Unexpected histological appearance of breast implant associated fibrous pseudocapsules

Abstract

Insertion of a breast implant induces formation of a fibrous pseudocapsule. This pseudocapsule may be submitted in its entirety or partially for histological assessment in a number of circumstances. The whole pseudocapsule may be received at the time of implant exchange, e.g., due to pseudocapsular contracture or implant leak, or it may be partially sampled, e.g., when there is concern that a peri-implant seroma or pseudocapsular thickening may be due to implant-associated anaplastic large cell lymphoma (IA-ALCL).1Bui J.M. Perry T. Ren C.D. Nofrey B. Teitelbaum S. Van Epps D.E. Histological characterization of human breast implant capsules.Aesthet Plast Surg. 2015; 39: 306-315Crossref PubMed Scopus (47) Google Scholar, 2De Boer M. van Leeuwen F.E. Hauptmann M. et al.Breast implants and the risk of anaplastic large-cell lymphoma in the breast.JAMA Oncol. 2018; 4: 335-341Crossref PubMed Scopus (186) Google Scholar Acellular dermal matrix (ADM) is a connective tissue graft created by decellularisation of donor skin (e.g., cadaveric, bovine, porcine). In nipple and skin sparing mastectomy with implant based breast reconstruction (NSMIBR), ADM is used chiefly for lower pole coverage and improving the cosmetic outcome in subpectoral implant placement, and is also used in prepectoral implant placement.3Onesti M.G. Maruccia M. Di Taranto G. et al.Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing ‘wrap’ technique: a single-center experience.J Plast Reconstr Aesthet Surg. 2017; 70: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The ADM acts as scaffolding in tissue repair, and provides structural strength and shape, aiding positioning of the implant in the inframammary fold, and purportedly prevents the formation of contractile pseudocapsule around the breast implant.3Onesti M.G. Maruccia M. Di Taranto G. et al.Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing ‘wrap’ technique: a single-center experience.J Plast Reconstr Aesthet Surg. 2017; 70: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 4Cavallo J.A. Gangopadhyay N. Dudas J. et al.Remodeling characteristics and collagen distributions of biologic scaffold materials biopsied from postmastectomy breast reconstruction sites.Ann Plast Surg. 2015; 75: 74-83Google Scholar In a meta-analysis study, its use did not seem to change acute/intermediate post surgical complications such as skin necrosis, nipple necrosis, infection, haematoma and seroma formation, requirement for implant explantation and unplanned return to the operating room.5Heidemann L.N. Gunnarsson G.L. Salzberg C.A. Sørensen J.A. Thomsen J.B. Complications following nipple-sparing mastectomy and immediate acellular dermal matrix implant-based breast reconstruction – a systematic review and meta-analysis.Plast Reconstr Surg Glob Open. 2018; 6: e1625Google Scholar ADM undergoes a series of histological changes/remodelling following implantation,6Yu D. Hanna K.R. LeGallo R.D. Drake D.B. Comparison of histological characteristics of acellular dermal matrix capsules to surrounding breast capsules in acellular dermal matrix-assisted breast reconstruction.Ann Plast Surg. 2016; 76: 485-488Crossref PubMed Scopus (18) Google Scholar, 7Boháč M. Danišovič Ľ. Koller J. Dragúňová J. Varga I. What happens to an acellular dermal matrix after implantation in the human body? A histological and electron microscopic study.Eur J Histochem. 2018; 62: 2873Google Scholar which may be influenced by a number of factors including type of ADM used,8Carruthers C.A. Dearth C.L. Reing J.E. et al.Histologic characterization of acellular dermal matrices in a porcine model of tissue expander breast reconstruction.Tissue Eng A. 2015; 21: 35-44Crossref PubMed Scopus (34) Google Scholar, 9Lucke S. Hoene A. Walschus U. Kob A. Pissarek J.W. Schlosser M. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.Biomed Res Int. 2015; 2015: 938059Google Scholar and factors such as chemotherapy and radiotherapy, smoking and corticosteroid exposure.4Cavallo J.A. Gangopadhyay N. Dudas J. et al.Remodeling characteristics and collagen distributions of biologic scaffold materials biopsied from postmastectomy breast reconstruction sites.Ann Plast Surg. 2015; 75: 74-83Google Scholar, 10Myckatyn T.M. Cavallo J.A. Sharma K. et al.The impact of chemotherapy and radiation on the remodeling of acellular dermal matrices in staged, prosthetic breast reconstruction.Plast Reconstr Surg. 2015; 135: 43-57eCrossref PubMed Scopus (19) Google Scholar Two examples of implant-associated pseudocapsules were received, containing ADM, the unfamiliarity of which prompted consideration of a necrobiotic process such as rheumatoid nodule formation, which is rarely described in the breast.11Cooper N.E. Rheumatoid nodule in the breast.Histopathology. 1991; 19: 193-194Crossref PubMed Scopus (12) Google Scholar, 12Iqbal F.M. Ali H. Vidya R. Breast lumps: a rare site for rheumatoid nodules.BMJ Case Rep. 2015; 2015 (bcr2014208586)Google Scholar Case 1 was a 55-year-old female who developed recurrence of grade 3 invasive ductal carcinoma, no special type, within subcutaneous tissue overlying a left implant-based breast reconstruction, with use of ADM learned in retrospect. No other history could be obtained. Skin and subcutaneous adipose tissue received contained a 13 mm deposit of recurrent carcinoma within a scar. Breast implant pseudocapsule was received in multiple pieces including with overlying skin. The pseudocapsule was up to 5 mm thick. Histologically (Fig. 1) it displayed synovial metaplasia of the inner (implant facing) surface, and a linear strip of acellular collagen (representing ADM) surrounded by palisading histiocytes, resembling rheumatoid nodule formation. There was little ingrowth of vessels or fibroblast-like cells into the ADM. Small aggregates of lymphocytes and plasma cells, and an occasional lymphoid follicle was seen in the surrounding tissue. The ADM was differentially highlighted by an Alcian blue, diastase periodic acid–Schiff (ABDPAS) stain in which it stained weakly DPAS positive, whereas there was additional Alcian blue uptake elsewhere. A trichrome stain showed no marked difference between the ADM and host collagen, but it was still distinguishable. An elastic-Van Gieson (EVG) stain demonstrated few elastic fibres within the ADM. Case 2 was a 43-year-old female with a BRCA2 mutation, who 3 years prior had prophylactic left mastectomy and implant based reconstruction preceded by contralateral (right) breast carcinoma treated by mastectomy, chemotherapy and radiotherapy. She developed a thickened plaque on the left and the pseudocapsule was sampled to exclude IA-ALCL. The limited implant pseudocapsule sample received measured 17 × 11 × 3 mm and histologically (Fig. 2) displayed inner synovial metaplasia and a zone of degenerate appearing collagen bordered by palisading histiocytes, representing a histiocytic reaction to ADM, resembling a rheumatoid nodule. There was more apparent ingrowth of fibroblast-like cells into the ADM as compared to Case 1, but less material overall for assessment. Small aggregates of lymphocytes and plasma cells were also seen in the surrounding tissue. No cellular atypia was seen and a CD30 immunohistochemical marker was negative, excluding IA-ALCL. Again, the ADM was differentially highlighted by an ABDPAS stain. A trichrome stain similarly showed no marked difference between the ADM and host collagen. An EVG stain again showed little elastic material within the ADM. Pseudocapsular contraction is an adverse clinical outcome and may be influenced by a number of exogenous factors, e.g., surgical technique, pocket fit, plane of implant placement, bleeding, radiotherapy and implant leak. A fibrous pseudocapsule forms following a foreign body response, with recruitment of fibroblasts, which lay down collagen, and myofibroblasts which cause contracture. The latter eventually undergo apoptosis. Pseudocapsule thickness is positively correlated with implant duration and implant contracture. Histologically, implant contracture is associated with a thickened pseudocapsule, aligned collagen fibres and persistence of myofibroblasts.1Bui J.M. Perry T. Ren C.D. Nofrey B. Teitelbaum S. Van Epps D.E. Histological characterization of human breast implant capsules.Aesthet Plast Surg. 2015; 39: 306-315Crossref PubMed Scopus (47) Google Scholar Among other reasons, ADM is utilised with the aim of reducing pseudocapsular contracture.3Onesti M.G. Maruccia M. Di Taranto G. et al.Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing ‘wrap’ technique: a single-center experience.J Plast Reconstr Aesthet Surg. 2017; 70: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 4Cavallo J.A. Gangopadhyay N. Dudas J. et al.Remodeling characteristics and collagen distributions of biologic scaffold materials biopsied from postmastectomy breast reconstruction sites.Ann Plast Surg. 2015; 75: 74-83Google Scholar However, it too induces histological changes that may present as pseudocapsular thickening, as in Case 2. Animal models8Carruthers C.A. Dearth C.L. Reing J.E. et al.Histologic characterization of acellular dermal matrices in a porcine model of tissue expander breast reconstruction.Tissue Eng A. 2015; 21: 35-44Crossref PubMed Scopus (34) Google Scholar, 9Lucke S. Hoene A. Walschus U. Kob A. Pissarek J.W. Schlosser M. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.Biomed Res Int. 2015; 2015: 938059Google Scholar and assessment of pseudocapsule samples from human subjects provide insight into the histological response to ADM insertion.3Onesti M.G. Maruccia M. Di Taranto G. et al.Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing ‘wrap’ technique: a single-center experience.J Plast Reconstr Aesthet Surg. 2017; 70: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 6Yu D. Hanna K.R. LeGallo R.D. Drake D.B. Comparison of histological characteristics of acellular dermal matrix capsules to surrounding breast capsules in acellular dermal matrix-assisted breast reconstruction.Ann Plast Surg. 2016; 76: 485-488Crossref PubMed Scopus (18) Google Scholar, 7Boháč M. Danišovič Ľ. Koller J. Dragúňová J. Varga I. What happens to an acellular dermal matrix after implantation in the human body? A histological and electron microscopic study.Eur J Histochem. 2018; 62: 2873Google Scholar ADM and the surrounding tissue undergoes a number of changes over time, with an initial acute inflammatory response, foreign body histiocytic response such as palisaded histiocytes surrounding the ADM as seen in the two cases reported here, neovascularisation and ingrowth of myofibroblasts and fibroblasts into the collagenous scaffolding to varying degrees dependent upon type of ADM used and influences of chemo-radiotherapy, smoking and corticosteroid use, which reduce ADM incorporation.3Onesti M.G. Maruccia M. Di Taranto G. et al.Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing ‘wrap’ technique: a single-center experience.J Plast Reconstr Aesthet Surg. 2017; 70: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 6Yu D. Hanna K.R. LeGallo R.D. Drake D.B. Comparison of histological characteristics of acellular dermal matrix capsules to surrounding breast capsules in acellular dermal matrix-assisted breast reconstruction.Ann Plast Surg. 2016; 76: 485-488Crossref PubMed Scopus (18) Google Scholar, 7Boháč M. Danišovič Ľ. Koller J. Dragúňová J. Varga I. What happens to an acellular dermal matrix after implantation in the human body? A histological and electron microscopic study.Eur J Histochem. 2018; 62: 2873Google Scholar, 8Carruthers C.A. Dearth C.L. Reing J.E. et al.Histologic characterization of acellular dermal matrices in a porcine model of tissue expander breast reconstruction.Tissue Eng A. 2015; 21: 35-44Crossref PubMed Scopus (34) Google Scholar, 9Lucke S. Hoene A. Walschus U. Kob A. Pissarek J.W. Schlosser M. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.Biomed Res Int. 2015; 2015: 938059Google Scholar, 10Myckatyn T.M. Cavallo J.A. Sharma K. et al.The impact of chemotherapy and radiation on the remodeling of acellular dermal matrices in staged, prosthetic breast reconstruction.Plast Reconstr Surg. 2015; 135: 43-57eCrossref PubMed Scopus (19) Google Scholar Development of antibodies against the ADM, e.g., to porcine collagen, may also influence the rate of tissue regeneration.9Lucke S. Hoene A. Walschus U. Kob A. Pissarek J.W. Schlosser M. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.Biomed Res Int. 2015; 2015: 938059Google Scholar One way that ADM may reduce the risk of pseudocapsular contraction is that it has less migrating myofibroblasts than surrounding tissues in the healing response. By acting as a physical barrier or interface between the implant and the surrounding host tissue, it may reduce the ability of inflammatory cells and myofibroblasts to induce pseudocapsular contraction.6Yu D. Hanna K.R. LeGallo R.D. Drake D.B. Comparison of histological characteristics of acellular dermal matrix capsules to surrounding breast capsules in acellular dermal matrix-assisted breast reconstruction.Ann Plast Surg. 2016; 76: 485-488Crossref PubMed Scopus (18) Google Scholar, 10Myckatyn T.M. Cavallo J.A. Sharma K. et al.The impact of chemotherapy and radiation on the remodeling of acellular dermal matrices in staged, prosthetic breast reconstruction.Plast Reconstr Surg. 2015; 135: 43-57eCrossref PubMed Scopus (19) Google Scholar In the absence of a history or familiarity with ADM, the differential diagnosis of the histological appearance includes rheumatoid nodule formation, which is rarely encountered in the breast.11Cooper N.E. Rheumatoid nodule in the breast.Histopathology. 1991; 19: 193-194Crossref PubMed Scopus (12) Google Scholar, 12Iqbal F.M. Ali H. Vidya R. Breast lumps: a rare site for rheumatoid nodules.BMJ Case Rep. 2015; 2015 (bcr2014208586)Google Scholar There is controversy regarding the risk of connective-tissue disorders amongst breast implant patients, including rheumatoid arthritis, scleroderma, Sjögren's syndrome and systemic lupus erythematosus. However, the excess risk has not been adequately proven and the purported association may in part be anecdotal.13Brinton L.A. Buckley L.M. Dvorkina O. et al.Risk of connective tissue disorders among breast implant patients.Am J Epidemiol. 2004; 160: 619-627Crossref PubMed Scopus (39) Google Scholar It is important to be aware that a granulomatous response to breast carcinoma has also been observed in the breast and in tumour draining lymph nodes, particularly because the majority of NSMIBR follow a breast cancer diagnosis.14Coyne J.D. Necrobiotic palisading granulomas associated with breast carcinoma.J Clin Pathol. 2005; 58: 1290-1293Google Scholar Barr and Stegman15Barr R.J. Stegman S.J. Delayed skin test reaction to injectable collagen implant (Zyderm). The histopathologic comparative study.J Am Acad Dermatol. 1984; 10: 652-658Abstract Full Text PDF PubMed Scopus (65) Google Scholar compared the histological appearance of reactions to injectable bovine collagen to that of collagen in granuloma annulare, hypertrophic and keloid scars and a rheumatoid nodule. The injectable collagen showed pale blue staining with a trichrome stain, and polarised poorly, possibly reflecting intermixed native collagen bundles, whereas the central collagen in a rheumatoid nodule stained red with a trichrome stain and did not polarise. The collagen in injected bovine collagen is not directly comparable to implanted sheets of ADM as it is suspended in saline. In the two current cases, the ADM showed pale green staining with trichrome stain, similar to background host collagen and the collagen was polarisable. ABDPAS staining was particularly useful because the ADM stained with DPAS and did not tend to uptake Alcian blue. ABDPAS staining and the utilisation of polarised light microscopy are cheap and simple methods to aid in confirmation of the presence of ADM and to help distinguish it from histological mimics.