Breast implant-associated anaplastic large cell lymphoma: a diagnostic challenge
Linfoma anaplásico de células grandes associado a implante mamários: um desafio diagnóstico

INTRODUCTION

The 2016 World Health Organization’s (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues¹ recognizes Breast Implant- Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) as a provisional entity, with morphological and immunophenotypic features indistinguishable from those of ALK-negative anaplastic large cell lymphoma (ALCL). Unlike ALCL, BIA-ALCL arises primarily in association with breast implantation².

BIA-ALCL is a very rare disease (1 case per 1-3 million women with implants), which may be localized to the seroma cavity, or may involve the pericapsular fibrous tissue. Most patients present with a peri-implant effusion, and present less frequently with a mass. Diagnosis is performed by aspirating the effusion around the implant and confirming the CD30-positivity of cells within the sample. However, confirming the diagnosis may be difficult. Associating of presence of hallmark cells with the results of flow cytometry and immunohistochemistry can aid accurate diagnosis^3-4.

Most patients have an excellent prognosis upon complete removal of the capsule, and upon surgically implanting a prosthesis with negative margins.^5-6.

OBJECTIVE

To describe a BIA-ALCL case in which cytology and flow cytometry analysis suggested the presence of CD30-positive large cells in the effusion fluid.

CASE REPORT

A 52-year-old woman with a history of breast cancer presented with left breast swelling and local pain. Seven years before, she had undergone a modified radical mastectomy of her left breast and had thereafter undergone immediate breast reconstruction with tissue expander. She had then developed a surgical infection, and shortly thereafter had the expander removed. Six months after completing radiotherapy, she had undergone another breast reconstruction using a latissimus dorsi flap and textured anatomical-shaped implant. Upon presentation, imaging revealed a peri-implant effusion. Approximately 100 ml of cloudy, yellow fluid was collected and immediately sent to the flow cytometry lab. Cytological examination revealed numerous large, anaplastic cells with pleomorphic nuclei, prominent nucleoli, and moderate basophilic cytoplasm with frequent vacuoles (Figure 1). Multiparametric flow cytometry (MFC) immunophenotyping revealed large tumor cells (increased FSC/SSC scatter) with bright expression of CD30, CD45, CD25 and HLA-DR, as well as the absence of CD3 expression within T-lineage cells and a lack of the B-cell antigens CD19 and CD20 (Figure 2). The patient underwent a bilateral breast implant removal and a total capsulectomy. Pathological examination of the seroma then confirmed the presence of clustered large lymphoma cells that were immunohistochemically positive for CD30 and negative for CD20 and CD3 (Figure 3). However, histologic sections of the breast capsule showed only fibrin admixed with infiltrating reactive lymph histiocytes.

Figure 1 - Cytomorphology revealed diffuse infiltration by hallmark anaplastic lymphoma cells.

Figure 1 - Cytomorphology revealed diffuse infiltration by hallmark anaplastic lymphoma cells.

Figure 2 - Multiparameter flow cytometry showing abnormal large cells (red) that were positive to CD30 and HLA-DR. Normal T lymphocytes (blue) and monocytes (yellow) are also shown.

Figure 2 - Multiparameter flow cytometry showing abnormal large cells (red) that were positive to CD30 and HLA-DR. Normal T lymphocytes (blue) and monocytes (yellow) are also shown.

Figure 3 - Immunohistochemical analysis of seroma fluid revealed strong CD30 positivity.

Figure 3 - Immunohistochemical analysis of seroma fluid revealed strong CD30 positivity.

MFC was performed using an 8-color Becton Dickinson FACS Canto II cytometry system with FACS Diva 8 software for data acquisition, and Infinicyt™ for flow cytometry analysis. The neoplastic cell population exhibited bright co-expression of CD30, CD25 and HLA-DR, which was confirmed by immunohistochemistry of the seroma fluid. While this bright expression pattern may not be specific for ALCL, it is easily identifiable and may thus increase the sensitivity of BI-ALCL detection.

It is important to emphasize that the flow cytometry sample was immediately sent to the laboratory, in natura and at room temperature, and was immediately processed to prevent cell destruction and the loss of antigen strength.

CONCLUSION

CD30-positive BI-ALCL is a rare type of T-cell lymphoma that remains a diagnostic challenge. The challenging nature of BI-ALCL diagnosis underscores the importance of correlating precise immunophenotypic analysis with morphologic evaluation and clinical pathology. Multiparameter flow cytometry can aid in the diagnostic evaluation of effusions or tissue samples in association with breast implantation/prostheses.