Renal cell carcinoma (RCC) is the most common malignancy of kidney in adults, accounting for more than 90% of renal neoplasms. The most prevalent histologic subtype is clear cell carcinoma followed by papillary RCC. They are thought to be derived from the epithelium of  proximal tubules of nephron [1]. However, there are countable number of cases of extra-renal type that have been reported in the medical literature. Extra-renal RCC is defined as presence of cancerous tissue in regions other than the native kidney. Our case is the thirteenth case to be reported worldwide, with the first case being reported in 2003 [2] and first case of extrarenal papillary RCC reported in 2019 [3].
Synchronous primary malignancies are defined by Warren and Gates’s criteria, i.e they must be histologically confirmed, must be geographically separated and distinct lesions and the probability of metastasis of either has to be excluded.
Hereby, we present the first case of an extrarenal papillary RCC arising in the peri-renal adipose tissue along with synchronous primary adenocarcinoma of rectum. Literature review studies show that conventional clear cell RCC is the most common type of extra-renal RCC. However, our case was a papillary RCC; the second reported case at an extra–renal site.

Presenting symptoms and clinical evaluation

A 50-year-old male presented with abdominal pain, pain during defaecation, constipation, bleeding per rectum for 2 months. Colonoscopy showed an ulcero-proliferative growth that is 2.5 cm from anal verge.

Radiological findings

Further PET-CT was done for metastatic workup which confirmed the growth in lower rectum with mesorectal fat stranding. There was also an irregular, lobulated, encapsulated solid-cystic mass measuring 7 x 6 x 4 cm in right perinephric fat space separated from the renal capsule. Bilateral kidneys and adrenals were unremarkable. This perinephric mass was suggestive of metastasis radiologically with an SUV of 8.5 (Figure 1).

Initial histopathological and IHC findings

Biopsy of the rectum revealed a moderately differentiated adenocarcinoma. Biopsy from the right perinephric mass revealed a papillary neoplasm morphologically. The histopathologic findings favoured a papillary renal cell carcinoma. Further IHC was performed, which showed positivity for vimentin, CK7, AMACR, focally positive for CD10 and SATB2 and negative for PAX-8, RCC, CA IX CK20, CDX2 (Figure 2). On correlating with clinical, radiological findings; which had strong suspicion of metastasis, the SATB2 positivity, made us err towards a metastatic adenocarcinoma of rectum in spite of inconclusive immunomorphology.
As the lesion was encapsulated, excision of the mass was performed along with abdominoperineal resection (APR). Grossly, the APR had a 6 x 4 x 1.5 cm tumour infiltrating into the muscularis propria. The perinephric mass was completely encapsulated grossly measuring 7 x 5 x 4 cm with a solid-cystic grey-brown cut surface.

Final histopathologic evaluation

Histopathological evaluation of APR revealed a moderately differentiated adenocarcinoma of rectum, and pathologic stage of pT3 N1. Histopathological evaluation of right perinephric mass revealed a tumor arranged in papillary pattern composed of tumour cells exhibiting moderate nuclear pleomorphism, vesicular nuclei, prominent nucleoli and moderate eosinophilic cytoplasm. There were numerous psammoma bodies also identified. The above features were morphologically suggestive of a papillary renal cell carcinoma. However, the intact kidneys radiologically gave us a set back and could not explain it. The periphery of the mass showed dilated tubules lines by bland cuboidal epithelium, which were suspected to be renal tubules. Further sampling of the mass revealed a glomerulus and renal tubules exhibiting thyroidisation. This confirmed the mass to be a heterotopic kidney with papillary renal cell carcinoma arising from it. We ruled out the possibility of supernumerary kidney as radiologically, the mass did not have a separate collecting system.

IHC findings

Immunohistochemistry (IHC) performed on tumor from perinephric mass showed positivity in tumor cells for vimentin, AMACR and focally positive for CD10. PAX-8 was positive in the adjacent cystically dilated tubules. The tumor cells were negative for CK7, CK20, CAIX, NapsinA, CDX2 (Figure 3). The presence of psammoma bodies raised a suspicion of translocation associated RCC. However, TFE-3 was negative. IHC done on the rectal tumor revealed positivity for CDX2, CK20 and negative for PAX-8, CK7, AMACR and CD10 (Figure 4). This ruled out metastasis of either tumors. Summarised in Table 1.
The final diagnosis was given as dual malignancies with synchronous primary extra-renal papillary RCC and adenocarcinoma of rectum.

Extrarenal RCC is defined as the presence of RCC in regions other than normal native kidneys [4]. Based on urinary tract embryogenesis; the metanephric blastemal arises from the metanephros and ancestral intermediate mesoderm, which further develop into the bilateral native kidneys [5]. There is a school of thought which suggests that postnatal life has some remnants of mesonephric structures, identified in the perirenal adipose tissue, adrenal gland and adjacent to inferior vena cava that may be predispose to cancer transformation and are termed as extra-renal RCC [2]. These extrarenal RCCs arise from ectopic tissue or even supernumerary kidney, which were both part of our differentials initially after the perinephric mass biopsy. However, radiologically our case did not have a separate collecting system and blood supply related to the urinary system. This ruled out the possibility of a supernumerary kidney and the perinephric space mass was confirmed to be an ectopic kidney tissue being part of mesonephric remnants; which gave rise to the RCC.
There are twelve reported cases of extra-renal RCC [9] of them arising from prostate, 1 from adrenal gland, peri-nephric adipose tissue, retroperitoneum, adjacent to inferior vena cava each respectively. Summary of the reported cases in medical literature are represented in the Table 2. Eleven of twelve cases were clear cell RCC and 1 case was a type II papillary RCC. Our case is a type II papillary RCC. There were areas of psommomatous calcifications identified which was further worked up for Microphthalmia translocation associated RCC and turned out to be negative. The second synchronous primary in our case was adenocarcinoma of the rectum.
The differential diagnoses while working up these cases of extra-renal RCC is very intricate and unique for each case.  In our case, the first possibility considered was a metastasis as we had an established diagnosis of adenocarcinoma arising from rectum. The morphology and immunohistochemistry did not complement this possibility. The positivity of SATB2 and negativity of PAX-8 added on to the clinico-radiological suspicion, complicating the scenario. SATB2 shows variable positivity in RCCs and is shown to be a poor prognostic factor in clear cell RCC [5]. PAX-8 is negative in 10% of renal cell acrcinomas [7]. After the resection of the perinephric mass with APR, we worked up both the tumors extensively and arrived at the final diagnosis. This is first reported case of extra-renal RCC presenting as a dual malignancy and the second reported case of papillary extra-renal RCC in English literature.
The second synchronous primary in our case was adenocarcinoma of the rectum with tumour budding and deposits in serosa. The patient was in Stage III - pT3N2a. This case fulfilled the Warren and Gate’s criteria for multiple primary malignancies and was given this final diagnosis of Synchronous primaries being extrarenal Papillary RCC and carcinoma rectum. The patient is now planned for adjuvant chemotherapy for carcinoma rectum as priority following the resection.

Although accounting for its rarity, we would like to emphasise on the awareness of Extra-renal type of RCC being a unique and intriguing entity, which are hypothesised to arise from the mesonephric remnants. Establishing a precise diagnosis is essential for planning appropriate treatment and assessing the prognosis in such cases.

Acknowledgements

None.

Ethical policy

There were no human participants involved. The data was collected from archival resources.

Availability of data and materials

All data generated or analysed during this study are included in this publication.

Author contributions

SS: archival retrieval and collection of data, writing the report, review of literature; AP: manuscript correction and review of literature; CG: manuscript correction and review of literature; UA: manuscript correction and review of literature.

Competing interests

No conflicts of interest.

Funding

No funding required.

Consent

Institutional consent was obtained. However, no patient details are disclosed in the case report. IRB approval was not obtained as it was only a case report.

1. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, Heng DY, Larkin J, Ficarra V: Renal cell carcinoma. Nat Rev Dis Primers 2017, 3: 17009.
2. Singh H, Flores-Sandoval N, Abrams J: Renal-type clear cell carcinoma occurring in the prostate. Am J Surg Pathol 2003, 27(3): 407-410. 
3. Li Y, Qiu X, Li W, Yang Y, Yang R, Zhao X, Guo H, Li X: Primary Extrarenal Type 2 Papillary Renal Cell Carcinoma: A Case Report. Urology 2019, 123: e1-e3.
4. AlShalabi O, Alsaid B, AlShalabi A: A huge extrarenal cell carcinoma developing from a heterotopic renal anlage with distant metastases: Case report and literature review. J Surg Case Rep 2020, 2020(8): rjaa227.
5. Mansoor M, Young-Speirs M, Ren B, Gotto G, Merten L, Sawhney S, Siadat F, Acosta AM, Agaimy A, Trpkov K: Extrarenal renal cell carcinoma arising in the kidney proximity but without an identifiable renal primary - an intriguing dilemma: report of three cases and review of the literature. Histopathology 2022, 81(5): 635-643. 
6. Pal D, Chowdhury M: Renal type clear cell carcinoma of prostate. Indian J Surg 2007, 69(2): 81-84.
7. Permi HS, Laxminarayana KPH, Yeshvanth SK, Shetty JK: Renal Type Clear Cell Carcinoma of the Prostate: A Diagnostic Dilemma. J Lab Physicians 2011, 3(2): 132-133.
8. Terada T: Extra-renal clear cell renal cell carcinoma probably arising from mesodermal embryonic remnants. Pathol Int 2012, 62(4): 291-293. 
9. Hasan R, Kumar S, Monappa V, Ayachit A: Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge. Urol Ann 2015, 7(4): 513-515.
10. Patne SCU, Johri N, Katiyar R, Trivedi S, Dwivedi US: Renal-type clear cell carcinoma of the prostate: a diagnostic challenge. Diagn Pathol 2015, 10(1): 193.
11. Wang Q, Xue Y: Renal-type clear cell carcinoma of the prostate: A case report. Oncol Lett 2015, 9(5): 2149-2152.
12. Sato Y, Kataoka M, Hata J, Akaihata H, Ogawa S, Kojima Y: Renal-type Clear Cell Carcinoma Occurring in the Prostate With Zinner Syndrome. Urol Case Rep 2016, 5: 9-12.
13. Liao G, Zhang X, Li Z, Lan S, Huang M, Huang W: Renal-type clear cell carcinoma of prostate: A case report and review of literature. Indian J Pathol Microbiol 2018, 61(3): 431-433.
14. Han SI, Lim S-C: Rare Case of Renal-type Clear Cell Carcinoma of the Prostate and Review of the Literature. In Vivo 2020, 34(5): 2751-2756.
15. Petrinec B, Vargas BM, Harik LR, Master VA: Renal cancer without primary cancer in the kidney: Extra-renal TFE3 translocation associated renal cell carcinoma. Kidney Cancer 2021, 5(2): 107-112.