Rütten A, Burgdorf W, Hügel H, Kutzner H, Hosseiny-Malayeri H R, Friedl W, Propping P, Kruse R
Laboratory of Dermatohistopathology, University of Bonn, Germany.
Am J Dermatopathol. 1999 Oct;21(5):405-13. doi: 10.1097/00000372-199910000-00001.
Cystic sebaceous tumors (CST) are well-circumscribed, large, deeply located dermal sebaceous proliferations with a cystic growth pattern. We identified 12 CST in 8 of 19 patients with Muir-Torre syndrome (MTS). We interpret CST as a tumor spectrum with clearly benign cystic sebaceous adenomas at one end and proliferative atypical cystic sebaceous tumors at the other. When examining these proliferative atypical tumors on morphologic criteria alone, the possibility of an evolving cystic sebaceous carcinoma cannot be excluded. We have not observed recurrences or metastases, indicating that these lesions are not highly malignant carcinomas. In 10 of 12 cases of CST, we examined microsatellite instability (MSI). All 10 examined examples of CST from patients with MTS showed MSI characteristic for hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by autosomal dominant inherited DNA mismatch repair (MMR) defects. Mutational analysis of the MMR genes hMSH2 and hMLH1 had revealed different germline mutations in the hMSH2 gene in three of six examined patients with MTS with CST. We then found four more CST in patients without a history of internal malignancy. All four CST exhibited MSI. By mutational analysis in one of these patients we identified a truncating germline mutation in the MMR gene hMLH1. We conclude that CST is a marker for the mismatch repair-deficient subtype of MTS with a high risk for later internal malignancies. By recognizing CST, the histopathologist can suggest the great likelihood of MTS to the clinician.
囊性皮脂腺肿瘤（CST）是边界清晰、体积较大、位于真皮深层的皮脂腺增生，呈囊性生长模式。我们在19例穆尔-托雷综合征（MTS）患者中的8例中发现了12个CST。我们将CST解释为一种肿瘤谱系，一端是明显良性的囊性皮脂腺腺瘤，另一端是增生性非典型囊性皮脂腺肿瘤。仅根据形态学标准检查这些增生性非典型肿瘤时，不能排除其演变为囊性皮脂腺癌的可能性。我们未观察到复发或转移情况，这表明这些病变并非高度恶性的癌。在12例CST病例中的10例中，我们检测了微卫星不稳定性（MSI）。来自MTS患者的所有10个检测的CST样本均显示出遗传性非息肉病性结直肠癌（HNPCC）的MSI特征，这是由常染色体显性遗传的DNA错配修复（MMR）缺陷引起的。对MMR基因hMSH2和hMLH1的突变分析显示，在6例患有CST的MTS检测患者中，有3例在hMSH2基因中发现了不同的种系突变。然后我们在没有内脏恶性肿瘤病史的患者中又发现了4个CST。所有4个CST均表现出MSI。通过对其中1例患者的突变分析，我们在MMR基因hMLH1中鉴定出一个截短的种系突变。我们得出结论，CST是MTS错配修复缺陷亚型的标志物，后期发生内脏恶性肿瘤的风险较高。通过识别CST，病理学家可以向临床医生提示MTS的极大可能性。
