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.