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By Jeyashree Sundaram, MBA
As Extramammary Paget’s Disease (EMPD) includes a range of locations, how to buy tricor australia without prescription the diagnosis should be made using additional measures such as colonoscopy, mammography, cervical cytology, papanicolau staining, and colposcopy. In addition to biopsies that are performed to find the extent of the disease, some physicians also use noninvasive imaging procedures such as in vivo reflectance confocal microscopy.
Credit: Robert Przybysz/ Shutterstock.com
Primary and secondary types
According to the Wilkinson and Brown classification done in 2002, EMPD is categorized as:
- Primary EMPD, of cutaneous origin
- Secondary EMPD, of non-cutaneous origin
Primary EMPD is further divided into three subtypes, all of which are of intraepithelial cutaneous origin:
- usual type
- with invasion
- occurring as a feature of underlying skin adenocarcinoma arising in a skin appendage or the vulvar glans
Among the secondary types, there are three subtypes:
Paget disease of 1) anorectal origin, 2) urothelial origin, and 3) of other origin.
Useful markers for diagnosis among the primary types are cytokeratin 7(CK7), cytokeratin 20 (CK20), gross cystic disease fluid protein 15 (GCDFP-15), carcinoembryonic antigen (CEA), and uroplakin III (UPK). The cells are positive for CK7, GCDFP, and CEA and are negative for CK20 and UPK.
Useful markers for diagnosis among secondary types are the same as that of primary types; subtype 1 is positive for CK20 and CEA, but usually negative for CK7, and always negative for UPK and GCDFP-15 consistently. Sub type 2 is positive for UPK and CK7, variable for CK20, but negative for CEA and GCDFP-15.
The antigen expression noticed in the primary tumor is a useful marker for subtype 3. Immunocytochemistry for tumor-associated glycoprotein 72 (TAG-72), identified by monoclonal antibody B72.3 is useful to identify EMPD, similar to GCDFP-15.
The disease types may thus be differentiated by CK7, CK20, CEA, UPK, and GCDFP-15. This helps clarify the right mode of treatment and may obviate surgery in some cases. An accurate diagnosis significantly impacts the selection of treatment modality for the disease.
Invasive versus noninvasive types
In the invasive types of EMPD, the Paget cells penetrate the skin basement membrane and are found in the dermis. This invasive ability is linked to reduced E-cadherin expression and sometimes to abnormal gamma-catenin (plakoglobin) expression.
Another test used to differentiate invasive from non-invasive types of EPMD is the immunohistochemical stain for MUC5AC and MUC1. Malignant potential rises as MUC5AC expression is reduced or lost, with these Paget cells showing a high propensity to invade into the dermis.
Other studies have shown that markers such as Jak, Fak, and Erk ½, as well as the transcription factor Sp1 and vascular endothelial growth factor (VEGF) are associated with a higher grade of malignancy. Cyclin D1 and Ki67 expression levels also follow this trend.
The histology, clinical features and disease outcome are also related to Her2/neu expression, which is higher with the grade of the tumor, signaling increased invasiveness. The anti-Her2/neu antibody Trastuzumab may possibly be useful in the treatment of this condition for this reason.
Compared with in situ lesions, invasive lesions have shown noteworthy differences (higher differences) in:
Among the many biopsy types available, shave biopsy or punch biopsy is commonly used for diagnosing EMPD.
In shave biopsy, the physician shaves a few skin layers to obtain a tissue sample. In the punch biopsy technique, a sample is punched out of the top skin layer for examination. One or two stitches may be required occasionally. Depending on the location punched, it may take weeks or months to heal completely.
In vivo reflectance confocal microscopy (RCM) enables what are termed virtual biopsies. With RCM, the same area can be reviewed multiple times without tissue damage. It is possible to visualize the epidermis and deeper, up to the papillary dermis. Larger areas are covered without pain. Images can also be recorded to assess locations that are sensitive and difficult to target.
Differential diagnoses of EMPD include cutaneous neoplasms including malignant melanoma, mycosis fungoides, basalioma, clear cell papulosis, vulvar intraepithelial neoplasia/Bowen disease, histiocytosis, Merkel cell carcinoma, sebaceous carcinoma, and eccrine porocarcinoma.
Immunohistochemical findings have shown strong CK7 and CK8 expression in both Bowen disease and EMPD. However, no CEA expression was seen in the parts affected with Bowen disease. It is difficult to differentiate Bowen disease, VIN, and EMPD purely on histological examination. Metastatic breast cancer may also resemble EMPD as Paget cells express c-erb-2 oncogene and HER2/neu receptors that suggest a common biological origin with breast carcinoma.
The immunohistochemical profile is positive for antigen Melan A and S100 protein in skin melanomas and negative for Paget disease. Cytokeratins, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) are found to be negative in skin melanoma and positive for Paget disease.
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Last Updated: Feb 26, 2019
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