez E, Losada Buchillón R, Ávila Cabrera O, et al. Mieloma múltiple y embarazo: Primer reporte de caso en Cuba. Rev Cubana Hematol Inmunol Hemoter 2010; 26: 70-75.

Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21-33.

https://doi.org/10.4065/78.1.21

Rosenberg PS, Barker KA, Anderson WF. Future distribution of multiple myeloma in the United States by sex, age, and race/ethnicity. Blood 2015; 125: 410-412.

https://doi.org/10.1182/blood-2014-10-609461

Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116: 3724-3734.

https://doi.org/10.1182/blood-2010-05-282632

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66: 7-30.

https://doi.org/10.3322/caac.21332

Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin 2016.

https://doi.org/10.3322/caac.21357

Alvarado M, Álvarez JL, Anaya I, et al. Primer Consenso Nacional de Mieloma Múltiple por Hematólogos del ISSSTE. Rev Hematol México 2015; 16: 306-332.

World Health Organization, International Agency for Research on Cancer. Globocan 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012 - Population Fact Sheets: Colombia. 2012. Disponible: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.

World Health Organization, International Agency for Research on Cancer. Globocan 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012 - Online Analysis: Prediction. 2012. Disponible: http://globocan.iarc.fr/Pages/burden_sel.aspx.

Dispenzieri A. Myeloma: management of the newly diagnosed high-risk patient. Hematology Am Soc Hematol Educ Program 2016; 2016: 485-494.

https://doi.org/10.1182/asheducation-2016.1.485

Heusschen R, Muller J, Duray E, Withofs N, Bolomsky A, Baron F, et al. Molecular mechanisms, current management and next generation therapy in myeloma bone disease. Leuk Lymphoma 2018; 59: 14-28.

https://doi.org/10.1080/10428194.2017.1323272

Roodman GD. Myeloma bone disease: pathogenesis and treatment. Oncology (Williston Park) 2005; 19: 983-984, 986.

Shah V, Sherborne AL, Walker BA, Johnson DC, Boyle EM, Ellis S, et al. Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients. Leukemia 2017; 32: 102.

https://doi.org/10.1038/leu.2017.179

Fonseca R, Abouzaid S, Bonafede M, Cai Q, Parikh K, Cosler L, et al. Trends in overall survival and costs of multiple myeloma, 2000-2014. Leukemia 2016; 31: 1915.

https://doi.org/10.1038/leu.2016.380

Moeremans K, Annemans L. An update: health economics of managing multiple myeloma. Eur J Cancer 2006; 42: 1684-1691.

https://doi.org/10.1016/j.ejca.2005.11.036

Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, et al. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 2004; 21: 81-93.

https://doi.org/10.1016/j.immuni.2004.06.010

Zandi S, Mansson R, Tsapogas P, Zetterblad J, Bryder D, Sigvardsson M. EBF1 is essential for B-lineage priming and establishment of a transcription factor network in common lymphoid progenitors. J Immunol 2008; 181: 3364-3372.

https://doi.org/10.4049/jimmunol.181.5.3364

Shapiro-Shelef M, Calame K. Regulation of plasma-cell development. Nat Rev Immunol 2005; 5: 230-242.

https://doi.org/10.1038/nri1572

Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader B. Wintrobe's Clinical Hematology (ed 11a). Maryland, Estados Unidos: Lippincott Williams & Wilkins; 2004.

Goldman L, Schafer AI. Goldman-Cecil. Tratado de Medicina Interna. Vol. 1 (ed 25a). España: Elsevier Inc.; 2017.

Porwit A, McCullough J, Erber W. Blood and bone marrow pathology: Churchill Livingstone Elsevier; 2011.

Miale JB. Hematología : Medicina de Laboratorio (ed 6a). España: Reverté; 1985.

College of American Pathologists. 2017 Hematology, Clinical Microscopy, and Body Fluids Glossary. 2017. Disponible: http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/hematology-glossary.pdf.

Nikesitch N, Ling SC. Molecular mechanisms in multiple myeloma drug resistance. J Clin Pathol 2016; 69: 97-101.

https://doi.org/10.1136/jclinpath-2015-203414

Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer 2012; 12: 335-348.

https://doi.org/10.1038/nrc3257

Yun Z, Zhichao J, Hao Y, Ou J, Ran Y, Wen D, et al. Targeting autophagy in multiple myeloma. Leuk Res 2017; 59: 97-104.

https://doi.org/10.1016/j.leukres.2017.06.002

Ribourtout B, Zandecki M. Plasma cell morphology in multiple myeloma and related disorders. Morphologie 2015; 99: 38-62.

https://doi.org/10.1016/j.morpho.2015.02.001

Ho WK, Zantomio D. Auer rod-like inclusions in plasma cells in multiple myeloma. J Clin Pathol 2014; 67: 547-548.

https://doi.org/10.1136/jclinpath-2014-202195

Tejwani N, Tyagi S, Dass J. Multiple Auer Rod Like Inclusions in Multiple Myeloma. Indian J Hematol Blood Transfus 2017; 33: 121-122.

https://doi.org/10.1007/s12288-016-0744-1

Hutter G, Nowak D, Blau IW, Thiel E. Auer rod-like intracytoplasmic inclusions in multiple myeloma. A case report and review of the literature. Int J Lab Hematol 2009; 31: 236-240.

https://doi.org/10.1111/j.1751-553X.2007.01023.x

Zhu L, An L, Zhang XY, Ren XR, Song JW. Peroxidase-positive Auer bodies in plasma cells in multiple myeloma: a case report. Int J Clin Exp Pathol 2015; 8: 15301-15306.

Eyre TA, Littlewood TJ, Bain BJ. Dutcher bodies: cytoplasmic inclusions within the nucleus. Br J Haematol 2014; 166: 946-947.

https://doi.org/10.1111/bjh.12911

Ortíz-Hidalgo C. De las células plasmáticas al mieloma múltiple. Una breve perspectiva histórica. Patol Rev Latinoam 2011; 49: 120-131.

Pantanowitz L, Tranovich V, Ballesteros E. Flaming plasma cells. Arch Pathol Lab Med 2001; 125: 1394-1395.

Seili-Bekafigo I, Valkovic T, Babarovic E, Duletic-Nacinovic A, Jonjic N. Myeloma cell morphology and morphometry in correlation with clinical stages and survival. Diagn Cytopathol 2013; 41: 947-954.

https://doi.org/10.1002/dc.22986

You E, Cho SY, Yang JJ, Lee HJ, Lee WI, Yoon HJ, et al. Plasma cell neoplasms showing multilobulated nuclei. Acta Haematol 2013; 130: 98-100.

https://doi.org/10.1159/000347026

Ghevaert C, Fournier M, Bernardi F, Genevieve F, Pouyol F, Zandecki M. Non-secretory multiple myeloma with multinucleated giant plasma cells. Leuk Lymphoma 1997; 27: 185-189.

https://doi.org/10.3109/10428199709068286

Subramanian R, Basu D, Dutta TK. Prognostic significance of bone marrow histology in multiple myeloma. Indian J Cancer 2009; 46: 40-45.

https://doi.org/10.4103/0019-509X.48594

Bartl R, Frisch B, Fateh-Moghadam A, Kettner G, Jaeger K, Sommerfeld W. Histologic classification and staging of multiple myeloma. A retrospective and prospective study of 674 cases. Am J Clin Pathol 1987; 87: 342-355.

https://doi.org/10.1093/ajcp/87.3.342

Paule B, Quillard J, Bisson M, Kahn MF, Massias P. Prognostic significance of plasma cell morphology in multiple myeloma. Nouv Rev Fr Hematol 1988; 30: 209-212.

Bartl R, Frisch B, Burkhardt R, Fateh-Moghadam A, Mahl G, Gierster P, et al. Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging. Br J Haematol 1982; 51: 361-375.

https://doi.org/10.1111/j.1365-2141.1982.tb02791.x

Greipp PR, Raymond NM, Kyle RA, O'Fallon WM. Multiple myeloma: significance of plasmablastic subtype in morphological classification. Blood 1985; 65: 305-310.

https://doi.org/10.1182/blood.V65.2.305.305

De los Reyes N, Monserrat J, Martínez MV, Álvarez MR, Minguela A. Utilidad de la Citometría de Flujo en el diagnóstico y pronóstico del Mieloma Múltiple. Cuadernos de Hematología 2010: 1-12.

Flores-Montero J, de Tute R, Paiva B, Perez JJ, Bottcher S, Wind H, et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom 2016; 90: 61-72.

https://doi.org/10.1002/cyto.b.21265

Karthick R M, Kovarova L, Hajek R. Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol 2010; 149: 334-351.

https://doi.org/10.1111/j.1365-2141.2010.08121.x

Zandecki M, Facon T, Bernardi F, Izydorczyk V, Dupond L, Francois M, et al. CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance. J Clin Pathol 1995; 48: 548-552.

https://doi.org/10.1136/jcp.48.6.548

Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 2004; 121: 482-488.

https://doi.org/10.1309/74R4TB90BUWH27JX

An G, Xu Y, Shi L, Zou D, Deng S, Sui W, et al. t(11;14) multiple myeloma: a subtype associated with distinct immunological features, immunophenotypic characteristics but divergent outcome. Leuk Res 2013; 37: 1251-1257.

https://doi.org/10.1016/j.leukres.2013.06.020

Olteanu H, Wang HY, Chen W, McKenna RW, Karandikar NJ. Immunophenotypic studies of monoclonal gammopathy of undetermined significance. BMC Clin Pathol 2008; 8: 13.

https://doi.org/10.1186/1472-6890-8-13

Nair JR, Carlson LM, Koorella C, Rozanski CH, Byrne GE, Bergsagel PL, et al. CD28 expressed on malignant plasma cells induces a prosurvival and immunosuppressive microenvironment. J Immunol 2011; 187: 1243-1253.

https://doi.org/10.4049/jimmunol.1100016

Robillard N, Wuillème S, Moreau P, Béné MC. Immunophenotype of Normal and Myelomatous Plasma-Cell Subsets. Front Immunol 2014; 5: 137.

https://doi.org/10.3389/fimmu.2014.00137

Shim H, Ha JH, Lee H, Sohn JY, Kim HJ, Eom HS, et al. Expression of myeloid antigen in neoplastic plasma cells is related to adverse prognosis in patients with multiple myeloma. Biomed Res Int 2014; 2014: 893243.

https://doi.org/10.1155/2014/893243

Rawstron AC, Orfao A, Beksac M, Bezdickova L, Brooimans RA, Bumbea H, et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008; 93: 431-438.

https://doi.org/10.3324/haematol.11080

Davids MS, Murali MR, Kuter DJ. Serum free light chain analysis. Am J Hematol 2010; 85: 787-790.

https://doi.org/10.1002/ajh.21815

The International Myeloma Working Group, Kyle RA, Child J, Anderson K, Barlogie B, Bataille R, et al. Criteria for the classification monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121: 749-757.

https://doi.org/10.1046/j.1365-2141.2003.04355.x

Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842-854.

https://doi.org/10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U

Conté L G, Figueroa M G, Lois V V, Cabrera C ME, León R A, García L H, et al. Valor pronóstico del nuevo sistema de etapificación internacional en mieloma múltiple: Comparación con el sistema de Durie-Salmon. Rev Méd Chile 2008; 136: 7-12.

https://doi.org/10.4067/S0034-98872008000100001

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15: e538-548.

https://doi.org/10.1016/S1470-2045(14)70442-5

Sociedad Argentina de Hematología. Guías de diagnóstico y tratamiento Clin Chiest Med 2015; 20: 335-337.

Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 2016; 127: 2955-2962.

https://doi.org/10.1182/blood-2016-01-631200

Kaufman GP, Gertz MA, Dispenzieri A, Lacy MQ, Buadi FK, Dingli D, et al. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma. Leukemia 2016; 30: 633-639.

https://doi.org/10.1038/leu.2015.287

Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2017; 28: iv52-iv61.

https://doi.org/10.1093/annonc/mdx096

Cogbill CH, Spears MD, Vantuinen P, Harrington AM, Olteanu H, Kroft SH. Morphologic and cytogenetic variables affect the flow cytometric recovery of plasma cell myeloma cells in bone marrow aspirates. Int J Lab Hematol 2015; 37: 797-808.

https://doi.org/10.1111/ijlh.12411

Kyle RA, Rajkumar SV. Multiple myeloma. Blood 2008; 111: 2962-2972.

https://doi.org/10.1182/blood-2007-10-078022

Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book 2016; 35:

https://doi.org/10.14694/EDBK_159009

Cómo citar
1.
Rincón-Vásquez NJ, Jaramillo-Arbeláez PE, Llanos-Albornoz CM. Morfología e inmunofenotipo de las células plasmáticas en el mieloma múltiple. Med. Lab. [Internet]. 1 de septiembre de 2017 [citado 22 de abril de 2021];23(9-10):443-58. Disponible en: https://medicinaylaboratorio.com/index.php/myl/article/view/22
Publicado
2017-09-01
Sección
Hematología
Crossref Cited-by logo