Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection.

Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations / L. Melocchi, M. Mondoni, U. Malapelle, G. Rossi. - In: JOURNAL OF MOLECULAR PATHOLOGY. - ISSN 2673-5261. - 3:4(2022 Nov 03), pp. 286-292. [10.3390/jmp3040024]

Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations

L. Melocchi
Primo
;
M. Mondoni
Secondo
;
2022

Abstract

Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection.
Langerhans cell histiocytosis; adenocarcinoma; BRAF; mutations; lung;
Settore MED/10 - Malattie dell'Apparato Respiratorio
3-nov-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/949533
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