Abstract
IgG4 related disease (IgG4-RD) is a fibro-inflammatory disease, with tendency to affect any organ of the body. However, few cases affecting the skull base have been reported in literature. We report one such case in an elderly male, who presented us with a mass lesion in the skull base that mimicked nasopharyngeal malignancy. On thorough clinical history, examination, and investigations, IgG4 Related disease was diagnosed and treatment was started for it. The patient responded well to the treatment and is on follow up.
Keywords: IgG4 related disease, Skullbase, Nasophryngeal malignancy, Fibro-inflammatory disease
Introduction
IgG4 related disease is an immune mediated fibro-inflammatory disease, with tendency to form tumefactive lesions in any organ in a synchronous or metachronous fashion [1]. Various known diseases like Mikulicz’s disease, autoimmune pancreatitis to name a few, have been clustered under IgG4 Related disease spectrum [2]. Skull base involvement of IgG4-RD is a rare entity [3]. The relapsing and remitting nature of the disease needs early recognition and proper treatment of the same [2]. We report a case of IgG4-RD of the skull base that mimicked nasopharyngeal malignancy.
Case History
75 year old male, with no known comorbidities presented with sudden onset left sided hearing loss 1 year ago and was diagnosed with moderate to severe sensorineural hearing loss. He had remarkable improvement after treatment with steroids, however developed persistent left aural block and was treated as otitis media with effusion. He subsequently developed a left sided headache and was investigated by a neurologist with CT scan of the brain which was reported to be normal and was diagnosed with migraine and treated with Gabapentin.
Patient was apparently asymptomatic for a period of 2 months, following which he developed sudden onset hoarseness of voice and nasal regurgitation with persistent left ear block and was diagnosed with Left vocal cord and soft palate palsy. CT Brain with PNS showed a mass lesion in the left side of nasopharynx and involvement of an extracranial portion of the left vagus and left hypoglossal nerve. Diagnostic nasal endoscopy revealed a smooth bulge in the left fossa of Rosenmuller and otoendoscopy showed secretory otitis media in the left ear. Patient then underwent Endoscopic nasopharyngeal biopsy with left ear myringotomy and grommet insertion and histopathological examination showed chronic inflammation with lymphoplasmacytic infiltration. Patient’s vocal cord palsy recovered spontaneously. Due to a strong suspicion of malignancy, PET CT was done which showed 2.2 cm metabolically active mass lesion in the left Nasopharynx, with left level I and IIa nodes. A repeat punch biopsy was done which revealed mononuclear inflammatory infiltrate.
Patient was subsequently asymptomatic for another 2 months following which he developed Seizure disorder and was started on anti-epileptics. After 3 months, the patient developed a new onset headache, right aural block, tinnitus and hard of hearing and was referred to our center for further management. A repeat PET CT revealed a mass lesion in the nasopharynx, bilateral Level IB and Level II lymph nodes and circumferential wall thickening in the right carotid bulb causing luminal narrowing. Neurologist opinion was obtained in view of the seizure disorder and MRI brain and CSF analysis were done. MRI Brain revealed pachymeningeal thickening in bilateral cranial fossa and circumferential wall thickening and luminal narrowing in the right carotid bulb (Fig. 1a, b) and CSF analysis showed increased proteins with other normal parameters.
Fig. 1.
a T2- MRI brain shows pachymeningeal hypertrophy b T1- MRI showing circumferential wall thickening in the right carotid bulb causing luminal narrowing
Patient then underwent Endoscopic biopsy of nasopharyngeal mass with Right cervical lymph node biopsy and initial histopathological examination revealed fibro-inflammatory lesion with sclerotic stroma, and lymphoplasmacytic infiltrates with no evidence of malignancy (Fig. 2). Immediate postoperative period, patient developed slurring of speech which reverted back to normalcy immediately.
Fig. 2.
High power view, H&E, showing inflammatory component composed of dense infiltration of lymphocytes and plasma cells arranged in aggregates and sheets amidst the spindle cells (Blue arrow- indicates plasma cells)
In view of chronic illness with relapsing cranial nerve palsies, histopathological evidence of a fibro-inflammatory lesion with lymphocytic infiltration, radiological evidence of vascular involvement and pachymeningeal thickening, the case was discussed in multidisciplinary meet and a diagnosis of IgG4 related disease was suspected and further investigations were done. Serum IgG4 levels were found to be very high (4.480 g/L, normal upto 2 g/L) with elevated ESR, CRP and RF in low titer. IHC staining for IgG4 Related disease was done which revealed 10–15 IgG4 positive plasma cells per high power field and IgG4 to IgG ratio was > 40% indicative of definitive IgG4 related disease [4] (Fig. 3). Patient was referred to the Rheumatologist and started on steroids. The patient is in remission and in regular follow up for the same.
Fig. 3.
IgG4 plasma cells in IHC staining
Discussion
IgG4-RD is an upcoming clinical entity with a propensity for multi organ involvement [5]. The characteristic histopathological features of IgG4 related disease for diagnosis consist of storiform fibrosis, obliterative phlebitis and lymphoplasmacytic infiltration with IgG4 cell predominance [5].
IgG4- RD of head and neck is rarely reported in literature, with cases being reported on the involvement of Lacrimal and salivary glands [6]. Mean age of presentation is around 60 to 80 years of age with increased predilection in males [5]. The proposed pathogenic mechanisms include a trigger due to either allergens, or common pathogens, which act as self-antigens. The subsequent recruitment of T- helper cells and T-regulatory cells lead to the release of various pro-inflammatory and pro-fibrotic cytokines which results in the characteristic storiform fibrosis and a vicious cycle of chronic inflammation [7].
Radiological features of IgG4- RD include homogenous enhancement seen in CT and low to intermediate intensity in T2 weighted image on MRI, with contrast enhancement seen in T1 weighted images. 18 FDG PET is a very reliable imaging modality as it helps in highlighting inflammatory diseases and in discriminating from malignancy [8]. PET is also helpful in assessing the disease progression and the response to treatment [8]. There have also been suggestions to use Gallium SPECT/CT in diagnosis of IgG4- RD with SPECT/CT being superior in differentiating between inflammatory pseudotumor and IgG4-RD [9].
Serological diagnosis of IgG4 RD consists of demonstration of elevated IgG4 levels. However, it is not elevated in all patients, but can be used as a diagnostic marker in cases with high index of clinical suspicion. ANA & RF are found in low titre, with C- reactive protein and ESR being elevated [5]. Histopathology is the gold standard for diagnosis, with classical patterns of storiform fibrosis, obliterative phlebitis and plasmacytic infiltration. IgG4/IgG ratio > 40% and IgG4 cell infiltration > 10 per HPF suggest towards a diagnosis of definitive IgG4 related disease [4].
Corticosteroids form the first line of management with 97–100% response in disease remission. Steroid sparing agents like Azathioprine, Mycophenolate Mofetil, Methotrexate are used in steroid refractory cases [5]. Rituximab, an anti CD-20 antibody is indicated for steroid refractory cases and leads to IgG4 specific reduction. Surgical excision is recommended in obtaining representative samples for tissue diagnosis and in disease causing pressure symptoms especially in orbit and mandible. IgG4 related disease has a prognosis rate of 90% in steroid responsive cases, however relapse is a very common feature and requires high vigilance [10].
Conclusion
IgG4 Related disease of head and neck is an upcoming clinical entity which needs a lot of vigilance and clinical suspicion for diagnosis. Early diagnosis helps in achieving almost complete remission and prevents multi-organ dissemination. It should be borne in mind as a differential diagnosis especially in patients with suspected malignancies but repetitive negative biopsies.
Author Contributions
SN: Substantial contributions to the conception or design of the work, revising it critically for important intellectual content, analysis and interpretation of data for the work and drafting the work and final approval of the version to be published.
KR, PV, SK, GA, UK, SS: Revising the content critically for important intellectual content and final approval of the version to be published.
KR: Substantial contributions to the acquisition of data for the work.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no Conflict of interest.
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Footnotes
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