Metaplastic synovial cyst in male breast

Metaplastic synovial cyst (synovial metaplasia of the skin) refers to a cyst lined by a membrane resembling hyperplastic synovial villi. Synovial-like metaplasia has been described around prostheses and breast implant capsules and may occur in postsurgical cutaneous scars, unrelated to prostheses or implants. We describe a metaplastic synovial cyst occurring in the left breast of a 23-year-old man 2 years after surgical treatment of gynecomastia. The expanding clinicopathologic scenario of metaplastic synovial cyst, in scar tissue in male breast unrelated to mammary implants, and as a potential complication after surgical treatment of gynecomastia is highlighted.     

The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants

Implanted silicone medical prostheses induce a dynamic sequence of histologic events in adjacent tissue resulting in the formation of a fibrotic peri-prosthetic capsule. In some cases, capsular calcification occurs, requiring surgical intervention. In this study we investigated capsules from silicone gel-filled breast prostheses to test the hypothesis that this calcification might be regulated by the small vitamin K-dependent protein, matrix Gla protein (MGP), a potent inhibitor of arterial calcification, or by Fetuin-A, a hepatocyte-derived glycoprotein also implicated as a regulator of pathologic calcification. Immunolocalization studies of explanted capsular tissue, using conformation-specific antibodies, identified the mineralization-protective γ-carboxylated MGP isomer (cMGP) within cells of uncalcified capsules, whereas the non-functional undercarboxylated isomer (uMGP) was typically absent. Both were upregulated in calcific capsules and co-localized with mineral plaque and adjacent fibers. Synovial-like metaplasia was present in one uncalcified capsule in which MGP species were differentially localized within the pseudosynovium. Fetuin-A was localized to cells within uncalcified capsules and to mineral deposits within calcific capsules. The osteoinductive cytokine bone morphogenic protein-2 localized to collagen fibers in uncalcified capsules. These findings demonstrate that MGP, in its vitamin K-activated conformer, may represent a pharmacological target to sustain the health of the peri-prosthetic tissue which encapsulates silicone breast implants as well as other implanted silicone medical devices.     

Silicone rubber temporomandibular joint (TMJ) meniscal replacements: postimplant histopathologic and material evaluation

Medical grade silicone rubber has long been considered a suitable meniscal replacement, but there has been increasing concern about migration of this material into adjacent tissues. The objectives of this study were to determine the definitive composition of tissue-incorporated material which is presumed by light microscopy to be silicone and to identify long term histopathologic sequelae of meniscal replacements. Adult female patients underwent meniscectomy and replacement with silicone rubber (Silastic) implants. After 12 to 18 months, recurrence of symptoms in 8% of these cases led to implant removal with excision of peri-implant fibrous pseudocapsules. Excised tissues, including one preauricular lymph node and implants were submitted for light microscopy, SEM, and energy dispersive x-ray microanalysis (EDX) for the identification of elemental composition, critical surface tension measurement, and internal reflection infrared spectroscopy. EDX revealed prominent peaks for silicon in both pseudocapsular and nodal tissues. Morphologic findings surrounding the long-term implants included foreign body reaction, synovitis, dystrophic calcification, fibrocartilaginous metaplasia, hyalinization, and scarring. Particulate silicone debris induced a pathologic response in the tissues and migrated to nodes. These findings suggest that periodic evaluation be performed over the life of such implants to rule out breakdown under function. These findings should intensify the search for improvements or replacements for silicone rubber as an interpositional material in the temporomandibular joint.     

Silicone granulomas: report of three cases and review of the literature

Since silicone is rapidly becoming one of the most commonly used biomaterials in modern medicine, pathologists will be observing increasing numbers of cases of silicone-related disease. Although numerous case reports have established that silicone elicits a characteristic response in tissues, the varying tissue reactions to silicone gels, liquids, and elastomers (rubber) have not been emphasized. Three cases are reported, and the literature is reviewed to illustrate the varying features of tissue reaction to silicone in its different forms. The first case is an example of silicone lymphadenopathy in an inguinal lymph node. This case demonstrates exuberant foreign body granuloma formation in response to particles of silicone elastomer. The second case involves a patient who had facial subcutaneous liquid silicone injections, and the third case is that of a woman in whom breast carcinoma developed 13 years after mammary augmentation with liquid silicone injections. These two cases illustrate the characteristic reaction to silicone liquid, with numerous cystic spaces and vacuoles in the soft tissues but minimal or no foreign body giant cell reaction. Scanning electron microscopy and energy dispersive x-ray analysis were performed in the first two cases, confirming the presence of silicon. Silicone migration and the clinical significance of various silicone-induced lesions are discussed.     

Silicone lymphadenopathy: A complication of silicone elastomer finger joint prostheses

Two cases of lymphadenopathy resulting from a lymph node foreign body reaction to silicone are presented. In each case lymph node biopsy was performed because of the clinical suspicion of neoplastic disease. Histologic study in both cases revealed no evidence of malignant disease, but rather demonstrated multinucleated giant cells in reaction to irregular fragments of refractile foreign material. The foreign substance was consistent in appearance with silicone. In each case a history of long standing rheumatoid arthritis and previous joint replacement with implantation of silicone elastomer prostheses was elicited.     

Loss of heterozygosity in fibrocystic change of the breast: genetic relationship between benign proliferative lesions and associated carcinomas

Loss of heterozygosity (LOH), a genetic change frequently detected in cancer, can also occur in benign epithelial foci in the breast. To characterize LOH in benign breast tissue, 32 cases containing the various components of fibrocystic change in the absence of malignancy were studied. Microdissected foci of ductal hyperplasia, apocrine metaplasia, sclerosing adenosis, and morphologically normal terminal duct lobular units (TDLUs) were analyzed for LOH at 14 polymorphic loci representing seven chromosomal arms. LOH was detected in 22% of normal TDLUs (6/27), 17% of adenosis (4/23), 19% of hyperplasia (4/21), and 53% of apocrine metaplasia (10/19) specimens. Because of the high percentage of LOH in apocrine metaplasia in nonneoplastic specimens, the genetic relationship between apocrine metaplasia and cancer was studied in a panel of breast cancer cases. Of 14 examples of apocrine metaplasia adjacent to a carcinoma, seven were found to have LOH with at least one marker. In all seven cases, the tumor and apocrine metaplasia shared LOH at one or more markers. The results demonstrate that LOH occurs frequently in the components of fibrocystic change as well as in normal TDLUs and suggest that foci of apocrine metaplasia can share a genetically altered precursor cell with an associated carcinoma.     

Silicone gel-filled breast and testicular implant capsules: a histologic and immunophenotypic study.

The immunophenotypic characteristics of silicone gel-filled breast and testicular implant capsules have not been well described. Therefore, we studied 17 paraffin-embedded tissue sections from 9 breast implant patients and 1 testicular implant patient to assess the type and extent of inflammatory responses present. Immunohistochemical analyses were performed on paraffin-embedded tissue sections for expression of CD20, CD45RO, betaF1, CD68, CD44, kappa and A immunoglobulin light chains, and bcl-XL (a member of the bcl-2 family of proteins involved in apoptosis). The most common histologic features included prominent T-cell and foamy macrophage reactions with foreign body giant cells and granulomas in a dense fibrovascular connective tissue. Foci of polyclonal plasma cells and acute inflammatory cells were variably present. In one case, there was reactive germinal center formation, a novel finding. A "pseudosynovium" at the implant capsule interface was present in the majority of cases as previously described; it showed reactivity with CD68. Thin strands of highly refractile, nonpolarizable material, consistent with silicone, were regularly noted in intra- and extracellular locations. The immunohistochemical results included reactivity of the majority of lymphocytes with CD45RO and/or betaF1 (confirming an anamnestic reactive T-cell phenotype), and reactivity of the macrophages, giant cells, and "pseudosynovium" with the macrophage/histiocyte marker, CD68. The reactive germinal centers were positive for CD20. Reactivity for CD44, an activation and intracellular adhesion marker, was frequently observed in the foamy macrophages and foreign body giant cells and has not been previously reported. The plasma cells demonstrated polyclonal immunoglobulin light-chain reactivity, consistent with a reactive process. These findings suggest that silicone implants induce chronic inflammatory responses in many adjacent capsules, which consist of anamnestically responding T cells, reactive B-lymphocytes, and macrophages.     

乳房假体隆乳术后并发硬结的细针吸取细胞学观察

目的 观察乳房假体隆乳术后并发硬结的细针吸取细胞病理学(FNAC)改变。方法 对20例采用2种假体(凝胶、自体脂肪颗粒)隆乳术后引起的硬结进行FNAC检查，其中4例行病理组织学观察。结果 主要细胞学改变是见不同假体物，如紫蓝、淡蓝色胶样物或变性坏死的脂肪细胞，中性粒细胞及多核巨细胞等。4例FNAC与病理组织学检查基本相符。结论 乳房假体可引起不同程度的组织反应，还可出现其他并发症。首要表现为硬结；某些假体(如硅胶)可能对机体组织有一定的毒性作用。因此，隆乳应谨慎，特别是未婚妇女，隆乳术后须密切随访。     

Simple mucin-type carbohydrate antigens (T,sialosyl-T,Tn and sialosyl-Tn) in breast carcinogenesis

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of normal breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.This work was supported in part by a grant (no. 201240/92) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Brazil     

Platinum in silicone breast implants

Silicone elastomers are widely used in implantable devices, including silicone breast implants. These rubbers are generally formed/cured using platinum-catalyzed hydrosilylation. The current scientific literature on the chemistry of platinum is reviewed, as it applies to the use of platinum catalysts for cure of silicone elastomers destined for use in silicone breast implants. These discussions serve as a basis to examine the recent literature describing release of platinum into tissues adjacent to silicone breast implants, the chemical nature of the platinum present in breast implants and the possible association between platinum and clinical outcomes.     

Liquid- and solid-state high-resolution NMR methods for the investigation of aging processes of silicone breast implants

To investigate aging processes of silicone gel breast implants, which may include migration of free unreacted material from the gel and rubber to local (e.g. connective tissue capsule) or distant sites in the body, chemical alteration of the polymer and infiltration of body compounds, various approaches of multinuclear nuclear magnetic resonance (NMR) experiments (29Si, 13C, 1H) were evaluated. While 29Si, 13C, and 1H solid-state magic angle spinning (MAS) NMR techniques performed on virgin and explanted envelopes of silicone prostheses provided only limited information, high-resolution liquid-state NMR techniques of CDCl(3) extracts were highly sensitive analytical tools for the detection of aging related changes in the materials. Using 2D 1H, 1H correlation spectroscopy (COSY) and 29Si, 1H heteronuclear multiple bond coherence (HMBC) experiments with gradient selection, it was possible to detect lipids (mainly phospholipids) as well as silicone oligomer species in explanted envelopes and gels. Silicone oligomers were also found in connective tissue capsules, indicating that cyclic polysiloxanes can migrate from intact implants to adjacent and distant sites. Furthermore, lipids can permeate the implant and modify its chemical composition.     

Synovial metaplasia of the skin

We present two female patients, aged 15 and 45 years, with synovial metaplasia of the skin. Both lesions, localized in the knee and hand respectively, arose after preceding local trauma. Case 1 had intradermal irregular cystic spaces in the adjacent myxoid stroma of which large polygonal eosinophilic cells were found. In contrast, case 2 was characterized by a longitudinal space within the lower dermis and subcutis which was lined by a membrane similar to hyperplastic synovium. The cells of the membrane showed an eosinophilic spindle shaped cytoplasm with processes towards the lumen. In both cases the eosinophilic cells, strongly suggestive of fibroblasts, showed staining for vimentin only, whereas no reactivity could be obtained with antibodies to actin, desmin, S-100 protein, Factor VIII related antigen, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and CD 68. The absence of CD 68 positivity differs from that seen in normal and hyperplastic synovium. Delayed wound healing around a nidus seems the most likely cause of the change.     

Histological patterns of bone and articular tissues after orthopaedic reconstructive surgery (artificial joint implants).

Revision surgery after failures of joint replacements leads to histological studies on joint and bone tissues close to the implanted material. Aspectic loosening is the main complication. The surgical pathologist has to identify wear debris (metal, polyethylene, polymethylmethacrylate, chiefly) which promotes a histiocytic granuloma. Some surgical procedures such as cup or resurfacing arthroplasties create a new articular surface and a bone remodeling or necrosis. Cemented joint prostheses show various membrane structures between bone and the cement mantle while there is an association of bone resorption and formation. Non-cemented, porous-coated joint prostheses induce little bone ingrowth, even in satisfactory clinical results. Mechanical factors are predominant in massive limb prostheses. For silicone elastomer implants or artificial ligaments, wear of material promotes many tissular reactions. Often used bone grafts show little creeping substitution process in case of homografts, even well-incorporated on X-rays. More retrieval specimen studies are necessary to delineate precise topographical histological lesions, including non-loosened joint implants.     

Fine-needle aspiration cytology of silicone granulomas in the augmented breast

We studied 12 aspirates from 10 patients who underwent diagnostic fine-needle aspiration cytology (FNAC) of an augmented or reconstructed breast. Six patients were augmented with silicone gel-filled implants and four patients had silicone liquid injections. FNAC indications included a painful or suspicious mass. Excisional biopsy was performed in six cases after FNAC. The findings of eight cases included modestly cellular smears composed of loosely cohesive histiocytes containing vacuoles of various sizes. Multinucleated foreign body giant cells, fragments of dense, amorphous fibrous tissue, and fibroblast nuclei stripped of cytoplasm were also present Two patients showed a mixture of inflammatory cells characteristic of intramammary lymph nodes or lymphoid aggregates. We conclude that silicone granulomas of the breast show a characteristic set of findings on FNAC which enable a cytopathologist to render a specific diagnosis given an appropriate history of breast augmentation. Diagn Cytopathol 1993;9:498-502. © 1993 Wiley-Liss, Inc.     

Dysplasia of the gallbladder. Its histogenesis and correlation to gallbladder adenocarcinoma

A total of 50 cases of gallbladder dysplasia found adjacent to carcinoma were examined histologically and immunohistochemically for metaplastic changes in order to elucidate the characteristics of the dysplasia of the gallbladder. The incidence of metaplastic changes in the dysplastic mucosa such as the occurrence of endocrine cells, lysozyme-immunoreactive cells, goblet cells, and Paneth cells were 58%, 74%, 32%, and 22%, respectively. Based on the presence or absence of metaplastic changes, these 50 cases of dysplasia were divided into 40 cases (80%) of metaplastic type dysplasia showing at least one marker of metaplasia and 10 cases (20%) of non-metaplastic type dysplasia showing no metaplasia. On the other hand, these 50 cases of carcinoma were divided into 10 cases of non-metaplastic type carcinoma and 40 cases of metaplastic type carcinoma based on the presence or absence of metaplasia in the tumor tissue. The incidence of metaplastic changes in the dysplastic lesions was compared between the dysplasia adjacent to non-metaplastic type carcinoma and that adjacent to metaplastic type carcinoma. The incidence of metaplasia in the dysplastic mucosa adjacent to metaplastic type carcinoma was higher than that adjacent to non-metaplastic type carcinoma with a statistically significant difference. Moreover, the presence or absence of metaplastic changes was also examined in the surrounding dysplasia and non-tumorous mucosa in each case. Most cases of metaplastic type carcinoma were surrounded by dysplasia with metaplastic changes and by metaplastic epithelium, whereas most cases of non-metaplastic type carcinoma were surrounded by dysplasia without metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of silicone breast prostheses on the assessment of body composition by dual-energy X-ray absorptiometry.

We examined the influence of silicone breast prostheses on body composition as assessed by dual-energy X-ray absorptiometry (DXA). Eighteen women were measured with and without a pair of silicone breast prostheses placed on the upper part of the trunk simulating endogenous implants. Bone area, bone mineral content (BMC), areal bone mineral density (BMD), lean tissue mass (LTM) and fat tissue mass (FTM) of the total body and of the subregions of the body, i.e. the head, trunk, arms and legs, were measured by a Norland XR-36 DXA scanner. After application of the silicone prostheses, bone area, BMC and BMD of the total body significantly increased by an average of 3.7, 6.6 and 3.4% (P<0.0001), respectively. Total body LTM and FTM were not affected. In the trunk region, changes were more pronounced. Trunk BMC, for example, was overestimated by 17.9% (P<0. 0001). The prostheses also influenced measurements of truncal soft tissue composition, with a small but statistically significant overestimation of both LTM (1.1%) and FTM (2.1%) (P<0.05). No changes in bone mass and soft tissue composition were seen in the head, arms and legs. Activation of a high-density detection software utility provided by the manufacturer had no influence on any of the measurements. We conclude that silicone breast prostheses affect the assessment of body composition by DXA.     

Influence of curing agent on fibrosis around silicone implants

Severe capsular contracture around silicone expander breast implants leading to pain and failure is a major clinical problem. Even though earlier studies have implicated the immunogenicity of silicone, the role of physical and chemical properties of the silicone material in excessive collagen deposition and fibrosis has been less addressed. The present study investigates whether there is any correlation between the type of curing systems i.e. addition and free radical curing and the fibrosis around silicone elastomer. The experiment carried out uses commercially available silicone ventriculo-peritoneal shunt material elastomer cured by platinum and the results are compared with results obtained in a similar study carried out by the authors using commercially available silicone tissue expander material cured by peroxide. Ultra-high molecular weight poly-ethylene (UHMWPE), the standard reference for biocompatibility evaluation, was used as the control material. The materials were implanted in rat skeletal muscle for 30 and 90?days. Inflammatory cells, myofibroblasts, cytokines, and collagen deposition at the material–tissue interface were identified by haematoxylin–eosin and Masson’s Trichrome stains and semi-quantitated based on immunohistochemical studies. Results indicate that even though the cellular response in the initial phase of wound healing was similar in both platinum and peroxide-cured materials, the collagen deposition in the proliferative phase was more around peroxide-cured material in comparison to the platinum-cured silicone elastomer. There is a need to look into the molecular mechanisms of this interaction and the possibility of using curing systems other than free radical peroxide in the manufacture of silicone elastomer expanders for breast prosthesis.     

Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized clinical entity, with only 39 well-documented cases reported worldwide, including 3 fatalities. Because of its rarity, the clinical and pathologic features of this malignancy have yet to be fully defined. Moreover, the pathogenesis of ALCL in association with textured silicone gel breast implants is poorly understood. Here we report a case of BIA-ALCL arising in a 67-year-old woman with a mastectomy due to breast cancer followed by implantation of textured silicone gel breast prosthesis. The patient presented with breast enlargement and tenderness 8 years following reconstructive surgery. MRI revealed a fluid collection surrounding the affected breast implant. Pathologic examination confirmed the presence of malignant ALCL T cells that were CD30+, CD8+, CD15+, HLA-DR+, CD25+ ALK- and p53. A diagnosis of indolent BIA-ALCL was made since tumor cells were not found outside of the capsule. Interestingly, an extensive mixed lymphocytic infiltrate and ectopic lymphoid tissue (lymphoid neogenesis) adjacent to the fibrous implant capsule were present. The patient was treated with capsulectomy and implantation of new breast prostheses. Six months later, the patient was found to have BIA-ALCL involvement of an axillary lymph node with cytogenetic evolutionof the tumor. To our knowledge, this is the sixth reported case of aggressive BIA-ALCL. Unique features of this case include the association with lymphoid neogenesis and the in vivo cytogenetic progression of the tumor. This case provides insight into the potential role of chronic inflammation and genetic instability in the pathogenesis of BIA-ALCL.     

A formal risk assessment of silicone breast implants.

In 1992, the United States Food and Drug Administration (FDA) announced that breast implants filled with silicone gel would be available only through controlled clinical studies despite the fact that they had been used for mammoplasty in millions of women around the world for more than 30 years. The safety of silicone gel breast implants had come into question after several reports on a possible association between the implants and subsequent development of connective-tissue diseases. Risk assessment refers to the systematic, scientific characterization of potential adverse effects of human exposures to hazardous agents or activities. The following risk assessment is intended to review the current scientific evidence for the safety of silicone gel-filled breast implants since the FDA's decision in 1992. There now appears ample evidence from the scientific literature for the safety of these prostheses.