This case report describes an iRPF patient who was later diagnosed with endometrial cancer. At the time of admission, the patient has a 13-year history of iRPF. RPF is clinically rare with an age-standardized incidence of 0.1 cases/100,000 people per year . About 70% of RPF cases are idiopathic with no clear etiology. While the rest is secondary to certain medications, like inflammatory disorders, malignant diseases, radiation therapy and abdominal surgery, etc. . RPF commonly occurs in adults between the ages of 40 and 60, particularly in men (incidents occurring almost two to three times more than in women) [2, 8]. It is characterized by fibro-inflammatory tissue surrounding the abdominal aorta and compressing the retroperitoneal organs, in particular the ureters. Urological manifestations included ureteral obstruction, hypertension secondary to renal artery stenosis, renal failure or insufficiency, and nonfunctioning kidneys are common with ureteral involvement [1, 2]. Laboratory findings of elevated ESR and CRP inflammatory markers and reduced Hb often herald the active state of RPF. Studies have reported that 10–20% of RPF cases are ANA positive, and a higher frequency of ANA positivity (30–40%) has been observed in iRPF [9, 10]. Recent studies have proposed that iRPF belongs to IgG4-related diseases (IgG4-RD) which manifests as significantly elevated serum IgG4 and mass-like lesions that could easily be misdiagnosed as tumors . However, the specificity of serum IgG4 level is limited. Liao and colleagues compared the differences between IgG4-RPF and iRPF in a Chinese population that found elevated serum IgE concentration and tissue eosinophilia in the IgG4-RPF subgroup . For this patient, her total IgG was 27.4 g/L, with elevations of IgG1 and IgG2, while IgG3 and IgG4 were normal (Table 1). His serum IgE was also at a normal level of 25.8 IU/ml. Furthermore, IHC of his biopsied fibrous retroperitoneum showed no IgG4-related pathological features. Therefore, this case was probably not related to RPF IgG4.
Imaging examinations have played an essential role in the diagnosis and follow-up of RPF. This primarily included ultrasound, CT, MRI, and PET, and in which this disease often manifested as a homogeneous, well-defined plaque enveloping the retroperitoneal organs. A differential diagnosis must be made between iRPF and other diseases such as malignancies, infectious diseases, systemic problems, etc. CT scan is usually the modality of choice to visualize the location and extent of fibrosis and possible etiology. Baker et al. assessed the role of MRI in RPF which found that the apparent diffusion coefficient of inactive RPF was higher than that of active RPF or malignant RPF, and diffusion-weighted imaging may aid in the differentiation of inactive RPF malignant neoplasms . Moroni et al. reported that 18F-FDG PET/CT could accurately distinguish active disease from inactive disease (93.9%) . In particular, aseptic inflammatory processes, infections and malignant tumors could also increase the absorption of 18F-FDG. The study by Fernando et al. showed that 18F-FDG PET appeared to be able to distinguish cancer from non-cancerous RPF . However, in the present case, several enlarged lymph nodes, which were considered lymph node metastases by preoperative imaging methods such as CT, MRI, and PET/CT, were pathologically confirmed as fibrosis. Therefore, imaging methods to distinguish between RPF and malignant tumors still need to be evaluated and investigated further. The most definitive diagnostic test for RPF is retroperitoneal biopsy which can be performed under imaging guidance in cases with clinical symptoms and presentation of a retroperitoneal mass. The pathological hallmarks of iRPF are fibrosis and chronic inflammatory infiltration which consist of a large number of lymphocytes, plasma cells and the formation of lymphoid follicles.
Treatments for RPF include surgery to relieve symptoms of compression and medication to prevent the progression of inflammation. Drug treatment is suitable for patients with RPF with early mild symptoms or at an advanced stage of inoperability, or as prevention of postoperative recurrence. Glucocorticoid is currently considered one of the most effective drugs for the treatment of RPF. It is rapidly effective and can totally inhibit the early inflammatory response of RPF. However, long-term use of glucocorticoids has many adverse systemic effects and increases the risk of cardiovascular events. Tamoxifen (TMX) has been reported as a suitable alternative to glucocorticoids with no or mild side effects for RPF, particularly for patients who may not be able to tolerate steroid-related toxicity or who have contraindications to glucocorticoids [4, 5, 16]. TMX is a non-steroidal anti-estrogen drug that has potential anti-angiogenesis and anti-fibrotic properties . Vaglio and fellow researchers found that receiving TMX for 8 months was significantly less effective in preventing relapse than 8 months of treatment with prednisone in patients with iRPF through conducting a controlled trial randomized . Additionally, TMX has a weak estrogen-like effect, long-term use (especially for more than 5 years) may increase the risk of endometrial hyperplasia or even endometrial cancer. Studies have shown that the risk of endometrial cancer is increased after treatment with TMX in women with breast cancer (36/6101 versus 15/6131), mainly in women over 50 years of age. However, existing research has not reported any RPF patients who suffered from an increased risk of endometrial cancer when taking TMX. [4, 5, 16]. This may in part be explained by the small number of FPR patients included and the limited follow-up period recorded in these studies. Interestingly, the patient mentioned in this study had endometrial cancer after her treatment with TMX for iRPF, but the causal relationship was unknown. Therefore, the risk-benefit and long-term safety of TMX treatment in patients with RPF should be carefully evaluated in future studies. Close follow-up including inflammatory markers (ESR and CRP), creatinine and imaging (ultrasound, CT scan, MRI or PET) should be advised to monitor treatment response and allow early detection of relapses in patients with RPF. Researchers had reported that RPF relapse rates ranged from 22 to 69 percent [3, 8, 17]. Therefore, strategies for long-term monitoring and maintenance of remission should be considered.
For this case, there are a few key points that could be taken out. The diagnosis of RPF remains difficult due to nonspecific clinical symptoms and the lack of standardized diagnostic criteria. Imaging helped establish the diagnosis, but there were many limitations when it came to differentiating iRPF from other malignancies. Given this, biopsy may be the best way to get a reliable diagnosis. This patient was diagnosed with iRPF after splenectomy. Long-term use of tamoxifen may have been a high risk factor for endometrial cancer. An accurate diagnosis benefited from a careful history and a thorough physical examination. Organ damage was assessed before surgery. Her right kidney nearly lost function due to long-lasting obstructive uropathy, but the left kidney compensated so that she had nearly normal kidney function, which was enough for her to tolerate the surgery. Imaging tests, including CT, MRI, and PET/CT, all showed enlarged lymph nodes and increased FDG uptake on PET/CT. Clinicians believed it to be lymph node metastasis based on patient history and imaging findings. However, these enlarged lymph nodes have been surgically proven to have no cancerous involvement. This case report has highlighted the difficulty of distinguishing between lymph node metastases and inflammatory hyperplasia by imaging methods. Here, lymph node evaluation with biopsy seemed to be particularly important. For early-stage endometrial cancer, studies had shown that routine lymphadenectomy had no beneficial effect on overall survival but improved surgical staging [18, 19]. Thus, the clinical benefit of routine lymphadenectomy should be further investigated to avoid additional surgical complications and overtreatment. The criteria of myometrial invasion