Diagnosing IgG4-RD in head and neck proves tough, new study finds
18-case series shows symptoms can mimic cancer, other conditions
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Immunoglobulin G4-related disease (IgG4-RD) that’s marked by swelling and tumor-like masses in the head and neck can closely mimic cancer and other inflammatory conditions, making diagnosis challenging, according to a large case series study in India.
In the 18-patient study, the disease affected a broad range of head and neck areas, and the individuals’ ages also varied widely, ranging from 6 to 68.
The researchers noted that the investigations for all patients were “extensive.” Several individuals underwent multiple biopsies (tissue sample testing) and, in some cases, surgery before an IgG4-RD diagnosis was made, the researchers noted.
Tissue samples in all cases proved key to diagnosis, and treatment response was favorable for most, the team reported.
Overall, however, the researchers noted that “the most consistent theme across our series was diagnostic difficulty.”
“The central lesson from our series is that IgG4-RD must be considered in the differential diagnosis of any head and neck mass that does not conform to the expected behaviour of malignancy, infection, or conventional inflammatory disease — particularly when initial investigations are inconclusive or when disease progresses despite standard treatment,” the scientists wrote.
The study, “IgG4 Related Diseases in the Head and Neck Region: The Great Masquerader — (A Retrospective Multicentre Case Series),” was published in the Indian Journal of Otolaryngology and Head & Neck Surgery.
IgG4-RD occurs when immune cells — particularly activated plasma cells that secrete IgG4, a type of antibody — infiltrate the body’s tissues. This results in inflammation and tissue scarring that can lead to organ damage and cause IgG4-RD symptoms.
“Despite growing awareness, head and neck manifestations of IgG4-RD remain under-reported and frequently misdiagnosed,” the researchers wrote. The team noted that such manifestations can resemble cancer, chronic infections, and other conditions, “resulting in diagnostic delays, repeated biopsies, and in some instances surgical intervention prior to diagnostic confirmation.”
IgG4-RD affected 9 different regions in 18 patients
Now, a team of researchers in India sought to learn more about the clinical features, diagnostic challenges, treatment, and outcomes of people with IgG4-RD affecting the head and neck. To that end, the team retrospectively analyzed the cases of 18 head and neck IgG4-RD patients treated across eight specialized hospitals.
The patients were evenly split by sex and had a mean age of 36.4. The team noted that one patient was an 8-year-old girl with involvement of both parotid glands, the largest salivary glands, highlighting that IgG4-RD can rarely occur in children.
Among the patients, the disease affected several areas of the head and neck. The nasal cavities — air-filled spaces around the nose — and upper throat were the most frequently affected sites, seen in 44% of cases, followed by the salivary glands and deeper tissues at the base of the skull, each seen in 11%.
Less common sites were the thyroid gland, eye socket, ear, airway, tissues near the windpipe, and lymph nodes, which are immune structures in the neck.
“The breadth of involvement across nine distinct anatomical regions underscores the clinical [variability] of IgG4-RD in the head and neck,” the team wrote.
Using diagnostic criteria published in 2020, 11 people were classified as having definite IgG4-RD, while four were identified as having probable disease. Three other people had features of both IgG4-RD and Rosai-Dorfman disease, a rare condition in which certain immune cells accumulate abnormally in tissues; these individuals were not included among IgG4-RD definite cases.
Tissue samples proved key to diagnosis, researchers noted
Examining tissue samples was central to diagnosis, the researchers noted. All patients showed an abnormal buildup of immune cells, including plasma cells, in affected tissues, and most also had storiform fibrosis — an IgG4-RD hallmark characterized by scarring in a swirling or so-called cartwheel pattern.
Blood levels of IgG4 were available for 13 patients, with 11 showing results that were higher than normal. The other two had normal blood IgG4 levels despite having characteristic changes in their tissue samples.
According to the researchers, these findings highlight that normal blood IgG4 levels do not necessarily rule out the condition, particularly when the disease affects only one organ. The team noted that “higher [blood] IgG4 levels appeared to correlate with more extensive or multiorgan involvement in our [study], consistent with published observations.”
Altogether, the scientists say, this case series demonstrates the difficulty of diagnosing this rare disease. The team noted that “IgG-4-RD has been described as a great masquerader” because its symptoms mimic other conditions.
Applying established diagnostic criteria can help distinguish IgG4-RD from conditions with similar features and ensure that patients receive appropriate treatment, the team noted.
Increased awareness of IgG4-RD among [specialists] … is essential for timely diagnosis and appropriate management of this treatable but frequently misdiagnosed condition.
As for treatment, glucocorticoids, a type of anti-inflammatory and immunosuppressive medication, were the most commonly used, by 83% of the patients. This was followed by other immunosuppressive medications, such as methotrexate, azathioprine, or mycophenolate mofetil, which were prescribed for 61%.
Five patients (28%) whose disease returned or did not respond adequately to treatment were given rituximab, an antibody-based medicine that targets B-cells, the immature version of plasma cells.
One person with signs of Rosai-Dorfman experienced disease regression without treatment over six months. Most of the remaining patients showed a favorable response to treatment, with a reduction in symptoms and disease signs on imaging scans.
The most successful case involved a woman whose disease was particularly severe, resulting in narrowing of the airway, which required an emergency procedure to help her breathe. Following treatment, the airway recovered completely, and the patient remained symptom-free and off corticosteroids for at least four years.
No treatment guidelines or clinical trials are specifically focused on IgG4-RD affecting the head and neck, the researchers noted. As such, treatment was based on broader recommendations for IgG4-RD and individual patient needs, the team noted.
“Increased awareness of IgG4-RD among [specialists] … is essential for timely diagnosis and appropriate management of this treatable but frequently misdiagnosed condition,” the researchers concluded.
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