Diagnostic process for IgG4-related sclerosing cholangitis.

Decoding IgG4-Related Diseases: When Mimics Become the Mystery

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"Unraveling the complexities of IgG4-related sclerosing cholangitis and chronic sclerosing sialadenitis, and how to distinguish them from cancer and other conditions."

IgG4-related diseases (IgG4-RD) are a group of conditions that can affect various organs in the body. One such manifestation is IgG4-related sclerosing cholangitis (IgG4-SC), which impacts the bile ducts. A particular type, type 3 IgG4-SC, presents with narrowing (strictures) in the bile ducts, and can closely resemble cholangiocarcinoma (CC), a type of bile duct cancer.

Adding to the diagnostic challenge is chronic sclerosing sialadenitis, also known as Küttner tumor (KT). This uncommon, tumor-like lesion typically affects the salivary glands, often appearing as a mass in the neck. Similar to IgG4-SC, KT is now recognized as part of the IgG4-RD spectrum, but it can easily be mistaken for neck malignancies.

This article will discuss a rare case of type 3 IgG4-SC accompanied by KT and lymphadenitis (inflammation of the lymph nodes). This case is unique because it lacked pancreatic involvement, further complicating the initial suspicion of cancer. We'll explore how doctors navigated these complexities to reach the correct diagnosis and treatment.

The Case: A Diagnostic Puzzle

Diagnostic process for IgG4-related sclerosing cholangitis.

A 59-year-old woman from Northeast China presented with jaundice and itching for six months. She also had a mass in her right submandibular region, accompanied by minor salivary dysfunction for three months. Notably, she had undergone surgical removal of a similar mass in the left submandibular region a year prior. Crucially, the patient had no history of ulcerative colitis.

Physical examination revealed a painless, hard, fixed mass in the right submandibular region, raising initial concerns for cervical malignancy. Abdominal examination showed tenderness. Lab results showed elevated bilirubin and alkaline phosphatase levels, with a slightly elevated CA19-9 (a tumor marker) level. Additional tests for autoimmune markers were negative. Imaging scans, including CT and MRCP, revealed bile duct strictures, further complicating the picture.

Key Diagnostic Challenges:

Mimicking Cancer: The combination of bile duct strictures, a neck mass, and elevated CA19-9 strongly suggested cancer.
Lack of Pancreatic Involvement: The absence of pancreatic lesions, typical in some IgG4-RD cases, made the diagnosis less straightforward.
Previous Excision: The patient's history of a similar mass removal complicated the interpretation of the current neck mass.

To clarify the diagnosis, doctors performed an ultrasound-guided needle biopsy of the submandibular gland. Histological examination of the previously resected left submandibular gland revealed characteristic features of IgG4-RD: acinar atrophy, dense lymphoplasmacytic infiltration, and fibrosis. Immunohistochemical staining confirmed numerous IgG4-positive plasma cells, with a high IgG4/IgG ratio. These findings, along with similar results from the needle biopsy of the right submandibular gland, confirmed the diagnosis of KT as part of IgG4-RD.

Lessons Learned: Diagnostic Strategies

This case highlights the importance of considering IgG4-RD in patients presenting with bile duct strictures, salivary gland masses, or lymphadenitis, even when typical features like pancreatic involvement are absent. A thorough evaluation, including serological testing for IgG4 levels, imaging studies, and tissue biopsy with immunohistochemical staining, is crucial for accurate diagnosis.

Ultrasonography and fine-needle aspiration biopsy (FNAB) can be valuable tools in evaluating salivary gland masses and differentiating KT from other conditions like malignancies. However, it's essential to interpret these findings in the context of the patient's clinical presentation and other diagnostic results.

Distinguishing IgG4-SC from cholangiocarcinoma requires a comprehensive approach, integrating clinical, serological, morphological, and histological features. Newer techniques like intraductal ultrasonography and cholangioscopy can further aid in the differential diagnosis. Early and accurate diagnosis is critical, as IgG4-RD typically responds well to steroid therapy, preventing unnecessary surgical interventions.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/s1499-3872(17)60042-0, Alternate LINK

Title: Igg4-Related Sclerosing Cholangitis And Chronic Sclerosing Sialadenitis Mimicking Cholangiocarcinoma And Neck Malignancy

Subject: Gastroenterology

Journal: Hepatobiliary & Pancreatic Diseases International

Publisher: Elsevier BV

Authors: Li Sun, Hong-Yan Li, David R Brigstock, Run-Ping Gao

Published: 2017-08-01

Everything You Need To Know

What are IgG4-related diseases, and why are they important to understand in this context?

IgG4-related diseases (IgG4-RD) are a group of conditions where the body's immune system mistakenly attacks its own tissues. This can lead to inflammation and damage in various organs. In the context of this case, the article describes how IgG4-RD can mimic cancer, specifically focusing on IgG4-related sclerosing cholangitis (IgG4-SC) and chronic sclerosing sialadenitis (Küttner tumor or KT). This means that the symptoms and appearances of IgG4-RD can be very similar to those of cancer, making it difficult for doctors to tell the difference and leading to diagnostic challenges.

What is IgG4-related sclerosing cholangitis (IgG4-SC), and why is it significant in the context of the article?

IgG4-related sclerosing cholangitis (IgG4-SC) is a specific manifestation of IgG4-related disease (IgG4-RD) that affects the bile ducts. The article highlights type 3 IgG4-SC, which causes narrowing (strictures) in the bile ducts. This can obstruct the flow of bile, leading to symptoms like jaundice and itching, similar to what is seen in some types of bile duct cancer, specifically cholangiocarcinoma (CC). The diagnostic challenge arises because the strictures seen in IgG4-SC can appear identical to those caused by CC on imaging tests. Accurate diagnosis is crucial because the treatments for IgG4-SC and CC are very different.

What is chronic sclerosing sialadenitis (Küttner tumor), and what is its significance?

Chronic sclerosing sialadenitis, also known as Küttner tumor (KT), is another manifestation of IgG4-related disease (IgG4-RD). It primarily affects the salivary glands, often presenting as a mass or swelling in the neck. The key issue is that KT can be mistaken for a neck malignancy because it can create a tumor-like lesion. In this scenario, it's considered alongside IgG4-SC, since both are parts of IgG4-RD spectrum, and are difficult to distinguish from similar conditions, leading to diagnostic difficulties.

What are the key challenges in diagnosing IgG4-related diseases?

The primary diagnostic challenges include distinguishing IgG4-related diseases (IgG4-RD) from cancer. For instance, IgG4-related sclerosing cholangitis (IgG4-SC) mimics bile duct cancer (cholangiocarcinoma). The article also focuses on the absence of pancreatic involvement and previous excision of a mass. These complexities make the diagnosis more challenging because some IgG4-RD cases have pancreatic involvement, which is a distinguishing feature. Additionally, a history of similar masses further complicates diagnosis.

What diagnostic methods are used to identify IgG4-related diseases?

Doctors use several diagnostic strategies. These strategies include serological testing for IgG4 levels, imaging studies like CT and MRCP, and tissue biopsy with immunohistochemical staining. In the described case, doctors performed a needle biopsy of the submandibular gland and found histological features characteristic of IgG4-RD. The presence of acinar atrophy, lymphoplasmacytic infiltration, fibrosis, and a high IgG4/IgG ratio confirmed the diagnosis. It highlights the importance of considering IgG4-RD when patients have bile duct strictures, salivary gland masses, or lymphadenitis, even when typical features are absent.