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Null-Type Anaplastic Lymphoma Kinase–Negative Anaplastic Large Cell Lymphoma Arising in a Silicone Breast Implant Capsule

Lazzeri, Davide M.D.; Agostini, Tommaso M.D.; Giannotti, Giordano M.D.; Fanelli, Giovanni M.D.; Colizzi, Livio M.D.; Pantaloni, Marcello M.D.; Sordi, Elisabetta M.D.

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Plastic and Reconstructive Surgery: June 2011 - Volume 127 - Issue 6 - p 159e-162e
doi: 10.1097/PRS.0b013e318213a1bd
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A 58-year-old white woman who had undergone bilateral cosmetic breast augmentation with Inamed McGhan smooth silicone gel breast implants 19 years previously presented with a painful right breast and Baker grade III capsular contracture without evidence of breast mass or lymphadenopathy. In 2006, her device had already been replaced in a private clinical structure for the same complication. At admission, she was otherwise in good health. Her blood count and serum chemistry values were normal. No local mammary or systemic cutaneous manifestations were observed. Mammography was unremarkable. Both implants were removed and the submuscular pouch was explored, with drainage of a serous-hematic fluid surrounding the right prosthesis. Capsulectomy was performed and the removed fibrous tissue analyzed because of its altered aspect. The pathologic findings were consistent with a diagnosis of null-type, anaplastic lymphoma kinase–negative, non-Hodgkin's anaplastic large cell lymphoma (ALCL) (Figs. 1 and 2). Computed tomographic and positron emission computed tomographic scanning revealed no further lymphoma localization; thus, it was classified as a stage I systemic ALCL. Because the patient refused radiation therapy, she underwent a combined chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine, and prednisone. To date (21 months' follow-up), there is no evidence of recurrence.

Fig. 1.:
ALCL slide showing large blastic cells with abundant cytoplasm and eccentric nuclei that are generally horseshoe shaped or reniform with prominent nucleoli (hematoxylin and eosin; original magnification, ×400).
Fig. 2.:
Typical immunophenotype of null-type [no expression of T-cell marker CD3 (above, right) or the B-cell marker CD20 (above, left)] ALCL [intense expression of CD30 (below, left)] and showing no expression of anaplastic lymphoma kinase (below, right) (original magnification, ×200).

The presenting symptom in virtually all cases of primary breast lymphoma is a mass-type lesion, sometimes painful and located most often in the upper outer quadrant. In contrast, patients who developed breast lymphoma following prosthesis implantation had implant-related symptoms with or without a mass-type lesion, including breast mass or enlargement, tenderness, capsular contracture, swelling, seroma, and skin ulceration.1–4 Primary breast lymphoma arising in the setting of a breast prosthetic capsule has recently been supposed to be associated with breast implants, since 45 cases have been observed in the literature.5–7 Surprisingly, even if primary breast lymphomas are commonly phenotypically B-cell, those associated with implants are predominately T-cell type. In particular, 455–10 were ALCL, of which 33 cases were ALK-1 protein; in the remaining 12, the status was not proven. Among four more non-ALCL T-cell lymphomas observed,5 two patients had mycosis fungoides and two had Sezary syndrome, all arising in the skin overlying intact silicone implants. Only four B-cell lymphomas were diagnosed further and subtyped as follicular lymphoma, primary effusion lymphoma, and lymphoplasmacytic lymphoma.

ALCLs are lymphomas of activated lymphocytes. Thus, the apparent increase in prevalence of T-cell lymphomas must be highlighted, particularly of the ALCL type, in patients with breast implants compared with the overall more common B-cell lymphomas seen in the breast. In light of this, the development of ALCL in the proximity of breast implants might be a consequence of an immunologic reaction to the device components. Although various authors have proposed that activation of immunologic mechanisms secondary to exposure to silicone or toluene diamine from polyurethane covers on implants and Staphylococcus infection may lead to the development of a malignant T-cell clone, these hypotheses do not seem to be likely.1–4

Patients with a diagnosis of implant-related ALCL have had implants that were either ruptured or intact, filled either with saline or with silicone gel, and placed for either reconstructive or cosmetic purposes; these varying circumstances have not appeared to make any difference.5,6 Although large observational epidemiological studies in North American and Scandinavian women have disproved significant associations with breast cancer or other specific cancer sites or with autoimmune disease,11–17 currently, clinical and histological findings of two major reviews5,6 speak in favor of an association between breast implants and ALK-1–negative ALCL, which presumably is an indolent form of this group of non–Hodgkin's lymphoma that is completely distinct from the systemic disease with a clinical behavior more similar to primary cutaneous ALCL than to the systemic counterpart. Thus, several authors agree that implant-related ALCL should be recognized as a separate category in the World Health Organization's classification, with its own diagnosis and treatment.5,6 Thus, several authors agree that implant-related ALCL should be recognized as a separate category in the World Health Organization's classification, with its own diagnosis and treatment.5,6

The Danish Registry for Plastic Surgery of the Breast is the first registry in which preoperative, perioperative, and postoperative data for women undergoing breast augmentation in Denmark since 1999 are registered. Due to the newly emerging condition, a breast implant registry should be introduced worldwide in every country as a successful ongoing prospective registry of both cosmetic and reconstructive breast implantations, as recently established in the United States by the American Society of Plastic Surgeons in collaboration with the U.S. Food and Drug Administration.18,19

We presented the first case of primary null-cell type ALCL arising in a silicone breast implant capsule.


The authors have no financial interest to declare in relation to the content of this article.

Davide Lazzeri, M.D.

Plastic and Reconstructive Surgery Unit

Tommaso Agostini, M.D.

Burn Center Unit

Giordano Giannotti, M.D.

Plastic and Reconstructive Surgery Unit

Hospital of Pisa

Giovanni Fanelli, M.D.

Division of Surgical, Molecular, and Ultrastructural Pathology

Livio Colizzi, M.D.

Breast Cancer Surgical Unit

University Hospital of Pisa

Marcello Pantaloni, M.D.

Plastic and Reconstructive Surgery Unit

Hospital of Pisa

Elisabetta Sordi, M.D.

Division of Hematology

University Hospital of Pisa

Pisa, Italy


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