Difference between revisions of "TFE3-rearranged renal cell carcinoma"

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      = Xp11.2_translocation_renal_cell_carcinoma_-_high_mag.jpg
| Image      = Xp11.2_translocation_renal_cell_carcinoma_-_high_mag.jpg  
| Width      =
| Width      =
| Caption    = Xp11.2 translocation carcinoma. [[H&E stain]].
| Caption    = Xp11.2 translocation carcinoma. [[H&E stain]].  
| Synonyms  = Xp11 translocation renal cell carcinoma, renal tumour with Xp11 translocation, [[MiT family translocation renal cell carcinoma]] (obsolete term)
| Micro      = large cells with clear or eosinophilic cytoplasm, calcification (classic histomorphologic feature),  +/-papillae, +/-nests, +/-[[psammoma bodies]] (common), +/-[[hyaline bodies]] (common)
| Micro      = large cells with clear or eosinophilic cytoplasm, calcification (classic histomorphologic feature),  +/-papillae, +/-nests, +/-[[psammoma bodies]] (common), +/-[[hyaline bodies]] (common)
| Subtypes  =
| Subtypes  =
| LMDDx      = [[clear cell renal cell carcinoma]], [[papillary renal cell carcinoma]], [[epithelioid angiomyolipoma]], [[clear cell papillary renal cell carcinoma]]
| LMDDx      = [[clear cell renal cell carcinoma]], [[papillary renal cell carcinoma]], [[epithelioid angiomyolipoma]], [[clear cell papillary renal cell carcinoma]], [[unclassified renal cell carcinoma]], [[melanotic Xp11 translocation renal cancer]] (evolving entity)
| Stains    =
| Stains    =
| IHC        = TFE3 +ve (nucleus), CD10 +ve, vimentin +ve, CK7 -ve (usu.)
| IHC        = TFE3 +ve (nucleus), CD10 +ve, vimentin +ve, CK7 -ve (usu.)
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| IF        =
| IF        =
| Gross      =
| Gross      =
| Grossing  =
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Staging    = [[kidney cancer staging]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Assdx      =
| Assdx      =
| Syndromes  =
| Syndromes  =
| Clinicalhx =
| Clinicalhx = children or younger adults
| Signs      =
| Signs      =
| Symptoms  =
| Symptoms  =
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| ClinDDx    = other [[kidney tumours]]
| ClinDDx    = other [[kidney tumours]]
}}
}}
'''Renal tumour with Xp11.2 translocation''', also '''Xp11.2 translocation carcinoma''', is an uncommon [[malignant]] [[kidney tumour]].
'''TFE3-rearranged renal cell carcinoma''' is a rare type of [[renal cell carcinoma]] recognized by the WHO classification as a distinct entity.<ref name=pmid36645398>{{cite journal |authors=Alaghehbandan R, Siadat F, Trpkov K |title=What's new in the WHO 2022 classification of kidney tumours? |journal=Pathologica |volume=115 |issue=1 |pages=8–22 |date=February 2022 |pmid=36645398 |pmc=10342217 |doi=10.32074/1591-951X-818 |url=}}</ref>
 
It was previously known as '''renal tumour with Xp11.2 translocation''', also '''Xp11.2 translocation carcinoma''' and '''Xp11 translocation renal cell carcinoma'''. It was previously lumped with other entities in the category [[MiT family translocation renal cell carcinoma]].
 
It should '''not''' be confused with ''[[TFEB-rearranged RCC]]'', another [[translocation carcinoma]] found in the [[kidney]].


==General==
==General==
*Defined by the presence of a fusion gene formed with TFE3 @ Xp11.2.
*Defined by the presence of a fusion gene formed with TFE3 @ Xp11.2.
*TFE3 is the gene involved in the translocation seen in [[alveolar soft part sarcoma]] (ASPS).
*TFE3 is the gene involved in the translocation seen in [[alveolar soft part sarcoma]] (ASPS).
*Poor prognosis ~ 50% present at stage IV, majority of lymph node metastases.
*Poor prognosis - majority Stage III or Stage IV.<ref name=pmid25002378>{{Cite journal  | last1 = Su | first1 = HH. | last2 = Sung | first2 = MT. | last3 = Chiang | first3 = PH. | last4 = Cheng | first4 = YT. | last5 = Chen | first5 = YT. | title = The preliminary experiences of translocation renal cell carcinoma and literature review. | journal = Kaohsiung J Med Sci | volume = 30 | issue = 8 | pages = 402-8 | month = Aug | year = 2014 | doi = 10.1016/j.kjms.2014.03.003 | PMID = 25002378 }}</ref>
*~1/3 of childhood RCC.<ref name=pmid17667536>{{Cite journal  | last1 = Argani | first1 = P. | last2 = Olgac | first2 = S. | last3 = Tickoo | first3 = SK. | last4 = Goldfischer | first4 = M. | last5 = Moch | first5 = H. | last6 = Chan | first6 = DY. | last7 = Eble | first7 = JN. | last8 = Bonsib | first8 = SM. | last9 = Jimeno | first9 = M. | title = Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. | journal = Am J Surg Pathol | volume = 31 | issue = 8 | pages = 1149-60 | month = Aug | year = 2007 | doi = 10.1097/PAS.0b013e318031ffff | PMID = 17667536 }}</ref>
*~1/3 of childhood RCC.<ref name=pmid17667536>{{Cite journal  | last1 = Argani | first1 = P. | last2 = Olgac | first2 = S. | last3 = Tickoo | first3 = SK. | last4 = Goldfischer | first4 = M. | last5 = Moch | first5 = H. | last6 = Chan | first6 = DY. | last7 = Eble | first7 = JN. | last8 = Bonsib | first8 = SM. | last9 = Jimeno | first9 = M. | title = Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. | journal = Am J Surg Pathol | volume = 31 | issue = 8 | pages = 1149-60 | month = Aug | year = 2007 | doi = 10.1097/PAS.0b013e318031ffff | PMID = 17667536 }}</ref>


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*[[Epithelioid angiomyolipoma]].
*[[Epithelioid angiomyolipoma]].
*[[Clear cell papillary renal cell carcinoma]].
*[[Clear cell papillary renal cell carcinoma]].
*[[Renal cell carcinoma, unclassified]].
*[[Adrenal gland]] - cortex.
*[[Melanotic Xp11 translocation renal cancer]] - an evolving entity that looks like Xp11 translocation carcinoma, keratin negative.<ref name=pmid19065101>{{Cite journal  | last1 = Argani | first1 = P. | last2 = Aulmann | first2 = S. | last3 = Karanjawala | first3 = Z. | last4 = Fraser | first4 = RB. | last5 = Ladanyi | first5 = M. | last6 = Rodriguez | first6 = MM. | title = Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 609-19 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818fbdff | PMID = 19065101 }}</ref>


===Images===
===Images===
====Case 1====
<gallery>
<gallery>
Image:Xp11.2_translocation_renal_cell_carcinoma_-_intermed_mag.jpg | Xp11.2 translocation RCC - intermed. mag. (WC/Nephron)
Image:Xp11.2_translocation_renal_cell_carcinoma_-_intermed_mag.jpg | Xp11.2 translocation RCC - intermed. mag. (WC/Nephron)
Image:Xp11.2_translocation_renal_cell_carcinoma_-_high_mag.jpg | Xp11.2 translocation RCC - high mag. (WC/Nephron)
Image:Xp11.2_translocation_renal_cell_carcinoma_-_high_mag.jpg | Xp11.2 translocation RCC - high mag. (WC/Nephron)
Image:Xp11.2_translocation_renal_cell_carcinoma_-_very_high_mag.jpg | Xp11.2 translocation RCC - very high mag. (WC/Nephron)
</gallery>
====Case 2====
<gallery>
Image: Translocation carcinoma - kidney -- low mag.jpg | TCK - low mag.
Image: Translocation carcinoma - kidney -- intermed mag.jpg | TCK - intermed. mag.
Image: Translocation carcinoma - kidney -- high mag.jpg | TCK - high mag.
Image: Translocation carcinoma - kidney - alt -- high mag.jpg | TCK - high mag.
Image: Translocation carcinoma - kidney -- very high mag.jpg | TCK - very high mag.
</gallery>
</gallery>
www:
====www====
*[http://www.flickr.com/photos/40764007@N08/7403237732/in/photostream/ Translocation carcinoma (flickr.com)].
*[http://www.flickr.com/photos/40764007@N08/7403237732/in/photostream/ Translocation carcinoma (flickr.com)].


==IHC==
==IHC==
*TFE3 +ve (nucleus) - '''key feature'''.<ref name=Ref_WMSP285>{{Ref WMSP|285}}</ref>
Key stains - as per [[ISUP]]:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*TFE3 +ve (nucleus).<ref name=Ref_WMSP285>{{Ref WMSP|285}}</ref>
*TFEB +ve.
*Cathepsin K +ve.<ref name=pmid21602817>{{cite journal |author=Martignoni G, Gobbo S, Camparo P, ''et al.'' |title=Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions |journal=Mod. Pathol. |volume=24 |issue=10 |pages=1313–9 |year=2011 |month=October |pmid=21602817 |doi=10.1038/modpathol.2011.93 |url=}}</ref>
 
Others:
*CD10 +ve.
*CD10 +ve.
*Vimentin +ve.
*Vimentin +ve.
*CK7 -ve.
*CK7 -ve.
**Positive in ~20% of cases.<ref name=pmid21804394>{{Cite journal  | last1 = He | first1 = H. | last2 = Zhou | first2 = GX. | last3 = Zhou | first3 = M. | last4 = Chen | first4 = L. | title = The distinction of clear cell carcinoma of the female genital tract, clear cell renal cell carcinoma, and translocation-associated renal cell carcinoma: an immunohistochemical study using tissue microarray. | journal = Int J Gynecol Pathol | volume = 30 | issue = 5 | pages = 425-30 | month = Sep | year = 2011 | doi = 10.1097/PGP.0b013e318214dd4f | PMID = 21804394 }}</ref>
**Positive in ~20% of cases.<ref name=pmid21804394>{{Cite journal  | last1 = He | first1 = H. | last2 = Zhou | first2 = GX. | last3 = Zhou | first3 = M. | last4 = Chen | first4 = L. | title = The distinction of clear cell carcinoma of the female genital tract, clear cell renal cell carcinoma, and translocation-associated renal cell carcinoma: an immunohistochemical study using tissue microarray. | journal = Int J Gynecol Pathol | volume = 30 | issue = 5 | pages = 425-30 | month = Sep | year = 2011 | doi = 10.1097/PGP.0b013e318214dd4f | PMID = 21804394 }}</ref>
*HMB-45 -ve.
**Positive in ''epithelioid [[angiomyolipoma]]''.
*Melan A -ve/+ve.<ref name=pmid22207547>{{Cite journal  | last1 = Kuroda | first1 = N. | last2 = Mikami | first2 = S. | last3 = Pan | first3 = CC. | last4 = Cohen | first4 = RJ. | last5 = Hes | first5 = O. | last6 = Michal | first6 = M. | last7 = Nagashima | first7 = Y. | last8 = Tanaka | first8 = Y. | last9 = Inoue | first9 = K. | title = Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect. | journal = Histol Histopathol | volume = 27 | issue = 2 | pages = 133-40 | month = Feb | year = 2012 | doi =  | PMID = 22207547 }}</ref>
**Should exclude adrenal if +ve.
*EMA usually -ve.<ref name=pmid20679884>{{Cite journal  | last1 = Argani | first1 = P. | last2 = Hicks | first2 = J. | last3 = De Marzo | first3 = AM. | last4 = Albadine | first4 = R. | last5 = Illei | first5 = PB. | last6 = Ladanyi | first6 = M. | last7 = Reuter | first7 = VE. | last8 = Netto | first8 = GJ. | title = Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. | journal = Am J Surg Pathol | volume = 34 | issue = 9 | pages = 1295-303 | month = Sep | year = 2010 | doi = 10.1097/PAS.0b013e3181e8ce5b | PMID = 20679884 }}</ref>
*CD117 -ve (0 +ve/21 cases<ref name=pmid20679884/>).
*CK (pooled) -ve.<ref name=pmid20679884/> (???)
*WT1 -ve (0 +ve/21 cases<ref name=pmid20679884/>).
*PAX8 +ve (16 +ve/21<ref name=pmid20679884/>).


Others:
Notes:
*HMB-45 & Melan A -ve.
*Poor man's panel - if one doesn't have the more informative stains:
**Positive in ''epithelioid [[angiomyolipoma]]''.
**CK (pooled), EMA, Melan A, HMB-45, CK7, AMACR, CD10, vimentin, RCC.
*‡ The IHC (in comparsion to FISH) has both false negatives and false positives; in one study by Qu ''et al.'' the false positive rate was 7% (2/30) and false negative rate was 4% (2/46).<ref>{{Cite journal  | last1 = Qu | first1 = Y. | last2 = Gu | first2 = C. | last3 = Wang | first3 = H. | last4 = Chang | first4 = K. | last5 = Yang | first5 = X. | last6 = Zhou | first6 = X. | last7 = Dai | first7 = B. | last8 = Zhu | first8 = Y. | last9 = Shi | first9 = G. | title = Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population. | journal = Sci Rep | volume = 6 | issue =  | pages = 21677 | month =  | year = 2016 | doi = 10.1038/srep21677 | PMID = 26880493 }}</ref>


==Molecular==
==Molecular==
*[[Translocation]] involving TFE3, e.g. t(X;1)(p11.2;q21).<ref name=Ref_WMSP285>{{Ref WMSP|285}}</ref>
*[[Translocation]] involving TFE3.<ref name=Ref_WMSP285>{{Ref WMSP|285}}</ref>
**A very low list of partners have been described.
 
The most common are:<ref name=pmid24309327 >{{Cite journal  | last1 = Ellis | first1 = CL. | last2 = Eble | first2 = JN. | last3 = Subhawong | first3 = AP. | last4 = Martignoni | first4 = G. | last5 = Zhong | first5 = M. | last6 = Ladanyi | first6 = M. | last7 = Epstein | first7 = JI. | last8 = Netto | first8 = GJ. | last9 = Argani | first9 = P. | title = Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage. | journal = Mod Pathol | volume =  | issue =  | pages =  | month = Dec | year = 2013 | doi = 10.1038/modpathol.2013.208 | PMID = 24309327 }}</ref>
*t(x;1)(p11.2;q21) PRCC-TFE3.
*t(x;17)(p11.2;q25) ASPSCR1-TFE3.
**Also seen in [[alveolar soft part sarcoma]].


==See also==
==See also==
*[[Kidney tumours]].
*[[Kidney tumours]].
*[[Chromosomal translocation]].


==References==
==References==
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[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Kidney tumours]]

Latest revision as of 13:17, 26 March 2024

TFE3-rearranged renal cell carcinoma
Diagnosis in short

Xp11.2 translocation carcinoma. H&E stain.

Synonyms Xp11 translocation renal cell carcinoma, renal tumour with Xp11 translocation, MiT family translocation renal cell carcinoma (obsolete term)

LM large cells with clear or eosinophilic cytoplasm, calcification (classic histomorphologic feature), +/-papillae, +/-nests, +/-psammoma bodies (common), +/-hyaline bodies (common)
LM DDx clear cell renal cell carcinoma, papillary renal cell carcinoma, epithelioid angiomyolipoma, clear cell papillary renal cell carcinoma, unclassified renal cell carcinoma, melanotic Xp11 translocation renal cancer (evolving entity)
IHC TFE3 +ve (nucleus), CD10 +ve, vimentin +ve, CK7 -ve (usu.)
Molecular translocation involving TFE3, e.g. t(X;1)(p11.2;q21)
Grossing notes total nephrectomy for tumour grossing, partial nephrectomy grossing
Staging kidney cancer staging
Site kidney - see kidney tumours

Clinical history children or younger adults
Prevalence rare
Prognosis poor
Clin. DDx other kidney tumours

TFE3-rearranged renal cell carcinoma is a rare type of renal cell carcinoma recognized by the WHO classification as a distinct entity.[1]

It was previously known as renal tumour with Xp11.2 translocation, also Xp11.2 translocation carcinoma and Xp11 translocation renal cell carcinoma. It was previously lumped with other entities in the category MiT family translocation renal cell carcinoma.

It should not be confused with TFEB-rearranged RCC, another translocation carcinoma found in the kidney.

General

  • Defined by the presence of a fusion gene formed with TFE3 @ Xp11.2.
  • TFE3 is the gene involved in the translocation seen in alveolar soft part sarcoma (ASPS).
  • Poor prognosis - majority Stage III or Stage IV.[2]
  • ~1/3 of childhood RCC.[3]

Microscopic

Features:[4]

  • Large cells.
  • Clear or eosinophilic cytoplasm.
  • Papillae or nests.
  • Psammoma bodies - common.[5]
    • Calcification is considered the classic histomorphologic feature.
  • Hyaline bodies - common.

Notes:

DDx:

Images

Case 1

Case 2

www

IHC

Key stains - as per ISUP:[7]

  • TFE3 +ve (nucleus).[4]
  • TFEB +ve.
  • Cathepsin K +ve.[8]

Others:

  • CD10 +ve.
  • Vimentin +ve.
  • CK7 -ve.
    • Positive in ~20% of cases.[9]
  • HMB-45 -ve.
  • Melan A -ve/+ve.[10]
    • Should exclude adrenal if +ve.
  • EMA usually -ve.[11]
  • CD117 -ve (0 +ve/21 cases[11]).
  • CK (pooled) -ve.[11] (???)
  • WT1 -ve (0 +ve/21 cases[11]).
  • PAX8 +ve (16 +ve/21[11]).

Notes:

  • Poor man's panel - if one doesn't have the more informative stains:
    • CK (pooled), EMA, Melan A, HMB-45, CK7, AMACR, CD10, vimentin, RCC.
  • ‡ The IHC (in comparsion to FISH) has both false negatives and false positives; in one study by Qu et al. the false positive rate was 7% (2/30) and false negative rate was 4% (2/46).[12]

Molecular

  • Translocation involving TFE3.[4]
    • A very low list of partners have been described.

The most common are:[13]

See also

References

  1. Alaghehbandan R, Siadat F, Trpkov K (February 2022). "What's new in the WHO 2022 classification of kidney tumours?". Pathologica 115 (1): 8–22. doi:10.32074/1591-951X-818. PMC 10342217. PMID 36645398. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342217/.
  2. Su, HH.; Sung, MT.; Chiang, PH.; Cheng, YT.; Chen, YT. (Aug 2014). "The preliminary experiences of translocation renal cell carcinoma and literature review.". Kaohsiung J Med Sci 30 (8): 402-8. doi:10.1016/j.kjms.2014.03.003. PMID 25002378.
  3. Argani, P.; Olgac, S.; Tickoo, SK.; Goldfischer, M.; Moch, H.; Chan, DY.; Eble, JN.; Bonsib, SM. et al. (Aug 2007). "Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum.". Am J Surg Pathol 31 (8): 1149-60. doi:10.1097/PAS.0b013e318031ffff. PMID 17667536.
  4. 4.0 4.1 4.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 285. ISBN 978-0781765275.
  5. Prasad, SR.; Humphrey, PA.; Catena, JR.; Narra, VR.; Srigley, JR.; Cortez, AD.; Dalrymple, NC.; Chintapalli, KN.. "Common and uncommon histologic subtypes of renal cell carcinoma: imaging spectrum with pathologic correlation.". Radiographics 26 (6): 1795-806; discussion 1806-10. doi:10.1148/rg.266065010. PMID 17102051.
  6. Argani, P.; Aulmann, S.; Karanjawala, Z.; Fraser, RB.; Ladanyi, M.; Rodriguez, MM. (Apr 2009). "Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma.". Am J Surg Pathol 33 (4): 609-19. doi:10.1097/PAS.0b013e31818fbdff. PMID 19065101.
  7. Amin MB, Epstein JI, Ulbright TM, et al. (August 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): 1017–22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
  8. Martignoni G, Gobbo S, Camparo P, et al. (October 2011). "Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions". Mod. Pathol. 24 (10): 1313–9. doi:10.1038/modpathol.2011.93. PMID 21602817.
  9. He, H.; Zhou, GX.; Zhou, M.; Chen, L. (Sep 2011). "The distinction of clear cell carcinoma of the female genital tract, clear cell renal cell carcinoma, and translocation-associated renal cell carcinoma: an immunohistochemical study using tissue microarray.". Int J Gynecol Pathol 30 (5): 425-30. doi:10.1097/PGP.0b013e318214dd4f. PMID 21804394.
  10. Kuroda, N.; Mikami, S.; Pan, CC.; Cohen, RJ.; Hes, O.; Michal, M.; Nagashima, Y.; Tanaka, Y. et al. (Feb 2012). "Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect.". Histol Histopathol 27 (2): 133-40. PMID 22207547.
  11. 11.0 11.1 11.2 11.3 11.4 Argani, P.; Hicks, J.; De Marzo, AM.; Albadine, R.; Illei, PB.; Ladanyi, M.; Reuter, VE.; Netto, GJ. (Sep 2010). "Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers.". Am J Surg Pathol 34 (9): 1295-303. doi:10.1097/PAS.0b013e3181e8ce5b. PMID 20679884.
  12. Qu, Y.; Gu, C.; Wang, H.; Chang, K.; Yang, X.; Zhou, X.; Dai, B.; Zhu, Y. et al. (2016). "Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population.". Sci Rep 6: 21677. doi:10.1038/srep21677. PMID 26880493.
  13. Ellis, CL.; Eble, JN.; Subhawong, AP.; Martignoni, G.; Zhong, M.; Ladanyi, M.; Epstein, JI.; Netto, GJ. et al. (Dec 2013). "Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage.". Mod Pathol. doi:10.1038/modpathol.2013.208. PMID 24309327.