Keywords: Adolescence; carcinoma, childhood; clear cell; renal cell
The tumor size in the right kidney was 5.4×4.4×3 cm. It was well limited and associated to a satellite lymph node. On microscopic examination, a RCC with a solid, papillary, and glandular architecture was noted.
Tumor cells were large with clear-to-eosinophilic
granular cytoplasm, atypical nuclei, and irregular nucleoli
(Fig.
There were multiple and large necrosis areas without invasion of the perirenal fat, renal vein, hilum, or ureter. Tumor emboli and invasion of the pelvicalyceal system were noted.
The lymph node dissection found two metastatic paracaval lymph nodes: N2. The tumor was staged pT- 1bN2M0.
Immunohistochemical staining showed that the
tumor cells were positive for CD10, EMA, Vimentin,
and Cytokeratin. The diagnosis of renal cell carcinoma
associated with Xp11.2 translocation/TFE3 gene fusion
was confirmed (Figs.
Our patient did not receive adjuvant treatment. Cancer relapse occurred on the lungs and mediastinal lymph nodes one year after the surgery.
Our patient received oral Sunitinib once daily (50 mg/day) for four weeks every six weeks. CT scan showed progression of the disease. He received Vinblastine as a second line treatment with adrenal, bone, and lung progression. A palliative chemotherapy (Gemcitabine+Doxorubicine) associated with zoledronic acid was administered with disease progression. Our patient died after the third line treatment.
Case 2
A 14-year-old boy without comorbidities presented
with an isolated right thigh pain, noticed several days
before his admission to the hospital. MRI of the thigh
showed a rapidly evolving lesion of the femoral proximal
diaphysis without soft tissue invasion. An abdominal
computed tomography (CT) showed a left mediorenal
mass with a maximum diameter of 30 mm. The
bone scintigraphy showed metastases in the L5 vertebra,
right femur, left sacrum, and ilium. A bone biopsy
was performed. Histological examination revealed a
RCC metastasis. Large polygonal cells with round-toelongated
nuclei, abundant cytoplasm, and multiple areas
of necrosis were observed. Immunohistochemistry
was performed using monoclonal antibodies against
EMA, Cytokeratine, Actine, HMB45, CD99, PS100,
and Chromogranin A. Immunohistochemical analysis
of our patient depicted large cells positive for EMA. The
patient underwent transabdominal radical nephrectomy
with complete resection of the primary tumor.
The tumor size in the left kidney was 25×20 mm. Spindle cells arranged in fascicles were observed. Large cells with eosinophilic cytoplasm, ovoid nuclei, and large and hyperchromatic nucleolus were noted. The renal vein, hilum, and ureter were free of any invasion.
The tumor was a grade 4 pT1a with a fusocellular sarcomatoid component. Immunohistochemical staining showed that the tumor cells were positive for CD10 and Vimentin. Stains for CD117 and CK7 were negative.
The genetic study of the tumor cells revealed a deletion of the VHL gene without TFE3 and TFEB rearrangements. The histopathological, immunohistochemical, and cytogenetic profile of this neoplasm confirmed the diagnosis of clear-cell carcinoma T1aNXM2: stage IV.
The treatment involved a radical surgery followed by a tyrosine kinase inhibitor: Sunitinib once daily (50 mg/day) orally for four weeks every six weeks associated with monthly zoledronic acid. A progression of the disease was noted after six months of treatment. Lung metastases were noted in the chest CT scan. He underwent a second line treatment with Interferon and Vinblastine, and the CT scan still showed progression of the disease. The patient died before starting the third line treatment.
Case 3
A 9-year-old girl without any medical history presented
to the emergency department with a 3-month
history of macroscopic hematuria and flank pain. Ultrasound
showed a renal mass in the lower pole of the
right kidney with a diameter of 68 mm (Fig.
RCC accounted respectively for 1.4%, 15. 2%, and
52.6% of cancers in children younger than 4 years, aged 5 to 9 years, and 10 to 15 years according to a
survey of the Japanese Society of Pediatric Surgeons.
[
The clinical aspects of RCC in pediatrics patients
are the same as those in adults, including flank pain,
abdominal mass, hematuria, fever, and weight loss.[
Tuberous sclerosis, urogenital malformations,
chronic renal failure, neuroblastoma, and teratoma
with chemotherapy may be associated with RCC.[
RCC are classified as clear-cell, papillary, chromophobe,
Xp 11-translocation RCC, RCC associated with
neuroblastoma, and unclassified RCC according to
WHO classification (2004 classification).
The incidence of the pathological subtypes of RCC
include papillary (33%), translocation type (22%),
unclassified (16%), and rarely clear-cell.[
Xp11.2 translocation renal cell carcinomas are uncommon
tumors. They usually affect children and adolescents.
They result from gene fusions between the
transcription factor E3 (TFE3) gene located and at least 6 various partners. A Meta-analysis found that RCC
TFE3 positive patients had a poor prognosis (overall
survival and disease-free survival) and a higher stage
(III/IV) than RCC TFE3 negative patients. Xp11.2
translocation carcinomas appear to have a poorer
prognosis than non-Xp11.2 translocation carcinomas
in young adults and children. Therefore, those patients
must benefit from a much aggressive treatment.[
The cornerstone of the multidisciplinary treatment
of localized RCC is surgery. The role of surgery
is decisive in the success of the treatment. The resection
should be complete. Survival rate is significantly
increased when margins are negative.[
RCC is resistant to radiation therapy or chemotherapy.
The treatment of the metastases remains unclear.
Angiogenesis-inhibiting or immune-stimulating
agents, like vaccines, Interferon, Sorafenib, or Sunitinib
are possible therapeutic alternatives, with limited results
because of the lack of any prospective randomized
studies. Cytokines such as IL-2 and IFN-α provide
modest overall survival benefits.[
The prognosis in advanced stages of RCC is poor.
All patients with stage IV disease died in a series report
by Lack et al.[
Informed consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors declare no conflict of interest.
Authorship contributions: Concept - Y.Y., Y.Z., Z.G., E.C., A.M., ; Design - Y.Z., Z.G., M.K.M.; Supervision - Y.Y., A.M.; Data collection &/or processing - Y.Z., Z.G.; Analysis and/or interpretation - Y.Y., Y.Z., Z.G., ; Literature search - Y.Y., Y.Z., Z.G.; Writing - Y.Y., Y.Z., Z.G..; Critical review - F.L., A.G.
