Brain Pathology Case of the Month - March 2010

DIAGNOSIS  Idiopathic disseminated giant cell arteritis (GCA).


GCA is extremely rare in young patients, such that onset above age 49 is one of its American College of Rheumatology (ACR) diagnostic criteria. Due to the patient's atypical presentation, GCA was not suspected and an erythrocyte sedimentation rate and temporal artery sampling were not performed. Although GCA classically involves the temporal artery, it can involve other intracranial and extracranial arteries. The intracranial arteries most commonly affected are those of the vertebrobasilar system, but no histologically-confirmed cases of GCA involving the cerebral arteries have been reported. A rare form of GCA known as disseminated visceral giant cell arteritis (DVGCA) has been reported to involve exclusively the extracranial organs (4), but concurrent intracranial and extracranial involvement in GCA has never been reported in patients under age 50. The few reports describing concurrent involvement were all in older patients with intracranial involvement limited to the vertebrobasilar system (7, 9) or the anterior inferior cerebellar artery (6). In fact, intracranial GCA in patients under age 50 is a rare occurrence in itself; to our knowledge, only two such cases with histological features similar to ours have been described, but both were associated with infectious aetiologies (1, 2). Most of the cases of intracranial GCA, DVGCA and GCA with concurrent involvement (including our case) share the textbook histology of classic GCA. Takayasu arteritis (TA), which can resemble GCA histologically, was also considered since one of its ACR diagnostic criteria is onset below age 40. However, the patient did not demonstrate history or physical examination findings fulfilling other TA criteria and the aorta was uninvolved. Moreover, direct involvement of intracranial arteries by TA is extremely rare, with only a few reports to date (5, 10).

Granulomatous vasculitis of the CNS can be classified as primary angiitis of the CNS (PACNS) or secondary to systemic causes. By definition, PACNS is confined to the CNS and can only be established after ruling out secondary causes. It has been described to occur at any age, is male-predominant and lacks systemic symptoms (3). Histologically, small and medium leptomeningeal and cortical arteries are involved by a necrotizing granulomatous vasculitis. PACNS can also be indistinguishable from amyloid peptide-related angiitis without the appropriate immunohistochemical workup (8). The dissimilar microscopic picture, presence of extracranial arteritis and negative -amyloid staining rule out both diagnoses in our case. A secondary CNS vasculitis was also considered unlikely in our case as extensive workup and past medical history did not reveal any infection, systemic vasculitides, sarcoidosis or drugs.

We report the first occurrence of disseminated GCA with extracranial and anterior, middle and posterior cerebral arterial involvement causing fatal cerebral infarction in an atypical age group.


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Contributed by Zhongchuan Will Chen, MDCM, Sean P Symons, MD, Beverley Young, RTC, Juan M. Bilbao, MD

International Society of Neuropathology