Abstract
Background:
Langerhans cell histiocytosis (LCH) is a rare hematopoietic disorder with diverse clinical presentations and sequential or concurrent multi-organ involvement. The adult onset is particularly uncommon and challenging to diagnose early.
Case presentation:
A 36-year-old female patient initially presented with polydipsia, polyuria, and dry mouth, gradually developing bone pain, facial erythema, and lymph node enlargement. Cranial MRI showed pituitary stalk thickening with the absence of a posterior pituitary signal. Iliac bone biopsy with immunohistochemistry demonstrated S-100(+), CD1a(+), and CD68(+) expression. After Systemic Chemotherapy and DDAVP administration, follow-up showed improvement of polyuria, polydipsia, and polyphagia, remission of osseous pain, regression of cutaneous manifestations, normalized pituitary stalk morphology, and reduced lesion metabolic activity.
Conclusion:
This report documents a complex and rare case to improve early diagnosis, reduce misdiagnosis, and prevent poor outcomes from delayed treatment.
Introduction
Langerhans cell histiocytosis (LCH) represents a hematopoietic disorder characterized by the aberrant proliferation of immature dendritic cells, driven by the dysregulated activation of the mitogen-activated protein kinase (MAPK) signalling pathway (1, 2). The incidence is age-dependent, with pediatric rates of approximately 4.46 per million annually, while adult cases are significantly rarer at only 1.06 per million (3). Due to its insidious onset, diverse clinical manifestations, and the tendency for misdiagnosis resulting in poor prognosis, this article reports a case of adult-onset disease with arginine vasopressin deficiency (AVP-D) as the initial manifestation, ultimately diagnosed as LCH through bone lesion biopsy, providing a reference for early recognition and improved outcomes.
Case presentation
In 2014, a 36-year-old obese female developed symptoms of polyuria, polydipsia, and polyphagia following diet and exercise-induced weight loss. Symptoms included hourly urination and menstrual irregularities. An initial pituitary MRI at another hospital revealed a pituitary lesion (approximately 0.5 cm × 0.5 cm × 0.3 cm) with a prolactin level of 13.04 μg/L (within the normal reference range of 3.34–26.72 μg/L). The patient underwent radiotherapy for presumptive prolactinoma (radiographic documentation and treatment protocol unavailable). Despite the intervention, clinical symptoms persisted post-treatment. Two weeks later, a Water Deprivation Test with DDAVP at a local hospital was positive, establishing a diagnosis of “AVP-D.” Electrolytes, parathyroid hormone, and growth hormone were normal upon testing. Oral desmopressin significantly improved her polyuria and polydipsia, with concurrent estrogen therapy for menstrual regulation.
In 2016, the patient was hospitalized at a local medical center without other symptoms, where a repeat pituitary MRI revealed a lesion in the neurohypophyseal region (involving the pituitary stalk and infundibulum). During hospitalization at a local hospital, a follow-up pituitary MRI showed a slight reduction in pituitary volume with diffuse pituitary stalk thickening, uniform enhancement, and indistinct posterior pituitary visualization (Figure 1). The patient was diagnosed with complete AVP-D and post-radiation status. Subsequently, the patient continued on oral desmopressin therapy.
Figure 1
Longitudinal cranial MRI Follow-up of the LCH Patient. (A,B) Post-radiotherapy MRI of the pituitary gland (2016) demonstrating a slight reduction in pituitary volume with diffuse pituitary stalk thickening, uniform enhancement, and indistinct posterior pituitary visualization. (C,D) Underwent a follow-up cranial MRI at our hospital in 2019. Comparative analysis with imaging from February 16, 2016, demonstrates a subtle volumetric reduction of the pituitary gland. The infundibulum continues to exhibit nodular thickening with a homogeneous enhancement pattern, though notably diminished in diameter compared to the 2016 examination. (E,F) After being diagnosed with LCH and chemotherapy in 2022. Comparative analysis with imaging from December 17, 2019, reveals preserved adenohypophyseal dimensions. The pituitary infundibulum demonstrates physiological calibre with uniform morphology, homogeneous contrast enhancement, and absence of space-occupying lesions.
In 2017, she experienced left hip pain but did not undergo further examination or treatment. In November 2019, owing to progressively worsening bone pain and the development of a facial rash, she presented to our orthopaedic department. A pelvic MRI revealed pathological changes in the left hip bone, lymph nodes adjacent to the left iliac vessels, and inguinal lymph nodes. Bone lesion biopsy indicated eosinophilic granuloma of the left pelvis (Supplementary Figure 1).
No relevant past medical history or family history was reported.
Physical examination demonstrated bilateral symmetrical facial erythema, left hip deep tenderness, restricted range of motion in left knee flexion and extension, left lower limb shortening of approximately 2 cm relative to the right side, and significant left lower limb gait abnormality.
The patient was later admitted to our department on December 16, 2019, for further investigations (Table 1). Elevated ACTH and urinary free cortisol (24-h), with other laboratory tests, including blood cell counts, blood cell counts, cortisol, growth hormone, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), liver and kidney function, electrolytes, and bone metabolism markers were all within normal limits. Pituitary MRI showed: a slight reduction in pituitary volume compared to previous studies; the pituitary stalk still demonstrated nodular thickening with uniform enhancement, which had decreased in size compared to 2016 (Figure 1).
Table 1
| Items | Result | Reference range |
|---|---|---|
| Pituitary assessment | ||
| IGF-1 | 0.011 | 0.010–3.607 |
| ACTH (8 a.m.) | 69.20 | 0–46 pg./mL |
| Serum Cortisol (8 a.m.) | 14.06 | 3.09–22.4 μg/dL |
| Urinary Free Cortisol(24-h) | 403.00 | 28.5–213.7 μg/dL |
| PRL | 5.65 | 3.34–26.72 ng/mL |
| FSH | 6.62 | Follicular phase: 3.85–8.78 IU/L; Ovulatory phase: 4.54–22.51 IU/L; Luteal phase: 1.79–5.12 IU/L |
| LH | 7.20 | Follicular phase: 2.12–10.89 IU/L; Ovulatory phase: 19.8–103 IU/L; Luteal phase: 1.2–12.86 IU/L |
| E2 | 35.00 | Follicular phase: 23–139 pg./mL; Ovulatory phase: 83–495 pg./mL; Luteal phase: 42–338 pg./mL |
| Testosterone | 0.17 | 0.1–0.75 ng/mL |
| Urine Specific Gravity | 1.003 | 1.002–1.030 |
| Urine Osmolality | 205 | 400–1,000 mOsm/kg |
| Bone turnover markers | ||
| 25-(HO)D | 25.72 | 11–48 ng/mL |
| P1NP | 45.10 | 15.13–76.31 ng/mL |
| PTH | 43.38 | 15–65 pg./mL |
| Collagen Specific Sequence | 0.63 | 0.030–1.008 ng/mL |
| N-MID | 19.03 | 11–48 ng/ml |
| Tumor markers | ||
| AFP | 1.9 | 0–8.1 ng/mL |
| CEA | <0.50 | 0–5 ng/mL |
| Ferritin | 39.9 | 10–291 ng/mL |
| CA125 | 4.0 | 0–35 U/mL |
| CA199 | 3.93 | 0–37 U/mL |
| CA153 | <0.5 | 0–38.6 U/mL |
| Blood cell counts | ||
| WBC | 7.96 | 10^9/L |
| RBC | 3.97 | 10^12/L |
| HB | 113.0 | g/L |
| PLT | 304.0 | 10^9/L |
Pituitary assessment, bone turnover markers and tumor markers.
IGF-1, Insulin-like Growth Factor-1; ACTH, Adrenocorticotropic Hormone; PRL, Prolactin; FSH, Follicle-Stimulating Hormone; LH, Luteinizing Hormone; E2, Estradiol; 25-(HO)D, 25-Hydroxyvitamin D. P1NP, Total Collagen Type I Aminoterminal Propeptide. PTH, Parathyroid Hormone; N-IMD, N-terminal Mid-fragment; WBC, White Blood Cell; RBC, Red Blood Cell; HB, Hemoglobin; PLT, Platelet.
Considering the patient’s pituitary stalk thickening and symptoms of polyuria, dry mouth, polydipsia, bone pain, facial erythema, and lymphadenopathy, tumor markers were further evaluated in addition to pituitary function assessment (Table 1). PET-CT (Supplementary Figure 2) revealed Langerhans cell histiocytosis involving multiple skeletal sites and lymph nodes throughout the body. Histopathological examination of the bone lesion biopsy (Figure 2) confirmed the diagnosis of Langerhans cell histiocytosis.
Figure 2
Images demonstrate the typical histology of an LCH lesion obtained from a bone biopsy. (A) Hematoxylin and eosin stains demonstrated fine chromatin with visible nucleoli, exhibiting diffuse or nodular distribution with prominent eosinophilic infiltration, accompanied by neutrophils, lymphocytes, and multinucleated macrophages. Immunohistochemistry positive for (B) S-100, (C) CD68, (D) CD2scattered, (E) CD3, (F) CD1a. Immunohistochemistry negative for (G) CD21, (H) CK.
Based on the combined findings from MRI, PET-CT, and histopathological results, the definitive diagnosis was established as multisystem Langerhans cell histiocytosis (involving pituitary, osseous structures, lymph nodes, and cutaneous tissues). The patient received oral desmopressin 0.1 mg three times daily for symptom management and received regular chemotherapy from the hematology department for 1 year.
Follow-up in 2020: The patient showed significant improvement in left hip pain, normal menstrual cycle, resolution of facial erythema, and no obvious thirst, polydipsia, or polyuria. PET-CT (Supplementary Figure 2) demonstrated that multiple Langerhans cell histiocytosis lesions were in a suppressed state following treatment. Repeat cranial MRI (Figure 1) in 2022 showed stable pituitary volume with no interval changes; the pituitary stalk demonstrated normal thickness and homogeneous enhancement without mass lesions.
The whole timeline of clinical progression is shown in Figure 3. Pituitary assessment, bone turnover markers and tumor markers are shown in Table 1.
Figure 3
Appointment schedule. MS-LCH, multisystem LCH; PRL, Prolactin; AVP-D, Arginine vasopressin deficiency; DDAVP, Desmopressin acetate.
Discussion
LCH is a rare neoplastic disorder of bone marrow origin whose etiology remains incompletely understood. It is characterized by abnormal proliferation and infiltration of Langerhans cells into multiple organs (1). The lesions can involve multiple systems either sequentially or simultaneously, with bone (approximately 80%), skin (approximately 33%), and pituitary (approximately 25%) being the most commonly affected sites (2). While involvement of lungs, thyroid, liver, spleen, female reproductive system, hematopoietic system, and lymph nodes is relatively rare, pulmonary involvement shows a markedly higher prevalence in adult patients compared to pediatric cases. The clinical presentations of LCH are complex and varied, rendering diagnosis difficult. Based on the 2021 international expert consensus (4), LCH is categorized into four subtypes: single-lesion LCH, pulmonary isolated LCH, single-system multifocal LCH, and multisystem LCH. Treatment strategies and first-line drugs differ significantly among different subtypes. When risk organs such as the hematopoietic system, liver, and spleen are involved in pediatric LCH patients, treatment response is poor and patient prognosis is generally unfavourable (5, 6), but remains undefined in adults. The classic cutaneous presentations of LCH include red/brown rashes, papules, or ulcers accompanied by scaling or crusting (7, 8). While LCH primarily affects children, recent research demonstrates that the disease may also manifest in adults, though with a relatively low incidence of merely 1.06 per 1,000,000 (3). Among adults, LCH is uncommon and presents with varied clinical features, with AVP-D typically being the first endocrine manifestation (9). The natural progression of adult LCH is not completely understood, but studies suggest that the disease may extend from the pituitary to more extensive areas of the central nervous system (10). As defined in the consensus by Goyal et al. (2), the diagnostic criteria for multisystem LCH are the involvement of ≥2 organs or organ systems. This patient presented with multisystem involvement, initially manifesting as pituitary lesions with xerostomia, polydipsia, polyuria, and pituitary stalk thickening; subsequently developed skeletal involvement characterized by multiple osteolytic lesions and bone pain; and later developed lymph node and skin lesions manifesting as multiple lymphadenopathies and facial erythema.
The diagnosis of LCH requires consideration of clinical manifestations, radiological features, and pathological examination. Classic immunological markers comprise positive cellular immunostaining for CD1a, CD207, and S100 (1, 2, 4, 11). For challenging diagnostic cases, advanced imaging techniques such as PET-CT can assist in determining the extent of lesions (12, 13). Regarding treatment, local therapy is recommended for LCH patients with single-lesion involvement. Systemic chemotherapy or radiotherapy is preferably recommended for multisystem LCH and multifocal bone involvement (14). Additionally, bisphosphonate treatment for multifocal bone involvement has been proven to effectively alleviate symptoms (15). Prognosis varies due to the complexity of the disease course, with single-system LCH patients showing favorable outcomes under appropriate treatment, while multisystem cases have a 5-year overall survival rate of approximately 90% (2), particularly Hepatic or hematological involvement may indicate poor prognosis (16). The patient’s diagnosis was established based on an iliac bone biopsy, with pathological results indicating Langerhans cell histiocytosis. Immunohistochemical results showed CD1a and S100 protein positivity. Following radiotherapy and regular chemotherapy, the patient’s left hip pain significantly improved, facial erythema resolved, and symptoms of polydipsia, excessive drinking, and polyuria disappeared; cranial MRI showed uniform thickness of the pituitary stalk. PET-CT indicated lesion suppression after treatment.
Since LCH involves multiple systems and clinical manifestations often resemble other diseases, diagnosis is challenging. Particularly in adult patients, LCH lacks clear clinical symptoms for extended periods, leading to relatively severe disease at the time of initial diagnosis. Timely management is crucial, as early identification and treatment can reduce endocrine dysfunction and other potential systemic damage, improving patients’ quality of life (1, 14). Cases that fail to receive timely treatment may develop serious complications, such as bone marrow or pulmonary infiltration, further affecting prognosis (17).
This report presents a case of an adult-onset patient with AVP-D as the initial symptom, accompanied by a pituitary mass lesion. Early differential diagnosis of the pituitary mass etiology was not performed in detail, nor was screening for other systemic involvement conducted. It was not until the patient developed obvious bone pain, facial erythema, and lymphadenopathy that further PET-CT revealed multiple osteolytic lesions and lymph node infiltration. The diagnosis of Langerhans cell histiocytosis was confirmed through pathological biopsy of the iliac bone lesion. Following diagnosis, the facial skin erythema and multiple lymphadenopathies were identified as manifestations of multisystem involvement of this disease. Through timely and regular chemotherapy, the condition was effectively controlled, improving the patient’s quality of life. Due to typical early symptoms and timely diagnosis, this patient received appropriate early treatment regimens, significantly improving prognosis. This study has limitations regarding incomplete clinical data during the early disease onset, but this did not significantly impact the final diagnosis and treatment planning. Additionally, the specific parameters and administration details of the chemotherapy regimen were not sufficiently detailed, with genetic analysis for BRAF not performed, limiting the comprehensive evaluation of treatment efficacy.
Conclusion
In conclusion, LCH poses significant diagnostic and therapeutic challenges due to its unknown etiology and diverse clinical manifestations affecting multiple organ systems, with a rare adult-onset that is prone to misdiagnosis and missed diagnosis. Particularly in adults, the diagnostic and therapeutic challenges are enormous. Definitive diagnosis of LCH relies on pathological examination, combined with endocrine function assessment, imaging, and histopathological testing, providing the accurate foundation for early identification and promising to improve patient diagnostic and therapeutic outcomes and quality of life.
Statements
Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.
Ethics statement
The studies involving humans were approved by Shenzhen Second People’s Hospital Ethical Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
DZ: Writing – original draft. MH: Writing – original draft. LZho: Writing – original draft. YW: Writing – original draft. JL: Writing – original draft. SC: Writing – original draft. LZhe: Writing – original draft. YY: Writing – original draft. HL: Writing – review & editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0508200, 2023ZD0508205); Shenzhen Science and Technology Innovation Commission (JCYJ20210324103012033 and JCYJ20230807115303007); Shenzhen Clinical Research Center for Metabolic Diseases (NO: LCYSSQ20210621092535005), Shenzhen Center for Diabetes Control and Prevention (NO: SZMHC[2020]46); Sanming Project of Medicine in Shenzhen Municipality (SZSM202211026).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2025.1643331/full#supplementary-material
SUPPLEMENTARY FIGURE 1Pelvic MRI in 2019 revealed abnormal osseous changes in the left hip (A), suspicious for malignancy, and multiple enlarged lymph nodes in the para-iliac vascular and inguinal regions (B).
SUPPLEMENTARY FIGURE 2Pre- and post-treatment PET/CT Images. Upper row (A–C): Baseline 18F-FDG PET/CT imaging (2019) acquired prior to chemotherapy initiation revealed mild hypermetabolic activity within multiple lymphadenopathy and osseous lesions of the left iliac bone, consistent with multifocal nodal involvement of Langerhans cell histiocytosis. (A) Coronal PET showing hypermetabolic lesion in the left hip region. (B) Axial CT demonstrating osteolytic destruction of the left acetabulum and pubic bone. (C) Fused PET/CT confirming abnormal glucose metabolism in the left acetabular and pubic region. Lower row (D–F): Post-treatment PET/CT images (2020). Compared to pre-treatment imaging (December 2019), left iliac bone lesions showed no significant changes in size, morphology, or metabolic activity, with multiple residual foci. Lymph node lesions demonstrated reduced metabolic uptake and modest volume reduction, indicating partial suppression of multifocal Langerhans cell histiocytosis following therapy. (D) Coronal PET showing significantly decreased metabolic activity in the left hip lesion. (E) Axial CT revealing sclerotic margins and volume reduction of the lesion in the left acetabulum and pubic bone. (F) Fused PET/CT demonstrating markedly reduced metabolic activity, consistent with post-treatment suppression.
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Summary
Keywords
Langerhans cell histiocytosis, pituitary stalk thickening, arginine vasopressin deficiency, multisystemic involvement, case report
Citation
Zeng D, Hao M, Zhou L, Wang Y, Liu J, Chen S, Zheng L, Yang Y and Li H (2025) Adult onset multisystem Langerhans cell histiocytosis initially presenting with arginine vasopressin deficiency: a case report. Front. Med. 12:1643331. doi: 10.3389/fmed.2025.1643331
Received
08 June 2025
Accepted
23 October 2025
Published
01 December 2025
Volume
12 - 2025
Edited by
Eleni Gavriilaki, Aristotle University of Thessaloniki, Greece
Reviewed by
Ayman Youssef, Vanderbilt University Medical Center, United States
Claus Doberauer, Sankt Franziskus-Hospital, Germany
Updates
Copyright
© 2025 Zeng, Hao, Zhou, Wang, Liu, Chen, Zheng, Yang and Li.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Haiyan Li, haiyanli78@163.com
†These authors have contributed equally to this work
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.