Abstract

BackgroundIntradural extramedullary spinal eosinophilic granuloma is a very unusual manifestation of Langerhans Cell Histiocytosis (LCH) that is typically misdiagnosed due to its nonspecific clinical and radiological features.

Case DescriptionWe report a case of a 22-year-old female patient who presented with acute onset paraplegia. The magnetic resonance imaging was initially suggestive of tuberculoma, which is prevalent in tuberculosis-endemic regions. Intraoperative findings and histopathology, however, established the diagnosis of LCH. The lesion was intradural, and CD1a and S-100 protein staining demonstrated classic Langerhans cells.

ConclusionThe paper stresses the need for a multidisciplinary team in the proper diagnosis and handling of spinal LCH. Further research is needed to develop optimal management protocols for this rare condition.

Keywords: Histopathological diagnosis, Intradural extramedullary eosinophilic granuloma, Langerhans cell histiocytosis, Spinal lesion, Tuberculoma

INTRODUCTION

Intradural extramedullary spinal eosinophilic granuloma is a rare condition with difficult diagnostic strategies. The lesions may be mistaken for other pathology, for example, tuberculomas, in regions of the world where tuberculosis is endemic. Langerhans cell histiocytosis (LCH) is an abnormal proliferation of Langerhans cells, and these cells are specialized dendritic cells that are normally found in the epidermis. LCH can have a broad spectrum of presentations, from single lesions to multisystem disease, and although predominantly a disease of children, it does affect adults. Spinal involvement and an intradural extramedullary location are exceedingly unusual and may simulate other pathologies both clinically and radiologically.[ 9 , 13 , 16 ] The uncommon nature and nonspecific presentation of spinal LCH often lead to delayed diagnosis and treatment. Patients may present with a broad range of symptoms, including back pain, neurological deficits, and features suggestive of spinal cord compression. Imaging modalities like magnetic resonance imaging (MRI) are significant in recognizing these lesions, but definitive diagnosis typically requires histopathological examination. The differential diagnosis for spinal lesions would include infection (e.g., tuberculosis), inflammatory processes, and neoplastic disease.[ 18 , 24 , 25 ] The recent literature has emphasized the importance of early diagnosis and treatment in improving patient outcomes in LCH. Newer imaging techniques, including diffusion-weighted MRI and positron emission tomography-computed tomography, have been useful in differentiating LCH from other spinal pathologies. Furthermore, multidisciplinary input from radiologists, pathologists, and oncologists are important in the management of such difficult cases. Early intervention can prevent crippling neurological disability and improve the quality of life for such patients.[ 29 ]

In this report, we have a case of a 22-year-old female with intradural extramedullary eosinophilic granuloma of the spine. This case highlights the importance of LCH in the differential diagnoses for spinal lesions and re-emphasizes histopathology in arriving at a proper diagnosis.

CASE DESCRIPTION

A 22-year-old female presented with 1 week of constipation, followed by paresthesia in both lower extremities that progressed to paraparesis and then paraplegia over 5 days. The patient also reported a disturbed sensory level to the umbilicus. Severe neurological deficits were present on initial physical examination, and imaging studies were promptly ordered.

MRI of the spine was performed, which revealed a lesion at the T9 level. The lesion extended from the extradural space to the posterior bony elements of the lamina and spinous process, with further extension into the paraspinal muscles. On T2-weighted MRI, the lesion appeared hypointense, raising suspicion for a granulomatous process [ Figures 1a - d and 2 ]. The pattern of enhancement was ring-like, which is often suggestive of an infectious etiology, such as tuberculosis, which is endemic in Iraq. However, the differential diagnosis also included other possibilities, such as neoplastic and inflammatory conditions.

Figure 1:

(a) Preoperative (Preop) Sag-short tau inversion recovery. Shows the mass at the T9 level, with suspicion of extradural as there is an involvement of the spinous process and paraspinal soft tissues. (b) Preop Sag-T2 shows a mass in the T9, which is an intradural extramedullary lesion. (c) Preop Sag-T1-postcontrast shows the enhancement of the mass in a heterogeneous pattern with the enhancement of the spinous process and surrounding muscles up to the fascia. (d) Preop. The pattern of enhancement is ring enhancing, raising suspicion of infection and, most likely, TB, as it is endemic in our country.

Figure 2:

Preop axial-T2 showing the mass is hypointense and left-sided, displacing the spinal cord to the right.

The patient underwent emergency surgery due to the rapid progression of neurological symptoms. Intraoperatively, the lesion was found to be intradural rather than extradural, as initially suspected. The mass was noted to be firm and fibrous with clear demarcation from the surrounding spinal cord. Multiple biopsies were taken, and the lesion was totally resected to decompress the spinal cord [ Figures 3a - e ]. Postsurgery, she was referred to hematology for continued treatment.

Figure 3:

(a) Intraoperative image demonstrating the tumor (black arrows) compressing and displacing the spinal roots. (b) Intraoperative image showing meticulous dissection and preservation of an intact spinal root (green and blue arrows). (c) Intraoperative image revealing a fibrous granuloma that was initially biopsied for pathological evaluation. (d) Intraoperative image depicting the gross total resection of the lesion, ensuring decompression of the spinal cord.

Histopathological examination of the resected tissue revealed a proliferation of Langerhans cells with characteristic grooved, coffee bean-shaped nuclei [ Figure 4a ]. Immunohistochemical staining was positive for S-100 protein [ Figure 4b ] and CD1a [ Figure 4c ], confirming the diagnosis of LCH. The lesional cells were negative for glial fibrillary acidic protein [ Figure 4d ], excluding neural tumors, and negative for epithelial membrane antigen [ Figure 4e ], excluding metastatic tumors in the differential diagnosis. The patient experienced complete resolution of paresthesia on the 1^st postoperative day and regained sphincter control by the end of the 1^st week. By 1 month, she could stand and walk, and by 3 months, she was walking normally.

Figure 4:

(a) Hematoxylin and eosin (H&E) staining showing an infiltrate of eosinophils mixed with histiocytic cells. A Langerhans cell with a characteristic grooved, coffee-bean-shaped nucleus is indicated by the arrow, supporting the diagnosis of Langerhans cell histiocytosis (LCH), ×400 (Arrow). (b) Immunohistochemistry (IHC) demonstrating strong diffuse positivity for S-100 protein in lesional cells, confirming the presence of Langerhans cells, ×200. (c) CD1a IHC stain showing strong membrane positivity in lesional cells, a hallmark feature of LCH, ×200. (d) Glial fibrillary acidic protein (GFAP) IHC stain demonstrating negative staining, excluding glial-derived tumors, ×200. (e) Epithelial membrane antigen (EMA) IHC stain showing negative staining, helping to exclude metastatic carcinoma from the differential diagnosis, ×200.

Systematic review

Methodology

A systematic review was conducted to evaluate the management and outcomes of spinal (LCH ), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.[ 36 ] A comprehensive literature search was performed using PubMed and Scopus, employing the search terms (“Langerhans Cell Histiocytosis” OR “LCH”) AND (“spinal” OR “vertebral” OR “extramedullary”). The initial search yielded 197 articles from PubMed and 315 articles from Scopus, totaling 512 studies. After removing duplicates and resolving discrepancies, 340 studies remained for screening. Eligible studies were clinical studies (case reports, case series, retrospective or prospective studies) that presented full details of patient presentation, diagnosis, treatment, and follow-up. Only English language articles were included, and there were no date restrictions. Nonclinical studies, abstracts, reviews, animal studies, and studies with no detailed management information were excluded. Following an initial title and abstract screening, 81 studies were selected for full-text review. The final selection was made after applying quality assessment tools, including the CARE guidelines for case reports and the ROBINS-I tool for observational studies [ Tables 1 and 2 ].[ 17 , 49 ] Key variables, including patient demographics, lesion location, clinical presentation, treatment approach, neurological outcomes, recurrence, and follow-up duration, were systematically extracted and analyzed.

Table 1:

Quality assessment of case reports using Case Report (CARE) guidelines.

Table 2:

ROBINS-I assessment of the included studies.

A qualitative synthesis was performed to compare different treatment modalities and their effectiveness in spinal LCH management.

RESULTS

A total of 46 studies were included [ Table 3 ].[ 1 - 8 , 10 - 12 , 15 , 16 , 19 - 23 , 26 - 28 , 30 - 35 , 37 - 43 , 45 - 48 , 50 - 53 , 55 - 57 ] The patient population ranged from infancy to adulthood, with the youngest reported case being 11 months old and the oldest 71 years old. The majority of the cases were pediatric. Males were more frequently affected. The geographical distribution of cases included reports from China, the USA, Canada, South Korea, and several European nations. The majority of studies were case reports, with few retrospective series offering more comprehensive data on treatment outcomes. Patients presented with a broad range of symptoms, predominantly local pain, and restricted spinal mobility. Neurological deficits were also present, ranging from mild radiculopathy to quadriparesis. The other prominent symptoms included torticollis, abnormal gait, and polyuria-polydipsia syndrome in one patient with systemic involvement. The duration of symptoms before diagnosis was also extremely variable, ranging from acute over days to chronic over several years. Osteolytic vertebral lesions with variable degrees of vertebral plana and soft tissue extension characterized spinal involvement. Xu et al. (2018)[ 56 ] reported that multifocal disease was present in 11.8% of cases, with the cervical spine being the most commonly affected region (63.7%). Other affected regions included the thoracic (21.9%) and lumbar spine (13%), while sacral involvement was rare (1.4%). The majority of the patients presented with single vertebral involvement. Vertebral body collapse was a typical feature, as seen in the Xu et al.[ 56 ] study and Nakamura et al.[ 38 ] study, with extensive cases resulting in kyphotic deformities. MRI findings consistently showed hyperintense lesions on T2-weighted imaging with soft tissue extension in a small number of cases.

Table 3:

Study characteristics and patient data.

Management strategies varied depending on disease severity, neurological involvement, and lesion stability [ Table 4 ].[ 1 - 8 , 10 - 12 , 15 , 16 , 19 - 23 , 26 - 28 , 30 - 35 , 37 - 43 , 45 - 48 , 50 - 53 , 55 - 57 ] Many cases were successfully managed conservatively with immobilization, corticosteroids, or chemotherapy, particularly vinblastine-based regimens, which led to complete vertebral reconstitution in pediatric cases. Long-term follow-up showed minimal recurrence in nonsurgical cases. Surgical intervention was primarily reserved for cases with instability or neurological deficits. Surgical procedures such as posterior instrumentation and corpectomy were performed in instances of extreme collapse of the vertebrae or spinal cord compression, with often excellent neurological recovery. Tumor resection and stabilization were employed in a couple of instances with very large vertebral destruction. Adjuvant therapy in the form of radiotherapy for residual disease and LCH-II/LCH-III chemotherapy protocols were beneficial in instances with progressive or multifocal disease. Most patients, especially those treated conservatively, exhibited full neurological recovery. Spinal deformities requiring stabilization occurred in some cases, but recurrence rates were low. No perioperative mortality was reported. Follow-up ranged from months to over a decade, with spontaneous vertebral reconstitution frequently observed in pediatric cases. Patients undergoing surgery for unstable lesions showed sustained neurological improvement with minimal risk of recurrence.

Table 4:

Treatment outcomes and complications.

DISCUSSION

Intradural Extramedullary eosinophilic granuloma of the spine is an extremely rare manifestation of LCH, with very few cases reported in the literature. LCH is a clonal proliferative disorder of Langerhans cells, which are specialized dendritic cells involved in antigen presentation. The disease can present in a variety of forms, ranging from isolated bone lesions to multisystem involvement, and can affect both pediatric and adult populations.[ 16 , 29 , 48 ]

The diagnosis of spinal LCH can be challenging due to its nonspecific clinical and radiological features. Patients may present with symptoms of spinal cord compression, such as pain, paresthesia, and motor deficits, which can rapidly progress if not promptly addressed. MRI is the imaging modality of choice for evaluating spinal lesions, but the definitive diagnosis often requires histopathological confirmation. The characteristic histological features of LCH include the presence of Langerhans cells with grooved, coffee bean-shaped nuclei and positive immunohistochemical staining for CD1a and S-100 protein.[ 18 , 25 , 54 ]

In the present case, the initial suspicion was tuberculoma, a common differential diagnosis in tuberculosis-endemic areas. The ring-enhancing pattern on MRI was more toward an infectious etiology. However, the acute onset of neurological symptoms required surgical intervention and histopathological analysis, which ultimately diagnosed LCH. This emphasizes the importance of considering LCH in the differential diagnosis of spinal lesions, even in endemic areas for other diseases.[ 9 , 13 ] Our review of spinal LCH cases demonstrates that its radiological features can be highly variable, often mimicking infectious or neoplastic conditions. Xu et al. (2017) [ 56 ] reported vertebral plana, osteolytic lesions, and paravertebral soft tissue extension as common findings, while Jiang et al.(2010)[ 27 ] reported paravertebral involvement in up to 40% of cases. This was consistent with the MRI findings in our case, in which the lesion extended from the extradural space to the posterior bony elements and paraspinal muscles. The ring-like enhancement, though suggestive of infection, has been reported in LCH as well, emphasizing the need for histopathological confirmation.

Treatment of spinal LCH typically involves surgical resection for decompression of the spinal cord and symptomatic relief. In cases where complete resection is not possible, adjuvant therapy in the form of radiotherapy or chemotherapy may be employed. The prognosis of spinal LCH varies depending on the extent of the disease and the success of the initial treatment. Early diagnosis and intervention are crucial for improving outcomes and preventing permanent neurological deficits.[ 24 , 44 ] Although surgical decompression is often recommended, our findings indicate that many cases of spinal LCH can be effectively managed conservatively with corticosteroids and vinblastine-based chemotherapy.[ 32 , 56 ] Complete vertebral reconstitution was frequently observed, particularly in pediatric cases. However, surgery was necessary in cases presenting with instability or progressive neurological deterioration.[ 37 , 48 ] In such instances, posterior instrumentation and corpectomy were commonly performed, with excellent postoperative neurological recovery.[ 14 , 47 ] Long-term follow-up of our reviewed cases revealed favorable outcomes, with most patients achieving full neurological recovery and low recurrence rates. Spontaneous vertebral reconstitution was particularly observed in pediatric patients managed conservatively.[ 32 , 38 ] Surgical intervention for unstable lesions resulted in sustained neurological improvement without significant long-term complications.[ 14 , 37 ]

In conclusion, this case highlights the diagnostic challenges and importance of histopathological evaluation in cases of spinal lesions with atypical presentations. It also emphasizes the need for a high index of suspicion for LCH, particularly in regions where other granulomatous diseases are prevalent. Further research and case studies are needed to understand better the optimal management strategies and long-term outcomes for patients with spinal LCH.

CONCLUSION

The case report highlights the importance of considering LCH in diagnosing spinal lesions, especially in tuberculosis-endemic areas. Rapid neurological deterioration necessitated immediate surgical intervention, highlighting the role of biopsy in uncertain cases. A multidisciplinary approach is needed, involving neurosurgeons, radiologists, pathologists, and oncologists, for better understanding and management of this rare condition.

Ethical approval

Institutional Review Board approval is not required.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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