Metanephric adenoma. A case report and literature review

Overview

Metanephric adenoma is a rare renal tumor with almost exclusively benign behavior, which can clinically and radiologically imitate malignancy. The histological examination is therefore crucial in diagnosis. We report a case of a 69-year-old female with an incidental finding of metanephric adenoma of the left kidney and synchronous clear cell renal cell carcinoma of the contralateral kidney. In the report, we present our experience with this rare tumor and literature review with focusing on differential diagnosis. The histological differential diagnosis of metanephric adenoma includes papillary renal cell carcinoma in adult patients and nephroblastoma (Wilms tumor), particularly in children. Immunohistochemical examination and cytogenetic analyses may be useful in differential diagnosis of these neoplasms.

Keywords:

immunohistochemistry – metanephric adenoma – differential diagnosis – renal tumor

Metanephric adenoma (MA) is a rare renal tumor, which was first time described by Pages and Granier in 1980 as a nephrogenic nephroma (1). MA generally has a benign course, but clinically and radiologically it is difficult to distinguish this neoplasm from other particularly malignant renal tumors. Therefore microscopical diagnosis is crucial. Histological differential diagnosis includes nephroblastoma or Wilms tumor (WT), particularly in children and papillary renal cell carcinoma (PRCC) in adult patients. Especially histological appearances of the epithelial-predominant WT and solid variant of PRCC may be very similar to those of MA. In these cases, the immunohistochemical (IHC) examination and cytogenetic analyses may be useful. MA is usually unilateral solitary tumor and only rare cases of simultaneous diagnosis of MA with another different renal tumor were described. We report a case of the 69-year-old female with metanephric adenoma of the left kidney and synchronous clear cell renal cell carcinoma of the right kidney. Both of these tumors were revealed incidentally during the radiological examination of left ovary tumor. Another goal is to present the literature review of MA with focusing on morphological and immunohistochemical characteristics and histological differential diagnosis of this rare tumor.

CLINICAL HISTORY

The 69-year-old woman presented with diabetes mellitus, arterial hypertension, and ischemic heart disease was admitted to the Oncogynecology center of Hospital in Jihlava because of a huge left ovary tumor suspicious of cystadenoma. An ultrasound examination (USG) and computerized tomography scan (CT) of abdominal cavity were performed. Both radiological examinations revealed a huge cystic left ovarian tumor. Moreover, the radiological examination detected incidental findings of a well-circumscribed low-echo tumor 2cm in diameter on the convexity of the left kidney, which was suspicious of malignancy and multicystic lesion 10,8cm in diameter of the right kidney. The patient underwent hysterectomy with adnexectomy and the ovarian tumor was histologically diagnosed as a mucinous cystadenoma. Three months later the patient underwent partial nephrectomy of the left kidney. Because of a discrete progression of the right kidney cystic lesion on repeated CT imaging patient underwent complete nephrectomy of right kidney seven months after partial left nephrectomy.

MATERIALS AND METHODS

Sections from formalin-fixed, paraffin-embedded blocks were stained with hematoxylin-eosin (HE). Immunohistochemical stainings were performed using antibodies directed against the following antigens: cytokeratin cocktail (AE1/AE3), cytokeratin 7 (CK7), alpha methylacyl coenzyme A racemase (AMACR), Wilms’ tumor-1 protein (WT-1), CD57, epithelial membrane antigen (EMA) and vimentin (VIM). The characteristics of immunohistochemical antibodies (the clone, dilutions, and source) are listed in Table 1. Positive and negative controls gave appropriate results for each procedure.

RESULTS

Grossly, the well-circumscribed tumor measuring 2,5cm in diameter was present in the partial left nephrectomy specimen. On the cut surface, the tumor was homogenous, tan to yellow in color. Microscopically, the tumor was unencapsulated and sharply demarcated from the surrounding renal parenchyma (Fig.1). The tumor was composed predominantly of small round to oval tubules and acinar structures with minimal stroma (Fig.1,2). Focally a tubulopapillary structures (Fig. 3) and glomeruloid bodies (Fig. 4) were apparent. The tumor cells were tightly packed, small, uniform with the hyperchromatic round to oval partially overlapping nuclei and scant cytoplasm. No mitoses were visible. Nucleoli were inapparent (Fig. 5). Psammoma bodies, calcification or necrosis were not found. All surgical margins were negative. Immunohistochemically, the tumor cells exhibited diffuse positivity for WT1, CD57, vimentin, and cytokeratin cocktail AE1/AE3. IHC examinations for EMA, AMACR, and CK7 were negative (Fig. 6). Based on these findings, a diagnosis of metanephric adenoma was stated. Cytogenetic analysis was not performed.

The examination of right kidney revealed partially cystic and partially solid tumor of upper pole measuring 10,8cm in diameter. Microscopic examination showed moderately differentiated clear cell renal cell carcinoma with cystic changes. Infiltration of extrarenal tissues and angioinvasion were not present.

The patient was followed up for 22 months after partial left nephrectomy without signs of local tumor recurrence and metastasis.

DISCUSSION

MA is a rare epithelial tumor of the kidney, which accounts 0,2% of renal tumors (2). Clinicopathological characteristics of MA are obtained from few previously published series. The mean age of the patients was 41-51 years (range of 5 to 84 years) in reported studies (3-7). The females are affected more common than males with female-to-male ratio 2:1 – 9,5:1. (3,5-7). The size of MA ranges of 0,3 to 15cm (3,6). MA generally has a benign course. It was described only occasional case with lymph node metastases (8). Some authors consider the lymph node involvement as a result of passive mechanical seeding of tumor cells into the lymph node and not as a manifestation of metastatic disease (9). Approximately half of the patient have no clinical symptoms and the tumor is diagnosed incidentally. Symptomatic patients may present with microscopic haematuria, polycythaemia, arterial hypertension, palpable mass and flank of abdominal pain (3,5). Polycythaemia was associated with MA in 12%. (3). The tumor is solitary in the majority of cases, although multifocal and bilateral lesions have been reported (10,11). Very rare case reports of composite tumors with foci of MA and different malignant components or simultaneous MA and another renal tumor in different part of the same kidney or contralateral kidney have been reported (11-13). Grossly, MA is well circumscribed, soft or hard tumor with homogeneously gray to tan to yellow cut surface. Secondary changes like cyst formation, hemorrhage or necrosis may be present in large tumors. Calcification may be apparent macroscopically and may be extensive. Microscopically, the tumor is well circumscribed and composed of small uniform epithelial cells, that form small acinar and tubular formations, less frequently has a papillary architecture with glomeruloid bodies. The stroma is hypocellular and may be oedematous or hyalinized. The frequently overlapping tumor cells have scant pale cytoplasm, and round to oval hyperchromatic nuclei with inconspicuous nucleoli. Mitotic figures are rare or absent. Psammoma bodies and dystrophic calcification are frequently seen. Most tumors are unencapsulated or have the pseudocapsule only (3,14,15). In our case, macroscopic and microscopic findings of MA were consistent with cases reported previously. The differential diagnosis of renal MA includes WT, particularly in children and PRCC (mainly solid variant) in adult patients. Histologically, there is characteristic triphasic pattern for WT (including the epithelial, mesenchymal and blastemal component having high grade nuclear features) and significant mitotic activity in comparison to MA. PRCC usually have a thick fibrous pseudocapsule and occasional cells with abundant cytoplasm and nuclei with vesicular chromatin and variably prominent nucleoli in comparison to MA. Morphology of epithelial-predominant type of WT and the solid variant of PRCC may be similar to those of MA. IHC allows distinguishing MA from the two mentioned malignant neoplasms. The most useful IHC markers in differential diagnosis of MA, PRCC and WT are WT1, CD57, EMA, AMACR, RCC, CK7, S100. According some more recent studies the antibody cadherin 17 is a sensitive and highly specific marker in distinguishing MA from its mimics. In one study 81% of MA demonstrated membranous positivity, whereas all cases of WT and PRCC were negative (20). The typical IHC profiles of these tumors are listed in Table 2. In the majority of cases, a diagnosis can be stated by routine HE staining and by IHC analyses. In the most diagnostically challenging cases, a molecular analysis can be performed. A study of 29 MA and 129 non-MA renal neoplasms revealed, that approximately 90% of MA harbor BRAF V600E mutations, whereas similar mutations are exceedingly rare in other renal tumors (21). A recent study validated, that also positive IHC staining for BRAF V600E supports the diagnosis of MA. However, the absence of BRAF V600E staining does not exclude the possibility of MA (22). The accurate histological diagnosis of MA is important because of difficult clinical and radiological diagnosis of this tumor and different prognosis in comparison to other microscopically similar malignant neoplasms.

ACKNOWLEDGMENTS

We acknowledge MUDr. Eva Krejčí and prim. MUDr. Pavel Fabian, Ph.D. (Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic) for their contribution to this article.

CONFLICT OF INTEREST

The authors declare that there is not a conflict of interest regarding the publication of this paper.

Correspondence address:

MUDr. Radovan Kaštan,

Hospital Jihlava

Vrchlického 59, 586 33 Jihlava, Czech Republic

phone: +420722369538

e-mail: kastanr@nemji.cz