The probable diagnosis is
Case 327
【Progress】
Biopsy specimen revealed proliferation of clear cytoplasm cells on HE stain and positive CK7, GCDFP-15, CK20 and negative p63, CDX2, leading compatible diagnosis of extramammary Paget disease.
【Discussion】
Skin is composed of epidermis, dermis and subcutaneous tissue. Epidermis has no vessels, five kinds of cells in epidermis get nutrients and oxygen through diffusion from capillaries existed in dermis. Five kinds of cells include keratinocytes (squamous cells), melanocytes, dendritic cells, nerve ending cells (Merkel cells = tactile cells), and stem cells (1). Of these, keratinocytes occupy epidermis most. Sweat gland, sweat gland duct, and hair follicle exist in dermis whose sweat and hair pass through epidermis to skin surface (1). There are sweat pores at the bottom of digital marking. In other words, digital marking is formed by sweat pore.
Paget disease is a kind of skin cancer. Paget disease arise from epidermis. The origin cells of Paget disease are thought to arise not from the above five kind cells but from unknown sweat-related-cells probably because Paget disease appears from skin sites where sweat secrete more than other: breast papilla, areola, axilla, anus, genital area (1, 2).
Hemotoxin-eosin (HE) stain slice shows large cells with clear cytoplasm on Paget disease. However, HE stain slices are not definitive for Paget disease, needed further immunohistochemical stains are required for differentiation from benign Toker cell hyperplasia, melanoma, Bowen disease. Paget disease is determined with results of various immunohistochemical stains (S-100 -ve and HMB-45 -ve (both typically +ve in melanoma), CK7 +ve, CEA +ve (-ve in Bowen's disease, -ve in Toker cells) (1, 2).
Paget disease is largely classified breast origin and extra-breast origin (3-8). In these days, breast origin Paget disease is included in breast cancer. Extra-breast Paget disease occurs in elderly persons whose ages are 60 or older.
The real clinical problems on Paget disease are that its self-aware-symptoms are subtle, its occurrent sites are hardly noticeable, and it is susceptible to mis-diagnose as eczema or mycosis. The delay for correct diagnosis induces an advanced stage of Paget disease.
Treatment for Paget disease is basically radical surgical resection. If the lesion is localized in epidermis, resection is conducted with 3 cm margin in length and with subcutaneous tissue beneath muscle layer in depth (3-7). If lymph-nodes are swollen, lymph-node dissection and electron beam irradiation are conducted (3-7). The prognosis of localized Paget disease is well but advanced Paget disease with lymph-nodes metastases and/or distant metastasis are not well even though chemotherapy were served (3-7).
In our case, Paget disease of perianal site is served with radical surgical resection. Biopsy of inguinal nodes showed negative of tumor metastasis,expecting good prognosis.
【Summary】
We presented a seventy-six-year-old female with perianal nodule whose immune-histological specimen revealed Paget disease. She received radical resection with biopsy of inguinal nodes whose slices were negative on tumor existence. It is borne in mind that Paget disease arise not from basic five kinds of epidermis cells: keratinocytes, melanocytes, dendric cells, nerve ending cells, and stem cells but from sweat related cells. Paget disease occurs at sites whose sweat secrete more than others: for example, breast areola, breast papilla, axilla, genital regions, and anus. On imaging diagnosis, tumor presence and swollen regional lymph node should be investigated on CT.
【References】
1.Graham JH, Helwig EB: Cutaneous premalignant lesions; in Advance in Biology of Skin, （Montagna W, Dobson RL ed）, pergamon press, Oxford, 1966, 277-327.
2.Lloyd J, Flanagan AM (October 2000). "Mammary and extramammary Paget's disease". Journal of Clinical Pathology. 53 (10): 742–749.
3.上田英一郎ほか：京都府立医科大学皮膚科における最近10年間のPaget病の統計的観察. 西日皮膚 58：116−120, 1996.
4.石原和之：Paget病全国アンケートの集計と説明. Skin Cancer 9：37−43, 1994.
5.浅野一弘ほか：旭川医科大学皮膚科における乳房外Paget病の統計的観察. Skin Cancer 13; 12-17, 1998.
6.鶴岡利樹、露木重明：当科における乳房外Paget病25例の検討. Skin Cancer 11：248−253, 1996.
7.稲葉義方、石川剛、上出良一：乳房外Paget病48例の予後について. 臨皮 44：1143−1147, 1990.
8.Fukuda K, Funakoshi T (2018-02-16). "Metastatic Extramammary Paget's Disease: Pathogenesis and Novel Therapeutic Approach". Frontiers in Oncology. 8:
2024.3.15