Papillary renal neoplasm with reverse polarity: A case report

Abstract

Papillary renal neoplasm with reverse polarity is a rare, newly identified subtype of papillary renal cell carcinoma believed to originate from the distal renal tubules. It is characterized by distinct histomorphological features and an associated immunophenotype. Contrast-enhanced scans usually do not exhibit a rapid wash-in and wash-out enhancement pattern, and this tumor is generally associated with a favorable overall prognosis. This study reports a case of papillary renal neoplasm with reverse polarity in a male patient in his 50 s who was admitted with recurrent left lumbar pain and discomfort. Computed tomography showed a quasi-circular, isodense lesion measuring 1.3 × 0.8 cm in the left kidney. The contrast-enhanced scan demonstrated a rapid wash-in and wash-out enhancement pattern. Following comprehensive evaluation, the patient underwent laparoscopic partial nephrectomy.

Postoperative pathological examination with hematoxylin and eosin staining showed tumor cells forming papillary structures with eosinophilic cytoplasm and basally displaced nuclei. The tumor stroma exhibited focal proliferation of fibrous and adipose tissue along with thick-walled blood vessels. The pathological findings aligned with the classic characteristics of papillary renal neoplasm with reverse polarity. No tumor recurrence or distant metastasis was detected during an 18-month postoperative follow-up.

This case report highlights an atypical imaging enhancement feature of papillary renal neoplasm with reverse polarity, thereby enriching the clinical and imaging spectrum of this tumor. It also confirms that pathological examination combined with immunohistochemistry remains the gold standard for diagnosing papillary renal neoplasm with reverse polarity, providing a valuable clinical reference for the identification and differential diagnosis of this rare neoplasm.

Introduction

Papillary renal cell carcinoma (PRCC) is a low-grade malignant tumor arising from renal tubular epithelial cells, with a characteristic papillary neoplastic growth pattern. In the traditional classification, PRCC is divided into types I and II based on the detailed morphologic features of the tumor cells. ¹ However, dichotomizing PRCC may be challenging because many tumors frequently harbor mixtures of the two types, and the distributions of types I and II tumors do not influence patient outcomes. Therefore, the 2022 World Health Organization (WHO) classification has updated and expanded the subclassification of PRCC. In the 2022 WHO classification, the former PRCC type I is now referred to as “PRCC of classic pattern.” Three additional morphologic patterns of PRCC have been introduced: (a) bi-phasic (alveolo-squamoid) pattern exhibiting mostly solid growth; (b) papillary neoplasm with reverse nuclear polarity, previously described as “oncocytic low-grade PRCC;” and (c) Warthin-like PRCC, which exhibits brisk inflammation mimicking Warthin tumor of the salivary gland. Among these tumors, glomeruloid papillae, psammoma bodies, edematous papillae, and foamy macrophages in the papillary cores are uncommon in this subtype. ²

In 2003, Allory et al.³ classified 43 cases of PRCC according to morphologic subtypes and analyzed the prognostic value of this classification. Interestingly, four of these 43 cases exhibited distinct features that differed from those of other PRCC subtypes and were characterized by oncocytic cells with abundant eosinophilic cytoplasm and round, regular nuclei. ³ The authors therefore proposed naming this variant “oncocytoid-type papillary renal cell carcinoma.” All four patients with oncocytoid-type PRCC remained disease-free after radical nephrectomy, suggesting a favorable clinical outcome. In 2019, Al-Obaidy et al. ⁴ retrospectively reviewed 421 PRCC cases diagnosed in the pathology departments of three medical institutions between 2004 and 2017. Based on morphologic characteristics, they identified 18 tumors with distinct features that differed from conventional PRCC. Comprehensive analyses of the immunophenotype and chromosomal characteristics of these tumors revealed indolent biological behavior, and the authors subsequently named this novel entity papillary renal neoplasm with reverse polarity (PRNRP). In an imaging study of PRNRP by Wen et al., ⁵ the authors found that PRNRP typically manifests as a small hypoperfused renal mass characterized by a visible pseudocapsule on contrast-enhanced scans, as well as isoattenuating or mildly hyperattenuating signals on subtraction images. Since then, an increasing number of researchers have focused on this unique renal tumor subtype.

The typical morphologic feature of PRNRP is a papillary or tubulopapillary structure lined by a single layer of eosinophilic cells with finely granular cytoplasm, apically located round nuclei, and inconspicuous nucleoli. Immunohistochemically, PRNRP shows diffuse positivity for GATA-3, a feature that distinguishes it from other PRCC subtypes. However, PRNRP is relatively rare compared with conventional PRCC, and a larger number of clinical cases is still needed to conduct in-depth research on this tumor. Herein, we report a newly diagnosed case of PRNRP in our department.

Case report

In February 2025, a male patient in his 50 s presented to Northern Jiangsu People's Hospital (Yangzhou, China) with recurrent left-sided lumbago and discomfort for more than half a month. The patient had no significant past medical history, such as diabetes, hypertension, or coronary heart disease. Physical examination also revealed no obvious abnormalities. As the patient presented with low back pain, renal computed tomography (CT) was first performed to evaluate for abdominal organ abnormalities. CT showed a quasi-circular, isodense lesion measuring 1.3 × 0.8 cm in the left kidney. To further characterize the nature of the renal lesion, contrast-enhanced CT was performed. The contrast-enhanced scan demonstrated a rapid wash-in and wash-out enhancement pattern, with CT values of 9 ± 34 HU, 31 ± 68 HU, and 86 ± 53 HU, respectively (Figure 1). No adverse reactions were observed following contrast administration. Based on the examination findings, a diagnosis of a left renal tumor was established. After completing the preoperative evaluation, the patient provided informed consent for surgery and underwent laparoscopic partial nephrectomy.

Figure 1.

Radiological features of the left renal tumor on contrast-enhanced computed tomography (CT). (a) Arterial phase CT scan: Axial contrast-enhanced CT image in the arterial phase shows a well-defined, enhancing lesion in the upper pole of the left kidney (red arrow), demonstrating a rapid wash-in enhancement pattern. (b) Portal venous phase CT scan: Axial contrast-enhanced CT image in the portal venous phase shows the left renal tumor (red arrow) with rapid wash-out of contrast, a feature that may lead to misdiagnosis as another hypervascular renal neoplasms. (c) Delayed phase CT scan: Axial contrast-enhanced CT image in the delayed phase shows further reduction in enhancement of the left renal tumor (red arrow), consistent with the rapid wash-in and rapid wash-out enhancement pattern observed in this case. (d) Tumor specimen (intact).

CT: Computed tomography.

During the surgical procedure, the tumor was completely resected along with a portion of the adjacent normal renal tissue. The surface of the resected tumor specimen was smooth, the capsule was intact, and the tumor was closely adherent to the kidney (Figure 2). Hematoxylin and eosin (H&E) staining showed that the tumor cells formed papillary structures with eosinophilic cytoplasm and nuclei positioned away from the base. Focal proliferation of fibrous and adipose tissue was observed, along with thick-walled blood vessels (Figure 3). Immunohistochemical analysis showed that nearly all tumor cells were positive for CKpan, CK7, CK20, SDHB, PAX-8, and GATA-3 to varying intensities (Figure 4). The patient completed a total of four follow-up visits during the 18 months after surgery. A baseline follow-up was conducted 1 month postoperatively and included medical history, physical examination, complete blood count, liver and kidney function tests, and urinary system ultrasound. Subsequent follow-up visits were performed at 6, 12, and 18 months postoperatively. At the 6- and 18-month follow-up visits, medical history, physical examination, liver and kidney function tests, and contrast-enhanced abdominopelvic CT were performed. At the 12-month follow-up visit, a plain chest CT scan was added. If symptoms such as low back pain, hematuria, or unexplained weight loss occurred, the patient was instructed to seek immediate medical attention without waiting for the scheduled follow-up. No recurrence or metastasis was detected during the 18-month follow-up period. The reporting of this study conforms to the Case Report (CARE) guidelines.

Figure 2.

Macroscopic appearance of the resected tumor specimen. (a) Tumor specimen (intact): The figure shows the gross specimen of the left renal tumor resected by laparoscopic partial nephrectomy. The specimen is placed on a sterile surgical drape, with a 60-mL syringe positioned adjacent to it for size reference. The tumor appears ovoid, covered by a smooth, glistening fibrous capsule, and exhibiting a dark red in color. The specimen is intact and unsectioned, with a small amount of attached adipose tissue. Its appearance is consistent with the features of a well-circumscribed, exophytic small renal tumor. (b) Tumor specimen (sectioned): The figure shows the cut surface of the same tumor specimen after longitudinal bisection along its maximum dimension. The cut surface reveals a homogeneous reddish-brown tumor with a fine, solid texture. No definite areas of necrosis, hemorrhage, or cystic degeneration are observed. The tumor is clearly demarcated from the surrounding renal parenchyma, further confirming the “well-circumscribed” feature noted on preoperative imaging.

Figure 3.

Hematoxylin and eosin (H&E) staining of tumor stroma. This low-magnification (200×) H&E micrograph demonstrates the tumor stromal components adjacent to the neoplastic epithelial structures. Focal proliferation of fibrous connective tissue and mature adipose tissue is evident, accompanied by scattered thick-walled blood vessels within the stroma. These findings are consistent with the pathologic spectrum of papillary renal neoplasm with reverse polarity (PRNRP).

H&E: Hematoxylin and eosin; PRNRP: Papillary renal neoplasm with reverse polarity.

Figure 4.

Immunohistochemical staining of the resected tumor tissue. (a) CK7 staining: Diffuse, strong membranous and cytoplasmic positivity for CK7 was observed in nearly all tumor cells, consistent with the immunophenotype of renal epithelial neoplasms (original magnification 200×). (b) Vimentin staining: Vimentin expression was absent in the neoplastic epithelial cells, with only faint staining observed in the stromal fibroblasts and vascular endothelial cells, consistent with the characteristic immunophenotype of PRNRP (original magnification 200×). (c) GATA-3 staining: Nuclear staining for GATA-3 was detected in the majority of tumor cells, a key diagnostic feature supporting the classification of PRNRP (original magnification 200×).

PRNRP: Papillary renal neoplasm with reverse polarity.

The reporting of this study conforms to the CARE guidelines. ⁶ This study obtained the patient’s signed informed consent for treatment. The patient also provided signed consent for publication.

Discussion

In this report, the findings of the presented case of PRNRP were comprehensively compared with those of previously published studies. Regarding the clinical characteristics, this case involved a 54-year-old male patient, which falls within the reported age range of PRNRP onset (46–80 years) in previous studies. ⁷ The tumor was solitary and unilateral, consistent with the epidemiological features of PRNRP reported by Al-Obaidy et al.⁴ and Zhou et al. ⁸ Pathologically, the tumor cells formed papillary structures with eosinophilic cytoplasm. Immunohistochemically, the tumor showed strong positivity for GATA-3 and negativity for vimentin, which is highly consistent with the classic pathologic and immunophenotypic features of PRNRP described by Shen et al. and Han et al.^9–12 Radiologically, the tumor was well-circumscribed and exhibited features of a small exophytic lesion, also consistent with the common imaging manifestations of PRNRP reported in the single-center study by Nova-Camacho et al. ¹⁰

The uniqueness of this case mainly lies in its atypical clinical and imaging presentations, which provide an important addition to the literature on PRNRP. Previous studies have indicated that most patients with PRNRP have no obvious clinical symptoms and are often diagnosed incidentally during routine physical examinations. In contrast, this patient presented with a chief complaint of recurrent right lumbar pain and discomfort, expanding the spectrum of possible nonspecific clinical manifestations of PRNRP. Furthermore, although previous studies have consistently reported that PRNRP is a hypovascular tumor without a “rapid wash-in and wash-out” enhancement pattern on contrast-enhanced scans,^13–15 this case exhibited a typical “rapid wash-in and wash-out” enhancement pattern. This represents a rare atypical imaging manifestation among the currently reported cases of PRNRP. This finding enriches the imaging spectrum of PRNRP and provides a new reference for the differential diagnosis of PRNRP from other hypervascular renal tumors in clinical practice. Additionally, pathological examination revealed focal proliferation of fibrous and adipose tissue accompanied by thick-walled blood vessels within the tumor stroma, further expanding the histopathologic spectrum of PRNRP and providing additional morphologic evidence for its pathologic diagnosis.

This case has several limitations. First, this is a single-center case report, and the atypical clinical, imaging, and pathologic features identified require validation in additional clinical cases. Second, the follow-up period was limited to 18 months, which is relatively short and does not allow assessment of long-term recurrence, metastasis, or prognosis. As PRNRP is an indolent renal tumor, its long-term biological behavior requires evaluation through longer follow-up. Third, only routine histopathologic and immunohistochemical examinations were performed. Molecular testing, such as KRAS mutation analysis, was not conducted. ¹⁶ Therefore, the characteristics of PRNRP in this case could not be further confirmed at the molecular level, nor could the relationship between its molecular mechanisms and the atypical findings be evaluated. Finally, this study did not investigate the underlying cause of the atypical “rapid wash-in and wash-out” imaging enhancement pattern observed in this case, and no pathophysiologic mechanism was explored. Further studies including more cases are warranted.