Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Mod Pathol. 2011 Apr;24(4):596-605. doi: 10.1038/modpathol.2010.225. Epub 2010 Dec 17.
Current pathologic criteria cannot reliably distinguish cutaneous anaplastic large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin involvement, and transformed mycosis fungoides). We previously reported IRF4 (interferon regulatory factor-4) translocations in cutaneous anaplastic large cell lymphomas. Here, we investigated the clinical utility of detecting IRF4 translocations in skin biopsies. We performed fluorescence in situ hybridization (FISH) for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders from 182 patients at three institutions. In all, 9 of 45 (20%) cutaneous anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis with informative results demonstrated an IRF4 translocation. Remaining informative cases were negative for a translocation (7 systemic anaplastic large cell lymphomas; 44 cases of mycosis fungoides/Sézary syndrome (13 transformed); 24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T-cell lymphoproliferative disorders). Among all cutaneous T-cell lymphoproliferative disorders, FISH for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%, respectively (P=0.00002, Fisher's exact test). Among anaplastic large cell lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity and positive predictive value were 98 and 90%, respectively (P=0.005). FISH abnormalities other than translocations and IRF4 protein expression were seen in 13 and 65% of cases, respectively, but were nonspecific with regard to T-cell lymphoproliferative disorder subtype. Our findings support the clinical utility of FISH for IRF4 in the differential diagnosis of T-cell lymphoproliferative disorders in skin biopsies, with detection of a translocation favoring cutaneous anaplastic large cell lymphoma. Like all FISH studies, IRF4 testing must be interpreted in the context of morphology, phenotype, and clinical features.
目前的病理标准无法可靠地区分皮肤间变性大细胞淋巴瘤与其他 CD30 阳性 T 细胞淋巴增生性疾病（蕈样肉芽肿病、伴皮肤累及的系统性间变性大细胞淋巴瘤和转化性蕈样真菌病）。我们之前报道过皮肤间变性大细胞淋巴瘤中存在 IRF4（干扰素调节因子 4）易位。在此，我们研究了在皮肤活检中检测 IRF4 易位的临床应用。我们在三个机构的 182 名患者的 204 个 T 细胞淋巴增生性疾病受累的活检标本中进行了荧光原位杂交（FISH）检测 IRF4。共有 9 例（20%）皮肤间变性大细胞淋巴瘤和 1 例（3%）蕈样肉芽肿病，有意义的结果显示存在 IRF4 易位。其余有意义的病例为易位阴性（7 例系统性间变性大细胞淋巴瘤；13 例转化性蕈样肉芽肿病/Sezary 综合征 44 例；24 例外周 T 细胞淋巴瘤，其他类型未特指；12 例 CD4 阳性小/中等大小多形性 T 细胞淋巴瘤；5 例结外 NK/T 细胞淋巴瘤，鼻型；4 例γ-δ T 细胞淋巴瘤；5 例其他罕见 T 细胞淋巴增生性疾病）。在所有皮肤 T 细胞淋巴增生性疾病中，FISH 检测 IRF4 对皮肤间变性大细胞淋巴瘤的特异性和阳性预测值分别为 99%和 90%（P=0.00002，Fisher 确切检验）。在间变性大细胞淋巴瘤、蕈样肉芽肿病和转化性蕈样肉芽肿病中，特异性和阳性预测值分别为 98%和 90%（P=0.005）。除易位和 IRF4 蛋白表达外，还观察到 13%和 65%的病例存在 FISH 异常，但对于 T 细胞淋巴增生性疾病亚型无特异性。我们的研究结果支持在皮肤活检中，FISH 检测 IRF4 对 T 细胞淋巴增生性疾病的鉴别诊断具有临床应用价值，检测到易位有利于诊断皮肤间变性大细胞淋巴瘤。与所有 FISH 研究一样，IRF4 检测必须结合形态学、表型和临床特征进行解释。
