Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Department of Oral and Maxillofacial Surgery/Oral Pathology, Cancer Center Amsterdam, de Boelelaan, 1117, Amsterdam, The Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Otolaryngology, Cancer Center Amsterdam, de Boelelaan, 1117, Amsterdam, The Netherlands.
Mod Pathol. 2020 Jun;33(6):1033-1040. doi: 10.1038/s41379-019-0444-0. Epub 2020 Jan 2.
Oral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1-3% annually. The presence and grade of World Health Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.
口腔白斑病是最常见的口腔潜在恶性疾病，每年恶性转化为口腔鳞状细胞癌的转化率为 1-3%。世界卫生组织定义的异型增生的存在和分级是评估恶性转化风险的重要组织学标志物，但不够准确，无法实现个性化治疗和监测。分化型异型增生，来源于分化型外阴上皮内瘤变，迄今尚未用于口腔异型增生分级。我们假设评估分化型异型增生除了世界卫生组织定义的（经典）异型增生外，将改善口腔白斑病恶性转化的风险评估。我们调查了一个由 84 例口腔白斑病患者组成的回顾性队列。对活检进行异型增生的存在和分级评估，并检测角蛋白 13（CK13）和 17 的表达，这些蛋白在异型增生的外阴黏膜中被认为失调。在异型增生的口腔病变中，分化型异型增生与经典异型增生一样常见。在 84 例患者中，有 25 例（30%）在随访期间发展为上呼吸道和消化道的鳞状细胞癌。仅考虑经典异型增生，56 例非异型增生病变患者中有 11 例进展。纳入分化型异型增生后，30 例非异型增生病变患者中仅 2 例进展。当仅考虑经典异型增生时，进展的风险从 3.26（风险比，p=0.002）增加到同时考虑经典和分化异型增生时的 7.43（风险比，p=0.001）。CK13 缺失，同时存在异型增生，与恶性进展的风险增加相关（p=0.006）。这项研究表明，分化型异型增生应被视为口腔黏膜中一种单独的异型增生类型，其与经典异型增生的区别具有病理和临床意义，因为它是口腔恶性转化的一个强有力的（共同）预后组织病理学标志物。在无异型增生且 CK13 染色保留的口腔病变中，进展的风险非常低。
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