Light and Electron Microscopic Study of an Invasive Cribriform Carcinoma with Extensive Microcalcification Developing in a Breast with Silicone Augmentation

Although recent epidemiologic studies suggest that silicone augmentation of the breast is not associated with an increased risk of mammary carcinoma, cases of breast carcinoma arising in augmented breasts are being increasingly encountered as a large number of patients who had augmentation are getting older. A case of a 51-year-old woman with a 20-year history of breast augmentation who developed an invasive cribriform carcinoma associated with extensive microcalcification is presented. The patient had submammary silicone implants 20 years ago that were replaced, because of local complications, in subpectoral positions 10 years later. Dispersive X-ray microanalysis failed to demonstrate silicone in sections of the tumor and adjacent breast tissue. Appropriately fixed tumor tissue was available for electron microscopic examination. The tumor cells were rich in mitochondria, and their luminal surfaces were endowed with abundant microvilli, but the cell surfaces that came closest to the calcified microspheriols were devoid of microvilli and had cellular buddings between the microspheriols. It is suggested that the tumor cells might have been actively involved in the process of microcalcification.     

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.     

硅胶材料隆乳对人体口腔黏膜细胞状态的影响

背景：既往研究显示,口腔黏膜细胞的生存状态直接受人体营养状态的影响,因此可能是外科营养状态的良好指标,但该指标是否同样会受到外科手术创伤刺激影响这一问题的答案尚不明确。 目的：观察硅胶隆乳相关外科创伤性刺激对口腔黏膜细胞生存状态的影响。 方法：选择拟行硅胶隆乳的女性患者32例,其中有生育史13例,无生育史19例,年龄23-45岁,分别采用亚G1峰法及Ki-67法于硅胶隆乳前后检测患者口腔黏膜细胞的增殖率及凋亡率,对数据进行统计学比较。 结果与结论：32例硅胶隆乳者均顺利完成手术,围术期未发生严重不良反应。32例硅胶隆乳患者隆乳前口腔黏膜细胞凋亡率及增殖率分别为(27.3±6.2)%与(27.8±5.8)%,隆乳后口腔黏膜细胞凋亡率及增殖率分别为(27.8±5.8)%与(20.2±7.7)%,隆乳前后口腔黏膜细胞凋亡率及增殖率比较差异均无显著性意义(P > 0.05)。表明人体口腔黏膜细胞的增殖及凋亡并未受到硅胶隆乳相关外科创伤的明显影响,口腔黏膜细胞生存状态用于硅胶隆乳受者营养状态的评估可能具有一定的价值。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

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.     

A study of the localization of transferrin receptor in malignant tumor cells

In several studies, numerous microvilli were found on the surfaces of malignant tumor cells which had high growth potentials, and some tumor-related antigens were identified on these microvilli. Transferrin receptor (TfR) is expressed in proliferating cells and regarded as a tumor marker. In human carcinoma cell lines (HeLa cells, KB cells, and HSC-7 cells), significantly more microvilli were observed in the subconfluent phase than in the confluent phase. Also, TfR was found along the plasma membranes, especially well developed microvilli, coated pits, and coated vesicles in both phases by the immunoelectron microscopic method. These results indicate that the proliferative ability of the tumor cells might correlate with the development of microvilli. This study was presented at the 26th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Kochi, October, 5–7, 1994.     

Malignant adenomyoepithelioma of the breast with matrix production may be compatible with one variant form of matrix-producing carcinoma: a case report

We examined a 77-year-old woman who suffered from a left breast tumor. She had undergone right mastectomy for invasive ductal carcinoma at 68 years of age, and rectal resection for mucinous carcinoma at the age of 74 years. The left breast tumor measured 3.8x2.5x1.6cm. Neoplastic cells consisted of atypical epithelial and myoepithelial cells. The former cells were polygonal and large. They were located in the periphery of the tumor, arranged in a ductal pattern, and expressed cytokeratins, S-100 protein, maspin, and MIC2. The latter cells were composed of dark cells which proliferated in a periductal pattern, and stellate cells which were located in the center of the tumor. They invaded the chondromyxoid tissues, and proliferated in a lace-like pattern. Atypical myoepithelial cells expressed vimentin, S-100 protein, maspin, and MIC2. We conclude that malignant adenomyoepithelioma of the breast with matrix production might be compatible with a variant form of matrix-producing carcinoma.     

Glycogen-rich clear cell carcinoma of the breast. An autopsy case

An autopsy case of glycogen-rich clear cell carcinoma (GRCCC) which arose in the right breast of a 72-year-old woman is reported. Light microscopic examination of the small finger-tip-sized tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Immunohistochemically, most of the clear tumor cells were stained for epithelial membrane antigen (EMA) and alpha-lactalbumin, whereas a few eosinophilic tumor cells were positive for S-100 protein, EMA and actin. Electron microscopically, aggregates of glycogen particles, numerous empty glycogen lakes, microvilli, tight junctions and basal lamina were identified. Autopsy disclosed marked metastases to the liver, lung, adrenal, skin and lymph nodes. Primary breast cancer was confirmed by exclusion of a primary at any other site. It is suggested that although rare, GRCCC of the breast is as aggressive as usual invasive ductal carcinoma, and is associated with severe nodal and blood-borne metastases, followed by death.     

Micropapillary Carcinoma of the Breast with Necrosis-like Cell Death: A Case Report

A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.     

Metaplastic spindle-cell (fibromatosis-like) carcinoma of the breast--report of 4 cases

The authors report about clinico-morphological features in four cases of spindle-cell metaplastic carcinoma of the breast, closely mimicking benign soft tissue fibromatosis or nodular fasciitis. All patients were females aged 54-72 years with a palpable nodule within the breast, 20-35 mm in size. Histologically, the tumor infiltrated surrounding tissue; it consisted of spindle cells with relatively bland morphology, arranged in a fascicular, storiform or random fashion. Mitotic activity was low, focally the tumors revealed regressive changes (hyalinization, myxoid degeneration). Cytokeratin expression was proven in all four cases. In two patients the tumor metastasized and the patients died of it; this fact confirms recently published data that despite its deceptively benign appearance, fibromatosis--like carcinoma of the breast is undoubtedly a malignant process with potentially aggressive behaviour. Differential diagnosis of this unusual variant of metaplastic breast carcinoma is discussed together with related therapeutic issues.     

Micropapillary carcinoma of the breast with necrosis-like cell death: a case report

A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.     

Do biomaterials cause implant-associated mesenchymal tumors of the breast? Analysis of 8 new cases and review of the literature

Implant-associated mesenchymal tumors (IAMT) of the breast are rare, and most are fibromatoses. There has been no systematic analysis of IAMT to determine their full histologic spectrum, whether there is an association with implant type or rupture, and if evidence supports a causal or fortuitous relationship between tumor and implant. We, therefore, analyzed all mesenchymal tumors associated with breast implants from our soft tissue consultation database spanning a period from 1989 to 2005. Information regarding location, type, and integrity of implant and its temporal relationship to tumor was recorded. Eight IAMT were identified exclusively in female patients (ages 28-64 years; median, 38 years), all of whom presented with a palpable mass. Tumors developed after placement of either a silicone (n = 7) or saline (n = 1) implant (median, 2 years; range, 1.8-10 years), which was usually inserted for cosmetic purposes (n = 7). All tumors arose in or around the capsule of a grossly intact implant, and in one case, the tumor was confined exclusively to the implant capsule. In patients with silicone implants, silicone granulomas were identified within the capsule and associated neoplasm despite the integrity of the implant. Six cases were fibromatoses; one was a pleomorphic undifferentiated sarcoma; and one was a fibrosarcoma. None of the patients with fibromatosis was known to have familial adenomatous polyposis (FAP) or Gardner syndrome, although one had Poland syndrome (aplasia of the thorax). One patient with a sarcoma had received radiation 10 years previously for breast carcinoma. Six patients were treated with local excision, one with a wide excision, and one patient with fibromatosis was treated with medical therapy. Median follow-up was 3.2 years (range, 16-92 months). One of the 5 patients with fibromatosis developed 2 recurrences. Neither of the 2 patients with sarcomas has developed metastasis. No patient has died of disease. We conclude that IAMT comprise 2 distinct groups—fibromatosis and sarcoma. Surgical trauma, perhaps occurring in patients with a predisposition to develop desmoid tumors, could account for fibromatosis in this setting. The causal relationship between implants and sarcomas is difficult to assess given the rarity of these tumors and that some may be radiation induced. However, at present, there is insufficient evidence to claim that they are biomaterial related.     

Glycogen-rich Clear Cell Carcinoma of the Breast An Autopsy Case

An autopsy case of glycogen-rich clear cell carcinoma (GRCCC) which arose in the right breast of a 72 year old woman is reported. Light microscopic examination of the small finger tip-sized tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Im-munohistochemically, most of the clear tumor cells were stained for epithelial membrane antigen (EMA) and alpha lactalbumin, whereas a few eosinophilic tumor cells were positive for S 100 protein, EMA and actin. Electron microscopically, aggregates of glycogen particles, numerous empty glycogen lakes, microvilli, tight junctions and basal lamina were identified. Autopsy disclosed marked metastases to the liver, lung, adrenal, skin and lymph nodes. Primary breast cancer was confirmed by exclusion of a primary at any other site. It is suggested that although rare, GRCCC of the breast is as aggressive as usual invasive ductal carcinoma, and is associated with severe nodal and blood borne metastases, followed by death. Acta Pathol Jpn 39: 469 472, 1989.     

医用聚丙烯酰胺水凝胶注射隆乳后硅凝胶假体置入时机的选择

背景：医用聚丙烯酰胺水凝胶注射隆乳的并发症较多,取出后再次置入硅凝胶假体的时机尚不明确。 目的：探讨医用聚丙烯酰胺水凝胶注射隆乳后取出,再次行硅凝胶假体置入隆乳的最佳时机。 方法：纳入聚丙烯酰胺水凝胶注射隆乳后出现不良反应的18例患者,共33只乳房,聚丙烯酰胺水凝胶取出6个月后行硅凝胶假体置入隆乳。置入后随访,调查内容包括局部体征、乳房的轮廓形态、大小、位置、手感、影像学检查结果和心理状况等,将反馈信息分为优、良、中、差4个等级。 结果与结论：随访6个月~2年,聚丙烯酰胺水凝胶取出6个月后行硅凝胶假体置入隆乳优良率超过90%,乳房外形丰满圆润,呈水滴形,轮廓自然柔美,手感柔软有弹性,无压痛,无硬结及游走性包块。提示医用聚丙烯酰胺水凝胶注射隆乳后出现不良反应或患者要求取出者,取出6个月后再行硅凝胶假体置入隆乳可最大限度地避免聚丙烯酰胺水凝胶以及取出手术创伤对隆乳后效果的影响。 关键词：聚丙烯酰胺水凝胶;注射隆乳;硅凝胶假体置入;手术时机;并发症 doi:10.3969/j.issn.1673-8225.2012.12.022     

Weddellite calcification in the breast: eighteen cases with implications for breast cancer screening

Breast tissue obtained from 18 of 246 women (7.3%) having localization biopsy for microcalcification contained crystals of Weddellite (calcium oxalate dihydrate). This was characterized by microscopic infra-red spectroscopy in three cases. Weddellite calcification was associated with benign lesions in 16 cases, but incidental atypical lobular hyperplasia and lobular carcinoma in situ were present, each in one case. Pathologists should be aware of this common non-haematoxyphilic, birefringent form of breast micro-calcification. Its presence has implications for the examination of biopsy specimens resulting from breast cancer screening using mammography.     

Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer.

Microcalcifications are a common phenomenon associated with breast cancer and are often the only mammographic sign of a malignant breast disease. Although microcalcifications are not restricted to breast cancer and can be also associated with benign lesions, it is noteworthy that they are composed exclusively of hydroxyapatite in breast carcinoma. Hydroxyapatite is the bone-associated phosphocalcic crystal the deposition of which in bone tissue requires the coordinated expression of several molecules such as osteonectin (OSN) and osteopontin (OPN), synthesized by cells of the osteoblastic lineage. In this study, we evaluated the expression of these two bone matrix proteins, using an immunoperoxidase technique and specific antibodies, in 79 breast lesions including 28 benign and 51 cancerous specimens. We found that normal mammary tissue associated with the lesions examined expressed generally undetectable or lightly detectable (0 or 1+) amounts of OSN and OPN (92 and 81%, respectively). Benign breast lesions, including fibroadenoma and fibrocystic dysplasia, were generally weakly stained (0 or 1+) with both anti-OSN and anti-OPN antibodies (96.4 and 60.7%, respectively). Interestingly, the majority of both in situ and invasive breast carcinoma lesions showed a strong expression (2+ or 3+) for OSN or OPN (74.5 and 84.3%, respectively). High expression of these two bone matrix proteins was associated with frequent microcalcification deposition in the lesion. This study is the first extensive study of OSN and OPN expression in mammary cancers. Our data suggest that OSN and OPN could play a role in the formation of ectopic microcalcifications often associated with breast cancer. It is also tempting to speculate that the expression of these two glycoproteins by breast cancer cells play a role in the preferred bone homing of breast metastases.     

Ultrastructure of early phase hepatic metastasis of human colon carcinoma cells with special reference to desmosomal junctions with hepatocytes

To demonstrate ultrastructural events in the early phase of hepatic metastasis of human colon carcinoma, we intrasplenically injected a highly metastasizable, human colon carcinoma cell line LM-H3 (1 x 10(6) cells) into nude mice, and electron microscopically investigated the hepatic metastasis. At 24 h, tumor cells adhered to the endothelial wall of terminal portal venules and periportal sinusoids. At 48-72 h, after extravasation, they deeply invaded the hepatic cell plate and the interstitial tissue of the portal tract, in which they underwent proliferation and made the metastatic foci. Tumor cells were linked with each other or with surrounding hepatocytes by desmosomes. Desmosomes were maintained during the mitosis. When invading tumor cells were exposed to the bile canaliculi, they generated microvilli on the surface. Microvilli were also formed at the luminal surface of intracytoplasmic inclusions. In the interstitial tissue of the portal tract, tumor cells were closely associated with fibroblasts. However, no junctional specializations were seen between them. The present study demonstrated that human colon carcinoma cell line LM-H3 formed desmosomes with hepatocytes soon after invasion of the hepatic cell plate, suggesting the regulatory role of an interaction with hepatocytes in the growth of metastatic foci within the liver parenchyma.     

注射聚丙烯酰胺水凝胶隆乳后的乳腺病变

背景：聚丙烯酰胺水凝胶是一种人体软组织填充剂,主要用于注射隆乳,大量文献报道它会引起乳房硬结、感染、凝胶移位、乳房变形、乳腺增生甚至乳腺癌等并发症。 目的：观察聚丙烯酰胺水凝胶注射隆乳后乳腺的病理学改变。 方法：收集聚丙烯酰胺水凝胶注射隆乳后病例35例,采用苏木精-伊红染色、免疫组织化学染色、PAS和AB染色进行病理学观察。 结果与结论：35例注射隆乳后的病例,26例发生了异物肉芽肿,发生率为74%(26/35);3例发生了乳腺癌,发生率为9%(3/35)。病灶内见大小不等的囊腔,部分囊腔完全由组织细胞、异物巨细胞和纤维组织填充。病变处和周围乳腺组织、脂肪及横纹肌组织均可见变性坏死,部分呈凝固性坏死。部分病例病变周围乳腺导管部分呈增生性改变,表现为普通型增生、不典型增生、原位癌或浸润癌,提示聚丙烯酰胺水凝胶对人体组织有毒性作用,会导致组织的变性坏死和引起异物肉芽肿反应,其和乳腺癌的发生有一定的相关性。     

Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils.

Invasive micropapillary carcinoma, originally described as a distinctive type of invasive carcinoma in the breast, is being increasingly recognized as a separate entity in many other organs; however, it has not yet been documented in the pancreas or periampullary region. In this study, 313 pancreatic and 73 periampullary carcinomas were reviewed to investigate the micropapillary pattern in this location. Eight periampullary and eight pancreatic cases (4%) were composed at least focally (>20%) of invasive micropapillary carcinoma. The patients were 10 males and six females, mean age 69 years. The mean tumor size was 3.2 cm. Lymph node metastasis was detected in 11/15 cases. The median survival was 8 months (all were resected). Invasive micropapillary carcinoma was characterized by small, closely packed micropapillary clusters (without fibrovascular cores) lying within clefts. The cells had moderate degree of nuclear atypia. In nine cases, there was abundant inflammation composed of neutrophils concentrating around the tumor cells, both intraepithelial ('cannibalism') and stromal. Molecules implicated in abnormalities of tumor cell-stroma adhesion, galectin-3 and E-cadherin were expressed in the cytoplasm of 11/11 and 9/11 cases, respectively. Reversal of cell polarity was observed by MUC 1 in all 11 cases tested, which showed labeling in the stroma-facing surfaces of the micropapillary clusters, also confirming that the clefts are not merely a processing artifact, but indeed a true biologic alteration. In conclusion, invasive micropapillary carcinoma constitutes 4% of carcinomas in the pancreatic/periampullary region and is commonly associated with abundant neutrophilic infiltrates. Invasive miropapillary carcinoma appears to be more common in periampullary than in pancreatic invasive micropapillary carcinoma would qualify as poorly differentiated both based on pattern and the median survival (8 months)..     

Mammary Paget's disease: evidence of diverse origin of the disease with a subgroup of Paget's disease developing from the superficial portion of lactiferous duct and a discontinuous pattern of tumor spread

The pattern of spread of intraductal carcinoma associated with mammary Paget's disease has not been well studied. The purpose of this study was to examine the site of origin and the pattern of tumor spread with a three-dimensional view by serial sectioning of the tissue blocks from 19 cases of Paget's disease. Intraductal carcinoma in the superficial portion of the lactiferous ducts was seen in continuity with the overlying epidermis with Paget's disease in all 19 cases. In seven cases that had adequate tissue sampling, five showed a continuous pattern of the intraductal carcinoma within the superficial as well as the deep breast tissue. In the remaining two cases, a portion of benign duct was identified between the intraductal carcinoma in the superficial lactiferous duct and the deep breast tissue. This discontinuous pattern of spread of the intraductal carcinoma was also identified in the foci of carcinoma in deep tissue. In the five cases in which the tumor involved the skin and only the superficial portions of the lactiferous duct, the leading edge of the intraductal carcinoma was seen orientated in the direction of the nipple towards the deep breast tissue. Our study of Paget's disease demonstrated that in addition to tumor spread along the lactiferous ducts from intraductal carcinoma in the deep tissue towards the nipple, there was a group of Paget's disease arising from the nipple. These lesions included: (i) lesions limited to the areolar tissue; and (ii) lesions with intraductal carcinoma involving the duct system in both superficial and deep breast tissue with and, possibly, without skip areas pattern of spread. Although certain cases of Paget's disease may appear superficial, an independent associated carcinoma in deep breast tissue has to be ruled out.     

乳腺浸润性微乳头状癌的形态改变与生物学行为的关系

目的 观察乳腺浸润性微乳头状癌的形态与生物学行为之间的关系。方法 对2088例术前没有作活检取材(仅经细胞学或细针穿刺活检诊断)的乳腺癌乳腺切除标本做全乳腺切片检查,其中浸润性导管癌1880例,观察浸润性微乳头状癌的临床病理学特征及光镜、电镜下的形态学表现。结果 浸润性微乳头状癌的发生率为6．2％(117／1880),其淋巴管侵犯(54．7％,58／106)、淋巴结转移阳性率(76．4％,81／106)及转移的个数(平均9．6)均明显的高于浸润性导管癌。光镜下特征性表现为癌巢由呈集块型或(和)腺管型的微乳头状癌巢组成,与网状间质间形成明显的空隙(主间质分离)。电镜下见癌巢与间质接触侧的细胞表面有大量的微绒毛,与间质的结合弱;癌细胞质内含有丰富的细丝;间质内见丰富的脉管。结论 浸润性微乳头状癌的淋巴管侵袭力强和淋巴结转移率高,这种恶性程度高的生物学行为可能与其癌巢的容易脱离及肿瘤细胞本身所具有的高度运动能力以及富含脉管的网状间质有关。