Papillary renal tumors
2023-09-02 Paola Dal Cin, PhD , Michelle S. Hirsch, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Classification
Definition
Papillary renal epithelial tumors can be either benign or malignant. Papillary adenoma (PA) is a benign lesion which is morphologically similar to papillary renal cell carcinoma (PRCC) but is unencapsulated and typically smaller in size (less than 1.5 cm). There is some evidence to suggest that PAs are a precursor to PRCC as both tumor types can share a KMT2C-specific mutation. 1 Both PA and PRCC are also frequently seen in end-stage kidney disease. PRCC has been shown to demonstrate chromosomes 7 and 17 gains; acquiring additionally polysomies represents the progression of low to high tumor grade. Some tumors with papillary architecture and high-grade eosinophilic cytology (previously classified as “type 2 PRCC”), are now known to represent a heterogeneous group of tumors which includes PRCC, but also includes other previously unrecognized, but distinctive types of renal cell carcinomas characterized by distinct molecular findings (e.g., FH-deficient RCC), and already incorporated in the renal tumor WHO 2022 classification. 2,3
In addition, new entities with overlapping morphologic and genetic feature to PRCC are emerging (e.g. Biphasic squamoid alveolar RCC and Warthin-like PRCC) as well as tumors with overlapping morphologic yet distinct molecular features (e.g., Biphasic hyalinizing psammomatous RCC and papillary renal neoplasms with reversed polarity) have been described. 3-5
| Papillary renal tumors | Genetic marker(s) |
|---|---|
| Papillary renal adenoma | Frequently trisomies 7 and 17, and loss of the Y chromosome, changes that are typical seen in papillary RCCs. 6,7 However, it is deemed benign on the basis of the size cutoff of 15 mm and the lack of a capsule, and is based on the clinical behavior rather than the biological nature of these lesions. The presence of additional karyotypic abnormalities is highly suggestive of malignancy. |
| KMT2C mutations by whole exome sequencing are present in both papillary adenomas and papillary RCCs. 1 | |
| Papillary renal cell carcinoma (PRCC) | Papillary renal cell carcinoma (PRCC) is the second most frequently identified subtype of RCC, representing 10 to 15% of cases. Historically two subtypes PRCC were reconignezed by histological and genetic features: Type 1 was more homogenous and commonly associated with gains of chrs. 7 and 17 and activating somatic MET mutation, while Type 2 was more heterogeneous and was associated with gains of chrs. 12, 16, and 20. 8 However, these desigations are not longer recognized by the WHO (5th edition, 2022) as it has been shown the the latter actually represents a heterogenous group of tumors with spcific molecular alterations. |
| The “classical” form of PRCC demonstrates polysomies of chrs. 7 and 17, loss of the Y chromosome, and additional aberrations of chrs. 2, 3, 12, 16 or 20.9 | |
| Molecular testing is indicated to achieve the correct diagnosis for high grade renal cell caricnomas with papillary architecture.5,10 Some may in fact be PRCC, but others may be FH-deficient RCC, ALK-rearranged RCC, etc. | |
| An activating missense mutation of the MET gene and duplication of chromosome 7 along with the mutated MET is present in 81% of sporadic PRCC cases. 11-13 Loss of 9p /CDKN2A mutations, strongly associated with aggressive PRCC. | |
| Additional genes recurrently mutated are KDM6A, SMARCB1, NFE2L2 , PTPN14 , SAV1, NF2, EGFR and TERT 2,3,9,14-17 However, some of these mutations may represent molecular alterations in high grade RCC with papillary architecture and may not be true PRCC. | |
| Although no loss of 3p has not been reported in PRCC, mutation of SETD2, BAP1 and PBRM1 have been described .18 | |
| Bilateral tumors are present in individual hereditary papillary RCC, HPRCC syndrome OMIM:605074 | |
| PTEN hamartoma tumor syndrome (PHTS) hereditary OMIM:158350 associated with PRCC.19 | |
| Emerging papillary entities | Biphasic squamoid alveolar (BSA) RCC: gains of chrs. 7 and 17 , and the prevalence of MET mutations. 20-22 |
| Warthin-like PRCC : Great variability ranging from a loss of one single chromosome to complex genome rearrangements , gains of chrs. 7 and 17 in a single case23 | |
| Biphasic hyalinizing psammomatous (BHP) RCC: Somatic mutations of the neurofibromin 2 (NF2) gene. 24 However, NF2 mutation have been found in other RCC types, as well as in “unclassified and aggressive RCCs”. 25 Copy number variants were also present, with gain of chr. 20, and loss of chrs. 6 , 1p and 22q. 24 BHP is likley distinct from PRCC. | |
| Papillary renal neoplasm with reverse polarity (PRNRP): Distint subtype of RCC with papillary architecutre. PRNRP demonstrates recurrent KRAS mutations 26-29. Only 1/2 of cases showed classic gain of chrs. 7 and 17, and loss of Y-chromosome. 30 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 31381885 | 2019 | Integrated Molecular Analysis of Papillary Renal Cell Carcinoma and Precursor Lesions Unfolds Evolutionary Process from Kidney Progenitor-Like Cells. | Saleeb RM et al |
| 2 | 30507616 | 2019 | Papillary Renal Cell Carcinoma (PRCC): An Update. | Akhtar M et al |
| 3 | 35674688 | 2022 | Papillary renal cell carcinoma: current and controversial issues. | Angori S et al |
| 4 | 34680535 | 2021 | The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth. | Lobo J et al |
| 5 | 35596618 | 2022 | WHO 2022 landscape of papillary and chromophobe renal cell carcinoma. | Lobo J et al |
| 6 | 2801608 | 1989 | Renal cortical tumors. Cytogenetic characterization. | Dal Cin P et al |
| 7 | 1958590 | 1991 | Cytogenetics of papillary renal cell tumors. | Kovacs G et al |
| 8 | 28984673 | 2017 | Toward Biological Subtyping of Papillary Renal Cell Carcinoma With Clinical Implications Through Histologic, Immunohistochemical, and Molecular Analysis. | Saleeb RM et al |
| 9 | 29617669 | 2018 | The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. | Ricketts CJ et al |
| 10 | 30372384 | 2018 | Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers. | Signoretti S et al |
| 11 | 9715275 | 1998 | Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours. | Fischer J et al |
| 12 | 31867475 | 2019 | A Review of Papillary Renal Cell Carcinoma and MET Inhibitors. | Rhoades Smith KE et al |
| 13 | 34034966 | 2021 | Papillary renal cell carcinoma: Review. | Mendhiratta N et al |
| 14 | 26536169 | 2016 | Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. | Linehan WM et al |
| 15 | 27604489 | 2016 | Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney. | Mehra R et al |
| 16 | 28592388 | 2018 | Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling. | Pal SK et al |
| 17 | 30478013 | 2020 | Mutations in renal cell carcinoma. | D'Avella C et al |
| 18 | 31278395 | 2019 | The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications. | Linehan WM et al |
| 19 | 22381246 | 2012 | Papillary renal cell carcinoma is associated with PTEN hamartoma tumor syndrome. | Mester JL et al |
| 20 | 26999503 | 2016 | Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma? | Hes O et al |
| 21 | 32770124 | 2021 | MET alterations in biphasic squamoid alveolar papillary renal cell carcinomas and clinicopathological features. | Denize T et al |
| 22 | 36201928 | 2022 | Biphasic squamoid alveolar papillary renal cell carcinoma: A unique papillary renal cell carcinoma with distinctive morphology, immunophenotype and molecular genetic features. | Li Y et al |
| 23 | 28325361 | 2017 | Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases. | Skenderi F et al |
| 24 | 32217839 | 2020 | Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma (BHP RCC): A Distinctive Neoplasm Associated With Somatic NF2 Mutations. | Argani P et al |
| 25 | 27713405 | 2016 | Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets. | Chen YB et al |
| 26 | 1534204 | 1992 | Central ANP administration in conscious dogs responding to dehydration and hypovolemia. | Szczepanska-Sadowska E et al |
| 27 | 31953522 | 2020 | Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity-a comparative study with papillary renal cell carcinoma. | Kim SS et al |
| 28 | 35936734 | 2022 | Papillary renal neoplasm with reverse polarity: A clinicopathological and molecular genetic characterization of 16 cases with expanding the morphologic spectrum and further support for a novel entity. | Shen M et al |
| 29 | 36170616 | 2023 | Papillary Renal Neoplasm With Reverse Polarity: A Clinical, Pathologic, and Molecular Study of 8 Renal Tumors From a Single Institution. | Nova-Camacho LM et al |
| 30 | 34352808 | 2022 | Papillary Renal Neoplasm With Reverse Polarity Is Often Cystic: Report of 7 Cases and Review of 93 Cases in the Literature. | Wei S et al |
Citation
Paola Dal Cin, PhD ; Michelle S. Hirsch, MD
Papillary renal tumors
Atlas Genet Cytogenet Oncol Haematol. 2023-09-02
Online version: http://atlasgeneticsoncology.org/solid-tumor/209203
