Objective  To analyze the difficulties and coping strategies in the diagnosis of bone Langerhans cell histiocytosis (BLCH).

  Methods  The clinical, imaging, and pathological data of BLCH patients diagnosed at Shanghai General Hospital between January 2014 and December 2020 were analyzed retrospectively. The diagnosed and undiagnosed cases were analyzed and discussed individually.

  Results  1) The clinical diagnostic rate was 7% (2/30), and the difficulty laid in the lack of diagnostic awareness and specificity of clinical features. Patient age < 14 years; Occurs in bone tissues such as skull and spine; Local pain, disease progression is relatively slow; Involving other systems, such as involving pituitary, causing diabetes insipidus, and recurrent cases are suggestive of diagnosis. 2) The diagnostic rate with imaging was 27% (8/30), and the difficulty laid in the fact that the diversity of imaging manifestations makes the disease easily confused with infection, benign lesions, and malignant lesions. During diagnosis, we should carefully identify the imaging features and closely combine clinical with comprehensive analysis. Further, 3D computed tomography (CT) reconstruction, magnetic resonance imaging (MRI), and positron emission tomography-CT (Pet-CT) can improve the diagnostic rate of this disease. 3) The primary, secondary, and tertiary pathological diagnostic rates were 60%, 33%, and 7%, respectively. Diagnosis was difficult when the number of puncture specimens was small and when there was abundant inflammatory background or atypical tumor cells. Clinical and imaging suggestive diagnoses can greatly reduce the difficulty of pathological diagnosis and, therefore, the potential risk of misdiagnosis and missed diagnosis.

  Conclusions  BLCH is a rare tumor of histiocytes of the hematopoietic system in bones. Clinical, imaging, and pathological diagnoses are difficult; thus, diagnosticians need to improve their understanding and diagnostic awareness of the disease. It is especially important to adopt multidisciplinary diagnostic and treatment modalities, such as clinical imaging and pathology to improve the diagnostic accuracy.