RÉSUMÉ
BACKGROUND: Mammary Paget disease and extramammary Paget disease (EMPD) have different prognoses. Because they are indistinguishable on histopathological grounds, they must be distinguished on a topographical basis. OBJECTIVE: To study cases of Paget disease of the breast, which show similarities to EMPD. METHODS: Cases were selected by 2 different approaches: (1) those with an exceptionally good evolution and no evidence of subjacent tumor and (2) those expressing MUC5AC. RESULTS: Five cases were collected. All cases showed an indolent behavior with a known long clinical history in 2 cases (9 and 25 years, respectively) and a long follow-up in all cases but one (4-8 years). In all cases but one, surgery was performed, and no parenchymal tumor was found (either intraductal or infiltrating). All cases expressed cytokeratin 7 and MUC5AC without expression of MUC2, S100, or p40. LIMITATIONS: The short number of cases is a limitation of this study. In addition, case 5 is recent, so we have a very short follow-up. CONCLUSIONS: Some cases of mammary Paget disease behave like EMPD with slow progression and with no underlying associated tumor. Immunoexpression of MUC5AC might be a clue to identify them.
Sujet(s)
Tumeurs du sein/anatomopathologie , Maladie de Paget extramammaire/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Marqueurs biologiques tumoraux/analyse , Biopsie , Tumeurs du sein/composition chimique , Tumeurs du sein/chirurgie , Diagnostic différentiel , Évolution de la maladie , Femelle , Humains , Immunohistochimie , Adulte d'âge moyen , Mucine-5AC/analyse , Maladie de Paget extramammaire/composition chimique , Maladie de Paget extramammaire/chirurgie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/chirurgie , Valeur prédictive des tests , PronosticRÉSUMÉ
Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's disease. An accumulation of melanin within the lesion imparts a brow color to the affected area, so the lesion might clinically as well as histologically mimic melanoma. We present a case of PPD in a 60-year-old woman.
Sujet(s)
Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Mélanines/analyse , Mélanocytes/composition chimique , Mamelons/composition chimique , Maladie de Paget du sein/composition chimique , Biopsie , Tumeurs du sein/anatomopathologie , Tumeurs du sein/thérapie , Diagnostic différentiel , Femelle , Humains , Immunohistochimie , Mélanocytes/anatomopathologie , Adulte d'âge moyen , Mamelons/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Maladie de Paget du sein/thérapie , Valeur prédictive des tests , Résultat thérapeutiqueSujet(s)
Tumeurs du sein/diagnostic , Mélanome/diagnostic , Maladie de Paget du sein/diagnostic , Tumeurs cutanées/diagnostic , Sujet âgé , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Tumeurs du sein/imagerie diagnostique , Tumeurs du sein/anatomopathologie , Dermoscopie , Diagnostic différentiel , Faux négatifs , Femelle , Humains , Mammographie , Mamelons/anatomopathologie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/imagerie diagnostique , Maladie de Paget du sein/anatomopathologie , Pigmentation de la peauRÉSUMÉ
AIMS: Toker cells are clear cells present in the squamous epithelium of the nipple of some women. In contrast to squamous epithelium, they are cytokeratin 7 (CK7) positive. The origin of these cells is not completely understood. It has been suggested that they may represent abortive glands or migratory ductal cells; and may be precursors of Paget's disease of the nipple. Our aim was to investigate the incidence and distribution of Toker cells and their relationship with lactiferous ducts. METHODS: We examined nipple sections from 100 consecutive mastectomies performed at Charing Cross hospital. New sections were stained for CK7 using the immunoperoxidase technique. RESULTS: Toker cells were identified in 11 cases. They were always clustered within the squamous epithelium superficial to sebaceous glands with no relationship with lactiferous ducts. Two cases in the study had Paget's disease and these were not associated with underlying sebaceous glands. CONCLUSIONS: This study suggests that Toker cells are more likely to be developmentally related to sebaceous glands rather than lactiferous ducts. This raises doubts about the presence of a relationship between Toker cells and the common forms of Paget's disease, as the latter are commonly seen in association with ductal carcinoma in situ (DCIS) involving underlying lactiferous ducts. Toker cells, however, may be related to a less common form of Paget's disease which is not associated with underlying DCIS.
Sujet(s)
Tumeurs du sein/anatomopathologie , Carcinome intracanalaire non infiltrant/anatomopathologie , Glandes mammaires humaines/anatomopathologie , Mamelons/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Glandes sébacées/anatomopathologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Marqueurs biologiques/analyse , Biopsie , Tumeurs du sein/composition chimique , Tumeurs du sein/chirurgie , Carcinome intracanalaire non infiltrant/composition chimique , Carcinome intracanalaire non infiltrant/chirurgie , Femelle , Humains , Immunohistochimie , Kératine-7/analyse , Londres , Glandes mammaires humaines/composition chimique , Glandes mammaires humaines/chirurgie , Mastectomie , Adulte d'âge moyen , Mamelons/composition chimique , Mamelons/chirurgie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/chirurgie , Glandes sébacées/composition chimique , Glandes sébacées/chirurgieRÉSUMÉ
Paget's disease of the breast is a disorder of the nipple-areola complex that, while rare, is often associated with an underlying carcinoma. It is characterized by eczematoid changes of the nipple. Two theories have been proposed to explain the pathogenesis of Paget's disease. The Epidermotropic, which is the most accepted theory, suggests that Paget's cells originate from ductal cancer cells that had migrated from the underlying breast parenchyma. It is supported by the predominance of breast cancer markers found in Paget's disease. This article provides an overview of Paget's disease of the breast with special attention to immunohistochemistry and raises the question of new therapeutic approaches.
Sujet(s)
Tumeurs du sein/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Tumeurs du sein/diagnostic , Tumeurs du sein/étiologie , Tumeurs du sein/thérapie , Tumeur du sein de l'homme/composition chimique , Tumeur du sein de l'homme/diagnostic , Tumeur du sein de l'homme/étiologie , Tumeur du sein de l'homme/anatomopathologie , Tumeur du sein de l'homme/thérapie , Mouvement cellulaire , Transformation cellulaire néoplasique , Association thérapeutique , Diagnostic différentiel , Imagerie diagnostique/méthodes , Épiderme/anatomopathologie , Femelle , Humains , Kératinocytes/anatomopathologie , Mâle , Mastectomie/méthodes , Adulte d'âge moyen , Protéines tumorales/analyse , Mamelons/anatomopathologie , Maladie de Paget extramammaire/anatomopathologie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/diagnostic , Maladie de Paget du sein/étiologie , Maladie de Paget du sein/thérapie , Pronostic , Jeune adulteRÉSUMÉ
This case describes new onset mammary Paget disease arising in the background of Darier disease. Clinically and histologically, lesions of Darier disease can mask the lesions of mammary Paget disease. A high index of suspicion is necessary to diagnose Paget disease in a patient with Darier disease, for a potentially fatal disease could easily be missed.
Sujet(s)
Tumeurs du sein/diagnostic , Maladie de Darier/diagnostic , Maladie de Paget du sein/diagnostic , Sujet âgé , Marqueurs biologiques tumoraux/analyse , Biopsie , Tumeurs du sein/composition chimique , Tumeurs du sein/complications , Tumeurs du sein/thérapie , Maladie de Darier/complications , Maladie de Darier/thérapie , Femelle , Humains , Immunohistochimie , Kératine-7/analyse , Mamelons/anatomopathologie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/complications , Maladie de Paget du sein/thérapie , Valeur prédictive des tests , Peau/anatomopathologieSujet(s)
Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Tumeurs du sein/anatomopathologie , Invasion tumorale/anatomopathologie , Diagnostic différentiel , Femelle , Humains , Immunohistochimie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/anatomopathologieSujet(s)
Tumeurs du sein/diagnostic , Hyperpigmentation/étiologie , Mamelons/anatomopathologie , Maladie de Paget du sein/diagnostic , Adulte , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Tumeurs du sein/complications , Tumeurs du sein/chirurgie , Dermoscopie , Diagnostic différentiel , Femelle , Humains , Mastectomie partielle , Mélanome/diagnostic , Mamelons/composition chimique , Mamelons/chirurgie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/complications , Maladie de Paget du sein/chirurgie , Récepteur ErbB-2/analyse , Tumeurs cutanées/diagnosticRÉSUMÉ
Pigmented mammary and extramammary Paget disease are rare entities in both males and females that mimic melanoma both clinically and histologically. Furthermore, Paget disease can be associated with increased number of benign melanocytes, thus resulting in additional diagnostic difficulty, especially when only hematoxylin and eosin-stained sections are examined and a limited immunohistochemical study is performed. Using standard hematoxylin and eosin-stained sections and routine immunohistochemical studies, we describe and characterize 7 cases of pigmented extramammary and mammary Paget disease. In all cases, malignant epithelial cells showed intracytoplasmic pigment, along with an immunohistochemical epithelial phenotype. In 2 of the cases, immunohistochemistry revealed numerous dendritic processes positive for melanocytic markers, thus resulting in an initial diagnosis of melanoma. Careful analysis confirmed that the immunolabeling corresponded to cytoplasmic labeling of melanocyte dendrites surrounding tumor cells. The correct diagnosis of pigmented Paget disease can be reached after close histologic examination and detailed evaluation of immunohistochemical studies. The latter are especially important in some extraordinary cases in which there may be an associated intraepithelial melanocytic hyperplasia.
Sujet(s)
Tumeurs du sein/anatomopathologie , Erreurs de diagnostic/prévention et contrôle , Hyperpigmentation/anatomopathologie , Mélanocytes/anatomopathologie , Mélanome/anatomopathologie , Maladie de Paget extramammaire/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Adulte , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Diagnostic différentiel , Femelle , Humains , Hyperpigmentation/métabolisme , Immunohistochimie , Mâle , Mélanocytes/composition chimique , Adulte d'âge moyen , Maladie de Paget extramammaire/composition chimique , Maladie de Paget du sein/composition chimique , Pigments biologiques/analyse , Valeur prédictive des testsRÉSUMÉ
BACKGROUND: Paget's disease of the nipple is generally associated with an underlying invasive cancer or an underlying ductal carcinoma in situ. Epidermotropic theory maintains that Paget's cells are derived from an underlying mammary in situ adenocarcinoma. Because p16 protein plays a major role in cell-cycle control and in tumoral cell mobility, we analyzed p16 expression in Paget's disease of the nipple and in associated underlying ductal carcinoma in situ. METHODS: The expression of p16 protein was analyzed by immunohistochemistry in eight cases of Paget's disease of the nipple with associated underlying ductal carcinoma in situ. The Student's t-test (2-tailed) was used to establish the equality of means. RESULTS: The expression of p16 protein was observed in 87.5% (7/8 cases) both in the nipple disease and in the associated underlying ductal carcinoma in situ. The difference between the two populations was not statistically significant. In normal breast tissue, no expression of the protein was observed. CONCLUSION: The positive p16 expression in Paget's disease of the nipple and the underlined ductal carcinoma in situ and its role in cell motility lead us to propose a role of p16 in the spread of this disease.
Sujet(s)
Protéines tumorales/analyse , Maladie de Paget du sein/composition chimique , Épithélioma in situ/composition chimique , Carcinome canalaire/composition chimique , Inhibiteur p16 de kinase cycline-dépendante , Femelle , Humains , Immunohistochimie , Mamelons/composition chimiqueRÉSUMÉ
Mammary Paget's disease (MPD) is an uncommon in situ neoplasm of the nipple-areolar complex and surrounding skin. It is almost always associated with mammary ductal carcinoma in situ (DCIS), high-grade or invasive carcinoma, usually of ductal origin. MPD has only rarely been described in association with specialized forms of breast carcinoma. We report an unusual case of an acinar pattern of MPD with low-grade cytological atypia, associated with invasive papillary carcinoma and micropapillary DCIS of the lactiferous ducts, in an 83-year-old woman. Most cases of MPD are characterized by intraepidermal spread of discohesive glandular epithelial cells with high-grade nuclear atypia. A predominant acinar pattern of MPD is extremely uncommon and, to our knowledge, has not been formally reported. The histological features and differential diagnosis are discussed.
Sujet(s)
Tumeurs du sein/anatomopathologie , Épithélioma in situ/anatomopathologie , Carcinome canalaire du sein/anatomopathologie , Carcinome papillaire/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Tumeurs du sein/composition chimique , Épithélioma in situ/composition chimique , Carcinome canalaire du sein/composition chimique , Carcinome papillaire/composition chimique , Femelle , Humains , Immunohistochimie , Maladie de Paget du sein/composition chimiqueSujet(s)
Tumeurs du sein/anatomopathologie , Kératine-7/analyse , Mélanome/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Tumeurs cutanées/anatomopathologie , Tumeurs du sein/composition chimique , Tumeurs du sein/complications , Diagnostic différentiel , Femelle , Humains , Hyperpigmentation/complications , Adulte d'âge moyen , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/complications , Coloration et marquageRÉSUMÉ
BACKGROUND: Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties. METHODS: Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed. RESULTS: Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease. CONCLUSION: An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases.
Sujet(s)
Kératines/analyse , Tumeurs épithéliales épidermoïdes et glandulaires/diagnostic , Tumeurs épithéliales épidermoïdes et glandulaires/anatomopathologie , Tumeurs cutanées/diagnostic , Tumeurs cutanées/anatomopathologie , Maladie de Bowen/composition chimique , Maladie de Bowen/diagnostic , Maladie de Bowen/anatomopathologie , Diagnostic différentiel , Humains , Kératose/diagnostic , Kératose/anatomopathologie , Tumeurs épithéliales épidermoïdes et glandulaires/composition chimique , Maladie de Paget extramammaire/composition chimique , Maladie de Paget extramammaire/diagnostic , Maladie de Paget extramammaire/anatomopathologie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/diagnostic , Maladie de Paget du sein/anatomopathologie , Analyse de régression , Tumeurs cutanées/composition chimique , Tumeurs des glandes sudoripares/composition chimique , Tumeurs des glandes sudoripares/diagnostic , Tumeurs des glandes sudoripares/anatomopathologieRÉSUMÉ
HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.
Sujet(s)
Maladie de Paget du sein/composition chimique , Récepteur ErbB-2/analyse , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Amplification de gène , Humains , Immunohistochimie , Hybridation fluorescente in situ , Adulte d'âge moyen , Protéines tumorales/analyse , Maladie de Paget du sein/anatomopathologie , Récepteurs des oestrogènes/analyseRÉSUMÉ
The present paper documents an investigation of the morphology, immunohistochemistry, and ultrastructure of Toker cells (TC), aiming for a better definition of these elements and better understanding of their histogenesis. We studied 12 nipples removed for nipple adenoma from twelve patients and a case of supernumerary nipple. In addition four cases of Paget's carcinoma (PC) restricted to the nipple without underlying tumor were studied for comparison. All cases were stained with hematoxylin and eosin (H&E), Alcian blue pH 2.5 and periodic acid-Schiff (PAS) preceded by diastase digestion and with immunohistochemistry using antisera anti cytokeratin 7, cytokeratin 20, protein S100, GCDFP-15, c-Erb-B2, CAM 5.2, and epithelial membrane antigen (EMA). Two cases from the nipple adenoma series were studied by electron microscopy. In seven cases within the series of 12 nipple adenomas as well as in the case of supernumerary nipple, keratin 7 antibody highlighted numerous cells located within the nipple epidermis which in three cases showed dendritic processes. These same elements were also positive with CAM 5.2. All these same elements were negative with Alcian Blue (AB), PAS and the other antisera employed. Ultrastructural examination demonstrated that these cells differed from keratinocytes while they presented the same features as the glandular cells seen in the related nipple adenoma. The cells constituting Paget's carcinoma showed more irregular nuclei and were more easily seen in the context of the epidermis. The immunocytochemical profile of the cancer cells was similar to that of TC, but in addition the neoplastic cells were c-Erb-B2 and EMA positive in all cases, and one case also displayed numerous cells immunoreactive with anti GCDFP-15 antibody. Keratin 7 highlighted dendritic cells in two cases and AB, PAS was negative in all patients. The immunocytochemical profile and the ultrastructural features of TC are similar to those of the glandular cells constituting the ducts and the adenoma. These findings together with the localization of TC near or around the openings of the lactiferous sinuses indicate that TC might be ductal cells with a dendritic aspect and migrate through the galactophorous ostia. PC cells not related to ductal carcinomas have a similar but not superimposable immunohistochemical profile to TC, and in two cases the neoplastic elements were also dendritic which suggests that these same cells are likely to be the neoplastic counterpart of TC.
Sujet(s)
Tumeurs du sein/anatomopathologie , Mamelons/anatomopathologie , Maladie de Paget du sein/anatomopathologie , États précancéreux/anatomopathologie , Adénomes/composition chimique , Adénomes/anatomopathologie , Adulte , Sujet âgé , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Noyau de la cellule/ultrastructure , Cytoplasme/ultrastructure , Femelle , Humains , Immunohistochimie , Mâle , Adulte d'âge moyen , Protéines tumorales/analyse , Mamelons/composition chimique , Maladie de Paget du sein/composition chimique , États précancéreux/composition chimiqueRÉSUMÉ
OBJECTIVE: Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma. METHODS: Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index). RESULTS: p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%. CONCLUSION: Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.
Sujet(s)
Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Antigène KI-67/analyse , Maladie de Paget extramammaire/composition chimique , Maladie de Paget du sein/composition chimique , Protéine p53 suppresseur de tumeur/analyse , Tumeurs de la vulve/composition chimique , Adulte , Sujet âgé , Femelle , Humains , Immunohistochimie , Adulte d'âge moyen , Pronostic , Facteurs de risqueRÉSUMÉ
BACKGROUND AND OBJECTIVES: Molecular markers are increasingly being analyzed in tumor specimens because of their relevance to both prognosis and choice of therapy. Paget disease of the breast is an uncommon form of breast cancer, in which molecular markers have not been well characterized. The objective of this study was to investigate the expression of c-erbB-2, p53, Ki-67, Cyclin D1, Bcl-2, estrogen receptors (ER), and progesterone receptors (PR) in mammary Paget disease. METHODS: Archival tumor tissues from 14 patients diagnosed between 1990 and 1999 with Paget disease of the breast were analyzed for these molecular markers by using an automated immunohistochemical assay. Both the intraepidermal Paget cells and the underlying carcinoma were assessed for these markers. RESULTS: The majority of Paget cells were positive for c-erbB-2 (92.9%), Cyclin D1 (100%), and Ki-67 (85.7%), but very few were positive for Bcl-2 (14.3%). p53 was overexpressed in 42.9% of the cases, and only 28.6% were positive for ER and PR. The rate of expression of these biologic markers was similar in both the Paget cells and the underlying intraductal and/or ductal carcinoma cells. CONCLUSIONS: Tumors from patients with Paget disease of the breast were positive for c-erbB-2, Cyclin D1, and Ki-67, molecular markers commonly associated with more aggressive tumor behavior and poorer survival in breast cancer patients. Few of these tumors expressed Bcl-2 or ER and PR, which are generally associated with a better prognosis. Similar expression of these markers in both Paget cells and the underlying carcinoma supports the theory that these cells are the result of an intraepidermal spread of ductal carcinoma.
Sujet(s)
Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Maladie de Paget du sein/composition chimique , Tumeurs du sein/anatomopathologie , Cycline D1/analyse , Femelle , Humains , Immunohistochimie , Antigène KI-67/analyse , Maladie de Paget du sein/anatomopathologie , Pronostic , Protéines proto-oncogènes c-bcl-2/analyse , Récepteur ErbB-2/analyse , Récepteurs des oestrogènes/analyse , Protéine p53 suppresseur de tumeur/analyseRÉSUMÉ
AIMS: The histogenesis of mammary Paget's disease is controversial. The purpose of this study was to investigate the mechanism of tumour spread in the nipple epidermis by examining 28 cases of mammary Paget's disease associated with underlying intraductal carcinoma. METHODS AND RESULTS: The atypical cells in the epidermis displayed a spectrum of cytological changes ranging from small-sized atypical cells located in the basal cell layer to large-sized atypical cells characteristic of Paget's cells in the upper layer of the epidermis. Serial sectioning revealed the presence of isolated, scattered and small atypical cells in the basal cell layer at the periphery of the epidermal lesion. The atypical cells, including those in the basal cell layer showed positive immunostaining for cytokeratin 7 and Her2/neu oncoprotein. Electron microscopy examination demonstrated the presence of intercellular junctions of desmosomal-like or desmosomal types between tumour cells and adjacent squamous cells. Furthermore, examination of the intraductal carcinoma of the breast tissue in cases of Paget's disease as well as control cases of intraductal carcinoma also revealed areas of skip lesions of intraductal carcinoma. CONCLUSIONS: In view of these changes, it is unlikely that tumour expansion or tumour cell motility are sufficient explanations to account for the pattern of tumour spread in both the epidermis and the duct epithelium with skip lesions. A 'field effect' in the duct system harbouring intraductal carcinoma and the adjacent epidermis may play an important role in the tumour cell spread in the epidermis as well as in the ductal epithelium.
Sujet(s)
Tumeurs du sein/anatomopathologie , Maladie de Paget du sein/anatomopathologie , Tumeurs du sein/composition chimique , Tumeurs du sein/étiologie , Épithélioma in situ/composition chimique , Épithélioma in situ/anatomopathologie , Carcinome intracanalaire non infiltrant/composition chimique , Carcinome intracanalaire non infiltrant/complications , Carcinome intracanalaire non infiltrant/anatomopathologie , Épiderme/anatomopathologie , Femelle , Humains , Immunohistochimie , Kératine-7 , Kératines/analyse , Invasion tumorale , Mamelons/anatomopathologie , Maladie de Paget du sein/composition chimique , Maladie de Paget du sein/étiologie , Récepteur ErbB-2/analyseRÉSUMÉ
A 99m Tc MIBI prone scintimammography (PSM) was performed in a case of underlying Paget's disease of the breast. 99m Tc MIBI PSM showed a diffuse scintigraphic image like a spread of uptake from the deeply located zones of the breast toward epidermis. In vivo, 99m Tc MIBI PSM represents the spread of neoplastic Paget's cells probably attracted by chemotactic factors released by keratinocytes. This spread in Paget's disease is correlated to neu oncogene overexpression which increases the metastatic activity as a consequence of motility enhancement and growth stimulation effect. These scintigraphic images suggest that 99m Tc MIBI PSM could be relevant in management of Paget's disease of the breast.
Sujet(s)
Tumeurs du sein/imagerie diagnostique , Épithélioma in situ/diagnostic , Carcinome canalaire du sein/diagnostic , Tumeurs primitives multiples/diagnostic , Maladie de Paget du sein/imagerie diagnostique , Technétium (99mTc) sestamibi , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/composition chimique , Facteurs chimiotactiques/métabolisme , Épiderme/anatomopathologie , Femelle , Humains , Kératinocytes/métabolisme , Mammographie , Adulte d'âge moyen , Invasion tumorale , Protéines tumorales/analyse , Cellules souches tumorales/composition chimique , Cellules souches tumorales/imagerie diagnostique , Cellules souches tumorales/anatomopathologie , Maladie de Paget du sein/composition chimique , Décubitus ventral , Scintigraphie , Récepteur ErbB-2/analyse , ÉchographieRÉSUMÉ
Sagebiel (1969) electronmicroscopically observed that desmosomes are present between adjacent Paget cells, as well as between Paget cells and adjacent keratinizing epidermal cells. Desmosomes contain the proteins desmoglein (Dsg) and desmocollin as their transmembrane components, and Dsg has three isotypes. Among the three isotypes of Dsg, Dsg1 and Dsg3 are autoantigens for pemphigus foliaceus and pemphigus vulgaris (PV), respectively. We examined the expression of Dsgs in Paget cells of mammary and extramammary Paget's disease. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 with extramammary Paget's disease. One part of the samples was cut into small pieces and epidermal sheets were separated with dispase, then treated with a mixture of EDTA and trypsin. The resulting cell suspensions were cultured in low Ca++ medium, then the cells were incubated in high Ca++ medium. Paget cells identified with anti-epithelial membrane antigen (EMA) antibody were positive for serum from a PV patient which was confirmed to react with both Dsg1 and Dsg3. However, the intensity of fluorescence of Paget cells was weaker than that of EMA-negative keratinocytes. In the cryostat sections, Paget cells identified with anti-EMA antibody showed the same staining pattern as cultured cells in high Ca++ medium. The data presented in this study confirm that Paget cells express Dsgs, and are consistent with the electronmicroscopical data by Sagebiel (1969). However, our data do not support the hypothesis that Paget cells are of keratinocyte origin, because sweat ducts or sweat glands could be positive for sera from PV patients. It is necessary to confirm whether or not sweat ducts or sweat glands express Dsgs, because sera from PV patients exhibit high background in the dermis.