Wei Jiaying, Li Qingshu, Wu He, Yin Xuedong, Ren Guosheng
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Pathology, Chongqing Medical University, Chongqing, China.
Front Med (Lausanne). 2022 Feb 23;9:781693. doi: 10.3389/fmed.2022.781693. eCollection 2022.
Hyperkeratosis of the nipple and areola (HNA) is a rare skin disease with unknown etiology. Some patients are misdiagnosed or never diagnosed, especially during the early stage of this disease. In addition, the mechanism involved in the development of HNA is still unknown, and genomic alterations have not been reported anywhere.
A 26-year-old female suffered gradual bilateral areola thickening and enlargement, with accompanying intense itching, and was diagnosed with HNA at the First Affiliated Hospital of Chongqing Medical University. No obvious abnormalities were found in laboratory test examinations such as hormone testing for estrogen, progesterone, or prolactin. Typical papillomatous skin with orthokeratotic hyperkeratosis and numerous infiltrating lymphocytes was detected through a histopathological examination. The results from RNA-sequencing showed that the molecular expression between HNA and a normal nipple and areola (NNA) was obviously different. No significant difference was found in the bilateral lesions. In addition, immune-related cell signaling pathways were overactivated in HNA compared to the control HNA.
The typical symptoms, clinical features, and histopathological alterations presented in this case lead to a profound understanding of HNA, which can avoid the misdiagnosis and missed diagnosis of this disease at an early stage. The dysfunction of the local immune system, which was demonstrated by pathological examination and genomic analysis, suggests that anti-autoimmune therapy, such as steroid medication, may be an effective treatment for HNA at an early stage.
乳头乳晕角化过度症（HNA）是一种病因不明的罕见皮肤病。一些患者被误诊或从未被诊断出来，尤其是在该病的早期阶段。此外，HNA发生发展的机制仍不清楚，基因组改变也未见任何报道。
一名26岁女性双侧乳晕逐渐增厚、增大，并伴有剧烈瘙痒，在重庆医科大学附属第一医院被诊断为HNA。雌激素、孕激素或催乳素等激素检测等实验室检查未发现明显异常。通过组织病理学检查发现典型的乳头瘤样皮肤伴正角化过度和大量浸润淋巴细胞。RNA测序结果显示，HNA与正常乳头乳晕（NNA）之间的分子表达明显不同。双侧病变未发现显著差异。此外，与对照HNA相比，HNA中免疫相关细胞信号通路过度激活。
该病例呈现的典型症状、临床特征和组织病理学改变有助于深入了解HNA，可避免该病在早期的误诊和漏诊。病理检查和基因组分析显示的局部免疫系统功能障碍表明，抗自身免疫治疗，如类固醇药物，可能是HNA早期的有效治疗方法。
