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Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia
Cancer Genetics and Cytogenetics 133 (2002) 172–173
Short communication
Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia Ada I. Riveraa, Marilyn M. Lib, German Beltranc, John R. Krausea,* a
Department of Pathology and Laboratory Medicine, Tulane Health Sciences Center, New Orleans, LA 70131, USA b Hayward Genetics Center, Tulane Health Sciences Center, New Orleans, LA 70131, USA c Department of Medicine, Tulane Health Sciences Center, New Orleans, LA 70131, USA Received 27 June 2001; accepted 16 August 2001
Abstract
We report a case of Waldenström macroglobulinemia with trisomy 4 as the sole cytogenetic abnormality. Trisomy 4 has been reported previously in Waldenström macroglobulinemia, but only in conjunction with multiple chromosomal aberrations. Trisomy 4 has been reported in other hematologic malignancies including acute myeloid and lymphoid leukemias. © 2002 Elsevier Science Inc. All rights reserved.
1. Introduction Waldenström macroglobulinemia is a disease characterized by a clonal malignant lymphoplasmacytic proliferation and production of monoclonal IgM [1]. Clinically, Waldenström macroglobulinemia is characterized by hypergammaglobulinemia, hyperviscosity manifestations, and hemorrhage. The morbidity of this disorder frequently is mild and may be compatible with prolonged survival. As the disease progresses, hepatomegaly, splenomegaly, and adenopathy become prominent features [2]. Morphologically the tissue infiltrate consists of a mixture of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. This lesion corresponds to the lymphoplasmacytic lymphoma in the proposed World Health Organization classification of lymphoid neoplasms [3]. Abnormal and complex karyotypes are common in Waldenström macroglobulinemia and most frequently involve a gain or loss of chromosomes 10, 12, or 20 [4]. Also frequently observed are rearrangements characteristic of other B-cell lymphoproliferative disorders including t(8;14) (commonly observed in Burkitt lymphoma), t(14;18) (follicular lymphomas), and trisomy 12 (chronic lymphocytic leukemia/small lymphocytic lymphoma) [5].
able except for pallor. Peripheral blood counts showed hemoglobin 6.9 g/dl, platelets 134109 L, and leukocytes 3.1109 L with 42% neutrophils, 33% lymphocytes, 19% monocytes, 5% basophils, and 1% eosinophils. The bone marrow biopsy was hypercellular with an infiltrate of lymphocytes, plasmacytoid lymphocytes, mast cells, and plasma cells (Fig. 1). Focal residual hematopoiesis with trilinear maturation was present. Flow cytometry of the bone marrow showed a B cell lymphocytic population positive for CD19, CD20, and CD22 with kappa light chain restriction. Bone scan was negative for lytic lesions or metastatic disease. Serum protein electrophoresis showed a paraproteinemia in the gamma region of 2.7 g/dl (normal 0.4–1.3 g/dl). Immunofixation showed an IgM kappa of 1,060 mg/dl (normal 60– 263 mg/dl). Bone marrow samples were used for three different cultures without mitogens. Cell cultures were harvested for 24, 48, and 72 hours. Metaphase chromosomes were studied with GTW-banding. The International System for Human Cytogenetic Nomenclature was used to describe the karyotype. Cytogenetic analysis showed two cell lines in the specimen. Seventy percent (14/20) of the cells studied contained an extra chromosome 4 (trisomy 4; Fig. 2). The remaining four cells were normal (46,XY).
2. Case report A 77-year-old male presented with a 2-year history of fatigue and weight loss. Clinical examination was unremark* Corresponding author. Tel: 504-588-5210; fax: 504-587-7389. E-mail address: [email protected] (J.R. Krause).
3. Discussion No definite chromosomal abnormality is specifically associated with Waldenström macroglobulinemia. Several chromosomal abnormalities have been reported, but there is no
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 7 7 - 5
A.I. Rivera et al. / Cancer Genetics and Cytogenetics 133 (2002) 172–173
Fig. 1. Bone marrow biopsy. Infiltrate of lymphocytes, plasmacytoid lymphocytes, and plasma cells (Waldenström macroglobulinemia). (H&E 400).
specific genetic marker for this disease. Trisomy 4 has been previously reported in conjunction with multiple chromosomal aberrations but not as the sole abnormality [4,6]. The structural change, der(4)t(4;?)(q32), and 5q also have been reported [7]. Trisomy 4 may occur as a single karyotypic abnormality in primary and secondary acute myeloid leukemia, most frequently in French–American–British M4 or M2 subtypes [8]. Trisomy 4 has also been reported in acute lymphocytic leukemia in children and is associated with a favorable event-free survival [9]. To our knowledge, this is the first case of Waldenström macroglobulinemia exhibiting trisomy 4 as the sole chromosomal abnormality.
Fig. 2. Chromosomal pattern of bone marrow sample showing three copies of chromosome 4 (trisomy 4).
[4]
[5]
[6] [7]
References [1] Handin R. Blood, principles & practice of hematology. Philadelphia: J.B. Lippincott Co., 1994. [2] Lee GR, Bithell T, Foerster J, Athens JW, Lukens JN. Wintrobe’s clinical hematology. Philadelphia: Lea & Febiger, 1993. [3] Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister A, Bloomfield CD. The World Health Organization
173
[8]
[9]
classification of hematologic malignancies. Report of the Clinical Advisory Committee, Airie House, Virginia November 1997. Mod Pathol 1997;13:193–207. Palka G, Spadano A, Geraci L, Fioritoni G, Dragani A, Calabrese G, Guanciali Franchi P, Stuppia L. Chromosome changes in 19 patients with Waldenström’s macroglobulinemia. Cancer Genet Cytogenet 1987;29:261–9. Nishida K, Taniwaki M, Misawa S, Abe T. Nonrandom rearrangement of chromosome 14 at band q32.33 in human lymphoid malignancies with mature B-cell phenotype. Cancer Res 1989;49:1275. Contrafatto G. Marker chromosome of macroglobulinemia identified by G banding. Cytogenet Cell Genet 1977;18:371–3. Carbone P, Caradonna F, Granata G, Marceno R, Cavallaro AM, Barbata G. Chromosomal abnormalities in Waldenström’s macroglobulinemia. Cancer Genet Cytogenet 1992;61:147–51. Weber E, Nowotny H, Hass OA, Kasparu H, Grois N, Lutz D. Trisomy 4: a specific karotype anomaly in primary and secondary acute myeloid leukemia. Leukemia 1990;4:219–21. Martin PL, Look AT, Schnell S, Harris MB, Pullen J, Shuster JJ, Carrol AJ, Pettenati MJ, Rao PN. Comparison of fluorescence in situ hybridization, cytogenetic analysis and DNA index to detect chromosome 4 and 10 aneuploidy in pediatric acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Pediatric Hematol Oncol 1996;18:113–21.
Short communication
Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia Ada I. Riveraa, Marilyn M. Lib, German Beltranc, John R. Krausea,* a
Department of Pathology and Laboratory Medicine, Tulane Health Sciences Center, New Orleans, LA 70131, USA b Hayward Genetics Center, Tulane Health Sciences Center, New Orleans, LA 70131, USA c Department of Medicine, Tulane Health Sciences Center, New Orleans, LA 70131, USA Received 27 June 2001; accepted 16 August 2001
Abstract
We report a case of Waldenström macroglobulinemia with trisomy 4 as the sole cytogenetic abnormality. Trisomy 4 has been reported previously in Waldenström macroglobulinemia, but only in conjunction with multiple chromosomal aberrations. Trisomy 4 has been reported in other hematologic malignancies including acute myeloid and lymphoid leukemias. © 2002 Elsevier Science Inc. All rights reserved.
1. Introduction Waldenström macroglobulinemia is a disease characterized by a clonal malignant lymphoplasmacytic proliferation and production of monoclonal IgM [1]. Clinically, Waldenström macroglobulinemia is characterized by hypergammaglobulinemia, hyperviscosity manifestations, and hemorrhage. The morbidity of this disorder frequently is mild and may be compatible with prolonged survival. As the disease progresses, hepatomegaly, splenomegaly, and adenopathy become prominent features [2]. Morphologically the tissue infiltrate consists of a mixture of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. This lesion corresponds to the lymphoplasmacytic lymphoma in the proposed World Health Organization classification of lymphoid neoplasms [3]. Abnormal and complex karyotypes are common in Waldenström macroglobulinemia and most frequently involve a gain or loss of chromosomes 10, 12, or 20 [4]. Also frequently observed are rearrangements characteristic of other B-cell lymphoproliferative disorders including t(8;14) (commonly observed in Burkitt lymphoma), t(14;18) (follicular lymphomas), and trisomy 12 (chronic lymphocytic leukemia/small lymphocytic lymphoma) [5].
able except for pallor. Peripheral blood counts showed hemoglobin 6.9 g/dl, platelets 134109 L, and leukocytes 3.1109 L with 42% neutrophils, 33% lymphocytes, 19% monocytes, 5% basophils, and 1% eosinophils. The bone marrow biopsy was hypercellular with an infiltrate of lymphocytes, plasmacytoid lymphocytes, mast cells, and plasma cells (Fig. 1). Focal residual hematopoiesis with trilinear maturation was present. Flow cytometry of the bone marrow showed a B cell lymphocytic population positive for CD19, CD20, and CD22 with kappa light chain restriction. Bone scan was negative for lytic lesions or metastatic disease. Serum protein electrophoresis showed a paraproteinemia in the gamma region of 2.7 g/dl (normal 0.4–1.3 g/dl). Immunofixation showed an IgM kappa of 1,060 mg/dl (normal 60– 263 mg/dl). Bone marrow samples were used for three different cultures without mitogens. Cell cultures were harvested for 24, 48, and 72 hours. Metaphase chromosomes were studied with GTW-banding. The International System for Human Cytogenetic Nomenclature was used to describe the karyotype. Cytogenetic analysis showed two cell lines in the specimen. Seventy percent (14/20) of the cells studied contained an extra chromosome 4 (trisomy 4; Fig. 2). The remaining four cells were normal (46,XY).
2. Case report A 77-year-old male presented with a 2-year history of fatigue and weight loss. Clinical examination was unremark* Corresponding author. Tel: 504-588-5210; fax: 504-587-7389. E-mail address: [email protected] (J.R. Krause).
3. Discussion No definite chromosomal abnormality is specifically associated with Waldenström macroglobulinemia. Several chromosomal abnormalities have been reported, but there is no
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 7 7 - 5
A.I. Rivera et al. / Cancer Genetics and Cytogenetics 133 (2002) 172–173
Fig. 1. Bone marrow biopsy. Infiltrate of lymphocytes, plasmacytoid lymphocytes, and plasma cells (Waldenström macroglobulinemia). (H&E 400).
specific genetic marker for this disease. Trisomy 4 has been previously reported in conjunction with multiple chromosomal aberrations but not as the sole abnormality [4,6]. The structural change, der(4)t(4;?)(q32), and 5q also have been reported [7]. Trisomy 4 may occur as a single karyotypic abnormality in primary and secondary acute myeloid leukemia, most frequently in French–American–British M4 or M2 subtypes [8]. Trisomy 4 has also been reported in acute lymphocytic leukemia in children and is associated with a favorable event-free survival [9]. To our knowledge, this is the first case of Waldenström macroglobulinemia exhibiting trisomy 4 as the sole chromosomal abnormality.
Fig. 2. Chromosomal pattern of bone marrow sample showing three copies of chromosome 4 (trisomy 4).
[4]
[5]
[6] [7]
References [1] Handin R. Blood, principles & practice of hematology. Philadelphia: J.B. Lippincott Co., 1994. [2] Lee GR, Bithell T, Foerster J, Athens JW, Lukens JN. Wintrobe’s clinical hematology. Philadelphia: Lea & Febiger, 1993. [3] Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister A, Bloomfield CD. The World Health Organization
173
[8]
[9]
classification of hematologic malignancies. Report of the Clinical Advisory Committee, Airie House, Virginia November 1997. Mod Pathol 1997;13:193–207. Palka G, Spadano A, Geraci L, Fioritoni G, Dragani A, Calabrese G, Guanciali Franchi P, Stuppia L. Chromosome changes in 19 patients with Waldenström’s macroglobulinemia. Cancer Genet Cytogenet 1987;29:261–9. Nishida K, Taniwaki M, Misawa S, Abe T. Nonrandom rearrangement of chromosome 14 at band q32.33 in human lymphoid malignancies with mature B-cell phenotype. Cancer Res 1989;49:1275. Contrafatto G. Marker chromosome of macroglobulinemia identified by G banding. Cytogenet Cell Genet 1977;18:371–3. Carbone P, Caradonna F, Granata G, Marceno R, Cavallaro AM, Barbata G. Chromosomal abnormalities in Waldenström’s macroglobulinemia. Cancer Genet Cytogenet 1992;61:147–51. Weber E, Nowotny H, Hass OA, Kasparu H, Grois N, Lutz D. Trisomy 4: a specific karotype anomaly in primary and secondary acute myeloid leukemia. Leukemia 1990;4:219–21. Martin PL, Look AT, Schnell S, Harris MB, Pullen J, Shuster JJ, Carrol AJ, Pettenati MJ, Rao PN. Comparison of fluorescence in situ hybridization, cytogenetic analysis and DNA index to detect chromosome 4 and 10 aneuploidy in pediatric acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Pediatric Hematol Oncol 1996;18:113–21.