Mature -B-Cell Neoplasms
Description:
TESTS AVAILABLE: Karyotyping and FISH.
FISH:
Chronic lymphocytic leukaemia/small lymphocytic/B-cell pro lymphocytic lymphoma (CLL/SLL/B-PLL) FISH Panel: 11q22.3 deletion ATM 11q22 Deletion Probe Trisomy 12 and deletions of chromosome 13q14, 13q34 LSI D13S319 / LSI 13q34 / CEP 12 Multi-colour Probe; 17p13.1 deletion TP53 Spectrum Orange/ CEP 17 Spectrum Green Probe; 14q32 rearrangement IGH Dual Colour, Break Apart Rearrangement Probe.
Lymphoproliferative disorders NOS: 14q32 rearrangement IGH Dual Colour, Break Apart Rearrangement Probe
Extranodal marginal zone B-cell lymphoma (MALT lymphoma) t(11;18)(q21;q21): 14q32 rearrangement; Trisomy for chromosome 3 ; API2/MALT1 t(11;18)(q21;q21) Dual Colour, Dual Fusion Translocation ; IGH Dual Colour, Break Apart Rearrangement Probe; CEP 3
Nodal marginal zone lymphoma: Trisomy for chromosome 3, CEP 3
Splenic marginal zone lymphoma: Trisomy for chromosome 3, t(9;14)(p13;q32), CEP 3, PAX 5 Break Apart Rearrangement Probe, Follicular lymphoma t(14;18)(q32;q21) IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe
Mantle cell lymphoma: t(11;14)(q13;q32) IGH/CCND1 Dual Colour, Dual Fusion Translocation Probe
Diffuse large B-cell lymphoma (probes can be ordered individually): 3q27 rearrangements, 18q21 rearrangements, t(14;18)(q32;q21) and t(8;14)(q24.1;q32) 8q24 rearrangements BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe
Burkitt lymphoma/leukaemia: t(8;14)(q24.1;q32) and t(14;18)(q32;q21), 8q24 rearrangements, 3q27 rearrangements, 18q21 rearrangements, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe, BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe.
B-cell Lymphoma unclassifiable with features intermediate between DLBCL and Burkitt Lymphoma : t(14 ;18)(q32;q21) and t(8;14)(q24.1;q32) and variants 8q24 rearrangements, 3q27 rearrangement, 18q21 rearrangements, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe, BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe.
Please note these probes will be undertaken on all cases where morphology indicates disease infiltration in conjunction with cytogenetics where appropriate.
For all disease types with a positive result for IGH rearrangement a panel consisting of IGH/CCND1, IGH/BCL2 and when appropriate IGH/MYC/CEP8 will be applied.
In the case of new diagnostic Burkitt lymphomas where a sample is received before 12 noon a same day FISH result will be available on a direct culture for MYC rearrangement.
FISH:
Chronic lymphocytic leukaemia/small lymphocytic/B-cell pro lymphocytic lymphoma (CLL/SLL/B-PLL) FISH Panel: 11q22.3 deletion ATM 11q22 Deletion Probe Trisomy 12 and deletions of chromosome 13q14, 13q34 LSI D13S319 / LSI 13q34 / CEP 12 Multi-colour Probe; 17p13.1 deletion TP53 Spectrum Orange/ CEP 17 Spectrum Green Probe; 14q32 rearrangement IGH Dual Colour, Break Apart Rearrangement Probe.
Lymphoproliferative disorders NOS: 14q32 rearrangement IGH Dual Colour, Break Apart Rearrangement Probe
Extranodal marginal zone B-cell lymphoma (MALT lymphoma) t(11;18)(q21;q21): 14q32 rearrangement; Trisomy for chromosome 3 ; API2/MALT1 t(11;18)(q21;q21) Dual Colour, Dual Fusion Translocation ; IGH Dual Colour, Break Apart Rearrangement Probe; CEP 3
Nodal marginal zone lymphoma: Trisomy for chromosome 3, CEP 3
Splenic marginal zone lymphoma: Trisomy for chromosome 3, t(9;14)(p13;q32), CEP 3, PAX 5 Break Apart Rearrangement Probe, Follicular lymphoma t(14;18)(q32;q21) IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe
Mantle cell lymphoma: t(11;14)(q13;q32) IGH/CCND1 Dual Colour, Dual Fusion Translocation Probe
Diffuse large B-cell lymphoma (probes can be ordered individually): 3q27 rearrangements, 18q21 rearrangements, t(14;18)(q32;q21) and t(8;14)(q24.1;q32) 8q24 rearrangements BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe
Burkitt lymphoma/leukaemia: t(8;14)(q24.1;q32) and t(14;18)(q32;q21), 8q24 rearrangements, 3q27 rearrangements, 18q21 rearrangements, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe, BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe.
B-cell Lymphoma unclassifiable with features intermediate between DLBCL and Burkitt Lymphoma : t(14 ;18)(q32;q21) and t(8;14)(q24.1;q32) and variants 8q24 rearrangements, 3q27 rearrangement, 18q21 rearrangements, IGH/BCL2 Dual Colour, Dual Fusion Translocation Probe, IGH/MYC, CEP 8 Tri-colour, Dual Fusion Translocation Probe, MYC Dual Colour, Break Apart Rearrangement Probe, BCL6 Dual Colour, Break Apart Rearrangement Probe, BCL2 Dual Colour, Break Apart Rearrangement Probe.
Please note these probes will be undertaken on all cases where morphology indicates disease infiltration in conjunction with cytogenetics where appropriate.
For all disease types with a positive result for IGH rearrangement a panel consisting of IGH/CCND1, IGH/BCL2 and when appropriate IGH/MYC/CEP8 will be applied.
In the case of new diagnostic Burkitt lymphomas where a sample is received before 12 noon a same day FISH result will be available on a direct culture for MYC rearrangement.
Clinical details:
The WHO classification takes account of 29 mature B-cell neoplasms of which only the most relevant will be dealt with here. It would be advisable to consult the latest WHO Classification of tumours of Haematopoietic and Lymphoid tissues when and where necessary.
1. Chronic lymphoblastic leukaemia /small lymphocytic lymphoma (CLL/SLL). This is a neoplasm with a persistent lymphocytosis and CD5 and CD23 expression. Approximately 80% of cases have cytogenetic abnormalities detected by FISH . The most common are deletion of 13q14, trisomy 12, 11q22 (ATM) deletion, 17p123 (TP53) deletion and IGH@ rearrangement. Prognosis is good for isolated 13q14 deletion, intermediate for trisomy 12 and poor for TP53 and ATM deletion. Approximately 2-8% of patients with CLL develop DLBCL (Richter’s transformation) and this has very poor survival rates.
2. B-Cell Prolymphocytic leukaemia(B-PLL). This is an extremely rare disease and has poor survival outcomes. Complex karyotypes are common with TP53 deletion and inv(14).
3. Extranodal marginal zone Lymphoma (MALT). Chromosomal translocations associated with MALT include t(11;18)(q21q21) (APL12/MALT), t(1;14)(p22q32), t(14;18)(q32;q21) and t(3;14)(p14.1q32) causing up regulation of BCL10, MALT1 and FOXP1 respectively. Cases with t(11;18) are resistant to H.pylori eradication therapy but otherwise prolonged remissions are common.
4. Follicular Lymphoma (FL) . This neoplasm is genetically characterised by the t(14;18)(q32;q21) or another BCL2 rearrangement. FISH seems to be the most sensitive technique for picking this up. Abnormalities of 3q27(BCL60) have also been reported. More complex karyotypes or those with TP53 deletion, +12, +18 have a poor outcome and a greater chance of transformation. The use of FISH for BCL6 in t(14;18) NEG cases could be considered.
5. Mantle Cell Lymphoma. This neoplasm is genetically characterised by the t(11;14)(q13;q32) (IGH/CCND1). Variant CCND1 translocations have been reported. MCL also carries a high number of non random secondary chromosomal aberrations including gains of 3q26, 7p21 and trisomy 12. MCL may also demonstrate tetraploid clones.
6. Burkitts Lymphoma (BL). This is a neoplasm with an extremely short doubling time that often presents in an extra nodal site or as an acute leukaemia. Most of the cases have MYC translocation (8q24), most commonly to IGH (14q32), but also to 22q11(lambda), and 2p12 (kappa). MYC translocation is not specific for Burkitts. Other genetic alterations seen in BL involve TP53 and BCL6. Bone marrow involvement in Burkitts is a poor prognostic factor but high intensity chemotherapy regimes have seen response rates improve.
7. Diffuse large B-cell Lymphoma (DLBCL). No defining cytogenetic abnormalities are required for the diagnosis of DLBCL. This neoplasm of large B-lymphoid cells shows in up to 30% of cases abnormalities of 3q27(BCL6), 20-30% have the t(14;18)(q32;q21). A MYC rearrangement can be seen in 10% of cases but these are now best reclassified as grey zone lymphoma. DLBCL has a number of subtypes including plasmablastic lymphoma (in the mouth), T-cell rich large B-cell lymphoma (aggressive variant), and primary effusion lymphoma (HIV associated).
8. ALK - Large B-cell Lymphoma (ALBCL). This neoplasm is associated with the t(2;17)(p23;q23) (CLTC-ALK) fusion protein and is associated with a poor prognosis
9. B-cell Lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitts Lymphoma (Grey Zone Lymphomas). Approximately 35-50% of cases have MYC translocations but usually non IG-MYC. Some have BCL2 and MYC rearrangement (Double hit) and some have BCL2, MYC and BCL6 (triple hit). Cases are usually associated with a complex karyotype. These are aggressive lymphomas.
1. Chronic lymphoblastic leukaemia /small lymphocytic lymphoma (CLL/SLL). This is a neoplasm with a persistent lymphocytosis and CD5 and CD23 expression. Approximately 80% of cases have cytogenetic abnormalities detected by FISH . The most common are deletion of 13q14, trisomy 12, 11q22 (ATM) deletion, 17p123 (TP53) deletion and IGH@ rearrangement. Prognosis is good for isolated 13q14 deletion, intermediate for trisomy 12 and poor for TP53 and ATM deletion. Approximately 2-8% of patients with CLL develop DLBCL (Richter’s transformation) and this has very poor survival rates.
2. B-Cell Prolymphocytic leukaemia(B-PLL). This is an extremely rare disease and has poor survival outcomes. Complex karyotypes are common with TP53 deletion and inv(14).
3. Extranodal marginal zone Lymphoma (MALT). Chromosomal translocations associated with MALT include t(11;18)(q21q21) (APL12/MALT), t(1;14)(p22q32), t(14;18)(q32;q21) and t(3;14)(p14.1q32) causing up regulation of BCL10, MALT1 and FOXP1 respectively. Cases with t(11;18) are resistant to H.pylori eradication therapy but otherwise prolonged remissions are common.
4. Follicular Lymphoma (FL) . This neoplasm is genetically characterised by the t(14;18)(q32;q21) or another BCL2 rearrangement. FISH seems to be the most sensitive technique for picking this up. Abnormalities of 3q27(BCL60) have also been reported. More complex karyotypes or those with TP53 deletion, +12, +18 have a poor outcome and a greater chance of transformation. The use of FISH for BCL6 in t(14;18) NEG cases could be considered.
5. Mantle Cell Lymphoma. This neoplasm is genetically characterised by the t(11;14)(q13;q32) (IGH/CCND1). Variant CCND1 translocations have been reported. MCL also carries a high number of non random secondary chromosomal aberrations including gains of 3q26, 7p21 and trisomy 12. MCL may also demonstrate tetraploid clones.
6. Burkitts Lymphoma (BL). This is a neoplasm with an extremely short doubling time that often presents in an extra nodal site or as an acute leukaemia. Most of the cases have MYC translocation (8q24), most commonly to IGH (14q32), but also to 22q11(lambda), and 2p12 (kappa). MYC translocation is not specific for Burkitts. Other genetic alterations seen in BL involve TP53 and BCL6. Bone marrow involvement in Burkitts is a poor prognostic factor but high intensity chemotherapy regimes have seen response rates improve.
7. Diffuse large B-cell Lymphoma (DLBCL). No defining cytogenetic abnormalities are required for the diagnosis of DLBCL. This neoplasm of large B-lymphoid cells shows in up to 30% of cases abnormalities of 3q27(BCL6), 20-30% have the t(14;18)(q32;q21). A MYC rearrangement can be seen in 10% of cases but these are now best reclassified as grey zone lymphoma. DLBCL has a number of subtypes including plasmablastic lymphoma (in the mouth), T-cell rich large B-cell lymphoma (aggressive variant), and primary effusion lymphoma (HIV associated).
8. ALK - Large B-cell Lymphoma (ALBCL). This neoplasm is associated with the t(2;17)(p23;q23) (CLTC-ALK) fusion protein and is associated with a poor prognosis
9. B-cell Lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitts Lymphoma (Grey Zone Lymphomas). Approximately 35-50% of cases have MYC translocations but usually non IG-MYC. Some have BCL2 and MYC rearrangement (Double hit) and some have BCL2, MYC and BCL6 (triple hit). Cases are usually associated with a complex karyotype. These are aggressive lymphomas.
Synonyms or keywords:
Burkitt's, MCL, MZL, DLBCL, CLL/SLL MYC, CCND1
Department:
Location:
Sample type and Volume required:
In case of CLL/SLL Blood in Lithium Heparin
Bone Marrow Aspirate -first draw for both Cytogenetics and FISH studies. BM smears slides are accepatable for FISH studies only.
Bone Marrow Aspirate -first draw for both Cytogenetics and FISH studies. BM smears slides are accepatable for FISH studies only.
Turnaround time:
Please refer to Cytogenetics User Guide
Special sample instructions:
All samples must be delivered to the laboratory within 24 hours of collection.
Contacts:
SE-HMDS Department at King's College Hospital
020 3299 9000 ext 32414
c/o Central Specimen Reception
Blood Sciences Laboratory
Ground Floor Bessemer Wing
King’s College Hospital
Denmark Hill
London SE5 9RS
Mon-Fri, 9.00am-5.30pm
Blood Sciences Laboratory
Ground Floor Bessemer Wing
King’s College Hospital
Denmark Hill
London SE5 9RS
Mon-Fri, 9.00am-5.30pm
Laboratory:
Last updated: 03/07/2017
