ANCA-Negative Granulomatosis of Polyngiitis of Paranasal Sinuses with Cerebellar Involvement

Abstract

Granulomatosis of polyangiitis (GPA) is a multisystem necrotizing vasculitis, which affects small- and medium-sized blood vessels and characterized by frequent involvement of the upper and lower respiratory tract and kidneys. Altough anti-neutrophil cytoplasmic antibodies (ANCA) are higly associated with GPA and play an important role in the pathogenesis of this disease, ANCA positivity is not essential for clinical diagnosis. We describe a patient with ANCA-negative granulamatosis of polyangiitis involving cerebellum, having complaints due to sinusitis.

Introduction

Granulomatosis of polyangiitis (GPA) is a disease which may affect entire body, involving small arteries and veins and is characterized by anti-neutrophil cytoplasmic antibody (ANCA) related autoimmune, idiopathic necrotizing granulomatous vasculitis [1, 2]. The disease may manifest in a limited or systemic form. GPA characteristically involves the lungs, kidneys, head and neck [3]. While the systemic form is always observed with kidney involvement, the self-limited form has no kidney involvement and systemic vasculitis findings and its prognosis is better. Another form of the disease is purely granulomatous disease which primarily involves the ears, nose, throat, eyes or lungs without findings of vasculitis [4].

The limited form of the disease manifests with head and neck symptoms. The number of cases reported in this form is limited. In our case report, we aimed to emphasize the importance of radiological evaluation in a limited GPA case with head and neck involvement in the forefront, which created diagnostic difficulty due to the negative antibody tests and showed central nervous system (CNS) involvement.

Case Presentation

A 26-year-old male patient presented with headache had complaints of nasal obstruction, nasal discharge, fatigue and diplopia. The patient had no family history. He had complaints of sinusitis that became more evident for the last 6 months. Despite repeated medical therapies upon the diagnosis of acute sinusitis, there was no regression in his complaints, and patient’s headache became more severe. Perinasal pain, numbness and diplopia were added to his complaints in 4 days. On the ophthalmological examination, diplopia complaint was ameliorated when he closed a single eye, and his left eye movements were restricted on looking toward medial and lateral directions. The endoscopic examination revealed subcutaneous edema in the right zygomatic area, and middle meatus originated polyps were detected in the right nasal cavity and stage 1 polyps in the left nasal cavity. Intense crusting and pus were observed in sphenoethmoidal recess in the right nasal cavity. On the examination, bilateral middle meatal mucosae had degenerated, polypoid appearance. Patient’s paranasal sinus computer tomography (CT) examination revealed polypoid mucosal thickening in both maxillary, sphenoid, frontal sinuses and at the level of ethmoid cells, and bone erosion in the medial wall of maxillary sinus. There was bony dehiscence at the left lamina papricea (Fig. 1). A soft tissue appearance extending to the medial extraconal area was observed at the level of the left orbital apex. In addition to the intense contrast enhancement in paranasal and orbital areas on magnetic resonance imaging (MRI) (Fig. 2); a mass lesion localized in the left cerebellar hemisphere, extending to the cerebellopontine cistern, which was surrounded by extensive vasogenic edema expanding to adjacent brain stem especially at the level of pons, had a cystic component, and showed marked contrast enhancement (Fig. 3). In laboratory outcomes of the patient, p-ANCA and c-ANCA were negative.

Fig. 1.

On coronal CT scan bilateral maxillary mucosal and bony thickening, soft tissue density in nazal cavity on the left ethmoidal level (arrow), bony destruction at left fovea ethmoidalis, left lamina papyracea and left ethmoidal lamellae (arrow heads) can be seen. Left middle turbinate is indistinguishable due to soft tissue density

Fig. 2.

On coronal contrast enhanced fat sat T1W MR image left sided maxillary, ethmoidal, and middle meatal (arrow) mucosal thickening with significant contrast enhancement can be seen. At the vicinity of bony defects at left sided fovea ethmoidalis and lamina papyracea contrast enhanced soft tissue can be seen at basal anterior cranial fossa ( short arrow) and inside left orbit (arrow head)

Fig. 3.

On axial contrast enhanced fat sat T1W MR image in the left cerebellar hemisphere a mass (arrow) with heterogenous contrast enhancement can be seen

Biopsy outcomes of the frontal sinus and right nasal cavity of the patient resulted in necrotizing, abscessing granulomatous inflammation and widespread vasculitis findings in the middle diameter vessels. In parallel with the other pathological outcomes, excisional biopsy of the lesion in the cerebellum was also interpreted as GPA with abscessing-necrotizing granulomatous reaction. Informed consent was obtained from the patient for the images and publication.

Discussion

Granulomatosis of polyangiitis (GPA) is a disease primarily involving the upper-lower respiratory tracts and kidneys, and is characterized by multisystemic granulomatous vasculitis. It is frequently seen in 20–40 age range. The male to female ratio is 1.5 / 1. Its etiology is not certain but GPA is accepted to be an autoimmune disease. Head and neck involvement is common, and 63% are initially presented with head and neck symptoms. [5] Incidence of renal, pulmonary and systemic involvement increase in the elderly [6].

The majority of patients have nasal and paranasal sinus involvement. The symptoms usually include nasal obstruction, crusting, nasal discharge and bleeding. Systemic symptoms such as fever, night sweats, arthralgia, weight loss, weakness and fatigue may be seen [6]. Ear involvement can occur as an initial symptom at a variable incidence. Nasal and paranasal sinus involvement together with ear involvement has also been reported [7]. Cranial involvement has been reported in 2–8% of cases. CNS involvement may develop as invasion of the extracranial granulomatous lesion, intracranial granuloma formation or CNS vasculitis [8].

GPA requires a multidisciplinary practice as it may progress with multisystemic involvement. Numerous granulomatous and autoimmune diseases such as sarcoidosis, Churg-Strauss disease, polyarteritis nodosa, and microscopic polyangiitis are involved in the differential diagnosis [5].

In addition to clinical findings, GPA has characteristic findings on CT and MRI. CT findings include bone destruction especially in nasal cavity, maxillary sinus and mastoid cellules, granulomatous lesions, sclerosing osteoid and bony thickening affecting especially the mastoid and maxillary sinuses, and mucosal thickening effecting especially the maxillary sinuses [9]. Paranasal sinus mucosal involvement progresses as a chronic nonspecific inflammatory process. When septal involvement results in ulceration, it leads to saddle-nose deformity. In patients without a history of sinonasal surgery, especially sclerotic wall appearance on MRI and/or bone destruction and new bone formation on CT may be helpful in the diagnosis in the cases which clinical signs are obscure and c-ANCA is negative [10].

Biopsy from the suspicious regions and laboratory tests are used in the diagnosis in GPA [5]. The diagnostic criteria described by the American College of Rheumatology for GPA and the presence of ANCA are clinically used for the diagnosis [1]. c-ANCA serologic test is helpful at an early stage and can become positive with progression of the disease in initially negative cases, if left untreated [11]. Immunosuppressive and corticosteroid agents are essential elements of the treatment [5, 6]. Based on the clinical, laboratory and histopathological findings, our patient was considered as ANCA (-) limited GPA. Necrosis, vasculitis and granulomatous inflammation that are characteristic in GPA, can be demonstrated in 16% head and neck biopsies [12]. Therefore, GPA should be considered in the differential diagnosis in the cases where the pathological outcome indicates an atypical inflammatory disease [7].

In conclusion although characteristic CT and MRI findings are helpful in the diagnosis of Granulomatosis of polyangiitis (GPA), ANCA negativity may cause difficulty especially in the head-neck limited form of the disease. Although rarely seen even in the cases with isolated head and neck complaints and negative laboratory tests, considering GPA in the differential diagnosis and multisystemic investigations may prevent possible serious complications by early treatment.

Declarations

Conflict of interest

No conflict of interest was declared by the authors.

Financial Disclosure

The authors declared that this study has received no financial support. No Artificial Intelligence related technology is used during preparation of this manuscript.