Keywords
ALCL - late seroma - breast augmentation - PIP - implants - capsular contracture -
autologous fat transfer - breast reconstruction - implant rupture
The exact rate of implant-related complications is unknown.[1] More frequent complications after breast implant surgery include rupture, silicon
leakage, infection, capsular contracture, asymmetry, and migration of the implant.
Most of such complications occur in the early postoperative period.[2]
Although seroma formation is clinically perceived as a well-known complication after
implant removal, especially if the capsule is left unmodified in situ, peer-reviewed
scientific literature on this subject is rare.
Various publications have defined late seroma as a predominant serous accumulation
of periprosthetic liquid (exudate or effusion) within the implant capsule developing
at least 12 months after the implantation.[3]
[4] Late seroma development after primary breast augmentation is rare with an incidence
between 0.88%[5] and 1.84%.[6] The range of incidence for early (until 6 months) or intermediate seroma varies
between 3% and 10%.[7] Late seroma formation was found to be associated mainly with textured implants.[8] Affected patients showed a sudden progressive swelling of the breast and discomfort
as the main clinical symptoms. Its definite origin remains unknown, but most publications
agree on an apparently multifactorial pathophysiology:
-
Vascular and/or lymphatic leakage occurring in comorbid conditions such as chronic
inflammation due to subclinical bacterial infection or a local inflammatory response,
leading to the release of mediators increasing, eventually, the interstitial fluid
drainage.[3]
[7]
-
Recurrent trauma with synovial metaplasia due to shearing forces and micromotions
between the implant and surrounding tissues.[5]
[9]
-
Idiopathic reasons related to reconstructive surgery after malignant diseases.[10]
Furthermore, late seroma seems to be associated with specific entities of anaplastic
large cell lymphoma (ALCL), a rare type of non-Hodgkin lymphoma. These types of ALCL
are CD30+, with anaplastic lymphoma kinase 1 (ALK-1) negative T cell neoplasms accounting for
0.5% of all breast cancers.[11]
In recent times, two distinct clinical pathological entities with different prognostic
outcomes have been described:
-
In-situ implant-associated ALCLs have an indolent clinical course and tend to show
complete remission after complete removal of the capsule.
-
Infiltrative ALCLs seem to have a more aggressive clinical course with a less favorable
outcome even after additional therapy.[12]
It is important to mention that the clinical symptoms of in situ ALCLs typically do
not differ from those of a late seroma.[13] More rarely, it can be in the form of a capsular contracture or solid mass within
the implant capsule.[11]
Patient Case
A 52-year-old patient presented herself at our clinic with a history of recurring
seroma of the right breast over a period of 8 years. Her surgical records showed bilateral
epipectoral breast augmentation in 2002 with cohesive Silicone Gel implants manufactured
by PIP (Poly Implants Prothèse, France). Clinical history revealed a unilateral implant
rupture confirmed by mammography and recurrent episodes of local pain and swelling
of the corresponding lymph nodes, leading to unilateral implant removal without capsulectomy
in 2008.
Painful seroma formation recurred in the right breast after several years and was
treated repeatedly by transcutaneous needle aspiration. Clinical records mention a
fluid of a pale yellowish color without cell debris. Clinical records or anamnestic
history could not confirm any cytological or bacteriological tests.
A primary physical examination at our clinic showed the right breast had hardened
and was painful at palpation. An ultrasound examination revealed a large intracapsular
mass with liquid and solid portions. No clinical signs of infection were noticed;
the axillary, subclavian, and parasternal lymph nodes were unsuspicious. A considerable
asymmetry of the breasts, with the right breast being significantly bigger than the
left, was noted ([Fig. 1A] and [B]).
Fig. 1 Preoperative and postoperative views. Preoperative imaging: frontal (A) and right oblique view (B); 3-month postoperative result: frontal (C) and right oblique view (D); 6-month postoperative result: frontal (E) and right oblique view (F).
Suggested preoperative needle aspiration with cytological and microbiological testing
was declined by the patient with reference to her year-long, painful history of symptomatic
treatment by needle aspiration; the patient wished for a one-stage solution and was,
therefore, scheduled for complete bilateral capsulectomy, removal of the remaining
implant on the left side, and reconstruction with autologous fat transfer.
Intraoperative Findings
The capsule on the left side was removed en bloc with the remaining implant and showed
no signs of capsular contracture, double capsule, or implant rupture. After the removal
of the capsule, the implant could be identified as a textured 380 cc round and high
profile device manufactured by PIP. Explanation data was entered into the Spanish
Registry.
An intact capsule with macroscopic signs of chronic inflammation, hypervascularity
of the outer surface, and stiff, thickened walls was found on the right side. No pericapsular
liquid was present. To facilitate en bloc capsulectomy on the right side, transcapsular
needle aspiration was performed under direct vision removing 600cc of dark, serous
liquid. After en bloc capsulectomy through a periareolar access, the capsule was opened
and showed a large amount of a brownish, hematofibrous content without macroscopic
evidence of intact, tissue-like structures ([Fig. 2A] and [B]).
Fig. 2 Intraoperative views. Macroscopic aspect of capsule and contents after explantation
(A–B); resulting skin excess of right breast envelope after capsulectomy with a view inside
the wound (C), and lateral view (D).
Immediate volume reconstruction was performed using WAL-assisted (Body Jet, Human
Med AG, Germany) autologous fat transfer from the abdomen. Using a multichannel, multilayer
technique (subcutaneous, intramuscular, and subglandular), 880 cc of fat was injected
into the right breast and 720 cc into the left breast. To reduce the large skin excess
resulting from the seroma-induced soft tissue expansion ([Fig. 2C] and [D]) while respecting the patients wish for a minimal scar solution without vertical
uplift, a large periareolar lift, using a modified Benelli's technique, was performed.
Postoperative Evolution and Aesthetic Outcome
Postoperative Evolution and Aesthetic Outcome
Postoperative recovery was complication-free. No signs of infection, fat necrosis,
or recurrent seroma were observed during the 6-month follow-up period.
An acceptable aesthetic result was achieved with a single-session autologous fat transfer.
The high-volume transfer was feasible due to the largely extended tissue matrix resulting
from the tissue expansion effect of the recurrent seroma on the right side and the
implant on the left side. Three-month and 6-month postoperative follow-ups ([Fig. 1C]–[F]) showed a good bilateral fat graft survival with volume and symmetry judged as satisfactory
by the patient and the authors.
Histological, Microbiological, and Immunohistochemical Findings
Histological, Microbiological, and Immunohistochemical Findings
Histological examination of the capsule after embedding and hematoxylin and eosin
(HE) and periodic acid–Schiff staining showed tissue changes compatible with a chronic
inflammatory reaction characterized by large quantities of inflammatory cells and
an abundant presence of foreign body granuloma ([Fig. 3]).
Fig. 3 Histopathology. Hematoxylin and eosin staining showing typical signs of chronic inflammation
and foreign body granuloma (A–B).
The presence of malignant cells or especially cells compatible with an entity of ALCL
could not be confirmed histologically in the capsule tissue or its content. Neither
cytological analysis of the aspirate in HE nor Papanicolaou and Giemsa staining detected
atypical cells. Microbiological examination of the needle aspirate showed the presence
of a multisensible Staphylococcus aureus.
Aspirate and capsule were sent for immunohistochemical testing regarding hematopathological
markers correlating with ALCL. Results were negative for K
i-1/Ber-H2 (CD 30) and ALK. They were positive for CD 5, CD20/L26/PAN-B, CD 79a, and
CD3/UCHL-1/PAN-T, indicating a lymphoid inflammatory process without atypical cell
proliferation.
Discussion
The authors conducted a PubMed database query to find similar cases and possible causes
described in literature for the recurrence of late seroma after implant removal. The
terms used for the query were (breast implant removal) AND seroma; (PIP implant) AND
seroma; (residual capsule) AND seroma; (breast implant removal) AND (periprosthetic
fluid), (implant rupture) AND seroma.
Apart from a study published in Radiology,[14] which focuses mainly on mammographic and echographic findings of late seroma, only
four other case reports were found describing late seroma within the capsule after
implant removal.
Anaplastic Large Cell Lymphoma
Anaplastic Large Cell Lymphoma
An increasing number of meta-analyses shows the possibility that ALCL, in cases with
persistent, implant-related late seroma, may not be as rare as previously stated in
literature, although the direct causality between textured breast implants and ALCL
is not yet proven.[15]
One of the four case reports similar to our case describes an ALCL-related malignant
effusion. In this case, the patient suffered from recurrent fluid formation within
the capsule after implant removal. Repeated biopsies and needle aspirations of the
fluid failed to detect ALCL. Only after capsulectomy and complete histological examination,
could ALCL be histologically confirmed.[16]
[17] Other studies confirmed that ALCL tumor cells can be discontinuously distributed
in the capsule or confined to the surface of the capsule as a discontinuous layer.[18]
[19] Histological examination of the whole capsule and fluid and complete capsulectomy
in cases suspicious for ALCL is, therefore, recommendable. In cases where ALCL is
clinically highly probable, additional immunohistochemical tests should be performed
even if cytology is not suspicious.[13]
[15]
[16]
These recommendations—the intraoperative findings described above and the long clinical
history of recurrent seroma—demanded histopathological and immunohistochemical exclusion
of ALCL in our case.
The microbiological finding of capsule contamination with S. aureus in our case is interesting within the context of the current discussion literature
of possible causality between textured implants, biofilm formation, and ALCL. In a
study by Hu et al, the numbers of B and T cells showed a linear correlation with the
number of detected bacteria in implant capsules in humans.[20] In an implanted pig model, the same group proved that the lymphocytic infiltrate
on the surface of textured implants had a significantly higher number of B and T cells
than the infiltrate on smooth implants. In polyurethane-coated implants, the load
of bacteria and B and T cells was even higher.[20] The majority of ALCL has been associated with textured implants and particularly
with the aggressive BioCell texture.[21]
[22] It is the CD4+ T cells, which undergo malignant transformation in ALCL. In the study
by Hu et al, it was also the CD4+ T cells which showed the most significant correlation
with an increasing number of bacteria.[20] A study by Allan et al also supports the idea of an interrelationship between bacterial
charge and ALCL.[23] A recent study by Kellogg et al describes the development of both T and B cell lymphoma
in the context of a variety of other prosthetics.[24] Therefore, the behavior of the CD4+ T cells in the lymphocytic infiltrate within
the capsule reacting to the bacterial load might be the missing link in the development
of ALCL.
In our opinion, additional microbiological testing should be performed in all cases
of late seroma. In clinically highly suspicious cases for ALCL, immunohistochemical
testing of the capsule and its content should be performed even if the histopathological
tests do not detect any signs for ALCL.
Treatment Recommendations of ALCL
Immediate volume reconstruction through autologous fat transfer was performed. The
authors discussed this procedure preoperatively and decided in favor of immediate
reconstruction, despite the intraoperative findings. Clinically, the ongoing process
was limited to the capsule and its content. In case of an intracapsular or strictly
capsular ALCL, complete capsulectomy can be a definite treatment. Further chemotherapy
can be spared.[14] Furthermore, the patient explicitly wished for a definitive solution within only
one operative procedure. Therefore, the authors performed the reconstruction before
eliminating a possible ALCL.
Other treatment options in our case with a severe lack of soft tissue density would
have been an open wound treatment or the implantation of a placeholder, aiming to
fill the immense wound cavity until the completion of the definite histological analysis.
Later, subsequent secondary breast reconstruction through fat grafting, with implants
or even through autologous breast reconstruction via deep inferior epigastric perforator
flap or analogue techniques could have been performed.
PIP Implants: Rupture Rate and Late Seroma
PIP Implants: Rupture Rate and Late Seroma
The rupture rate of PIP implants was found to be 35.2% per patient and 21.3% per implant
over a mean implantation period of 7.8 years by one group. A statistical difference
(p < 0.001) in rupture rates between implants inserted prior to 2003 and those inserted
from 2003 was demonstrated.[25] Other groups state the rupture rate to be 21.8%, with most of the ruptures being
asymptomatic, causing no further irritations. An increase in seroma incidence was
not observed.[26] In the described case, the patient underwent right implant removal in 2008 due to
a unilateral implant rupture after primary implantation in 2002. The distribution
of PIP implants containing nonmedical grade silicone began probably not until 2003,[27] and even the nonmedical grade silicone used from 2003 onward has not proven to be
irritating or cytotoxic by itself.[28]
Inflammatory Response and Biofilm
Inflammatory Response and Biofilm
In the described case, the capsule showed macroscopic signs of chronic inflammation,
tissue hardening, and capsular contraction. As the patient had complained about discomfort
and swollen axillary lymph nodes before implant removal in 2008, chronic low-grade
infection could also be a possible pathomechanism for the recurrent seroma. In the
case of an existing periprosthetic biofilm in 2008, implant removal alone would probably
not have eliminated the bacterial load,[20] especially in combination with a foreign body reaction due to implant rupture. Histopathology
of the capsule after complete capsulectomy confirmed signs of enhanced chronic inflammatory
response and foreign body reaction. These factors could be responsible for the recurrent
production of periprosthetic fluid.[6] Microbiological analysis of the capsule and contents confirmed the presence of a
strain of multisensible coagulase-negative S. aureus that could be the cause a chronic low-grade infection, but due to multiple transcutaneous
needle aspirations of the seroma over the last year it remains unclear if perioperative
implant contamination or secondary contamination is the source of infection.
Capsulectomy versus Capsulotomy after Implant Removal
Capsulectomy versus Capsulotomy after Implant Removal
A study by Soo et al in 1995 on 84 patients showed intracapsular seroma formation
after implant removal in six cases, while no seroma formation could be observed in
patients who underwent complete caspulectomy. Five other case reports also mentioned
seroma formation within the capsule.[7]
[16]
[17]
[29]
[30]
The elimination of dead space after the removal of any implant or tissue is generally
recommended for the prevention of seroma and is especially important in case of inflamed
capsules. The hardened tissue may prevent the fusion of the anterior and posterior
layer and, thereby, leave space for the formation of a potential seroma.[7] Complete capsulectomy and implant removal are the recommendation in cases of a suspected
biofilm/low-grade infection as well in cases of pre-existing seroma.[31]
[32]
Conclusion
The exact cause of recurrent seroma formation in the described case remains unclear.
Further investigation is needed to identify the risk factors behind recurrent seroma
after implant removal without complete capsulectomy. Complete capsulectomy should
be performed in cases with confirmed implant rupture, excessive silicone bleeding,
recurrent seroma formation, histopathological changes of the capsule, or proven bacterial
load.
Since 1997, only 173 cases have been identified so far in the world literature review.[21] In the light of the ongoing discussion and the actual research concerning ALCL,
a high number of undiagnosed cases may be suspected. As some of the cases have been
associated with late seroma, ALCL should be excluded in these instances by histopathological
and where appropriate immunohistochemical examination of the capsule and the seroma
fluid.
As implant removal and complete capsulectomy are considered the only local treatment
so far, volume restoration with fat grafting seems to be a valid reconstructive option.
Taking advantage of the tissue expansion caused by the implants, one single session
of high-volume fat grafting may be sufficient to restore an adequate volume and to
achieve an acceptable aesthetic outcome even in breasts with notable skin excess.
