Langerhans cell-rich fibroinflammatory pulmonary lesion presenting as a pulmonary mass with atypical extrapulmonary lymphadenopathy: a case report and review of the literature

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare clonal myeloid neoplasm driven by MAPK pathway mutations, occurring predominantly in young adult smokers. However, Langerhans cells (LC) may also accumulate in reactive, non-clonal settings, creating significant diagnostic uncertainty. We describe an unusual case of a reactive LC-rich fibroinflammatory pulmonary lesion that closely mimicked clonal histiocytosis, including an atypical pattern of extrapulmonary cervical nodal involvement not previously reported in this context. A 71-year-old woman with minimal remote tobacco use, discontinued 40 years earlier, presented with progressive dyspnea, weight loss, and a unilateral FDG-avid pulmonary mass with mediastinal and cervical lymphadenopathy encasing major neck vasculature. Surgical wedge resection demonstrated fibroinflammatory infiltrates with increased CD1a⁺/CD207⁺ (langerin-positive) cells, but without bronchiolocentric architecture, granuloma formation, or cystic remodeling. Next-generation sequencing of the wedge resection specimen was negative for canonical MAPK pathway alterations. Multidisciplinary consensus, supported by the adequate surgical tissue sample, absence of canonical histopathologic features of PLCH, negative MAPK-pathway sequencing, and atypical clinical-radiographic phenotype, favored a reactive LC-rich fibroinflammatory process. The patient showed rapid clinical and radiographic improvement with corticosteroid therapy, with sustained remission after taper. LC-rich pulmonary infiltrates are not synonymous with PLCH. Integration of clinical, radiographic, histopathologic, and molecular findings is essential to avoid misclassification and ensure appropriate therapy. In the current era of MAPK-targeted therapies, accurate distinction between reactive and clonal LC proliferations is increasingly consequential.