BRAF V600E expression in langerhans cell histiocytosis: Clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases

Anja Roden, Xiaowen Hu, Sertac Kip, Edgardo R. Parrilla Castellar, Kandelaria M. Rumilla, Julie A. Vrana, Robert Vassallo, Jay H Ryu, Eunhee S. Yi

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Abstract

Pulmonary Langerhans cell histiocytosis (PLCH) has been postulated to be a smoking-related non-neoplastic condition, distinct from extrapulmonary LCH, which is generally regarded as a clonal, neoplastic process. Recent genomic studies demonstrated BRAF V600E mutation in 38% to 57% of extrapulmonary LCH cases by polymerase chain reaction. We evaluated the BRAF V600E expression by immunohistochemistry (IHC) in PLCH and extrapulmonary LCH cases. We compared BRAF V600E expression in PLCH and extrapulmonary LCH with BRAF V600E mutation status. Our study included 25 PLCH (age 42.0±11.4, 10 men) and 54 extrapulmonary LCH (age 27.6±21.8, 37 men) cases. Seven of 25 (28%) PLCH cases were positive for BRAF V600E expression (age 45.3±8.1, 2 men); 6 of 7 cases with BRAF V600E expression were also positive by mutation analysis. Nineteen of 54 (35%) extrapulmonary LCH cases were positive for BRAF V600E expression (age 27.6±22.1, 13 men) as well as mutation. Two IHC-negative cases, however, were positive by mutation analysis. All PLCH cases were current or former smokers, whereas 28 of 54 extrapulmonary LCH patients were never-smokers. The cumulative tobacco exposure at the time of diagnosis was significantly higher in BRAF V600E-positive than in BRAF V600E-negative PLCH patients (mean pack-years 48.3 vs. 23.7, 2-tailed t test P=0.01). BRAF V600E expression by IHC correlated with BRAF V600E mutational status in most of the cases in our study except in 3 patients (4.4%). In conclusion, a subset of PLCH with BRAF V600E expression may be a clonal proliferative process, in which cigarette smoking might play a role.

Original languageEnglish (US)
Pages (from-to)548-551
Number of pages4
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Langerhans Cell Histiocytosis
Lung
Mutation
Immunohistochemistry
Smoking
Neoplastic Processes
Clinical Studies
Tobacco
Polymerase Chain Reaction

Keywords

  • BRAF V600E
  • Clonal
  • Langerhans cell histiocytosis
  • Pulmonary
  • Smoking

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

BRAF V600E expression in langerhans cell histiocytosis : Clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases. / Roden, Anja; Hu, Xiaowen; Kip, Sertac; Parrilla Castellar, Edgardo R.; Rumilla, Kandelaria M.; Vrana, Julie A.; Vassallo, Robert; Ryu, Jay H; Yi, Eunhee S.

In: American Journal of Surgical Pathology, Vol. 38, No. 4, 2014, p. 548-551.

Research output: Contribution to journalArticle

Roden, Anja ; Hu, Xiaowen ; Kip, Sertac ; Parrilla Castellar, Edgardo R. ; Rumilla, Kandelaria M. ; Vrana, Julie A. ; Vassallo, Robert ; Ryu, Jay H ; Yi, Eunhee S. / BRAF V600E expression in langerhans cell histiocytosis : Clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases. In: American Journal of Surgical Pathology. 2014 ; Vol. 38, No. 4. pp. 548-551.
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abstract = "Pulmonary Langerhans cell histiocytosis (PLCH) has been postulated to be a smoking-related non-neoplastic condition, distinct from extrapulmonary LCH, which is generally regarded as a clonal, neoplastic process. Recent genomic studies demonstrated BRAF V600E mutation in 38{\%} to 57{\%} of extrapulmonary LCH cases by polymerase chain reaction. We evaluated the BRAF V600E expression by immunohistochemistry (IHC) in PLCH and extrapulmonary LCH cases. We compared BRAF V600E expression in PLCH and extrapulmonary LCH with BRAF V600E mutation status. Our study included 25 PLCH (age 42.0±11.4, 10 men) and 54 extrapulmonary LCH (age 27.6±21.8, 37 men) cases. Seven of 25 (28{\%}) PLCH cases were positive for BRAF V600E expression (age 45.3±8.1, 2 men); 6 of 7 cases with BRAF V600E expression were also positive by mutation analysis. Nineteen of 54 (35{\%}) extrapulmonary LCH cases were positive for BRAF V600E expression (age 27.6±22.1, 13 men) as well as mutation. Two IHC-negative cases, however, were positive by mutation analysis. All PLCH cases were current or former smokers, whereas 28 of 54 extrapulmonary LCH patients were never-smokers. The cumulative tobacco exposure at the time of diagnosis was significantly higher in BRAF V600E-positive than in BRAF V600E-negative PLCH patients (mean pack-years 48.3 vs. 23.7, 2-tailed t test P=0.01). BRAF V600E expression by IHC correlated with BRAF V600E mutational status in most of the cases in our study except in 3 patients (4.4{\%}). In conclusion, a subset of PLCH with BRAF V600E expression may be a clonal proliferative process, in which cigarette smoking might play a role.",
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AU - Parrilla Castellar, Edgardo R.

AU - Rumilla, Kandelaria M.

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