Case of the Week

2020-28 / July 13 (Contributor: Liwei Jia)

A woman in her early 30s presented with flank pain. Subsequent MRI confirmed a mixed solid and cystic renal mass (Bosniak IV) measuring 4 cm in greatest dimension, favored to be a cystic carcinoma. Gross and histological images from the partial nephrectomy specimen are shown below.

Click on the below thumbnails to enlarge photos.

Quiz

1. What is the diagnosis?

a. Epithelial predominant Wilms tumor

b. Metanephric adenoma

c. Papillary renal cell carcinoma, solid variant

d. Ewing sarcoma

e. Nephrogenic adenoma

2. What immunohistochemistry is most helpful in resolving your differential diagnosis?

a. CK7

b. AMACR

c. CD57

d. WT1

e. CD117

3. What is the typical molecular alteration associated with this lesion?

a. EWS-FLI1 gene fusion

b. BAP-1 loss

c. Trisomy 7 and 17

d. BRAF V600E mutation

e. VHL mutation

The renal tumor predominantly shows cystic change with solid areas. The solid area of this well-demarcated cellular tumor is composed of tightly packed tubules, focally with long branching and angulated ducts and papillary areas. The tumor cells show scant cytoplasm, with small oval nuclei, delicate chromatin, and no nucleoli. Mitotic figures are absent. Stroma is also scant.

The morphology seen in this case is typical of metanephric adenoma (MA). MA is a rare neoplasm, accounting for less than 0.5% of all renal neoplasms, with a wide age range (range 5 - 84 years; mean 54 years) and female predominance (60% are female). Patients often present as asymptomatic, although symptoms can include abdominal pain, abdominal mass, hematuria, dysuria, fever, or hypertension. MA has the highest incidence (12%) of polycythemia among renal lesions. Grossly, it is circumscribed and the cut surface is tan to grey and can be soft or firm. Occasionally, hemorrhage and necrosis is present in larger tumors. Rarely, cystic change can be seen. The classic morphology is as described above. In some cases, psammomatous calcifications can be abundant, which is not seen in this case. Tumor cells have immunoreactivity for PAX8, WT1, and CD57. BRAF mutation V600E is highly sensitive. More recently, a study of 11 cases with overlapping histologic features of epithelial Wilms tumor and MA concluded that BRAF V600E mutations are not entirely restricted to typical MA, as they may be seen in MAs showing mitotic activity along with a subset of epithelial-predominant WTs in adults and children that have foci which overlap morphologically with MA.

Major differential considerations include papillary renal cell carcinoma, solid variant and adult epithelial predominant nephroblastoma/Wilms tumor. Papillary renal cell carcinoma, type 1 is generally CK7 positive, AMACR positive, WT1 negative, CD57 negative, and lacks BRAF mutation. In contrast, metanephric adenoma is WT1 positive, CD57 positive, CK7 negative, and has BRAF V600E mutations. Adult nephroblastoma is positive for WT1 but negative for CD57.

Davis CJ, et al. Metanephric adenoma. Clincopathological study of fifty patients. Am J Surg Pathol. 1995;19:1101–14.

Udager AM, et al. Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma. Am J Surg Pathol. 2015;39(4):549-57.

Choueiri TK, et al. BRAF mutations in metanephric adenoma of the kidney. Eur Urol. 2012;62(5):917-22.

Wobker SE, et al. Metanephric Adenoma-Epithelial Wilms Tumor Overlap Lesions: An Analysis of BRAF Status. Am J Surg Pathol. 2019 Sep;43(9):1157-1169.

About GUPS

The Genitourinary Pathology Society (GUPS) was formed with the vision of advancing the care of patients with urologic diseases through enhancements of best practices, research, and education in the subspecialty of Urological Pathology.

GUPS is an official Companion Society of the United States and Canadian Academy of Pathology (USCAP).

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