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Year : 2017  |  Volume : 60  |  Issue : 3  |  Page : 405-408
Multicentric papillary and chromophobe renal cell carcinomas in a patient with autosomal dominant polycystic kidney disease: Report of a rare case

1 Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

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Date of Web Publication22-Sep-2017


The causal relationship of autosomal dominant polycystic kidney disease (ADPKD) with the development of renal cell carcinoma (RCC) is still not known. We describe a case of bilateral PKD complicated with a large enhancing mass and multiple small nodules in the left kidney. The histopathological study of the nephrectomy specimen revealed the synchronous occurrence of eosinophilic variant of chromophobe RCC (EVCRCC) and multicentric papillary RCC (PRCC) in a background of ADPKD. To the best of our knowledge, this case is the first to describe the collision tumor of EVCRCC and multicentric PRCC in ADPKD.

Keywords: Autosomal dominant polycystic kidney disease, eosinophilic variant of chromophobe renal cell carcinoma, papillary renal cell carcinoma, renal cell carcinoma

How to cite this article:
Sahoo N, Patra S, Senapati S, Mishra TS. Multicentric papillary and chromophobe renal cell carcinomas in a patient with autosomal dominant polycystic kidney disease: Report of a rare case. Indian J Pathol Microbiol 2017;60:405-8

How to cite this URL:
Sahoo N, Patra S, Senapati S, Mishra TS. Multicentric papillary and chromophobe renal cell carcinomas in a patient with autosomal dominant polycystic kidney disease: Report of a rare case. Indian J Pathol Microbiol [serial online] 2017 [cited 2021 Jul 23];60:405-8. Available from: https://www.ijpmonline.org/text.asp?2017/60/3/405/215375

   Introduction Top

Renal cell carcinoma (RCC) developing in a background of autosomal dominant polycystic kidney disease (ADPKD) is not uncommon. Several case reports of different histologic subtypes have been described in the literature. Till date, about sixty cases of RCC associated with ADPKD have been reported in the literature, among which most common being clear cell followed by papillary type.[1],[2],[3] There are only a few cases of coexistence of different histological subtypes of RCC in ADPKD patients.[3] Here, we report a rare case of multifocal papillary RCC (PRCC) with synchronous chromophobe RCC (CRCC) in a patient with ADPKD, which is the first case to report such combination.

   Case Report Top

A 69-year-old male presented to our surgery outpatient department with a complaint of lump in left side abdomen for 5 months, which was gradually increasing in size. The patient also complained of passing coca-colored urine, malaise, and anorexia. He was a chronic smoker, and his family history was unremarkable. Physical examination revealed a thin built man with essentially normal vital parameters. His blood pressure was 114/74 mmHg with antihypertensive medication. Per abdominal examination revealed a ballotable lump of size 10 cm × 10 cm present in the left upper abdomen. The lump was nontender, moving with respiration with a smooth surface. Complete hemogram, serum electrolytes, coagulation profile, and liver and renal function tests were within normal limits except for mild anemia (hemoglobin- 11.5 g/dl). Urine examination revealed plenty of red blood cells/HPF, approximately 100 mg/dl proteinuria (2+ in reagent strip test) and other parameters within normal limits. Contrast-enhanced computed tomography of abdomen and pelvis showed bilateral enlarged kidneys with multiple simple cysts of varying sizes involving the cortex and medulla. Left kidney showed a large exophytic cyst in the upper pole (displacing spleen superiorly) and a solid lobulated upper pole mass showing heterogeneous but less enhancement than that of renal cortex in the nephrogenic phase of postcontrast image, without calcification and with a stellate-shaped central nonenhancing area suggestive of central scar [Figure 1]a. Liver, spleen, and pancreas were normal. The patient underwent left radical nephrectomy, and the specimen was sent for histopathological study.
Figure 1: (a) Contrast-enhanced computed tomography of abdomen showing multiple simple cysts and upper pole mass (thick arrow) and another small heterogeneous mass at lower pole (thin arrow). (b) Multiple cysts and an encapsulated tumor with central scar. One smaller nodule at outer aspect (arrow) and another nodule on the posterior aspect of lower pole (Inset)

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On gross examination, the kidney was enlarged measuring 14 cm × 9 cm × 9.5 cm with external surface bosselated containing multiple cysts. On cut section, there was a large well-circumscribed, encapsulated tumor occupying the upper and middle pole of kidney of size 8 cm × 8 cm × 7.5 cm. The tumor was solid, homogenous, tan brown in color occupying the cortex, medulla, and renal sinus with central stellate-shaped scar [Figure 1]b. No areas of hemorrhage or necrosis were present. There were also two discrete tumor nodules identified at the lower pole, which was yellow in color on both external as well cut surface and of size 1.5 cm each [Figure 1]b - arrow and Inset]. Renal capsule and renal vein were free of tumor involvement. Microscopy of the larger mass showed sheets, tubules, and cords of polygonal to columnar cells with round to oval centrally placed nuclei and a moderate amount of granular eosinophilic cytoplasm with apical cilia and interspersed delicate vascular channels [Figure 2]a,[Figure 2]b,[Figure 2]c. Colloidal iron stain demonstrated intracytoplasmic granular and foci of luminal staining patterns [Figure 2]d. Immunohistochemically, tumor cells showed strong and diffuse cytoplasmic positivity with peripheral accentuation by CK7, AE1/AE3 [Figure 2]e and [Figure 2]f weak membrane positivity for CD-117 and completely negative for vimentin, S-100, racemase (AMACR), and CD-10. Based on gross, histomorphology, special stain, and immunohistochemical findings, a diagnosis of CRCC and eosinophilic variant was made. Section from the smaller mass showed closely packed papillary structures with delicate fibrovascular cores covered by tumor cells with round to oval vesicular nuclei and inconspicuous nucleoli corresponding to Fuhrman nuclear grade 2 [Figure 3]a and [Figure 3]b. Focal alveolar pattern containing collection of foam cells and patchy calcifications was also present. Cells of papillary tumor were strongly and diffusely positive for RCC markers (CK-7, vimentin, and AMACR) [Figure 3]d,[Figure 3]e,[Figure 3]f. CD-117 and CD-10 were negative. Based on the morphology and immunohistochemical findings, a diagnosis of multifocal PRCC was made.
Figure 2: (a) Chromophobe renal cell carcinoma with capsule (H and E, ×100). (b) Higher magnification of the same. (c) Apical cilia (thin arrow) and ciliary tuft (thick arrow) (H and E, ×1000). (d) Colloidal iron stain demonstrating intracytoplasmic granular and focal luminal pattern (×400). (e and f) Immunohistochemistry demonstrating cytoplasmic positivity by AE1/AE3 and CK7 with membrane accentuation (×200) respectively

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Figure 3: (a) Papillary renal cell carcinoma showing papillary configuration (H and E, ×200). (b) Higher magnification of the same showing collection of foamy macrophages (H and E, ×400). (c) Renal parenchyma with cysts and showing papillary epithelial hyperplasia (arrow) (H and E, ×100). (d-f) Immohistochemistry demonstrating positivity for CK7, vimentin, and AMACR, respectively (×200)

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Adjoining renal parenchyma showed multiple cysts of varying sizes lined by low cuboidal to flattened and attenuated epithelium. Focal intratubular papillary hyperplasia of the epithelium is also noted [Figure 3]c. The intervening normal parenchyma showed preserved glomeruli. Tubules show focal thyroidization with hyaline casts and interstitial nephritis with lymphomononuclear infiltrates. Occasional medium-sized vessels show myointimal hyperplasia reflecting hypertensive state.

The patient was discharged on the 10th day of surgery, and he was on regular follow-up for the past 1 year. His blood urea nitrogen (BUN) and creatinine levels were found to be 69 mg/dl and 2 mg/dl, respectively, in the first visit which was 3 months following surgery. There was no clinical or radiological evidence of tumor recurrence or metastasis.

   Discussion Top

Walter and Braasch were first to describe the association between RCC and ADPKD.[4] End-stage renal disease (ESRD) is a well-established risk factor for the development of RCC. Progression of ADPKD to ESRD increases the overall risk of RCC.[2],[5] However, there is no literature showing the direct relation of ADPKD with the development of RCC.[5],[6] The present case of concern did not show any evidence of renal failure before surgery. Although his BUN and creatinine were found to be elevated in his follow-up visit, he is continuing to be asymptomatic, with no evidence of uremia, or requiring any dialysis.

The typical clinical presentation of RCC developing in ADPKD patients includes younger age of presentation (average 47 years) often bilateral (29%) and multicentric (25%) unlike sporadic cases of RCC, where the median age of onset is 61 years, bilateral in 2%–6% cases, and multicentric in 5% of cases.[3],[6] However, our patient is of 69 years old with unilateral kidney showing multifocal tumors of different histomorphology. There are only a few case reports with synchronous occurrence of different histological types such as clear cell RCC and PRCC but no case of eosinophilic variant of chromophobe RCC (EVCRCC) and PRCC.[3]

CRCC is a morphologically, cytogenetically, and genetically distinct entity accounts for approximately 5% of RCC first described in 1985. It has significantly better prognosis than conventional RCCs. There are two morphological subtypes: typical and eosinophilic.

The EVCRCC closely mimics oncocytoma in gross as well as microscopically, often making difficult to differentiate between the two.

The tumors having features of both renal oncocytoma and CRCC have been described in the literature, and the term hybrid tumors (HTs) are applied in such cases.[7],[8],[9] The so-called HT is unrelated either to oncocytoma or CRCC, but rather represent specific type as seen in renal oncocytosis and Birt–Hogg–Dube syndrome.[10]

Subsequently, reports of sporadic cases of HT were described by Delongchamps et al. They have noted admixture of architectural and cytological features of both oncocytoma and CRCC.[8] Tumor cells in EVCRCC are characteristically arranged in nesting pattern with wrinkled, raisinoid hyperchromatic nuclei in contrast to the tumor cells in oncocytoma which has small, round, and regular nuclei. Fuhrman nuclear grade is not validated for CRCC. Hale's colloidal iron stain shows diffuse granular cytoplasmic positivity in EVCRCC whereas oncocytoma may show focal positivity confined to the luminal border. Here, both patterns are appreciated. Immunohistochemically, EVCRCC cells are reactive for CK7 and negative for vimentin and S-100. In our case, the tumor cells of larger mass show cytoplasmic positivity for Hale's colloidal iron stain and immunohistochemistry demonstrates strong and diffuse CK7 positivity with membrane accentuation and complete absence of vimentin, S-100, and AMACR.

Even though gross morphology is in favor of oncocytoma, special staining and immunohistochemical findings are not supporting the diagnosis in the present case of concern. As there are several controversies related to the radiology, microscopic, and special techniques, the so-called HT is yet not well characterized.

There are several speculations saying that renal oncocytoma (RO) and CRCC might be both extremities of a same spectrum or HT constitute a spectrum of tumors between RO and CRCC.[10] Molecular data on HT are lacking. Hence, considering the management prospective, it would be more appropriate to consider such tumor as CRCC.[8]

The association of RCC with ADPKD is still debatable. One of the suggested hypotheses is chronic kidney injury in ADPKD may favor certain genetic mutations in the renal parenchymal cells leading to malignant transformation.[11] Another circumstantial evidence of epithelial hyperplasia in the form of intracystic papillary tuft such as proliferation may act as a precursor lesion for the development of malignancy in ADPKD patients.[3] In our case, several intratubular papillary precursor lesions were identified in the adjoining residual tubules. Different hypotheses regarding histogenesis of collision tumors are either both the tumors arise from different cell lines with simultaneous proliferation and differentiation or cancer stem cells differentiate into different cell lines.[12]

The diagnosis of associated RCC in ADPKD patients is usually delayed because of overlapping clinical features between the two entities. Although flank pain and gross hematuria are common, fever is a frequent presenting symptom (32%) of RCC in ADPKD patients in contrast to sporadic cases.[6] The radiological diagnosis of ADPKD-related RCC is also challenging as intracystic hemorrhage and necrosis mask the neoplastic lesions.

Therefore, in every case of ADPKD, there must be a high degree of alertness among the clinicians to exclude associated RCC. Literatures published till date are mostly as case reports and case series of few cases. Thus, larger studies with a longer follow-up period and molecular analysis are necessary to characterize the unclassified RCCs and to understand the molecular events in ADPKD-associated RCCs, which in turn would help in developing targeted therapy.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Konosu-Fukaya S, Nakamura Y, Fujishima F, Kasajima A, Takahashi Y, Joh K, et al. Bilateral papillary renal cell carcinoma and angiomyolipoma in the patients with autosomal dominant polycystic kidney disease: Case report of two cases and literature review. Pol J Pathol 2013;64:303-7.  Back to cited text no. 1
Hajj P, Ferlicot S, Massoud W, Awad A, Hammoudi Y, Charpentier B, et al. Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure. Urology 2009;74:631-4.  Back to cited text no. 2
Na KY, Kim HS, Park YK, Chang SG, Kim YW. Multifocal renal cell carcinoma of different histological subtypes in autosomal dominant polycystic kidney disease. Korean J Pathol 2012;46:382-6.  Back to cited text no. 3
Walters W, Braasch WF. Surgical aspects of polycystic kidney. Surg Gynecol Obstet 1934;58:647-50.  Back to cited text no. 4
Hansen CC, Derrick M, Warriach I, Underwood LF, Cammack JT, de Riese W. The association between autosomal dominant polycystic kidney disease and renal cell carcinoma. Open J Urol 2015;5:84-90.  Back to cited text no. 5
Keith DS, Torres VE, King BF, Zincki H, Farrow GM. Renal cell carcinoma in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1994;4:1661-9.  Back to cited text no. 6
Tickoo SK, Reuter VE, Amin MB, Srigley JR, Epstein JI, Min KW, et al. Renal oncocytosis: A morphologic study of fourteen cases. Am J Surg Pathol 1999;23:1094-101.  Back to cited text no. 7
Delongchamps NB, Galmiche L, Eiss D, Rouach Y, Vogt B, Timsit MO, et al. Hybrid tumour 'oncocytoma-chromophobe renal cell carcinoma' of the kidney: A report of seven sporadic cases. BJU Int 2009;103:1381-4.  Back to cited text no. 8
Waldert M, Klatte T, Haitel A, Ozsoy M, Schmidbauer J, Marberger M, et al. Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes. Eur Urol 2010;57:661-5.  Back to cited text no. 9
Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, et al. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol 2002;26:1542-52.  Back to cited text no. 10
Nishimura H, Ubara Y, Nakamura M, Nakanishi S, Sawa N, Hoshino J, et al. Renal cell carcinoma in autosomal dominant polycystic kidney disease. Am J Kidney Dis 2009;54:165-8.  Back to cited text no. 11
Zhang Z, Min J, Yu D, Shi H, Xie D. Renal collision tumour of papillary cell carcinoma and chromophobe cell carcinoma with sarcomatoid transformation: A case report and review of the literature. Can Urol Assoc J 2014;8:E536-9.  Back to cited text no. 12

Correspondence Address:
Susama Patra
Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar - 751 019, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_357_16

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