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Papillary RCC

Papillary renal cell carcinoma is the second most common sub-type after clear cell. The mere mention of "papillary" or "tubulo-papillary" in your pathology report does not necessarily mean you have papillary RCC. Papillary RCC is diagnosed based on the growth pattern of the cells in the tumor along with various other technical criteria. Clear cell RCC can have areas which have a papillary growth form but this doesn't predominate in clear cell tumors. If you have true papillary RCC this should be clearly stated as the final diagnosis. Unfortunately, according to an informal comment by a well known kidney cancer expert, more than half of the slides sent to his institution with a diagnosis of papillary RCC turn out to be clear cell RCC with papillary features. Based on this, I think it's appropriate for anyone who has metastatic disease and a diagnosis of papillary RCC to be sure their pathology has been read by an expert in the pathology of renal tumors. If you don't have metastatic disease, then knowing for sure if it's clear cell or papillary won't change much since nephrectomy is the only standard treatment and any reputable clinical trial of an adjuvant therapy will include a review of your slides anyway.


Papillary RCC actually has two sub-types, type I and type II. This distinction is relatively recent [Delahunt 1997] , but recent pathology reports should specify type I or type II. Type I is also called "basophilic" and type II is also called "eosinophilic". These names reflect standard dyes that are used to stain the tissue as part of the pathology exam. Eosinophilic means it takes up the dye Eosin. Basophilic means it takes up the dye hematoxylin which is a base. Eosin is acidic.

Type I is on average diagnosed at a lower stage, and lower grade than type II and also has a better prognosis. Type I appears to be more common than type II in general but in a study of patients being treated for metastatic RCC, Upton 2003 found 14 type II patients and only 2 type I patients. This remarkable reversal of the prevalence of type I and type II strongly suggests that type II metastasizes much more commonly than type I.

Papillary RCC seems overall to have a better prognosis than clear cell of the same stage and grade for lower stages and grades but about the same for high stage and grade which seem to do about as well as clear cell[Cheville 2003]. Given the enrichment in high stage and grade cases in type II, I suspect this actually is a reflection of a prognosis difference between type I and type II. In short, I think type I has a significantly better prognosis than clear cell RCC, and type II has about the same prognosis as clear cell.

Other than surgery, there is almost no information on the treatment of papillary RCC. This is surprising considering that papillary is the second most common sub-type. It may partially reflect a smaller than expected number of metastatic cases due to the better prognosis of most papillary RCC.


Localized Papillary RCC

Follow-Up Implications: Since papillary RCC seems to generate multiple primary kidney tumors more often than clear cell RCC[Levin 2000], I suggest that follow-up include appropriate imaging of the kidney(s).


IL-2 for Metastatic Disease

Unfortunately, IL-2 is unlikely to be a good option for patients with metastatic papillary RCC, at least for those who have type II papillary RCC. On the KIDNEY-ONC E-Mail List we had been hearing that most of the experts think papillary RCC doesn't respond to IL-2 for some time, but were unable to find data in the literature to support this. At ASCO 2003, the first real data was presented. Upton 2003 reviewed response of the various sub-types of RCC to IL-2 based therapy. There were 14 patients with type II papillary RCC and 2 with type I. Unfortunately, none responded.

14 consecutive type II non-responders to IL-2 is enough to suggest that IL-2 works poorly in this sub-type. If there were a 20% response rate, only 5% of the time would you'd see no responses in 14 randomly selected patients. On the other hand, I don't think no response in the two type I patients says much about the chance of response with type I. One weakness here is that the study included patients treated with a variety of IL-2 regimens and we don't know how many of these got high dose IL-2, which seems to be the most potent form.

I do know of a single patient with type II papillary RCC who did respond to IL-2. This member of the KIDNEY-ONC E-Mail List had multiple tumors in both kidneys which shrank more than 50% after treatment with low dose bolus IV regiment (72,000IU/kg/dose, 10% of high dose). His response lasted 15 months before he relapsed. His pathology had been reviewed at NCI, so I believe the chance of a misdiagnosis is low.


Other Drug Therapies for Metastatic Disease

Unfortunately, even although papillary is the second most common sub-type of RCC, I have found no published data on other drug treatment just for papillary cell RCC.


Surgery for Metastatic Disease

Papillary RCC is often relatively slow growing, and especially given the lack of other options, I think aggressive surgery to remove metastatic disease is well worth considering, if all of it can be removed. Even if papillary RCC is biologically a different disease than clear cell RCC, surgery for metastasis is well known to be an effective treatment for such disparate forms of cancer as osteosarcoma and colon cancer when all disease can be removed. See our reviews of surgery for metastatic disease for results in metastatic RCC. Note that the data here unfortunately does not break out the results by sub-type.

Anti-Angiogenic Therapies for Metastatic Disease

Unlike clear cell RCC, Papillary RCC isn't very vascular and it lacks the VHL mutation which causes the extreme vascularity of clear cell RCC. While this doesn't automatically prove antiangiogenic drugs (and especially those targeting the VEGF pathway which is activated in clear cell RCC) won't work, they are less of a natural fit for papillary RCC than for clear cell.


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