Bing–Neel Syndrome: An Unknown GCA Mimicker

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing–Neel Syndrome (BNS) presenting as biopsy-proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77-year-old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5 days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro-ophthalmologist. She was discharged home on 60 mg of prednisone. At follow up with her neuro-ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized.


Introduction
Giant cell arteritis (GCA) is the most common systemic autoimmune-mediated vasculitis in adults over the age of 50.It is a granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations.It can involve extracranial branches of carotid artery, subclavian, axillary, brachial, aorta, and less commonly iliac and femoral arteries.Temporal artery biopsy remains the gold standard for diagnosis, although its sensitivity is reported to be only 47% [1].It is part of the ACR criteria for diagnosis of GCA along with the "halo sign" on ultrasonography [2].Terefore, mimickers of GCA need to be ruled out prior to making a defnitive diagnosis Bing-Neel Syndrome (BNS) is a rare neurological complication of Waldenström's Macroglobulinemia (WM), characterized by the infltration of lymphoplasmacytic cells into the central nervous system (CNS), afecting approximately 1% of WM patients [3].Tis current report highlights a unique case where BNS presented as biopsy proven GCA, challenging the conventional diagnostic and therapeutic pathway and emphasizing the importance of understanding expected characteristic histopathology in such cases.Patient consent was obtained to publish this report.

Case Presentation
A 77-year-old female with a history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome presented with a 5-day history of progressive vision loss in her left eye.Initial fundoscopic examination revealed "pseudophakic pseudopallor" without optic disc edema.OCT (ocular coherence testing) was remarkable for reduced RNFL (retinal nerve fbre layer) as seen in Figure 1.Intraocular pressure exceeding 40 mmHg, which normalized following administration of acetazolamide.Patient was referred to the Emergency Department by her neuro-ophthalmologist.Patient was started on methylprednisolone 1 g daily for 5 days followed by 60 mg of prednisone.Patient was on this dose.On follow up with neuro-ophthalmology, new dot blot hemorrhages were noted in left eye.Patient was readmitted for pulse dose steroids for 3 days.Her initial labs were remarkable for CRP 23.7 mg/L (<8), ESR 62 mm/hr (0-29).Work up for GCA mimickers revealed quantitative IgM 4000 (52-257), serum immunofxation with IgG and IgM kappa, serum FLC+ with elevated free kappa 34, elevated lambda 4.5, and elevated ratio 7.58 (<1.68).Temporal artery biopsy performed on previous admission showed changes consistent with GCA including mural lymphohistiocytic infammation, mostly adventitia based, with focal involvement of the outer muscle layer and its elastic lamina, while largely sparing the intima, media, and internal elastic lamina, but without giant cells (Figure 2).Given patient's plasma cell dyscrasia and to work up the diferentials for GCA, bone marrow biopsy was requested.It confrmed the diagnosis of WM, with fow cytometry identifying 2% aberrant B cells with a phenotype suggestive of lymphoplasmacytic lymphoma (Figure 3).After discussion with pathology, the temporal artery biopsy was revisited, and additional stains performed.Tese demonstrated a mononuclear cell infltrate composed of small numbers of scattered small-sized lymphoid cells (positive for CD20 and kappa light chain, Figure 4) and rare histiocytes (positive for CD68, Figure 5) without forming a solid mass lesion.Te changes were consistent with small B cell lymphoma involving temporal artery, causing clinical temporal arteritis pattern of injury.Patient was treated with 6 cycles of bendamustine and rituximab which halted the ophthalmic symptoms from worsening.

Discussion
Te diagnosis of GCA is challenging due to its variable presentation and the limitations of temporal artery biopsy.GCA is characterized by transmural infammation, intimal hyperplasia, and fragmentation of elastic lamina [4].Granulomatous infammation consisting of macrophages and CD4 cells is seen in the vessel wall.Even though giant cells have been historically considered pathognomonic for GCA, they are only seen in half of the biopsy results [4].In GCA, CD4 cells play the main role in pathogenesis, which are normally not present in healthy arteries (refer to Table 1).
It is postulated that they permeate adventitia through vasa vasorum [5].CD4 cells are polarised towards T1 and T17 cells in the milieu rather than Treg and T2 [5,6].Tey produce interferon gamma and IL17, respectively, which lead to cytokine production and subsequent neo-angiogenesis and infammation of arterial wall leading to narrowing of vascular lumen.Unlike the granulomatous infammation seen in GCA, BNS is characterized by the infltration of LPCs and plasma cells within the CNS, including the brain, spinal cord, and lepto meninges [7].
Te immunophenotype characteristic of BNS includes positive B cell surface markers (CD19, CD20, CD79a, and CD79b), positive plasma cell markers (CD138 and CD38), and variable CD27, CD52, CD5, and CD3 expression [7].Kappa light chain restriction is usually observed though lambda light chain restriction has been occasionally reported.Hence, immunohistochemical staining of tissues play a crucial role in helping to diagnose direct infltration by the LPC cells.
Manifestations of BNS include gait defcits and balance abnormalities in 48% of the patients [8].It can also present with sensory and motor defcits, headache, altered mental status, and cranial nerve abnormalities [2].Cases of BNS have been reported demonstrating vision changes through involvement of cranial nerves V, VII, VIII, optic nerve, and optic chiasma [9], but none showing vision loss through infltration of temporal artery.Our case is the rare example of such complex manifestations, which is, to the best of our  Case Reports in Rheumatology 3 knowledge, the frst report of mimicking GCA.BNS is typically diagnosed after identifying WM, but in our case, it was the presenting feature which makes this case even more unique [10].It is important to consider BNS along with other complications associated with WM, such as hyperviscosity syndrome and neuropathy related to antimyelin-associated glycoprotein antibodies, hence patients present with atypical symptoms [7].
GCA presents with myriad of nonspecifc symptoms including headache, jaw claudication, weight loss, fatigue, fever, and vison loss.Many symptoms overlap in patients with lymphoma or clonal haematological disorder.Terefore, a high clinical suspicion is required in such cases.In our case, at initial presentation of GCA symptoms, the patient relapsed quickly while being treated with high-dose prednisone which alerted us to consider an alternative diagnosis

Conclusion
Tis case illustrates the diagnostic challenge posed by BNS when it presents with clinical features mimicking GCA.It underscores the importance of considering a broad diferential diagnosis in patients with atypical presentations and highlights the role of immunohistopathological evaluation.Clinicians should adopt an interdisciplinary approach to diagnose and manage such cases as it can infuence treatment considerations and prognosis.

Table 1 :
Comparison of characteristics and fndings of our patient with typical GCA patient.Identifying the correct diagnosis in our patient led to directed therapy and was crucial to maximize the patient's outcome.