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  Table of Contents    
CASE REPORT  
Year : 2018  |  Volume : 61  |  Issue : 1  |  Page : 123-126
Mixed epithelial and stromal tumor – A solid-cystic renal neoplasm undergoing malignant transformation: A rare case report


1 Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Urology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India

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Date of Web Publication22-Mar-2018
 

   Abstract 


We present a case of 53-year-old female who came with the complaints of mass on the right side of the abdomen noticed 3 weeks back. There was no history of localized swelling or rise of temperature, no history of weight loss, or evening rise of temperature. On examination, there was a flank mass which was bimanually palpable and tender. Routine laboratory investigations were within normal limits, except for the presence of hematuria in routine urinalysis. Computed tomography scan abdomen revealed a large multiloculated solid-cystic mass lesion with septation in the right-sided kidney. Cystic renal cell carcinoma was suspected and conventional open right radical nephrectomy was done. Grossly, the tumor was solid-cystic containing blood-tinged fluid. Microscopy revealed a complex tumor with both epithelial and stromal proliferation and with the aid of immunohistochemistry a diagnosis of mixed epithelial and stromal tumor undergoing malignant transformation was concluded.

Keywords: Immunohistochemistry, malignant transformation, mixed epithelial, solid-cystic, stromal tumor

How to cite this article:
Khadilkar UN, Basavaiah SH, Laxman Prabhu G G, Tapadia R, Rakesh B H. Mixed epithelial and stromal tumor – A solid-cystic renal neoplasm undergoing malignant transformation: A rare case report. Indian J Pathol Microbiol 2018;61:123-6

How to cite this URL:
Khadilkar UN, Basavaiah SH, Laxman Prabhu G G, Tapadia R, Rakesh B H. Mixed epithelial and stromal tumor – A solid-cystic renal neoplasm undergoing malignant transformation: A rare case report. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Oct 21];61:123-6. Available from: http://www.ijpmonline.org/text.asp?2018/61/1/123/228184





   Introduction Top


Adult renal tumors have seen a tremendous change in its classification in recent times and the addition of new tumors such as familial renal cell carcinoma (RCC), translocation RCC, RCC after neuroblastoma, tubular mucinous and spindle cell carcinoma, and mixed epithelial and stromal tumors (MESTs) have been introduced.[1] MEST is a newer neoplasm that has been added and is seen affecting the perimenopausal females.[2] It was first defined by Michal and Syrucek and Adsay et al. in the year 1998, MEST is now recognized as a different entity is on the rise but in literature only around 100 cases have been reported.[1] MEST has a better prognosis as mostly these tumors are benign, but there have been reported cases of malignant transformation, and till date, only 11 cases of malignant MEST are reported.[1],[2] We present a case of solid-cystic renal neoplasm that was diagnosed clinically as RCC, and an incidental diagnosis of MEST with malignant transformation on histopathology was made.


   Case Report Top


A 53-year-old female came with the history of flank mass on the right side of the abdomen noticed 3 weeks back when she had acute pain here which was gradually progressive in intensity and nonradiating type. Her physical examination confirmed the flank mass which was bimanually palpable and tender. Her laboratory examination showed no remarkable abnormality, except for hematuria in the urinalysis. She denied taking any hormonal therapy but reported having undergone hysterectomy in the past, records which were not available. The contrast-enhanced computed tomography (CT) scan showed a large multiloculated solid-cystic mass lesion with septation in the right-sided kidney, based on which a cystic RCC had been suspected. A conventional open right radical nephrectomy was done. The renal mass was confined to the Gerota's fascia, the renal vein was free, and there were no hilar/regional lymph nodes made out intraoperatively.

The cut section of the specimen showed a solid-cystic mass in the upper pole of the kidney which measured 7 cm × 6 cm × 3.5 cm [Figure 1]a. The cystic spaces contained blood-tinged fluid and the adjacent renal parenchyma was compressed. The pelvi-ureteric junction was patent but narrowed. On microscopy, a complex tumor was noted and the tumor cells were seen lining many large and small cysts, and also the tubules. The stroma was composed of fascicles of spindle cells with plump nuclei and moderate cytoplasm, at places forming nodules [Figure 1]b. Ovarian like-stroma was present with less cellular areas of spindle cells showing peripheral condensation around the cystic spaces [Figure 1]b. Hobnailing of the nuclei was noted [Figure 1]c. Densely collagenous stroma and fat were occasionally present. Infiltration of the capsule and invasion into the pelvi-ureteric junction was present [Figure 1]d. Scattered mitoses were observed in neoplastic stromal cells [Figure 1]e. The differential diagnoses considered in this case were MEST with malignant transformation and primary renal synovial sarcoma (PRSS). Immunohistochemistry markers were performed and it was seen that the epithelial component was positive for cytokeratin, stromal cells strongly expressed CD99, bcl2 [Figure 1]f, and vimentin. Both the epithelial and stromal cells did not express ER, SMA, desmin, and CD10. A conclusive diagnosis of MEST with malignant transformation was established. The patient had an unremarkable postoperative recovery and is symptom-free for the past 1 year.
Figure 1: (a-f) Histomorphology of mixed epithelial and stromal tumor with malignant transformation: (a) Right kidney with a solid-cystic tumor involving the upper pole. (b) The stromal component showed areas resembling ovarian-like stroma (H and E, ×200). (c) Cystic spaces lined by flattened cuboidal epithelium. Hobnailing of nuclei is noted (H and E, ×100). (d) The pelvi-ureteric junction revealed infiltration by the tumor cells (H and E, ×40). (e) Numerous mitoses were noted in the stromal component (arrow heads) (H and E, ×400). (f) BCL2 showing strong positivity in tumor cells (IHC, ×400)

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   Discussion Top


The WHO classification of renal tumors has now termed an adult benign tumor that has a morphology comprising of epithelial and mesenchymal cells as benign MEST.[3] Only few isolated case reports of MEST and very sparse few series, if any, are seen in the literature. Earlier this entity was coined different names such as solitary multilocular cysts of the kidney, leiomyomatous renal hamartomas, congenital mesoblastic nephroma in an adult, cystic hamartoma of renal pelvis, multilocular renal cyst with mullerian-like stroma, and adult metanephric stromal tumor.[3]

MESTs are known to affect predominantly the perimenopausal women, mainly those who are on long-term oral contraceptive use or any hyperestrogenic conditions with a mean age of 46 years.[1],[4] The male to female ratio is 1:10 with an age range of 19–78 years. These tumors present like any other renal tumors with flank pain, palpable abdominal or flank mass, hematuria, or urinary tract infection-like symptoms, but even incidental detection are also noted in about a quarter of cases.[3]

Pathogenesis of MEST is still obscure, but the most accepted hypothesis is that this tumor arise from the renal fetal primitive mesenchyme.[4] Another well-accepted theory is the origin of this tumor from the ovarian stromal cells that gets abnormally migrated during embryogenesis. These ovarian stromal cells after getting incorporated into the metanephric tissue, are activated and transformed in a hyperestrogenic environment.[4] To strongly support this theory, MEST most commonly affects those females who have a close association with hyperestrogenemia and those men who are on long-term sex steroids. And also, these tumors strongly express the estrogen and progesterone receptors (PRs) in their mesenchymal component.[5] Hou et al. reported a case of MEST with 62% and 85% expression of estrogen and PR, respectively.[6]

MEST do not have any definite criteria for diagnosis on imaging by CT/magnetic resonance. However, like other benign renal tumors, MEST, when they are large, can masquerade either as RCC or urothelial carcinoma. When a renal tumor is single solid or solid-cystic with a well-defined delay during contrast enhancement in a background history of perimenopausal female on hormone therapy, a diagnosis of MEST should be considered.[6]

MEST behaves in a benign fashion, with no report of recurrence till date and rare case reports are available on its malignant transformation.[4],[7] The malignant MEST, in the literature, are documented as affecting only the females so far, with a age range of 24–56 years. The epithelial or the mesenchymal component can undergo malignant transformation. The cytological features such as high cellularity, striking nuclear atypia, irregular nuclear borders, prominent nucleoli, frequent mitotic activity ranging from 15 to 25 mitoses per 10 high-power fields, with condensed chromatin are observed and mosaic pattern is frequently noted.[7] The mesenchymal component can sometimes show rhabdoid, rhabdomyosarcomatous, and chondrosarcomatous transformation.[7] In our case, there was increased cellularity and increased mitotic rate in the mesenchymal component with evidence of infiltration into the renal capsule and pelvi-ureteric junction.

MEST has many differential diagnoses and has been most frequently misdiagnosed as cystic nephroma, cystic hamartoma, or mesoblastic nephroma. Cystic nephroma differs from MEST grossly by being solid-cystic or completely cystic tumor whereas MEST can be predominantly solid.[8] Renal pelvic cystic hamartoma can be differentiated from MEST as cystic hamartoma is a developmental disorder and the stromal cells in this tumor are fibrous in nature as compared to MEST where the cells are muscular.[8] Mesoblastic nephroma is a pure mesenchymal tumor that can affect both genders equally unlike MEST.[6] PRSS is a rare primary renal tumor. Morphological features of malignant MEST and PRSS are similar and pose a diagnostic challenge. PRSS shows macroscopic or microscopic cysts with tubular pattern and the hobnailing of the lining epithelium. Cytokeratin expression, predominant spindle cell element forming fascicles with frequent mitoses are also seen in PRSS.[9] However, the most characteristic microscopic feature in MEST is the presence of peripheral condensation of stroma, i.e., ovarian stroma which is not observed in PRSS. The epithelial cells in PRSS are flattened to polygonal and the pattern observed can be solid sheets, acinar or tubular. The neoplastic epithelial cells show atypia in PRSS. In contrast, in MEST the malignant transformation is noted more in the stromal cells.[9]

The epithelial component of the MEST is positive for low- and high-molecular-weight cytokeratin and Ulex europaeus.[3] The stromal cells generally express smooth muscle actin (SMA) and desmin but can also show estrogen receptor (ER) and PR positivity.[5] However, ER and PR positivity in MEST is not a diagnostic criteria. Hence, the morphological features should assist in interpreting the immunohistochemistry. Turbiner et al.[4] studied 14 cases of MEST that showed CD10 (77%), calretinin, (69%), and inhibin (42%) positivity. Malignant MEST immunoprofile differs from that of its benign counterpart by absence of ER expression with focal expression of PR. In our case, the epithelial components were positive for cytokeratin; the stromal component for vimentin, CD99, bcl-2. CD10, desmin, SMA, and ER were negative. Immunohistochemical features of tumor in our case favored malignant MEST.[3]

Jung et al. proposed the following criteria which should be fulfilled for the diagnosis of malignant transformation of MEST:[10] (1) Location of tumor – the tumor should originate from kidney; (2) presence of both epithelial and stromal components. Epithelial cells should be seen lining either the tubules or cysts with the presence of peripheral condensation of stromal cells giving an appearance of ovarian-like stroma; (3) malignant and benign components should be associated with each other; and (4) other differential diagnosis such as PRSS or metastasis should be ruled out. In our case, even though the criteria 1–3 were fulfilled for the diagnosis of malignant MEST, PRSS could not be ruled out completely as it requires a further cytogenetic analysis for t(x; 18), the absence of which can rule out PRSS.


   Conclusion Top


MEST is a rare benign tumor of the kidney predominantly affecting perimenopausal women, and only few cases of its malignant transformation are available in the literature. Due to overlapping histologic and immunohistochemical findings, it is difficult to differentiate MEST with the malignant transformation from PRSS.

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.
Ramya G, Sowmya S. Mixed epithelial and stromal tumor of the kidney – A case report in a 45 year male. Int J Recent Trends Sci Technol 2013;9:303-4.  Back to cited text no. 1
    
2.
Moslemi MK. Mixed epithelial and stromal tumor of the kidney or adult mesoblastic nephroma: An update. Urol J 2010;7:141-7.  Back to cited text no. 2
    
3.
Mohanty SK, Parwani AV. Mixed epithelial and stromal tumors of the kidney: An overview. Arch Pathol Lab Med 2009;133:1483-6.  Back to cited text no. 3
    
4.
Turbiner J, Amin MB, Humphrey PA, Srigley JR, De Leval L, Radhakrishnan A,et al. Cystic nephroma and mixed epithelial and stromal tumor of kidney: A detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. Am J Surg Pathol 2007;31:489-500.  Back to cited text no. 4
    
5.
Pierson CR, Schober MS, Wallis T, Sarkar FH, Sorensen PH, Eble JN,et al. Mixed epithelial and stromal tumor of the kidney lacks the genetic alterations of cellular congenital mesoblastic nephroma. Hum Pathol 2001;32:513-20.  Back to cited text no. 5
    
6.
Hou CP, Chiang YJ, Chu SH, Ng KF, Wang HH. Mixed epithelial and stromal tumor of the kidney – A case report. Chang Gung Med J 2010;33:693-8.  Back to cited text no. 6
    
7.
Jung SJ, Shen SS, Tran T, Jun SY, Truong L, Ayala AG,et al. Mixed epithelial and stromal tumor of kidney with malignant transformation: Report of two cases and review of literature. Hum Pathol 2008;39:463-8.  Back to cited text no. 7
    
8.
Adsay NV, Eble JN, Srigley JR, Jones EC, Grignon DJ. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000;24:958-70.  Back to cited text no. 8
    
9.
Shannon BA, Murch A, Cohen RJ. Primary renal synovial sarcoma confirmed by cytogenetic analysis: A lesion distinct from sarcomatoid renal cell carcinoma. Arch Pathol Lab Med 2005;129:238-40.  Back to cited text no. 9
    
10.
Jung SJ, Shen SS, Tran T, Jun SY, Truong L, Ayala AG,et al. Mixed epithelial and stromal tumor of kidney with malignant transformation: Report of two cases and review of literature. Hum Pathol 2008;39:463-8.  Back to cited text no. 10
    

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Correspondence Address:
Sridevi H Basavaiah
Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_627_16

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