Discussion:
Here, we report the third case of isolated bilateral renal RDD without any evidence of significant adenopathy during diagnostic work-up. RDD is a rare non-malignant histiocytosis disorder with poorly-understood pathogenesis. Frequent association with immunologic abnormalities suggests a probable immune-mediated etiology 5. RDD most commonly manifests with massive painless cervical lymphadenopathy, occurring as a result of proliferation and aggregation of distinctive histiocytes within the expanded sinuses of lymph nodes. Nevertheless, it is not solely limited to the lymph nodes and lymphoid organs, as in 43% of cases, RDD manifests as extranodal involvement, either with or without associated lymphadenopathy.
Kidney involvement develops in only four percent of patients with RDD and is rarely isolated 6. In general, renal RDD is an indicator of poor prognosis and due to complications of mass effect that compromises the function of the kidneys and adjacent organs, the mortality rate can be as high as 40% 6. Moreover, survivors usually suffer from chronic kidney disease10. A history of autoimmune diseases, as in our case, also makes patients susceptible to a more severe disease course5. This implies that early identification of patients with renal RDD, in particular those with a positive history of immunologic disorders, is of paramount importance.
Based on the site of involvement, RDD displays a wide range of non-specific clinical and radiologic presentations, making its diagnosis challenging. The definite diagnosis of RDD must only be confirmed through histopathologic and IHC examination 11. In patients with indistinguishable radiological and clinical features, preoperative image-guided biopsy could be worthwhile to avoid further invasive interventions; however, in some cases, as in our patient, needle biopsy is not adequate for drawing definite diagnosis and surgical biopsy is required. The histological hallmark of RDD is emperipolesis, in which lymphocytes, plasma cells, erythrocytes, and neutrophils are engulfed within histiocytes without being degraded1. However, even this pathognomonic feature is less frequent in extranodal forms of RDD and might be difficult to identify5. The most prominent IHC marker for distinguishing SHML histiocytes is the S100 protein. Other macrophage markers such as CD68 and CD163 also stain positive. However, the SHML histiocytes do not stain for CD1a and dendritic markers such as CD21, CD23, or CD355, 6. Also, as in our case, the absence of expression of markers such as CK AE1/AE3 helps differentiate renal RDD from carcinoma with epithelial origin such as ovarian or renal parenchymal tumors 12, 13.
In patients with renal RDD, laboratory data ranges from normal to non-specific findings such as leukocytosis, increased ESR, and hypergammaglobulinemia 11. Although imaging studies are also not highly discriminative, they will help narrow the diagnosis. Modalities such as renal ultrasound, abdominopelvic CT, and MRI, along with FDG PET/CT scan could be considered as beneficial tools for identification of the lesion, evaluation of the extent of disease, image-guided biopsy, and even monitoring disease activity and response to therapy 14, 15. Due to the rarity of RDD, it is less likely for the urologist or radiologist to consider this diagnosis when observing an abnormal renal lesion on imaging; however, having a suspicion in mind might favorably change patient management and help prevent unnecessary nephrectomy.
The radiologic features of renal RDD include hilar masses, distinct nodules in the cortex, subcapsular infiltrative lesions, lobular irregularity, or kidneys with distorted calyces. Occasionally, large para-aortic lymph nodes might also be noted 4, 16. Nevertheless, imaging findings of renal RDD may mimic that of important differential diagnoses such as Erdheim-Chester disease, renal cell carcinoma, lymphoma, leukemia, multiple myeloma, or metastasis from melanoma or lung cancer 17; thus, it is essential to exclude the possibility of these potentially life-threatening diseases. Table 1 compares the common imaging features of important differential diagnoses of RDD. In the case presented here, bilateral isodense renal pelvis masses without calcification were seen on unenhanced CT. MRI revealed hypo-to-isointense masses on T1-weighted images and isointense to hyperintense signals on T2-weighted images with slight heterogeneity. ADC maps were suggestive of mild restricted diffusion and delayed phase imaging showed gradual enhancement of the masses without washout. In 1999, Bain and colleagues reported the first case of bilateral renal RDD. They noted heterogeneous hypoechoic masses with calcification foci on ultrasound and non-cystic masses with soft tissue attenuation on unenhanced CT. They also performed contrast-enhanced CT, which showed less homogeneous enhancement as compared with the renal parenchyma18. Another study in 2001, describing three cases with RDD and renal involvement showed that RDD manifests as infiltrative renal hilar masses and subcapsular infiltration on contrast-enhanced CT19. Gumeler and colleagues reported infiltrative renal hilar mass with ill-defined borders as a characteristic feature of renal RDD and suggested hypo-attenuated renal cortical nodules and subcapsular infiltration as other important imaging findings on CT. In the case described in their study, T1W and T2W imaging showed low signal intensity with mild enhancement on post-contrast images14. In 2019, Kmetz et al. reported the most recent case of bilateral renal RDD in a 60-year-old Caucasian man with a history of anemia and thrombocytopenia of unknown etiology. Subsequent to identifying a left upper quadrant mass on palpation, CT scan was performed for the patient, revealing bilateral soft tissue masses in the perinephric space, measuring up to 22 cm on the left side9.
For the first time in 2004, Yu et al demonstrated moderately increased FDG accumulation in mediastinal lymph nodes affected by RDD, mainly due to excess radioglucose metabolism of the proliferating histiocytes and other inflammatory cells 20. After that, several studies investigated the usefulness of 18F-FDG PET/CT for evaluating nodal and extranodal RDD. In general, the findings of 18F-FDG PET/CT are nonspecific for RDD and histological examination is still needed to establish the diagnosis; however, this modality is valuable for assessment of disease burden and predicting prognosis. Furthermore, it could be advantageous for monitoring response to therapy and detecting foci of disease progression during follow-up 15, 21, 22. This will consequently facilitate decision-making and treatment planning for patients with RDD.
Conclusively, as demonstrated in this case, when encountering a renal mass on imaging with an accompanying renal dysfunction, the clinician should be aware to keep the diagnosis of RDD in mind and consider further evaluation as soon as possible, even in a symptomless patient. This will help to favorably change the patient’s management and prevent unnecessary nephrectomy. Furthermore, performing FDG PET/CT scan on follow-up can be beneficial for evaluation of disease extension, monitoring of disease, and planning future treatment strategies in patients with renal RDD.
Ethics approval and consent to participate: This study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences and written informed consent was obtained from the patient.
Consent for publication: Written informed consent was obtained from the patient for permission of publication.
Availability of data and material: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.