Author of

• 11946

  +

  P2.24 - Poster Session 2 - Supportive Care (ID 157)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11955

    +

    P2.24-009 - Atypical CT findings in a patient with a BRAF V600E mutated pulmonary Langerhans cell histiocytosis (PLCH) (ID 850)

    09:30 - 09:30  |  Author(s): J. Loeffler-Ragg
    • Abstract

    Background
    PLCH is an orphan disease of unknown etiology, occurring almost exclusively in smokers, histopathologically characterized by focal Langerhans cell granulomas infiltrating and destroying distal bronchioles and lung parenchyma. Unlike other types of histiocytosis, PLCH was considered to be a polyclonal disease, but recently the monoclonal presence of the BRAF V600E mutation was demonstrated in some patients.

    Methods
    A 51-year old caucasian male smoker was referred due to lymphadenopathy and disseminated, progressive, apical accentuated pulmonary nodules (up to 12 mm) with beginning cavitation on CT-scans and elevated 18F-FDG uptake on PET/CT. The patient negated any B symptoms, while complaining of frequent coughs. Lung function tests showed a worsening restrictive pattern Hematological work up proved the diagnosis of a stage IV A SCL-NHL with marrow infiltration by a CLL-like lymphocyte population (Matutes score 4/5).No extrapulmonary involvement of PLCH was observed. Due to the CT findings suspicious of infectious disease, lymphoma infiltration or metastasis a CT-guided lung biopsy was performed. For BRAF analysis DNA was extracted from formalin-fixed paraffin-embedded lung biopsies and subsequent pyrosequencing.

    Results
    The biopsy revealed a granulomatous infiltration with CD1a positive Langerhans cells, molecular analysis confirmed a BRAF V600E mutation. Treatment with steroids and nicotine abstinence was initiated with impressive regression of pulmonary nodules after 1 month of therapy, as well as a decrease of F-18 FDG uptake on PET-CT. Lung function returned to normal.

    Conclusion
    PLCH should be considered in smokers with upper lobe predominant small nodules associated with cysts on high-resolution CT scans. These characteristic radiologic features are sufficient to establish a presumptive diagnosis. In case of doubt a lung biopsy should be performed. Our patient did not show typical PLCH HRCT aspects, presenting with large randomly distributed pulmonary nodules (up to 12 mm). The histological diagnosis of PLCH was clinically unexpected. The FDG uptake is compatible with this diagnosis, but unspecific. Predominant nodular patterns of PLCH have been described and may determine the early phase of the disease, whereas cystic patterns prevail later on. To the best of our knowledge, it has still to be determined how cystic lesions are formed, and how rapidly the dynamics of lung parenchymal abnormalities evolve. We demonstrate within a surprising short clinical course progressive nodular lesions, beginning with cavitation and partial regression after one month of therapy. Low incidence and spontaneous recovery of PLCH hamper the performance of clinical trials. Glucocorticoid therapy is successful only in a subgroup of patients and is advocated on empirical grounds in the treatment of nodular PLCH to accelerate the resolution of inflammation. Because of the predominantly macronodular pattern our patient received steroids in addition to nicotine abstinence and showed impressing regression within one month. The long-term impact of this strategy in BRAF V600E positive PLCH patients and the possible superiority of a targeted therapy with vemurafenib remain to be elucidated. But early therapeutic intervention, before conversion into cystic stages of PLCH may have the largest benefit.