Characteristics of 3 patients with ALK-positive LBCL
Characteristics . | Case 1 . | . | Case 2 . | Case 3 . |
|---|---|---|---|---|
| Age, y | 10 | 13 | 26 | |
| Sex | M | F | M | |
| Date of examination mo/y | 2/2002 | 5/2000 (at diagnosis) | 9/2001 (at relapse) | 2/1998 |
| Clinical presentation | Cervical mass | Cervical mass | Cervical lymph nodes, mediastinal mass, spleen, liver | Cervical adenopathy, tumor of base of tongue |
| Stage | 2 | 2 | 3 | 2 |
| Phenotype | CD3−, CD4−, CD5−, CD45−, CD15−, CD30−, EMA−, CD68−, ALK1+, CD20−, CD79a+ (w), CD138+ (s), lgκ−, lgλ+, lgA+, lgG− | Initial: CD2−, CD3−, CD4−, CD5−, CD45−, CD15−, CD30+, EMA+, ALK1+, CD20−, CD79a− | CD2−, CD3−, CD4−, CD5−, CD45−, CD15−, CD30+, EMA+, ALK1+, CD20−, CD22−, CD23−, CD79a+ (w), CD138+, lgκ−, lgλ+, lgA−, lgG+ | Initial: CD2−, CD3−, CD5−, CD20−, lgκ+, lgλ−, lgA+ |
| Reviewed: CD138+, lgκ−, lgλ+, lgA−, lgG+ | Reviewed: CD138+, ALK1+, CD30− | |||
| EBV* | Negative | Negative | Negative | nd |
| Genotype | PCR: IGH(FR3)-R; TCRβ-R, TCRγ-R | PCR: IGH(FR1)-R; TCRγ-R | PCR: IGH-R (FR1/2/3), Kde-R, IGL-R | SB: IGH-R, Kde-R, TCRγ-G |
| SB: IGH-R, Kde-R, TCRγ-G | ||||
| Diagnosis | ALK-positive LBCL | Initial: ALK-positive null-type ALCL | ALK-positive LBCL | Initial: DLBCL with plasma cell differentiation |
| Revised: ALK-positive LBCL | Revised: ALK-positive LBCL | |||
| Therapy | SFOP-LMB 96, group B | ALCL-99 HR | NHL-BFM ALCL99 with ALCL relapse, ABMT | CHOP 4×, VIM 1×, DHAP 1×: NR, RT 40 Gy (Waldeyer ring and neck), 30 Gy upper mediastinum: PD with new skeletal lesions in 1/1999: Hyper-C-VAD 3×: CR, 6/1999 ABMT after BEAM |
| Outcome | CR | CR | PR | CR |
| Follow-up, mo | 6 | 12 | 3‡ | 44 |
| Cytogenetics | Not successful | Not successful | 46-47,XX,i(1)(q10),der(2) add(2)(p13)t(2;3)(q37;q21), der(5)t(3;5)(q25;q34), add(6)(q10),+der(6) t(6;14)(p21;q11),+8,del(10) (p12),?inv(12)(q15q24),−14, add(17)(p11),add(17)(q15), +19,inc[cp7]§ | 44-46,XY,-Y,idic(1)(p11),del(2)(p23), del(5)(q23),+14,add(17)(?q23)[cp5]§ |
| RT-PCR | ALK-EC mRNA− | ALK-EC mRNA− | nd | ALK-EC mRNA− |
| ALK-C mRNA+ | ALK-C mRNA+ | nd | ALK-C mRNA+ | |
| FISH† (LSI ALK) | 1GO/2O/1G→ALK rearrangement | 1GO/1O/1G→ALK rearrangement | 1GO/1O/1G→ALK rearrangement→ der(2)add(2)(p13)t(2;3) (q37;q21).ish der(2)t(2;17) (p23;q23)t(2;3)(q37;q21); add(17)(q15).ish der(17)t(2;17) (p23;q23)§ | 1GO/1O/1G→ALK rearrangement→ del(2)(p23).ish der(2)t(2;17)(p23;q23); add(17)(?q23).ish der(17)t(2;17)(p23;q23)§ |
Characteristics . | Case 1 . | . | Case 2 . | Case 3 . |
|---|---|---|---|---|
| Age, y | 10 | 13 | 26 | |
| Sex | M | F | M | |
| Date of examination mo/y | 2/2002 | 5/2000 (at diagnosis) | 9/2001 (at relapse) | 2/1998 |
| Clinical presentation | Cervical mass | Cervical mass | Cervical lymph nodes, mediastinal mass, spleen, liver | Cervical adenopathy, tumor of base of tongue |
| Stage | 2 | 2 | 3 | 2 |
| Phenotype | CD3−, CD4−, CD5−, CD45−, CD15−, CD30−, EMA−, CD68−, ALK1+, CD20−, CD79a+ (w), CD138+ (s), lgκ−, lgλ+, lgA+, lgG− | Initial: CD2−, CD3−, CD4−, CD5−, CD45−, CD15−, CD30+, EMA+, ALK1+, CD20−, CD79a− | CD2−, CD3−, CD4−, CD5−, CD45−, CD15−, CD30+, EMA+, ALK1+, CD20−, CD22−, CD23−, CD79a+ (w), CD138+, lgκ−, lgλ+, lgA−, lgG+ | Initial: CD2−, CD3−, CD5−, CD20−, lgκ+, lgλ−, lgA+ |
| Reviewed: CD138+, lgκ−, lgλ+, lgA−, lgG+ | Reviewed: CD138+, ALK1+, CD30− | |||
| EBV* | Negative | Negative | Negative | nd |
| Genotype | PCR: IGH(FR3)-R; TCRβ-R, TCRγ-R | PCR: IGH(FR1)-R; TCRγ-R | PCR: IGH-R (FR1/2/3), Kde-R, IGL-R | SB: IGH-R, Kde-R, TCRγ-G |
| SB: IGH-R, Kde-R, TCRγ-G | ||||
| Diagnosis | ALK-positive LBCL | Initial: ALK-positive null-type ALCL | ALK-positive LBCL | Initial: DLBCL with plasma cell differentiation |
| Revised: ALK-positive LBCL | Revised: ALK-positive LBCL | |||
| Therapy | SFOP-LMB 96, group B | ALCL-99 HR | NHL-BFM ALCL99 with ALCL relapse, ABMT | CHOP 4×, VIM 1×, DHAP 1×: NR, RT 40 Gy (Waldeyer ring and neck), 30 Gy upper mediastinum: PD with new skeletal lesions in 1/1999: Hyper-C-VAD 3×: CR, 6/1999 ABMT after BEAM |
| Outcome | CR | CR | PR | CR |
| Follow-up, mo | 6 | 12 | 3‡ | 44 |
| Cytogenetics | Not successful | Not successful | 46-47,XX,i(1)(q10),der(2) add(2)(p13)t(2;3)(q37;q21), der(5)t(3;5)(q25;q34), add(6)(q10),+der(6) t(6;14)(p21;q11),+8,del(10) (p12),?inv(12)(q15q24),−14, add(17)(p11),add(17)(q15), +19,inc[cp7]§ | 44-46,XY,-Y,idic(1)(p11),del(2)(p23), del(5)(q23),+14,add(17)(?q23)[cp5]§ |
| RT-PCR | ALK-EC mRNA− | ALK-EC mRNA− | nd | ALK-EC mRNA− |
| ALK-C mRNA+ | ALK-C mRNA+ | nd | ALK-C mRNA+ | |
| FISH† (LSI ALK) | 1GO/2O/1G→ALK rearrangement | 1GO/1O/1G→ALK rearrangement | 1GO/1O/1G→ALK rearrangement→ der(2)add(2)(p13)t(2;3) (q37;q21).ish der(2)t(2;17) (p23;q23)t(2;3)(q37;q21); add(17)(q15).ish der(17)t(2;17) (p23;q23)§ | 1GO/1O/1G→ALK rearrangement→ del(2)(p23).ish der(2)t(2;17)(p23;q23); add(17)(?q23).ish der(17)t(2;17)(p23;q23)§ |
All cases showed monomorphic proliferation of large cells and a granular cytoplasmic ALK1 immunostaining pattern.
EMA indicates epithelial membrane antigen; EBV, Epstein-Barr virus; PCR, polymerase chain reaction; M, male; F, female; s, strong; w, weak; SB, Southern blot; SFOP-LMB, Société Française d'Oncologie Pédiatrique, étude lymphomes B; HR, high risk; NHL-BFM, non-Hodgkin lymphoma-Berlin-Frankfurt-Munster; ABMT, autologous bone marrow transplantation; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; VIM, etoposide, ifosfamide, and mitoxantrone; DHAP, dexamethasone, cytosine, arabinoside, and cisplatin; NR, no remission; RT, radiation therapy; PD, progressive disease; BEAM, BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), etoposide, cytosine, arabinoside, and melphalan; CR, complete remission; PR, partial remission; ALK-EC, extracellular portion of ALK; ALK-C, cytoplasmic portion of ALK; nd, not done; G, green signal; and O, orange signal.
Analyzed using anti-latent membrane protein 1 antibody and EBV-encoded RNA in situ hybridization.
Interphase and metaphase FISH experiments were performed on tissue imprints (case 1), cytogenetic specimen (case 2 [at diagnosis and relapse], case 3), and frozen section (case 2 [at relapse]).
Death.
Chromosomal aberrations are presented in accordance with the International System for Human Cytogenetic Nomenclature.13