Risk of Anaplastic Large-Cell Lymphoma (ALCL) in Cases of Late Seroma Formation After Breast Implant Insertion

Kun Hwang, MD, PhD; Hun Kim, PhD; Hyung Mook Kim, MD; Joo Ho Kim, MD


ePlasty. 2021;21:e4 

In This Article


Breast implant–associated ALCL is a rare type of lymphoma that was first described in 1997.[31] In this review, the term "late seroma" encompassed any fluid accumulation that occurred more than 1 year after surgery in patients with breast implants, following the definition presented by Bengtson et al.[6]

In total, the US Food and Drug Administration (FDA) is aware of approximately 733 case reports of ALCL in women with breast implants worldwide. The total number of implants worldwide is estimated to be between 5 million and 10 million.[32] On the basis of these figures, the frequency of breast implant–associated ALCL can be estimated as 12 per million (1 case/86,000 population) to 453 per million (1 case/2207 population).

As of January 5, 2020, the FDA has received a total of 733 medical device reports of breast implant–associated ALCL, including 36 deaths, of which 17 reports included information on the implant surface. Of the 733 total unique cases of breast implant–associated ALCL reported to the FDA, 496 cases were reported to have textured implants and 209 cases did not specify the implant surface. Of the 36 total patient deaths reported to the FDA, 16 cases reported textured implants and 19 cases did not contain information on the implant surface.[33]

To investigate the association of silicone breast implants with immunological abnormalities, Karlson et al[34] selected 200 women who had been exposed to silicone breast implants and 500 age-matched, nonexposed women as controls. No increased frequency of any immunological abnormalities was found in women exposed to silicone breast implants, except for anti-ssDNA.[34]

Despite the apparent strong association between breast implants and ALCL, which typically surrounds the implants, suggesting an etiologic relationship, the cause of breast implant–associated ALCL remains unknown.[1]

Since concerns have been raised regarding seroma in breast implants, we searched the literature and found 3 articles that could be used to calculate the incidence.[5–7]

For ALCL and breast implants, we could not find articles containing many clinical cases. In the Lipworth et al[8] review, 48 cases of NHL were found in 43,537 breast implants (Table 2, top). de Jong et al[9] reported that 11 patients had ALCL among 389 patients with primary lymphoma of the breast (2.83%) (Table 2, bottom). Primary lymphomas of the breast are almost always NHL, and only 29 cases of Hodgkin lymphoma have been reported.[10–29] Therefore, the incidence of ALCL in breast implants was calculated by multiplying the incidence of NHL in breast implants by the incidence of ALCL in patients with breast lymphoma (0.0031%).

It is interesting that late seromas had not been mentioned in the era of smooth implants; instead, late seromas were only reported after the introduction of textured implants.[5]

The studies used for our analysis included confirmed ALCL cases. In our present review, seroma was reported in 0.16% of patients with implants and ALCL was found in 0.0031% of patients with implants. Moreover, 60.59% of patients with ALCL had seroma. The expected incidence of ALCL in patients with seroma was 1.21% (Figure 2).

The risk of ALCL was significantly higher in patients with late seroma than in those without seroma (OR = 998.93).

Clemens et al[35] emphasized that is important to differentiate between breast implant–associated ALCL and late seroma, as they are distinct unrelated processes, despite the common misperception that they are on a continuum, with one leading into the other. Benign fluid collections are not precursors to the development of breast implant–associated ALCL, and, to date, no cases have been reported of recurrent benign seromas converting to a CD30-positive effusion.[35]

Recently, Hanson et al[36] utilized in situ enzyme-linked immunosorbent assay (ELISA) to screen 9 patients with breast implant–associated ALCL and demonstrated that CD30 was detected in all breast implant–associated effusions at full and all serial concentrations. However, the breast implant–associated ALCL serum specimens and all control specimens showed negative findings.[36]

On the basis of the aforementioned studies, it is recommended to test all delayed seromas that are not otherwise readily explainable with CD30 immunohistochemistry.

We suggest the following protocol for managing patients presenting with a late seroma:

  1. Ultrasonography-guided aspiration is performed with ELISA for CD30.

  2. In recurrent seroma with persistently negative markers, the implant is removed.

  3. If an abnormal capsule is seen, it is biopsied and sent for a pathological examination.

  4. A smooth-surfaced implant is inserted if necessary.