Giant cell myositis confined to the lower extremities without associated thymoma or myasthenia gravis: a case report

Giant Cell Myositis (GCMm) is an exceptionally rare inflammatory myopathy, historically reported in association with Myasthenia Gravis (MG), Thymoma, or Giant Cell Myocarditis (GCMc). The prognosis is often dictated by the frequently co-occurring, highly lethal GCMc. We describe the case of a 31-year-old male presenting with a three-month history of progressive, painful, and diffuse pseudohypertrophy of the lower extremities. Laboratory findings, including normal creatine kinase, were largely unremarkable, but a muscle biopsy demonstrated the pathognomonic infiltration by multinucleated giant cells. Extensive work-up, including cardiac magnetic resonance imaging and a full autoantibody panel, showed no evidence of cardiac, ocular, or associated thymic disease or MG. This is, to our knowledge, the first reported case of GCMm presenting as an isolated skeletal muscle disease without any known associated systemic conditions, underscoring the importance of considering GCMm in the differential diagnosis for unexplained limb pseudohypertrophy, even in the absence of typical comorbidities or profound muscle weakness.

Introduction

Giant Cell Myositis (GCMm) is an extremely uncommon inflammatory myopathy, characterized by the hallmark histological finding of infiltration of skeletal muscle fibers by multinucleated giant cells ^1,2. Since its initial description by Giordano and Haymond in 1944, the majority of reported cases have exhibited strong clinical and pathological associations with other autoimmune conditions, most notably Myasthenia Gravis (MG), Thymoma, or concomitant and often fatal Giant Cell Myocarditis (GCMc) ³. Due to the high lethality of GCMc, which approaches a 1-year mortality of 70% without aggressive treatment, research and case reports have primarily focused on patients with cardiac involvement ⁴. Consequently, little is known about the natural history, spectrum of presentation, or optimal treatment response of GCMm when it is restricted to skeletal muscle. We present a unique case of GCMm isolated to the lower extremities in a young patient, completely devoid of any associated cardiac, ocular, thymic, or myasthenic involvement, thereby expanding the known clinical phenotype of this rare disease.

Clinical case

A previously healthy 31-year-old male presented with a 3-month history of progressive, diffuse pain and noticeable enlargement of his lower extremities, alongside constitutional symptoms including weight loss and night sweats. Physical examination revealed prominent, diffuse pseudohypertrophy of the lower limbs, though a formal assessment of muscle strength was within normal limits.

Initial laboratory screening was largely non-contributory, showing normal creatine kinase (CK) levels and a negative autoantibody panel. Magnetic resonance imaging (MRI) of the lower extremities revealed diffuse myositis involving the muscle, fascia, and subcutaneous tissue. A subsequent Fluorodeoxyglucose F-18 Positron Emission Tomography-Computed Tomography scan showed increased metabolic uptake in these affected areas, with a maximum Standardized Uptake Value (SUVmax) of 6.93.

A muscle biopsy ultimately provided the definitive diagnosis of GCMm, disclosing the pathognomonic diffuse infiltration of giant, multinuclear cells.

Given the strong association between GCMm and potentially lethal myocardial inflammation, a thorough cardiac evaluation was performed. The patient’s ultrasensitive troponin-I was mildly elevated at 33 pg/mL (reference range < 14 pg/mL), and an electrocardiogram (ECG) showed a left anterior fascicular block. However, both a formal echocardiogram and a gadolinium-enhanced cardiac magnetic resonance imaging (CMR) were unremarkable for active myocarditis or structural heart disease. Furthermore, no clinical or radiological evidence of MG or an underlying Thymoma was found.

The patient was initiated on a therapeutic regimen consisting of pulse corticosteroid therapy, completing a total of 1.5 g of intravenous methylprednisolone, followed by oral immunosuppression with prednisone 60 mg once daily (1 mg/kg/day) in combination with methotrexate. Prednisone was gradually tapered to 30 mg by two months and to 10 mg by one year. At the six-month follow-up, the patient reported substantial symptomatic improvement, and lower extremities MRI demonstrated a marked reduction in inflammatory findings. By the one-year evaluation, surveillance cardiac studies showed no progression of the previously noted minor ECG abnormalities or troponin elevation, and no new associated systemic conditions were identified.

Discussion

GCMm is a notoriously rare inflammatory myopathy, with a literature review identifying only about 15 reported cases since the initial description in 1944 ^3,4. A critical characteristic of nearly all these historical cases is their co-manifestation with MG, Thymoma, or GCMc ⁵. The case we describe is notable as it represents a highly unusual presentation of GCMm: an isolated skeletal myopathy predominantly involving the lower limbs with clinical pseudohypertrophy, in the complete absence of the classic associated conditions (MG/Thymoma or GCMc). This case highlights several important clinical points.

First, this report expands the phenotype of GCMm, demonstrating that it can present as an isolated, non-syndromic inflammatory myopathy. This challenges the notion that the disease is obligatorily linked to MG/Thymoma or GCMc. Second, the diagnosis was challenging because the presentation was dominated by pseudohypertrophy and pain, rather than the typical proximal muscle weakness often described in myositis (4). Crucially, the normal CK level further obscured the diagnosis. Although literature exists describing CK elevation in up to 90% of GCM cases, most of those cases are associated with Myasthenia Gravis/Thymoma or cardiac involvement, which could explain the elevation, and in turn its normality in this case. This emphasizes that a myopathy with giant cell pathology should be considered even with normal CK, particularly in cases of unexplained limb enlargement with inflammatory features on imaging. Third, the absence of GCMc, confirmed by cardiac magnetic resonance imaging (CMR), suggests that this isolated form may carry a more favorable prognosis than the highly lethal systemic forms ⁵. This reinforces the necessity of aggressive cardiac screening in all GCMm patients, even if clinically asymptomatic.

Prompt diagnosis via muscle biopsy and the initiation of immunosuppressive therapy (pulse steroids and methotrexate) led to marked symptomatic improvement in our patient. This case serves as a vital addition to the sparse literature, broadening the known clinical spectrum of GCMm and guiding clinicians to consider this diagnosis in unexplained limb pseudohypertrophy, even when common associated conditions are absent.

Acknowledgements

The authors have no acknowledgements to declare.

Funding

This study received no specific funding.

Conflicts of interest statement

The authors declare that they have no conflicts of interest related to this article.

Author Contribution

E.E.: Conceptualization, clinical management, data analysis, manuscript writing (original draft preparation, review, and editing). F.A.: Clinical management, data acquisition, manuscript writing (review and editing).

Ethical Consideration

The patient provided written informed consent for the publication of this case report and any accompanying images.

History

Received: October 22, 2025

Accepted: December 2, 2025

Figures and tables

Figure 1. A) Diffuse pseudohypertrophy of lower extremities. B) Magnetic Resonance (STIR, coronal view) showing marked inflammation of muscle, fascia and subcutaneous tissue. C PET-CT (fusion, axial view) of lower extremities demonstrating diffuse hypermetabolism of muscle and fascia.