ABSTRACT
Context: TFE3 translocation renal cell carcinoma (RCC) is a rare tumor that represents approximately 1% of RCC. It was classifed as a member of MiT family translocation RCCs by the World Health Organization in 2016. It is characterized by Xp11 translocation gene fusions involving TFE3. The diagnosis of TFE3 translocation RCC is based on immunohistochemical analysis and TFE3 break apart probes in FISH analysis, rather than histological characteristics and imaging examination. Aims: To determine the clinico-pathological, immuno-phenotypic, and cytogenetic characteristics of TFE3 translocation RCC. Methods and Materials: The clinical data of a 52-year-old-female patient with TFE3 translocation RCC exhibiting rare morphological characteristics was analyzed, and the tumor tissues were probed using histopathological staining, immunohistochemistry, and fluorescence in situ hybridization (FISH). In addition, the relevant literature was reviewed. Results: This case is a TFE3 translocation RCC with rare morphological features. It composed of two types of tumor cells. TFE3 and pax-8 were diffusely and strongly expressed in both tumor cells, and they were partially positive for CAIX, RCC, CK, EMA, CD10, Vim, Melan-A, and p504s. Only 2% of the cells were positive for the proliferation marker Ki-67, and the tumor was negative for CK7, CD117, Inhibin-?, HBM45, and p53. FISH showed a positive signal for TFE3 translocation. Conclusions: This case was a TFE3 translocation RCC with rare morphological features. Through this case report, we emphasize the importance of in situ detection of TFE3 gene translocation and protein in TFE3 translocation RCC.
ABSTRACT
【Objective】 To investigate the effects of the loss of exon 1 of TFE3 on nuclear localization of chimeric TFE3 protein in TFE3 translocation renal cell carcinoma (TFE3 tRCC). 【Methods】 The localization of TFE3 protein in TFE3 tRCC and clear cell renal cell carcinoma (ccRCC) were detected with immunochemistry. The exon retention of TFE3 gene in TFE3 tRCC was analyzed in databases and literatures. The plasmids containing TFE3 full-length and different-length of TFE3 exons which were constructed to pCDH-MCS-EGFP-Puro were transfected into HEK293T using Lipo FiterTM. The localization of EGFP protein in HEK293T cells were detected with confocal microscopy. The localization of TFE3 protein and truncated TFE3 protein were detected with Western blotting. The mRNA expression of the downstream genes of TFE3 protein were detected with q-PCR. 【Results】 Strong nuclear signal of TFE3 protein was observed in TFE3 tRCC, whereas TFE3 protein in ccRCC was mainly localized in cytoplasm. The results of fluorescence imaging and Western blotting showed that TFE3 full-length protein was expressed both in nucleus and cytoplasm, and the expression of truncated TFE3 protein was mainly localized in nucleus. The q-PCR analysis demonstrated that the deletion of exon 1 in TFE3 gene led to a higher transcriptional level of targeted genes of TFE3 protein. 【Conclusion】 The loss of exon 1 in TFE3 played a critical role in preventing TFE3 protein from entering the nucleus. In TFE3 tRCC, the loss of exon 1 in TFE3 gene leads to the nuclear localization of TFE3 fusion protein and activation of its downstream target genes. This mechanism promises to uncover the occurrence and development of TFE3 tRCC.
ABSTRACT
Objective:A single-center analysis was performed to assess the significant clinical features and prognostic factors of TFE3-rearranged renal cell carcinoma (TFE3 rRCC).Methods:The clinical data of 85 confirmed cases of TFE3 rRCC patients at the Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2007 to February 2023 were analyzed retrospectively. Among these patients, there were 39 males and 46 females, with a median age of 32 (26, 45) years. All patients underwent preoperative CT scans, 21/85 cases (24.7%) of TFE3 rRCC exhibited the characteristic feature of "circular calcification" with plain CT imaging, and enhanced CT scan showed that the tumor enhancement during the arterial phase was lower than the adjacent renal cortex. Among the 85 patients in this cohort, the median tumor diameter was 4.8(3.2, 6.5). Thirty-two patients underwent partial nephrectomy (NSS), while 51 patients underwent radical nephrectomy (RN). Two patients with distant metastasis at the time of diagnosis received only sunitinib therapy. Forty-three patients received adjuvant treatment, including 14 patients who received targeted therapy. There were 29 patients in AJCC stage Ⅲ/Ⅳ, with 10 patients presenting with venous tumor thrombus and 14 patients with lymph node metastasis. Histopathology, TFE3 immunohistochemistry, and break-apart TFE3 FISH probe detection were performed on all 85 cases, while 52 patients underwent RT-PCR and/or DNA sequencing. By combining the clinical and pathological data, we summarized the diagnostic Methods for TFE3 rRCC, evaluated the impact of surgical approaches (RN and NSS) on the survival outcomes of cT 1a/b patients, and assessed the influence of genetic subtypes (ASPL, NONO, PRCC, SFPQ, and others) on the survival outcomes of all patients. Furthermore, we analyzed the risk factors for disease progression. Results:TFE3 rRCC exhibited variable histopathological features, and the presence of acinar-like structures with psammoma bodies may be a relatively typical characteristic. All 85 patients showed positive TFE3 immunohistochemical staining. In 6 cases of TFE3 rRCC, break-apart TFE3 FISH probe yielded negative results. However, final confirmation was achieved through genetic sequence, with 5 cases diagnosed as NONO-TFE3 subtype and 1 case as RBM10-TFE3 subtype. Among the 85 patients, 52 underwent RT-PCR and/or DNA sequencing, revealing a total of 8 TFE3 fusion subtypes, including 11 cases of ASPL-TFE3, 8 cases of PRCC-TFE3, 10 cases of NONO-TFE3, 15 cases of SFPQ-TFE3, 1 case of CLTC-TFE3, 2 cases of LUC7L3-TFE3, 4 cases of MED15-TFE3, and 1 case of RBM10-TFE3. The survival analysis results revealed that among the 12 patients with cT 1b stage tumors who underwent radical nephrectomy (RN), the progression-free survival (PFS) was 35 (14, 109) months, which was significantly better than the NSS group ( P=0.041). However, for the 14 patients with cT 1a stage tumors who underwent RN, there was no statistically significant difference in overall survival (OS) and PFS compared to the NSS group, with OS being 55(27, 134) months and PFS being 71(41, 134) months. Stratifying according to TFE3 fusion subtypes, it was found that patients with ASPL-TFE3 fusion had a significantly lower PFS compared to those with non-ASPL-TFE3 fusion subtypes ( P=0.029). Survival analysis revealed that tumor diameter, surgical approach, adjuvant therapy, AJCC staging, venous tumor thrombus, and lymph node metastasis were associated with OS and PFS( P<0.05). The results of the multivariate Cox regression analysis showed that AJCC stage Ⅲ/Ⅳ( HR=2.393, 95% CI 1.418-4.039, P=0.001) and venous tumor thrombus ( HR=3.543, 95% CI 1.159-10.827, P=0.026) were independent risk factors for progression-free survival (PFS). Conclusions:During the non-enhanced phase of CT scan, TFE3 rRCC tumors can exhibit a circular calcification. TFE3 immunohistochemistry is an important screening method for TFE3 rRCC.Break-apart TFE3 FISH probe detection is considered the diagnostic gold standard, and gene sequencing, if feasible, can provide the subtype diagnosis of TFE3 rRCC. For cT 1a stage TFE3 rRCC, partial nephrectomy (NSS) is a viable option, while caution should be taken in selecting NSS for cT1b stage patients. Patients with ASPL-TFE3 fusion subtype have a worse prognosis. AJCC stage Ⅲ/Ⅳ and venous tumor thrombus indicate poor prognosis in TFE3 rRCC.
ABSTRACT
Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.
ABSTRACT
Objective:To compare the imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) with chromophobe RCC.Methods:From November 2016 to January 2020, 28 patients with Xp11.2 RCC and 28 patients with chromophobe RCC confirmed by pathology were retrospectively analyzed in Peking University First Hospital. All 23 patients underwent preoperative CT examination, and 5 patients underwent routine MRI in each group. The clinical and imaging features were observed and recorded. The CT features including side, location, size, boundary, shape, uniform density, composition (solid, cystic-solid, cystic), hemorrhage, calcification, lymph node metastasis of the lesions and distant metastasis were observed, and the CT value of the solid part of the tumor at each stage was measured. On MRI images, the signal of the lesion in each sequence and enhancement mode were observed. The differences in clinical and imaging characteristics between the 2 groups were compared using independent samples t test or χ 2 test. Results:The Xp11.2 RCC more frequently affected young [(27±10) years] patients, while chromophobe RCC more frequently involved middle-aged [(37±7) years] patients asymptomatically, and the difference was statistically significant ( t=-4.99, P<0.001). The lesion size of Xp11.2 RCC [(5.4±2.2) cm] were significantly smaller than that of chromophobe RCC [(6.9±1.8) cm] ( t=-2.93, P=0.005). There were significant differences in the density and composition of lesions between Xp11.2 RCC and chromophobe RCC (χ 2=4.60, 18.67, P=0.032,<0.001). There were no significant differences in the side, location, boundary, shape, hemorrhage, calcification, fat, lymph node metastasis and distant metastasis between the 2 kind of lesions (all P>0.05). The CT values of solid components in Xp11.2 RCC in cortico-medullary phase and delayed phase were higher than those in chromophobe RCC, and the difference were statistically significant ( t=11.80, 20.15, both P<0.001). Five cases of Xp11.2 RCC showed iso- or slightly hyperintense signal on T 1WI and slightly hypointense signal on T 2WI. Two cases showed delayed enhancement after enhancement, and 3 cases showed a slight decrease in delayed phase enhancement. Conclusion:Compared with chromophobe RCC, Xp11.2 RCC has certain characteristics in imaging manifestations (lesion size, density uniformity, composition, CT value of post-enhanced cortico-medullary phase and delayed phase). Imaging manifestations combining the clinical manifestations (age of onset) are helpful for preoperative diagnosis of Xp11.2 RCC.
ABSTRACT
Objective:To summary the problems that may be encountered in the diagnosis of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinomas (Xp11 RCC) and to improve the understanding and diagnostic level.Methods:The clinical and pathological data of 5 children with Xp11 RCC pathologically diagnosed in Children′s Hospital of Capital Institute of Pediatrics from January 2015 to December 2019 were collected for retrospective analysis.Results:The 5 cases included 2 males and 3 females with the age of 4-8 years old.All cases presented with abdominal mass.Four cases received radical nephrectomy and radical tumor resection, and 1 case received simple tumor resection after related examination.Routine HE staining, immunohistochemical staining and fluorescence in situ hybridi-zation (FISH) were performed after surgery.The histological morphology of tumor was varied, and the tumor cells were arranged in nest flake, acinar or papillary pattern, with abundant cytoplasm form completely transparent to eosinophilic staining (pink), and gravel-like calcification was visible.Micropapillary arranged tumor cells appeared in 1 case besides classic pattern; in another case, the tumor cells were highly eosinophilic with abundant cytoplasm and visible round or elliptic eosinophilic bodies.The tumor cells in 5 cases showed diffuse and strong expression of TFE3, and FISH assay showed abnormal separation signal.Conclusions:Xp11 RCC is a relatively rare renal malignant tumor with diverse histological morphology, which should be distinguished from other common renal tumors in children.Its immunohistochemical expression and molecular detection are of specificity, and it should be diagnosed based on clinical incidence.
ABSTRACT
Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.
Subject(s)
Adolescent , Female , Humans , Actins , Breast , Carcinoma, Renal Cell , Epithelioid Cells , MART-1 Antigen , Muscle, Smooth , Perivascular Epithelioid Cell Neoplasms , Sarcoma, Alveolar Soft PartABSTRACT
Xp11 translocation renal cell carcinoma is a rare renal cell carcinoma subtype harboring a TFE3 translocation, which is grouped into the MiT family translocation renal cell carcinomas together with t (6;11) translocation renal cell carcinomas. With the de-velopment and application of immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reac-tion, and RNA sequencing, increasingly more Xp11 translocation renal cell carcinomas have been diagnosed and studied, and many new insights have been elucidated and advances have been made in clinicopathology, molecular genetics, and clinical treatment. The latest progress in Xp11 translocation renal cell carcinoma research is introduced and reviewed in this paper.
ABSTRACT
Objective To explore the clinical and pathological characters of Xp1 1.2 translocation renal cell carcinoma.Method We screened patients of renal cell carcinoma of PUMCH between Jan.2011 and Dec.2015,6 patients with Xp11.2 translocation renal cell carcinoma were found.There were 2 males and 4 females,with average age of 39 (ranging from 16 to 73 years old).Diameter of tumor ranged from 1.9cm to 19.0cm,and 9.6cra in average.Among which,3 cases were detected by routine physical examination,1 by severe anemia (Hb 66g/L),1 by gross hematuria,and 1 by flank discomfort.Before treatment,2 cases had local metastasis (local lymph node,renal pelvis invasion),1 had distant metastasis (pulmonary metastasis).CT examination showed that the tumors had soft tissue density / low density,with significant enhancment or uneven enhancement in enhanced scanning,and were all considered malignancy.6 patients were all treated with surgeries,of which 5 patients received radical nephrectomy,1 patient received nephron sparing surgery.Result Pathologically,most clear cells arranged in a papillary,nest like structure,with psaamoma bodies in them.Immunohistochemical examination showed that all patients were positive for TFE3.AE1/AE3,RCC,Vimentin,CD10,EMA,P504 were positive in different degree.According to pathological result,all 6 patients were proved to be Xp1 1.2 translocation renal cell carcinoma.After surgery,2 patients received immunotherapy,2 received targeted drug therapy,and 1 received local radiotherapy.The follow-up duration ranged from 9 to 56 months (average 37 months).Among which,1 patient died from tumor recurrence and multiple metastasis 22 months after surgery,1 had pulmonary metastasis 12 months after surgery,and the tumor had no significant progress after receiving targeted drug therapy.All the other patients survive without tumor recurrence.Conclusions Xp1 1.2 translocation renal cell carcinoma predominantly occurs in children and adults younger than 40 years.Arterial phase enhancement is slightly lower for Xp1 1.2 translocation renal cell carcinoma in CT scan than that of renal clear cell carcinoma.Histological features and immunohistochemical staining of TFE3 positive expression are important means of diagnosis of this disease.If necessary,gene detection could be done to make better diagnose.Surgery is preferred treatment option.Metastatic leads to poor prognosis,and need to be supplemented by targeted drug therapy.
ABSTRACT
Alveolar soft part sarcoma (ASPS) of the uterine cervix is a rare malignancy, and 21 cases have been reported the literature from every language (including our case). Herein, we describe a 17-yearold female patient who presented with active vaginal bleeding. Pelvic examination revealed a 1.6 x1.0x0.5-cm-sized soft mass protruding from the uterine cervix. The final pathological diagnosis was ASPS of the uterine cervix. Immunohistochemically, tumor cells were strongly nuclear positive for transcription factor E3. The patient remained disease free for 24 months without adjuvant therapy. The prognosis of ASPS in the cervix is considerably better than that of ASPS in soft tissues due to early clinical detection, small size, and resectability. ASPS should be considered in the differential diagnosis of an unusual epithelioid neoplasm showing organoid appearance with mild cytologic atypia and no/rare mitotic figures, particularly in young women. Pathologists should be aware of those unusual locations where ASPS may originate.
Subject(s)
Female , Humans , Cervix Uteri , Diagnosis , Diagnosis, Differential , Gynecological Examination , Immunohistochemistry , Organoids , Prognosis , Sarcoma, Alveolar Soft Part , Transcription Factors , Uterine Hemorrhage , ViperidaeABSTRACT
We represent a pathologically proven case of a four-year-old male patient with renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion, which is rare but more frequent in children or young adults. Computed tomography showed about 2.5 cm size ill-defined mass in the right kidney. The mass was hyperechoic on ultrasound. Magnetic resonance imaging demonstrated a mass with capsular enhancement and diffusion restriction. We present a case of Xp11.2 renal cell carcinoma and provide review of the literature.
Subject(s)
Child , Humans , Male , Young Adult , Carcinoma, Renal Cell , Diffusion , Gene Fusion , Kidney , Magnetic Resonance ImagingABSTRACT
O hepatoblastoma é uma neoplasia embrionária hepática que ocorre na faixa pediátrica, rara, sendo bastante heterogênea devido aos seus diferentes componentes epiteliais e mesenquimais. Pouco ainda se sabe a respeito de sua patogênese. Utilizando um microscópio de captura a laser foram dissecadas áreas de componente epitelial do hepatoblastoma e áreas de tecido hepático adjacente não acometido. Destas amostras obtidas de pacientes não submetidos ao tratamento prévio, foram extraídos RNA e confeccionados cDNA microarrays, para análise comparativa da expressão gênica, seguida de validação por método imunohistoquímico de alguns genes selecionados. Comparando neoplasia e tecido hepático em duas amostras criopreservadas foram identificados 70 genes diferencialmente expressos, sendo 19 hiperexpressos e 51 hipoexpressos no tumor. A maioria dos genes encontrados foi mapeada nos cromossomos 1 e 2. Dos genes selecionados para validação por método imuno-histoquímico, destacaram-se o receptor de Insulina e o TFE3 (genes hipoexpressos no cDNA microarray). A imunomarcação para o receptor de insulina foi positiva tanto no tecido hepático não acometido quanto no componente epitelial fetal do hepatoblastoma , mas foi consistentemente negativa nas amostras de componente embrionário (9/9). A imunomarcação para o TFE3 foi positiva no tecido hepático não acometido, e nos componentes epitelial fetal e embrionário, em proporção variável das células com expressão mais intensa no componente embrionário. As reações imuno-histoquímicas para os outros genes selecionados não permitiram interpretação conclusiva. A alta proporção dos genes diferencialmente expressos localizados nos cromossomos 1 e 2 reflete os achados citogenéticos relatados na literatura relacionada ao hepatoblastoma . Achados de imunoexpressão de proteínas relacionadas aos genes TFE3 e receptor de insulina no tecido hepático e nos diferentes componentes do hepatoblastoma são inéditos e sugerem participação da via...
Hepatoblastoma is a rare tumor, and little is known about its pathogenesis and genetic alterations. Using a laser capture microdissection microscope we sampled areas of epithelial component of hepatoblastoma prior chemotherapy and their normal liver counterpart in order to perform the comparative gene expression analysis followed by the validation of selected genes by immunohistochemistry. Comparing tumor and non-diseased liver in two frozen samples, 70 differentially expressed genes were found, 19 overexpressed and 51 underexpressed in the tumor. Most of the genes were located at chromosomes 1 and 2. Of the genes selected for validation by immunohistochemistry, the most interesting findings came from Insulin receptor and TFE3 (both underexpressed genes). Insulin receptor was positive in non diseased liver and in the fetal component of the Hepatoblastoma but was consistently negative in the embryonal component (9/9 cases). The TFE3 staining was positive in the normal liver and fetal and embryonal components of the tumor in variable proportion of the cells, more marked in the embryonal component. The higher proportion of genes located at chromosomes 1 and 2 corroborates the cytogenetics findings reported in the literature related to Hepatoblastoma . The immunohistochemistry findings of different expression of insulin receptor in the fetal and embryonal components of Hepatoblastoma and the positivity of TFE3 in normal liver and in the tumors epithelial components deserves further investigation regarding the role of these genes to the pathogenesis of Hepatoblastoma.
Subject(s)
Humans , Gene Expression , Hepatoblastoma , Immunohistochemistry , Oligonucleotide Array Sequence Analysis , Receptor, InsulinABSTRACT
Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor of uncertain origin, and it has a strong propensity for metastasis to the lungs, bones and brain. We report upon an unusual case of ASPS, presenting as multiple lung nodules with no other detectable primary site, in a 44-year-old man. A fine needle aspiration of the nodules yielded scattered, discohesive cells, each containing an eccentrically displaced nucleus and prominent nucleolus, on a granular background. Tumor cells with numerous bared nuclei, and occasional sheets of epithelioid cells were also found. Under the cytological diagnosis of an unclassified epithelioid malignant tumor, resection of the lung nodules was performed. The histologic findings were consistent with ASPS, showing positive TFE3-nuclear immunoreactivity. There is limited literature concerning cytological findings associated with pulmonary ASPS: especially in cases where the primary site is unknown. Here, we present a cytological review of pulmonary ASPS, investigating the significance of TFE3 staining in the diagnosis of ASPS.
Subject(s)
Adult , Humans , Biopsy, Fine-Needle , Brain , Epithelioid Cells , Lung , Neoplasm Metastasis , Sarcoma, Alveolar Soft Part , ViperidaeABSTRACT
BACKGROUND: The new WHO classification includes the recently described renal cell carcinomas (RCC) that are associated with several different translocations, involving chromosome Xp11.2, and they all result in gene fusions involving the TFE3 gene. The authors describe the clinicopathologic and immunohistochemical findings of 4 patients who had the morphologic features of RCC with Xp11.2 translocations. METHODS: Among 9 surgically resected and pathologically proven pediatric RCCs, 4 showed a typical RCC histopathology with the Xp11.2 translocation. Immunohistochemical stains were performed for TFE3, AE1/AE3, epithelial membrane antigen, vimentin, HMB45, S-100 protein and CD10. RESULTS: The 4 study subjects included one male and 3 females, and their chief complaints were gross hematuria and abdominal pain. Histologically, the tumors showed two different histologic types: type 1 tumors (2 cases) that corresponded to those of ASPL-TFE3 RCC, and type 2 tumors (2 cases) that corresponded to PRCC-TFE3 RCC. Nuclear TFE3 immunostaining was seen in 3 cases. All the tumors were immunoreactive for CD10, and vimentin and cytokeratin were expressed in 3 cases and HMB-45 was expressed in 2 cases. CONCLUSIONS: Our results show that significant numbers of pediatric RCC are translocation-related. Therefore, when one encounters an RCC in the pediatric population, the possibility of a translocation-related RCC should be kept in mind.