Bilateral acquired cystic kidney associated renal cell carcinoma with ...

Human Pathology: Case Reports 12 (2018) 52–55

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Case Report

Bilateral acquired cystic kidney associated renal cell carcinoma with sarcomatoid features – A rare entity

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Mahmut Akgul, MDa, , Nafiseh Janaki, MDa, RajMohan Paspulati, MDb, ⁎ Gregory T. MacLennan, MDa, a b

Department of Pathology, University Hospitals Cleveland Medical Center, 11100, Euclid Ave, Cleveland, OH 44106, USA Department of Radiology, University Hospitals Cleveland Medical Center, 11100, Euclid Ave, Cleveland, OH 44106, USA

A B S T R A C T Acquired cystic kidney disease associated renal cell carcinoma (ACKD-RCC) is known to be the most common primary renal cell malignancy in patients with end stage renal disease, particularly those who have endured long-term hemodialysis. Most such cases present at a low clinicopathologic stage and exhibit indolent biologic behavior. Conversely, the rare cases that harbor components of sarcomatoid or rhabdoid change tend to present at an advanced stage, exhibiting aggressive behavior and a propensity to prove fatal. Our case is that of a 47-year old male who developed renal failure necessitating 13 years of hemodialysis and culminating in the development of bilateral ACKD-RCC with extensive sarcomatoid differentiation.

1. Introduction

2. Case report

About 90% of patients with end stage renal disease (ESRD) on hemodialysis (HD) for more than five years develop acquired cystic kidney disease (ACKD), a condition associated with a 100-fold risk of developing renal cell carcinoma (RCC) when compared to the general population [1]. Although any type of RCC may arise in kidneys with ACKD, acquired cystic kidney disease-associated renal cell carcinoma (ACKD-RCC) is the most prevalent subtype, accounting for 36% of such cancers [2]. ACKD-RCC is typically detected through routine surveillance screening [2]. The vast majority of them are at low clinicopathologic stage when detected, lack sarcomatoid or rhabdoid morphology and exhibit indolent behavior [2]. We present a case of bilateral ACKD-RCC with sarcomatoid differentiation.

A 47-year-old African-American male developed renal failure characterized by the presence of bilateral polycystic kidneys. His mother had been on dialysis for many years, but clinical details of the precise nature of the mother's renal disease and patient's underlying polycystic kidney disease could not be obtained from their clinical records. Nonetheless, after being maintained on hemodialysis for 13 years, he presented with flank pain and hematuria. Computed tomographic assessment was hampered by lack of contrast, but both kidneys appeared to harbor lesions suspicious for neoplasia (Fig. 1A). The patient underwent bilateral nephrectomy. All renal parenchyma was replaced by numerous cysts of variable size. Tan-yellow firm masses were identified in each kidney, a 1.9 cm mass on the right and a 7.3 cm mass on the left (Fig. 1B). Microscopically, tumors with ill-de-

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Corresponding author. E-mail addresses: [email protected] (M. Akgul), Nafi[email protected] (N. Janaki), [email protected] (R. Paspulati), [email protected] (G.T. MacLennan). https://doi.org/10.1016/j.ehpc.2018.02.005 Received 3 July 2017; Received in revised form 8 February 2018; Accepted 12 February 2018 2214-3300/ © 2018 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).


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Fig. 1. (A) Axial CT images of the left kidney shows multiple cysts and a soft tissue attenuation mass in the lower pole (arrow heads). (B) Bisected left kidney demonstrates main mass with multiple satellite nodules.

fined borders were identified bilaterally, containing numerous oxalate crystals and composed of large cells with abundant granular, eosinophilic cytoplasm, with large round to oval nuclei and prominent nucleoli. Tumor cells were arranged architecturally to form small acinar structures, microcysts or macrocysts, and exhibited no immunoreactivity to antibodies against CK7. These findings were considered diagnostic of ACKD-RCC. (Fig. 2A-D). The solid masses in each kidney were formed by hypercellular populations of spindle cells with abundant inflammatory infiltrate; extensive necrosis was present. (Fig. 2D and E). Spindle cells had bland morphology with few mitotic figures (Fig. 2F and G). Immunohistochemical stains of these sarcomatoid areas showed lack of pankeratin and desmin expression (Fig. 3A and B) with focal CAM5.2 expression (Fig. 3C) and widespread CD68 expression (Fig. 3D). Despite thorough evaluation, areas with clear cell, papillary or other RCC types were not identified. Within 2 months following surgery, the patient developed ascites and widespread metastases to the liver, adrenal, and bone (Fig. 4), and expired 3 months after nephrectomy.

ACKD-RCC is localized when diagnosed, and infrequently of high nuclear grade [2]. Of 24 patients in one study, 2 had lymph node metastases, and 2 had areas of sarcomatoid morphology in their tumors, one of whom died of cancer, accounting for the only cancer death in this series [3]. Sarcomatoid morphology is associated with aggressive behavior in ACKD-RCC, and it was first reported in a renal cancer in an ACKD setting in 1994 [4]. Since then, fewer than 10 cases of ACKD-RCC with sarcomatoid differentiation have been reported, and with only one exception [3], patients had a dismal outcome, dying of widespread metastases within a short time [3–7]. Renal tumors with spindle cell morphology include a broad range of entities, including xanthomatous pyelonephritis, various mesenchymal neoplasms, and renal cell carcinoma with sarcomatoid change. Renal cell carcinoma with sarcomatoid change is the most common of these entities, and is reported in many different types of renal cell carcinoma [2]. Clinical context and thorough sampling and evaluation are critical to determine the cell of origin, since immunohistochemistry may not provide a definitive diagnosis, particularly in the sarcomatoid elements of renal cell carcinoma [2]. Expression of epithelial markers (Pankeratin, Cam5.2, EMA) may be weak or equivocal, and it must be borne in mind that sarcomas sometimes show aberrant expression of epithelial markers [2]. Our case lacked any compelling morphologic features of xanthomatous pyelonephritis. The coexistence of a readily recognizable and well characterized renal cell carcinoma with a spindle cell neoplasm in the same kidney, expressing a keratin marker and showing no expression for a smooth-muscle marker, prompted a diagnosis of ACKDRCC with sarcomatoid change, an entity well accepted in the published literature. Interpretation of CD68 expression can be misleading; RCC with sarcomatoid differentiation may show CD68 positivity in tumor cells, not macrophages, as seen in our case [8]. Our case illustrates that the prognosis for patients with ACKD-RCC is guarded. Although most are associated with a favorable outcome,

3. Discussion ACKD-RCC occurs exclusively in patients with ACKD, a condition uniquely associated with long-term hemodialysis. Such tumors are well circumscribed, tan to yellow, variable in size, bilateral in > 20% and multifocal in > 50% [2]. Tumor architecture can be quite variable acinar, alveolar, tubular, multicystic, papillary, and/or solid [2]. The presence of intra- and inter-cytoplasmic lumina or holes may create a sieve-like appearance in solid areas. Tumor cells possess abundant eosinophilic cytoplasm and exhibit prominent nucleoli [2]. A feature unique to this type of RCC is the presence in most but not all tumors of calcium oxalate crystals within epithelial cell clusters and within the stroma. ACKD-RCC lacks immunoreactivity for CK7 [2]. Typically,

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Fig. 2. Bilateral ACKD-RCC (A and B from right kidney; C and D from left kidney). Malignant cells with abundant eosinophilic cytoplasm line multiple cysts and form characteristic syncytial pattern with intercellular cleft-like spaces and lack of CK7 expression. Calcium oxalate crystals (C, under polarized light) are frequently seen in association with the cysts. Fig. 2 con't. Photomicrograph of the largest mass in the left kidney shows hypercellular sarcomatoid areas (E) with frequent necrosis (F). High power evaluation shows bland spindle cell proliferation without specific growth pattern accompanied by many lymphocytes (G and H).

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Fig. 3. Photomicrograph of the immunohistochemical profile of the largest mass in the left kidney. Cells with sarcomatoid differentiation infiltrating the normal renal tubules lack expression of pankeratin (A) and desmin (B). Focal Cam 5.2 and CD68 expression were present (C and D).

Fig. 4. CT (A, B, and C) and corresponding PET images (D, E, and F) at post-operative two months demonstrating multiple lesions in the liver (arrows at A, B, D and E), left adrenal gland (arrowhead D and E), and right iliac bone (arrowhead C and F).

aggressive behavior may be anticipated when sarcomatoid or rhabdoid morphology is present, and can even occur in the absence of these features.

[4] N. Kuroda, M. Tamura, N. Hamaguchi, et al., Acquired cystic disease–associated renal cell carcinoma with sarcomatoid change and rhabdoid features, Ann. Diagn. Pathol. 15 (2011) 462–466. [5] S. Tajima, M. Waki, D. Wataru, et al., Acquired cystic kidney disease associated renal cell carcinoma with a focal stromal component: report of a case showing more pronounced polysomy of chromosomes 3 and 16 in the sarcomatoid component, Pathol. Int. 65 (2015) 89–94. [6] A.A.M. Nouh, N. Kuroda, M. Yamashita, et al., Renal cell carcinoma in patients with end-stage renal disease: relationship between histological type and duration of dialysis, BJU Int. 105 (5) (2010 Mar) 620–627. [7] N. Kuroda, T. Karashima, K. Inoue, et al., Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects, Pol. J. Pathol. 66 (1) (2015 Mar) 3–8. [8] J.D. Khoury, D. Dawson, C. Cornell, et al., Expression of the macrophage associated antigen CD68/KP1 by tumor cells of sarcomatoid renal cell carcinoma, J. Urol. Pathol. 11 (1999) 81–87.

References [1] M. Hosseini, T. Antic, G. Paner, et al., Pathologic spectrum of cysts in end-stage kidneys: possible precursors to renal neoplasia, Hum. Pathol. 45 (2014) 1406–1413. [2] H. Moch, P.A. Humprey, T.M. Ulbright, et al., World Health Organization Classification of Tumors of Urinary System and Male Genital Organs, 4th edition, International Agency for Research on Cancer, Geneva, Switzerland, 2016. [3] S.K. Tickoo, M.N. deParelta-Venturina, L.R. Harik, et al., Spectrum of epithelial neoplasms in end stage renal disease: an experience from 66 tumor bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia, Am. J. Surg. Pathol. 30 (2) (2006 Feb) 141–153.

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