Development of pulmonary Langerhans cell histiocytosis in a patient with established adenocarcinoma of the lung

Abstract

Newly-appearing lung nodules on surveillance imaging in patients with pre-existing lung cancer can present a diagnostic dilemma when attempting to differentiate between metastatic disease, infection, and other inflammatory conditions. Here we report a case of an // metastatic adenocarcinoma patient who underwent lung biopsy for evaluation of upper-lobe predominant lung nodules revealed to represent pulmonary Langerhans cell histiocytosis (PLCH). The patient was a heavy smoker and admitted to increase her smoking habit after initially learning about her diagnosis with lung cancer. Interestingly, despite the association of both lung adenocarcinoma and PLCH with the mutation in smokers, pyrosequencing of the patient's PLCH lesions was negative for this mutation. Co-occurrence of PLCH with lung cancer is extremely rare. While most reported cases of PLCH tend to precede the occurrence of lung cancer, a minority of cases appear after a diagnosis of lung cancer has already been established and are thought to represent a local immunologic reaction to the tumor. It is therefore postulated that the appearance of PLCH lesions in this patient's lungs is a result of her increase in cigarette smoking, possibly augmented by co-existence of adenocarcinoma.

General features of patients with Pulmonary Langerhans Cell Histiocytosis followed in our instution

“…vemurafenib, BRAF inhbitor, has been reported to be beneficial in the treatment of advanced PLCH. A similar benefit has been observed in 1-3% of patients with non small cell lung cancer, mostly adenocarcinomas (3)(4)(5). Definitive diagnosis of the disease is possible by bronchoscopic or surgical lung biopsy.…”

Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients

“…A possible clonal relationship for thyroid carcinoma and both LCH and Erdheim-Chester disease has been reported [35,36], which is remarkable due to the putatively different tissues of tumor origin. In addition, for lung carcinoma that mostly occurred concurrent to LCH, a clonal association was reported in one patient [37]. However, as LCH is known to develop independently of lung carcinoma in smokers, this may not be a universal relationship.…”

BRAF-Mutant Pulmonary Langerhans Cell Histiocytosis Mimicking Recurrence of Early-Stage KRAS-Mutant Lung Adenocarcinoma

“… 4 Although pulmonary Langerhans cell histiocytosis is rarely diagnosed in the setting of lung cancer, reports in association with primary lung cancers exist. 5 It is challenging to exclude lung cancer recurrence on the basis of imaging and clinical findings alone, and, in our patient, coexisting lymphadenopathy increased the concern for malignant progression. 3 Although recurrent malignancy must be considered with new or progressing imaging findings, histopathologic analysis is critical in distinguishing cancer recurrence from alternative diagnoses.…”