Clinical, pathological, and molecular features of breast implant–associated DLBCLs
| Case . | Clinical presentation and staging . | Treatment and follow-up . | Pathological features . | Phenotypical features . | EBV status . | Cell of origin . | Clonality . | Cytogenetic and molecular features . |
|---|---|---|---|---|---|---|---|---|
| 1 | 72-y-old female, no symptoms. Removal of silicone macrotextured implant (Allergan) for esthetical issues 8 y after left breast adenocarcinoma | “Watch and wait” | Left capsulectomy showing patchy infiltrate of large pleomorphic cells invading the capsule with fibrinous deposits and necrotic areas | Positive markers: CD45, CD19 (w), CD20, CD22 (w) CD79a, PAX5, CD30, MUM1, CD43, CD138(w), BCL2, MYC (40%), Ki67 (∼100%) | Tumor*: LMP1+ EBNA2+ EBER+ Plasma: 3183 U/mL† | ABC according to IHC (unclassified according to RT-MLPA) | Major monoclonal Ig rearrangement and minor TCR rearrangement (1-2% T cells‡) | FISH: no rearrangement of BCL2, BCL6, MYC. aCGH: no detectable aberration |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 19 mo from surgery | Inflammatory background of plasma cells and neutrophils | P-STAT3: negative; CD56 and HHV8: negative | tNGS (30% tumor cells‡): damaging somatic mutations of IRF4 (p.L24F; VAF 10.4%), ARID1A (p.H684Y; VAF 3.37%), TET2 (p.R1465§; VAF 4.5%) | ||||
| 2 | 61-y-old female, no symptoms. Incidental detection of PET fixation around silicone macrotextured implants (Allergan) 13 y after right breast adenocarcinoma | Watch and wait | Right capsulectomy showing a plurinodular infiltrate of large cells with plasmablastic features invading the capsule with fibrinous deposits | Positive markers: CD45, CD79a (w/F), CD4 (w/F), CD30 (F), MUM1, CD10 (F), Bcl6 (F), κ, MYC (70%), PD1 (20%), EMA (F), Ki67(∼100%) | Tumor*: LMP1- EBNA2- EBER+; plasma: 1990 U/mL† | ABC according to RT-MLPA (unclassified according to IHC) | Major monoclonal IG rearrangement and minor TCR rearrangement (10% T-cells‡) | FISH: IGH-MYC translocation, no rearrangement of BCL2 or BCL6. aCGH: X monosomy, 7q deletion, 13q deletion involving RB1) and 14q deletion (involving IGH) |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 21 mo from surgery | Inflammatory background of plasma cells and reactive lymphoid follicles | P-STAT3: positive; CD56, CD138 and HHV8: negative | tNGS (90% tumor cells‡): damaging somatic mutations of STAT3 (pG1618R; VAF 48%), SOCS1 (p.Y203N; VAF 46%), FOXO1 (pS205R; VAF 45%), CCND2 (pV284G, VAF 43%) | ||||
| 3 | 69-y-old female, no symptoms. Removal of silicone macrotextured implant (Allergan) for esthetical issues 9 y after cosmetic breast augmentation | Chemotherapy (3 R-CHOP cycles) with intrathecal prophylaxis | Right capsulectomy showing patchy infiltrate of large pleomorphic cells invading the capsule with fibrinous deposits and necrotic areas | Positive markers: CD45, CD19, CD20, CD22, CD79a, CD30, MUM1, Bcl2, Λ light chain, Ki67 (80%) | Tumor§: LMP1+ EBNA2+ EBER+; plasma: ND | ABC according to IHC | Major monoclonal Ig rearrangement and minor TCR rearrangement (1-2% T-cells‡) | FISH: no rearrangement of BCL2, BCL6, MYC. aCGH: no detectable aberration |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 20 mo from end of treatment | Inflammatory background of plasma cells and reactive lymphoid follicles | P-STAT3: negative; CD56, CD138 and HHV8: negative | tNGS (20% tumor cells‡): damaging somatic mutations of ARID5B (p.P79T, VAF 12%), EXT2 (p.S270L, VAF 10%), CREBBP (p.M721I, VAF 8.5%), GNA13 (p.P6L, VAF 5.1%) |
| Case . | Clinical presentation and staging . | Treatment and follow-up . | Pathological features . | Phenotypical features . | EBV status . | Cell of origin . | Clonality . | Cytogenetic and molecular features . |
|---|---|---|---|---|---|---|---|---|
| 1 | 72-y-old female, no symptoms. Removal of silicone macrotextured implant (Allergan) for esthetical issues 8 y after left breast adenocarcinoma | “Watch and wait” | Left capsulectomy showing patchy infiltrate of large pleomorphic cells invading the capsule with fibrinous deposits and necrotic areas | Positive markers: CD45, CD19 (w), CD20, CD22 (w) CD79a, PAX5, CD30, MUM1, CD43, CD138(w), BCL2, MYC (40%), Ki67 (∼100%) | Tumor*: LMP1+ EBNA2+ EBER+ Plasma: 3183 U/mL† | ABC according to IHC (unclassified according to RT-MLPA) | Major monoclonal Ig rearrangement and minor TCR rearrangement (1-2% T cells‡) | FISH: no rearrangement of BCL2, BCL6, MYC. aCGH: no detectable aberration |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 19 mo from surgery | Inflammatory background of plasma cells and neutrophils | P-STAT3: negative; CD56 and HHV8: negative | tNGS (30% tumor cells‡): damaging somatic mutations of IRF4 (p.L24F; VAF 10.4%), ARID1A (p.H684Y; VAF 3.37%), TET2 (p.R1465§; VAF 4.5%) | ||||
| 2 | 61-y-old female, no symptoms. Incidental detection of PET fixation around silicone macrotextured implants (Allergan) 13 y after right breast adenocarcinoma | Watch and wait | Right capsulectomy showing a plurinodular infiltrate of large cells with plasmablastic features invading the capsule with fibrinous deposits | Positive markers: CD45, CD79a (w/F), CD4 (w/F), CD30 (F), MUM1, CD10 (F), Bcl6 (F), κ, MYC (70%), PD1 (20%), EMA (F), Ki67(∼100%) | Tumor*: LMP1- EBNA2- EBER+; plasma: 1990 U/mL† | ABC according to RT-MLPA (unclassified according to IHC) | Major monoclonal IG rearrangement and minor TCR rearrangement (10% T-cells‡) | FISH: IGH-MYC translocation, no rearrangement of BCL2 or BCL6. aCGH: X monosomy, 7q deletion, 13q deletion involving RB1) and 14q deletion (involving IGH) |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 21 mo from surgery | Inflammatory background of plasma cells and reactive lymphoid follicles | P-STAT3: positive; CD56, CD138 and HHV8: negative | tNGS (90% tumor cells‡): damaging somatic mutations of STAT3 (pG1618R; VAF 48%), SOCS1 (p.Y203N; VAF 46%), FOXO1 (pS205R; VAF 45%), CCND2 (pV284G, VAF 43%) | ||||
| 3 | 69-y-old female, no symptoms. Removal of silicone macrotextured implant (Allergan) for esthetical issues 9 y after cosmetic breast augmentation | Chemotherapy (3 R-CHOP cycles) with intrathecal prophylaxis | Right capsulectomy showing patchy infiltrate of large pleomorphic cells invading the capsule with fibrinous deposits and necrotic areas | Positive markers: CD45, CD19, CD20, CD22, CD79a, CD30, MUM1, Bcl2, Λ light chain, Ki67 (80%) | Tumor§: LMP1+ EBNA2+ EBER+; plasma: ND | ABC according to IHC | Major monoclonal Ig rearrangement and minor TCR rearrangement (1-2% T-cells‡) | FISH: no rearrangement of BCL2, BCL6, MYC. aCGH: no detectable aberration |
| ECOG = 0, normal PET scan, normal LDH; stage I, aaIPI = 0 | Complete remission 20 mo from end of treatment | Inflammatory background of plasma cells and reactive lymphoid follicles | P-STAT3: negative; CD56, CD138 and HHV8: negative | tNGS (20% tumor cells‡): damaging somatic mutations of ARID5B (p.P79T, VAF 12%), EXT2 (p.S270L, VAF 10%), CREBBP (p.M721I, VAF 8.5%), GNA13 (p.P6L, VAF 5.1%) |
aaIPI, age-adjusted International Prognostic Index; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; EBER, EBV-encoded small RNA: F, focal; FISH, fluorescence in situ hybridization; Ig, immunoglobulin; IHC, immunohistochemistry; LDH, lactate dehydrogenase; ND, not done; RT-MLPA; reverse transcriptase multiplex ligation-dependent probe amplification; TCR, T-cell receptor; VAF, variant allele frequency; w, weak.
Positivity for EBER restricted to virtually all large (CD30+) lymphoma cells, with negativity of reactive T cells.
Highest detected value among different postresection time points (detailed in supplemental Results).
Percentage of cells in the macrodissected area used for DNA extraction.
Stop codon.