Recurrent endocrine mucin-producing sweat gland carcinoma

Endocrine mucin-producing sweat gland carcinoma is a rare skin tumor that most commonly involves the eyelid of elderly women. Morphologically and immunohistochemically, it is analogous to endocrine ductal carcinoma in situ of the breast and mammary solid papillary carcinoma; also, like the analogous breast lesion, there is an often associated invasive mucinous carcinoma with neuroendocrine differentiation. We describe the case of a 65-year-old woman with endocrine mucin-producing sweat gland carcinoma of the eyelid that recurred 3 years after an apparently complete excision.     

Endokrines muzinproduzierendes Schweißdrüsenkarzinom

Endocrine mucin-producing sweat gland carcinoma (EMPS) is a rare low-grade sweat gland carcinoma with an infiltrating growth pattern. It occurs mostly in women and shows a predilection for the periorbital region. Histopathologically, the tumor shows analogous features to endocrine ductal carcinoma/solid papillary carcinoma of the breast and shares some clinical and morphological similarities with primary mucinous carcinoma of the skin. The tumor is characterized by large monomorphous epithelial cells with little nuclear pleomorphism and only a few mitotic figures. The solid cystic tumor shows mucin-filled small cystic spaces, cribriform areas and expresses the neuroendocrine markers synaptophysin, chromogranin and neuron-specific enolase with varying staining intensities. The tumor cells are also positive for estrogen and progesterone receptors. We present three cases of this rare tumor with typical clinical, histopathological and immunohistochemical findings, give a short summary of the literature and discuss the most relevant differential diagnoses.     

Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters.

Mucinous carcinoma of the breast is a specific good prognostic type malignancy occurring in elderly patients. Neuroendocrine differentiation has long been described in mucinous carcinoma, but the significance of such finding is uncertain. We evaluated the neuroendocrine differentiation profiles of 38 cases of pure mucinous carcinoma and compared the clinicopathological differences between those with and those without neuroendocrine differentiation. The parameters assessed included patients' age, tumor size, nuclear grade, axillary lymph node status at time of diagnosis, percentage area of intratumoral mucin, and the expression of estrogen and progesterone receptors, cerbB2 oncoprotein, and three neuroendocrine markers, namely neurone-specific enolase, chromogranin, and synaptophysin by immunohistochemistry. Patients' outcome and follow-up period were also documented. Of the 38 cases of pure mucinous carcinoma, 28, 11 and six cases showed positive staining for 1, 2 and 3 of the neuroendocrine markers. For all the groups with variable neuroendocrine differentiation and compared to those without such differentiation, they all showed older patients' age, higher proportion of tumors with lower nuclear grade, lower incidence of axillary lymph node metastasis, a higher progesterone receptor, and lower cerbB2 oncoprotein expression. No difference was detected between tumor size, intratumoral mucinous area, and estrogen receptor status. In all, 37 patients did not have distant metastases or local recurrences at the end of follow-up period, while one patient with coexisting high-grade ductal carcinoma in situ at time of diagnosis died of breast carcinoma. Our findings suggest that the identification of neuroendocrine differentiation in pure mucinous carcinoma is associated with more favorable histologic and immunohistochemical parameters.     

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.     

Breast carcinoma with predominant neuroendocrine differentiation

Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.     

Morphological characteristics of mucinous cancer of the breast containing endocrine cells

It was established that mucus-forming mammary gland carcinoma containing endocrine cells may have a structure of an ordinary colloid mammary gland carcinoma or carcinoid carcinoma with mucus formation. The presence of amyloid in the stroma of colloid carcinoma containing endocrine cells may serve as an additional sign of the endocrine cell differentiation. Simultaneous observation in the tumour cells of both mucous inclusions and endocrine granules may be regarded as a proof of an origin of epithelial and endocrine cells of the mammary gland from a pluripotent stem cell.     

Mucinous carcinoma of the breast (clinico-morphological characteristics)

The main criteria for the morphological diagnosis of the "pure" and mixed mucinous carcinoma are established on the basis of studying 83 mucinous carcinomas of the mammary gland. The necessity to differentiate is pointed out between the "pure" from of this carcinoma and the mixed one as the former has a much more favourable prognosis as compared to the latter which, in its turn, has a more favourable prognosis than an infiltrative ductal carcinoma. Total 10-year-survival of patients with "pure" and mixed variants of the mucinous carcinoma is 90.46 +/- 7.27 and 58.29 +/- 11.1, respectively. The radical mammary gland resection is recommended in patients with a "pure" variant of mucinous carcinoma at 1 and 11 A stages of the disease.     

Composite type of breast carcinoma with endocrine differentiation: a cytological and immunohistochemical study

We describe a case of breast carcinoma with endocrine differentiation containing a mixture of three different histological features that occurred in a 71-year-old woman. Histologically, the tumor was predominantly intraductal, but slightly invasive. In the intraductal lesion, the tumor consisted mainly of ovoid to round cells with a modest to abundant amount of granular eosinophilic cytoplasm or intracytoplasmic mucin (mucin-producing carcinoma in situ ). It also consisted, in part, of plump spindle cells with scant cytoplasm that contained argyrophilic granules in a trabecular pattern or an arrangement of perivascular pseudorosettes (atypical carcinoid tumor like-features). Mucous lake and tumor cells floating in mucin were seen in the invasive lesion (mucinous carcinoma). Immunohistochemical staining revealed endocrine differentiation of the tumor cells of both intraductal and invasive lesions. These findings suggest that the different histological features derived from pluripotent cells upon endocrine differentiation, and that endocrine differentiation of the tumor cells had already occurred at an earlier stage of carcinogenesis, prior to the appearance of the mucinous carcinoma. Cytologically, plasmacytoid tumor cells appeared in loosely cohesive clusters or as sparsely single cells in a background of a mucinous substance.     

Case of clear cell hidradenoma with mucinous metaplasia in the forehead--immunohistochemical analysis of the mucin

Mucinous metaplasia rarely develops in the non-neoplastic skin or its appendages, and almost exclusively confined to the genitalia, palms and soles. Similarly, mucinous metaplasia is quite uncommon in the cutaneous neoplasms and only few cases of clear cell hidradenomas and squamous cell carcinomas with mucinous metaplasia have been reported in the literature. Here we report a new case of clear cell hidradenoma with mucinous metaplasia in the forehead. Our immunohistochemical analysis revealed MUC5AC in the mucinous metaplastic cells of this tumor as in the extramammary Paget's disease, and expression of this gastric foveolar epithelial mucin core protein in these two neoplastic conditions seem to related to their common apocrine origin.     

Micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma

We describe a 45-year-old man who had a 2-year history of a slowly enlarging tumor in the left parotid gland. Histologically, the tumor was a mucinous cystadenoma with focal apocrine differentiation, which revealed a widespread invasive micropapillary adenocarcinoma component. A rim of lymphoid tissue surrounded the margins of the micropapillary carcinoma. The invasive micropapillary adenocarcinoma component was morphologically identical with the invasive micropapillary carcinoma of the mammary gland. The tumor is different from so-far recognized salivary gland tumor entities. Received: 25 October 1999 / Accepted: 13 June 2000     

Divergent differentiation in endocrine and nonendocrine tumors of the skin

In the skin, endocrine tumors showing areas with nonendocrine features and nonendocrine tumors showing endocrine differentiation are present. (1) Neuroendocrine carcinomas with nonendocrine differentiation: Merkel cell carcinoma (MCC) of the skin has been frequently described in association with squamous cells carcinoma (SCC) which can arise separately (as synchronous or metachronous lesions) from MCC as well as closely intermixed. In the first event the possibility that the lesions are sustained by same causative factors (among which sun exposure is the most probable) is suggested. In cases of lesions closely intermixed the possibility of an origin from a common precursor is suggested. Furthermore, cases of MCC have been described to contain glandular, melanocytic, striated muscle, and lymphoepithelioma-like features. These latter findings further support the hypothesis of tumors showing divergent differentiations. (2) Nonendocrine tumors showing endocrine differentiation: Basal cell carcinoma (BCC) was the first cutaneous nonendocrine tumor described to contain neuroendocrine granules. Presence of endocrine features were subsequently confirmed with immunohistochemical studies. Endocrine features were then described in sweat gland apocrine and eccrine carcinomas. Endocrine elements present in BCC and in sweat gland carcinomas do not show morphological and immunohistochemical features of Merkel cells. Thus the possibility that these tumors develop an immature Merkel cell or a new type of endocrine cell of the skin is suggested. Tumors with follicular differentiation such as trichoblastomas and trichofolliculomas contain a high number of Merkel cells. As Merkel cells are numerous in hair follicles of human fetal skin, the possibility that these tumors recapitulate the human skin embryogenesis is suggested.     

Sebaceous carcinoma of the breast: case report and review of the literature

Sebaceous differentiation has been described in only limited examples of benign and malignant epithelial lesions of the breast. We report a rare case of mammary sebaceous carcinoma to further delineate its morphologic features. Microscopically, the tumor, arising in the right mammary gland of a 63-year-old woman, was composed of well-defined solid sheets or lobules of atypical epithelial cells including many large pale or clear cells with often scalloped nuclei and coarsely vacuolated cytoplasm, in which abundant lipid droplets were identified with oil-red-O staining. Immunohistochemical expressions of cytokeratin, epithelial membrane antigen, and receptors of estrogen and progesterone were detected, whereas GCDFP-15, S-100 protein, vimentin, α-smooth muscle actin, p63, androgen receptor, and the HER2/neu protein were not expressed. Besides, a subset of the tumor cells co-expressed synaptophysin, neurofilament, and PGP9.5, suggesting neuroendocrine differentiation that is a hitherto undescribed phenomenon in the mammary tumors with sebaceous features. This case would expand the morphologic diversity of carcinoma of the breast.     

Sebaceous carcinoma of the breast in a patient with a pathogenic BRCA2 (886delGT) mutation – focus on histopathologic and immunohistochemical features

Sebaceous carcinoma of the breast (SCB) is a rare variant of ductal carcinoma arising within the mammary gland and containing at least 50% of malignant cells with sebaceous differentiation. Only 11 cases that adjust to the criteria delineated in the WHO classification have been published in the English literature, to the best of our knowledge. Here, we present the first SCB arising in the context of a deleterious BRCA2 mutation, focusing on the histopathologic and immunohistochemical features of this exceedingly rare tumor.     

Immunohistochemical examination of mucinous cystadenoma of the testis

A case of mucinous cystadenoma of the testis in a 55-year-old man is reported. The tumor was confined to the testis and was clearly separated from the epididymis. There was no connection between the tumor cyst and the rete testis. The lumen of the cyst was lined with a single-layer of columnar cells interspersed with goblet cells. There was neither stromal invasion nor metastasis to other organs and there were no ovarian or germ cell neoplastic elements in the tumor. Immunohistochemical analysis revealed that MUC2, MUC5AC, carcinoembryonic antigen, CA19-9, CK7 and CK20 proteins were expressed on the tumor epithelial cells, whereas expression of MUC6, alpha-fetoprotein, CA125, human chorionic gonadotrophin, estrogen receptor, progesterone receptor, calretinin, chromogranin A, p53, cyclin D1 and bcl-2 proteins was absent. Ki-67 protein was weakly and sparsely expressed in the nuclei of epithelial cells. The mucinous cystadenoma in the present case, which was devoid of a connection to testicular appendices and had the immunohistochemical characteristics of gastrointestinal mucosa, might have originated from one-sided differentiation of teratoma cells.     

Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman

Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case of this rare variant of breast carcinoma was reported in 1996, only 10 cases have been reported in the English-language literature. Reported herein is the first case of primary acinic cell carcinoma of the breast in a Japanese woman. To the naked eye, the tumor appeared well circumscribed and the cut surface was grayish-pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a monotonous proliferation of cells with a finely granular cytoplasm, resembling acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm. In spite of extensive sampling, no common histological patterns of breast carcinoma such as in situ and invasive ductal carcinoma were recognized in the present case, indicating that the present case was pure acinic cell carcinoma. In addition, the immunohistochemical profile of this tumor was identical to that of the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were positive. The patient has been well for 22 months since the wide local excision of the tumor and no signs of salivary neoplasm are evident to date.     

A case of endocrine mucin-producing sweat gland carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC), which is an uncommon sweat gland tumor with a predilection for the eyelids, is morphologically analogous to solid papillary carcinoma of the breast. We report the case of a 55-year-old man with a subcutaneous tumor of the upper cheek. The pathological findings for this patient were compatible with those of reported cases of EMPSGC, and p63 staining revealed partial microinvasion into the dermis. On the basis of these findings, the patient was diagnosed with EMPSGC. It is reported that EMPSGC is a precursor of invasive mucinous carcinoma of the skin. Therefore, this patient was treated and followed up as if he had mucinous carcinoma of the skin. To the best of our knowledge, this is the first report of such a case from Japan.     

Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma

AIMS: Mucinous carcinoma of the breast usually shows less frequent lymph node metastasis and more favourable outcome compared with invasive ductal carcinoma. The aim of this study is to compare the expression profiles of several mucins in mucinous carcinomas and invasive ductal carcinomas to gain insight into the relationship between the less aggressive biological nature of mucinous carcinoma and the role of mucins. METHODS AND RESULTS: We examined the expression profiles of MUC1 (membrane-bound mucin) of different glycoforms (from non-glycosylated form to fully glycosylated form), MUC2 (intestinal type secretory mucin), MUC5AC (gastric surface type secretory mucin) and MUC6 (gastric pyloric gland type secretory mucin) in 17 mucinous carcinomas and 46 invasive ductal carcinomas using immunohistochemistry. Various glycoforms of MUC1 were expressed frequently in both mucinous carcinomas (65-100%) and invasive ductal carcinomas (92-100%), although non-glycosylated MUC1 (MUC1/CORE) and fully glycosylated MUC1 (MUC1/HMFG-1) showed significantly lower expression rates in mucinous carcinomas compared with those in invasive ductal carcinomas. The expression rates of MUC2 (94%) and MUC6 (71%) in mucinous carcinomas were significantly higher than those of MUC2 (15%) and MUC6 (15%) in invasive ductal carcinomas. There was no significant difference in the expression rate of MUC5AC in mucinous carcinomas (12%) and that in invasive ductal carcinomas (4%). CONCLUSIONS: The expression rate of MUC1/CORE and MUC1/HMFG-1, which is related to poor prognosis in the gastric and colorectal cancers, is low in mucinous carcinomas. The high expression rate of gel-forming secretory mucins (MUC2 and MUC6) in mucinous carcinoma suggests that high production of these types of mucins may act as a barrier to cancerous extension resulting in their less aggressive biological behaviour.     

Mucinous carcinoma of the breast with neuroendocrine differentiation

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.     

Human mucinous breast carcinomas and their lymph node metastases. A histological review of 247 cases

In a histologic reevaluation of 247 primary human mucinous breast carcinomas, 207 tumors fullfilled the criteria for further histopathological evaluation. The criteria for entrance in this survey are that at least 25% of the tumor consists of areas of extracellular mucin with small islands of solid epithelial tumor tissue floating in the mucin, and that the extracellular mucin should comprise at least 33% of the total tumor volume. The 247 carcinomas that have been further evaluated have been subclassified into two groups: "pure" mucinous breast carcinomas that consist solely of tumor tissue with extracellular mucin production (95 tumors), and "mixed" mucinous carcinomas that also contain infiltrating carcinoma without extracellular mucin (112 tumor). A significantly greater number of mixed carcinomas than pure carcinomas have an aggressive growth pattern--as defined by tumor size, adherence to overlying skin/bottom fascie, and primary axillary lymph node metastases. The histogenesis of the mucinous carcinomas is briefly discussed in relation to the present observations and the literature. The importance of clearly distinguishing between the mixed and the pure mucinous carcinomas in the diagnosis of these tumors is emphasized.     

24例乳腺黏液癌临床病理分析

目的：探讨乳腺黏液癌的临床病理特点,临床进展及预后。方法：对24例乳腺黏液癌进行病理学形态观察,并采用Max Vision法进行免疫组织化学雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、Her-2、Ki-67染色,对其进行随访和分析并回顾相关文献。结果：18例单纯型乳腺黏液癌,其中1例伴有微乳头结构的乳腺黏液癌,6例混合型。免疫组织化学肿瘤细胞22例ER阳性,19例PR阳性,1例混合型黏液癌HER-2阳性,单纯型黏液癌HER-2均阴性,单纯型乳腺黏液癌和混合型乳腺黏液癌两者具有统计学意义(P<0.05)。结论：乳腺单纯型黏液癌特征是细胞巢漂浮在黏液湖中,并由富含毛细血管的纤维分割。细胞团大小和形态各异,核异型性不明显,ER、PR阳性,HER-2阴性。单纯型乳腺黏液癌(pure mucinous carcinoma,PMCs)生长缓慢,转移率低,可以行保乳手术。伴有微小乳头结构的乳腺黏液癌(mucinous micropapillary carcinoma,MUMPC)与混合型乳腺黏液癌易发生转移,建议行乳腺改良根治手术,术后辅助放化疗。