1. IgG4-Related Disease
Amir Mohammad Ghorbani, MD, Internal Medicine Resident
IKHC, TUMS

3. The disease was not recognized as a systemic condition until 2003, when extrapancreatic manifestations were
identified in patients with autoimmune pancreatitis.
Autoimmune pancreatitis had been linked to elevated serum IgG4 concentrations as early as 2001.

13. Clinical Presentation
Acute, fulminant or highly inflammatory clinical presentations do not occur in IgG4- RD.
Does not cause fever and seldom leads swiftly to organ failure.
The slowly evolving nature of IgG4- RD is one of its characteristic features; it is also, unfortunately,
one of the traits most responsible for the potential of this disease to cause harm.
• ~60% of all patients with IgG4-RD have some degree of irreversible organ dysfunction owing to damage at the time of
diagnosis.

14. Clinical Presentation
Some organs, such as the pancreas, lacrimal glands and
major salivary glands, become diffusely enlarged,
whereas ductal organs (such as the bile duct and
bronchus) assume the appearance of a pipe stem and
have diffuse wall- thickening.

19. Panel A shows
bilateral enlargement
of the submandibular
glands in a 45-year-old
woman. Her serum
IgG4 concentration
was 240 mg per
deciliter (normal level,
<121).

20. Panel B shows bilateral
enlargement of the parotid gland in
a 54-year-old man, who also had
asthma, marked enlargement of
the extraocular muscles, swelling
of the left fifth cranial nerve, and
abnormal soft tissue extending
from his left orbit through the left
greater palatine foramen into the
pterygomaxillary cistern, causing
proptosis. His serum IgG4
concentration was 1560 mg per
deciliter.

21. Panel C shows proptosis
of the left eye, caused by
enlargement of the
lacrimal gland, in a 62-
year-old man. His serum
IgG4 concentration was
30 mg per deciliter,
indicating that patients
can have classic
histopathological and
immunohistochemical
features of IgG4-related
disease within tissue yet
have normal serum IgG
values.

22. Histological Features
Whorled pattern of fibrosis: storiform (woven mat)
•highly distinctive feature of IgG4-RD, albeit non-diagnostic
dense lymphoplasmacytic infiltrate rich in IgG4 +plasma cells and CD4 +T cells
Eosinophils to a moderate degree, but do not dominate the overall composition of immune cells
Obliterative phlebitis

23. Histological Features
Increased numbers of IgG4+ plasma cells and high IgG4+:IgG+ plasma cell ratios provide
important information that is complementary to the results from H&E- stained tissue
samples
≥50 IgG4+ plasma cells per HPF and an IgG4+:IgG+ plasma cell ratio of >40% strongly
support a diagnosis of IgG4-RD
The thresholds for the absolute number of IgG4+ plasma cells per high-power field do vary
to some degree from organ to organ and between methods of obtaining tissue samples
• In such retroperitoneal biopsies, as few as 10 IgG4+ plasma cells per HPF can be regarded as supportive of the
diagnosis of IgG4-RD

24. A tissue specimen from a patient
with IgG4-related aortitis shows
virtually the entire wall of the
aorta (Panel A, hematoxylin and
eosin). Although the media (inner
layer, asterisk) is relatively
unaffected, a dense
lymphoplasmacytic infiltrate is
present on the adventitial aspect
(outer layer) of the aorta, and a
vein obliterated by inflammation
is indicative of obliterative
phlebitis (arrow).

25. Storiform fibrosis (Panel B,
hematoxylin and eosin) is
characteristic of IgG4-
related disease, such as
IgG4-related
dacryoadenitis. The pattern
is often likened to a
cartwheel, with the bands
of fibrosis (arrowheads)
emanating from the center
(asterisk) representing the
spokes of the wheel.

26. On immunoperoxidase staining, nearly all the plasma cells in
specimens from a patient with IgG4-related aortitis (Panel C) and a
patient with IgG4-related dacryoadenitis (Panel D) are strongly
positive for IgG4, whereas the small lymphocytes are negative.

27. A specimen of a venous channel (Panel E, hematoxylin and eosin) is characterized by total
obliteration (i.e., obliterative phlebitis). Arrowheads mark the periphery of the vein. A high-
power image of the specimen shown in Panel E (Panel F) shows lymphocytes, plasma cells
(long arrow), eosinophils (arrowhead), and fibroblasts (short arrow).