Letter: Pigmented extramammary Paget disease of the abdomen: A potential mimicker of melanoma1. Department of Pathology
Jeremy Vincent MD1, Janis M Taube MD2
Dermatology Online Journal 17 (8): 13
2. Department of Dermatology and Pathology
The Johns Hopkins Hospital, Baltimore, Maryland
Extramammary Paget disease (EMPD) is a rare condition that usually presents in areas that are rich in apocrine sweat glands such as the vulva, scrotum, and perianal areas. The majority of these tumors represent cutaneous extension from a visceral adenocarcinoma, whereas a smaller proportion arise in the cutaneous apocrine glands themselves. Women in their sixth to eighth decades are most commonly affected. It is exceedingly rare for EMPD to present on the face, chest, or abdomen, and even more unusual for it to present as a pigmented lesion. We report the case of a 63-year-old woman with an underlying colon cancer who presented with a pigmented lesion in the midline of the abdomen above the umbilicus. Immunohistochemical stains demonstrated the lesion to be CK7+/CK20- as well as negative for melanocytic markers (S100, MiTF, Melan-A, HMB-45). Further, the immunophenotype of the EMPD differed from the patient's underlying colon adenocarcinoma (CK20+/CK7-), arguing against an ectopic focus of her established disease. Making the distinction between pigmented EMPD and melanoma is a potential diagnostic pitfall because of the histologic similarities. Extramammary Paget disease should be considered in the morphologic differential diagnosis of melanoma and, if necessary, supporting studies should performed to aid in this distinction.
Extramammary Paget disease (EMPD) is a rare condition that usually presents in areas that are rich in apocrine sweat glands such as the vulva, scrotum, and perianal areas [1, 2, 3, 4]. The majority of cases represent cutaneous extension from a visceral adenocarcinoma, whereas a smaller proportion arise in the cutaneous apocrine glands themselves [1, 5]. Very rarely, cases of ectopic EMPD are seen in association with an underlying visceral adnenocarcinoma [5, 6]. Women in their sixth to eighth decades are most commonly affected. It is exceedingly rare for EMPD to present on the face, chest, or abdomen, and even more unusual for it to present as a pigmented lesion. Herein, we report the case of a 63-year-old woman with a history of recently diagnosed colonic adenocarcinoma who presented with a pigmented lesion suspicious for melanoma.
A 63-year-old woman with no history of melanoma or other atypical melanocytic lesions was being surgically treated for colonic adenocarcinoma stage T2 when a pigmented lesion suspicious for melanoma was noticed approximately two cm above the umbilicus in the midline of the abdomen. The skin lesion was removed at that time and sent for pathologic evaluation. Routine hematoxylin and eosin (H&E) sections (Figure 1) revealed an intraepidermal proliferation of nested and single cells, which were located above the basilar layer of keratinocytes. Pagetoid spread of atypical cells was a prominent feature. The cells were epithelioid in morphology, with abundant, pink cytoplasm and prominent nucleoli. Intracellular melanin pigment was observed. Immunohistochemical stains demonstrated the lesion to be CK7+/CK20- (Figure 2) as well as negative for the melanocytic markers S100, MiTF, Melan-A, and HMB-45 (Figure 3), supporting the diagnosis of EMPD. To determine whether this lesion represented a primary cutaneous EMPD or an ectopic focus of the underlying colonic adenocarcinoma, the immunophenotype of the colonic lesion was also assessed. The colon adenocarcinoma was CK20+/CK7-, indicating that the lesion is a primary cutaneous EMPD. A wide excision of the site was performed and there has been no recurrence or evidence of progression with 1 year follow-up to date.
Pigmented EMPD is a very rare finding, but has the potential to be a diagnostic pitfall by mimicking melanoma both clinically and histologically [7, 8]. On histology, the neoplastic cells are epithelioid with prominent nucleoli and they contain melanin pigment, closely resembling melanocytes. A helpful architectural feature is that the atypical cells are located suprabasilarly in EMPD, whereas a true melanocytic proliferation also involves the dermal-epidermal junction. If necessary, the diagnosis may then be further substantiated by immunohistochemical stains. EMPD stains positive with epithelial markers such as CK7, Cam 5.2, EMA, and CEA, and is negative for the melanocytic markers S100, MART-1, MITF and HMB-45 [9, 10, 11, 12].
In a recent review, the authors found only four well documented cases of pigmented EMPD; these cases exhibited lesions of the vulva, perineum, and axilla . To our knowledge, this is the first report of pigmented EMPD on the abdomen. Pigmented EMPD may be clinically indistinguishable from melanoma and the very unusual upper abdominal location in this case made the diagnosis even more challenging. Histologic analysis is essential in securing a definitive diagnosis. If necessary, supporting immunohistochemical studies should be performed to aid in this distinction. Immunohistochemical studies may also be of value if the patient has a visceral malignancy, to determine whether the EMPD is a primary cutaneous lesion or represents direct extension or an ectopic focus of the underlying adenocarcinoma.
References1. Y. Merot, G. Mazoujian, G. Pinkus, K. Momtaz-T, G. F. Murphy. Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation. Archives of Dermatology 1985; 121: 750-752. [PubMed]
2. J. P. Curtin, S. C. Rubin, W. B. Jones, W. J. Hoskins, J. L. Lewis. Paget's disease of the vulva. Gynecologic Oncology 1990; 39: 374-377. [PubMed]
3. W. R. Heymann. Extramammary Paget's disease. Clinics in Dermatology 1993; 11: 83-87. [PubMed]
4. J. Lloyd, A. M. Flanagan. Mammary and extramammary Paget's disease. Journal of Clinical Pathology 2000; 53: 742-749. [PubMed]
5. S. J. Allan, K. McLaren, R. D. Aldridge. Paget's disease of the scrotum: a case exhibiting positive prostate-specific antigen staining and associated prostatic adenocarcinoma. The British Journal of Dermatology 1998; 138: 689-691. [PubMed]
6. K. J. Kim, D. P. Lee, M. W. Lee, J. H. Choi, K. C. Moon, J. K. Koh. Penoscrotal extramammary Paget's disease in a patient with rectal cancer: double primary adenocarcinomas differentiated by immunoperoxidase staining. The American Journal of Dermatopathology 2005; 27: 171-172. [PubMed]
7. N. J. Hilliard, C. Huang, A. Andea. Pigmented extramammary Paget's disease of the axilla mimicking melanoma: case report and review of the literature. Journal of Cutaneous Pathology 2009; 36: 995-1000. [PubMed]
8. T. Meyer-Gonzalez, A. Alcaide-Martin, M. Contreras-Steyls, M. Mendiola, E. Herrera-Acosta, E. Herrera. Pigmented mammary Paget disease mimicking cutaneous melanoma. International Journal of Dermatology 2010; 49: 59-61. [PubMed]
9. O. E. Battles, D. L. Page, J. E. Johnson. Cytokeratins, CEA, and mucin histochemistry in the diagnosis and characterization of extramammary Paget's disease. American Journal of Clinical Pathology 1997; 108: 6-12. [PubMed]
10. E. Diaz de Leon, M. L. Carcangiu, V. G. Prieto et al. Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor. American Journal of Clinical Pathology 2000; 113: 572-575. [PubMed]
11. Y. Kondo, K. Kashima, T. Daa, S. Fujiwara, I. Nakayama, S. Yokoyama. The ectopic expression of gastric mucin in extramammary and mammary Paget's disease. The American Journal of Surgical Pathology 2002; 26: 617-623. [PubMed]
12. S. Ramachandra, C. E. Gillett, R. R. Millis. A comparative immunohistochemical study of mammary and extramammary Paget's disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. Virchows Archiv: An International Journal of Pathology 1996; 429: 371-376. [PubMed]
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