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  Table of Contents    
CASE REPORT  
Year : 2017  |  Volume : 60  |  Issue : 4  |  Page : 574-576
Renal cell carcinoma with t(6,11): A case report and review of literature


1 Department of Pathology, Center for Renal and Urological Pathology, Chennai, Tamil Nadu, India
2 Department of Urology, Sree Paduka Speciality Hospital, Tiruchirappalli, Tamil Nadu, India

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Date of Web Publication12-Jan-2018
 

   Abstract 


Renal cell carcinomas (RCCs) with t(6,11) are very rare tumours. Only a few cases have been reported so far. t(6,11) results in fusion of alpha gene and transcription factor EB (TFEB) gene resulting in the overexpression of TFEB. The specific light and immunohistochemical features help in the diagnosis of this rare type of tumor. We report a case of t(6,11) RCC in a 38-year-old female who was incidentally found to have a right renal mass. We present this case to emphasize the typical light microscopic picture of this extremely rare tumor. Two population of cells are seen: larger cells with abundant cytoplasm and smaller cells with scant cytoplasm. Smaller cells are arranged around hyaline nodules resulting in the formation of characteristic pseudorosettes. Immunohistochemically, these tumors are diffusely positive for vimentin and focally positive for HMB 45 and CD 117. Knowledge about the typical biphasic light microscopic appearance and the characteristic immunohistochemical features help in the diagnosis of this rare type of translocation associated RCC.

Keywords: CD 117 positivity, HMB 45 positivity, pseudorosettes

How to cite this article:
Jansi Prema K S, Devanathan K S, Kurien AA. Renal cell carcinoma with t(6,11): A case report and review of literature. Indian J Pathol Microbiol 2017;60:574-6

How to cite this URL:
Jansi Prema K S, Devanathan K S, Kurien AA. Renal cell carcinoma with t(6,11): A case report and review of literature. Indian J Pathol Microbiol [serial online] 2017 [cited 2019 Sep 20];60:574-6. Available from: http://www.ijpmonline.org/text.asp?2017/60/4/574/222990





   Introduction Top


Renal cell carcinomas (RCCs) with t(6,11) are very rare tumours. Only about 50 cases have been reported so far. It was first described in 2001 by Dr. Argani et al.[1] and was recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia in 2013[2] and by the WHO in 2016. The specific light microscopic and immunohistochemical features help in the diagnosis of this rare type of tumor. t(6,11) results in the fusion of alpha gene and transcription factor EB (TFEB) gene resulting in the overexpression of TFEB.[3],[4]


   Case Report Top


This patient is a 38-year-old female who was found to have a right renal mass while being evaluated for irregular menstrual cycles. Contrast-enhanced computed tomography showed contrast enhancing right renal mass [Figure 1]a. Laparoscopic right radical nephrectomy was performed. There was a well-circumscribed tumor measuring 4.8 cm in the middle pole of the kidney which was firm, nodular, and gritty to cut [Figure 1]b. Focal hard areas were also present. Corticomedullary junction was not preserved. Grossly perinephric fat was not involved.
Figure 1: (a) Computed tomography scan: Contrast enhancing mass. (b) Gross: A large well-circumscribed tumor is seen in the middle pole of the kidney

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Light microscopy showed a well-circumscribed neoplasm consisting of two populations of cells: large and small cells [Figure 2]a. The large cells were arranged in sheets. They were polygonal with abundant clear-to-granular eosinophilic cytoplasm with small round nucleus and visible nucleoli. The smaller cells were arranged in an alveolar pattern around hyaline nodules forming pseudorosettes [Figure 2]b. They had scant cytoplasm and small round nucleus with dense chromatin. Large sheets of hyaline, areas of calcification and ossification were seen between the tumor cells. Psammoma bodies were also seen focally. Mitosis was not present in both the population of cells. Dark brown pigment granules were seen in the cytoplasm of tumor cells. Perl's stain for iron was negative. Immunohistochemistry showed diffuse positivity for vimentin and focal positivity for HMB 45 and CD 117 in the tumor cells [Figure 2]c,[Figure 2]d,[Figure 2]e. A diagnosis of RCC with t(6,11) was made based on the characteristic light microscopic features and immunohistochemical studies.
Figure 2: Light microscopic appearance of t(6,11) renal cell carcinoma: (a) Typical biphasic appearance of cells with cytoplasmic brown pigment granules (×10) (b) pseudorosettes (×20). Immunohistochemistry findings: (c) HMB 45-focally positive (d) CD 117-focally positive (e) vimentin-diffusely positive

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   Discussion Top


The WHO has classified t(6,11) RCC under the MiT family (microphthalmia transcription factor) of translocation RCC. MiT family of transcription factors includes TFE3, TFEB, TFEC, and MITF. t(6,11)(p21; q12) leads to fusion of alpha gene on 11q12 or q13 with another gene called TFEB on chromosome 6p21 causing TFEB protein overexpression.[3],[4] Alpha gene is an untranslated gene and its function is not known so far. Gene fusions involving TFE3 occur in Xp11 translocation RCC. The WHO has recognized Xp11 translocation RCC in the year 2004. Both Xp11 translocation RCC and t(6,11) RCC have many common features; hence, these two types have been classified under the MiT family translocation RCC.

t(6,11) RCC most commonly involves children and young adults, unlike clear cell RCC. Only rarely are older adults affected. The mean age of presentation is in the fourth decade, though age range of 3–68 years has been reported, with equal frequency in both sexes. The initial presentation includes fever, abdominal pain or right hypochondriac mass. It may be found incidentally as in our case.

Microscopically, two population of cells are seen: large cells with abundant cytoplasm and smaller cells typically arranged around the hyaline material. Melanin pigment may also be present in the cytoplasm.[5]

Unlike other RCCs, t(6,11) RCC under express epithelial markers such as epithelial membrane antigen and cytokeratin. At least focally, t(6,11) RCC is positive for CD10 (RCC marker) and Cam 5.2(low molecular weight cytokeratin). They more often express cathepsin K, HMB45 and Melan A.[6] Melan A is diffusely positive and HMB 45 is only focally positive. Our case also showed focal positivity for HMB45. But t(6,11) RCC, unlike melanoma, do not label for MiTF and S 100. PAX8 is a transcription factor for renal tubular epithelium, and these tumors are positive for PAX8. PAX8 positivity helps to distinguish t(6,11) RCC from epitheloid angiomyolipoma, which is also positive for melan A and HMB 45. Immunohistochemistry for antibodies to TFE3 was negative in all the cases performed so far, thus differentiating it from Xp11 translocation RCC. In t(6,11) RCC, CD117 positivity is more frequent than in Xp11 translocation RCC. In Xp11 translocation RCC, vimentin is either negative or only focally positive, whereas in t(6,11) RCC, vimentin is diffusely positive.[7],[8] Our case showed diffuse positivity for vimentin and focal positivity for CD117.

In some patients, t(6,11) RCC has occurred following cytotoxic chemotherapy for other unrelated conditions. No such history was present in our patient. They are generally considered as indolent neoplasms, though recurrence has been reported in 17% of the patients.[9] In one patient, metastasis to the ribs occurred 8 years after the initial diagnosis.[10] This underscores the importance of long-term follow-up. Our patient did not have any evidence of metastasis by imaging studies. She is currently on regular follow-up.

Knowledge about the typical biphasic light microscopic appearance and the characteristic immunohistochemical features helps in the diagnosis of this rare type of translocation associated RCC.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Argani P, Hawkins A, Griffin CA, Goldstein JD, Haas M, Beckwith JB, et al. A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;ql2) chromosome translocation. Am J Pathol 2001;158:2089-96.  Back to cited text no. 1
    
2.
Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, et al. The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 2013;37:1469-89.  Back to cited text no. 2
    
3.
Davis IJ, Hsi BL, Arroyo JD, Vargas SO, Yeh YA, Motyckova G, et al. Cloning of an alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. Proc Natl Acad Sci U S A 2003;100:6051-6.  Back to cited text no. 3
    
4.
Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E, Bridge J, et al. Upregulation of the transcription factor TFEB in t(6;11)(p21;ql3)-positive renal cell carcinomas due to promoter substitution. Hum Mol Genet 2003;12:1661-9.  Back to cited text no. 4
    
5.
Ishihara A, Yamashita Y, Takamori H, Kuroda N. Renal carcinoma with (6;11)(p21;q12) translocation: Report of an adult case. Pathol Int 2011;61:539-45.  Back to cited text no. 5
    
6.
Hora M, Hes O, Urge T, Eret V, Klecka J, Michal M, et al. A distinctive translocation carcinoma of the kidney [“rosette-like forming,” t(6;11), HMB45-positive renal tumor]. Int Urol Nephrol 2009;41:553-7.  Back to cited text no. 6
    
7.
Argani P, Ladanyi M. Translocation carcinomas of the kidney. Clin Lab Med 2005;25:363-78.  Back to cited text no. 7
    
8.
Skinnider BF, Folpe AL, Hennigar RA, Lim SD, Cohen C, Tamboli P, et al. Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue: Potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol 2005;29:747-54.  Back to cited text no. 8
    
9.
Inamura K, Fujiwara M, Togashi Y, Nomura K, Mukai H, Fujii Y, et al. Diverse fusion patterns and heterogeneous clinicopathologic features of renal cell carcinoma with t(6;11) translocation. Am J Surg Pathol 2012;36:35-42.  Back to cited text no. 9
    
10.
Smith NE, Illei PB, Allaf M, Gonzalez N, Morris K, Hicks J, et al. T(6;11) renal cell carcinoma (RCC): Expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases. Am J Surg Pathol 2014;38:604-14.  Back to cited text no. 10
    

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Correspondence Address:
Dr. K S Jansi Prema
Renopath lab, No 27 and 28, VMT nagar, Kolathur, Chennai - 600 099, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_751_16

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