Renal cell carcinoma (RCC) is the most common malignant neoplasm of the kidneys. The World Health Organization recognizes distinct types of RCC, e.g., papillary renal cell carcinoma (pRCC). pRCC are often diagnosed incidentally; they are unlikely to cause any symptoms until advanced stages of the disease. Diagnosis of pRCC relies on histological, immunological, and genetic tests. pRCC are highly resistant to chemotherapy and radiotherapy, so most pRCC patients undergo surgery. Surgically non-resectable tumors are associated with a very poor prognosis because efficient molecular targeted therapies are not yet available.
Most RCC are detected incidentally when patients undergo imaging studies in order to identify the causes of urological or non-urological complaints. The symptom triad of flank pain, hematuria and a palpable abdominal mass is sometimes described as characteristic of RCC - and it should surely prompt further studies - but most patients remain asymptomatic for prolonged periods of time. pRCC are even less likely to cause clinical disease than the more common clear cell variant of RCC . Thus, RCC don't usually cause specific symptoms, and even less so are there any symptoms that would allow for the distinction between subtypes of RCC.
In case of advanced disease, patients may present constitutional symptoms like fatigue, fever, night sweats, loss of appetite and weight. If metastases have formed in other organs, e.g., in lungs, liver, or bones, these may interfere with organ function. Accordingly, RCC patients may suffer from dyspnea, nausea and vomiting, and bone pain, among others.
Upon diagnosis, pRCC are usually confined to the kidney. They are well-circumscribed tumors with a preference for peripheral locations, don't typically measure more than a few centimeters in diameter and have a homogeneous structure. However, larger pRCC possibly contain necrotic areas or cystic lesions that confer a more heterogeneous appearance in images. Calcifications are seen in up to one third of pRCC . Most pRCC are hypointense on T2-weighted images, and this feature may help to distinguish pRCC from clear cell RCC, which correspond to hyperintense lesions on T2-weighted images. Additionally, pRCC are hypovascular neoplasms, while hypervascularity is attributed to clear cell RCC . There are several other imaging features that have been proposed to indicate one or another subtype of RCC, but not a single one allows for a reliable diagnosis of pRCC. In order to obtain a reliable diagnosis, tissues samples have to be examined. Tissue samples may be obtained by means of fine-needle aspiration or biopsy, or during surgery.
Macroscopically, pRCC appear as solid but friable, yellow, yellowish-grey or brown, well-circumscribed nodules, which are frequently encapsulated by a thick fibrous capsule or pseudocapsule   . They have a papillary or tubulopapillary architecture that can be recognized histologically, but it should be noted that papillary architecture is not unique to pRCC . In any case, papillae formed by pRCC may either be delimited by a single layer of cuboidal cells with scant cytoplasm, or by large cells with abundant eosinophilic cytoplasm and pseudostratified nuclei . The former is characteristic of type 1 pRCC, the latter indicates type 2 pRCC. Subtype distinction is recommended because type 2 pRCC are usually associated with higher tumor grades, an advanced stage of the disease, and a worse prognosis. For tumor grading, nuclei and nucleoli have to be observed: conspicuous, eosinophilic nucleoli indicate higher tumor grades, particularly if they are visible at low magnifications. Nuclear pleomorphism, the presence of multinucleated giant cells, and rhabdoid or sarcomatoid differentiation are suggestive of grade 4 RCC . Foamy macrophages are encountered independent of the type of pRCC, but necrotic foci are more commonly observed in type 2 pRCC and may be considered an indicator of advanced disease . Immunohistochemical staining for CK7, a low-molecular weight-keratin, may further help to differentiate between type 1 and type 2 pRCC, since diffuse staining is to be expected only in case of type 1 pRCC. AMACR, CD10, EMA, PAX2, PAX8, and vimentin staining should yield positive results in both pRCC and clear cell RCC  .
Besides macroscopic and microscopic examinations, genetic analyses may be carried out to identify possible targets for molecular therapies. Unfortunately though, there is little evidence as to the efficacy of targeted cancer therapies in pRCC patients. Further studies and clinical trials are required to improve that situation, and data regarding the molecular background of pRCC are necessary to promote such research.
The presence of multiple pRCC, either in one or both kidneys, indicates a predisposition for the disease and is more likely to be encountered in patients with hereditary renal cancer. However, this does not apply to hereditary leiomyomatosis and renal cell cancer .
In case of surgically unresectable pRCC, systemic therapy may be carried out with axitinib, erlotinib, pazopanib, sorafenib, sunitinib, temsirolimus, or bevacuzimab in combination with interferon, but response rates are unsatisfactorily low  . Most investigators pin their hopes on targeted therapies that may counteract the molecular causes of tumor growth, e.g., tyrosine kinase inhibitors to antagonize the constitutive activation of enzymes, and enzyme replacement therapy to compensate for enzyme deficiencies. Indeed, the NCCN Guidelines for Kidney Cancer explicitly recommend the enrollment in an appropriately designed clinical trial for patients with pRCC .
pRCC are slow-growing neoplasms and they are less likely to metastasize than clear cell RCC . Still, no differences were found regarding long-term prognosis and five-year survival rates: Schrader and colleagues reported five-year survival rates of 78 and 77% for pRCC and clear cell RCC, respectively . Rather than on tumor (sub-)types, the individual patient's prognosis depends on specific tumor characteristics such as tumor grade and tumor stage. Clinical disease hints at more aggressive renal cancer and advanced disease, but imaging and histological data have to be considered before making any favorable or unfavorable prognosis: Upon diagnosis, type 2 pRCC have often reached a higher stage. Additionally, they tend to be of higher tumor grades than type 1 pRCC and to grow more aggressively. In sum, type 2 pRCC tend to be associated with worse outcomes .
Little is known about the precise causes of sporadic pRCC. Nevertheless, certain risk factors have been identified that augment the individual risk of developing this type of cancer: For instance, there is a significant correlation between cigarette smoking and pRCC  . While obesity has been linked to clear cell RCC, such a correlation has not yet been confirmed for pRCC . It is known, though, that acquired diseases like acquired cystic kidney disease considerably increase the individual risk of pRCC. Hypertension, urinary tract infection, dietary intake of fat and other food ingredients, and occupational exposure to solvents like trichloroethylene are controversially discussed as potential risk factors for pRCC  .
Hereditary pRCC is diagnosed in patients with determined chromosomal or gene aberrations. The following list shall provide an overview of hereditary disorders that may be associated with pRCC :
RCC accounts for about 3% of malignancies diagnosed in adult patients and is the most common type of malignant tumor originating from the kidneys. Histopathological analyses allow for the identification of pRCC in approximately 10% of those cases . The majority of cases corresponds to sporadic pRCC, but individuals with certain DNA sequence anomalies are predisposed to develop this type of tumors. Hereditary renal cancer syndromes comprise hereditary papillary renal cancer and hereditary leiomyomatosis and renal cell cancer, but also Birt–Hogg–Dubé syndrome and tuberous sclerosis  .
Men are affected much more frequently than women; male-to-female ratios range between 1.8 to 1 and 3.8 to 1 . The individual risk of developing RCC increases with age: This type of tumor is most commonly diagnosed in patients aged >60 years. Pediatric RCC are rare, but if a child develops RCC, the likelihood of it being pRCC is higher than in adult patients.
Numerous chromosomal and gene aberrations have been detected in pRCC:
At this time, no measures can be recommended to prevent sporadic pRCC with certainty. The individual risk of pRCC, however, may be diminished by means of lifestyle adaptations. For instance, people should be encouraged not to start or stop smoking.
Families affected by hereditary pRCC may benefit from genetic counseling. In this context, distinct recommendations may be given depending on the underlying disease.
Approximately 90% of all kidney cancers are RCC, so this type of tumor is the most common malignancy affecting the kidneys . According to their histological features, several types of RCC are distinguished, namely clear cell, papillary, and chromophobe RCC. Other entities listed in the Classification of Tumors of the Urinary System, as published by the World Health Organization, comprise clear cell papillary RCC, RCC due to hereditary or non-hereditary disorders, and unclassified RCC . More than 10% of RCC are pRCC .
In this context, "papillary" refers to the tumor's architecture as recognized upon histological examination. Other histological and immunohistochemical features allow for a further distinction of pRCC subtypes, namely subtype 1 and 2. Both subtypes are associated with certain tumor grades and stages and thus, affect the patients' prognosis.
Renal cell carcinoma (RCC) is the most common malignancy of the kidneys. There are distinct types of RCC, e.g., clear cell, papillary, and chromophobe RCC. Papillary RCC account for about 10% of all cases. Here, "papillary" refers to the tumor's architecture as recognized upon histological examination. Clinical presentation and diagnosis don't differ between clear cell and papillary RCC: Patients usually remain asymptomatic for prolonged periods of time, and many tumors are detected incidentally when imaging studies are realized for non-related reasons. With regards to papillary RCC, surgery is the therapy of choice and aims at a complete resection and cure of the patient. Surgically unresectable papillary RCC are associated with a poor prognosis because those molecular defects favoring tumor development cannot yet be remedied pharmacologically. Current research is focused on the characterization of molecular features inherent to this type of RCC, and on the development of drugs targeting those underlying defects.