Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets

Caliò, Anna; Brunelli, Matteo; Segala, Diego; Pedron, Serena; Remo, Andrea; Ammendola, Serena; Munari, Enrico; Pierconti, Francesco; Mosca, Alessandra; Bollito, Enrico; Sidoni, Angelo; Fisogni, Simona; Sacco, Cosimo; Canu, L; Sentinelli, Steno; Fraccon, Anna Paola; Fiorentino, Michelangelo; Scott, Cathryn Anne; Milella, Michèle; Camillo, Porta; Argani, Pedram; Martignoni, Guido

doi:10.1016/j.pathol.2019.11.006

Cited by 40 publications

(33 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our report on TFE3 RCC, classical morphology was documented in only about half of the TFE3 RCC (42 of 85; 49.4%). 5 This result may seem in contrast with the findings of recently published TFE3 RCC cohorts, 3,4,9,10 although 65 of 121 TFE3 RCC cases (53.7%) in these studies were identified in patients younger than 40 years, whereas in our cohort, a much smaller proportion of patients (21 of 85; 24.7%) were younger than 40 years. Among these studies, Argani et al 4 described that classical microscopic features were present in the majority of TFE3 RCC cases regardless of the TFE3 gene fusion partner.…”

contrasting

confidence: 99%

“…1,2 TFE3 RCC may present with various macroscopic features, such as solid mass with a flesh-colored cut surface (Figure 1, A) or multicystic appearance. 3 Large tumor cells with abundant clear or eosinophilic cytoplasm with at least focal true papillary formations (Figure 1, B), with occasional psammoma bodies and/or intracytoplasmic hyaline globules, have been underscored as classical histomorphologic features. However, microscopic features also vary significantly (Figure 1, C), partly because of the TFE3 gene's promiscuous fusion arrangements by multiple gene partners.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Simplified Diagnostic Approach on TFE3 Gene Fusion–Associated Renal Cell Carcinoma

Akgul

Cheng

Idrees

2020

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

contrasting

confidence: 99%

mentioning

confidence: 99%

A Simplified Diagnostic Approach on TFE3 Gene Fusion–Associated Renal Cell Carcinoma

Akgul

Cheng

Idrees

2020

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

“…Among the renal cell carcinomas with clear cells and a papillary architecture, cathepsin K is the most reliable immunohistochemical tool to discern translocation renal cell carcinoma from the most common clear cell renal cell carcinomas and papillary renal cell carcinomas, which are consistently negative for this marker [ 41 , 65 ]. Meaningfully, as above mentioned, immunolabeling for cathepsin K is observed in approximately half of TFE3-rearranged renal cell carcinomas, the neoplasm most confused with clear cell renal cell carcinomas and papillary renal cell carcinoma [ 66 ]. Thanks to the consistent reactivity of neoplastic cells for cathepsin K in TFEB-rearranged renal cell carcinoma, it is easily distinguishable from the usual types of renal cell carcinomas [ 67 ].…”

Section: Cathepsin K In the Differential Diagnosismentioning

confidence: 99%

Cathepsin K: A Novel Diagnostic and Predictive Biomarker for Renal Tumors

Caliò

Brunelli

Gobbo

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by osteoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.

show abstract

“…MiTF‐RCCs may mimic melanoma due to frequent patchy expression of melanocytic markers 28‐30 and underexpression of epithelial markers 23,31 . Inconsistent expression of PAX8 in MiTF‐RCC further adds to this diagnostic challenge 25,26,32,33 . Finally, a subset of renal epithelioid neoplasms may contain melanin pigment, although it remains unclear whether these represent PEComas with TFE3 translocations or true Xp11 RCCs 31,34 .…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of PAX8, PAX2, and cytokeratin in melanomas

et al. 2021

View full text Add to dashboard Cite

Background Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF‐RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas. Methods Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h‐score. Results PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases. Conclusions PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF‐RCC, and other PAX8+ tumors are in the differential diagnosis.

show abstract

Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets

Cited by 40 publications

References 43 publications

A Simplified Diagnostic Approach on TFE3 Gene Fusion–Associated Renal Cell Carcinoma

A Simplified Diagnostic Approach on TFE3 Gene Fusion–Associated Renal Cell Carcinoma

Cathepsin K: A Novel Diagnostic and Predictive Biomarker for Renal Tumors

Immunohistochemical expression of PAX8, PAX2, and cytokeratin in melanomas

Contact Info

Product

Resources

About