Clinical analysis for 15 patients with pulmonary Langerhans cell histiocytosis and literature review

Abstract

Objectives: Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal disease, characterized by proliferation of Langerhans cells that derived from bone marrow infiltrating the lungs and other organs. Due to the rarity of the disease, the current understanding of the disease is insufficient, often misdiagnosed or missed diagnosis. This study aims to raise clinicians' awareness for this disease via summarizing the clinical characteristics, imaging features, and treatment of PLCH.

Methods: We retrospectively analyzed clinical and follow-up data of 15 hospitalized cases of PLCH from September 2012 to June 2021 in the Second Xiangya Hospital of Central South University.

Results: The age of 15 patients (9 men and 6 women, with a sex ratio of 3 to 2) was 21-52 (median 33) years. Among them, 8 had a history of smoking and 5 suffered spontaneous pneumothorax during disease course. There were 3 patients with single system PLCH and 12 patients with multi-system PLCH, including 7 patients with pituitary involvement, 7 patients with lymph node involvement, 6 patients with bone involvement, 5 patients with liver involvement, 2 patients with skin involvement, 2 patients with thyroid involvement, and 1 patients with thymus involvement. The clinical manifestations were varied but non-specific. Respiratory symptoms mainly included dry cough, sputum expectoration, chest pain, etc. Constitutional symptoms included fever and weight loss. Patients with multi-system involvement experienced symptoms such as polyuria-polydipsia, bone pain, and skin rash. All patients were confirmed by pathology, including 6 by lung biopsy, 3 by bone biopsy, 2 by lymph node biopsy, and 4 by liver, skin, suprasternal fossa tumor, or pituitary stalk biopsy. The most common CT findings from this cohort of patients were nodules and/or cysts and nodular and cystic shadows were found in 7 patients. Three patients presented simple multiple cystic shadows, 3 patients presented multiple nodules, and 2 patients presented with single nodules and mass shadows. Pulmonary function tests were performed in 4 patients, ventilation dysfunction was showed in 2 patients at the first visit. Pulmonary diffusion function tests were performed in 4 patients and showed a decrease in 3 patients. Smoking cessation was recommended to PLCH patients with smoking history. Ten patients received chemotherapy while 2 patients received oral glucocorticoid therapy. Among the 11 patients with the long-term follow-up, 9 were in stable condition.

Conclusions: PLCH is a neoplastic disease closely related to smoking. The clinical manifestations and laboratory examination are not specific. Pneumothorax could be the first symptom which is very suggestive of the disease. Definitive diagnosis relies on histology. There is no unified treatment plan for PLCH, and individualized treatment should be carried out according to organ involvement. Early smoking cessation is essential. Chemotherapy is the main treatment for rapidly progressing PLCH involved multiple organs. All diagnosed patients can be considered for the detection of BRAF^V600E gene and relevant targeted therapies have been implemented recently.

Keywords: clinical manifestation; imaging features; prognosis; pulmonary Langerhans cell histiocytosis; treatment.

图1

PLCH患者(病例8)肺部影像学表现 Figure 1 Pulmonary imaging manifestations of a PLCH patient (Case 8) In the left upper lung field, a small, slightly dense nodule with a size of about 6 mm×8 mm can be seen. The arrow points to nodular shadow.

图2

PLCH患者(病例5)肺部影像学表现 Figure 2 Pulmonary imaging manifestations of a PLCH patient (Case 5) Multiple cystic low-density shadows in both lungs, mainly distributed in both upper lungs. Pneumothorax in the right lung. The arrow points to cystic lesion.

图3

PLCH的病理特点 Figure 3 Pathological features of PLCH A: Microscopically, fibrous hyperplasia and glassy changes are observed in lung interstitial tissue (HE, ×100). B: A small amount of monocyte cells have infiltrated into the focal alveolar stroma (HE, ×100). C: CD1a is positively expressed on the lung tissues (HE, ×400). D: CD207 is positively expressed on the lung tissues (HE, ×400).

图4

PLCH患者(病例7)化学药物治疗前后肺部CT表现 Figure 4 CT images of PLCH patient (Case 7) before and after chemotherapy A: Before chemotherapy, multiple cystic cavities and small nodules in both upper lungs, with varying sizes and irregular shapes; B: After chemotherapy, cystic shadows and small nodules in both lungs smaller than before.