Lymphoepithelioma-like carcinoma of the breast: not Epstein-Barr virus-, but human papilloma virus-positive

Lymphoepithelioma-like carcinoma of the breast is a rare tumor, with fewer than 20 cases documented in the literature. None of the published cases was Epstein-Barr virus positive, and our case was also Epstein-Barr virus negative. However, in our case, human papilloma virus (HPV) types 18 and 33 DNA could be demonstrated within the tumor tissue. Many years previously, the patient underwent hysterectomy for cervical carcinoma in situ which showed the presence of HPV-33. To the best of our knowledge, this is the first report on lymphoepithelioma-like carcinoma of the breast where high-risk HPV infection may be suggested as an etiological factor in a patient with a previous history of cervical carcinoma in situ.     

Lymphoepithelioma-like carcinoma of the colon

An 85-year old female had a polypoid tumour in the sigmoid colon that histologically conformed to a lymphoepithelioma-like (LEL) carcinoma. The tumour was arranged in cords, chains, clusters and microalveoli of pleomorphic, irregular cells set within a dense intratumoral lymphocytic stroma. The tumour was EBV-negative and showed loss of MLH-1 and PMS-2 mismatch repair proteins. The patient did not fulfil the criteria for HNPCC. Only 5 other cases of primary colonic LEL carcinoma have been described previously and only one case appears to have an unequivocal association with EBV. In addition, one of the cases was encountered in a HNPCC patient. This is an unusual morphologic variant of a microsatellite unstable tumour with a LEL pattern, not associated with EBV.     

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.     

Lymphoepithelioma-like carcinoma of the urinary bladder

A 78-yr-old woman presented with gross hematuria for 2 weeks. On cystoscopy, a frond-like mass was observed at the bladder trigone. Transurethral resection of bladder tumor was performed for the mass. Histopathological findings showed that 90% of lesions were lymphoepithelioma-like carcinoma (LELCA) and a few lesions were non-invasive transitional cell carcinoma. On microscopy, syncytial growth pattern and indistinct cytoplasmic borders were observed with the severe infiltration of lymphoid cells. The case was followed-up for 8 months without recurrence. This is the first report of a LELCA case in Korea.     

Mammographically detected in situ lobular carcinomas of the breast

We present ten cases of mammographically detected lobular carcinoma in situ (LCIS), involving a single area of variable size (up to a quadrant) in seven cases and the entire gland in three cases. Histologically, calcifications were associated with necrotic central areas within the in situ carcinomatous foci. Multiple foci of LCIS were observed in all five cases in which mastectomy had been performed. Cytologically, the lesions were characterized by a solid proliferation of round noncohesive cells with nuclei of intermediate size. Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2, GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with Ki67, was in the low range. Four cases were associated with foci of infiltrating lobular carcinoma (ILC). These findings contradict the commonly held opinion that LCIS is not mammographically detectable because of its lack of necrosis and calcification. This study documents the existence of a variant of LCIS exhibiting the mammographic features and central necrosis classically associated with ductal carcinoma in situ (DCIS), while retaining the spatial distribution, cytological composition and immunocytochemical features of lobular carcinoma. Received: 23 July 1999 / Accepted: 22 October 1999     

Adenoid cystic carcinoma arising in an adenomyoepithelioma of the breast

 Adenomyoepithelioma is a mixed epithelial and myoepithelial tumour. In rare cases adenomyoepitheliomas give rise to carcinomas with epithelial, myoepithelial, or mixed epithelial and myoepithelial differentiation. Carcinomas arising in adenomyoepithelioma range from low grade to high grade, and 15 cases have been reported in the literature. We describe a 36-year-old woman with a very rare adenoid cystic carcinoma arising in a tubular adenomyoepithelioma. The histogenesis of carcinoma arising in an adenomyoepithelioma is discussed. Received: 15 September 1997 / Accepted: 10 October 1997     

乳腺浸润性小叶癌的组织学类型观察

目的：研究浸润性小叶癌（ＩＬＣ）的各种组织类型特点。方法：对７５３侵浸润性乳腺癌存档资料回顾性分析。结果，在７５３例浸润性乳腺癌中ＩＬＣ４３例（占５．７１％），复查前后对ＩＬＣ诊断误差率为９３．０２％，该组ＩＬＣ平均年龄５１．２岁，肿瘤平均直径３．５ｃｍ，有腋下淋巴结转移者２５例（５８．１３％），按ＩＬＣ组织形态可分出１０个亚型：经典型１３例（３０．２３％），腺泡型６例（１３．９５％），多形型４例     

Lymphoepithelioma-like carcinoma of rectum: possible relation with EBV

Lymphoepithelioma-like carcinoma (LEC) of the colon is very rare. Here we report a case of LEC originating in the rectum that was closely associated with Epstein-Barr virus (EBV) infection. The histologic and immunohistologic features, namely, poorly differentiated adenocarcinoma with lymphoid stroma, showed this tumor to be an LEC. The EBV genome was detected by PCR using DNA obtained from tumor tissue sections. Immunohistochemically, EBV-determined nuclear antigen 2 was detected in the tumor cells, and in situ hybridization using EBV-encoded small RNAs probe showed positive labeling in some tumor cells together with a few stromal lymphoid cells. There are some reports of LEC cases that originated in the colon; however, a relation with EBV was not demonstrated. We report here a case of LEC of the rectum demonstrating a possible relation with EBV.     

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。     

Cytological characteristics of invasive lobular carcinoma of the human breast

In contrast to invasive ductal carcinoma, invasive lobular carcinoma (ILC) of the breast is characterized by multiple ipsilateral occurrences and a higher incidence in the contralateral breast. It is therefore necessary to examine thoroughly whether there is any other carcinoma present before any breast-conserving surgery is carried out. We cytologically, histologically, and ultrastructurally investigated ILC and pure scirrhous carcinoma (PSC), a subtype of invasive ductal carcinoma, to establish cytological diagnostic criteria for the differential diagnosis of these two types of carcinoma that have high histological similarity. Cytologically, ILC cells showed linear or isolated cell arrangements and had small nuclei with round homogeneously distributed fine granular chromatin. The cytoplasm was light, and individual cells lacked cohesion. The carcinoma showed a rosary-like configuration. PSC cells, however, showed linear or cordlike arrangements. Individual cells showed a vertical arrangement. PSC cells had a linear cytoplasmic edge and were characterized by nuclear molding with coarse granular chromatin. These cytological findings were supported by histological and ultrastructural findings. These findings may contribute to histological estimation of ILC in preoperative cytological diagnosis.     

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.     

Histologic variants of infiltrating lobular carcinoma of the breast.

Thirty-eight breasts with lobular carcinoma in situ and an additional intraductal or infiltrating cancer were studied. Twenty-six of the additional cancers were diagnosed as infiltrating lobular cancer on the basis of a single population of small uniform cells cytologically identical to those in lobular carcinoma in situ. In 20 of these cases the conventional pattern of infiltrating lobular cancer was evident with an individual cell infiltrate with foci of single filing. In the other six there was a confluent arrangement of cells in solid sheets. This pattern has not been previously reported as a pattern of infiltrating lobular cancer. Because of the identical cytologic appearance, we believe it is a variant of infiltraing lobular cancer and should be diagnosed as such.     

Ultrastructural and immunohistochemical features of lobular carcinoma of the breast

Twenty cases of infiltrating lobular carcinoma (12 of classical type, five of trabecular type and three of alveolar type) and one case of lobular carcinoma in situ were studied by transmission electron microscopy. The in situ component in three of the infiltrating carcinomas was also studied. The ultrastructure of the tumour cells in the alveolar variant of infiltrating lobular carcinoma was the same as seen in the tumour cells of lobular carcinoma in situ. The tumour cells in infiltrating lobular carcinoma of the classical and trabecular types had more irregular nuclei and were more organelle- and filament-rich. Immunohistochemical staining for the presence of alpha-lactalbumin was proved in 19 per cent of the cases, casein 81 per cent, CEA in 65 per cent and prekeratin in 90 per cent. The light microscopic separation of some subgroups of infiltrating lobular carcinoma may be difficult, in particular the distinction between the classical and the trabecular variants. Unfortunately, our study shows that these distinctions cannot easily be made either by electron microscopy or by light microscopic immunohistochemistry with antibodies against prekeratin, CEA, casein and alpha-lactalbumin.     

Diagnostic cytological features of neuroendocrine differentiated carcinoma of the breast

 Neuroendocrine (NE) features characterize a minority of carcinomas of the breast corresponding to definite subtypes, which cover a wide spectrum of differentiation. Breast metastases from NE tumours of gastrointestinal origin are not rare, and to determine whether NE carcinomas in the breast could be differentiated from other tumours on fine needle aspiration (FNA) we analysed the cytological features of 13 primary NE breast carcinomas of different types (7 carcinoid-like, 5 mucinous and 1 solid spindle cell). Smears of carcinoid-like carcinomas showed specific features that made it possible to differentiate them from other primary tumours, but not from breast metastases of NE carcinomas. These features were: cell clusters with rigid borders, single cells with a plasmacytoid appearance and peripheral cytoplasmic granules evident on Giemsa staining and immunoreactive for chromogranin A. In mucinous NE carcinomas such granules were less apparent, and the cytological features could have been mistaken for those of fibroadenomas, as in the case of non-NE mucinous carcinomas. The solid spindle cell type showed noncohesive fusiform cells and moderate nuclear pleomorphism, a pattern similar to that of atypical carcinoids of the lung. Received: 8 December 1997 / Accepted: 7 May 1998     

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     

Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas

 The biological significance of the differential expression of cytokeratin (CK) polypeptides in breast carcinomas is unclear. We examined the CK profiles of 101 primary infiltrating ductal breast carcinomas using monoclonal antibodies directed against 11 different CKs and against vimentin. Two major CK phenotypes were distinguished: first, a phenotype expressing only the simple-epithelial CKs 7 (variably), 8, 18 and 19, and secondly, a bimodal phenotype co-expressing significant amounts of one or more of the stratified-epithelial CKs 4, 14 and 17. The vast majority of G1 and G2 carcinomas had the simple-epithelium phenotype, as did a subgroup of G3 carcinomas. Interestingly, the majority (62%) of G3 carcinomas exhibited the bimodal phenotype, with the expression of CKs 4, 14 and 17 being statistically correlated with poor histological differentiation and absence of steroid hormone receptors. The distribution of vimentin only partially overlapped with that of these stratified-epithelial CKs. Prognostic analyses suggested that the presence of CKs 4, 14 and/or 17 was associated with short overall and disease-free survival in subgroups comprising G3, oestrogen-receptor-negative and vimentin-negative tumours. In node-positive tumours the correlation between these CKs and a shorter disease-free interval attained statistical significance (log rank, 0.0096). Thus, abnormal CK profiles in ductal breast carcinomas appear to reflect disturbed regulation of differentiation-related gene expression programmes and may prove to be of clinical value. Received: 26 August 1997 / Accepted: 11 February 1998     

Lobular carcinoma of the breast: Cytological features supporting the diagnosis of lobular cancer

Lobular carcinomas have a distinct natural history with a better response to endocrine therapy and a higher incidence of local recurrence and are more often bilateral. The cytological diagnosis of lobulur carcinoma permits a discriminating therapeutic approach with pre-operative Tamoxifen, more generous resection margins, and assessment of the contralateral breast. The cytological features of lobular cancer however are not well defined and the low cell yield from such neoplasms can result in a high false negative rate. To determine whether we could improve the pre-operative diagnosis, we reviewed the cytological features of 112 lobular carcinomas. They had small uniform sized nuclei with irregular outlines and inconspicuous nucleoli. The degree of dissociation was similar to duct carcinomas and the incidence of inadequate aspirates was no higher. We found no features that confidently diagnosed lobular cancer or its sub-types. However, using a combination of features, typing of lobular cancer on aspirated material is possible and should be attempted. © 1995 Wiley-Liss, Inc.     

Association of leptomeningeal carcinomatosis in carcinoma of the breast with infiltrating lobular carcinoma. An autopsy study

We analyzed the autopsy records of 261 patients with breast carcinoma, who died at The Institute of Oncology, Ljubljana, Yugoslavia, for the presence of metastases to the central nervous system, particularly for the presence of leptomeningeal carcinomatosis. Metastases to the central nervous system were found in 41 (18.1%) of 226 patients who had metastatic cancer. In 24 cases (10.6%), metastases were seen in brain parenchyma; in 11 cases (4.9%), only dura mater was involved, and in six cases (2.6%), leptomeningeal carcinomatosis was found. All patients with leptomeningeal carcinomatosis showed some symptoms of central nervous system involvement while alive. The patients died between 2 weeks and 2 months after the onset of central nervous system symptoms. Four of six patients with such a complication presented with locally advanced or disseminated carcinoma on the first admission. With regard to histologic findings, three patients had infiltrating lobular carcinoma, two had infiltrating ductal carcinoma, and one had mixed infiltrating lobular and ductal carcinoma, with a metastasizing lobular component. Metastases to the brain parenchyma were found exclusively in infiltrating ductal carcinoma. We stress that infiltrating lobular carcinoma represents a distinctive type of breast cancer with an unusual propensity to disseminate into leptomeninges, as this occurred in almost 14% of all cases of infiltrating lobular carcinoma in our series in contrast to a 1% incidence in cases of infiltrating ductal carcinoma.     

In situ and infiltrating lobular carcinoma of the male breast

An 82-year-old man presented with a right breast mass. Histologic examination of an excisional biopsy showed lobular in situ and infiltrating carcinoma. The patient was phenotypically male and had fathered children. There was no history of predisposing factors to breast lesions, such as drug use or gynecomastia. In our review, this is the first case of lobular in situ and infiltrating carcinoma of the male breast in a phenotypic and apparently genotypic male.