Contributed by Daniel Geisler, MD and Gabriela Quiroga-Garza, MDFINAL DIAGNOSIS
Papillary renal neoplasm with reverse polarity (PRNRP)
DISCUSSION
Papillary renal cell carcinoma, the second most common renal cell carcinoma, encompasses a spectrum of tumors with different clinical, morphologic, histologic, and molecular features. Due to the poor interobserver reproducibility and overlapping histologic features, the prior division into type 1 and 2 subtypes is no longer recommended [1-5]. New tumor variants have been recently emerging within the papillary renal cell carcinoma spectrum with specific histomorphology, immunoprofile, and clinical behavior [5]. PRNRP is one such newly proposed entity that was originally recognized in 2008 and described as a favorable papillary renal cell carcinoma characterized by oncocytic cells with nonoverlapping, peripheralized low-grade nuclei [6]. Al-Obaidy et al [7] further characterized these tumors, showing consistent KRAS mutations, and proposed the name PRNRP.
Typical clinicopathologic features include a mean age of presentation of 63 years old (range, 36-82 years old), a slight male predominance (56:44 M:F ratio), and an average tumor size of 2.1 cm (range, 0.8 to 8.5 cm) [8]. PRNRP accounts for 4% of papillary renal cell carcinomas [7]. Characteristic histomorphologic findings include a well-circumscribed, solid to partially cystic tumor with predominant thin papillary to tubulopapillary growth patterns. Papillae cores are variably hyalinized to cystically dilated with floating macrophages. The epithelial lining is formed by cuboidal cells with finely granular, eosinophilic cytoplasm. The nuclei are characteristically apically located, away from the basement membrane, and show lower Fuhrman and WHO/International Society of Urological Pathology (ISUP) nuclear grades of 1-2. Necrosis, mitotic figures, psammoma bodies, and tight clusters of foamy macrophages are absent [6-11]. The immunohistochemical profile of PRNRP shows CKAE1/AE3, CK7, GATA3, EMA, and L1CAM positivity. CD117 and vimentin are consistently negative. Alpha-mehtylacyl-CoA-racemase (AMACR) and CD10 shows variable staining [5-12]. Unique KRAS missense mutations have been identified in 85% of cases tested, with the most common KRAS mutation being p.G12V in 54% of cases [7, 8, 11, 12]. FISH analysis has shown trisomy 7, trisomy 17, and chromosome Y deletion in 33%, 33%, and 14% of PRNRP cases, which is more classically associated with other papillary renal cell carcinomas [7]. Most cases present with low pathologic stage (pT1a, 97%), and patient follow-up has shown no recurrence, metastasis, or tumor-related death during the follow up period [7, 8, 11].
The differential diagnosis includes kidney neoplasms with eosinophilic cytoplasm and papillary growth patterns. High grade eosinophilic kidney neoplasms with papillary growth could include fumarate hydratase-deficient renal cell carcinoma, MiT/TFE family translocation renal cell carcinomas, acquired cystic disease-associated renal cell carcinoma, and other renal papillary carcinoma variants. These tumors, however, will show high grade histologic features, including high WHO/ISUP nuclear grade. Tumors in the low grade spectrum that can mimic PRNRP include oncocytoma and chromophobe carcinoma, however, these tumors will not typically show a papillary growth pattern and will be positive for CD117. Other low-grade papillary renal cell carcinomas or morphologic variants of clear cell renal cell carcinoma may also be included in the differential, and ancillary immunohistochemical or molecular testing to show classic PRNRP CK7 and GATA3 positivity or KRAS mutations may be helpful in these scenarios.
REFERENCES
Contributed by Daniel Geisler, MD and Gabriela Quiroga-Garza, MD
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