Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes

Abstract

Background: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants.

Patients and methods: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed.

Results: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively.

Conclusions: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

Keywords: anaplastic/Hodgkin-like subtypes; cytotoxic T-cell; implant-ALCL; mass; seroma.

Figure 1.

Distribution of lymphoma subtypes in 300 breast lymphomas registered in Lymphopath network from 2010 to 2014. Repartition of main lymphoma categories of all breast lymphomas in total number (n) and in percentage (%) (A). Relative frequencies of B- and T-cell lymphoma subtypes in total number (n) and in percentage (%) (B) (MALT L, mucosae-associated lymphoid tissue lymphoma; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; NHL NOS, non-Hodgkin lymphoma not otherwise specified; PTCL NOS, peripheral T-cell lymphoma not otherwise specified, ALK⁺ or ALK⁻ ALCL, anaplastic lymphoma kinase positive or negative anaplastic large cell lymphoma).

Figure 2.

Pathological features of i-ALCL subtypes. The in situ i-ALCL subtype shows a lymphoproliferation confined to the surface of the breast implant (black arrows), H&E ×400 (A). Tumor cells line the fibrous capsule, H&E ×200 (B), and consist in large pleomorphic tumor cells with irregular nuclei surrounded by a clear halo, H&E ×400 (C), with variable number anaplastic ‘hallmark’-like cells, H&E ×600 (D). The infiltrative i-ALCL subtype shows a lymphoproliferation invading capsule and surrounding tissue H&E ×400 (E). This subtype sometimes associated with fibrosis H&E ×100 (F) consist in sheets of large tumor cells with variable number of Hodgkin or Reed–Sternberg-like cells with an abundant inflammatory background H&E ×400 (G) and ×600 (H).

Figure 3.

i-ALCL with the two morphologic patterns. The case N°10 shows, beside a proliferation confined to the fibrous capsule (*), a focally bulging proliferation that invades capsule tissue (**) H&E ×40 (A), ×200 (B), ×200 (C), ×600 (D) and ×600 (E).

Figure 4.

Kaplan–Meier curve showing overall survival estimates for the in situ and infiltrative i-ALCL subtypes.

Figure 5.

Immunophenotype of i-ALCL. Tumor cells are positive for CD30, ×200 (A) and ×100 (B); EMA, ×600 (C); CD3, ×400 (D); CD4, ×200 (E); express cytotoxic granules of granzyme B, ×200 (F); PAX5, (×400) (G) and pSTAT3 (×200) (H).