Langerhans cell sarcoma of the right calf: a case report

Introduction

Langerhans cell sarcoma (LCS) is characterized by aggressive clinical behavior and a poor prognosis. Langerhans cells, as a type of dendritic cell, are normally involved in antigen presentation and immune regulation, but their malignant transformation mechanism is not yet clear. LCS can develop in multiple organs, including lymph nodes, skin, bone, and lungs. Its clinical manifestations are highly heterogeneous and can be easily confused with Langerhans cell histiocytosis (LCH) or other tissue sarcomas. Definitive diagnosis relies on histopathology, immunohistochemistry, and molecular testing.

With an extremely low incidence, LCS is predominantly documented in isolated case reports. To date, fewer than 100 confirmed cases have been reported worldwide (1). The disease may occur at any age but is more frequently observed in adults, without a clear sex predilection. Given its rarity, no standardized treatment regimen has been established. Current management often involves surgical resection combined with chemotherapy or radiotherapy. However, the recurrence rate is high and the long-term survival rate is low.

The present case is notable for the patient’s prolonged survival following surgical and systemic chemotherapy-even in the setting of radiologically confirmed widespread dissemination. This report aims to contribute to the understanding of LCS, explore potential therapeutic and long-term management approaches, and offer insights to guide clinical practice. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0071/rc).

Case description

The patient was a 46-year-old woman of Han Chinese ethnicity. She had no significant past medical, family, or psychosocial history. She sought medical attention on December 19, 2016, due to persistent pain in the right calf. The physical examination indicated tenderness in the right lower leg, but no mass. Contrast-enhanced magnetic resonance imaging (MRI) of the right tibia indicated the possible chronic osteomyelitis with bone abscess formation. As the mass gradually enlarged, a contrast‑enhanced computed tomography (CT) scan of the right tibia was performed on January 17, 2017, at the Department of Orthopedics of Shanghai Sixth People’s Hospital, which indicated a high probability of bilateral tibiofibular osteomyelitis, with local cortical destruction and sinus tract formation, accompanied by abscess in the upper right tibia.

The patient underwent tumor resection on January 25, 2017. Pathological examination confirmed LCS with a maximum diameter of approximately 3.0 cm. The tumor extensively infiltrated the bone and extended through the cortex into the surrounding soft tissue. The tumor cells showed nuclear atypia, numerous atypical mitotic figures, and high Ki-67 expression (40%+). Immunohistochemistry of the tumor tissue showed the following profile: S100 (partial +), CD1a (partial +), Langerin (partial +), HMB45 (−), MelanA (−), Ki67 (40%+), SOX10 (cytoplasmic +), CD30 (−), EMA (−), PAX5 (−), Kp1 (+), PGM1 (+), CD163 (+), INI-1 (+), Lysozyme (+), CD34 (−), CD43 (lymphocytes +), MPO (−). A postoperative positron emission tomography/computed tomography (PET/CT) scan was performed 24 days later, which indicated bilateral femoral and tibial lesions. Combined with the pathological findings, these results supported a diagnosis of LCS.

The anthracycline chemotherapy was initiated on March 29, 2017, and administered for a total of six cycles, of which the final cycle was completed on July 24, 2017. The treatment was well-tolerated, with no significant adverse effects reported. Follow-up abdominal contrast-enhanced CT on August 24, 2017, indicated a site of disease in the right hepatic lobe (Figure 1). PET/CT on August 29, 2017, indicated a local cortical defect in the upper right tibia consistent with postoperative changes, along with increased density and diffusely mild glucose metabolism in the bone marrow of both femurs and tibias. The above results raised the consideration of Erdheim-Chester disease—a rare non-LCH and a high likelihood of liver dissemination.

Figure 1 Multiphase contrast-enhanced CT of the liver. (A) Plain scan; (B) arterial phase; (C) portal venous phase; (D) delayed phase. CT, computed tomography.

Between September 5 and December 26, 2017, the patient received six cycles of ifosfamide chemotherapy. Throughout the course of treatment, the patient experienced no significant adverse drug reactions. Upon completion, the patient chose not to receive further chemotherapy. Subsequently, follow-up evaluation indicated stable disease. MRI on January 4, 2019, indicated persistent LCS in the right tibia and disease involvement in the left tibia (Figure 2). But the patient declined further treatment. On December 5, 2019, abdominal contrast-enhanced CT indicated complete resolution of the previously noted liver dissemination. The patient continues to be followed regularly and remains in stable condition, with an overall disease duration exceeding 9 years. The patient remains optimistic about her condition and reports feeling well, stating that she doesn’t feel anything is wrong.

Figure 2 MRI sequences of both lower legs demonstrating bone lesions. (A) T1 weighted sequence; (B) T1-weighted fat suppression sequence; (C) T2 weighted sequence; (D) T2-weighted fat suppression sequence. MRI, magnetic resonance imaging.

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Langerhans cells are dendritic antigen-presenting cells that function as a part of the immune system. The World Health Organization classification, Langerhans cell tumors are divided into two categories: LCH and LCS. LCS is a rare, malignant neoplastic disorder of Langerhans cells, which are epidermal dendritic cells. It is not associated with any form of histiocytosis, despite historical hypotheses suggesting otherwise (2). Most cases arise de novo. The diagnosis of LCS relies on the detection of malignant cytological features and characteristic immunophenotypes, among which the expression of specific markers CD1a, S100 and Langerhans protein (CD207) is the key diagnostic indicator (3,4).

LCS occurs almost exclusively in adults, with an incidence of 0.02 cases per million. It typically presents as a single or multiple masses (5,6). A recent systematic review reports a median age at diagnosis of 59.5 years and a male-to-female ratio of 1.6:1. Lymph nodes are the most frequently involved site (65%), followed by the skin (51%), lungs (28%), bones (23%), spleen (20%), liver (19%), and soft tissues (8%) (1). Dissemination most commonly occurs in the lymph nodes, initially spreading via local lymphatic vessels and subsequently throughout the body. Other common sites of involvement include the lungs. In advanced stages, the disease may spread to organs such as the bone marrow, liver, spleen, and kidneys (7).

Given the rarity of LCS, there is insufficient evidence to establish standardized adjuvant therapy protocols, whether for localized or systemic disease, including the use of radiotherapy or chemotherapy. Treatment approaches, particularly surgical strategies and adjunct therapies, also vary widely across different anatomical sites. Table 1, which summarizes the cases from the literature, demonstrates the current lack of consensus on treatment options for LCS involving only the bone.

It is noteworthy that, despite the cessation of treatment, the prolonged stable disease observed in this case may be partially attributed to the patient’s resilient psychological state and the adoption of a watchful treatment approach. The case offers an alternative perspective on the clinical behavior of LCS and provides insights into its long-term management across the disease continuum.

Conclusions

LCS is generally associated with a poor prognosis. However, due to its extreme rarity, our current understanding of the disease remains limited, and standardized management protocols have yet to be established. This case indicates that for localized disease, surgical resection followed by adjuvant chemotherapy, coupled with a patient’s optimistic psychological quality, may be important factors in effective disease control. Further research is necessary to develop evidence‑based management guidelines aimed at optimizing long‑term outcomes for patients with LCS.

Acknowledgments

We acknowledge the patient for her cooperation and providing informed and written consent for this case report.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0071/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0071/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0071/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 case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report 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/.

References

1. Dezzani A, Punziano C, Berti E, et al. Langerhans cell sarcoma is a clinically, biologically, and prognostically heterogeneous "malignant" histiocytosis: a systematic review of 88 cases from the literature. Virchows Arch 2025;487:1195-207. [Crossref] [PubMed]
2. Brunning RD, Matutes E, Flandrin G, et al. Myeloid sarcoma. In: Jaffe ES, Harris NL, Stein H, et al. editors. Vardiman Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. 3rd ed. Lyon: IARC; 2001:104-105.
3. Yi W, Chen WY, Yang TX, et al. Langerhans cell sarcoma arising from antecedent langerhans cell histiocytosis: A case report. Medicine (Baltimore) 2019;98:e14531. [Crossref] [PubMed]
4. Obid R, Green AR, Jasmine SW, et al. An Unusual Case of Cutaneous Langerhans Cell Sarcoma Lacking S100 Expression: A Case Report and Review of the Literature. J Cutan Pathol 2025;52:554-67. [Crossref] [PubMed]
5. Tella SH, Kommalapati A, Rech KL, et al. Incidence, Clinical Features, and Outcomes of Langerhans Cell Sarcoma in the United States. Clin Lymphoma Myeloma Leuk 2019;19:441-6. [Crossref] [PubMed]
6. Guyot-Goubin A, Donadieu J, Barkaoui M, et al. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004. Pediatr Blood Cancer 2008;51:71-5. [Crossref] [PubMed]
7. Howard JE, Dwivedi RC, Masterson L, et al. Langerhans cell sarcoma: a systematic review. Cancer Treat Rev 2015;41:320-31. [Crossref] [PubMed]
8. Pileri SA, Grogan TM, Harris NL, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002;41:1-29. [Crossref] [PubMed]
9. Kawase T, Hamazaki M, Ogura M, et al. CD56/NCAM-positive Langerhans cell sarcoma: a clinicopathologic study of 4 cases. Int J Hematol 2005;81:323-9. [Crossref] [PubMed]
10. Zwerdling T, Won E, Shane L, et al. Langerhans cell sarcoma: case report and review of world literature. J Pediatr Hematol Oncol 2014;36:419-25. [Crossref] [PubMed]