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A case of follicular small cleaved cell lymphoma with t(14;18) and t(8;11)
A Case of Follicular Small Cleaved Cell Lymphoma with t(14;18) and t(8;11) S. Bal, G. Williams, and M. Ray
ABSTRACT: Follicular small cleaved cell lymphoma is a common B-cell lymphoma exhibiting a t(14;18)(q32;q21) chromosomal translocation, which has been found in most cases studied. In our case of follicular small cleaved cell lymphoma, the chromosome translocation 14;18 was observed. This case also exhibits a second consistent chromosomal translocation, t(8;11)(p21;q13), along with t(14;18).
INTRODUCTION Multiple chromosomal aberrations are a feature of non-Hodgkin's lymphomas and are believed to relate to tumor evolution and aggressiveness [1, 2]. Studies show a consistent chromosomal anomaly, t(14;18)(q32;q21) to be associated with follicular lymphoma. We report one case of follicular lymphoma, specifically a small cleaved cell lymphoma with this particular t(14;18)(q32;q21) chromosomal translocation, but also exhibiting in addition a consistent translocation t(8;11)(p21;q13).
CASE REPORT
We studied cytogenetically a 41-year-old man with an 8-week history of left cervical lymphadenopathy unresponsive to antibiotics. He had discomfort on opening his mouth but no dysphagia. He was a heavy drinker and smoker, but was otherwise healthy. Physical examination showed a 6-cm mass in the left upper neck. There was no other lymphadenopathy or hepatosplenomegaly. Fluoroscopy was negative. Excision biopsy of the mass confirmed a malignant lymphoma, nodular with diffuse areas, lymphocytic poorly differentiated (Rappaport), follicular small cleaved cell, low- to intermediate-grade (Working Formulation). Staging procedures including chest roentgenogram, abdominal computed tomography scan, bilateral bone marrow aspirates, and biopsies were negative. He was treated with local radiotherapy to the involved neck nodes and remains well 18 months later.
MATERIALS AND METHODS
Tissue samples obtained before treatment were minced and cultured for 24 hours according to standard techniques. Slides were aged for 8-10 days before G-banding. From the Departments of Anatomy (S. B.), Pathology (G. W.), Pediatrics and Child Health (M. R.), and Human Genetics (M. R.).
Address reprint requests to: M. Ray, Ph.D., Cytogenetics Laboratory, FE028, Community Services Bldg., 685 William Ave., Winnipeg, Manitoba, Canada B3E OZ2. Received May 2, 1989; accepted December 1, 1989.
199 © 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet 48:199 201 (1990] 0165-4608/90/$03.50
200
s. Bal et al.
Table 1
Frequency of chromosomal aberrations in 26 cells of follicular small cleaved cell lymphoma
Chromosomal defects
Frequency
+7 -8 -X t(8;ll)(p21;q13) t(14;18)(q32;q21) t(8;11) and t(14;18) t(8;11}, t(14;18), +7, - 8 and - X
17 14 9 24 21 21 9
Cytogenetic Studies Twenty-six m e t a p h a s e cells were analyzed. All cells exhibited m u l t i p l e chromosomal abnormalities. Thirteen of the 26 cells had a total chromosome count of 48; six showed 47 and three showed 46. Four cells had a total chromosome count of 45, 42, 41, and 40, respectively. In this particular case of follicular small cleaved cell l y m p h o m a , the t(14;18)(q32;q21) chromosomal translocation is observed in most of the cells. The presence of t(8;11)(p21;q13) has been detected in 24 of the 26 cells analyzed. Two of the cells did not have the t(8;11). Trisomy 7 appears in 17 cells, w h i c h also exhibit the t(8;11), and t(14;18). Loss of chromosome 8 and chromosome X is observed in 14 and nine cells, respectively (Table 1). Nine of 26 cells have all of the a b o v e m e n t i o n e d c h r o m o s o m a l aberrations [ + 7 , - 8,-X,tf8;11), and t(14;18)].
DISCUSSION The translocation (14;18)(q32;q21) has been observed in most cases of follicular l y m p h o m a [3, 4]. In this case of follicular small cleaved cell l y m p h o m a the t(8;11) (p21;q13) has been observed along with t(14;18)(q32;q21). Whether the t(8;11) resulting in trisomy for 1 1 q 1 3 - qter plays any significant role is unknown. The other consistent aberration observed in this case is the presence of an extra c h r o m o s o m e 7. Previous studies have demonstrated the importance of trisomy 7 in l y m p h o m a s ; particularly follicular or diffuse large cell l y m p h o m a [1-3]. These often evolve from follicular small cell l y m p h o m a , and several particular genomic defects have been suggested to be associated with clonal evolution of this disease [4]. Trisomy 7 has also been observed in other forms of neoplasia. Kaprowski et al. showed that expression of the receptor for e p i d e r m a l growth factor correlates with increased dosage of c h r o m o s o m e 7 in malignant melanoma; i.e., a + 7 or dup(7p) could contribute to a selective growth advantage in the malignant cells [5]. Histologically in this case the follicular pattern is beginning to show diffuse areas, suggesting progression of the l y m p h o m a to a more aggressive subtype. The n o n r a n d o m a p p e a r a n c e of t(8;11) in this case of follicular small cleaved cell l y m p h o m a is unusual. The karyotype t(8;11), t(14;18), + 7, - 8, - X may be indicative of the l y m p h o m a type and its progression.
The financial support from the Children's Hospital of Winnipeg Research Foundation, inc. is greatly appreciated.
Follicular Small Cleaved Cell L y m p h o m a
201
REFERENCES 1. Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ (1983): Nonrandom chromosome abnormalities in lymphoma. Cancer Res 43:2975-2984. 2. Koduru PRK, Filippa DA, Richardson ME, Jhanwar SC, Chaganti SR, Koziner B, Clarkson BD, Lieberman PH, Chaganti RSK (1987): Cytogenetic and histological correlations in malignant lymphoma. Blood 69:97-102. 3. Levine EG, Arthur DC, Frizzera G, Peterson BA, Hurd DD, Bloomfield CD (1985): There are differences in cytogenetic abnormalities among the non-Hodgkin's lymphomas. Blood 66:1414-1422. 4. Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides A, Arnesen M (1987): Multiple recurrent genomic defects in follicular lymphoma. N Engl J Med 316:79-84. 5. Kaprowski H, Herlyn M, Balaban G, Parmiter A, Ross A, Nowell PC (1985): Expression of the receptor far epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. Somatic Cell Mol Genet 11:297-302.
ABSTRACT: Follicular small cleaved cell lymphoma is a common B-cell lymphoma exhibiting a t(14;18)(q32;q21) chromosomal translocation, which has been found in most cases studied. In our case of follicular small cleaved cell lymphoma, the chromosome translocation 14;18 was observed. This case also exhibits a second consistent chromosomal translocation, t(8;11)(p21;q13), along with t(14;18).
INTRODUCTION Multiple chromosomal aberrations are a feature of non-Hodgkin's lymphomas and are believed to relate to tumor evolution and aggressiveness [1, 2]. Studies show a consistent chromosomal anomaly, t(14;18)(q32;q21) to be associated with follicular lymphoma. We report one case of follicular lymphoma, specifically a small cleaved cell lymphoma with this particular t(14;18)(q32;q21) chromosomal translocation, but also exhibiting in addition a consistent translocation t(8;11)(p21;q13).
CASE REPORT
We studied cytogenetically a 41-year-old man with an 8-week history of left cervical lymphadenopathy unresponsive to antibiotics. He had discomfort on opening his mouth but no dysphagia. He was a heavy drinker and smoker, but was otherwise healthy. Physical examination showed a 6-cm mass in the left upper neck. There was no other lymphadenopathy or hepatosplenomegaly. Fluoroscopy was negative. Excision biopsy of the mass confirmed a malignant lymphoma, nodular with diffuse areas, lymphocytic poorly differentiated (Rappaport), follicular small cleaved cell, low- to intermediate-grade (Working Formulation). Staging procedures including chest roentgenogram, abdominal computed tomography scan, bilateral bone marrow aspirates, and biopsies were negative. He was treated with local radiotherapy to the involved neck nodes and remains well 18 months later.
MATERIALS AND METHODS
Tissue samples obtained before treatment were minced and cultured for 24 hours according to standard techniques. Slides were aged for 8-10 days before G-banding. From the Departments of Anatomy (S. B.), Pathology (G. W.), Pediatrics and Child Health (M. R.), and Human Genetics (M. R.).
Address reprint requests to: M. Ray, Ph.D., Cytogenetics Laboratory, FE028, Community Services Bldg., 685 William Ave., Winnipeg, Manitoba, Canada B3E OZ2. Received May 2, 1989; accepted December 1, 1989.
199 © 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet 48:199 201 (1990] 0165-4608/90/$03.50
200
s. Bal et al.
Table 1
Frequency of chromosomal aberrations in 26 cells of follicular small cleaved cell lymphoma
Chromosomal defects
Frequency
+7 -8 -X t(8;ll)(p21;q13) t(14;18)(q32;q21) t(8;11) and t(14;18) t(8;11}, t(14;18), +7, - 8 and - X
17 14 9 24 21 21 9
Cytogenetic Studies Twenty-six m e t a p h a s e cells were analyzed. All cells exhibited m u l t i p l e chromosomal abnormalities. Thirteen of the 26 cells had a total chromosome count of 48; six showed 47 and three showed 46. Four cells had a total chromosome count of 45, 42, 41, and 40, respectively. In this particular case of follicular small cleaved cell l y m p h o m a , the t(14;18)(q32;q21) chromosomal translocation is observed in most of the cells. The presence of t(8;11)(p21;q13) has been detected in 24 of the 26 cells analyzed. Two of the cells did not have the t(8;11). Trisomy 7 appears in 17 cells, w h i c h also exhibit the t(8;11), and t(14;18). Loss of chromosome 8 and chromosome X is observed in 14 and nine cells, respectively (Table 1). Nine of 26 cells have all of the a b o v e m e n t i o n e d c h r o m o s o m a l aberrations [ + 7 , - 8,-X,tf8;11), and t(14;18)].
DISCUSSION The translocation (14;18)(q32;q21) has been observed in most cases of follicular l y m p h o m a [3, 4]. In this case of follicular small cleaved cell l y m p h o m a the t(8;11) (p21;q13) has been observed along with t(14;18)(q32;q21). Whether the t(8;11) resulting in trisomy for 1 1 q 1 3 - qter plays any significant role is unknown. The other consistent aberration observed in this case is the presence of an extra c h r o m o s o m e 7. Previous studies have demonstrated the importance of trisomy 7 in l y m p h o m a s ; particularly follicular or diffuse large cell l y m p h o m a [1-3]. These often evolve from follicular small cell l y m p h o m a , and several particular genomic defects have been suggested to be associated with clonal evolution of this disease [4]. Trisomy 7 has also been observed in other forms of neoplasia. Kaprowski et al. showed that expression of the receptor for e p i d e r m a l growth factor correlates with increased dosage of c h r o m o s o m e 7 in malignant melanoma; i.e., a + 7 or dup(7p) could contribute to a selective growth advantage in the malignant cells [5]. Histologically in this case the follicular pattern is beginning to show diffuse areas, suggesting progression of the l y m p h o m a to a more aggressive subtype. The n o n r a n d o m a p p e a r a n c e of t(8;11) in this case of follicular small cleaved cell l y m p h o m a is unusual. The karyotype t(8;11), t(14;18), + 7, - 8, - X may be indicative of the l y m p h o m a type and its progression.
The financial support from the Children's Hospital of Winnipeg Research Foundation, inc. is greatly appreciated.
Follicular Small Cleaved Cell L y m p h o m a
201
REFERENCES 1. Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ (1983): Nonrandom chromosome abnormalities in lymphoma. Cancer Res 43:2975-2984. 2. Koduru PRK, Filippa DA, Richardson ME, Jhanwar SC, Chaganti SR, Koziner B, Clarkson BD, Lieberman PH, Chaganti RSK (1987): Cytogenetic and histological correlations in malignant lymphoma. Blood 69:97-102. 3. Levine EG, Arthur DC, Frizzera G, Peterson BA, Hurd DD, Bloomfield CD (1985): There are differences in cytogenetic abnormalities among the non-Hodgkin's lymphomas. Blood 66:1414-1422. 4. Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides A, Arnesen M (1987): Multiple recurrent genomic defects in follicular lymphoma. N Engl J Med 316:79-84. 5. Kaprowski H, Herlyn M, Balaban G, Parmiter A, Ross A, Nowell PC (1985): Expression of the receptor far epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. Somatic Cell Mol Genet 11:297-302.