在台灣原發性皮膚型淋巴瘤從未根據有共識的WHO/EORTC分類法分類，因此其臨床病理特徵及其與Epstein-Barr病毒感染的相關性並不清楚。這個回溯性的研究收集了從1990到2006年皮膚型淋巴瘤的病人檢體，本研究利用形態學，Epstein-Barr病毒原位雜交染色法及免疫組織化學染色法將這些病例重新依照最新的WHO/EORTC分類法分類進行分析。本研究共收集了54病例，包括29例原發性皮膚型淋巴瘤和25例次發性皮膚淋巴瘤病例，年齡分布於在21-86歲之間（平均62歲）。29例原發性皮膚型淋巴瘤中，有21例（72.4%）是原發性皮膚型T細胞和NK細胞淋巴瘤，包括5例淋巴結外鼻腔型NK/T細胞淋巴瘤（17.2%），5例原發性皮膚型非特異性週邊T細胞淋巴瘤（17.2%），4例蕈型黴菌病（13.8%），1例Sezary症候群（3.4%），3例原發性皮膚型退化性大細胞淋巴瘤（10.3%），2例原發性皮膚型小至中CD4+ T細胞淋巴瘤（6.9%），1例皮下脂肪炎性淋巴瘤（3.4%）；其它8例是原發性皮膚型B細胞淋巴瘤（27.6%），包括3例皮膚型邊緣區B細胞淋巴瘤（10.3%），3例皮膚型濾泡性淋巴瘤（10.3%）和2例皮膚型瀰慢性大B細胞淋巴瘤，腿型（6.9%）。25例次發性皮膚淋巴瘤病例，17例是次發性皮膚T細胞和NK細胞淋巴瘤，其中有5例是淋巴結外鼻腔型NK/T細胞淋巴瘤，其它8例是次發性皮膚B細胞淋巴瘤。Epstein-Barr病毒原位雜交染色法染色實驗結果顯示所有原發性及次發性淋巴結外鼻腔型NK/T細胞淋巴瘤，皆為陽性反應。本研究為台灣第一個依據WHO/EORTC分類法針對皮膚型淋巴瘤的臨床病理研究結果，相較於西方國家，原發性皮膚型淋巴瘤在台灣蕈型黴菌病是較少見，然而原發性淋巴結外鼻腔型NK/T細胞淋巴瘤和原發性皮膚型非特異性週邊T細胞淋巴瘤的發生率是比較高的（各為17.2%），在次發性皮膚淋巴瘤方面，相較於日本，在台灣成人T細胞淋巴瘤是較少見，而血管性免疫母細胞型T細胞淋巴瘤的發生率是比較高的（20%）。Epstein-Barr病毒原位雜交染色法在診斷淋巴結外鼻腔型NK/T細胞淋巴瘤是有明顯幫助的，特別是在癌細胞沒有破壞血管和圍繞血管生長以及組織壞死的現象時。在台灣原發性淋巴結外鼻腔型NK/T細胞淋巴瘤的高發生率及好發年輕人的情況下,提供準確的診斷及尋求新的有效治療方式是應努力的目標。

The clinicopathological feature of primary cutaneous lymphomas according to WHO/EORTC classification and their relationship to EBV in Taiwan has never been reported. This retrospective study collected the patients with cutaneous lymphomas from 1990 and 2006. The morphology, EBER in situ hybridization and immunohistochemistry of primary cutaneous lymphomas were studied to reclassify based on the WHO/EORTC classification. A total of 54 patients were included. Twenty-nine were primary cutaneous lymphomas and 25 were secondary cutaneous lymphomas. The age ranged from 21 to 86 years old (mean 62 years old). Twenty-one (72.4%) were primary cutaneous T-cell and NK-cell lymphoma, including 5 extranodal NK/T-cell lymphoma, nasal type (17.2%), 5 primary cutaneous peripheral T-cell lymphoma, unspecified (17.2%), 4 mycosis fungoides (13.8%), 1 Sezary syndrome, 3 primary cutaneous anaplastic large cell lymphoma, 2 primary cutaneous small-medium CD4+ T-cell lymphoma and 1 subcutaneous panniculitis-like T-cell lymphoma. Eight cases were primary cutaneous B-cell lymphoma (27.6%) including 3 cutaneous marginal zone B-cell lymphoma (10.3%), 3 cutaneous follicle center B-cell lymphoma (10.3%), and 2 diffuse large B-cell lymphoma, leg type (6.9%). Seventeen cases were secondary cutaneous T-cell and NK -cell lymphoma. Eight cases were secondary cutaneous B-cell lymphoma. All primary and secondary extranodal NK/T-cell lymphoma, nasal type, were positive for EBER, however, one of them (10%) without both angiocentric growth pattern and necrosis in histomorphological examination. This is the first clinicopathological study of cutaneous lymphoma according to recent WHO/EORTC classification in Taiwan. In comparison with the Western countries, mycosis fungoides is less common whereas primary extranodal NK/T-cell lymphoma, nasal type, and peripheral T-cell lymphoma, unspecified, is more common in Taiwan. EBER in situ hybridization study is helpful in the diagnosis of extranodal NK/T-cell lymphoma, nasal type, especially in tumor without both angiocentric growth pattern and necrosis.

中文摘要...........................................................................................................4
英文摘要...........................................................................................................6
縮寫.................................................................................................................8
導論.................................................................................................................9
淋巴系統..............................................................................................................9
淋巴瘤....................................................................................................................10
皮膚型淋巴瘤........................................................................................................11
皮膚型淋巴瘤分類................................................................................................12
Epstein-Barr病毒與疾病.......................................................................................13
材料和方法.........................................................................................................16
臨床資料...........................................................................................................16
常規組織病理切片染色........................................................................................16
免疫組織化學染色法............................................................................................18
Epstein-Barr病毒原位雜交染色法.......................................................................20
WHO/EORTC分類法...........................................................................................22
Ann Arbor分期系統...........................................................................................22
統計分析...........................................................................................................23
結果..............................................................................................................24
討論...........................................................................................................29
結論.............................................................................................................33
表和圖.. ..........................................................................................................34
Table 1. Monoclonal antibody panel................................................................35
Table 2. Primary cutaneous lymphoma............................................................36
Table 3. Secondary cutaneous lymphoma........................................................37
Table 4. 29 patients with primary cutaneous lymphomas and compared with other countries................................................... .........................................................38
Table 5. The relative frequency of secondary cutaneous lymphomas and compared with Japan.......................................................................................................39
Table 6. Clinical data, histlolgical, and immunophenotypical features of cutaneous NK/T-cell lymphoma......................................................................................40
Table 7. Disease survival of 29 primary cutaneous lymphomas....................41
Fig. 1. H-E stain for skin tissue.......................................................................42
Fig. 2. Immunohistochemistry on the paraffin section..........................................43
Fig. 3. In situ hybridization for Epstein-Barr virus-encoded small RNA(EBER).44
Fig. 4. Extranodal NK/T-cell lymphoma, nasal type..................................................45
參考文獻.............................................................................................................46
附錄.......................................................................................................................53
附錄一、WHO/EORTC classification of cutaneous lymphomas.............................54
附錄二、Disease associated with EBV infection.................................................55
附錄三、Patterns of EBV latent infection and diseases.......................................56

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