Molecular subtyping of mammary Paget's disease using immunohistochemistry.

OBJECTIVE: To evaluate the molecular subtypes of Mammary Paget's disease (MPD) and the associated breast carcinomas. METHODS: This retrospective study was carried out at King Khalid University Hospital and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Data from MPD patient cases from January 2010 to June 2016 were reviewed. The molecular subtypes were determined based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression with immunohistochemical staining. The relative frequencies of the luminal A and B, HER2-enriched and basal-like molecular subtypes were calculated and compared for MPD and the associated breast carcinomas. Results: Among 22 patients with MPD, HER2-enriched was the most frequently occurring molecular subtype and was observed in 11 (50%) patients. Mammary Paget's disease was classified as basal-like in 5 (22.7%) patients, and luminal A and B were each detected in 3 (13.6%) patients. The molecular subtype of MPD corresponded with the subtype of the associated breast carcinoma in 18 out of 20 patients (90%). CONCLUSIONS: The HER2-enriched subtype is the most frequently occurring molecular subtype in MPD. The molecular subtype of the associated breast carcinoma is usually similar to that of MPD. The molecular subtypes vary between MPD associated breast carcinoma and overall breast carcinoma. The HER2-enriched subtype is the most frequently occurring subtype of MPD associated breast carcinoma, while luminal subtypes are more common in overall breast carcinoma.

HER2 molecular subtype is a dominant subtype of mammary Paget's cells. An immunohistochemical study.

AIMS: To test the hypothesis that the similarity of the molecular subtypes of Paget's cells to the molecular subtypes of the underlying breast carcinomas favours the epidermotrophic theory of the origin of Paget's cells. METHODS AND RESULTS: The immunohistochemical expression of markers that define particular molecular subtypes of breast carcinomas were analysed. The whole analysis was performed by means of tissue microarrays in mammary Paget's disease and in the underlying breast carcinoma(s). Human epidermal growth factor receptor type 2 (HER2)-overexpression subtype [oestrogen receptor (ER(-) ); HER2(+) ] was a dominant molecular subtype of Paget's cells (37 of 43 analysed cases; 86%). Luminal B (ER(+) ; HER2(+) ) and luminal A (ER(+) ; HER(-) ) subtypes were identified in 12% and 2% of cases, respectively. None of the analysed tumours presented a basal-like phenotype. A similar distribution of molecular subtypes was identified in the underlying in situ breast carcinomas (HER2 subtype, 82%; luminal A, 6%; luminal B, 6%; basal-like, 6% of cases) and in the invasive component (HER2 subtype, 84%; luminal A, 8%; luminal B, 8%; basal-like, 0% of cases). CONCLUSIONS: HER2 molecular subtype is the dominant, but not the sole subtype seen in Paget's cells of the nipple. A similar distribution of molecular subtypes in both Paget's cells and in the underlying carcinomas strongly suggests their common origin.

[TNM classification of breast cancer: changes and comments on the 7th edition]. / TNM-Klassifikation beim Mammakarzinom : Neuerungen und Anmerkungen zur 7. Auflage.

The 7th edition of the TNM classification includes only minor changes in the main TNM categories for breast cancer. Only ductal and lobular carcinoma in situ (DCIS, LCIS), and isolated Paget's disease of the nipple are classified as pTis, but not precursor lesions such as atypical ductal or lobular hyperplasia (ADH, ALH). AJCC emphasizes that microscopic measurement is the most accurate and preferred method to determine pT in small invasive cancers and stresses the importance of strict adherence to criteria for T4 cancers. For better distinction from micrometastases in regional lymph nodes, small clusters of cells not greater than 0.2 mm, or nonconfluent or nearly confluent clusters of cells not exceeding 200 cells in a single histologic lymph node cross section are classified as isolated tumour cells (pN0(i+)). The pN classification has otherwise remained unchanged. In the setting of patients having received neoadjuvant therapy, ypT1-ypT3 is based on the total extent of viable tumour cells, irrespective of tumour regression. Stage I breast tumours have been subdivided into Stage IA and Stage IB; Stage IB includes small tumours (TI) with lymph node micrometastases (N1mi). These changes and clarifications will contribute to maintaining the clinical and prognostic relevance of TNM in breast cancer.

Clinically silent Paget disease of male nipple.

Male breast cancer constitutes less than 1% of all breast cancer cases. Special types, such as Paget disease of the breast, are extremely rare. To our knowledge there are less than 50 cases of Paget disease of male breast described in world medical literature. Authors present pathologically proven but clinically silent case of Paget disease of the nipple in an 86-year old male with breast cancer. Literature data suggest that the prognosis of male Paget cancer is worse than in "ordinary" male breast cancer. Therefore, the histologic diagnosis of Paget disease, even in an asymptomatic male patient, may have negative prognostic value.

Anaplastic Paget's disease.

Six cases of a distinct, histologically anaplastic variant of mammary Paget's disease are described. Patients ranged in age from 40 to 85 years. All patients had scaling erythematous lesions confined to the nipple; none had palpable breast masses. Histologically, the lesions had features resembling Bowen's disease, including full-thickness epidermal atypia, loss of nuclear polarity, and marked cytologic anaplasia. Intraepidermal acantholysis was a distinctive feature in all cases. In some biopsies, small groups and single typical Pagetoid cells were seen within the areas of confluent Bowen-like change. Immunohistochemically, carcinoembryonic antigen (CEA) was positive in three of six patients; epithelial membrane antigen (EMA) in five of six patients, and cytokeratin AE1/AE3 in three of six patients. Mucicarmine stains were uniformly negative. In our series, anaplastic Paget's disease was associated with concomitant invasive ductal carcinoma in three of six patients (50%). This percentage is significantly higher than that previously reported for patients with Paget's disease and without palpable breast mass. Histologic features that are helpful in distinguishing between anaplastic Paget's disease and Bowen's include cleft-like acantholysis, absence of dyskeratotic cells, and persistence of basal cell layer. More rarely, but very helpful when present, are underlying ductal carcinoma, intracellular lumina, and associated conventional Paget's disease. Immunohistochemistry results were variable and of relative value. Our study suggests that a nipple lesion histologically resembling Bowen's disease is likely to represent anaplastic Paget's disease.

[Histological classification of breast cancer].

The characteristics of histological classification of breast cancer by Stewart F.W., WHO and Japan Mammary Cancer Society (published in 1971 and revised in 1984) are discussed. The classification of JMCS is fundamentally the same as WHO classification with a subclassification of invasive ductal carcinoma. Invasive ductal carcinoma has three subgroups; papillotubular, solid-tubular and scirrhous carcinoma. In these three subgroups, papillotubular carcinoma shows mainly ductal spread, well histologic differentiation, the lowest lymph node metastasis and the best prognosis. Scirrhous carcinoma shows diffuse stromal infiltration, poor histologic differentiation, the highest metastasis and the worst prognosis. Solid-tubular carcinoma with expansive stromal invasion shows intermediate biological behavior. Thus, the JMCS classification contains in itself not only histologic type but also the mode of spread, grade of histologic differentiation, ratio of lymph node metastasis and prognosis.

[Histological types of 876 breast cancers according to the 1981 WHO classification]. / Types histologiques de 876 cancers du sein selon la classification de l'OMS 1981.

This work presents the results of the classification by histological types of 876 cancers, operated on between November 1979 and December 1982, according to the new WHO's classification of 1981. Noninfiltrating cancers represent 6.5 per cent of the total. Among the infiltrating cancers (93.5%), the individualization of the type "infiltrating duct carcinoma with a marked intraductal component" (14.5%) is interesting for this form justifies a special treatment in consideration of its multicentric and sometimes bilateral character. Its purely quantitative criteria of definition is subject to criticism and discussion.

Histologic classification of pure primary epithelial breast cancer.

Current classifications of breast cancer are based on either morphologic descriptive or histogenetic criteria. The positive features and shortcomings of the most commonly used systems are presented. Our knowledge of breast cancer leads validity to a histogenetic topographic classification, a modification of which is suggested.