The significance of argyrophilia in human breast carcinomas

Summary The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that true carcinoid tumours of the breast are rare.A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells.Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of the 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/ peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction.It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells.     

A case of basaloid-squamous carcinoma of the esophagus: Immunohistochemical and ultrastructural studies

A case of basaloid-squamous carcinoma of the esophagus in an 83 year old man is reported. The esophageal tumor showed a fungating growth at the junction of the middle and lower esophagus and was composed microscopically of submucosal multiple nests with solid and cribriform-like patterns accompanied with a small focus of squamous cell carcinoma adjacent to the overlying esophageal epithelium. The structural features closely resembled those of basaloid-squamous carcinoma. The submucosal tumor cells were immunohistochemicaliy positive for epithelial membrane antigen, wide spectral keratin, alpha actin and S-100 protein. By electron microscopy, the tumor cells had microvilli, des-mosomes and bundles of myofilaments, and replicated basement membranes were frequently observed adjacent to the nests. The positive immunoreaction of S-100 protein and alpha actin and the existence of bundles of myofilaments indicated that the present tumor did not correspond well with basaloid-squamous carcinoma. In addition, there was no evidence of true glandular lumina in the tumor nests, a finding which was inconsistent with that of adenoid cystic carcinoma. From the immunoreactivity of S-100 protein and ultrastructural features, it was considered that the present submucosal tumor had originated from undifferentiated pluripotential primitive cells, which differentiated to myoepithelial cells.     

Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study

The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35–80 years of age. One case recurred after 4 years, and in two cases axillary lymph-node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland.The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast. Received: 19 November 1999 / Accepted: 7 February 2000     

Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma

Androgens and androgen receptors (AR) are involved in the pathogenesis of breast cancer. Epidemiological studies have shown a significant association between the risk of breast cancer and androgens. However, the functional role and clinical value of AR expression in breast carcinoma have still not been clearly defined. The present study was set up to investigate the prevalence of ARs in a series of consecutive invasive breast carcinomas (IBCs) and to evaluate the patterns of AR phenotypes in a series of selected invasive lobular carcinomas (ILCs). Among the 250 consecutive IBCs (consisting of 212 ductal and 38 lobular neoplasms), AR immunoreactivity was observed in 151/250 (60.4%) cases, being expressed in 118/212 (56%) ductal and 33/38 (87%) lobular carcinomas (a statistically significant difference, χ²=11.82). AR expression was frequently associated with ER (65.2%, χ²=14.33) and PR positivity (66.9%, χ²=7.36). Most AR positive cases showed a low proliferative index (63.7%) and a low or intermediate histological grade (G1–G2, 63.9%). Among the 80 selected ILCs, AR expression was observed in 64/80 (80%) cases. Our results confirm that ARs are expressed in most breast cancers. Moreover, we demonstrated that AR positivity is particularly marked in lobular neoplasms. In addition, AR positive carcinomas are frequently characterized by a low or intermediate grade, a low proliferative index and ER and/or PR co-expression.     

Histiocytoid breast carcinoma: Histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies

Histiocytoid breast carcinoma (HBC) is a rare variant of breast carcinoma and often causes a diagnostic dilemma because of its histological similarities to some types of breast cancer and benign lesions. To elucidate the incidence of HBC and its biological properties, histological specimens from 1010 breast cancer patients treated at Yokohama Minami Kyosai Hospital between 1972 and 1996 were reviewed. Three cases of pure HBC and three cases of combined HBC (two with pleomorphlc lobular carcinoma and one with apocrine ductal carcinoma) were found, yielding an Incidence of 0.3% for each. Two of the three pure HBC cases contained foci of in situ lobular carcinoma. Targetoid and Indian file invasive patterns, the features characteristic of lobular carcinoma, were present in all three pure HBC cases and in two of the three combined HBC with pleomorphic lobular carcinoma. These results, together with those of previous studies, suggested that the majority of HBC are of lobular origin, although the apocrine ductai origin is also possible in a small number of HBC. Diastase-resistant periodic add-Schiff-positive granules and granular immunoreactivities for gross cystic disease fluid protein-15 (GCDFP-15) were characteristic of the histiocytoid tumor cells in both the pure and combined HBC, suggesting the apocrine differentiation of tumor cells. All three pure HBC cases were in stage 1 and were free of the disease for up to 5 years and 1 month after the lumpectomy. Thus, the prognosis of HBC appears to be dependent on the stage of the disease and may not always be poor, as indicated by the original report mentioning a preferential eyelid metastasis.     

Glycogen-rich clear cell carcinoma of the breast: Report of a case with fine-needle aspiration cytology and immunocytochemical and ultrastructural studies

Fine-needle aspiration cytology, immunocytochemistry, and electron microscopic findings are described in a case of glycogen-rich clear cell carcinoma of the breast. the aspirate contained many small and large papillary cell groups and numerous single tall columnar cells with apical cytoplasmic projections and mild to moderate degree of nuclear pleomorphism. Cytochemical localisation of glycogen and immunostaining on air-dried smears with CEA and actin monoclonal antibodies permitted the correct identification and differential diagnosis of the tumor. Electron microscopic examination of the resected specimen confirmed the diagnosis of glycogen-rich clear cell carcinoma. the differential diagnosis and potential diagnostic pitfalls are discussed, and recommendation are offered to prevent misdiagnosis.     

Immunohistochemical and cytogenetic characterization of acantholytic squamous cell carcinoma of the breast

Primary acantholytic squamous cell carcinoma (ASCC) of the breast is a rare and aggressive variant of invasive breast cancer. Here we report two new cases of ASCC and their immunohistochemical and cytogenetic characterization. One case was associated with systemic metastases and death and the other with local failure prior to loss of follow-up. Using comparative genomic hybridization (CGH), both tumors showed a high overall number of chromosomal imbalances with a similar pattern of gains and losses. Genetic aberrations common to both tumors included losses at 3p11-p25, 5q21-q31, 8p, 9, 13p13-q21, 16q12-q21, and 17p and gains at 1q31-qter, 7p, 18q12-qter, 19q, and 20. Immunohistochemically, the tumors were characterized by high proliferative activity, an uncommon cytokeratin expression profile, reduced E-cadherin staining, and overexpression of p53 and epithelial growth factor receptor (EGFR). The results of our analyses suggest that genetic alterations observed in ASCC of the breast include imbalances commonly observed in both mammary adenocarcinoma and squamous cell carcinoma of other locations. Furthermore, the overexpressed EGFR could be a possible therapeutic target for individual cases of this aggressive tumor type.     

Pigmented carcinoma of the breast: an ultrastructural study

A pigmented skin lesion on a breast removed for carcinoma resembled melanoma by routine light microscopy, but correlation with immunohistochemistry and electron microscopy established that carcinoma cells within the upper dermis were intermingled with a proliferation of non-neoplastic melanocytic cells. Ultrastructurally, the tumor cells possessed desmosomes and intracytoplasmic lumina and mature melanosomes were present in their cytoplasm. The melanocytic cells were identified as melanocytes or melanophages, and it was concluded that the tumor in the skin was a passively pigmented carcinoma and not a melanoma or metaplastic breast carcinoma.     

Electron microscopic studies of primary apocrine carcinoma of the breast

Three cases of apocrine carcinoma of the breast were investigated by light and electron microscopy. Histologically, the tumor cells were shown to have eosinophilic granular cytoplasm and occasional cytoplasmic snouts protruding into the lumen. Ultrastructurally, light and dark tumor cells were identified, and there were many lysosome-like dense bodies of various sizes and small dense granules grouped in the subapical region. Many mitochondria with incomplete cristae and numerous small vacuoles were distributed in the cytoplasm. Occasionally, intracytoplasmic lumen were visible in the tumor cells. These ultrastructural findings are quite similar to those found in normal apocrine sweat glands. However, the presence of an intraductal component of carcinoma suggests the origin to be mammary epithelial cells. This study was presented at the 25th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Matsumoto, September 28–30, 1993.     

Elastosis in lung carcinoma: Immunohistochemical, ultrastructural and clinical studies

Elastosis is the pathological finding of focal deposits of elastic fibers in abnormal amounts within tissue. It is well described in the case of infiltrating carcinoma of the breast, but elastosis in lung carcinoma has not been previously documented in detail. We investigated the characteristics of elastosis in lung carcinoma with light and electron microscopies, and immunohistochemistry for alpha-1-antitrypsin. A total of 184 surgically resected primary lung carcinomas were studied. Elastosis was detected in adenocarcinomas (85/106), squamous cell carcinomas (11/60) and adenosquamous carcinomas (5/7), but not in small-cell carcinomas (n = 4) or large-cell carcinomas (n = 5). The degree of elastosis in each case was divided into one of five grades, graded as 3+ to 1-. The score of elastosis was significantly higher in adenocarcinoma than that in squamous-cell carcinoma (P < 0.01). In the cases of adenocarcinoma, the mean score of elastosis in the well-differentiated type (WD n = 43) was higher than that in the moderately differentiated (MD) (n = 39; P = 0.012) and poorly differentiated (PD) types (n = 24; P < 0.01). The mean score of elastosis in MD adenocarcinoma was also higher than that in the PD type (P < 0.01). Light- and electron-microscopic analyses revealed that these elastic fibers in elastosis were composed of aggregates of thick mature and fine immature elastic fibers, and were positive for alpha-1-antitrypsin. It is suggested that both degraded elastic fibers and newly synthesized fibers are contained in the elastosis of lung carcinoma. Although no significant evidence was detected to suggest any correlation between elastosis and the degree of tumor invasion, the survival curves of adenocarcinomas with elastosis showed a significantly improved prognosis than of those without elastosis in the cases of stages IA and IB (n = 52; P = 0.026).     

Collagenous spherulosis of the breast. Immunohistochemical and ultrastructural studies

Collagenous spherulosis of the breast is a recently described benign breast lesion that has previously been seen only incidentally. The authors report two cases of this lesion studied by immunohistochemistry and electron microscopy and a third case studied by light microscopy alone. The results demonstrate the participation of two cell types in the process: myoepithelial cells, which stained positively for cytokeratin, S-100 protein, and muscle-specific actin and contained intermediate filaments with dense bodies, pinocytotic vesicles, and formed cell junctions; and epithelial cells, which reacted for cytokeratin but not for S-100 protein or muscle-specific actin and contained intracytoplasmic lumina, formed lumina with microvilli, and desmosomes. Material constituting the spherules stained intensely for type IV collagen, and its ultrastructure was similar to that of basement-membrane material. The authors conclude that collagenous spherulosis results from a proliferation of epithelial and myoepithelial cells, the latter of which produce basement-membrane material.     

Lymphoepithelioma-like carcinoma of the breast

Lymphoepithelioma-like carcinoma (LELC) of the breast is a rare, newly recognized subtype of breast carcinoma. Distinction from medullary carcinoma is important because of the difference in biologic behavior of these two neoplasms and LELC of the breast is regarded as an unusual form of lobular carcinoma. We present the case of a 56-year-old female with a breast mass measuring 2 cm in diameter, which was diagnosed as invasive lobular carcinoma with LELC pattern. This is the ninth case reported in the English literature and to the best of our knowledge the first one with lymph node metastasis.     

Immunohistochemical staining patterns of tenascin in invasive breast carcinomas

Summary Eighty-two cases of primary invasive breast carcinoma and adjacent normal mammary glands were examined immunohistochemically for tenascin expression and distribution. Formalin-fixed tissues pretreated with actinase were processed by the avidin-biotin complex method using anti-human tenascin monoclonal antibody (RBC1). In normal mammary glands, tenascin was distributed around the ducts and ductules but not around the acini. In carcinomas, a high incidence of tenascin-positive cases (>67%) was seen with various histological appearances, with the exception of lobular carcinoma where a low incidence was found (25%). Although intense staining was seen around cancerous foci when compared with normal mammary glands, tenascin was often expressed at cancer-mesenchymal junctions with dense fibrotic stroma, but not at junctions with active inflammatory change and a loose fibrotic stroma. Tenascin expression is not an all-or-none marker for mammary malignancy and the staining pattern suggests either a role in stimulating cancer cells or a host defence mechanism accompanied by a desmoplastic response to them.     

Electron microscopic and immunohistochemical studies of spindle cell carcinoma of the breast

A spindle cell carcinoma of the breast was investigated by electron microscopy and immunohistochemistry. Histologically, the tumor was composed of an admixture of carcinomatous parts and sarcomatoid element composed of atypical spindle cells. Ultrastructurally, carcinomatous cells had numerous tonofilaments and desmosomes, and occasional intracytoplasmic lumina. In contrast, spindle cells possessed numerous intermediate filaments and a few weak junctions. Immunohistochemically, carcinomatous cells showed positive reactions for epithelial markers, but spindle cells for vimentin, only. Thus, the carcinomatous cells had characteristics of epithelial cells, but the spindle cells had characteristics of mesenchymal cells. These features were distinguishable by both electron microscopy and immunohistochemistry. This study was presented at the 24th Annual Meeting of the Clinical Electron Microscopy Socienty of Japan, Okayama, September 17, 1992.     

乳腺浸润性导管癌与小叶癌的超声诊断分析

目的探讨乳腺浸润性导管癌和浸润性小叶癌的超声声像图特征。方法对2006年1月至2008年6月经手术、病理证实为乳腺浸润性导管癌（IDC）136例和浸润性小叶癌61例的超声声像图、彩色多普勒表现进行对比分析。结果两种病理类型的肿瘤的超声声像图在肿块形状、内部与后方回声以及血流图上差异有统计学意义（P〈0．05）。在侧方回声与内部钙化情况上差异无统计学意义（P〉0．05）。结论乳腺浸润性导管癌和浸润性小叶癌可以根据各自超声声像的特点进行诊断，组织学的不同影响乳腺癌的超声影像表现。     

Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma

Rsf-1 protein is a member of a chromatin-remodeling complex that plays an important role in regulating gene expression and cell proliferation. Our previous study showed that Rsf-1 was an amplified gene that participated in the development of ovarian serous carcinoma. To further elucidate the role of Rsf-1 in ovarian cancer, we studied Rsf-1 immunoreactivity in 294 ovarian tumors of various histologic types. Because the Rsf-1 amplicon overlaps an amplified region reported in breast cancer, we included 782 neoplastic and normal breast tissues for comparison. Immunohistochemistry was performed on tissue microarrays using a 4-tiered scoring system. Overexpression of Rsf-1 was defined as a nuclear immunointensity of 3+ to 4+ because of a strong correlation between 3+ and 4+ immunointensity and Rsf-1 gene amplification, based on our previous fluorescence in situ hybridization analysis. Rsf-1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in only rare cases (<7%) of low-grade ovarian serous, ovarian endometrioid, and invasive breast carcinomas but not in any ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, intraductal carcinomas of the breast, and normal ovaries and breast tissues. Thus, overexpression of Rsf-1 was significantly associated with high-grade ovarian serous carcinoma (P < .05), as compared with other types of ovarian tumors and breast carcinomas. Our results provide evidence that Rsf-1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer. Because Rsf-1 overexpression occurs in only a small number of breast carcinomas, it is unlikely that Rsf-1 is a critical gene in the development of breast carcinoma.     

Stromal changes in invasive breast carcinoma: an ultrastructural study

The stroma in infiltrating breast carcinomas, with particular reference to stromal spindle cells, has been studied by electron microscopy. A mixture of cells including resting fibroblasts, active fibroblasts, early myofibroblasts, and mature myofibroblasts has been identified. In loose stroma, myofibroblasts possessed prominent organelles and showed secretory products along the cell surface, whereas in dense stroma, there was relative prominence of cytoplasmic filaments as well as other features consistent with a contractile state of myofibroblasts. The degree of myofibroblastic proliferation was related to the growth pattern of the tumour. It is suggested that the infiltrating process of cancer cells is analogous to wound production and healing with continuous granulation tissue and scar formation resulting in the characteristic desmoplastic reaction seen in certain breast carcinomas.     

Immunohistochemical study ofneu protein overexpression in clinging in situ duct carcinoma of the breast

The expression ofneu protein in 26 cases of clinging carcinoma (CC) of the breast was investigated. A distinction is made between two types of CC: one with pleomorphic nuclei (PN) and the other with monomorphic nuclei (MN). The PN type of CC overexpresses theneu protein in almost all cases (85.7%), its cells generally exhibit abundant cytoplasm and intraluminal necrosis is frequently observed. The MN type of CC does not overexpress theneu protein, exhibits bland cytological features and shows no necrosis. It is suggested that CC with PN is related to comedo-type carcinoma, while CC with MN is the forerunner of cribriform carcinoma in situ.     

Oat cell carcinoma of the oesophagus

Summary The small oat cell type of carcinoma is only rarely seen in extrapulmonary sites. To date, nineteen cases have been described in the oesophagus, almost all by Japanese authors. In this report we review the relevant literature and add one more case of pure type to the total.The histopathological, histochemical and ultrastructural findings and the similarity of this tumour to the oat cell bronchial carcinoma, lead one to propose that it originates in the cells of the APUD series, which have been demonstrated in the normal oesophageal epithelium. Thus it represents on endocrine carcinoma of the oesophagus.     

Mucoepidermoid carcinoma of the breast

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.