Neural variant of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c- erb B-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c- erb B-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c- erb B-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c- erb B-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.     

Histiocytoid breast carcinoma: an apocrine variant of lobular carcinoma

Two cases of in situ and invasive histiocytoid breast carcinoma are described. The invasive components of both tumours showed architectural and cytological similarities to lobular carcinoma. The in situ components showed areas of classical lobular carcinoma in situ, areas of lobular carcinoma with apocrine features and areas with transitional features. It is concluded that histiocytoid carcinoma represents an apocrine variant of lobular carcinoma. Differentiation of this tumour from chronic sclerosing inflammation may be difficult in both primary and secondary lesions.     

Salivary gland-type neoplasm of the lung

Salivary gland-type tumours of the lung, which include adenoid cystic carcinoma and mucoepidermoid carcinoma, are rare entities. Histologically, they show morphologies that are similar to those of salivary gland origin. For classification purposes, the terminology applied to tumours of salivary gland origin is also applied to their pulmonary counterparts. Of these types of tumours, adenoid cystic carcinoma is the most common followed by mucoepidermoid carcinoma. Epithelial-myoepithelial carcinoma and pleomorphic adenoma are uncommon. The possibility of metastasis from the salivary glands is important to exclude through careful examination of patients' medical history because low-grade salivary cancers can metastasize after long latencies. A gene rearrangement analysis is helpful in making a definitive diagnosis, particularly in cases with an unusual morphology. Molecular-based classification may be useful to understand the nature of morphologically varied tumours. The immunohistochemical profile of the tumours is also a valuable tool for an accurate diagnosis in difficult cases.     

Transitional cell carcinoma of the bladder mimicking lobular carcinoma of the breast: a discohesive variant of urothelial carcinoma

AIMS: To describe a series of 10 cases of transitional cell carcinoma which show morphological features which mimic lobular carcinoma of the breast and diffuse carcinoma of the stomach. METHODS AND RESULTS: Ten cases were identified from the files at Southampton University Hospitals NHS Trust and from the authors' consultation files. Immunostains were performed and clinical information was obtained. Eight of the patients were male and two female. Ages ranged from 52 to 77 years at presentation. All of the tumours showed areas where the tumour was composed of uniform cells with a discohesive single-cell, diffusely invasive growth pattern. In areas the tumour cells were arranged in linear single-cell files and in separate areas solid sheets of discohesive cells. In all of the cases some tumour cells showed prominent intracytoplasmic vacuoles. In addition to this pattern, four cases showed typical transitional cell carcinoma or carcinoma in situ. The majority of the tumours expressed cytokeratin 20 but not oestrogen receptors. CONCLUSION: This study highlights a pattern of diffusely invasive transitional cell carcinoma not previously described and one which is important to recognize in order to avoid misdiagnosis of metastatic lobular carcinoma of the breast, especially in small biopsies.     

Poorly differentiated myoepithelial cell rich carcinoma of the breast

Three unusual cases of invasive breast carcinoma are reported, each comprising a dual malignant cellular proliferation consisting of ‘ordinary’ epithelial cells as well as myoepithelial cells haphazardly intermingled. The cases displayed features which did not match any of the four main types of invasive malignant breast tumours containing myoepithelial elements, i.e. adenomyoepithelioma, adenoid cystic carcinoma, pure myoepithelioma and low-grade adenosquamous carcinoma. The designation of ‘poorly differentiated myoepithelial cell rich carcinoma’ (PDMC) is proposed for these tumours.     

Invasive ductal carcinoma associated with tubular adenoma of the breast

We report an extremely rare case of the colocalization of a tubular adenoma and an invasive ductal carcinoma occurring in a 55-year-old woman. Following radiographical evaluation, fine-needle aspiration cytology of the left breast tumor was undertaken. Because cytological examination revealed malignancy, a partial mastectomy was performed. Histologically, the tumor (measuring 1.7 x 1.3 cm) comprised two distinct parts: tubular adenoma and invasive ductal carcinoma. The invasive ductal carcinoma showed a solid pattern, high nuclear and structural atypia and frequent mitotic figures, while the tubular adenoma consisted of a proliferation of small ducts lined by single layers of epithelial and myoepithelial cells with bland nuclei and inconspicuous nucleoli. The histological boundary was clearly defined between the tubular adenoma and the invasive ductal carcinoma, and between the tubular adenoma and the surrounding breast tissue. The current case might be a collision between separate tubular adenoma and invasive ductal carcinoma, but the malignant transformation of a tubular adenoma cannot be ruled out. Both the long-term observation of this case and analysis of more cases may enable us to determine the histological characteristics and clinical significance of invasive ductal carcinoma associated with tubular adenoma.     

An ultrastructural study of mucoid carcinoma of the breast: variability of cytoplasmic features

The ultrastructural characteristics of 14 cases of mucoid carcinoma of the breast, with different histological appearances, have been examined. Thirteen of the tumours were observed to consist of two populations of tumour cells, one showing secretory changes while the other group showed no evidence of activity. In one tumour only synthetically active cells were observed. Ultrastructurally, six different types of cytoplasmic granules, comprising typical mucin plus glycoprotein or protein-containing granules, were identified within the synthetically active tumour cells. The number of types of granules and the relative proportion of the various granules varied between tumours with only mucin granules present in all tumours. It would appear that synthetic pathways are activated in certain tumours which result in protein/glycoprotein granules associated with the argyrophilia observed histologically. In addition, the tumours varied with respect to luminal differentiation, presence of intracytoplasmic lumina, intracytoplasmic mucin pools, lipid droplets, ciliated cells and areas of calcification. The marked heterogeneity of the ultrastructural features of the mucoid carcinoma of the breast prevents the tumours from being readily divided into distinct subgroups.     

Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry

AIMS: Non-invasive carcinoma ex pleomorphic adenoma is defined as a carcinoma arising within the boundaries of a pleomorphic adenoma (PA), but which fails to display invasion beyond the capsule of host PA. Alternative names are intracapsular, in situ, or focal carcinoma. The true nature of non-invasive carcinoma ex-PA is still controversial; for example, it is not clear whether it represents early but genuine carcinomatous changes with the genetic make-up of malignant cells, or simply cytological, possibly metaplastic or 'bizarre' changes in PA. Strong overexpression and amplification of HER-2/neu protein has recently been demonstrated in invasive carcinoma ex-PA. In addition, data from breast cancer studies suggest that amplification of HER-2/neu and overexpression of its gene product is mainly involved in the initiation of breast oncogenesis. We sought to establish whether this method could help to demonstrate that what is described as non-invasive carcinoma ex-PA is really a genuine malignancy, albeit in an early phase. METHODS AND RESULTS: Eleven cases of non-invasive carcinoma (in situ) ex-PA were studied for HER-2/neu status using immunohistochemistry and fluorescent in-situ hybridization (FISH). Cells of focal non-invasive carcinoma ex-PA were strongly positive for HER-2/neu protein, while the cells of the maternal PA were always negative. Two cases of low-grade non-invasive myoepithelial carcinoma ex-PA were negative. In four cases out of a total of six tumours studied by FISH, we detected amplification of HER-2/neu gene signals in tumour cells of focal, non-invasive, carcinoma. CONCLUSIONS: The current data suggest that non-invasive carcinoma ex PA is a genuine carcinoma within a PA. However, the presence of cyto-nuclear atypia is not sufficient to make a definite diagnosis of malignant change, which requires a combination of morphology and immunohistochemistry.     

Poorly differentiated myoepithelial cell rich carcinoma of the breast

Three unusual cases of invasive breast carcinoma are reported, each comprising a dual malignant cellular proliferation consisting of 'ordinary' epithelial cells as well as myoepithelial cells haphazardly intermingled. The cases displayed features which did not match any of the four main types of invasive malignant breast tumours containing myoepithelial elements, i.e. adenomyoepithelioma, adenoid cystic carcinoma, pure myoepithelioma and low-grade adenosquamous carcinoma. The designation of 'poorly differentiated myoepithelial cell rich carcinoma' (PDMC) is proposed for these tumours.     

Ultrastructural similarities of adenoid cystic carcinoma and pleomorphic adenoma

Ultrastructural examination of five adenoid cystic carcinomas, three breast and two salivary gland, reveals identical patterns of tumour cell differentiation, organization and distribution of cellular products (Zaloudek, Oertel & Orenstein 1984). In both sites, there is proliferation of two populations of cells, one with characteristics and organization of duct-type luminal epithelial cells and a second that forms the principal proliferating component and has the overall organization and appearance that would suggest that they represent modified myoepithelial cells. Recent ultrastructural studies also indicate that tumour cell types and histological organization similar to those described for adenoid cystic carcinoma occur during histodifferentiation of salivary gland pleomorphic adenoma (Dardick et al. 1983a, b). The characteristic histological pattern of adenoid cystic carcinoma is dependent on the formation of pseudolumina containing proteoglycans and reduplicated basal lamina. Similar, but smaller, lumina of like organization and contents are evident in some cases of pleomorphic adenoma. Both the ultrastructural similarities of the tumour cell types and their organization, in adenoid cystic carcinoma and pleomorphic adenoma, suggest that these tumours have a similar histogenetic basis. The fact that one lesion is malignant and the other benign does not preclude common types of tumour cells and developmental processes.     

Invasive cribriform carcinoma of the breast†

A histological review of 1003 invasive breast carcinomas identified 51 tumours in which the invasive component showed a predominantly cribriform pattern. These separated into two groups; 35 which showed exclusively cribriform or cribriform with a limited extent of tubular invasive elements only, designated ‘classical’ invasive cribriform carcinoma and 16 which also contained areas of less well differentiated invasive carcinoma, designated ‘mixed’ invasive cribriform carcinoma. At follow-up, 10 to 21 years after diagnosis, none of the 35 patients with classical invasive cribriform carcinoma had died as a result of this initial carcinoma and 30 remained alive. Of the 16 remaining patients, whose tumours showed areas of less well differentiated carcinoma, only six remained alive. However, the adjusted 10 year survival rate of these patients in this mixed group was significantly better than that of invasive carcinoma in Edinburgh. Invasive cribriform carcinoma in its classical form, is a histological subgroup of invasive carcinoma with the same excellent prognosis as that of invasive tubular carcinoma.     

Phenotypic alteration in malignant transformation of colonic villous tumours: with special reference to a comparison with tubular tumours

AIMS: To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma). METHODS AND RESULTS: Forty-nine cases of colorectal villous tumours [six cases of low-grade villous adenoma, 21 of high-grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low-grade and 17 of high-grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P < 0.05). CD10 expression of high-grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P < 0.05). CONCLUSIONS: There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.     

Carcinomas of the breast with endocrine differentiation: a review

The occurrence of endocrine differentiation in some mammary carcinomas seems well-established, but pathologists continue to debate its significance. Contemporary thinking suggests that endocrine tumours of the breast do not constitute a single clinicopathological entity with a consistent histogenesis but rather that endocrine differentiation represents a pathway of neoplastic development available to a range of breast cancers. This pattern of differentiation occurs in tumours with vastly different morphological appearances, such as: ductal carcinoma in situ, mucinous carcinoma, a variant of lobular carcinoma, and low grade invasive ductal carcinoma. Although such tumours share some characteristics with intestinal endocrine neoplasms, the typical pattern of intestinal carcinoid virtually never occurs in mammary lesions. Conventional microscopy permits the diagnosis in most cases. Specialized techniques (histochemistry, immunohistochemistry, and electron microscopy) can serve as the basis for diagnosis in the absence of the appropriate morphological features. Although the system of nomenclature proposed by the World Health Organization for use with endocrine tumours in other organs can be used for endocrine tumours of the breast, only a minority of lesions will fit the established criteria. Most lesions are classifiable in the conventional categories of mammary carcinomas. No special prognostic significance is attached to these tumours at the present time.     

''Carcinoid'' tumours of the breast: the morphological spectrum of argyrophil carcinomas

Fourteen 'carcinoid' tumours of the breast are described. They are separable into five with and nine without intracellular mucin. All the tumours are argyrophil, but none is argentaffin. Four tumours studied ultrastructurally contain dense-core granules. Argyrophil carcinomas represent the endocrine analogues of ductal carcinoma in situ, of invasive ductal carcinoma and probably of lobular carcinoma also. Current views vary between the one that the so-called carcinoid is a rare and totally distinct entity to the view, at the other extreme, that it is a very common variant of conventional breast cancer. On the basis of our findings, an intermediate view is justified: argyrophil carcinomas constitute about 5% of breast carcinomas and some varieties at least have non-argyrophil analogues. Factors influencing the prognosis in individual cases are discussed. Argyrophil carcinomas of the breast form a tumour spectrum with a wide range of morphological and histochemical appearances and a variable prognosis.     

Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry

AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.     

Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII-related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA-1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.     

Apocrine adenoma of the breast coexistent with invasive carcinoma

We describe a case of apocrine adenoma with simultaneous occurrence of invasive ductal carcinoma in the breast of a 53-year-old woman. Apocrine adenoma affecting the breast is very rare. The lesion is composed of back-to-back ducts and papillary fronds covered with apocrine cells, and it is sharply demarcated from the surrounding breast tissue. The patient presented with a palpable nodule with skin retraction in her right breast, where ultrasound examination identified a 5-mm hypoechogenic nodule. The ultrasound also revealed in the surrounding breast parenchyma an additional abnormal finding suggestive of carcinoma. Histologic examination of the excised specimen showed that the hypoechogenic nodule represented an apocrine adenoma in proximity to the invasive ductal breast carcinoma. This is the first report that describes the simultaneous occurrence of these two lesions in the same breast.     

Salivary gland-like tumours of the breast: surgical and molecular pathology

Breast glands and salivary glands are tubulo-acinar exocrine glands that can manifest as tumours with similar morphological features, but that differ in incidence and clinical behaviour depending on whether they are primary in breast or salivary glands. Salivary gland-like tumours of the breast are of two types: tumours with myoepithelial differentiation and those devoid of myoepithelial differentiation. The first and more numerous group comprises a spectrum of lesions ranging from "bona fide" benign (such as benign myoepithelioma and pleomorphic adenoma), to low grade malignant (such as adenoid cystic carcinoma, low grade adenosquamous carcinoma, and adenomyoepithelioma), to high grade malignant lesions (malignant myoepithelioma). The second group comprises lesions that have only recently been recognised, such as acinic cell carcinoma, oncocytic carcinoma of the breast, and the rare mucoepidermoid carcinoma.     

Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients

Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients
Aims : Metaplastic spindle cell carcinomas may be difficult to distinguish histologically from other spindle cell lesions in the breast. Variable staining with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We evaluated the diagnostic utility of anti-cytokeratin polyclonal antibody, wide spectrum screening keratin, to assess spindle cell breast lesions.
Methods and results : Twenty-four patients with spindle cell breast carcinoma and 31 patients with benign or malignant spindle cell tumours were studied using a panel of antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of origin for the 31 controls included breast, bone, and soft tissue. All but one (95.8%) metaplastic carcinomas stained positively with wide spectrum screening keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2 and eight cases were immunoreactive with EMA. All control cases lacked immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin.
Conclusions : Wide spectrum screening keratin may be the most useful and convenient antibody in differentiating metaplastic spindle cell carcinoma from other spindle cell lesions in the breast.     

Epstein-Barr virus-associated carcinomas: facts and fiction

The Epstein-Barr virus (EBV) is associated with several human tumours including lymphoid and epithelial malignancies. Most EBV-associated tumours are rare or occur at higher incidence only in certain geographical regions. The recently reported detection of EBV in gastric, breast, and hepatocellular carcinomas raises the possibility of involvement of the virus in the pathogenesis of common cancers. This article reviews the evidence linking EBV infection to epithelial tumours. It is concluded that at present, there is no convincing evidence to suggest that breast carcinoma and hepatocellular carcinoma are EBV-associated tumours.