The t(2;12)(p12;p13), leading to the juxtaposition of the cyclin D2 CCND2 gene with the immunoglobulin kappa locus (IGK), defines a small subset of mantle cell lymphomas lacking cyclin D1 expression.

2015-02-01  S Nicolas Duployez, Laurent Pascal, Judith Bruge, Marie Fatoux, Catherine Roche-Lestienne

Institut de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU, Avenue E Avinée, 59037 Lille, (ND, CRL); Service d Onco-Hématologie, GHICL Hopital St Vincent de Paul, Bd de Belfort, 59020 Lille, (LP) France; Laboratoire de Biologie, GHICL, Rue du Grand But B.P. 249, 59462 Lomme Cedex, (JB, MF) France. [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-

Clinics case report

Age
89 yrs
Sex
F
Liver
-
Spleen
+ (moderate)
Lymph nodes
+
Cns involv
-

Blood data

Wbc
144 (lymphoma cells : 93%) Morphology showed small to medium sized lymphoid cells with pale cytoplasm and slightly to markedly irregular nuclear contour, sometimes mimicking centrocytes. Nucleoli were inconspicuous or absent.
Hb
12.8
Platelets
196
Blasts
NA
Bone marrow
Bone marrow involvement (stage IV Ann Arbor).
Note
Rapid progression of the disease because 6 months ago laboratory analyses were normal (notably blood count).

Cyto path

Phenotype
NA
Immunophenotype
lymphoma cells CD19+ CD5+ CD20+ (strong), CD22+ (strong), CD23+, FMC7+, monotypic kappa light-chain expression (moderate); Matutes score = 2/5.
Rearranged ig tcr
Not performed.
Pathology
Mantle cell lymphoma
Electron microscopy
Not performed.
Precise diagnosis
Mature B-cell neoplasm, cyclin D1-negative mantle cell lymphoma.

Survival data

Date diagnosis
10-2014
Treatment
10/2014: Patient first received chloraminophene and rituximab (2 courses). 12/2014: Patient was then treated with ibrutinib (140 mg x 4/day).
Complete remission
-
Treatment relat death
-
Relapse
-
Status
D
Date last follow
01-2015
Survival
4

Karyotype

Sample
Bone marrow
Culture time
96h DSP30/IL2
Banding
GTG
Results
45,XX,t(2;12)(p12;p13),add(9)(p13),add(11)(q23),-22[7]/46,XX[7]
Mol cytogenet technics
FISH
Mol cytogenet results
45,XX,t(2;12)(p12;p13). ish der(2)t(2;12)(WCP12p+), der(12)t(2;12)(WCP12p+)[2].

Other molec studies

Technics
CCND1 (BCL1) expression evaluated by RT-PCR.
Results
No CCND1 overexpression.

Images

Atlas Image
Partial GTG-banding karyotype of the t(2;12)(p12;p13).
Atlas Image
FISH analysis of the t(2;12)(p12;p13)translocation, using painting probe of the short arm of chromosome 12 (WCP12p probe)in green. Arrows indicate the der(2) and der(12) chromosomes.
Atlas Image
FISH analysis of the t(2;12) translocation, using BAC probe CCND2 RP11-264F23 in red and BAC probe RP11-530J6 located at 2q33 in green. Figure 3A is a normal metaphase and Figure 3B revealed the der(2) chromosome harboring CCND2 red signal.
Atlas Image
Leukemic phase of mantle cell lymphoma. Peripheral blood. Small to medium sized lymphoid cells with pale cytoplasm and slightly too markedly irregular nuclear contour, sometimes mimicking centrocytes. From a patient with 46,XX,t(2;12)(p12;p13).

Comments section

Comments
According to the WHO classification of hematopoietic tumours, mantle cell lymphoma (MCL) is defined as a B-cell neoplasm composed of monomorphic small to medium-sized lymphoid cells with a CCND1 (cyclin D1) translocation. In recent years, it has been observed a small subset of lymphomas resembling conventional MCL both morphologically and phenotypically, with a similar gene expression profile but lacking the CCND1 translocation (Fu et al, Blood, 2005). In 2013, Salaverria et al. investigated 40 well-defined CCDN1-negative MCL and identified 22 cases (55%) with CCND2 (cyclin D2) translocations (Salaverria et al, Blood, 2013). Interestingly, it was noted that CCND2 predominantly translocates to IG light chain genes (15/22, 68%) in contrast with CCND1 translocations. Finally, in CCND1-negative MCL, the identification of CCND2 gene rearrangement provides a very robust marker for diagnosis.

Article Bibliography

Pubmed IDLast YearTitleAuthors
161232182005Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling.Fu K et al
232555532013CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma.Salaverria I et al

Citation

S Nicolas Duployez, Laurent Pascal, Judith Bruge, Marie Fatoux, Catherine Roche-Lestienne

The t(2;12)(p12;p13), leading to the juxtaposition of the cyclin D2 CCND2 gene with the immunoglobulin kappa locus (IGK), defines a small subset of mantle cell lymphomas lacking cyclin D1 expression.

Atlas Genet Cytogenet Oncol Haematol. 2015-02-01

Online version: http://atlasgeneticsoncology.org/case-report/208879/the-t(2