Cerroni L, Zenahlik P, Höfler G, Kaddu S, Smolle J, Kerl H
Department of Dermatology, University of Graz, Austria.
Am J Surg Pathol. 1996 Aug;20(8):1000-10. doi: 10.1097/00000478-199608000-00009.
The clinical and histopathologic features of specific skin infiltrates in patients with B-cell chronic lymphocytic leukemia (B-CLL) have rarely been reported in detail. In this study we analyzed the clinical, histopathologic, immunophenotypic, and molecular features of 84 skin lesions from 42 patients (M:F = 1.3:1; mean age, 66.0 years; range, 42-83 years) with specific cutaneous manifestations of B-CLL. The duration of B-CLL before skin manifestations varied from 0 to 142 months (mean, 39 months). In seven patients (16.7%), skin lesions represented the first sign of disease. Clinical presentations included localized or generalized erythematous papules, plaques, nodules, and large tumors. Ulceration was uncommon. In six patients lesions were confined at the sites of scars from previous herpes zoster (four patients) or herpes simplex (two patients) eruptions. Histologically, three main patterns were recognized: (a) patchy perivascular and periadnexal, (b) nodular-diffuse, and (c) band-like. Cytomorphologically, small monomorphous lymphocytes predominated. Proliferation centers were observed in only four specimens. In two patients presenting with tumors, a high content of large cells with feature of centroblasts and immunoblasts was found (Richter's syndrome). Immunohistologic analyses were performed on paraffin-embedded specimens in 40 biopsies from 20 patients and on cryostat sections in 17 biopsies from 11 patients. Neoplastic B lymphocytes in all cases showed an aberrant phenotype (paraffin sections: CD20+/CD5+/CD43+; cryostat sections: CD19+/CD5+; immunoglobulin light-chain restriction). Proliferation markers (Ki67, PCNA, MIB1) stained 5 to 80% of cells (mean, 25%; median, 20%). Polymerase chain reaction performed in nine cases on paraffin-embedded tissues using consensus primers for immunoglobulin heavy-chain genes showed a monoclonal population of B lymphocytes in all cases. Several discrete bands in addition to the prominent ones were noted in five cases, indicating the additional presence of B lymphocytes whose immunoglobulin genes were not monoclonally but oligoclonally rearranged. Follow-up data could be obtained from 31 patients. The two patients with Richter's syndrome died after 5 and 8 months, respectively. The 5-year survival of patients with small-cell cutaneous B-CLL was 66.6%. Our study indicates that cutaneous specific manifestations of B-CLL present with characteristic histologic, immunophenotypic, and molecular patterns. Prognosis in these patients is probably not affected by skin involvement.
B 细胞慢性淋巴细胞白血病（B-CLL）患者特定皮肤浸润的临床和组织病理学特征鲜有详细报道。在本研究中，我们分析了 42 例（男∶女 = 1.3∶1；平均年龄 66.0 岁；范围 42 - 83 岁）有 B-CLL 特异性皮肤表现患者的 84 处皮肤损害的临床、组织病理学、免疫表型和分子特征。皮肤表现出现前 B-CLL 的病程为 0 至 142 个月（平均 39 个月）。7 例患者（16.7%）中，皮肤损害是疾病的首发症状。临床表现包括局限性或全身性红斑丘疹、斑块、结节及大肿瘤。溃疡少见。6 例患者的损害局限于既往带状疱疹（4 例）或单纯疱疹（2 例）发作瘢痕部位。组织学上，可识别出三种主要模式：（a）斑片状血管周围及腺管周围型，（b）结节 - 弥漫型，（c）带状型。细胞形态学上，以小的单形性淋巴细胞为主。仅在 4 个标本中观察到增殖中心。2 例有肿瘤表现的患者中，发现大量具有中心母细胞和免疫母细胞特征的大细胞（里氏综合征）。对 20 例患者的 40 份活检石蜡包埋标本及 11 例患者的 17 份活检冰冻切片进行了免疫组织学分析。所有病例中的肿瘤性 B 淋巴细胞均表现为异常表型（石蜡切片：CD20+/CD5+/CD43+；冰冻切片：CD19+/CD5+；免疫球蛋白轻链限制）。增殖标志物（Ki67、PCNA、MIB1）染色 5%至 80%的细胞（平均 25%；中位数 20%）。对 9 例石蜡包埋组织使用免疫球蛋白重链基因通用引物进行聚合酶链反应，结果显示所有病例中均存在 B 淋巴细胞单克隆群体。5 例病例中除主要条带外还注意到几条离散条带，表明还存在免疫球蛋白基因非单克隆而是寡克隆重排的 B 淋巴细胞。可获得 31 例患者的随访数据。2 例里氏综合征患者分别于 5 个月和 8 个月后死亡。小细胞皮肤型 B-CLL 患者的 5 年生存率为 66.6%。我们的研究表明，B-CLL 的皮肤特异性表现具有特征性的组织学、免疫表型和分子模式。这些患者的预后可能不受皮肤受累影响。
