Cas 0807872

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  Femme de 51 ans, lésion rougeâtre suitante et pigmentée hétérogène mal circonscrite de la peau aréolaire du sein.  

41 yo female, flat weeping lesion, erythematous more or less pigmented, ill circumscribed of the breast peri-areolar skin.

  Biopsie chirurgicale:   Surgical biopsy:  
  CK7   CK7  
  EMA   EMA  
  Melan A   Melan A  
  Parties profondes de la biopsie   Deep aspects of the biopsy  

Diagnostic proposé:









Maladie de Paget sur carcinome intracanalaire


Proposed diagnosis:









Paget's disease with ductal carcinoma in situ

  En gras dans le texte de la référence ci-dessous (cliquez pour visualiser l'image):   In the highlighted text of the reference below:  

Paget's disease in Ackerman's Surgical Pathology (8th Ed.)

Paget's disease is the name given to a crusted lesion of the nipple caused by breast carcinoma, as originally described by Sir James Paget in 1874. It is accompanied in nearly all instances by an underlying breast carcinoma of in situ ductal type, with or without associated stromal invasion. In this regard, the presence of Paget's disease is only a secondary, albeit dramatic, feature of the tumor. The management and prognosis depend largely on the intraductal versus invasive nature of the underlying carcinoma and on the presence or absence of axillary lymph node involvement, rather than on the presence or appearance of the intraepithelial component in the nipple.

  Clinically, these weeping, eczema-like lesions are centered in the nipple. Later they may involve the areola and surrounding epidermis, but they rarely extend more than a few centimeters. If a definite mass can be palpated beneath the diseased nipple, the underlying tumor will have an invasive component in over 90% of the cases. Conversely, 66% of the cases without a palpable mass are exclusively intraductal.  
  Microscopically, large clear cells with atypical nuclei are seen within the epidermis, usually concentrated along the basal layer but also permeating the malpighian layer. The cells can be isolated or in clusters, and sometimes they form small glandular structures. In rare instances they have an anaplastic appearance. Occasionally, intracytoplasmic melanin granules are present, a feature that may result in a mistaken diagnosis of malignant melanoma; these granules have probably been transferred from neighboring melanocytes by the process of cytocrinia. The underlying breast carcinoma is always of ductal type and is composed of cells similar to those present within the nipple. If enough sections are taken, a connection between the carcinoma within the duct and the Paget's disease will be demonstrated in most instances. However, in some cases the underlying tumor is found 2 cm or more from the nipple.  
  Mucin stains may or may not be positive, in contrast to their almost universal presence in extramammary Paget's disease. Ultrastructurally, the tumor cells have microvilli and other features indicative of glandular differentiation. Immunohistochemically, they show reactivity for EMA and the related milk fat globule membrane antigen, CEA (at least when using polyclonal antibodies), low-molecular-weight keratin, and (in half of the cases) GCDFP-15. In general, they are negative for S-100 protein and involucrin.  

The main differential diagnosis is with Bowen's disease and malignant melanoma. Examples of these disorders located in the nipple have been reported, and there is no reason why they could not involve this structure. We can only say that, in our experience, whenever this differential diagnosis was considered for a lesion of the nipple (because of pigmentation, transepidermal atypia, or any other reason), the definitive diagnosis invariably turned out to be Paget's disease.

The heated controversies in the past regarding the glandular versus keratinocytic versus melanocytic origin of Paget's disease have subsided. There can no longer be any doubt that Paget's cells exhibit glandular differentiation. However, a point still unsettled is whether the Paget's cells in the nipple have migrated there from deeper ductal structures (probably as a result of keratinocyte-induced chemotaxis or whether they represent an in situ malignant transformation either of the intraepidermal portion of the mammary ducts or of basally located multipotential epithelial cells capable of glandular differentiation. The similarities in immunohistochemical profile and oncogene expression (such as c-erb B-2 or ras 21) favor the former. On the other hand, the existence of rare cases of Paget's disease without underlying ductal carcinoma or with very limited in situ carcinoma of the most distal lactiferous ducts suggests that in some cases the latter mechanism may be operating. In this regard, the observation made by Toker about the presence of clear cells in nipples without clinical evidence of Paget's disease and without microscopic evidence of breast carcinoma is of great interest. We have also observed these cells (although not nearly with that frequency) and found not only that they react immunohistochemically like Paget's cells but also that they may exhibit mild nuclear atypical changes, suggesting the possibility of a dysplastic or "pre-Paget's" change. From a practical standpoint, these cells are distinguished from those of Paget's disease because of the lack of eczema-like changes clinically and the absence of clear-cut cytologic features of malignancy.