Clinical features and pathological analysis of primary rib Langerhans cell histiocytosis: case series and literature review
Case Series

Clinical features and pathological analysis of primary rib Langerhans cell histiocytosis: case series and literature review

Guangsheng Ni, Yaxuan Ou, Runyu Ming, Jin Yang

Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China

Contributions: (I) Conception and design: G Ni; (II) Administrative support: J Yang; (III) Provision of study materials or patients: Y Ou; (IV) Collection and assembly of data: G Ni, J Yang; (V) Data analysis and interpretation: G Ni, Y Ou, R Ming; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Jin Yang, MM. Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 95 Shaoshan Middle Road, Changsha 410007, China. Email: 253867418@qq.com.

Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by the abnormal proliferation of Langerhans cells, which can infiltrate various tissues throughout the body, leading to a spectrum of organ damage. This study aims to explore the clinical characteristics, imaging manifestations, and pathological features of the disease to enhance clinical diagnosis and understanding of such conditions.

Case Description: This study reviews the clinical data of four patients diagnosed with LCH at The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine. All patients met the diagnostic criteria outlined in the LCH guidelines by the American Society of Hematology, with Langerhans cells expressing CD1a, S-100, and Langerin (CD207).

Conclusions: LCH can involve various organs and systems, presenting with diverse clinical manifestations; in particular, rib Langerhans cell histiocytosis (RLCH) primarily manifests as asymptomatic or mildly painful bone swelling. Computerized tomography (CT) imaging of RLCH typically reveals localized masses and focal bone destruction, with or without surrounding soft tissue invasion. Conversely, magnetic resonance imaging provides a clearer assessment of lesion size and the extent of adjacent soft tissue involvement, offering advantages in guiding surgical excision. Diagnosis requires correlation with pathological and immunohistochemical results. For single-system, single-site (SS-s LCH), R0 surgical resection is feasible; however, single-system, multi-site (SS-m LCH) cases necessitate combined chemotherapy or targeted therapies. Overall, the treatment outcomes for this disease remain reasonably favorable.

Keywords: Langerhans cell histiocytosis (LCH); rib Langerhans cell histiocytosis (RLCH); adult; case series

Received: 18 November 2024; Accepted: 11 April 2025; Published online: 15 July 2025.

doi: 10.21037/acr-24-251

Highlight box

Key findings

• By enhancing the understanding of the clinical characteristics, imaging manifestations and pathological features of rib Langerhans cell histiocytosis (RLCH), and conducting timely diagnosis and treatment, the prognosis of patients with RLCH is relatively good.

What is known and what is new?

• RLCH is rare and there are no major clinical case reports, no unified consensus on the treatment methods and effects.

• The several patients we included achieved good short-term therapeutic effects after strict surgical assessment.

What is the implication, and what should change now?

• After strict assessment, thorough surgical resection is an effective method for the treatment of RLCH.

Introduction

Langerhans cell histiocytosis (LCH) is a rare histiocytic tumor characterized by abnormal proliferation of Langerhans cells, which infiltrate various tissues throughout the body, leading to multi-organ damage (1). While the exact etiology of LCH remains unclear, it can occur at any age, though it predominantly affects children, with an incidence of approximately 1–2 cases per million (2). Clinically, LCH is classified based on the number of affected organs and sites into single-system LCH (SS-LCH), multisystem LCH (MS-LCH), single-system single-site LCH (SS-s LCH), and single-system multi-site LCH (SS-m LCH) (3). Among them, organs such as bones, skin, pituitary gland, liver, and lungs are the most commonly affected in adult LCH (4). Rib Langerhans cell histiocytosis (RLCH), a subtype of LCH, is relatively common among LCH lesions. To further summarize and discuss the clinical and pathological features of RLCH, this study retrospectively analyzes the clinical data of four cases of primary RLCH treated at The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine. Combined with the existing literature, we aim to explore the clinical characteristics, imaging findings, pathological features, treatment, and prognosis of primary RLCH to enhance the understanding and diagnosis of this disease and reduce clinical misdiagnoses. We present this article in accordance with the AME Case Series reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-251/rc).

Case presentation

Clinical data were gathered from four cases of primary RLCH diagnosed at the Department of Pathology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, between June 2012 and August 2024. All patients were male, aged between 32 and 44 years. Each case met the diagnostic criteria outlined in the LCH guidelines issued by the American Society of Hematology (5). This study was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine (No. HN-LL-LW-2024-051). All procedures performed in this study were in accordance with the ethical standards of the institutional research committee, and in line with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patients for publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

This study is a single-center, retrospective case series. All four patients exhibited primary rib involvement. Two patients were diagnosed with SS-s RLCH, presenting with localized bone destruction, while the other two had SS-m RLCH with multiple foci of bone damage. One patient with SS-s RLCH was asymptomatic, with the lesion discovered during a routine physical examination. The remaining three patients experienced mild, tolerable rib pain at the affected sites. Chest computerized tomography (CT) scans revealed localized masses and bone destruction, with or without surrounding soft tissue invasion (Figure 1). Following CT, all patients underwent non-contrast and contrast-enhanced chest magnetic resonance imaging (MRI) scans, which demonstrated iso-signal intensity on T1-weighted images (T1WI), high signal intensity on T2-weighted images (T2WI), and significant enhancement on contrast scans. MRI was instrumental in defining lesion size and assessing soft tissue involvement (Table 1, Figure 2). The study patients were treated with surgical resection or surgical resection combined with chemotherapy and were followed up for 1 year.

Figure 1 The imaging manifestations of chest CT in patients with primary RLCH are mainly local space-occupying lesions and bone destruction, with or without peripheral soft tissue invasion. (A) Chest CT showed local space-occupying lesions and bone destruction with surrounding soft tissue (marked by the red arrow). (B) Three-position CT imaging of the chest showed the location and extent of bone destruction more clearly. CT, computerized tomography; RLCH, rib Langerhans cell histiocytosis.

Table 1

Clinical symptom and imaging characteristics of the cases included in the study

Patient number Invasion site Clinical symptom Imaging characteristics
Non-contrast chest CT Non-contrast and contrast-enhanced chest MRI
1 Left 5th posterior rib Admitted after detection during a physical examination, with no clinical symptoms A mass and bone destruction are observed in the left fifth posterior rib, with a high likelihood of malignancy. Metastasis should be ruled out The left fifth posterior rib shows isointense signals on T1-weighted imaging and hyperintense signals on T2-weighted imaging, measuring approximately 22 mm × 14 mm. The lesion exhibits marked, uneven enhancement, with adjacent pleural thickening at the margins
2 Right 7th anterior rib in the axillary region; right 6th and 7th posterior ribs There is a feeling of distension and pain in the right chest and rib area, which intensifies with deep inhalation The right seventh anterior rib at the axillary segment shows slight enlargement with surrounding soft tissue shadow. Bone destruction is evident in the right seventh posterior rib, accompanied by pleural thickening The right seventh anterior rib at the axillary segment shows an irregularly shaped lesion with slightly elongated T1 and T2 signals. On T2-weighted imaging, it presents a mixed hyperintense signal, measuring 22 mm × 14 mm. Additionally, lesions are observed on the right sixth and seventh posterior ribs, measuring 25 mm × 16 mm and 18 mm × 12 mm, respectively. These lesions exhibit isointense signals on T1-weighted imaging, hyperintense signals on T2-weighted imaging, and display marked enhancement upon contrast administration
3 Lesion in the left 3rd anterior rib in the axillary region and two lesions in the posterior ribs There is a sensation of distension and discomfort in the left chest, rib, and back areas, without significant worsening during deep inhalation or coughing Bone destruction is observed in two areas of the left third rib, involving both the axillary and posterior segments. The surrounding soft tissue appears indistinct, with slight pleural thickening in the affected region. Clinical correlation is recommended Bone destruction lesions, measuring 21 mm × 11 mm and 28 mm × 16 mm, are noted in the axillary and posterior segments of the left third rib, respectively. On T1-weighted imaging, they present as isointense, while T2-weighted imaging shows hyperintense signals. The lesions exhibit marked, uneven enhancement with adjacent tissues showing slightly elevated signals on T2-weighted imaging
4 Left 3rd posterior rib There is intermittent pain in the left chest and back, with no significant increase in intensity during deep inhalation or coughing There is pleural thickening on the left side, with a spindle-shaped soft tissue shadow in the chest wall near the posterior segment of the left third rib, measuring approximately 31 mm × 21 mm. The boundary between this mass and the surrounding muscle tissue is indistinct, and there is disruption of cortical continuity in the adjacent left third posterior rib A mass lesion, approximately 29 mm × 25 mm in size, is observed in the posterior segment of the left third rib. It exhibits isointense signals on T1-weighted imaging and hyperintense signals on T2-weighted imaging, with uneven enhancement upon contrast administration. The adjacent rib shows irregular morphology

CT, computerized tomography; MRI, magnetic resonance imaging.

Figure 2 The imaging manifestations of chest MRI: LCH-MRI showed equal signals on T1WI and high signals on T2WI, and there was significant enhancement to varying degrees during enhanced scan. (A) Plain and enhanced chest MRI: low signal on T1WI indicates destruction of the left 9th rib (marked by the red arrow). (B) Plain and enhanced chest MRI: T2WI shows destruction of the left 9th rib along with high signal change on fat-suppressed images. Enhancement can be seen on enhanced scanning (marked by the red arrow). (C) Whole-body bone scan reveals a single-system, single-site bone destruction lesion (marked by the red arrow). LCH, Langerhans cell histiocytosis; MRI, magnetic resonance imaging; T1WI, T1-weighted images; T2WI, T2-weighted images.

Among all LCH cases, the skeletal system is the most commonly affected. Diagnosis relies on pathological and immunohistochemical examination of the lesion tissue. According to the 2022 diagnostic criteria from the American Society of Hematology’s LCH guidelines, a diagnosis can be made if one of the following is positive: CD1a expression, Langerin immunohistochemical staining, or the presence of Birbeck granules in the affected cells under electron microscopy. Both CD1a and Langerin have high sensitivity and specificity, but their specificity is somewhat limited, so they are often used together for diagnosis (4). A variety of molecular tests can be carried out on pathological tissues. Among them, the determination of BRAF V600E is relatively commonly used for the diagnosis and differential diagnosis of LCH, and it can guide the targeted treatment of patients with single-system multi-lesion or multi-system lesions (6). The detection of BRAF V600E mutations, either through direct analysis or next-generation sequencing, further aids in diagnosis and differential diagnosis, and it provides valuable guidance for targeted therapy, particularly in patients with multisystem or multifocal lesions (7). In LCH cases involving bone tissue, histopathological examination often reveals clusters of Langerhans cells, with significant infiltration of eosinophils, lymphocytes, neutrophils, and histiocytes, frequently accompanied by cortical bone destruction. In chronic cases, extensive fibrosis may be observed (8,9). When numerous eosinophils are found in bone biopsy samples, LCH should be strongly considered.

In this study, all included cases were diagnosed with RLCH. Pathological examination of the tissue samples revealed clusters of Langerhans cells, accompanied by significant eosinophil infiltration (Figure 3). There was evidence of destruction in both bone tissue and surrounding fibrous tissue. Immunohistochemistry results showed positive staining for CD1a, Langerin, and S-100. Of the four patients, three were found to carry the BRAF V600E mutation, with an overall positivity rate of 75.00%. Additionally, the Ki-67 proliferation index was greater than 8% in all cases.

Figure 3 Conventional microscopic examination of pathology and IHC analysis. (A) Routine microscopic examination indicates that there is sheet-like hyperplasia of eosinophils and Langerhans cells (HE, ×100). (B-D) IHC for S-100, Langerin, and CD1a shows positive results (EnVision method, ×40). The red arrows in the figure represent the positive markers of the cells after special staining. HE, hematoxylin and eosin; IHC, immunohistochemistry.

In patients with RLCH, surgical resection is mostly used for SS-s LCH and can basically achieve cure. For SS-m LCH and MS-LCH, comprehensive treatment including surgery, chemotherapy, and targeted therapy is often adopted. However, there is currently no standardized clinical diagnosis and treatment guideline for adults. Among the four patients with RLCH in this study, two patients with focal RLCH underwent complete surgical resection. The surgical margins were all negative during the operation, and there was no tumor invasion. After complete surgical resection, two patients with multifocal RLCH were treated with surgery plus chemotherapy. All four patients were continuously followed up and had a good survival. Follow-up observations indicated that the patients had a good quality of life and were satisfied with the treatment plan.

Regarding intervention adherence/compliance and tolerability, the assessment was carried out comprehensively. The results demonstrated that the patients showed excellent adherence to the intervention. The assessment methods included regular patient interviews to record their actual implementation of the treatment plan, as well as reviewing their medical records to check for any missed doses or deviations from the treatment protocol. For tolerability, patients were regularly asked about any adverse reactions they experienced during the treatment period, and relevant physical examinations and laboratory tests were conducted to monitor their physical conditions. The evaluation results indicated that the patients had a high level of tolerance to the treatment, with no significant adverse reactions that would affect the continuation of the treatment. In terms of loss to follow-up, the percentage of loss to follow-up was 0%. In conclusion, the patients showed good adherence and tolerability to the intervention, and the follow-up process was successfully implemented with no loss to follow-up.

Our study is a retrospective study, and the completeness of the clinical data collection is insufficient. It remains to be supplemented by more systematic research.

Discussion

In patients with RLCH, SS-s LCH can often be effectively treated through surgical resection, leading to a high rate of recovery. For SS-m LCH and MS-LCH, a variety of comprehensive treatments are mostly adopted, including surgery, chemotherapy, and targeted therapy. In addition to surgery, chemotherapy and targeted therapy, there are also the options of waiting after bioptic confirmation with or without cortisone instillation or (10), in the case of multifocal osseous involvement, the supportive administration of bisphosphonates (11). In adults, local radiotherapy could also be considered (12).

Currently, no standardized clinical guidelines exist for treating adult RLCH. LCH is characterized by the abnormal proliferation of immature CD1a+/CD207+ dendritic cells, which infiltrate organs and lead to functional impairments. Due to its rarity and multi-organ involvement, LCH presents with complex and variable clinical manifestations, making diagnosis challenging and prone to misdiagnosis (13).

Traditionally, LCH was classified into three clinical subtypes based on symptoms and severity: Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma. Letterer-Siwe disease primarily involves visceral and skin lesions, representing the most severe form with the poorest prognosis. Hand-Schüller-Christian disease is mainly associated with bone damage, characterized by chronic progression and alternating new and old lesions, with many patients achieving recovery. Eosinophilic granuloma, which involves only bone, is the least severe and tends to be self-limiting. However, there is no clear demarcation between these subtypes (14).

Modern classifications provide more precise guidance by dividing LCH based on the number of affected organs and sites into SS-LCH, MS-LCH, SS-s LCH, and SS-m LCH. This classification, based on the extent of organ involvement, offers more accurate direction for current treatment strategies.

The pathogenesis of LCH remains unclear; however, studies suggest it may be associated with viral infections, immune dysregulation, trauma, metabolic abnormalities, and genetic factors (15). The diagnosis of LCH relies on pathological examination, with hallmark features including the infiltration of lymphocytes, macrophages, eosinophils, typical Langerhans cells, and granuloma formation (1). In LCH cases involving bone, histopathology often reveals clusters of Langerhans cells, along with a significant infiltration of eosinophils, lymphocytes, neutrophils, and histiocytes, frequently accompanied by cortical bone destruction. In chronic cases, extensive fibrosis can be observed. Immunohistochemical staining for CD1a, Langerin, and S-100 is the gold standard for diagnosing LCH, with CD1a and Langerin showing high sensitivity and specificity (16).

With the advancement of modern molecular biology and gene sequencing technologies, the MAPK signaling pathway is now recognized as one of the most crucial intracellular pathways in LCH (17). The BRAF gene plays a pivotal role in this pathway, regulating processes such as cell growth, differentiation, aging, and apoptosis (18). Mutations in the BRAF gene, particularly the BRAF V600E mutation, are now considered key indicators for the diagnosis and prognosis of LCH and serve as the basis for targeted therapies using specific BRAF V600E inhibitors (19).

LCH can occur at any age, but it is more commonly observed in children (20). This condition may affect various organs and systems throughout the body, with the bones being the most frequently involved target organ. SS-s LCH is more prevalent than SS-m LCH. RLCH, a subtype of LCH, is typically asymptomatic or presents with mild symptoms, the most common being bone pain, often described as a dull, aching sensation. Other symptoms may include skin itching and enlarged affected lymph nodes.

RLCH lacks distinctive radiological features, making diagnosis through imaging challenging. Based on existing literature and the findings of this study, primary RLCH on CT typically presents as localized bone destruction with surrounding tissue shadows. MRI provides a clearer assessment of lesion size and the extent of soft tissue invasion, offering an advantage in guiding local surgical resection. In imaging diagnostics, RLCH must be differentiated from bone metastases, primary malignant bone tumors, and multiple myeloma. In addition to CT and MRI, PET-CT can assist in determining the condition of systemic metastasis, which is of great significance for guiding systemic treatment (21).

Currently, there are limited large-scale case reports on LCH, but clinical case reports and basic research have increased in recent years, closely related to advances in pathological diagnosis and molecular testing techniques. As our understanding of the clinical characteristics, imaging findings, and pathological features of this rare disease improves, the rates of misdiagnosis and mistreatment are expected to significantly decrease in the future.

Conclusions

In conclusion, we report four cases of RLCH. The findings from these cases suggest that surgical resection is an effective treatment for patients with localized RLCH. For patients with multifocal RLCH, complete surgical removal followed by surgery combined with chemotherapy, along with continuous follow-up, has resulted in favorable survival outcomes. In the future, a larger-scale prospective cohort study is warranted.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-251/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-251/prf

Funding: The study was supported by the Natural Science Foundation of Hunan Province (No. 2024JJ9431).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-251/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee, and in line with the Helsinki Declaration and its subsequent amendments. This study was approved by the Ethics Committee of The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine (No. HN-LL-LW-2024-051). Written informed consent was obtained from the patients for publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/acr-24-251
Cite this article as: Ni G, Ou Y, Ming R, Yang J. Clinical features and pathological analysis of primary rib Langerhans cell histiocytosis: case series and literature review. AME Case Rep 2025;9:106.

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