Background: Adenocarcinoma is the most common type of lung cancer
with a specific molecular landscape and EGFR mutations accounting
for 10–20% of driver mutations. Langerhans cell histiocytosis (LCH) is a
chronic interstitial lung disease usually found in young adults and strongly
associated with smoking, with a high prevalence of BRAF (35–50%)
and NRAS(10–15%) mutation. The association of these two diseases is
rare with exceptional cases reported, especially in non-smoking patients.
Methods: We report the case of a 50 years-old non-smoking woman who
presented with multiple lung lesions on CT-scan (5 cm mass in the upper
right lobe, satellite nodules in the two other ipsilateral lobes and pleural
metastasis). Biopsies of the upper lobe mass and of a pleural lesion were
performed. The following immunomarkers were tested: TTF1, Napsin,
S100, CD1a and Langerin. Furthermore, gene sequencing was performed
in order to detect EGFR and BRAF mutations.
Results: H&E slides revealed and unexpected finding: the association of
lung adenocarcinoma (TTF1+ and Napsin+) with Langerhans cell histiocytosis/hyperplasia
(S100+, CD1a+, Langerin+). Molecular study revealed
EGFR mutation (c.2573T>G (p.L858R), exon 21) in the adenocarcinoma.
No BRAF mutation was found.
Conclusions: This is the first reported case of lung adenocarcinoma admixed
with Langerhans cell histiocytosis/hyperplasia in a non-smoking patient.
As no BRAF mutation was identified and the same association of adenocarcinoma
and Langerhans cell was present in both biopsies, we hypothesize
that the Langerhans cell proliferation was “reactive” in nature, rather
than neoplastic. Furthermore, after anti-EGFR therapy, most of the nodules
present on CT-scan regressed and no typical CT-image of LCH was present.