IgG4-related disease or tumor?

*For medical professional reading reference only

Seeing flowers in the fog, flowers are not flowers

Although "IgG4-related disease" was only recognized by the public in the 21st century, it has existed for a long time in human history and is not uncommon in clinical practice

A few years later, doctors from various disciplines have also discovered that the swelling, inflammation, fibrosis and other changes of various tissues and organs are related to IgG4

After a few years, today's rheumatologists are no longer easily deceived by IgG4-RD disguised as tumors

Let's follow the footsteps of Dr.

Case data

 

Luo XX, a 77-year-old male

Chief complaint: fatigue for 3 years, diarrhea for 3 months

History of present illness: consciously fatigued 3 years ago, anemia (unknown) was found in physical examination, no diagnosis and treatment

Past history: positive fecal occult blood for 4 years; hypertension for 5 years, highest blood pressure 200/100mmHg, discontinuation of antihypertensive drugs 1 year ago due to low blood pressure; 100UG; 5 years of pulmonary embolism, asymptomatic untreated; tinnitus for 30 years, right otitis media for 20 years, bilateral hearing loss for more than 10 years; "appendicitis" surgery 40 years ago, "subdural hemorrhage" surgery 1 year ago; sulfa allergy

Personal history: smoked for more than 10 years, 15 cigarettes/day, has quit for more than 10 years, and occasionally socially drinks
.

Physical examination: body temperature: 36.
4°C, pulse: 72 beats/min, respiration: 18 beats/min, blood pressure: 138/71mmHg; swelling of the right eyelid; cardiopulmonary abdomen (-)
;

test:

• WBC 3.
  62×10 ⁹ /L↓, EOS 0.
  96×10 ⁹ /L↑, HGB 88g/L (large cytochrome), RET% 2.
  19%↑;

• Urine routine, 24h UP-, OB weakly positive in stool;

• ALT, AST, TBIL, Cr (-), ALB 12.
  7g/L↓;

• ESR 121mm/1h↑, CRP(-);

• Peripheral blood smear: 43.
  0% neutrophils, 27.
  0% eosinophils, 19.
  0% lymphocytes, 1.
  0% neutrophils, 5.
  0% monocytes, and 5% atypical lymphocytes
  .
  
  Mature RBCs are slightly different in size, with obvious arrangement in the shape of a coin, and large platelets are rare;
  

• IgG 170g/L↑, IgM 3.
  23g/L↑, C3 18.
  50mg/dl↓, C4 2.
  41mg/dl↓, IgG4 91.
  80g/L↑, IgE 541.
  301U/ml↑;

• Coombs+, ANA+1:80 (cytoplasm, speckle), anti-ENA profile, ANCA(-);

• Ultrasound: Diffuse lesions of the lacrimal, parotid, and submandibular glands
  .
  
  

an examination:

• Paranasal sinus MRI scan + enhanced (Figure 1): thickening of the double ethmoid sinus and maxillary sinus mucosa: enlargement of the right lacrimal gland, fullness of the double parotid gland and submandibular gland: right middle ear mastoiditis: intracranial hypertrophic dura mater
  .
  
  

Figure 1 Paranasal sinus MRI scan + enhanced

• PET-CT:

Figure 2 Vascular PET-CT (1)

Figure 3 Vascular PET-CT (2)

According to PET-CT, doesn't it look like IgG4-RD with lumps all over the body? The lesions involved the lacrimal gland, pancreas, lung, the above multiple blood vessels, ascending colon, peritoneum, bile duct, prostate, lymph nodes and other organs and tissues
.

In addition, the radiology teacher also suggested that malignant diseases such as lymphoma should be excluded in combination with pathology
.

So the question is, can the patient be diagnosed with IgG4-RD? Can IgG4-RD explain the full picture of the patient's condition?

lgG4-RD? CTD? Malignant tumor?

Don't worry, there is too much information about this case, let's summarize the characteristics of the case first:

• Older men, insidious onset, long course of disease, and multi-system involvement;

• Diarrhea, hypoalbuminemia, negative urine protein;

• Low white blood cells, elevated eosinophils, anemia, IgG↑, IgG4↑, IgE↑, low complement;

• Lacrimal glands, salivary glands, sinuses, ILD, dura mater, pancreas, hepatobiliary duct, ascending colon, peritoneum and mesentery, prostate;

• Multiple serous cavity effusions, multiple vascular lesions;

• Multiple lymphadenopathy
  .
  
  

Based on these characteristics, 3 main diagnoses can be generated:

1lgG4-RD?

■Support points:

• Older men with multisystem involvement:

• EOS, IgG, IgG4, IgE↑;

• Lesions involving lacrimal glands, salivary glands, sinuses, hypertrophic dura mater, mastoiditis, pancreas, hepatobiliary ducts, ILD, prostate, blood vessels, and lymph nodes
  .
  
  

■Not supported points:

• Gastrointestinal lesions are rare;

• Low white blood cells, anemia;

• Lymph node fusion
  .
  
  

2 Connective tissue disease (CTD)?

Systemic lupus erythematosus (SLE) support points: multi-system involvement, low white blood cells, anemia, high EOS, high IgG, Coombs positive, ANA 1:80
.

Unsupported point: no typical manifestations of lupus, anti-ds-DNA, anti-Sm negative
.

ANCA-associated vasculitis (AAV) support points: elderly men, sinuses, otitis media, hypertrophic dura mater, high EOS
.

Unsupported points: ANCA negative, macrovascular disease
.

It also appears that CTD is difficult to explain the full picture of the disease
.

3 Malignant tumors?

For this patient, the most important thing is the differential diagnosis of malignant tumors
.

The patient has multi-system damage, increased globulin, thick colon wall, lymph node fusion lesions, and needs to be alert to lymphoma/multiple myeloma/digestive tract tumor
.

IgG4-RD and tumors can mimic each other, but rarely meet real tumors
.

So the current situation is: clinical experience and evidence-based medicine are saying "impossible" in the ears of the doctors, while the patient's medical history and examination results are frantically suggesting that "nothing is impossible"!

Therefore, further immunofixation electrophoresis, bone biopsy, lymph node biopsy, endoscopy, and intestinal protein loss imaging were performed.
The results are as follows:

• CBC 3.
  12×10 ⁹ /L, HGB 83g/L, PLT 83×10 ⁹ /L, EOS 0.
  86×10 ⁹ /L;

• APTT 42.
  1s, PT 19.
  4s, INR 1.
  81, FBG 0.
  85g/L, PT(A) 49%, DD 1.
  16ug/ml;

• CA125 208.
  60U/ml, CA724 119.
  15U/ml;

• PBMC EBV-DNA：2275；EBV-DNA；

• T-SPOT、CMV；

• ：IgMλM；；

• κ、λ；

• CT：，，，，，；

• ：，、，IgG4>10/HPF，IgG4/IgG40%，、，；

• ：60%，，：：CD38、CD138（+，），Kappa、Lambda+，；，IgG、IgG4；

• ：，，；

• ：、，；

• ：、，；；

• （4）：（3），1（），，
  。
  

4

，：

1.
IgG4（、、、、，、、，//？）
。

2.

：？， 、、，3（），，、、、（II-IV）
。

，

？：，，IgG170g/L
。
PET-CTIgG4-RD，，“”
。
，
。

• ，IgG4-RD，IgG410，50；IgG4-RD，
  。
  

• ，IgG4-RD mimic（）
  。
  ，IgG4-RD“，”
  。
  ，，
  。
  IgG4-RD mimic，IgG4-RD，，，“”
  。
  

• ，IgG4-RD，
  。
  、，“”，
  。

，IgG4-RD，
。

The patient was eventually treated and followed up for IgG4-RD and colon cancer:

• During hospitalization, the patient could not tolerate surgery due to poor general condition.
  With full informed consent, in order to improve the general condition and strive for the opportunity for surgery, methylprednisolone 40mg qd→Pred 35mg qd, reduced by 5mg in two weeks;

• Diarrhea was relieved quickly after treatment, and stools were formed 1-2 times/day
  .
  
  The lacrimal glands are swollen and edema subsided
  .
  
  During the 2-month follow-up, the body weight increased by 5kg, and the EOS was normal, ALB 29g/L; IgG22.
  3g/L, IgM 3.
  52g/L, complement normal; IgG4 16.
  5g/L
  .
  
  

Re-examination in March after discharge:

• Contrast-enhanced CT of the abdomen and pelvis: colon cancer may be large in the ascending colon, multiple abnormal enhancement nodules in the liver do not exclude metastasis, multiple lymph nodes in the paraintestinal, mesenteric and retroperitoneum, thickening of the right peritoneum, and thickening of the right prerenal fascia with nodules Section, nature to be determined;

• Exploratory laparotomy: biopsy of liver tumor: metastatic cancer, palliative right hemicolectomy was performed
  .
  
  

Small

Knot

The main symptom of the patient on admission was diarrhea with IgG up to 170 g/L
.

After a series of examinations, the patient was diagnosed with IgG4-RD combined with colon cancer and was treated accordingly
.

It is suggested that when we encounter the situation that IgG4-RD and tumor mimic each other in clinical work, we need to discriminate carefully, and formulate diagnosis and treatment plans need to consider the overall situation
.

There are still unsolved mysteries in this patient: although the patient has not been traced back to a clear past IgG4-RD-related manifestation, IgG4-RD should not be a recent new occurrence, and the protein loss imaging of this diarrhea inspection is not limited to the tumor site, and it is not Except that protein-losing enteropathy is associated with IgG4-RD, which is rare; patients with positive IgMλ-type M protein and small focal positive bone marrow Congo red should be highly alert to plasma cell disease
.

Guests participating in the ward rounds: Professor Zhang Wen (Peking Union Medical College Hospital), Professor Jiang Lindi (Zhongshan Hospital Affiliated to Fudan University), Professor Wei Na (Friendship Hospital Affiliated to Capital Medical University)
.
Brief introduction of the final reviewing expert

Professor Liu Yanying

• Chief physician, professor, doctoral supervisor

• Deputy Director, Department of Rheumatology, Beijing Friendship Hospital

• Deputy Director, Department of Rheumatology, Capital Medical University

• Youth Committee of Rheumatology Branch of Chinese Medical Association

• Youth Committee of Rheumatology and Immunology Branch of Chinese Medical Doctor Association

• Member of the Standing Committee and Secretary General of the IgG4-related Diseases Group of the Cross-Strait Medical and Health Association

• Member of the Standing Committee and Deputy Secretary-General of the Immunopurification and Cell Therapy Group of the Internal Medicine Branch of the Chinese Medical Association

• Member of the Rheumatology and Immunization Committee of the Chinese Women's Physician Association

• Chinese Medical Doctor Association National Physician Regular Assessment Distinguished Expert

• He has presided over 10 national key research and development programs (sub-projects) of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Doctoral Program of the Ministry of Education.
  

• Editor-in-chief and co-editing (translation) of 9 monographs on rheumatism

• 3 national invention patents were approved

• Published 77 Chinese and English articles, including 42 first author or corresponding author articles

Cases provide expert briefings

Zhang Xia

• Attending Physician, Department of Rheumatology and Immunology, Beijing Friendship Hospital

• Doctor of Medicine, graduated from Peking Union Medical College Hospital

• Published a total of 30 articles in Chinese and English, and participated in the compilation of 5 books

Where can I find more rheumatism clinical knowledge?
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