The "retroperitoneal mass" was thought to be cancer, and the differential diagnosis was finally made clear!

*For medical professionals to read and reference the truth is far more complicated than imagined.
It is related to abdominal pain, and it must be a gastroenterology disease! No! No! No! In the following case, the Department of Gastroenterology said that it does not carry this "pot"! Brief medical history A woman in her 20s was admitted with abdominal pain for 2 months and a retroperitoneal hypoechoic lesion on ultrasonography (Figure 1A) [1]
.

 Physical examination of the cardiovascular system, respiratory system, nervous system, skin, and musculoskeletal system was unremarkable
.

 Clinically, we are not afraid of abnormality, but the most fearful thing is "no abnormality".
.
.
The medical history seems to be very simple, and the physical examination is normal, but since abdominal pain, routine examination and abdominal examination are a set! Blood counts, eosinophil counts, and biochemistry (including liver and kidney function and serum IgG4) were normal
.

Serum protein electrophoresis did not reveal polyclonal hypergammaglobulinemia
.

CT scan revealed a retroperitoneal mass (Fig.
1B), adjacent to the body and tail of the pancreas, left adrenal gland, and spleen, associated with regional lymphadenopathy, with homogeneous contrast enhancement
.

The thorax and mediastinum were unremarkable
.

MRI showed a 39-mm lesion that was hypointense on T1-weighted (Fig.
1C, D) and hyperintense on T2-weighted, enhanced enhancement, and gradually enhanced around the equilibrium phase
.

Figure 1: Ultrasonography (A) shows a hypoechoic mass
.

Contrast-enhanced CT scan (B) confirms the presence of a mass in the retroperitoneal space
.

On MRI, the mass appears as an oval, hypointense lesion on T1-weighted images (C); in the venous phase (D), the lesion has a "marginal" contrast-enhancing pattern
.


A false alarm, not cancer! Looking at the current examination results, the diagnosis is still a bit confusing.
Is it a malignant tumor? A 3.
5 cm diameter mass with an adherent structure was surgically removed
.

 Pathological biopsy results showed that the lesions consisted of dense fibrous tissue infiltrated by lymphocytes and plasma cells, with germinal centers mixed with eosinophils (Fig.
2A)
.

Plasma cells are polytypes of kappa and lambda Ig-light chains
.

There were 20 IgG4+ plasma cells per high-power field (Figure 2B), and the ratio of IgG4+ plasma cells/IgG+ plasma cells was 20%–25%
.

There were 'Castleman-like' changes in the mass and adjacent lymph nodes (Fig.
2C)
.

Proliferation of CD23-positive follicular dendritic cells was seen (Fig.
2D)
.

HHV8 immunostaining was negative
.

 Figure 2: Microscopically (A) the lesion is composed of dense fibrous tissue with infiltration of lymphocytes, plasma cells, and eosinophils observed; the mass is adherent to the adjacent pancreas (arrow), but not infiltrated; IgG4 (B) Immunostaining shows scattered positive plasma cells within the lesion; germinal centers of various sizes, some of which atrophic sclerosis is present in the mass and adjacent lymph nodes (C); expansion of CD21-positive follicular dendritic cells is seen (D)
.

 I believe that after seeing the pathological biopsy, my friends are even more confused.
.
.
It's not cancer, what is it? Let's think about it again, the patient's symptoms (abdominal pain), retroperitoneal space mass, MRI shows low signal on T1, a large number of lymphocytes, plasma cells are seen under the microscope.
.
.
and so on! This disease is not retroperitoneal fibrosis (RPF)
.

Thought iRPF was the result, didn't expect it was just the beginning.
.
.
■ Is it idiopathic or secondary? RPF is rare.
Due to the lack of specific manifestations and the insidious early clinical symptoms, many patients develop obstructive symptoms caused by the compression of intra-abdominal cavity organs, which are easily ignored by doctors due to lack of clinical understanding of it
.

RPF is divided into idiopathic (iRPF) and secondary (sRPF)
.

 iRPF was first reported by Ormond in 1948.
It has no clear incentive and accounts for about 70% of RPF.
It is a rare disease with an incidence rate of about 1/500,000 to 1/200,000 [2]
.

iRPF is a rare type of connective tissue disease characterized by chronic non-specific inflammation and fibrosis in retroperitoneal tissue.
Abdominal aorta and its adjacent structures such as ureter, inferior vena cava,
etc.

There are definite reasons for the occurrence of sRPF, such as tumors, drugs, trauma, inflammation, radioactive substances, endometriosis, etc.
, accounting for about 30% of RPF
.

The patient clearly ruled out the above reasons, so the diagnosis of iRPF was made
.

 Is it the end of a diagnosis of iRPF? Do not! Continue to dig what is the cause of iRPF? ■ Related to IgG4-RD? Careful friends can see that the key indicator of IgG4 appears in the above inspections
.

In recent years, with the deepening of the understanding of IgG4-related diseases (IgG4-RD), it has been found that some iRPFs are closely related to IgG4-RD, that is, IgG4-RPF, and IgG4-RPF accounts for about 30% to 60% of iRPF patients
.

 So, is this case IgG4-RPF? Don't read the version: Let's review how to diagnose IgG4-RD? Swipe up to read IgG4-RD is a type of immune-mediated fibro-inflammatory disease that can invade multiple organs throughout the body, with highly heterogeneous clinical manifestations, such as some autoimmune pancreatitis, Mikulicz's disease, Riedel's thyroiditis, interstitial Nephritis, RPF, etc.
[3-4]
.

The diagnosis of IgG4-RD relies on the characteristic clinical and histopathological features (ie, dense lymphoplasmacytic infiltration, striate fibrosis, and obliterative phlebitis), and an increased number of IgG4+ plasma cells (ie, IgG4+/IgG+ plasma cells) ratio >40% and >10 IgG4+ plasma cells per HPF)
.

 IgG4-RPF has three characteristic histopathological manifestations: (1) aortic involvement and a large number of inflammatory cells (predominantly lymphocytes and plasma cells) infiltration in the surrounding soft tissue; (2) fibrosis (such as typical striated Fibrosis); (3) Inflammatory cell infiltration in and around the venule wall, fibrous occlusion of the lumen, leading to obliterative phlebitis
.

Microscopic appearance of IgG4-RPF is similar to iRPF, but IgG4-RPF is more prone to obliterative phlebitis
.

Although IgG4+ plasma cells were also found in iRPF tissues, IgG4+ plasma cells accounted for more than 40% of IgG+ plasma cells in IgG4-RPF
.

 Combined with the patient in this case, although there are lymphocytes and plasma cells infiltrated in the pathological tissue, and there are 20 IgG4+ plasma cells in each high-power field of view, the ratio of IgG4+ plasma cells/IgG+ plasma cells is 20%–25%, and there is no striae.
Fibrosis and obliterative phlebitis, not in line with the diagnosis of IgG4-RPF! Hence the diagnosis of non-IgG4-RPF
.

 Do you think this diagnosis is completely clear? Do not! And.
.
.
■ Castleman's disease confusing the diagnosis again? Careful friends can see such a term in the above medical history - "Castleman-like" change, what is this? When it comes to "Castleman-like" changes, we have to mention Castleman disease (CD).
CD is a group of lymphoproliferative diseases with characteristic histopathological features, and the etiology and pathogenesis are unknown
.

The disease can be divided into unicentric CD (UCD) and multicentric CD (MCD) based on the number of areas of lymphadenopathy with characteristic histopathologic features, with prominent histopathologic features of lymphoid follicles, blood vessels, and plasma Different degrees of cell proliferation can be divided into hyaline vascular type, plasma cell type and mixed type according to histopathology
.

It has been recognized that the pathogenesis of CD is related to IL-6 and HHV-8 (HHV-8 is also known as Kaposi's sarcoma herpes virus)
.

 It is well known that in addition to CD, many diseases (including malignant tumors, infectious diseases and autoimmune diseases, etc.
) are also associated with "Castleman-like" pathological changes in lymph nodes
.

The first step in diagnosing CD is to exclude related diseases that may be associated with pathological changes in lymph nodes similar to CD, including (but not limited to) infectious diseases (such as HIV, syphilis, Epstein-Barr virus infection, tuberculosis, etc.
), neoplastic diseases (such as POEMS) Syndrome, lymphoma, follicular dendritic cell sarcoma, plasmacytoma, etc.
), autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, autoimmune lymphoproliferative syndrome, etc.
)
.

Unfortunately, iRPF also exhibits overlapping clinical and pathological findings with multicentric and unicentric CD; CD can also present with numerous IgG4+ plasma cells and elevated serum IgG4 levels
.

Therefore, the identification of these two diseases is challenging
.

 Unfortunately, the lack of lymph node pathological findings in this case, in addition, C-reactive protein (CRP), platelet count, IL-6, and HHV-8 were all normal, making a definitive diagnosis of CD impossible
.

Currently, this is the first non-IgG4-RPF case report with "Castleman-like" alterations in the literature
.

Seeing this, this case has finally been introduced.
I did not expect such a simple medical history, but it leads to so many thought-provoking things.
It is really endless.
.
.
.
Summary iRPF can occur in IgG4-RD or non-IgG4-RD
.

iRPFs, especially IgG4-RPFs, can sometimes mimic CD clinically and/or histologically; currently, this is the first case of a non-IgG4-RPF with "Castleman-like" alterations described in the literature; in this case, Differentiating iRPF from CD can be difficult and requires other tests, such as CRP, IL-6, and platelet count
.

References [1] Covelli C, et al.
When idiopathic retroperitoneal fibrosis mimics Castleman disease: a challenging differential diagnosis.
BMJ Case Rep, 2022;15:e248051.
doi:10.
1136/bcr-2021-248051[2] VAGLIO A, SALVARANI C, BUZIO C.
Retroperitoneal fibrosis［J］.
Lancet, 2006, 367(9506): 241-251.
[3] LIAN L, WANG C, TIAN JL.
IgG4-related retroperitoneal fibrosis: a newly characterized disease［J］.
Int J Rheum Dis, 2016, 19(11): 1049-1055.
[4] UMEHARA H, OKAZAKI K, MASAKI Y, et al.
Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011［J］.
Mod Rheumatol, 2012, 22(1): 21-30.