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<p>Labial mucosal macules (LMMs) are well-demarcated, hyperpigmented, and flat lesions. Although generally benign, accurate diagnosis of LMMs is essential because they have a broad differential diagnosis, may mimic malignant lesions such as mucosal melanoma, and can be associated with systemic syndromes. This systematic review aimed to investigate the clinical characteristics, etiology, and histopathology of LMM and its association with systemic diseases. A systematic literature search was conducted across PubMed, Google Scholar, and Web of Science databases to identify all reported cases of LMMs and their associated syndromic conditions, including Laugier–Hunziker syndrome (LHS), Peutz–Jeghers syndrome (PJS), and Addison’s disease (AD). The search covered publications from June 1, 1981, to May 7, 2025. A total of 90 studies encompassing 130 patients with labial melanotic macules were included in this review. Among these, 70 patients were diagnosed with LHS, 49 with PJS, and 2 with AD, while 9 patients had isolated LMMs without any associated systemic conditions. LHS presented with melanonychia and hand pigmentation without malignancy, PJS with gastrointestinal tumors, and AD with systemic features. Histopathology (31 studies) revealed basal layer hyperpigmentation, epidermal hyperplasia, pigment incontinence with melanophages, and normal to slightly increased melanocytes without atypia. Our findings suggest that labial melanotic macules may serve as important clinical indicators of underlying systemic diseases and syndromic conditions. Therefore, a comprehensive evaluation to assess potential systemic involvement is essential to exclude clinically significant disorders, including genetic, endocrine, and gastrointestinal syndromes.</p>

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Labial melanotic macules: clinical features, etiology, histopathology, and association with syndromes—a systematic review

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Sümeyye Aktaş,
  • Amor Khachemoune

摘要

Labial mucosal macules (LMMs) are well-demarcated, hyperpigmented, and flat lesions. Although generally benign, accurate diagnosis of LMMs is essential because they have a broad differential diagnosis, may mimic malignant lesions such as mucosal melanoma, and can be associated with systemic syndromes. This systematic review aimed to investigate the clinical characteristics, etiology, and histopathology of LMM and its association with systemic diseases. A systematic literature search was conducted across PubMed, Google Scholar, and Web of Science databases to identify all reported cases of LMMs and their associated syndromic conditions, including Laugier–Hunziker syndrome (LHS), Peutz–Jeghers syndrome (PJS), and Addison’s disease (AD). The search covered publications from June 1, 1981, to May 7, 2025. A total of 90 studies encompassing 130 patients with labial melanotic macules were included in this review. Among these, 70 patients were diagnosed with LHS, 49 with PJS, and 2 with AD, while 9 patients had isolated LMMs without any associated systemic conditions. LHS presented with melanonychia and hand pigmentation without malignancy, PJS with gastrointestinal tumors, and AD with systemic features. Histopathology (31 studies) revealed basal layer hyperpigmentation, epidermal hyperplasia, pigment incontinence with melanophages, and normal to slightly increased melanocytes without atypia. Our findings suggest that labial melanotic macules may serve as important clinical indicators of underlying systemic diseases and syndromic conditions. Therefore, a comprehensive evaluation to assess potential systemic involvement is essential to exclude clinically significant disorders, including genetic, endocrine, and gastrointestinal syndromes.