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Review Article Open Access

Does Age Affect the Outcomes of Translocation Renal Cell Carcinoma? A

Retrospective Analysis from A Middle Eastern Cohort
Ali Al-Daghmin*, Sohaib Alhamss, Weam Al-Qasem, Khloud Al-Qasem, Lujain Al-Omari, Hani Al-Najjar and Duaa DAhbour
Department of Surgery, King Hussein Cancer Center Surgery, Jordan

Abstract
Background: The natural history of Translocation renal cell carcinomas (tRCC) is variable from indolent
behaviors to aggressive disease that demonstrates lymph node and widespread metastasis. Translocation renal cell
carcinomas (TRCC) represent 1% to 5% of all cases of renal cell carcinoma (RCC).
Objectives: We sought to characterize the associations between age at presentation of tRCC patients and stage,
grade, survival and recurrence of the disease in Middle Eastern institution. Materials and methods: Retrospective
review of clinical and pathological data from a single institution for 23 patients diagnosed with tRCC between 2005
and 2017. Patients were categorized into two group based on age group 1 (>40 years) and group 2 (≤ 40 years). We
evaluated the association between tumor grade, gender, disease free survival (DFS), overall survival (OS) and age.
Results: The tumor was on the right kidney in 52.2% of the patients, and bilateral in one patient. Ten patients
(43.5%) were above 40 years of age, and 13 patients (56.5%) were less than or equal to 40 years old regarding the
tumor characteristics, the mean tumor size was 9 cm; 4 patients (17.3%) had pathologic T1, seven patients (30.4%)
had pathologic T2, 10 patients (43.4%) had pathologic T3 or more and two patients (8.7%) had no surgery. Eleven
patients (47.8%) had lymph node dissection for clinically enlarged lymph nodes and seven (64%) of them had lymph
nodes metastasis. Nineteen patients (83%) underwent radical nephrectomy and two (8%) had partial nephrectomy.
Bilateral renal tumors were managed with left radical and right partial nephrectomy. There were no differences in
DFS in patients above and below 40 years of age. No statistically significant associations between Disease-Free
survival, gender, pathologic T staging, overall survival and age.
Conclusion: tRCC has variable clinical behavior from indolent to aggressive disease. Age may not affect this
clinical behavior.

Keywords: Renal cell carcinoma; Translocation renal cell
carcinomas; Microphthalmia-associated transcription
Introduction
Renal cell carcinomas (RCCs) are a heterogeneous group of tumors
which account for around 90% of all adult renal malignancies [1]. The
most common subtypes are clear cell (60-75%), followed by papillary
(10-15%), chromophobe (5%) and collecting duct carcinoma [2]. Recent
advances in the understanding of molecular alterations implicated in
the pathogenesis of RCC have led to the development of a new sub-
classification of these tumors [3]. Translocation renal cell carcinoma
(tRCC) is a newly recognized subtype of RCC with chromosomal
translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21)
[4]. Microphthalmia-associated transcription (MiT) family tRCC entails
Xp11 tRCC and t (6;11) RCC. Xp11 tRCC and t (6;11) RCC are also known
as TFE3- and TFEB-rearranged RCC, respectively. TFE3 and TFEB belong
to the MiT family that regulates melanocyte and osteoclast differentiation.
TFE3- and TFEB-rearranged RCC show distinguished clinicopathological
and immunohistochemical features [5]. Xp11 tRCC comprises 20-40%
of childhood RCC and about 4% of adult RCC with an average age of
50 years at diagnosis [6,7]. The natural history of Xp11 tRCC is variable
from indolent behaviors [8,9] to aggressive disease that demonstrates
lymph node and widespread metastasis. Xp11 tRCCs have the potential
to metastasize as late as 20-30 years after diagnosis [7,10]. The associations
between age, stage, grade of the disease, survival and recurrence of the
disease have not been addressed in the literature. The aim of this study is
to identify if these associations exist.
Materials and Methods
Study settings
The study was conducted at King Hussein Cancer Centre (KHCC),
a comprehensive center that serves cancer patients in both inpatient
and outpatient settings. RCC patients receive treatment according to
KHCC-clinical practice guidelines (CPG). Approval was gained from
the KHCC Institutional Review Board and the KHCC ethics committee.
Data for all patients who underwent radical or partial nephrectomy and
pathology that revealed tRCC between December 2005 and August
2017 were reviewed retrospectively.
Study design
All patients underwent staging assessment at the time of diagnosis,
including clinical examination, blood tests, chest x-ray and computed
tomography (CT) of the abdomen and pelvis. Pathological staging was
performed using 2010 TNM classification system. Follow-ups were
performed according to KHCC-CPGs, which included laboratory
and radiological examinations according to the final TNM stage and
tumor grade. Additional imaging was ordered as clinically indicated.
For those with metastatic disease, tumors were evaluated by physical
examination and CT scans at baseline and every 3 to 6 months. Overall
disease responses were documented using RECIST criteria [11].
*Corresponding author: Ali Al-Daghmin, Urologic Oncology & Robotic Surgery
Consultant, Surgery Department King Hussein Cancer Center, Jordan, Tel:
00962798917748; E-mail: A_daghamin@hotmail.com
Received December 24, 2018; Accepted December 31, 2018; Published January
07, 2019
Citation: Al-Daghmin A, Alhamss S, Al-Qasem W, Al-Qasem K, Al-Omari L, et
al.(2019) Does Age Affect the Outcomes of Translocation Renal Cell Carcinoma?
A Retrospective Analysis from A Middle Eastern Cohort J Oncol Res Treat 4: 128.
Copyright: © 2019 Al-Daghmin A, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.

J Oncol Res Treat, an open access journal Volume 4 • Issue 1 • 1000128

Citation: Al-Daghmin A, Alhamss S, Al-Qasem W, Al-Qasem K, Al-Omari L, et al.(2019) Does Age Affect the Outcomes of Translocation Renal Cell
Carcinoma? A Retrospective Analysis from A Middle Eastern Cohort J Oncol Res Treat 4: 128.

Page 2 of 5

TFE3 stain was performed for tumors with histological Statistical analysis
features suggestive of tRCC, like papillary architecture and clear to
eosinophilic cytoplasm. The diagnosis of Xp11 tRCC was confirmed The Chi-squared test was used to identify associations between
by immunohistochemistry (IHC) analysis for nuclear TFE3 staining. results, responses, and demographics. The strength of associations
Xp11.2 tRCC was analyzed by IHC staining to detect TFE3 in each was assessed by calculating odds ratios (ORs) and 95% confidence
tumor and tissue microarray block (catalog No. sc5958; Santa Cruz intervals. Relations between categorical and continuous variables were
Biotechnology, Santa Cruz, CA, USA). Angiogenesis markers IHC evaluated in independent t tests. Cross-tabulation was used to explore
analysis of the tumor tissue samples was performed by using the associations between categorical data, and chi-squared tests were used
Ventana XT auto immunostainer (Roche, San Francisco, CA, USA) to assess the statistical significance of associations. P values less than
with the Optiview Dab Detection Kit (Roche) according to the 0.05 were considered statistically significant.
manufacturer’s instructions. The results were independently evaluated Results
by two specialized pathologists blind to the clinical data. The Fuhrman
nuclear grading system, which uses a four point multi-parametric Clinical characteristics
scale based on nuclear features, size, shape, color, and nucleolar Twenty-three patients were identified, 15 (65%) of the patients
prominence was used [12] as shown in Figures 1-3. Data including the were males. The mean age at diagnosis was 37 years. The majority of the
patients’ characteristics, clinical manifestations, surgical techniques, patients (65%) were diagnosed incidentally during abdominal imaging
pathological findings, radiology, and clinical outcomes was collected. for other indications. The remaining 35% suffered from pain, gross
Response to treatment based on cancer-specific survival (CCS), overall hematuria, metastasis, abdominal distension or weight loss at the time
survival (OS) and progression-free survival (PFS) were analyzed. of the first presentation. Patients’ characteristics are shown in Table 1.
Patients were categorized into two group based on age group 1 (>40
years) and group 2 (≤ 40 years) and association between tumor grade, The tumor was on the right kidney in 52.2% of the patients, and
sex, disease free survival (DFS) and age were studied across groups. bilateral in one patient. Ten patients (43.5%) were above 40 years of
age, and 13 patients (56.5%) were less than or equal to 40 years old.
Regarding the tumor characteristics, the mean tumor size was 9 cm;
4 patients (17.3%) had pathologic T1, seven patients (30.4%) had
pathologic T2, 10 patients (43.4%) had pathologic T3 or more and
two patients (8.7%) had no surgery and thus were not evaluated
for pathologic T staging. Eleven patients (47.8%) had lymph node
dissection for clinically enlarged lymph nodes and seven (64%) of them
had lymph nodes metastasis. Patients were categorized into two group
based on age group 1 (<40 years) and group 2(<=40 years). Tumor T
stage distribution among groups are shown in Table 2.
Figure 1: The results were independently evaluated by two specialized
pathologists blind to the clinical data. Patient Age at Sex Presenting Symptom Laterality
Number Presentation
(years)
1 41 Male Incidental Diagnosis Left
2 36 Male Incidental diagnosis Right
3 58 Male Incidental diagnosis Bilateral
4 33 Male Incidental diagnosis Right
5 13 Female Incidental diagnosis Right
6 2 Female Abdominal Distension Right
7 26 Male Fatigue and hematuria Left
8 51 Male Incidental diagnosis Right
9 38 Male Incidental diagnosis Left
Figure 2: The Fuhrman nuclear grading system, which uses a four point 10 48 Male Incidental diagnosis Right
multi-parametric scale based on nuclear features, size, shape, color, and
11 31 Female Incidental diagnosis Right
nucleolar prominence was used.
12 25 Female Incidental diagnosis Left
13 43 Male Incidental diagnosis Right
14 44 Female Incidental diagnosis Left
15 33 Female Abdominal Pain Left
16 22 Female Loin Pain Right
17 41 Male Neck mass Right
18 35 Male Hematuria Left
19 32 Male Incidental diagnosis Right
20 47 Male Incidental diagnosis Left
21 43 Male Incidental diagnosis Right
22 66 Male Loin pain and hematuria Left
Figure 3: The Fuhrman nuclear grading system, which uses a four point 23 37 Female Fatigue, weight loss and Left
multi-parametric scale based on nuclear features, size, shape, color, and loin pain
nucleolar prominence was used.
Table 1: Demographic data of patient population.

J Oncol Res Treat, an open access journal Volume 4 • Issue 1 • 1000128

Citation: Al-Daghmin A, Alhamss S, Al-Qasem W, Al-Qasem K, Al-Omari L, et al.(2019) Does Age Affect the Outcomes of Translocation Renal Cell
Carcinoma? A Retrospective Analysis from A Middle Eastern Cohort J Oncol Res Treat 4: 128.

Page 3 of 5

Patient Number Disease-Free Period Postoperatively Site of Recurrence

1 No recurrence or metastasis No recurrence or metastasis
2 No recurrence or metastasis No recurrence or metastasis
3 No recurrence or metastasis No recurrence or metastasis
4 No recurrence or metastasis No recurrence or metastasis
5 No recurrence or metastasis No recurrence or metastasis
6 No recurrence or metastasis No recurrence or metastasis
7 No recurrence or metastasis No recurrence or metastasis
8 No recurrence or metastasis No recurrence or metastasis
9 3 months Local recurrence
10 5 months Lung
11 3 years Bone, soft tissue, adrenal glands, peritoneum
12 3 years Lung
13 No recurrence or metastasis No recurrence or metastasis
14 No recurrence or metastasis No recurrence or metastasis
15 No recurrence or metastasis No recurrence or metastasis
16 5 years Regional lymph nodes
17 Metastasis on presentation Bilateral lung, left cervical, mediastinal and para-aortic Lymph nodes
18 Metastasis at presentation Lung and retroperitoneal lymph nodes
19 No recurrence or metastasis No recurrence or metastasis
20 No recurrence or metastasis No recurrence or metastasis
21 Metastasis on presentation Multiple para-aortic lymph nodes
22 No recurrence or metastasis No recurrence or metastasis
23 No recurrence or metastasis No recurrence or metastasis
Table 2: Disease-free period and site of recurrence and metastasis.

Surgical intervention T stage Total Age<=40 Age>40

Not available 2 2 0
Nineteen patients (83%) underwent radical nephrectomy and two
T1 3 2 (18%) 1 (10%)
(8%) had partial nephrectomy. Bilateral renal tumors were managed
T1b 1 0 1 (10%)
with left radical and right partial nephrectomy. Eighteen patients (78%)
T2 2 1 (9%) 1 (10%)
had an open approach and three patients (13%) had a laparoscopic
T2a 3 2 (18%) 1 (10%)
approach. Eight patients (35%) had metastasis, and three of the eight
T2b 1 1 (9%) 0
patients had metastasis at the time of diagnosis. Six patients (26%)
T3 2 1 (9%) 1 (10%)
received sunitinib for their metastatic disease, and one of them had
T3a 4 1 (9%) 3 (30%)
a complete response with a disease free period of 18 months. Four
T3b 3 2 (18%) 1 (10%)
patients had a stable disease for an average of 19 months, and only
T4 2 1 (9%) 1 (10%)
one had disease progression without any response (Table 3). There
were no differences in DFS in patients above and below 40 years of Table 3: T staging of patients (n=23).
age. No statistically significant associations between disease-free period
postoperatively, sex, pathologic T staging, overall survival and age were
found across the groups, using 40 years as a cut point (Figures 4 and 5).

Follow up
Three patients died during follow-up time; one patient died
4 months after surgery, one 21 months after surgery (both due to
metastasis) and one died of brain hemorrhage. The mean follow-up
time is 35 months, and 3-year disease overall free survival was 75%.

Discussion
The median age at diagnosis of RCC is approximately 64, according
to the 2003 to 2007 National Cancer Institute (NCI) and the Surveillance,
Epidemiology and End Results (SEER) Cancer Statistics Review. RCC
is unusual in patients under 40 years of age and is rare in children [13-
15]. tRCC, is a distinct variant of RCC and is associated with fusion of
the TFE3 gene to other genes located on chromosome Xp11.2 [8,9,16]. Figure 4: No statistically significant associations between Disease-Free
Xp tRCC was initially thought to be a malignancy of pediatrics and Period postoperatively, sex, pathologic T staging, overall survival and age
young adults. However, more recent data has increasingly identified were found across the groups, using 40 years as a cut point.
this tumor in older adults as well [17]. Adequate immunohistochemical
workup is not routinely done for adults with RCC, which results Furthermore, the similar gross and histological findings to other RCCs
in most cases of adult tRCC misdiagnosed as conventional [18]. also contributed to the underestimation of tRCC frequency in adults [19].

J Oncol Res Treat, an open access journal Volume 4 • Issue 1 • 1000128

Citation: Al-Daghmin A, Alhamss S, Al-Qasem W, Al-Qasem K, Al-Omari L, et al.(2019) Does Age Affect the Outcomes of Translocation Renal Cell
Carcinoma? A Retrospective Analysis from A Middle Eastern Cohort J Oncol Res Treat 4: 128.
Figure 5: No statistically significant associations between Disease-Free
Period postoperatively, sex, pathologic T staging, overall survival and age
were found across the groups, using 40 years as a cut point.
Translocation carcinoma tens to occur at a younger age compared
with other RCCs: In our study the mean age at diagnosis is 37 years and
is more common in males (65%) than in females.
Nevertheless, current data depending on many cohort studies
as well as some meta-analyses show that the course of tRCC is more
indolent in pediatric populations. Adults tend to present with advanced
stage and distant metastases and thus have a poorer prognosis [17,20].
The treatment of Xp11.2 tRCC remains a major challenge for health
care providers. Many advances in the treatment of clinically localized
and metastatic RCC disease have been accomplished [21]. This is not
the case in tRCC management due to the small number of patients
to run clinical trials. Thirty cases of t(6;11) RCC were reported in the
International Society of Urological Pathology Conference. Of these,
the majority of pediatric cases were indolent with recurrence in only
17% of them. Most of the adult population in the same study presented
with metastasis or pursued an aggressive clinical course causing death
[22]. Another study which focused on regional lymph node metastasis
as a prognostic factor for tRCC showed that regional lymph node
metastasis in pediatrics doesn’t necessarily predict poor prognosis as it
nearly does in adults [8]. Another multivariate analysis by Peckova et al.
demonstrated that the more aggressive t(6,11) RCC appeared to affect
older patients (mean age of 45.2 years) rather than younger patients
(mean age of 31.5 years) [23]. The management of clinically localized
Xp11.2 tRCC is similar to general RCC guidelines [24]. Currently, there
is no standard treatment for patients with MiT family tRCC. Most
studies depend on the PFS, CSS and OS as indicators of the efficiency of
different treatment modalities. Currently, the most favorable outcomes
have been reported with patients who undergo a radical nephrectomy
and lymph node dissection before the development of metastasis.
However, the true challenge lies in the postoperative follow-up process;
special follow-up protocols are seemingly promising in improving the
quality of life of tRCC adult patients and in prolongation of the three
mentioned parameters [25]. Future studies will focus on genomic
technologies to identify prognostic factors and therapeutic targets in
tRCC. One study found that high chromosome copy number alterations
in Xp11 tRCC are associated with aggressive behavior [24]. Another
found that chromosome 17q gain correlated with older age and worse
outcome which corroborates the effect of age reported by Ellis et al.
[10]. The scope of this study is to address the association between age (>
or ≤ 40 years) and disease free period postoperatively, sex, pathologic
J Oncol Res Treat, an open access journal
Page 4 of 5
T staging, and overall survival in patients with tRCC treated in KHCC.
No significant associations were found across the groups.
This study is limited by a retrospective design and the absence
of long-term follow-up. Furthermore, the small sample size makes it
difficult to draw a definitive conclusion regarding associations between
age and the factors studied.
Conclusion
tRCC, is a variant of RCC with unique characteristics. tRCC has
variable clinical behavior from indolent to aggressive disease. Age may
not affect this clinical behavior. Future studies with larger sample size
and a longer follow up period is required.
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Carcinoma? A Retrospective Analysis from A Middle Eastern Cohort J Oncol Res Treat 4: 128.
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