BREAST

Managing Late Periprosthetic Fluid Collections (Seroma) in Patients with Breast Implants: A Consensus Panel Recommendation and Review of the Literature
Bradley Bengtson, M.D. Garry S. Brody, M.D. Mitchell H. Brown, M.D. Caroline Glicksman, M.D. Dennis Hammond, M.D. Hilton Kaplan, M.D., Ph.D. G. Patrick Maxwell, M.D. Michael G. Oefelein, M.D. Neal R. Reisman, M.D., J.D. Scott L. Spear, M.D. Mark L. Jewell, M.D. Late Periprosthetic Fluid Collection after Breast Implant Working Group
Grand Rapids, Mich.; Los Angeles, Goleta, and Irvine, Calif.; Toronto, Ontario, Canada; Sea Girt, N.J.; South Nashville, Tenn.; Houston, Texas; Washington, D.C., and Eugene, Ore.

Background: The goal of this consensus is to establish an algorithm for the management of patients who develop a late or delayed periprosthetic fluid collection. A work group of practicing plastic surgeons and device industry physicians met periodically by teleconference and discussed issues pertinent to the diagnosis and management of late periprosthetic fluid collections in patients with breast implants. Based on these meetings, treatment recommendations and a treatment algorithm were prepared in association with an editorial assistant. Method: The work group participants discussed optimal care approaches developed in their private practices and from evidence in the literature. Results: The consensus algorithm and treatment and management recommendations represent the consensus of the group. Conclusions: The group concluded that late periprosthetic fluid collection (arbitrarily defined as occurring 1 year after implant) is an infrequently reported occurrence (0.1 percent) after breast implant surgery and that, at a minimum, management should include clinically indicated ultrasound-guided aspiration of fluid, with appropriate cultures and cytologic testing. Further evaluation and additional treatment is recommended for recurrence of periprosthetic fluid collection after aspiration, or clinical suspicion of infection or neoplasia. (Plast. Reconstr. Surg. 128: 1, 2011.)

here are multiple risks and complications inherent in breast augmentation and reconstruction surgery with implants.13 The delayed periprosthetic collection of fluid that may occur months to years following breast augmentation or reconstruction surgery, commonly labeled late seroma, is an uncommon problem that may complicate management of the breast implant patient. The term blood serum or serum is defined as the clear liquid, without fibrinogen or other clotting factors, that can be separated from clotted
From the Bengtson Center for Aesthetics and Plastic Surgery; the Division of Plastic Surgery, Keck School of Medicine, University of Southern California; private practice; the Center for Breast and Body Contouring; Allergan Medical; Maxwell Aesthetics; Allergan, Inc.; Baylor College of Medicine; Georgetown University Hospital; and Jewell Plastic Surgery Center. Received for publication December 3, 2010; accepted February 15, 2011. Copyright 2011 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0b013e318217fdb0

Disclosure: Dr. Bengtson is a consultant for Allergan, Inc., and LifeCell Corporation; is a recipient of an Aesthetic Surgery Education and Research Foundation grant for high-resolution ultrasound research; and is an investigator in the Adjunct and Allergan 410 implant clinical studies. Drs. Brody and Reisman report no conflicts of interest. Drs. Brown and Spear are both consultants for Allergan and LifeCell. Drs. Glicksman and Maxwell are both consultants and investigators for Allergan. Dr. Hammond is a consultant for Mentor, LLC, and Allergan. Dr. Jewell is a consultant for Allergan, an approved clinical investigator for Mentor and Allergan, and an assistant clinical professor of plastic surgery at Oregon Health Science University, Portland, Oregon. Drs. Oefelein and Kaplan are both employees of Allergan. Allergans involvement in this study was limited to the participation of Drs. Kaplan and Oefelein, as authors. Allergan funded the editorial support of manuscript development.

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Plastic and Reconstructive Surgery July 2011

blood. Serum differs from plasma in that plasma is the liquid portion of normal unclotted blood in which the blood cells are suspended. It is the clotting factors (e.g., fibrinogen) that make the difference between serum and plasma. The term serum is commonly used to designate any normal or pathologic fluid that resembles serum, such as the fluid in a blister. Seroma is the generic term in common use for collections of clear serous fluid that may develop in dissected spaces after surgery. The term late seroma is a vague and poorly defined term that has established itself in the literature; however, the periprosthetic fluid accumulation around an implant may not be precisely serous in origin. If on examination the fluid is acellular with small quantities of protein (2.0 g/dl), it is a serous effusion. However, if the effusion fluid contains cells and protein (2.9 g/dl), it is an exudate. If the cells are predominantly red blood cells, it is a hematoma. Alternatively, if the cells are predominantly white blood cells, the effusion is inflammatory. Lastly, if cancer cells are present, the effusion is malignant. Further analysis (appearance, specific gravity, cell count, protein content, albumin, glucose, and lactate dehydrogenase concentration and cytologic analysis) may be required to more thoroughly characterize a periprosthetic fluid collection.4 6 For the purposes of this review, the term late periprosthetic fluid collection will be used for any fluid accumulation that may occur, in a delayed (arbitrarily defined as 1 year) fashion after surgery, in patients with breast implants. Late periprosthetic fluid collection is probably an underreported occurrence after breast implantation surgery, and few data exist as to the epidemiology, incidence, prevalence, and cause of this phenomenon in patients with breast implants.714 This work group was convened, in the absence of a controlled, clinical trial based evaluation, to examine the available literature on the development of late periprosthetic fluid collection in patients with breast implants, and to develop a consensus and best practice consensus algorithm for evaluation and management. This collected opinion should not suggest a standard of care. Instead, this algorithm is designed to provide a guideline for care and recommendations for the evaluation and management of late periprosthetic fluid collection in patients with breast implants, and not to define or limit the choices of the patient or surgeon.

PERIPROSTHETIC FLUID COLLECTION AFTER BREAST IMPLANT SURGERY: LITERATURE REVIEW

To identify published cases of clinically apparent late seroma occurring in breast implant recipients, a PubMed literature search was conducted from January of 1990 to October of 2010 using the search terms seroma and breast implant. Small amounts of fluid not uncommonly seen in magnetic resonance imaging or ultrasound studies were excluded. A manual search of the retrieved references returned eight relevant publications, most of which were case reports documenting the development of periprosthetic fluid collections 1 year or more after breast implant surgery (Table 1). Patients diagnosed with late seroma presented with swelling or breast asymmetry, often with breast tenderness, and with or without palpable fluid collection around the breast.714 In addition, at surgical exploration, some patients were found to have a double capsule, defined as a dual layer of circumferential fibrous capsular adherence (the inner layer adherent to the device and the outer layer adherent to tissue) with a potential space between each layer.14 Seroma in the early postoperative period is a common occurrence after surgical procedures that create a dead space but is infrequently reported as a late complication (1 year after surgery).7 The epidemiology of late periprosthetic fluid collection in breast implant patients is poorly characterized, but the occurrence of late periprosthetic fluid collection from individual case series ranges from 0.88 to 1.84 percent.10,14 In addition, clinical trial data show a low overall risk of periprosthetic fluid collection at any time after

The views, opinions, and techniques set forth in this article addressing anaplastic large cell lymphoma in women with breast implants are those of the individual author(s) and do not reflect the views, opinions, or recommendations of the American Society of Plastic Surgeons, the Journal or the Journal editors. Any treatment recommendations contained in the article are those of the individual author(s) and are not to be considered or construed as practice guidelines, practice standards, or practice parameters. The use of any treatment technique described in the article is at the sole discretion of the physician in the exercise of his or her independent medical judgment taking into account the patients individual circumstances.

Volume 128, Number 1 Late Periprosthetic Fluid Collection

Table 1. Summary of Literature Reports of the Occurrence of Late Periprosthetic Fluid Collection*
Characteristics Mean age of seroma patients, yr Mean time to seroma diagnosis, yr Total cases of seroma Procedure, no. Augmentation Revision-augmentation Unknown Fill type, no. Silicone Unknown Surface, no. Textured Unknown Outcome 37.8 10.9 4.8 1.4 13 10 2 1 12 1 12 1

was low, and in a case-control study examining the risk of this disease in women with breast implants, the incidence of anaplastic large T-cell lymphoma was estimated at one per 1 million women per year.25 An additional unresolved question is whether the entity identified as anaplastic large T-cell lymphoma represents a malignancy when associated with late periprosthetic fluid collection in breast implant recipients, or a reactive lymphoid hyperplasia with a variable clinical course.21

*The statistics in this table are derived from analysis of eight published case reports of seroma only (12 patients) occurring in women with breast implants: Chourmouzi et al., 20097; Fodor and Moscona, 20098; Hasham et al., 20069; Mazzocchi et al., 201010; Oliveira et al., 200711; Tansley and Powell, 201112; Wuest 199213; and Pinchuk and Tymofii, 2011.14 Mazzocchi et al., reported eight cases of late seroma; one case is counted as an occurrence, but this case is not included in the analysis, as no epidemiologic data were provided in the case report.

DIFFERENTIAL DIAGNOSIS OF LATE PERIPROSTHETIC FLUID COLLECTION OCCURRING AFTER BREAST IMPLANT SURGERY
As this group defined late periprosthetic fluid collection as that occurring 1 year or more after implant surgery, these consensus guidelines do not address diagnosis and management of periprosthetic fluid collections occurring at less than 6 months (early) or more than 6 months to less than 1 year (intermediate) after implantation. Our focus is the clinical presentation and management of breast asymmetry with swelling that is confirmed by ultrasound or other diagnostic study to establish the presence of a periprosthetic fluid collection occurring greater than 1 year after implantation. A differential diagnosis of late periprosthetic fluid collection includes hematoma caused by trauma, infection with or without biofilm formation, implant rupture, synovial metaplasia, inflammation, double capsule, cancer, and idiopathic causes. Patients with a nonresolving periprosthetic fluid collection should be further evaluated. Additional causes of unilateral swelling would include generalized breast edema not associated with any specific fluid collection and breast mass. A history of trauma and a diagnostic ultrasound with aspiration will establish the diagnosis of hematoma, although this may occur spontaneously without apparent injury. Breast implant adherence and tissue integration may be disrupted by shear forces that can interrupt blood vessels and result in a hematoma or late periprosthetic fluid collection. The characteristics of the periprosthetic fluid may change over time; specifically, after trauma, a collection of frank blood can evolve into one of clear fluid. Bacterial infection or subclinical colonization with bacteria (biofilm forming or nonbiofilm forming) may also result in a periprosthetic fluid collection as characterized by cloudy, proteinaceous, or slime-like material that can be identified on exploration or percutaneous aspiration and provide clinical clues to this potential cause.26

breast implantation. Specifically, data from the adjunct (n 83,968) and core (n 940) clinical trials, sponsored by Allergan, Inc. (Irvine, Calif.), indicated that 47,028 patients had follow-up with 172 occurrences of periprosthetic fluid collection reported. Of the reported instances of periprosthetic fluid collection, 62 of 172 cases occurred 1 year or more after implantation. As such, the overall frequency of late periprosthetic fluid collection reported from these trials was 62 of 47,028 (0.13 percent).15 The cause and pathophysiology of late periprosthetic fluid collection is unknown but may include vascular or lymphatic leakage that occurs in comorbid conditions such as inflammation from a bacterial infection, hematoma or other trauma, idiopathic reasons related to breast augmentation or reconstructive surgery, cancer, or lymphoproliferative disorders.11 Synovial metaplasia resulting from mechanical shear forces, or sliding surfaces generated by micromotions between the implant and the surrounding tissue, may also give rise to periprosthetic fluid collections.9,14 Late periprosthetic fluid collection in the presence of breast implants has also been reported in association with malignancy. Several case reports have examined late periprosthetic fluid collection in association with the infrequently reported nonHodgkins T-cell lymphoma of the breast, currently known as anaplastic large T-cell lymphoma.16 24 The absolute risk of anaplastic large T-cell lymphoma associated with late periprosthetic fluid collection

Plastic and Reconstructive Surgery July 2011

The periprosthetic fluid collection accompanying the infrequently reported lymphoma of the breast in patients with implants often appears visibly cloudy, with debris and tumor cells in the fluid and/or an edematous or abnormal capsule. Malignant cytology should be further evaluated with immunohistochemical analysis of CD30 and cytokeratin expression.27 generalized breast swelling. Ultrasound can also be used to facilitate periprosthetic fluid drainage and to obtain fluid for culture, cell count, and/or cytology, all of which will assist in narrowing the differential diagnosis (consensus recommendation) (Table 2 and Fig. 1). Mammography may not be the ideal initial diagnostic tool in the case of acute or recent breast swelling. In this setting, the diagnostic benefit of a mammogram should be weighed against the potential for further harm. For example, mammography as a first step may produce more injury in the case of a hematoma, create a surgical emergency, or be painful, and usually provides information of less clinical benefit than ultrasound (optional recommendation) (Table 2). In addition, mammography performs poorly at detecting breast lymphoma.29 Magnetic resonance imaging can detect implant rupture (consensus recommendation) and provide a diagnosis of periprosthetic fluid collection versus generalized breast tissue swelling. There is increasing evidence that new high-resolution ultrasound may also be helpful in detecting implant shell failure, which may be associated with periprosthetic fluid collection.30 Cytologic analysis of the late periprosthetic fluid collection in consultation with a hematopathologist is recommended, as a diagnosis can be difficult. Although cytologic examination of periprosthetic fluid in the diagnosis of lymphoma is incompletely characterized, the group considers this test important to the decision-making process, especially if the aspirate is cloudy with debris. Aspirated periprosthetic fluid should be assessed for the presence of a lymphoproliferative disorder, including anaplastic large T-cell lymphoma or adenocarcinoma of the breast. If there is palpable or radiologic evidence of a mass, patients should be referred to an oncologist and a standard oncologic evaluation (i.e., imaging, biopsy, oncological consultation, and surgical exploration) should be performed (Fig. 1). If the standard oncologic evaluation is positive for cancer, multidisciplinary (i.e., surgical, medical, and radiologic) oncologic management is recommended, with the patient referred to a surgical oncologist and surgical treatment options planned and explored with the oncologic team (consensus recommendation). If the standard oncologic evaluation is ambiguous, the treatment options are focused specifically on the fluid collection. Those options include an open (i.e., surgical exploration, biopsy, and capsulectomy) or closed (i.e., imaging, percutaneous drainage, and fluid analysis) evaluation at physician discretion

EVALUATION AND MANAGEMENT OF LATE PERIPROSTHETIC FLUID COLLECTION OCCURRING AFTER BREAST IMPLANT SURGERY
Currently, there is no evidence-based consensus on how to manage women who present with breast swelling 1 year or more after breast implantation surgery. We present an algorithm for the evaluation and management of late periprosthetic fluid collections specifically in patients with breast implants based on personal clinical experience and, in part, on earlier recommendations made by the Breast Augmentation Surgeons for Patients Initiative Workgroup for management of seroma occurring more than 6 months after breast augmentation. The Breast Augmentation Surgeons for Patients Initiative algorithm sought to reduce reoperation rates in augmentation mammaplasty.28 The management algorithm described here addresses management of periprosthetic fluid collections that occur 1 year or more after breast implant surgery (Fig. 1). The evaluation and management approach may vary depending on the type of surgery (e.g., augmentation, reconstruction, revision-augmentation, and revision-reconstruction) and the clinical presentation and course of the patient with late periprosthetic fluid collection. Initially, infection should be ruled out as one of the most common possible causes (Fig. 1). Before initiation of antimicrobial therapy, aspiration of the periprosthetic fluid collection, culture, and cell counts are recommended. Empiric broadspectrum antimicrobial therapy after aspiration (pending laboratory results) is an option if clinical suspicion of infection is high, particularly if there may be a delay of more than 48 hours before culture results can be obtained. Alternatively, directed antimicrobial therapy can be postponed until culture results are available (Table 2). Imaging (i.e., ultrasound, magnetic resonance imaging, and mammography) is recommended for persistent and recurrent swelling, even after antimicrobial therapy and the resolution of any suspected infection. Preferably, ultrasound-guided or simple needle aspiration is recommended as a first step to distinguish between fluid collection and

Volume 128, Number 1 Late Periprosthetic Fluid Collection

Fig. 1. Management algorithm for late periprosthetic fluid collection (seroma) occurring (1 year) after breast implant surgery. *A standard oncologic evaluation includes imaging, biopsy, oncologic consultation, and surgical exploration. Cytologic evaluation should be performed in consultation with a hematopathologist.

based on clinical suspicion of neoplasia (Fig. 1). Factors that increase the suspicion for lymphoproliferative malignancy include the presence of lymphoma and/or constitutional B symptoms, defined as weight loss, night sweats and fever of unknown origin, and periprosthetic fluid turbidity. Malignant cytology in the periprosthetic fluid requires careful additional evaluation for primary and secondary malignancies of the breast, including lymphoproliferative disorders or anaplastic large T-cell lymphoma. A malignant cytologic examination should trigger a pathologic request for immunohistochemical stains (e.g., CD30 and cytokeratin) to narrow the differential diagnosis. Surgical exploration of the implant capsule, biop-

sies, and total capsulectomy are recommended. If the periprosthetic fluid evaluations are negative with no evidence of neoplasia, the therapy can be specifically focused on treating the fluid collection alone (Fig. 1). For surgical exploration conducted during an open evaluation, the capsule should be examined for the appearance of any abnormality, nodularity, thickening, or other apparent pathologic finding. Despite negative cultures, the possibility of subclinical infection should be considered. In the presence of a refractory periprosthetic fluid collection, a total capsulectomy (including implant removal) is recommended, with or without replacement of a new implant (consensus recommendation). Complica-

Plastic and Reconstructive Surgery July 2011

Table 2. Recommendations for Management of Late Periprosthetic Fluid Collection
Procedure Imaging Ultrasound Magnetic resonance imaging Mammography Percutaneous drainage Antimicrobial therapy Surgical intervention Fluid analysis Cytology Cell count Culture Flow cytometry Recommended X Optional Not Recommended

X X* X X X X X X X X X X

common cause for such late fluid collections is idiopathic. In the absence of a diagnosed infectious or neoplastic cause, most of these late fluid collections will require capsulectomy, with or without implant replacement. Some late fluid collections are associated with culture-positive infections and benefit from antimicrobial therapy. Many of these patients are treated empirically for subclinical culture-negative infections and undergo capsulectomy. Such fluid collections are infrequently associated with a neoplastic process. Nevertheless, such a process should be considered, and appropriate radiographic and laboratory tests should be undertaken, depending on the clinical findings.
Mark L. Jewell, M.D. Jewell Plastic Surgery Center 10 Coburg Road, Suite 300 Eugene, Ore. 97401 mjewell@teleport.com

*Mammography is not recommended in the acute setting of a swollen breast. If cytologic analysis reveals malignant cells, immunohistochemical assessment of CD30 and cytokeratin expression is recommended.

ACKNOWLEDGMENTS

tions such as capsular contracture have been shown to occur less frequently in patients with complete versus partial capsulectomy.31 A complete capsulectomy is recommended based on intraoperative assessment and if technically possible, only to the point that it is surgically prudent and without risk of damage to surrounding structures. If results of cytologic analysis are positive, with a normal or abnormal capsule, recommended treatment options are focused on treating the malignancy. This may include removal of the implant(s), capsulectomy, and drainage, with or without implant replacement (Fig. 1). Nontreatment, random biopsies, and closing the surgical incision and repeating ultrasoundguided aspiration of fluid that reaccumulates around the implant are not recommended (Fig. 1). Exploration alone will not help resolve a recurrent periprosthetic fluid collection with negative cultures that does not respond to antibiotics. It is rare for noninfectious fluid collections to resolve without total capsulectomy (consensus opinion).

SUMMARY
Late periprosthetic fluid collection is an infrequently reported occurrence after breast implant surgery. At a minimum, management should include image-guided aspiration of fluid, with appropriate fluid evaluation, including culture, cell count, and cytologic testing. Recurrent or refractory periprosthetic fluid collection that occurs despite appropriate antibiotic or supportive treatment warrants further evaluation and intervention. The most

Medical writing services and editorial assistance provided by Luana Atherly, Ph.D., of inScience Communications, a Wolters Kluwer business. This assistance was performed in compliance with good publishing practices outlined by the International Committee of Medical Journal Editors and was funded by Allergan, Inc. In her role, Dr. Atherly participated in several Web conferences with the authors to receive guidance and direction for their manuscript. Using their direction and output, she generated a draft outline. After review by the authors, Dr. Atherly incorporated any and all author-recommended changes into subsequent drafts of the manuscript. She also participated in a conference call with authors after the manuscript was reviewed by Plastic and Reconstructive Surgery and at their direction incorporated responses to comments received from the Journal. As is consistent with Good Publication Practice and International Committee of Medical Journal Editors guidelines, every draft of the manuscript was reviewed and approved by all authors, and all authors read and approved the final version. Documentation of this is available on request. Dr. Atherly has no financial involvement with any of the drugs, devices, or products mentioned in this article. The authors wish to thank William P. Adams, Jr., M.D., and Steven Teitelbaum, M.D., for invaluable expertise and thoughtful opinion during the development and review of the article.
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