Hematopathology / ROUTINE CYTOGENETICS FOR SUSPECTED LYMPHOMA
Utility of Routine Classical Cytogenetic Studies
in the Evaluation of Suspected Lymphomas
Results of 279 Consecutive Lymph Node/Extranodal Tissue
Biopsies
James R. Cook, MD, PhD,1 Sofia Shekhter-Levin, PhD,2 and Steven H. Swerdlow, MD3
Key Words: Cytogenetics; Lymphoma; Lymph node biopsies; Karyotype
DOI: 10.1309/NAFYB0XW0V3G2JD5
Abstract
Classical cytogenetic studies have a critical role in
the diagnosis of acute leukemias; however, they are
much less widely used in lymphoma diagnosis. To
evaluate their utility in this latter setting, G-banded
karyotyping was performed on 279 consecutive lymph
node or tissue biopsy specimens with suspected
lymphoma. Complete cytogenetic studies were
successfully obtained in 177 cases (63.4%), including
115 (69.3%) of 166 hematolymphoid neoplasms.
Success rates varied with the specific diagnosis (range,
33%-100%). The karyotypes were abnormal in 97
(84.3%) of the hematolymphoid neoplasms. In at least 3
cases of non-Hodgkin lymphoma, the findings
contributed directly to the specific diagnosis made. In a
much larger proportion of cases, characteristic but
nonspecific findings were identified. Abnormalities of
suggested prognostic importance in follicular
lymphoma and in diffuse large B-cell lymphoma were
identified in 14 (44%) of 32 cases and 8 (24%) of 33
cases, respectively. Most karyotyped lymphomas will
display abnormal findings including many that are not
completely specific but support the diagnosis, some that
provide additional prognostic information, and,
infrequently, some that help establish a diagnosis that
might otherwise have been missed.
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DOI: 10.1309/NAFYB0XW0V3G2JD5
The current World Health Organization (WHO) classification of hematolymphoid neoplasms is based on a
multidisciplinary approach that integrates morphologic
and immunophenotypic findings with additional ancillary
data, often including cytogenetic findings.1 Classical cytogenetic studies of bone marrow specimens have been used
routinely at many institutions for many years, and karyotypic findings are required to classify the acute myeloid
leukemias with certainty using the WHO classification.
Experience with routine cytogenetic analysis of diagnostic
lymph node biopsy specimens or extranodal tissue biopsy
specimens for suspected lymphoma has been much more
limited, and it is not a widely used diagnostic test. This is,
at least in part, due to insufficient data in the literature to
indicate how often, and in what setting, routine cytogenetic studies will be successful and will contribute useful
diagnostic or prognostic information. There is, however, a
large body of literature describing variably specific cytogenetic abnormalities in many types of lymphomas,
including some that are reported to be of prognostic
significance.2-6
We reviewed the results of routine classical cytogenetic
studies in 279 consecutive diagnostic lymph node and extranodal tissue biopsy specimens submitted for hematopathologic evaluation. In addition to assessing the overall
frequency of complete and abnormal studies, the findings
were analyzed based on the ultimate diagnosis. Specific
attention was given to how often and to what extent the
results helped establish the diagnosis, supported the diagnosis, or provided information reported in the literature to
be of prognostic importance. Finally, novel translocations
were catalogued.
© American Society for Clinical Pathology
Hematopathology / ORIGINAL ARTICLE
Materials and Methods
Case Selection
This report includes all cases with cytogenetic studies
from a 16-month period during which all diagnostic lymph
node biopsy specimens and extranodal tissue biopsy specimens
received for a complete hematopathologic evaluation were
submitted for classical cytogenetic studies as long as there was
sufficient material. In some cases in which the initial histologic
sections and flow cytometric studies were definitively benign,
cytogenetic studies were canceled; such cases were excluded
from this study. Diagnoses were made according to WHO
criteria1 based on the histologic findings (available in all cases)
together with the results of flow cytometric studies (available in
274 cases [98.2%]), paraffin section immunohistochemical
analysis (performed in 205 cases [73.5%]), genotypic studies
(performed in 38 cases [13.6%]), and fluorescence in situ
hybridization (FISH) studies (performed in 12 cases [4.3%]). In
the analysis of follicular lymphoma (FL), grade 1 and grade 2
cases were grouped together (grade 1-2). All reports were
reviewed to subjectively evaluate the role of the cytogenetic
findings in making the final diagnoses.
Cytogenetic Analysis
Tissue samples were minced as finely as possible using
sterile scissors and forceps. The resulting suspension was
cultured in flasks, with caps loosened, in Change B culture
media in a carbon dioxide incubator for 24 hours. Ethidium
bromide (10 µg/mL concentration) and colcemid (0.1 µg/mL
concentration) were added into the flasks before cell
harvesting to ensure accumulation of metaphase plates with
elongated chromosomes. Cell harvests were performed using
standard procedures as previously described.7 Metaphase
chromosomes were trypsin-Giemsa banded, karyotyped, and
identified according to the International System of Human
Cytogenetics Nomenclature.8
Cytogenetic studies were classified as complete when
clonal abnormalities were identified or when at least 20
metaphases were examined without demonstrable clonal
abnormalities. Cases lacking clonal abnormalities but with
fewer than 20 metaphases available for examination were
considered suboptimal, in accordance with standard cytogenetic practice. Results were analyzed based on the final
pathologic diagnoses. In addition, abnormal karyotypes
obtained in cases of FL and DLBCL were reviewed, and
abnormalities of reported prognostic significance were tabulated. Finally, to evaluate the role of classical cytogenetic
analysis as a screening tool for novel abnormalities, we
examined successfully obtained karyotypes for the presence
of isolated balanced translocations not previously reported in
the literature.
Statistical Analysis
Data were analyzed by using the Student t test or Fisher
exact test, as indicated, using GraphPad Prizm software
(GraphPad Software, San Diego, CA).
Results
Yield of Cytogenetic Analysis
Of the 279 specimens submitted for classical cytogenetic studies, complete cytogenetic studies were obtained in
177 cases (63.4%) and of those, 105 cases (59.3%) demonstrated karyotypic abnormalities. Among the 166 hematolymphoid neoplasms examined, 115 cases (69.3%) had
complete cytogenetic studies, and of those, 97 cases demonstrated abnormalities (84.3%). The remaining cases included
84 cases of benign lymphoid hyperplasia, 11 cases of atypical lymphoid hyperplasia, and 18 cases of other, nonhematolymphoid neoplasms. The yield of analysis varied significantly with the specific diagnosis made ❚Table 1❚. In addition
to the cases with complete cytogenetic studies, 2 suboptimal
studies with fewer than 20 metaphases available for examination (1 FL and 1 CD10+ diffuse large B-cell lymphoma
[DLBCL]) each demonstrated a nonclonal t(14;18)(q32;q21)
that was considered of potential significance. Complete cytogenetic studies were obtained in a significantly higher
proportion of cases of hematolymphoid neoplasia than in
lymphoid hyperplasias (115/166 [69.3%] vs 45/84 [54%]; P
= .02; Fisher exact test).
Specific Abnormalities Identified
Diffuse Large B-Cell Lymphoma
Complete cytogenetic studies were obtained in 33 of the
47 DLBCL cases analyzed ❚Table 2❚. Of the remaining 14
cases, 10 demonstrated no growth, and 4 were suboptimal
with 1 to 15 metaphases (median, 5 metaphases) lacking
clonal abnormalities. Overall, the most common abnormalities (>10% of cases) identified in DLBCL were as follows:
+mar (12 [36%]); +X and –Y (7 [21%] each); +7, +21,
t(14;18)(q32;q21), and del(6q) (5 [15%] each); and +8, +11,
–15, t(8;14)(q24;q32), del(11q), and add(1p) (4 [12%] each).
To determine whether cases of DLBCL with a germinal
center phenotype displayed different karyotypic abnormalities from other cases of DLBCL, we compared the findings
in CD10+ and CD10– DLBCL. CD10– cases were more
likely than CD10+ cases to yield a complete cytogenetic
study, although this difference did not reach statistical significance (22/27 [81%] vs 11/20 [55%]; P = .06; Fisher exact
test). The presence of either t(14;18) or trisomy 7 was associated significantly with the expression of CD10 (P = .03;
Am J Clin Pathol 2004;121:826-835
© American Society for Clinical Pathology
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❚Table 1❚
Yield of Classical Cytogenetic Analysis by Diagnosis*
Diagnosis
No. of Cases
Benign lymphoid hyperplasia
Atypical lymphoid proliferations
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
Lymphoplasmacytic lymphoma
Splenic marginal zone lymphoma
Plasma cell neoplasm
Extranodal marginal zone B-cell lymphoma (MALT lymphoma)
Nodal marginal zone B-cell lymphoma
Follicular lymphoma
Grade 1-2
Grade 3A
Grade 3B
Mantle cell lymphoma
Diffuse large B-cell lymphoma
CD10+
CD10–
B-cell lymphoma, not otherwise specified
Atypical Burkitt lymphoma
Lymphoblastic lymphoma, precursor T-cell type
Peripheral T-cell lymphoma
Angioimmunoblastic T-cell type†
Peripheral T-cell, unspecified
Anaplastic large cell type, ALK–
Hodgkin lymphoma, nodular lymphocyte predominant
Hodgkin lymphoma, classical
PTLD, monomorphic
Acute myeloid leukemia
Other tumors, nonhematolymphoid
84
11
16
1
4
2
10
5
36
23
12
1
3
47
20
27
3
3
2
7
3
2
2
3
22
1
1
18
Complete
45 (54)
8 (73)
7 (44)
1 (100)
4 (100)
0 (0)
8 (80)
4 (80)
32 (89)
20 (87)
11 (92)
1 (100)
3 (100)
33 (70)
11 (55)
22 (81)
1 (33)
2 (67)
1 (50)
6 (86)
3 (100)
2 (100)
1 (50)
2 (67)
10 (45)
1 (100)
0 (0)
9 (50)
Abnormal
1 (2)
0 (0)
7 (100)
0 (0)
2 (50)
—
7 (88)
4 (100)
31 (97)
19 (95)
11 (100)
1 (100)
3 (100)
31 (94)
10 (91)
21 (95)
1 (100)
2 (100)
1 (100)
5 (83)
2 (67)
2 (100)
1 (100)
0 (0)
3 (30)
0 (0)
—
7 (78)
ALK, anaplastic lymphoma kinase; MALT, mucosa-associated lymphoid tissue; PTLD, posttransplant lymphoproliferative disorder.
* Data are given as number (percentage).
† Includes cases diagnosed as angioimmunoblastic T-cell lymphoma (AITL) or AITL-like T-cell lymphoma.
Fisher exact test). The other abnormalities showed no significant difference between CD10+ and CD10– DLBCL. The 1
case of t(14;18)(q32;q21) in a CD10– DLBCL was shown
by further FISH analysis to represent an IGH/MALT1 rather
than an IGH/bcl-2 translocation, as previously described.9
Follicular Lymphoma
Complete cytogenetic studies were obtained in 32 of 36
cases of FL ❚Table 3❚. Of the remaining 4 cases, 3 demonstrated no growth, and 1 contained 4 metaphases with only a
single cell containing a t(14;18)(q32;q21). The mean ± SD
number of abnormalities identified per abnormal karyotype
was 6.1 ± 0.85 and was higher in grade 3 than in the grade 12 FL group (9.4 ± 1.6 vs 3.9 ± 0.6; P < .001; Student t test).
The most common abnormalities identified (>10% of cases)
were as follows: t(14;18)(q32;q21) (27 [84%]); +mar (8
[25%]); +7 and +12 (7 [22%] each); +X (6 [19%]); and +5,
+8, +21, del(5q), and del(10q) (4 [13%] each). Abnormalities with breakpoints at 1p36.1 or 1q21, previously reported
as frequent secondary changes in FL,10 were identified in 4
(13%) and 3 (9%) of the cases, respectively. The finding of
t(14;18) was more common in the grade 1-2 group (18/20
[90%]) than in grade 3 FL (9/12 [75%]), although this difference was not statistically significant (P = .27; Fisher exact
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test). The t(3;14)(q27;q32), presumably involving the bcl-6
gene, was identified in 2 grade 3 FLs and in none of the
grade 1-2 FLs.
Marginal Zone Lymphoma
Of the 19 cases of marginal zone lymphoma (MZL)
analyzed, 16 yielded complete cytogenetic studies,
including 4 of the nodal type, 4 of the splenic type, and 8 of
the extranodal mucosa-associated lymphoid tissue (MALT)
type ❚Table 4❚. The 3 remaining MZLs demonstrated no
growth (1 nodal and 1 MALT) or yielded a suboptimal
study (1 MALT with only 9 metaphases available). The
mean ± SD number of abnormalities per abnormal karyotype was lower in MALT lymphomas (1.7 ± 1.1) than in
splenic MZL (4.5 ± 3.5) and nodal MZL (4.0 ± 1.6),
although this difference did not reach statistical significance
(P = .15 and P = .11, respectively; Student t test). The only
recurring abnormalities within this category were: +X (1
splenic and 1 nodal MZL), +3 (1 nodal MZL and 2 extranodal MALT cases), and +18 (2 nodal MZLs and 2 extranodal MALT cases). The t(1;14)(p22;q32), believed to be
specific for MALT lymphoma,3,11,12 was identified in 1 case
of pulmonary MALT lymphoma. Two cases of splenic MZL
showed partial or complete loss of chromosome 7.
© American Society for Clinical Pathology
Hematopathology / ORIGINAL ARTICLE
❚Table 2❚
Diffuse Large B-cell Lymphomas With Complete Cytogenetic Studies
Case No.
CD10–
2274
2867
2935
3031
3816
3907
3987
4063
5172
5175
5351
6601
6708
6989
7037
7582
7613
8052
8497
9780
1432
2623
CD10+
2915
3429
4209
5145
6023
6168
8328
8332
9180
88
2393
Karyotype
45,X,–Y,inv(3)(p11.2q27),add(14)(q32)[cp3]
47,XX,dup(1)(q42q25),dup(2)(p21p23),t(9;12)(p13;p13),del(13)(q14q22),+21[8]/47,XX,+9[2]/46,XX[11]
46,X,–Y,t(9;22)(p13;p11.2),+mar[14]/46,X,–Y,idem,del(12)(p11.2p12.2)[9]
47-50,XX,+X,add(1)(p36.3),inv(1)(p13q25)del(1)(q25)x1-2,+del(1)(p13p36.1)x1-2,del(2)(q31q35),–3 or inv(3)(q21q26)add(3)(p12),+4,
–5,del(6)(q15),dup(7)(q31q34),t(8;14)(q24;q32),–10,del(11)(q23),+12x1-2,add(12)(p12),add(19)(p13.3),del(20)(q11.2q13.3),
+1-3mar[cp+1-11]/46,+1-XX[8]
45-47,XX,t(2;11)(q21;p11.2)[12],der(4;10)(p10;q10)[12],t(6;19)(p21.3;p13.3)[12],i(6)(p10)[12],+6[12],t(8;14)(q24;q32)[12],+8[3],
t(9;12)(q12;q13)[12],add(14)(p11.2)[12],del(16)(q22q24)[11][cp12]/46,XX[8]
46,XY,add(8)(q24)[2]/46,XY[5]
84-87,XXYY,i(1)(q10),–2,del(3)(p11.2p21),inv(4)(p12q21),–4,add(6)(q23)x2,add(8)(q24),add(9)(p22)x2,–11,–11,–13,t(13;14)(p10;q10),
–15,–16,add(16)(p12),i(17)(q10),add(17)(q23)x12,der(19)t(11;19)(q13;q13.3),add(20)(p13),–21,–22,–22,add(22)(p13),
+mar[cp17]/46,XY[3]
46,XX,t(6;10)(p23;p13)[4]/46,XX[6]
81-89,XXY,–Y,del(1)(p13)x2,del(3)(q21),add(4)(q21),–14,add(14)(q32),add(15)(q26),+16,add(17)(p13)x2[cp7]/46,XY[3]
46,XY,t(5;17)(p15.3;q12)[12]/46,XY[6]
45,t(X;2)(p22.1;q31),–X[15]/46,XX[5]
45,X,–Y,t(1;2)(p13;p23)[4]/45,X,–Y[15]
86-90,XXXX,+X,add(8)(p11.2)x2[3],del(11)(q13)x2[2],add(11)(q23)x3[1],add(13)(q34)x2,add(14)(q32)x2,+19,+1-4mar[3][cp3]/46,XY[17]
46,XX[19]
46,XX,–8,der(8)t(6;8)(p11.2;p23),der(11)t(8;11;15)(q13;q13;q24),der(15)t(8;11;15)(q13;q13;q24),der(20)t(12;20)(q13;q13.3),
+r[13]/46,XX[7]
44-48,XY,+X,del(1)(p34.3),del(7)(q22q32),+8,add(10)(q26),add(12)(q24)[cp18]/46,XX[2]
48-49,XX,+X,del(6)(q13q27),der(6)t(6;17)(p21.3;q11.2),+idic(9)(q12),dup(11)(q13q13),–17,+21[20],+mar[7][cp20]
49,X,+X,+X,–Y,add(5)(q35),+9,add(12)(q24),–12,+mar1,+mar2[cp11]/46,XY[9]
47,XY,+X,t(8;14)(q24;q32),del(11)(q13q23)[7]/46,XY,t(8;14)(q24;q32),del(11)(q13q23),t(11;17)(q13;q21)[8]/46,XY[6]
46,XY,t(3;12)(q23;p13)[2]
49-51,X,–Y,+3,del(6)(q13q25)x2,+der(6)t(1;6)(q12;p21.3),+7,+7,+12,der(14)t(14;?)(q32;?),+20[cp11]/46,XY[5]
46,XX,+3,del(6)(q15q21),+11,t(14;18)(q32;q21),der(14;21)(p10;q10),–15,–15,der(22)t(1;22)(q21;p11.2),+mar[20]
47,XY,+mar[7]/46,XY[11]
42-45,X,–X,del(2)(p23),add(2)(p25)[12-16],add(4)(p15.2),+4[59],add(8)(p23),+12,dup(13)(q12q34),add(13)(q32),add(13)(q32),
t(14;18)(q32;q21),–15,–17,hsr(21)(q22),–22,+1-2mar[14-16][cp16]/46,XX[4]
47-48,X,–Y,del(1)(q42),add(2)(q37),–6,+7,del(9)(p13),add(13)(q34)x2[16],add(15)(p11.2)[4],i(18)(q10)[16],+add(18)(p11.3),
i(21)(q10),+21,der(21;22)(p10;q10)[3-9],+22[14],+mar[9][cp16]/46,XY[4]
45,X,–X[11]/46,XX[9]
46-48,XX[5],t(X;15)(p22.1;q15)[8],add(1)(p36)[8],del(4)(q12)[8],+7[12],t(8;14)(q24;q32)[14],t(14;18)(q32;q21)[14],add(15)(q15)[5],
i(17)(q10)[14],add(17)(q25)[9],+18[9],del(22)(q11.2)[3],–22[3][cp14]/46,XX[6]
75-101,XX[4],X[2],add(2)(q33)[7],add(2)(q33)[6],–3,+7[3],+8[2],–9,–9,+11[3],del(11)(q23)[5],del(11)(q23),–14,t(14;18)(q32;q21)[3],
t(14;18)(q32;q21)[1],+17,+17[2],+18[4],+18[3],der(18)t(14;18)(q32;q21)[1],+20[2],+1-10mar[7][cp7]
74-80,XX,add(6)(q27)x2,add(7)(q36),+7,+8,t(8;22)(q24;q11.2),del(9)(p22),+11,–14,t(14;18)(q32;q21),–15,+21,+21,add(21)(q22),
add(22)(q13),+2-6mar[cp3]/46,XX[2]
46,XX[25]
51,XX,+X,add(1)(p36.3),+3,t(7;7)(p22;q32),+11,ins(12;?)(q13;?),+13,+21[10]/51,idem,der(3)t(1;3)(q21;q27)[4]
46,XY,trp(11)(q13q23),dup(21)(q21q22)?hsr(21)(q22)[20]
88-92,XXXX,add(1)(p36.3)x2,add(3)(p11.2),del(3)(p11.2),del(6)(q23)[cp4]/46,XX[8]
Other B-Cell Lymphomas
Complete cytogenetic studies were obtained in 15 of 27
cases of other B-cell lymphomas ❚Table 5❚. Two cases of
atypical Burkitt lymphoma each demonstrated relatively
simple karyotypes including t(8;14)(q24;q32). A third case
of atypical Burkitt lymphoma demonstrated no growth.
Each of 7 successfully studied cases of B-cell chronic
lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) was cytogenetically abnormal. The only recurring abnormality identified in the CLL/SLL cases was
trisomy 12 (4 cases). The remaining 9 cases of CLL/SLL
demonstrated no growth (3 cases) or were suboptimal (6
cases with 1 to 11 metaphases; median, 8 metaphases). Each
of 3 cases of mantle cell lymphoma was karyotypically
abnormal with findings that included t(11;14)(q13;q32).
One B-cell lymphoma that could not be further classified
demonstrated a complex karyotype with numerous nonspecific abnormalities. Two additional cases of unclassifiable
B-cell lymphoma yielded suboptimal studies with 6 and 8
metaphases available.
T-Cell Lymphomas
Complete cytogenetic studies were obtained in 7 of 9 Tcell lymphomas submitted for analysis ❚Table 6❚ . The
remaining cases, an anaplastic lymphoma kinase–negative
anaplastic large cell lymphoma (ALCL) and a γδ T-cell
lymphoblastic lymphoma, demonstrated no growth. Of the
cases with complete studies, 1 was diagnosed definitively as
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❚Table 3❚
Follicular Lymphomas With Complete Cytogenetic Studies
Case No./
Grade
Grade 1-2
930
1102
4657
4718
5459
5466
5481
5850
6033
6419
6525
6526
6674
6714
7402
8608
9160
9388
9456
5675A
Grade 3A
63
363
1765
4005
4088
4516
7071
8136
9100
8977A
9901A
Grade 3B
6404
Karyotype
46,XY[20]
47,XY,t(14;18)(q32;q21),+18[5]
46,XX,del(9)(p22)[6]/46,XX[13]
47,XY,t(14;18)(q32;q21),+21[2]/47,idem,del(1)(p32p36.1)[2]/50-51,idem,+X,+del(1)(p32p36.1),+12,+21[cp12]/46,XY[4]
46,XY,add(1)(p36),t(3;6)(p10;q10),del(4)(q21q25),del(10)(q24),del(13)(q14q22),t(14;18)(q32;q21)[8]/46,XY[11]
47,X,–Y,+X,+12,t(14;18)(q32;q21),add(14)(q32)[10]/46,XY[8]
49,XX,i(6)(p10),+7,inv(12)(p11.2q13),+12,t(14;18)(q32;q21),add(21)(p11.2),+mar[16]/46,XX[4]
45,X,–X,t(14;18)(q32;q21)[2]/45,X,–X,dup(1)(q21;q23),t(14;18)(q32;q21)[12]/90,XX,–X,–X,dup(1)(q21q23)x2,
t(14;18)(q32;q21)x2[2]/46,XX[4]
47,XY,+X,t(14;18)(q32;q21)[2]/47,XY,+8,t(14;18)(q32;q21)[5]/46,XY[11]
47,XY,del(6)(q15q25)[9],del(6)(q15q25)[6],add(7)(p22)[6],–12[8],t(14;18)(q32;q21)[9],+mar1[7],+mar2[8],+mar3[2][cp9]/46,XY[11]
46,XY,t(14;18)(q32;q21)[19]
46,XX,t(14;18)(q32;q21)[16]/46,XX[3]
47,XY,t(1;10)(q42;q24),del(2)(p23),t(14;18)(q32;q21),+der(18)t(14;18)(q32;q21)[3]/46-48,XY,t(1;10)(q42;q24),–2,–12,
t(14;18)(q32;q21),+der(18)t(14;18)(q32;q21),+der(?)t(?;12)(?;11.2)x1-2,+mar[cp15]/46,XY[2]
47,XY,del(5)(q22q31),add(9)(p24),t(14;18)(q32;q21),+der(18)t(14;18)(q32;q21)[14]/46,XY[6]
45,X,–X,t(14;18;22)(q32;q21;q11.2)[3]/44-48,X,–X,+5[7],i(6)(p10),+6,+7,t(14;18;22)(q32;q21;q11.2),add(22)(q13)[cp14]/46,XX[3]
46,XY,t(14;18)(q32;q21)[7]/46,XY[3]
47,X,add(X)(q21.3),add(2)(q34),–6,t(14;18)(q32;q21),add(17)(p11),+mar1,+mar2[11]/46,XX[8]
46,XY,add(1)(p36.3),t(14;18)(q32;q21)[3]/46,XY[3]
46,XY,–13,der(14)t(14;18)(q32;q21)del(14)(q13q22),der(18)t(14;18)(q32;q21),+r[7]/46,XY[8]
46,XY,t(14;18)(q32;q21)[2]/46,XY[4]
49,XX,+X,+X,add(1)(q42)x2,t(3;14)(q27;q32),+21[6]/50,idem,+7[4]/46,XX[9]
47-50,XY,+Y,der(1;6)(p10;q10),+8,+20,+21[cp15]/46,XY[4]
48,XY,+X,dup(1)(q21q44),+7,t(14;18)(q32;q21)[13]/46,XY[7]
46,XX,t(6;8)(q23;p23),t(14;18)(q32;q21)[16]/46,XY[4]
48,XX,add(4)(p16),del(5)(q12q33),+5,t(14;18)(q32;q21),add(15)(p11.2),+16[7]/49-50,XX,idem,+2[6],del(2)(q11.2q31)[3],
+12[4][cp7]/46,XX[6]
46,XX,del(3)(q12q21),t(14;18)(q32;q21)[6]/48,idem,+7,+9,del(10)(q24q26)
44-47,X,–X,der(2;12)(p10;q10),del(4)(q21q25),del(5)(q22q35),der(6;17)(p10;q10),dup(7)(q32q36)x2,+7,del(9)(q12q22),
–9,del(10)(q24q26),+10,t(14;18)(q32;q21),+17,+18,+18,add(19)(q13.3),del(22)(q12),+mar[cp21]
87-93,XXYY,t(1;19)(q23;p13.3)x2[14],del(3)(q21q25)x2[14],add(4)(q35)[4],–7[6],inv(9)(p11q13)x2[15],
del(10)(q24)x2[14],t(14;18)(q32;q21)x2[15],–14[3],del(15)(q24)[10],del(15)(q24)[4],–17[4],der(19)t(1;19)(q23;q13.3)[3],
–20[4],+mar1[4],+mar2[4][cp16]/46,XY[3]
50-51,XY,+del(5)(q11.2q33),del(6)(q21),+del(6)(q21),+del(7)(q22q36),–13,t(14;18)(q32;q21),+16,+17,+18,add(19)(q13),
+20,+21[cp12]/46,XY[6]
68-77,XY,+X,+Y,inv(1)(p22p36.1)x1-2,del(1)(p22p36.1),+del(1)(q11.2),add(2)(q21),+3,+5,+7,+8,+11,+12,t(14;18)(q32;q21)x2,
add(17)(p11.2),add(18)(q22),+22,+mar[cp5]
86-91,XXYY,add(2)(q31),add(4)(p16)x2,+5,add(6)(q21)x2,del(8)(p21)x2,–8,–8,t(9;14;18)(p24;q32;q21)x2,+9,+9,
–10,del(12)(q22)x2,+12,+12,add(13)(p11.2)x2,–14,–14,–15,–15,–16,+19,+mar1,+mar2,+mar3[cp16]/46,XY[4]
47-48,XY,dup(1)(q21q12),t(3;14)(q27;q32),del(6)(q21q25)[19],+8[2],+12,add(12)(q24.3),del(13)(q12q14)[19][cp19]/46,XY[1]
angioimmunoblastic T-cell lymphoma (AITL), while 2
others displayed AITL-like features. The karyotypes in these
cases were less complex than those obtained for the 2 cases
of peripheral T-cell lymphoma, unspecified (PTCLU), or the
1 case of anaplastic lymphoma kinase–negative ALCL. The
only recurring abnormalities within this category were: +5 (1
AITL-like case and 1 ALCL), del(1p) (1 ALCL and 1
PTCLU), and del(3q) (1 AITL-like case and 1 PTCLU).
Hodgkin Lymphoma
Twelve cases of Hodgkin lymphoma yielded complete
cytogenetic studies, with 9 demonstrating an apparently
normal chromosome complement ❚Table 7❚. An additional 13
cases demonstrated no growth (7 cases) or were suboptimal
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studies (6 cases with 1-19 metaphases; median, 12
metaphases). Abnormalities were noted in 3 cases of classical Hodgkin lymphoma and in none of the cases of nodular
lymphocyte predominant Hodgkin lymphoma analyzed. The
only recurring abnormality noted was trisomy 5, which was
present in 2 cases.
Reactive Hyperplasia and Nonhematopoietic Neoplasms
Among the 84 cases of reactive hyperplasia, 21 cases
demonstrated no growth and another 18 cases were suboptimal studies with 1 to 19 metaphases obtained (median, 13
metaphases). Of the 45 cases of benign lymphoid hyperplasia for which complete cytogenetic studies could be
obtained, 44 cases demonstrated only normal findings. In the
© American Society for Clinical Pathology
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❚Table 4❚
Marginal Zone Lymphomas With Complete Cytogenetic Studies
Case No./Tumor
Type and Location
Karyotype
Mucosa-associated lymphoid tissue
3214, lung
49,XY,t(1;14)(p22;q32),+3,+12,+18[11]/46,XY[7]
786, orbit
47,XY,del(3)(p12p21.1),+3[6]/46,XY[13]
794, orbit
48,XX,+18,+mar[cp9]
1001, orbit
46,XY[20]
4045, orbit
46,XX,del(11)(?q21)[7]/46,XX[12]
7768, orbit
47,XX,inv(9)(p11q13),+10[16]/46,XX,inv(9)(p11q13)[4]
7769, parotid
46,XY,i(18)(q10)[8]/46,XY[10]
8023, parotid
46,XX,add(11)(p15)[cp2]
Nodal
1237
47-48,X,del(X)(q22q26),add(1)(p36.3),dup(6)(p23p25)[11-13],dup(10)(p13p12)[3],del(16)(q13q22),+18,
der(19)t(13;19)(p13.3;q14.3),+21[13-15][cp15]/46,XX[4]
1357*
46,X,t(X;5)(q26;q15)[16]/46,XX[3]
5767
46,XY,der(1)t(1;1)(p36.1;q21),der(8)t(3;8)(q11.2;p11.2)[17]/46,XY[3]
8698
48,XX,+3,del(11)(q23),del(13)(q12q14),+18[8]/47,XX,+X[2]/46,XX[11]
Splenic
71
44-45,XX+X,del(6)(q12q23),–7,add(8)(p23),–17,add(20)(q13.3)[cp8]/81-89,XXXX,+X,del(6)(q12q23)x2,–7,–7,add(8)(p23)x2,
i(13)(q10),–17,–17,add(20)(q13.3)x2[cp3]/46,XX[13]
1288
46,XX[20]
1866
46,XY[20]
8350
46,XX,del(7)(q22q34)[13]/46,XX[7]
*
As described in detail elsewhere,14 the following revised karyotype was assigned following additional fluorescence in situ hybridization studies: 46,X,t(X;5)(q28;q22).
❚Table 5❚
Other B-Cell Lymphomas With Complete Cytogenetic Studies
Case No./
Diagnosis
Karyotype
Atypical Burkitt
3719
46,XY,t(8;14)(q24;q32)[10]
9189
46,XY,t(8;14)(q24;q32),t(9;22)(p24;q11.2)[7]/46,XY[11]
CLL/SLL
1217
47,XX,+12,add(14)(q32)[4]/47,idem,add(3)(p25)[5]/46,XX[6]
1970
47,XY,+12[11]/46,XY[9]
2214
46,XY,inv(1)(p13q44),del(6)(q23q25)[3]
5067
46,XY,i(17)(q10)[3]/45,XY,i(17)(q10),add(9)(q34),dic(19;21)(p13.3;p11.2)[cp12]/46,XY[5]
8086
47,XX,+12[3]/46,XX[17]
8428
47,XY,+12[17]/47,XY,add(11)(q25),+12[cp2]
9003
45,XY,–14,+r[4]/46,XY,t(7;10)(q22;q24),del(13)(q12q14),del(14)(q22q31)[2]/46,XY[13]
LPL
3852
46,XY[20]
Mantle cell
3070
46,XY,add(10)(q24),t(11;14)(q13;q32)[5]/46,XY[5]
5487
46,XX,add(3)(q27),t(9;18)(p13;p12),t(11;14)(q13;q32)[7]/46,XX[13]
6400
47,XY,add(1)(p36.3),add(1)(p22),del(2)(q33),add(2)(q37),–5,add(5)(q37),–7,t(11;14)(q13;q32),+17,+20,+1-2mar[cp9]/46,XY[7]
PTLD, monomorphic, DLBCL type
8862
46,XY[18]
B-cell lymphoma, NOS
9428
47,XY,+X[3]/50,XY,+X,+X,trp(1)(q21q32)[16],add(1)(p36.3)[11],+2[16],add(2)(p23),+der(3;4)(p10;q10)[11],
add(6)(p25)[16],+12[5],der(14;15)(p10;q10)t(14;?)(q32;?)[16],+18[11],i(21)(q10),add(22)(p11.2)[16],+mar[16][cp16]
CLL/SLL, B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma; DLBCL, diffuse large B-cell lymphoma; LPL, lymphoplasmacytic lymphoma; NOS, not
otherwise specified; PTLD, posttransplant lymphoproliferative disorder.
remaining case, a tonsillectomy specimen, the histopathologic and flow cytometric analyses demonstrated lymphoid
hyperplasia. Genotypic studies did not demonstrate evidence
of a clonal B-cell or T-cell population by polymerase chain
reaction or Southern blot studies. Cytogenetic analysis,
however, displayed the following karyotype:
46,XY,t(12;13)(q13;q32)[4]/46,XY[13]. The patient was
otherwise well, and the significance of this cytogenetic
abnormality identified remains unclear. Complete cytogenetic studies also were obtained for 7 cases of metastatic
carcinoma, 1 poorly differentiated malignant neoplasm of
uncertain lineage, and 1 benign thymoma. Apparently
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❚Table 6❚
T-Cell Lymphomas With Complete Cytogenetic Studies
Case No./
Diagnosis
Karyotype
T-cell lymphoma
Angioimmunoblastic
5276
46,XY[16]
Angioimmunoblastic-like
86
47,XY,+5[4]/46,XY[16]
419
46,XX,del(3)(q12q21)[7]/46,XX[13]
Peripheral, unspecified
5317
47,Y,–X,del(1)(p13p22),inv(2)(p11.2p13),del(3)(q11.2q25),+3,der(4)add(4)(p16)add(4)(q25),del(5)(q13q22),
del(6)(q21q25),del(8)(q21.1q22),dup(12)(q13q24.1),add(13)(q34),add(16)(p13),+mar[18]/46,XY[5]
9859
49,XY,+5,add(6)(p23),inv(11)(q14.2q23),+19,add(19)(p13.3),add(21)(q22),+22[14]/50,idem,+add(21)(q22)[2]/46,XY[1]
Anaplastic large cell lymphoma, ALK–
2258
42-47,X,t(X;6)(p11.2;p23),del(1)(p22p36),del(7)(q22q34),i(17)(q10),–22,+1-4mar[cp5]/89-93,idemx2[2]/46,XX[14]
Precursor T lymphoblastic lymphoma
9306
46,XX,add(7)(p11.2)[12]/46,XX[6]
ALK, anaplastic lymphoma kinase.
❚Table 7❚
Hodgkin Lymphomas With Complete Cytogenetic Studies
Case No/Type
Karyotype
Classical
120
5218
2423
9929
1025
2424
5326
5818
46,XX[20]
46,XY[20]
46,XY[20]
46,XY[19]
46,XY,del(13)(q12q14)[5]/46,XY[14]
54,XX,+5,+9,+10,+15,+18,+19,+21,+22[3]/46,XX[17]
46,XY[19]
52,X,–X,+i(2)(q10),add(4)(q35),+5,+i(5)(p10),
der(7)t(1;7)(q21;q34),+i(9)(p10),del(10)(p12.2),
add(13)(p13),+add(19)(p13.3),–21,add(22)(p13),
+2r[cp5]/46,XX[16]
9662
46,XY[20]
9858
46,XX[20]
Nodular lymphocyte predominant
1178
46,XY[20]
3606
46,XY[18]
❚Table 8❚
Abnormalities of Suggested Prognostic Significance
in Follicular Lymphoma*
Cytogenetic
Abnormality
≥6 breaks
1p21~22
6q23~27
17p
t(14;18) + c-myc
Any of the above
Grade 1-2 (n = 20)
Grade 3 (n = 12)
3 (15)
0 (0)
1 (5)
1 (5)
0 (0)
5 (25)
8 (67)†
1 (8)
4 (33)
2 (17)
0 (0)
9 (75)‡
All (n = 32)
11 (34)
1 (3)
5 (16)
3 (10)
0 (0)
14 (44)
*
Data are given as number (percentage).
† P = .006; grade 1-2 vs grade 3.
‡ P = .01; grade 1-2 vs grade 3.
normal karyotypes were found in 1 case of carcinoma and in
the thymoma, while the remaining cases each demonstrated
complex karyotypes with numerous numeric and structural
abnormalities (data not shown).
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Impact on Diagnosis Made
In 3 cases, the final diagnosis was based explicitly, in
part, on the cytogenetic abnormalities identified (2.6% of
hematolymphoid neoplasms successfully karyotyped).
Two of these cases were B-cell lymphomas that displayed
high-grade features but greater morphologic pleomorphism than classic Burkitt lymphomas. Following identification of t(8;14)(q24;q32) in each case, either as an
isolated finding or as part of a simple karyotype, a diagnosis of atypical Burkitt lymphoma was made. In the third
case, a diagnosis of splenic MZL was made based in part
on the demonstration of del(7)(q22q34), an abnormality
associated with up to 40% of splenic MZLs. 13 In the
remaining cases with abnormal karyotypes (81.7% of
hematolymphoid neoplasms karyotyped), the findings
were considered to provide variably significant additional,
although nonspecific, support for the final diagnosis
issued. For example, t(14;18)(q32;q21) was identified in
84% of cases of FL (27/32), strongly supporting that diagnosis. In no case did the results of cytogenetic analysis
alter a diagnosis that had been issued before completion of
such studies. Cytogenetic studies also did not assist in
further clarifying the 11 cases of atypical lymphoid proliferations or further classifying the 3 cases of B-cell
lymphoma, not otherwise specified, in this series.
Prognostic Information in Abnormal Karyotypes
As shown in ❚Table 8❚, 44% (14/32) of cases of FL
demonstrated at least 1 of the following abnormalities that
have been reported to be of prognostic significance: 6 or
more chromosome breaks, 1p21~22 abnormalities, 6q23~27
abnormalities, 17p abnormalities, or the presence of both
t(14;18)(q32;q21) and a rearrangement of c-myc at 8q24.3,4
These abnormalities were more likely to be present in grade
3 cases than in grade 1-2 cases (P = .01; Fisher exact test).
© American Society for Clinical Pathology
Hematopathology / ORIGINAL ARTICLE
❚Table 9❚
Abnormalities of Suggested Prognostic Significance in 33
Diffuse Large B-Cell Lymphomas
Cytogenetic Abnormality
der(1)(q21~23)
del(6)(q21~25)
+6
t(14;18) + c-myc
Any of the above
No. (%) of Cases
2 (6)
4 (12)
1 (3)
2 (6)
8 (24)
In DLBCL, 24% of cases (8/33) demonstrated one or
more of the following abnormalities reported to be of prognostic significance: abnormalities of chromosome 1 at band
1q21~q23, del(6)(q21~25), trisomy 6, or the presence of
both t(14;18)(q32;q21) and a c-myc rearrangement at
8q243,5,6 ❚Table 9❚. Comparison of CD10+ and CD10– cases
showed no significant difference in the incidence of these
abnormalities (data not shown).
Identification of Novel Abnormalities
Three cases of non-Hodgkin lymphoma (NHL)
contained previously unreported balanced translocations as
isolated karyotypic abnormalities (2.6% of cases of hematolymphoid neoplasms with complete cytogenetic studies).
One of these cases, a nodal MZL with t(X;5)(q28;q22), has
been described in detail elsewhere.14 In addition, 1 hepatic
DLBCL contained a t(6;10)(p23;p13), and analysis of 1
splenic DLBCL demonstrated a t(5;17)(p15.3;q12).
Discussion
Although the cytogenetic findings in malignant
lymphoma have been studied extensively for many years,2,3
there is little information in the literature concerning the
utility of the routine use of classical cytogenetic studies in
the evaluation of lymph node or other solid tissue biopsy
specimens for suspected lymphoma. This report demonstrates that in the course of routine practice, complete cytogenetic studies can be obtained for the majority of such
specimens. The rate of successful karyotyping was higher
in cases of hematolymphoid neoplasia than in benign
lymphoid hyperplasia. There was also considerable variation in the rate of complete analysis depending on the type
of lymphoma present. For example, 89% of FL cases
(32/36) yielded complete cytogenetic studies compared
with only 44% and 45% of cases of CLL/SLL (7/16) and
classical Hodgkin lymphoma (10/22), respectively. These
findings are similar to those in previous studies of these
specific entities, 2,3 although some investigators have
reported higher rates of successful analysis in classical
Hodgkin lymphoma.15,16
This series also demonstrates that in routine clinical
practice, more than 80% of karyotyped malignant
lymphomas will demonstrate abnormal findings, with 90%
to 100% abnormal karyotypes obtained for most types of
lymphoma. The lowest incidence of cytogenetic abnormalities was found in classical Hodgkin lymphoma (3/10 [30%]),
consistent with the results of previous studies.15
It is very difficult to precisely quantify the contribution
of abnormal cytogenetic findings to the final diagnosis in a
specific case, partially because the value of such studies will
vary depending on the nature of other ancillary studies
performed and the validity of the initial histopathologic evaluation. For example, in a case of FL with flow cytometric
studies demonstrating CD10 expression by monoclonal B
cells or a bcl-2 translocation identified by polymerase chain
reaction studies, the demonstration of t(14;18)(q32;q21) by
classic cytogenetic studies provides little additional diagnostic information. In the absence of such other ancillary
studies or if a mistaken diagnosis of follicular hyperplasia is
made, the finding of t(14;18) by classical cytogenetic studies
would be of far greater value. Within the present series,
performed at a tertiary medical center with ready access to a
wide array of immunohistochemical, flow cytometric, and
genotypic studies, classical cytogenetic analysis contributed
variably important, usually noncritical additional information
in many cases.
Classical cytogenetic studies provided critical information in 2.6% of the successfully analyzed neoplasms. Two
high-grade B-cell lymphomas were classified as atypical
Burkitt lymphomas based on the presence of
t(8;14)(q24;q32) as part of a simple karyotype. Because this
translocation involving c-myc and IGH may be seen as a
secondary abnormality in other forms of lymphoma, such as
with the t(14;18)(q32;q21), knowledge of any additional
karyotypic abnormalities is useful in reaching a final interpretation. The cytogenetic studies provide information,
therefore, that would not be obtained by using more focused
genotypic or FISH studies looking for a c-myc rearrangement alone. One splenic lymphoma was diagnosed as splenic
MZL in part owing to the presence of an isolated del(7q), an
abnormality reported in up to 40% of cases of splenic MZL
but in fewer than 10% of other B-cell lymphomas. 13
Although FISH could have been used to identify this abnormality, such a directed investigation would not have revealed
other diagnostically significant karyotypic abnormalities
such as those associated with a mantle cell lymphoma, FL,
or another splenic MZL mimic.17
In a much larger proportion of cases, the karyotypic
abnormalities that were identified, although not specific,
provided variably significant additional support for the diagnosis made. The abnormalities documented among the
specific forms of lymphoma in this unselected series were
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generally similar to those reported in the literature. For
example, t(14;18)(q32;q21) was identified in 84% of cases of
FL (27/32) and in 15% of cases of DLBCL (5/33), and each
of the cases of mantle cell lymphoma studies demonstrated
the t(11;14)(q13;q32).2,3 The three most common secondary
abnormalities found in the FL cases in this series also have
been reported by others in a similar proportion of cases: +7
(21%-23%), +12 (20%-30%), and +X (18%-23%). 10,18
Abnormalities with less specific but well-recognized diagnostic associations also were found, such as trisomy 12 in
CLL and trisomy 3 in some MALT lymphomas.12,19,20 Some
cytogenetic abnormalities with well-described diagnostic
associations, such as t(11;18)(q21;q21) with extranodal
MALT lymphoma 12,21 or isochromosome 7q with
hepatosplenic T-cell lymphoma,22 were not identified in this
unselected series, likely related to sample size and the overall
frequency of these abnormalities.
In general, the demonstration of any abnormal karyotype provides the pathologist with independent confirmation of the presence of a neoplasm; however, cases in which
this is the only nonhistologic supportive evidence are relatively few. Even this observation must be interpreted with
some caution, because a clonal population was identified in 1
specimen, even though no other evidence of a neoplasm
could be identified. The cytogenetic studies led to a more
extensive workup that could have led to the discovery of a
subtle neoplasm. Other investigators have reported that cases
of apparent benign lymphoid hyperplasia with clonal cytogenetic abnormalities are at very high risk for the subsequent
development of an overt lymphoma, although the same
authors also diagnosed a subsequent lymphoma in 7 of 17
cases in which the initial biopsies revealed benign hyperplasia, with normal or incomplete cytogenetic studies.23 In
addition, while it is reassuring not to have found cytogenetic
abnormalities in any of the atypical lymphoid proliferations
we examined, given that some overt neoplasms display
normal karyotypes, this observation also must be interpreted
cautiously. The finding of an abnormal karyotype in only 1
of 84 cases of reactive hyperplasia suggests that classical
cytogenetic studies are a poor screening tool and unnecessary in the workup of cases in which the histologic and
immunophenotypic findings indicate lymphoid hyperplasia.
Cases also can be cultured and then held pending a decision
about whether cytogenetic studies are appropriate.
Classical cytogenetic studies also have a role in
providing prognostic information in a moderate number of
cases, at least in the more common and extensively studied
NHL. Abnormalities of 1p21~22, 6q23~27, or 17p, or 6 or
more chromosome breaks have been reported to be adverse
prognostic indicators in FL and were identified in almost half
of the FL cases in this study. These adverse prognostic indicators were more frequently identified in the grade 3 FL. In
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addition, there are other histologic correlations with certain
abnormalities, such as trisomy 7 that has been associated
with the higher grade FL10 and transformation to DLBCL.24
In our series, grade 3 FL cases also demonstrated a greater
number of abnormalities, a greater number of chromosomal
breaks, and a lower incidence of the t(14;18)(q32;q21) than
did FLs in the grade 1-2 group. It should be recognized,
however, that simply finding other abnormalities in addition
to the t(14;18)(q32;q21) does not imply clinical or histologic
disease progression. Very few FLs have the latter translocation as an isolated finding (13% in the present series; 3% in
Horsman et al10), although they are all grade 1-2.
Similarly, abnormalities of 1q21~23, del(6)(q21~25),
+6, or t(14;18) with concurrent c-myc rearrangements have
been reported to be adverse prognostic indicators in DLBCL.
These abnormalities were present in 24% of the DLBCLs
(8/33) reported herein. Karyotypic abnormalities that might
influence prognosis or have treatment implications also have
been described in many other forms of NHL,2,3 but the
number of cases in many of the specific categories of NHL
limited further analysis in the present series.
In addition to identifying known prognostic factors,
cytogenetic studies also can further elucidate the heterogeneity of DLBCL. Both the t(14;18)(q32;q21) and trisomy
7 were associated significantly with CD10+ DLBCL, a
phenotype associated with DLBCL of a germinal
center–type gene profile.25 In fact, the only t(14;18) identified in a CD10– DLBCL in the present series was later
shown to represent an IGH/MALT1 translocation rather than
the expected IGH/bcl-2 translocation.9 Both trisomy 7 and
t(14;18) are common abnormalities in FL, and their significant association with CD10+ DLBCL likely reflects transformation of an underlying FL in these cases.3,4,26 As noted in
preceding text, trisomy 7 has been shown to be a frequent
abnormality in cases of FL that transform to DLBCL.24
Another advantage of classical cytogenetic analysis,
which is not possible using more directed FISH or genotypic
studies, is the ability to demonstrate unexpected novel cytogenetic abnormalities. Of the 115 hematopoietic malignant
neoplasms karyotyped in the present series, 3 cases (2.6%)
contained novel balanced translocations. These findings are
of great interest because they can lead to the discovery of
previously uncharacterized oncogenes involved in
lymphomagenesis.
Our study demonstrated that complete classical cytogenetic studies can be obtained in a large proportion of diagnostic lymph node and extranodal tissue biopsy specimens
in routine practice. Although the proportion of these unselected cases in which critical or novel information is
obtained is small, in many cases the results provide variably
specific support for the diagnosis made using a moderately
extensive multiparameter approach to lymphoma diagnosis.
© American Society for Clinical Pathology
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As illustrated, cytogenetic studies can provide prognostic
information in a significant minority of cases, although
further studies are required to assess the most cost-effective
manner to identify these abnormalities and to determine
how many are truly independent prognostic indicators. In
addition, the presence of at least 1 t(14;18)(q32;q21) in a
DLBCL that represents a MALT1 and not a bcl-2 translocation highlights 1 potential limitation of this technique,
which morphologically identifies chromosomal regions
rather than specific genes. While the ultimate relative value
of classical cytogenetic studies in the evaluation of
suspected lymphoma remains to be determined, the value of
such data likely will continue to increase with growing
experience and larger studies.
From the 1Department of Clinical Pathology, Cleveland Clinic
Foundation, Cleveland, OH; 2Department of Human Genetics,
University of Pittsburgh, Pittsburgh Cytogenetics Laboratory at
the University of Pittsburgh Medical Center, Magee-Women’s
Hospital, and University of Pittsburgh Cancer Institute; and
3Department of Pathology, Division of Hematopathology,
University of Pittsburgh School of Medicine, Pittsburgh, PA.
Address reprint requests to Dr Swerdlow: Dept of Pathology,
Division of Hematopathology Room C606-PUH, University of
Pittsburgh School of Medicine, 200 Lothrop St, Pittsburgh, PA
15213.
Acknowledgment: We are grateful to the expert technologists
of the Pittsburgh Cytogenetics Laboratory for their thorough
cytogenetic analysis and karyotyping.
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