Tonsillar langerhans cell sarcoma with gastrointestinal metastasis: a rare case report

Introduction

Langerhans cell sarcoma (LCS) is a rare and aggressive neoplasm arising from Langerhans cells, characterized by its ability to affect multiple organs. The World Health Organization classifies Langerhans cell tumors into two primary categories: LCS and Langerhans cell histiocytosis (LCH). While LCH is generally considered a benign condition, it can occasionally progress to LCS, which displays characteristics associated with malignant tumors, such as rapid growth, local invasion, and a high propensity for recurrence and metastasis (1).

Epidemiological data on LCS is limited, with most knowledge derived from individual case reports. The specific clinical symptoms and imaging findings associated with this condition are not well defined (2). However, LCS diagnosis primarily relies on histopathological examination revealing malignant histiocytoid cells with elongated, grooved nuclei and prominent nucleoli. The distinct Langerhans cell phenotype is confirmed through immunohistochemical markers, including CD68, variable S100, CD1a, and Langerin (1). Patients diagnosed with LCS typically face a poor prognosis, exhibiting limited survival rates despite standard treatments, including combination chemotherapy, surgery, and radiotherapy (3).

In contrast, LCH can present in various forms: unifocal, multifocal, single-system, or multi-system disease, leading to a diverse range of clinical manifestations. Less aggressive forms of LCH may resolve spontaneously, whereas multi-organ involvement can result in complications such as eosinophilic granuloma, distinctive papulosquamous lesions, diabetes insipidus, exophthalmos, radicular nerve pain, muscle weakness, and dysfunction of bowel and bladder, along with abnormalities in pituitary, thyroid, growth hormone, and gonadotropin levels. Gastrointestinal (GI) involvement in adults is exceedingly rare, especially in cases classified as unifocal or single-system disease. The unclear pathogenesis and limited information on managing GI LCH in adults contribute to ambiguous treatment strategies (4).

GI metastasis in the setting of LCS in the tonsil is exceedingly rare. This study aims to report a unique case of LCS in the tonsils with metastasis to the GI tract in an elderly female patient. The rarity of this combination highlights the need for increased awareness and further investigation into dual involvement in LCS, which may influence diagnostic and therapeutic approaches for similar cases in the future. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-25-20/rc).

Case presentation

An 83-year-old female with a history of heavy smoking for over 50 years presented in February 2024 with significant clinical symptoms, including progressive swelling of the left tonsil and dysphagia. She reported considerable weight loss and pain that hindered her ability to eat. Physical examination revealed a left tonsillar mass and palpable cervical lymphadenopathy. The patient’s performance status was classified as Eastern Cooperative Oncology Group 2–3, indicating a moderate level of impairment.

Initial laboratory investigations showed a hemoglobin level of 11.6 g/dL (reference range: 12–16 g/dL), a white blood cell count of 8.02×10⁹/L [reference range: (4.5 to 11.0) ×10⁹/L], and normal renal and liver function tests, with no evidence of tumor lysis syndrome.

A neck computed tomography (CT) scan performed on February 19, 2024, revealed a large, irregularly enhancing left oropharyngeal mass measuring 3 mm × 3.5 mm × 6.4 mm. This lesion exhibited significant ulceration with medial extension into the throat and caused obliteration of the parapharyngeal fat pad. It demonstrated invasive behavior, extending to the base of the tongue and involving the superior left aspect of the epiglottis. The mass was inseparable from adjacent structures, including the left submandibular gland and the left lateral pterygoid muscle. Additionally, there was enlargement of necrotic lymph nodes at levels 2a and 2b, the largest measuring 1.1 cm × 1.7 cm, as well as a suspicious necrotic lymph node at level 5 measuring 0.8 cm (Figure 1).

Figure 1 Neck CT scan performed revealed a large, irregularly enhancing left oropharyngeal mass measuring 3 mm × 3.5 mm × 6.4 mm. CT, computed tomography.

A subsequent positron emission tomography-computed tomography (PET-CT) scan conducted on March 4, 2024, demonstrated moderate to intense hypermetabolic activity within the asymmetrical thickening of the left nasopharyngeal region, with a maximum standardized uptake value (SUVmax) of 28.3. The diffuse, ulcerated, enhancing soft tissue mass exhibited substantial hypermetabolic activity, extending from the left tonsillar fossa down to the cricoid level and invading the base of the tongue on the left side, crossing the midline, and potentially involving the aryepiglottic folds and left epiglottis (SUVmax 29.35). Enlarged hypermetabolic bilateral deep cervical lymph nodes were also noted, with the largest at level 2a and 2b measuring approximately 12 mm (SUVmax 41). A hypermetabolic left supraclavicular lymph node showed an SUV max of 15. Additionally, mildly active mediastinal and bilateral hilar lymph nodes were observed, presumed to be reactive. Neck magnetic resonance imaging (MRI), performed on March 5, 2024, revealed an invasive ulcerative oropharyngeal soft tissue mass with necrotic lymph nodes suggestive of carcinoma (Figure 2).

Figure 2 Neck MRI showing invasive ulcerative oropharyngeal soft tissue mass with necrotic lymph nodes suggestive of carcinoma. MRI, magnetic resonance imaging.

Incisional biopsy of the left tonsillar mass confirmed the diagnosis of LCS. Histological analysis revealed atypical mitotic figures, ulceration, and a diffuse infiltrate of pleomorphic cells (Figure 3).

Figure 3 Histological analysis of the biopsy from the left tonsillar mass. (A) Unremarkable squamous mucosa with a deep infiltrative tumor cell (low power); (B,C) neoplastic cells are pleomorphic cells with prominent nucleoli and clumped chromatin and abundant amount of cytoplasm. Eosinophils are in the background with frequent mitotic figures. Hematoxylin and eosin stain. Magnification: A, ×4; B, ×40; C, ×40.

Immunohistochemical staining was positive for S100, CD1a, BCL6, and Langerin, with a high Ki-67 proliferation index of 90%, indicating aggressive tumor behavior (Figure 4).

Figure 4 Immunohistochemical staining of the left tonsillar lesion (×40). (A) CD1a positive; (B) Langerin positive; (C) S100 focally positive; (D) CD68 weak and variable; (E) Cd163 negative; (F) KI-67 proliferation index is high (more than 90%).

Following the diagnosis, the patient received radiation therapy, directed at the left tonsil mass, and immunotherapy with pembrolizumab for metastatic disease control. However, PET-CT scan, performed on July 9, 2024, indicated disease progression, with new hypermetabolic activity observed in abdominal lymph nodes as well as moderate pleural effusion. Additionally, the scan revealed circumferential wall thickening measuring 7.6 mm, which could be related to infectious or inflammatory enteritis, or metastasis (Figure 5A,5B).

Figure 5 PET-CT scan performed showing new hypermetabolic activity observed in abdominal lymph nodes as well as moderate pleural effusion. Additionally, the scan revealed circumferential wall thickening measuring 7.6 mm, which was related to infectious or inflammatory enteritis, or metastasis. (A) Circumferential hypodense lesion in the distal ileum, measuring approximately 4 cm in length. (B) Aneurysmal dilatation with reduced mucosal enhancement and a focal wall defect consistent with perforation. PET-CT, positron emission tomography-computed tomography.

In July, after the second PET-CT, the patient was admitted with acute upper GI bleeding, manifested by hematemesis and melena. The patient was stabilized with blood transfusions, proton pump inhibitors, and antibiotics for a urinary tract infection. Laboratory parameters during the GI bleeding event are summarized in Table 1. After patient stabilization, upper GI endoscopy was conducted, revealing an ulcerated mass. An endoscopic biopsy was taken from this lesion for histopathological examination, which confirmed the presence of metastasis (Figure 6).

Figure 6 Histological examination of the small bowel lesion biopsy showing similar morphology and immunohistochemistry results as the tonsillar mass confirming metastatic disease. Magnification: A, ×4; B, ×40; C, ×10.

In August 2024, the patient was readmitted with severe abdominal pain, tenderness, guarding and rebound tenderness indicating GI perforation, along with continuing signs of metastatic spread. Due to the rapid progression of LCS and the onset of severe complications, care was shifted to palliative management to control symptoms and support quality of life. The patient died 6 months after the initial diagnosis.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from patient consent according to the National Guard Hospital Ethics Committee.

Discussion

The presented case of an 83-year-old female with tonsillar LCS progressing to GI metastasis provides critical insights into the aggressive nature of this rare malignancy, especially in elderly patients. This case underscores significant challenges in treatment and highlights the importance of comprehensive, palliative care in managing advanced stages of systemic disease.

The uncommon nature of LCS makes it challenging to study its underlying causes. Various potential factors have been suggested, such as immunosuppression, previous haematological disorders, and viral infections, e.g., Epstein-Barr virus. Immunosuppression, in particular, has been associated with a significantly higher incidence of malignancy, ranging from a 2.7 to 13.7 times increase following transplantation, where the risk escalates with both the intensity and duration of immunosuppressive treatment (5).

LCS is characterized by the malignant proliferation of Langerhans cells and is known for its aggressive behaviour (6). The patient’s initial symptoms of left tonsillar mass, dysphagia, and cervical lymphadenopathy progressed to systemic GI involvement marked by bleeding and perforation. This progression is rare, as LCS typically involves regional lymph nodes or, in some cases, the lungs and bones (1).

Only two cases of tonsillar LCS were found in the literature, but neither had systemic GI involvement. One was in a 10-year-old Chinese child (3) and the second was in a 38-year-old Indian female (7). Our case differs by presenting with significant GI complications, including upper GI bleeding and perforation, highlighting a severe and uncommon progression of LCS with distant GI metastasis. Comparative literature, such as the LCH case reported by Atalay et al., described a 74-year-old male with similar tonsillar involvement but without GI metastasis (8).

Immunohistochemical analysis in our patient revealed markers such as S100, CD1a, BCL6, and CD30, aligning with documented LCS cases (1,3,7,9,10). The high Ki-67 index (90%), in our case, suggests a rapid proliferative capacity, consistent with the findings by Li et al. (2013), who highlighted that such markers often correlate with worse outcomes (11). This profile emphasizes the tumour’s invasive potential, contributing to its ability to metastasize beyond typical sites.

On the contrary, the high Ki-67 proliferation index, in the case studied by Ren et al. (12), was much lower (30–40%), suggesting a less aggressive phenotype despite similar immunohistochemical markers. This lower index may have contributed to the more localized disease observed in Ren’s case, as opposed to the extensive metastasis and systemic involvement seen in our patient. The difference in Ki-67 levels between these cases likely reflects the inherent heterogeneity of LCS, where tumors, even with similar histological and immunophenotypic profiles, can exhibit diverse proliferative capacities and clinical outcomes.

Advanced imaging techniques were pivotal for diagnosis and monitoring of LCS. Initial contrast-enhanced CT scans identified the primary tumor’s size and invasive local spread, while subsequent PET-CT scans provided detailed insights into metabolic activity, revealing both nodal and distant metastatic sites, including the GI tract. This approach, consistent with best practices noted in the literature (9,10,13), underscored the aggressiveness and atypical spread of LCS, guiding clinical management and informing prognosis. Imaging also played a crucial role in detecting complications like GI perforation, emphasizing the comprehensive role of multimodal imaging in diagnosing and managing such rare, aggressive cases.

Management of LCS remains a significant challenge due to the lack of established, effective treatment protocols. In our case, the initial response to radiotherapy and pembrolizumab was insufficient, as indicated by the new hypermetabolic activity in abdominal lymph nodes seen on follow-up PET-CT scans. This resistance is inconsistent with observations by Nascimento and colleagues, who reported clinical and laboratory improvement to combined pembrolizumab and radiotherapy in a high-grade LCS case (14). This discrepancy underscores the heterogeneous behavior of LCS and suggests that while some patients may respond to certain treatment modalities, others might exhibit resistance, emphasizing the need for further research into targeted and individualized therapeutic approaches.

Other treatment options reported in the literature, such as multi-agent chemotherapy regimens e.g., ESHAP (etoposide, carboplatin, cytarabine, and methylprednisolone) (15), MAID (mesna, doxorubicin, ifosfamide, and dacarbazine) (16), and E-CHOP (etoposide, cyclophosphamide, vindesine, dexamethasone) (17) showed variable success but are not widely validated due to the small number of cases. Surgical resection with clear margins remains the preferred approach for localized disease (18); however, our patient’s disseminated disease precluded this option.

Strengths and limitations

Documentation of this case is crucial for several reasons: it improves understanding of LCS manifestation and progression in older adults, highlights treatment challenges with standard approaches, and emphasizes the roles of palliative care. Given the limited comparative data, further research is needed to enhance clinical management of metastatic LCS. By sharing this case report, we hope to contribute to clinical practice guidelines and education, potentially improving outcomes in patients with LCS.

Conclusions

This case illustrates the aggressive progression of LCS in an elderly patient, emphasizing the need for early diagnosis and effective treatment strategies. The rapid development of complications highlights the challenges in managing this rare malignancy. Future research should focus on understanding the underlying mechanisms of LCS, exploring targeted therapies, and establishing clearer guidelines for the management of both localized and metastatic disease to improve patient outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-25-20/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-25-20/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-25-20/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 and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from patient consent according to the National Guard Hospital Ethics Committee.

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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