6p.21 translocation renal cell carcinoma in the elderly: radiological findings mimicking fat poor angiomyolipoma or papillary renal cell carcinoma

Abstract

6p21 translocation renal cell carcinoma (RCC) harboring TFEB gene fusion is a newly classified microphthalmia-associated transcription (MiT) factor-family translocation RCC with early onset. We present a case of 78-year-old man with a 6p21 translocation RCC that was diagnosed after partial nephrectomy for an incidental renal tumor on computed tomography (CT). Unenhanced CT showed a 20 mm, mildly low-density mass in the right kidney. Contrast-enhanced CT showed a heterogeneous and prolonged, mild enhancement in the tumor. On magnetic resonance imaging, the tumor showed iso-intensity within the renal parenchyma on T1-weighted-imaging (WI), low intensity on T2WI, and no restricted diffusion with low signal on diffusion-weighted imaging, with no clear tumor pseudocapsule. Fat poor angiomyolipoma and non-clear cell RCC were listed as differential diagnoses. Robot-assisted partial nephrectomy was successfully performed. Fluorescence in situ hybridization study of the resected tumor confirmed TFEB gene break, and the patient was diagnosed with a 6p21 translocation RCC. The patient is doing well without recurrence after 2.5 years of follow-up. Our patient is the oldest patient reported in previous literature.

Introduction

6p21 translocation renal cell carcinoma (RCC) is caused by the fusion of the TFEB gene in chromosome 6p21 with MALAT1 in 11q12 [1]. A 6p21 translocation RCC is a newly categorized subtype of microphthalmia-associated transcription (MiT) factor-family translocation RCC in the WHO 2016 classification, along with Xp11.2 translocation RCC [2]. 6p21 translocation RCC was relatively newly classified and still has limited reports. Here, we present a case of an elderly patient with 6p21 translocation RCC.

Case report

A 78-year-old man visited a local doctor with complaint of back pain. Unenhanced computed tomography (CT) showed a 20 × 20 × 18 mm mass with mildly low density in the posterior region of the right kidney, accidentally (Fig. 1a). The patient was then referred to our hospital for treatment. There was no personal or family history of RCC. There were no specific findings on blood and urine tests. Ultrasonography revealed a 20 mm, well-circumscribed mass in the renal parenchyma (Fig. 2). Contrast-enhanced CT revealed a heterogeneous and prolonged, mild enhancement in the tumor, with no clear tumor pseudocapsule (Fig. 1b, c). There were no findings suggestive lymph-node metastasis or distant metastasis. Magnetic resonance imaging (MRI) showed iso-intensity within the renal parenchyma on T1-weighted-imaging (WI) and low intensity on T2WI (Fig. 3a–c). The tumor was well circumscribed and no tumor pseudocapsules were observed. Diffusion-weighted imaging (DWI) revealed that the tumor showed no restricted diffusion with a low signal (Fig. 3d). On out-of-phase chemical shift imaging, the tumor showed a mildly less signal (Fig. 3b). Radiographically, fat poor angiomyolipoma (AML) and papillary RCC were listed as differential diagnoses for this renal tumor.

Fig. 1.

Unenhanced CT images of a 20 × 20 × 18 mm mass with mildly low-density in the posterior region of the right kidney, with no calcification found: a arterial phase; b excretory phase; c heterogeneous and prolonged, mild enhancement at excretory phase in the tumor, with no clear tumor pseudocapsule

Fig. 2.

Ultrasonography showed a 20 mm well-circumscribed isoechoic mass

Fig. 3.

MRI images of the tumor. a Tumor showing iso-intensity on T1WI (in phase). b Tumor showing iso-intensity on T1WI and mildly less signal in chemical shift imaging (out of phase). c Tumor showing low intensity on T2WI. The tumor was well circumscribed and no tumor pseudocapsule was observed. d Tumor showing no restricted signal on DWI

Robot-assisted partial nephrectomy was successfully performed. The renal tumor was resected with normal kidney tissue on the tumor side.

Macroscopically, the cut surface of the tumor showed a 20 mm, yellow-to-grayish-white, solid, and well-circumscribed mass, partial necrosis, and no hemorrhage (Fig. 4a). Microscopically, the two components of large and small tumor cells with eosinophilic and clear cytoplasm were arranged in an alveolar pattern, and basement membrane-like materials surrounded by small tumor cells and psammoma bodies were observed (Fig. 4b–d). Tumor pseudocapsule was not observed. The resection margin was negative. Immunohistochemical (IHC) analysis revealed positive staining for AMACR and CK7 (Fig. 5a, b). A consultation with a pathologist specialized in RCC led to an IHC analysis that revealed positive staining for TFEB and cathepsin-K (Fig. 5c, d), and a fluorescence in situ hybridization (FISH) study, using the TFEB gene Break Apart Probe (Empire Genomics, New York, USA), confirmed TFEB gene rearrangement in the tumor cells (Fig. 5e). The proportion of break-apart signal was 36.38% for 133 tumor cells counted. Thus, the patient was histopathologically diagnosed with a 6p21 translocation RCC. The patient is doing well without recurrence after 2.5 years of follow-up. Informed consent was obtained from the patient included in this study.

Fig. 4.

a Macroscopic finding of the tumor. b Microscopic findings with hematoxylin–eosin staining showing the two components of large and small tumor cells with eosinophilic and clear cytoplasm arranged in an alveolar pattern. c The rosette-like structures in which small cells are arranged around a core of basement membrane material. d Psammoma bodies

Fig. 5.

Immunohistochemistrical analysis (IHC) of positively stained cells. a AMACR. b CK7. c TFEB. d Cathepsin-K. e TFEB gene rearrangement as confirmed by FISH study

Discussion

6p21 translocation RCCs have rarely been reported globally [3–6]. This type accounts for less than 1% of all RCCs and is considered less common than as Xp11.2 translocation RCC, which is also classified as an MiT factor-family translocation RCC [1, 7]. 6p21 translocation RCCs occur in children and young adults in general, with a reported mean age of approximately 30 years (range 3–68 years) [7, 8]. Our patient was 78 years old during the time of examination, which is the oldest patient reported in the previous literature.

Macroscopically, the tumor is well circumscribed within the renal parenchyma and often has daughter nodules around the main tumor [4, 6]. Microscopically, the tumor shows a solid to alveolar growth pattern of large and small cells with eosinophilic and clear cytoplasm [1, 8]. Rosette-like structures, in which small cells are arranged around the core of the basement membrane material, and calcifications called psammoma bodies are observed [1, 4]. The diagnosis of a 6p21 translocation RCC requires confirmation of TFEB rearrangement, and not just morphological assessment [1]. Diffuse nuclear immunoreactivity for TFEB is a highly sensitive and definitive diagnostic marker for 6p21 translocation RCCs [1, 9]. This is because TFEB protein is highly expressed due to the fusion of the TFEB gene in chromosome 6p21 with MALAT1 in 11q12 in the pathogenesis of 6p21 translocation RCCs. In the patient, TFEB gene break was proven by FISH in consultation with a pathologist specialized in RCC, as it was not available at our institution. Because of its specialized examination, only a limited number of institutions are able to make a definitive diagnosis. Therefore, the potential prevalence of 6p21 translocation RCCs may be higher than previously identified. Histopathologically, since the number of reports on 6p21 translocation RCCs is still limited, further clinicopathological studies on a large number of patients are required.

There is no consensus on the imaging characteristics of 6p21 translocation RCC. Previous reports have shown that 6p21 translocation RCC has a clear boundary with surrounding tissues on CT [3, 4]. Contrast-enhanced CT showed a heterogeneous internal enhancement of the tumor [3, 6]. On MRI, the tumor showed high intensity on T1WI and low intensity on T2WI [3, 4]. In our patient, the tumor had a mildly low density on unenhanced CT, and a heterogeneous and prolonged, mild enhancement on contrast-enhanced CT. On MRI, the tumor showed iso-intensity on T1WI, low intensity on T2WI, and no restricted diffusion on DWI, with no clear tumor pseudocapsule. On out-of-phase chemical shift imaging, the tumor showed mildly less signal. Radiographically, fat poor AML and papillary RCC were listed in the differential diagnosis, rather than the typical clear cell RCC. Xp11.2 translocation RCCs of the MiT factor-family translocation similar to 6p11 RCCs show prolonged enhancement on contrast-enhanced CT and low intensity on T2WI on MRI [10]. Hence, it is difficult to differentiate these tumors preoperatively. Renal tumor biopsy is considered a potential method of preoperative diagnosis. If the typical histopathological findings of 6p21 translocation RCC, such as growth pattern of large and small cells and rosette-like structures, are included in the biopsy specimen, 6p21 translocation RCC can be diagnosed. Even in the absence of typical histopathological findings, if there is clinical suspicion of 6p21 translocated renal cell carcinoma, IHC analysis and FISH study can lead to a definitive diagnosis. However, based on his preference, the patient underwent partial nephrectomy instead of biopsy.

In conclusion, 6p21 translocation RCCs have been rarely reported, but they must be considered if the imaging pattern is not consistent with the most common clear cell RCC pattern. Break-apart FISH for the TFEB gene is required for accurate diagnosis, but institutions offering this facility are limited. Additionally, our report provided several clinically meaningful implications of the diagnostic imaging features of 6p21 translocation RCCs.

Declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

For this type of study, formal consent is not required. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from the patient included in this study.