Clinical Analysis Of 12 Cases Of Adult Langerhans Cell Histiocytosis

Background:Langerhans cell histiocytosis（LCH）is a rare histiocytic disease characterized by CD1a⁺/CD207⁺dendritic cell aggregates and extensive organ involvement.Pulmonary Langerhans cell histiocytosis（PLCH）is a specific type of LCH that may involve only the lung or may include extra-pulmonary involvement of other systems.The low prevalence of LCH and PLCH and the diversity of clinical presentations have led to a general lack of clinical recognition.This article summarizes information on the clinical features,systems involved,diagnostic modalities,and treatment of PLCH and extrapulmonary LCH in adults,with the aim of improving the understanding of the disease,providing assistance in diagnosis and treatment,and avoiding underdiagnosis and misdiagnosis.Methods:Clinical data of 12 patients diagnosed with LCH（≥18years old）in the Second Affiliated Hospital of Chongqing Medical University from 2015 to 2021 were collected,while 90 adult LCH cases in the same period were collected by searching.They were divided into two groups,27 cases in the PLCH group and 75 cases in the extrapulmonary LCH group.The clinical data of the 12 patients in our hospital were recorded in detail,the reasons for the missed and misdiagnosis were analyzed,and the clinical features,imaging characteristics,organ involvement,the pathway of confirmation and treatment were summarized and summarized in the literature,and the similarities and differences between the two groups were analyzed.Results:Of the 12 patients with LCH in our hospital,1 case of PLCH was a 19-year-old male with no history of smoking.There were 11 cases of extrapulmonary LCH,6 males and 5 females,and 5 smokers.Of the 12patients,10 had varying degrees of serologic abnormalities.There were 9cases of abnormal blood count,including 3 cases with increased eosinophils;3 cases with decreased trilineage;2 cases with decreased red and giant lineage;2 cases with decreased red lineage and increased white lineage;and 1 case with increased neutrophils.Autoimmune related indexes were abnormal in 8 cases and not examined in 4 cases,including 4cases of elevated immunoglobulin Ig G;3 cases of decreased immunoglobulin complement;3 cases of positive antinuclear antibody;1case of elevated immunoglobulin Ig M;1 case of positive Ro-52;and 1 case of positive anti-endothelial cell antibody.Among the inflammatory indexes,Procalcitonin（PCT）was elevated in 4 cases;C-reaction protein（CRP）was elevated in 3 cases;ultrasensitive CRP was elevated in 2 cases;no abnormality in 2 cases;and no examination was performed in 5 cases.Bone marrow examination was performed in 7 cases;4 cases had eosinophilia;1case had delayed granulocyte maturation and slightly active plasma reticulum cells;1 case’s bone marrow hyperplasia is active;1 case had increased primitive granulocytes and primitive monocytes,and the patient was diagnosed with chronic myelomonocytic leukemia.12 patients,most of whom did not undergo a comprehensive imaging evaluation;most of the imaging findings had varying degrees of abnormalities,and only the chest CT of PLCH patients had the majority of the imaging findings had varying degrees of abnormality,with only the chest computed tomography（CT）of PLCH patients having a typical presentation.Abnormal imaging findings included:pulmonary nodular shadow（5/9）,pleural thickening（1/9）,mediastinal lymph node enlargement（1/9）,and interstitial lung changes（1/9）;multiple abdominal lymph node enlargement（4/6）,splenomegaly（2/6）,hepatic cyst（1/6）,and hepatic nodules（1/6）;subcutaneous fatty layer occupancy in the left occipital region（1/6）,occupancy in the right parietal region（1/6）,and occipital thickening occupancy with bone destruction（1/6）,and soft tissue nodules in the right frontal scalp with bone destruction（1/6）;whole-body bone imaging suggested the possibility of metastatic bone tumors in 3 cases（3/5）.Ultrasound examination of superficial lymph nodes was performed in only 7 patients（7/12）,and all of them were found to have enlarged lymph nodes,including 3 cases with bilateral neck,axillary and inguinal lymph nodes;2 cases with bilateral neck and axillary lymph nodes;1 case with bilateral inguinal lymph nodes;and 1 case with bilateral neck lymph nodes.Most of the patients had visited multiple hospitals before diagnosis,with 2/3 of the patients visiting 2 or more hospitals,and the maximum number of visits was 8.6 patients had been misdiagnosed as meningioma,bone metastases,idiopathic eosinophilia,pulmonary tuberculosis,nephrotic syndrome,tuberculous meningitis,and Kimura disease,respectively.5 of the 12 patients received local surgical treatment,of which 4 were in stable condition,1 case was lost to follow-up;4 cases received chemotherapy,of which 3 died and 1 case was in stable condition;1 case received local radiotherapy,the prognosis of which was unknown due to lost to follow-up;1 case received herbal treatment and was in stable condition;1 case did not receive treatment and was in stable condition.Among the 102 patients,there was a statistical difference in age,gender and smoking history between the PLCH group and the extrapulmonary LCH group（P<0.05）,with the PLCH group being younger,more often male and more often smokers.Only 9 of the 27 patients with PLCH had typical pulmonary imaging,presenting as nodules（2-10 mm）with predominantly bilateral upper lung distribution and irregularly shaped cystic shadow.Abnormal imaging manifestations were most often seen as cystic and nodular shadows,followed by hilar and mediastinal lymph node enlargement and pleural fluid,and also pleural thickening and grid shadow,with a few complications of pneumothorax and mediastinal emphysema.18patients were diagnosed by lung biopsy,which was most often performed by video-assisted thoracoscopic surgery,followed by CT-guided lung aspiration biopsy.Bone was the most common site for biopsy in patients with single-system extrapulmonary LCH,followed by skin,liver,soft tissue,and lymph nodes,and bone and lymph nodes were the most common sites for biopsy in patients with multisystem extrapulmonary LCH,followed by skin.Five patients with LCH had combined tumors,including one benign tumor,a pulmonary sclerosing pneumocytoma,and four malignant tumors,one thyroid cancer,one esophageal cancer,one ovarian cancer,and one chronic myelomonocytic leukemia,respectively.The four patients with extrapulmonary LCH all had BRAF^V600E gene mutations.81patients had specific treatment information for one or more treatments,including smoking cessation,hormones,chemotherapy,surgery,and lung transplantation,respectively,and some patients were treated with symptomatic and herbal medicine only,or even did not receive any treatment measures.Conclusion:1.Compared to the extrapulmonary LCH group,the PLCH group was younger in age,more common in males,and had a higher percentage of smoking history,with a statistically significant difference between the two groups.There was no significant difference in the distribution and number of organs involved between the two groups.LCH most frequently involved bone,lung,skin,lymph nodes,and liver.2.Most patients with LCH have abnormalities in serology and bone marrow examination,with decreased trilineage（which can be mono-,bi-,and tri-lineage）and increased eosinophils most commonly seen in blood tests;non-specific abnormalities in autoimmune markers and increased inflammatory markers are common;and increased eosinophils are most often seen in bone marrow examinations.3.Thoracic imaging of PLCH is most often characterized by cystic and nodular shadowing,followed by hilar and mediastinal lymph node enlargement and pleural fluid,and most patients with PLCH do not have typical chest imaging.4.Abdominal imaging abnormalities are frequent but not characteristic in patients with LCH,including enlarged abdominal lymph nodes,hepatic cysts,splenomegaly,and hepatic nodules.Bone LCH most often involves the skull,and head CT screen for cranial and CNS involvement and,like whole-body bone imaging,does not identify bone metastatic tumors.5.LCH lymph node involvement often showed bilateral symmetrical enlargement features;enlarged lymph nodes were most commonly found in the neck,axilla and groin,followed by the abdomen;superficial enlarged lymph nodes were highly detected by ultrasound.6.Lung tissue biopsies are most commonly performed with video-assisted thoracoscopic procedures,followed by CT-guided lung puncture biopsies.Bone,skin,and lymph nodes were most often chosen as extra-pulmonary organ biopsy sites.7.Patients with LCH can have a combination of solid and hematologic tumors,and some patients have BRAF^V600E gene mutations.8.Most patients had multiple visits or visited multiple hospitals prior to diagnosis,and there was a significant delay in diagnosis,indicating a general lack of awareness of LCH among clinicians.9.Incomplete systemic assessment in most patients may lead to a higher percentage of patients with single system involvement statistics and a lower number of organ involvement statistics,affecting the development of treatment plans as well as prognostic judgments.