Transcript 46 y/o M with head trauma

Imaging spectrum of IgG4
RELATED disease involving
head and neck region
MARYAM GUL, MD
AMMAR CHAUDHRY, MD
SUNEEL MOVVA, MD
STEVEN CARSONS, MD
LUBASLOV WOROCH, MD
Presentation: eEdE-33
Disclosures

No relevant disclosures
Objectives

Review clinicopathologic spectrum of IgG4related disease

Discuss spectrum of imaging and pathologic findings in IgG4related
disease in the head and neck region

Review mimics with emphasis on key findings differentiating these entities

Treatment, prognosis and followup recommendations for IgG4 syndrome
Introduction

IgG4-related disease is an increasingly recognized syndrome of unknown
etiology with specific pathologic, serologic and clinical features

Common shared features include mass-like swelling of the effected
organ(s) with lymphoplasmacytic infiltrate enriched in IgG4-positive plasma
cells

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Variable degree of fibrosis is seen that has a characterisitic “storiform” pattern

Serum IgG4 titers are elevated in sixty-to-seventy percent of patients
Inicidence and prevalence are unknown given rarity and different descriptions

Age: all ages involved; most commonly between 59-68 y/o
Introduction

Inflammatory pseudotumor has been applied to a heterogeneous group of mass-forming
lesions in various anatomic regions and organs characterized by a proliferation of fibroblasts
or myofibroblasts admixed with an inflammatory infiltrate composed mainly of lymphocytes
and plasma cells.


sometimes used interchangeably with plasma cell granuloma and inflammatory myofibroblastic
tumor (IMT), which leads to confusion both clinically and in the literature
Unlike IMT, which is considered neoplastic with ALK-1 expression as a distinguishing feature,
many inflammatory pseudotumors of the orbit and central nervous system likely represent a
manifestation of inflammatory fibrosclerosis or idiopathic sclerosing inflammation.

Analogous to retroperitoneal fibrosis, sclerosing mediastinitis, sclerosing cholangitis, Riedel sclerosing
thyroidits and sclerosing pancreatitis, which have been linked to IgG4 sclerosing diseases

IgG4 staining in inflammatory mass lesions has been proposed as a marker of lesions with an
autoimmune or primary inflammatory etiology
Pathogenesis

Etiology: unknown, likely autoimmune trigerred molecular mimicry from
certain infectious agents


Specific auto-antigen has not been identified
IgG4- titers are not specific

Can be elevated in other diseases like Castleman’s disease, Churg-Strauss
syndrome, etc
Clinical Manifestations

Mikulicz’s disease (dacryoadenitis and sialadenitis)

Inflammatory orbital pseudotumor
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Chronic Sclerosing dacroadenitis
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IgG4-related Otic disease
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IgG4-related hypophysitis
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IgG4-related pachymeningitis
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Riedel’s thyroiditis
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Interstitial pneumonitis
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Autoimmune pancreatitis
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Intersitital nephritis
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IgG4-related sclerosing cholangitis
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Ormond’s disease (retroperitoneal fibrosis)
Differential Diagnosis

Lymphoproliferative conditions
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Lymphoid hyperplasia
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Lymphoma (non-Hodgkin’s)

Must exclude HIV

Sarcoidosis

Wegner’s granulomatosis
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Infectious (tuberculosis, histoplasmosis)
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Metastasis (melanoma, breast, lung)
Diagnosis

Challenge in the diagnosis of inflammatory central nervous system and Head & Neck
lesions is their relative rarity

IgG4-related disease should be considered in patients with intra- or extracranial
inflammatory mass lesions

Biopsy should be performed to confirm the diagnosis

Standard H&E evaluation

Immunohistochemistry offers a complimentary approach for characterization of intracranial
inflammatory mass

Lymphoproliferative disorders should be excluded through flow cytometry, immunohistochemistry,
and gene rearrangement studies.
Treatment


Systemic steroids are first-line therapy

80-85% of patients respond
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Dramatic and rapid improvement typical
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Recurrence after initial response in 25-40%
Second-line therapies for nonresponsive or refractory cases or when steroids contraindicated

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Low-dose radiotherapy
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Long-term control rates 50% or higher
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20-30 Gy, 2 Gy per fraction
Cytotoxic chemotherapy
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Antimetabolite drugs (e.g., methotrexate, azathioprine)
Other immunosuppressive agents
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Cyclosporin; monoclonal antibodies (e.g., against CD20, TNα)
Prognosis
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Intermittent disease more likely in younger patients
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5-10% resolve spontaneously
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Pattern of involvement affects prognosis
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Recurrence more likely with multifocal disease
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Poor outcome more likely in diffuse disease
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Systemic association in up to half with lacrimal disease, particularly if chronic or tumefactive
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Chronic sclerosing disease not as responsive, but therapy may slow progression

Exclude additional organ involvement
Case presentation
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Chief Complaint: Feeling of disequilibrium and hearing loss
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History of Present Illness: 48 year old male presented with intermittent ear
heaviness and hearing loss in both ears for approximately 2 years. He was told
he had otosclerosis leading to conductive hearing loss. Patient was referred to
an ENT who performed a stapedectomy and prosthesis placement. Post op
patient developed excessive proliferation of granulation tissue, canal stenosis,
and had an episode of facial paresis, as well as ear pain, complete left sided
hearing loss, and a feeling of disequilibrium. CT and MRI imaging revealed
complete opacification of the cochlea and labyrinth, a displaced prosthesis, and
erosions of the ossicular and temporal bones. He was treated with high-dose
corticosteroid with mild improvement in symptoms. The patient returned to the
operating room for tympanomastoidectomy. The patient was referred to
Rheumatology for workup of an autoimmune process. He complains of
worsening symptoms but denies pain, fevers, chills, nausea, vomiting,
arthralgias and rashes.
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Past Medical/Surgical History:. Bilateral otosclerosis and asthma
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Medications: Advair 100 mcg-50 mcg/dose powder for inhalation, Cefuroxime
axetil 500 mg tablet, CIPRODEX 0.3 %-0.1 % Ear Drops, Montelukast 10 mg
tablet and Proventil HFA 90 mcg.
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Physical Exam: Patient appears well developed/well nourished and in no
apparent distress.
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VITAL SIGNS: B/P: 128/82, pulse 92, temperature 98.5 ºF,
respiratory rate 17, O2 sat of 100% on room air.
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HEENT: Anicteric sclera, no conjunctival pallor, difficult to
visualize tympanic membrane, no nasal ulcers, no mucosal
inflammation, mucosa was moist without oral ulcers. Poor
dentition. numerous caries.

SKIN: Warm and dry, no rashes noted.
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LUNGS: Clear to auscultation, no wheezing and rales
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HEART: S1, S2, regular rate and rhythm.
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ABDOMEN: Soft, nontender, nondistended. No ascites or
organomegaly was noted.
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EXTREMITIES: No clubbing, cyanosis, or edema
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MUSCULOSKELETAL: With in normal limits
Labs
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Comprehensive Metabolic Panel : Sodium 144, potassium 4.6, chloride 105, bicarb 28, BUN 15,
creatinine 1.22, glucose 96.

CBC : White count 7.2, hemoglobin 16.2, hematocrit 47.0, platelets 283,000.
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ANA/MPO/PR3/anti-smith/RNP/RF/CCP/ESR were negative. IgG was slightly low, but other Ig's
normal. Ace level normal.
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Serum IgG: 786 (694-1618 mg/dL), serum IgA: 133 (81-463 mg/dL), serum IgM 37 ( )(48-271mg/dL)
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IgG subclass1: 432mg/dL (382-929mg/dL), IgG subclass2: 266mg/dL (241-700mg/dL) IgG subclass3:
77mg/dL(22-178mg/dL) IgG subclass4: 28.4mg/dL(4.8-8.6mg/dL).
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Quantification of serum IgG4 level was normal at 26.1 mg/dL
Imaging
Fig: 1
Fig: 2
Fig: 3
Coronal and Axial T1FS w/ contrast: wreveal abnormal soft tissue mass with post-contrast enhancement within the left tympanomastoid cavity and petrous apex air cells which extends into the external auditory canal. There is
abnormal enhancement seen within the fundus of the left IAC and membranous labyrinth. Nerves VII and VIII complexes appear grossly intact. Abnormal signal is seen in the cochlea, vestibule and semicircular canals
demonstrating T2 hypointensity and mild T1 hyperintensity with post contrast enhancement.
Pathology
•
H & E of biopsy specimens indicated a
florid inflammatory response composed of
mononuclear cells with areas of fibrous
reaction.
• Immunohistochemically, 60 % of
plasma cells stained positive for
IgG4 subtype.
• Immunohistochemically showing
IgG4 staining.
Companion Case: 58 year old female with leftside facial pain and swelling along with left eye
pain proptosis and pain with left eye movement
• Ill-defined hyperdense mass is seen in the left orbit with
infiltration and obliteration of the intra-orbital fat. There
is left eye proptosis and thickening of the
myotendinous junction of the extra-ocular muscles. The
mass appears to extend posteriorly and involves the
cavernous sinus
• There is sclerosis of the orbital walls, ipsilateral maxilla,
mandible and skull base
• There is suggestion of extension of this mass in the left
temporal fossa as well.
• Ill-defined hyperdense mass is seen
in the left orbit with infiltration and
obliteration of the intra-orbital fat.
There is left eye proptosis and
thickening of the myotendinous
junction of the extra-ocular muscles.
The mass appears to extend
posteriorly and involves the
cavernous sinus
• There is sclerosis of the orbital walls,
ipsilateral maxilla, mandible and
skull base
• There is suggestion of extension of
this mass in the left temporal fossa
as well.
• Ill-defined hyperdense mass is seen in
the left orbit with infiltration and
obliteration of the intra-orbital fat.
There is left eye proptosis and
thickening of the myotendinous
junction of the extra-ocular muscles.
The mass appears to extend posteriorly
and involves the cavernous sinus
• There is sclerosis of the orbital walls,
ipsilateral maxilla, mandible and skull
base
• There is suggestion of extension of this
mass in the left temporal fossa as well
Differential Diagnosis
Sarcoidosis
(A-D): Magnetic resonance images show normal
intraorbitaland intraocular contents (globe) in axial and
coronal T1WI (A), (C) withbetter anatomic detail, T2WI (B)
T2WI (D) with more contrast resolutionfor the soft
tissues. Apex is very well visualized (asterisk)
Hande PC, Talwar I. Multimodality imaging of the orbit. Indian J Radiol Imaging 2012;22:227-39
Polyangiitis with granulomatosis
(formerly Wegners Granulomatosis)
Computed tomography (CT) scans of the sinuses .
A, Normal maxillary sinuses in a recently diagnosed Wegener’s granulomatosis
(WG) patient. B, Sinus CT scan of a patient with long-standing WG: nasal septal
deviation to the left, destruction of the medial walls of the right maxillary sinus,
opacification of both sinuses with soft tissue densities (arrows), and neoossification of all maxillary bony structures due to chronic inflammation.
Ferri's Clinical Advisor 2015 505-506.e1
Clinical and Imaging Features Predictive of Orbital Granulomatosis with Polyangiitis and the Risk of Systemic Involvement, 2014-0601Z, Volume 121, Issue 6, Pages 1304-1309,
A, Soft-tissue axial computed tomography showing left proptosis due to a soft-tissue mass
extending along the medial wall and floor of the left orbit, occupying the extraconal and intraconal
compartments, with involvement of the neighboring extraocular muscles. Note the site of prior left
dacryocystorhinostomy ( arrow). B, Coronal reformats show the soft tissue mass extending along
the orbital floor and medial wall and completely enveloping the inferior rectus and inferior aspect of
the medial rectus. The infraorbital groove ( arrow) is widened and filled with enhancing soft tissue
density material, suggestive of infiltration.
PNS along V3
Perineural Spread along the left
infraorbital nerve (V3)
Esthesioneuroblastoma arises from the olfactory epithelium in the
nasal vault; key dx feature is cyst at tumor-brain junction best seen
on post-contrast images (red arrow)
Kallman syndrome is a rare genetic
disorder of hypogonadotropic
hypogonadism (isolated GnRH
http://radiopaedia.org/cases/kallmann-syndrome
deficiency) with anosmia.
NOTE: Seizure activity in lateral
olfactory area may produce
"uncinate fits: hallucinations of
taste & odor
46 y/o M with head trauma (Cribriform plate fx or anterior temporal lobe injury)  Anosmia
PNS Tumor – Pterygopalatine Fossa
PPF
Rotundum
Conclusion: IgG4 related disease

First, recognized in the early 2000s for its presentation as a form of autoimmune pancreatitis it is now known that the disease can affect nearly every organ system

IgG4 related disease is a systemic inflammatory process with a spectrum of presentation depending on specific organ involvement.

Significant proportion of patients have years of asymptomatic disease involvement until they present with signs of organ injury secondary to compressive mass lesions.

Affected organs share histopathologic findings characterized by lymphoplasmacytic infiltrate rich in IgG4 cells, and fibrosis in a “storiform” pattern resulting in tumor like swelling.
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Otic involvement is scarcely reported in the literature perhaps because affected patients are labeled as having an “inflammatory pseudotumor”.
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IgG4 related otic and orbital disease is an important consideration in patients presenting with aggressive, erosive disease of cranial and facial bones.

Recognizing this presentation of IgG4 related disease is critical to prevent end-organ damage

Earl therapy is appears to be more successful in achieving disease remission, decrease recurrence and improved quality of life

Consistent with previous studies our case confirms that serum IgG4 levels alone are a poor diagnostic test for this disease process. Rather, the serum levels are best utilized in
conjunction with clinical suspicion on the basis of history and physical exam, imaging findings, and histopathological findings including immunohistochemical staining
for IgG4 cells.

Pseudotumor is diagnosis of exclusion

Atypical onset, poor response, or recurrence should prompt biopsy for confirmation

Consider other systemic causes with bilateral, multifocal, lacrimal, or apical involvement
References

Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: 539–551.

Saeki T, Nishi S, Ito T, Yamazaki H, Miyamura S, Emura I, et al. Renal lesions in IgG4-related systemic disease. Intern Med. 2007;46(17):1365–
71.

D Takagi, Y Nakamaru, S Fukuda et al. Otologic Manifestations of Immunoglobulin G4-Related Disease. Annals of Otology, Rhinology. 2014 Mar
28.

Wallace ZS, Khosroshahi A, Jakobiec FA, Deshpande V, Hatton MP, Ritter J, et al. IgG4-related systemic disease as a cause of “idiopathic” orbital
inflammation, including orbital myositis, and trigeminal nerve involvement. Surv Ophthalmol 2012; 57: 26–33.

Wallace ZS, Khosroshahi A, Jakobiec FA, Deshpande V, Hatton MP, Ritter J, et al. IgG4-related systemic disease as a cause of “idiopathic” orbital
inflammation, including orbital myositis, and trigeminal nerve involvement. Surv Ophthalmol 2012; 57: 26–33.

Rauch SD, Ruckenstein MJ. Autoimmune inner-ear disease. In: Cummings CS, Haughey BH, Thomas JR, Harker LA, Flint PWCummings
otolaryngology: head and neck surgery. 4th ed. Philadelphia (PA): Elsevier Mosby; 2005. pp. 2926-2933.

Guma, M. & Firestein, G. S. IgG4-related diseases. Best Pract. Res. Clin. Rheumatol. 26, 425–438 (2012).