Discussion:
In the two present cases, we demonstrated two important clinical points.
First, in the presence of a granulomatous reaction associated with renal
cell carcinoma, systemic sarcoidosis must be ruled out before the
diagnosis of SLR was retained. Second, systemic sarcoidosis constitutes
a risk factor of neoplasia and can revealed renal cell carcinoma.
Relationships between sarcoidosis and cancers have been suspected for a
long time. Recently, in 2015, a meta-analysis of observational studies
in Epidemiology (MOOSE) group, including more than 25,000 patients
demonstrated that such an association does exist particularly for skin,
hematopoietic, renal, upper digestive, colorectal and liver cancers
[2]. However, although the relative risk for developing renal
carcinoma associated to sarcoidosis is relatively small (RR 1.55), it is
statistically significant [2]. Indeed, later studies have evoked a
causal link between granulomatosis and cancer [3]. Chronic
inflammation and immunologic disorder characterizing sarcoidosis are
known as pathogenic mechanisms in cancer development [3].
In the literature, there have been reports of both systemic
tumor-associated sarcoidosis and peritumoral granulomatous reaction
without sarcoidosis [1, 4-6]. Moreover, the association between
renal cell carcinoma (RCC) and a SLR has often been described [1,
5-9]. Researchers concluded that tumor cells secrete antigenic factors
inducing T-cell-mediated immune response responsible for the formation
of SLR leading to histological appearance and cell distribution similar
to that in sarcoidosis and other granulomatous conditions. Moreover,
sarcoidosis and SLR are thought to share a common inflammatory pathway
because both express angiotensin I converting enzyme in epithelioid and
giant cells [10]. The distinction between a tumor–related
granulomatous reaction and true sarcoidosis can be a problematic issue.
In SLR, granulomas were located in peritumoral and within the tumor in
most cases. So, peritumoral granulomas without intratumoral involvement
would be suggestive of a systematic granulomatosis. On the other hand,
the presence of clinical and radiological features tipped the balance in
favor of systemic sarcoidosis. In our first case, sarcoid granulomas was
located in the peritumoral region and in the adjacent renal tissue and
not within the tumor and did not contain neoplasic cell. The second
patient had the tumor in the right kidney while the granulomatosis
invaded the left kidney. In addition, the two patients presented several
clinical, biological and radiological manifestations consistent with the
diagnosis of sarcoidosis.
The prognostic impact of granulomatosis in cancer is still unclear.
Pavic et al suggested that SLR could play a role in preventing
metastatic dissemination and may associated with a better prognosis in
Hodgkin’s disease and gastric adenocarcinomas [11]. Granulomatous
reaction could play an important role in the host’s defense against
metastatic extension. In our cases, no metastasis was present at the
time of surgery and during follow-up.