Giant Cell Arteritis/Polymyalgia Rheumatica and Atypical Pulmonary Carcinoid Tumor: A Paraneoplastic Syndrome?

Introduction

Giant cell arteritis (GCA) is the most common type of large- and medium-vessel vasculitis in individuals over 50 years of age. While GCA typically affects the extracranial branches of the carotid artery, it can rarely involve the central nervous system, leading to ischemic strokes with significant prognostic implications [1].

Paraneoplastic syndromes, which are systemic manifestations of malignancy triggered by immune or humoral factors (rather than tumor invasion), are extremely rare in vasculitides [2]].

Paraneoplastic vasculitis, a subtype, is typically associated with hematologic cancers [3], and only a small number of cases have linked GCA with malignancies [4,5]. Therefore, given the rarity of this entity, it is necessary to document cases to better understand its pathophysiology.

We report a rare case of ischemic stroke revealing GCA, diagnosed concurrently with pulmonary neuroendocrine carcinoma, suggesting a paraneoplastic syndrome.

Case Report

A 59-year-old man, who was a current smoker with a history of chronic obstructive pulmonary disease and sleep apnea, was admitted in June 2024 for neurological symptoms. He had been experiencing temporal headaches for 3 weeks and balance disturbances for 2 weeks, along with right-hand paresthesia and a transient monocular vision loss episode in the left eye.

Brain MRI revealed a left thalamic ischemic stroke with FLAIR hypersignal in the right temporal artery, with no associated suspicious lesions. CT angiography showed significant stenosis of both vertebral arteries and the left carotid siphon, without evidence of atherosclerosis. He had no cardiovascular risk factors other than smoking.

Examination revealed temporal artery induration and hyperesthesia of the scalp. The patient also had shoulder and hip girdle pain consistent with polymyalgia rheumatica (PMR). C-reactive protein (CRP) was 15 mg/L and erythrocyte sedimentation rate (ESR) was 35 mm/h. Temporal artery Doppler imaging showed a right frontal branch halo sign (Figure 1), while a temporal artery biopsy (TAB) was negative. There was no evidence of an infectious cause, and blood cultures were negative, ruling out endocarditis.

Positron-emission tomography–computed tomography (PET-CT) revealed no vascular hypermetabolism but showed findings suggestive of PMR and a large hypermetabolic mediastinal mass (Figure 2A). Biopsy identified a small-cell neuroendocrine carcinoma of the lung.

The patient received 3 intravenous pulses of 500 mg methylprednisolone, followed by 1 mg/kg/day prednisone. All his symptoms resolved rapidly, and inflammatory markers normalized. Chemotherapy with carboplatin and etoposide was initiated.

In October 2024, a follow-up PET-CT scan showed partial oncologic response and resolution of PMR signs (Figure 2B). Corticosteroid tapering was limited by recurrence of symptoms at below 15 mg/day (increase in headaches, hyperesthesia of the scalp and biological inflammatory markers), prompting the addition of 15 mg methotrexate per week, orally, which failed to reduce corticosteroid requirements after 3 months.

A follow-up cerebral MRI was performed in early December 2024, showing improvement in cranial arterial stenoses with no recurrence of ischemia and no sign of malignancy. There was regression of the hypersignal in the right temporal artery, which retained normal caliber and enhancement, as well as regression of bilateral carotid stenosis.

In February 2025, the patient developed peripheral facial palsy. Brain imaging revealed both supra- and infra-tentorial metastases, along with a right adrenal lesion, indicating cancer progression. Chemotherapy was resumed, along with brain radiotherapy.

As of the latest follow-up, the patient remains corticosteroid-dependent at 20 mg/day, with no active signs of GCA, and is continuing oncological management.

Discussion

This case involved a rare and complex presentation of GCA diagnosed concurrently with a solid tumor; specifically, a small-cell neuroendocrine carcinoma of the lung. The significant hypermetabolism on PET-CT (SUV max 10.9) suggested an atypical carcinoid tumor. The simultaneity of both conditions raises the possibility of a paraneoplastic mechanism. While the literature has explored the association between GCA and malignancies, particularly hematologic ones, links with solid tumors remain uncommon and poorly understood [4,5].

From a diagnostic standpoint, the patient fulfilled the ACR/EULAR 2022 classification criteria for GCA [6], including characteristic clinical symptoms, Doppler findings (halo sign), and PMR features. However, certain atypical aspects of the presentation warranted a thorough differential diagnosis. The negative temporal artery biopsy (TAB), although not uncommon given its limited sensitivity [7], and a relatively low CRP level (15 mg/L), raised the question of alternative diagnoses. However, studies have shown that GCA cases presenting with ischemic complications often exhibit lower CRP levels, possibly due to localized vascular inflammation rather than systemic inflammation [8–11].

Several differential diagnoses needed to be considered. Atherosclerosis was initially contemplated, given the vascular stenoses observed on imaging. However, the absence of significant cardiovascular risk factors – apart from smoking – and the lack of atherosclerotic calcifications or plaques on CT angiography made this diagnosis unlikely. More importantly, the improvement of the vascular stenoses on follow-up imaging after corticosteroid therapy argued strongly against atherosclerosis, which would not be expected to show such reversibility.

An infectious etiology, particularly endocarditis, was also ruled out. Other forms of systemic vasculitis, such as ANCA-associated vasculitis, were excluded based on the absence of renal involvement, pulmonary hemorrhage, or positive autoantibodies. Similarly, primary central nervous system vasculitis seemed improbable, given the presence of extracranial features (scalp hyperesthesia, and temporal artery abnormalities) and symptoms suggestive of polymyalgia rheumatica.

Taken together, these elements supported the diagnosis of GCA despite some atypical findings.

While the concurrent diagnosis of cancer and GCA could be coincidental, there appears to be no increased risk of malignancy after a GCA diagnosis [12]]. The patient’s smoking habit was a major risk factor for the malignancy.

The simultaneous occurrence of GCA and neuroendocrine carcinoma, along with persistent corticosteroid dependency prior to tumor progression, supports a potential paraneoplastic mechanism. Indeed, temporal relationship between tumor diagnosis and rheumatic symptoms is the main critical issue [2]. A syndrome is generally considered either paraneoplastic, when its musculoskeletal manifestations appear simultaneously or within 1 year and in some studies up to 2 years before the detection of the malignancy. Another important argument is that total elimination of the tumor induces complete remission of paraneoplastic symptoms. This could not be achieved in our patient, who did not benefit from optimal treatment due to his underlying pulmonary pathology.

While few associations between GCA and malignancies, particularly hematological cancers, have been documented, paraneoplastic GCA remains exceedingly rare [4,5].

Deshayes et al reported 49 GCA patients with concurrent malignancy. There were more cases of PMR in the GCA with concurrent malignancy group than in the comparative group (55% vs 34% respectively, P<0.01) as well as more men (59% vs 27%, respectively, P<0.001). Solid tumors were present in 67% of the cases (gastrointestinal, pleuropulmonary, genitourinary, and breast cancers), and clonal hematologic disorders were found in 33%. In 14% of the cases, GCA and malignancy were diagnosed simultaneously, with only 2 showing a paraneoplastic course (GCA and cancer relapsed simultaneously). Notably, no increase in cancer mortality was found in this study [4]. Liozon et al identified 7.4% of GCA patients with concomitant cancer, but paraneoplastic syndromes were rare among these cases [5].

Regarding pathophysiology, the mechanisms underlying paraneoplastic vasculitis, including GCA, are not fully elucidated. The immunological hypothesis is plausible: tumors may secrete antigens or induce immune responses that trigger vasculitis via cross-reactivity. Notably, large-vessel vasculitis, including GCA, has been reported as a complication of immune checkpoint inhibitors, reinforcing the idea of T-cell-mediated vascular injury in response to tumor antigens [13]. The neuroendocrine tumor could potentially share antigenic similarities with vascular structures, or secrete pro-inflammatory cytokines, favoring vasculitic phenomena.

Conclusions

This case highlights an exceptionally rare association between giant cell arteritis and a solid tumor, specifically a small-cell neuroendocrine carcinoma of the lung. While GCA has been sporadically reported in association with hematologic malignancies, its occurrence as a paraneoplastic manifestation of solid tumors remains extremely uncommon and poorly characterized. The simultaneous onset of symptoms, along with persistent corticosteroid dependency prior to tumor progression, supports a potential paraneoplastic mechanism, likely of immunological origin. This is in line with emerging evidence linking large-vessel vasculitis to immune dysregulation in oncologic contexts, such as with immune checkpoint inhibitors [13].

Clinically, this case underscores the importance of considering underlying malignancy in patients with atypical features of GCA, particularly when there is low systemic inflammation, negative biopsy, or persistent corticosteroid dependence.

Future studies could help clarify whether certain neoplasms are more likely to trigger vascular inflammation, and how this might influence diagnostic and therapeutic strategies.