個案報告：成人的WT1陰性未分化胚層威式腫瘤

王伯皓¹ 黃立華¹ 林益聖¹ 許兆畬¹ 歐宴泉¹ 童敏哲¹

¹童綜合醫療社團法人童綜合醫院 泌尿科

Adult WT1-Negative Blastemal-Predominant Wilms Tumor : A Rare Case Report

Po-Hao Wang¹, Li-Hua Huang¹, Yi-Sheng Lin¹, Chao-Yu Hsu¹, Yen-Chuan Ou¹, Min-Che Tung¹

¹Division of Urology, Department of Surgery, Tungs' Taichung Metroharbor Hospital

Introduction

Wilms tumor, also known as nephroblastoma, compromises more than 90% of renal malignancy in pediatric patients, but extremely rare with incidence less than 0.2 per million per year in adults. East Asian is the least population.  In adult populations, its image feature may lead to diagnosis of renal cell carcinoma. We present a case of Wilms tumor in adult with WT1 negative genotype.

Case Presentation

A 48-year-old woman visited urology outpatient department for gross hematuria. She had no history of malignancy or remarkable systematic diseases. There was no radiopaque stones, but a filling defect in left upper ureter via intravenous pyelography (IVP).  Contrast-enhanced computed tomography (CT) scan confirmed a 5.7 cm hyperdense irregular mass in left renal pelvis with hypoenhancement and parenchyma invasion. Left middle calyx tumor was found under ureteroscopy (URS), and left ureter and renal pelvis as patent under retrograde pyelography (RP). Ultrasound-guided biopsy was done and pathological report was poorly differentiated invasive renal carcinoma. 3D laparoscopic nephroureterectomy and bladder cuff excision were performed. The tumor was WT1 negative Wilms tumor, involved perirenal fat but completed resected (Children's Oncology Group, stage II). Histopathological evaluation was blastema predominant (>90%) consists of small to medium sized undifferentiated cells, less epithelial component (<10%) with moderately differentiation, and absent of stromal. There is diffuse anaplasia with large to pleomorphic giant cells differentiation. Immunohistochemical analysis revealed WT1 negativity and PAX8 focal positivity, and positive to CD56, INI1, CK8/18, AMACR, BCL-1/2, EMA (10%), and Vimentin. She was currently under adjuvant chemotherapy with Cyclophosphamide (endoxan), Vincristine (Oncovin), Doxorubicin (Adriamycin), Etoposide (VP-15) for 4 courses.

Discussion

Wilms tumor could be incidentally found or by clinical manifestation as flank pain, abdominal mass, hematuria. In our case, renal cell carcinoma, most common renal tumor in adults and 90% patients present hematuria, is of course taken into first consideration as it shares similar pattern with Wilms tumor by image modalities. However, the histology pattern was totally incompatible with renal cell carcinoma (RCC). There was diverse morphology on the microscopic images. Both CK and Vimentin was positive represented as neither sarcoma nor carcinoma. In addition to BCL-1/2, CD56, PAX8 positivity as well as diffuse anaplasia with large to pleomorphic giant cells differentiation, the tumor favored Wilms tumor.

Wilms tumor demonstrates a triphasic pattern on histology with blastema, epithelial and stromal tissues. The International Society of Pediatric Oncology (SIOP) protocol stratifies tumors as low (necrotic), intermediate (stromal or epithelial predominant, triphasic, regressive, focal anaplastic) or high risk (blastemal predominant, diffuse anaplastic), to guide therapeutic regimens. WT1, a tumor suppressor gene located on chromosome 11p13, is the most sensitive and specific marker on Wilms tumor. Interestingly, WT1 especially presents mutation in the blastemal components; yet in our case, it is a WT1 negative genotype. There was no current study to point out another pathway to induce blastemal components formation. A study detected strong nuclear staining of miRNA processing genes and the transcription factors SIX1/2 in blastemal cells of nephroblastoma, while epithelial and stromal components remained almost completely negative; however, there was no obvious difference between blastemal tumors with or without SIX1/2 mutations. A case report that is also blastemal-predominated WT1 negative Wilms tumor conducted an extensive NGS examination, but the result was still uncertain. It is somehow a new type of tumor.

Wilms tumor is rare in adults, and currently remains unclear about its biological characteristics as pediatric counterpart or not.  The existing therapy options are “borrowed” from the juvenile equivalent. Therapy is governed by the National Wilms Tumor Study Group, according to which a double or triple combination of treatment modalities is preferred, i.e., primarily radical surgical resection, chemotherapy and (or) radiotherapy. However, the prognosis of adult Wilms tumors is generally considered to be extremely poor, owing to unfavorable histological findings and a lack of effective treatment guidelines

According to NCCN guideline, unilateral resectable with diffuse anaplasia Wilms tumor take nephrectomy, revised Regime UH-2 (Vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide) and local radiotherapy at local flank area.

In hindsight, our case is the second reported WT1 negative blastemal predominated Wilms tumor in adults. Due to its rarity and distinctive mutation, more surveys should be conducted and keep in mind when making a differential diagnosis in cases with similar clinical and histopathological features.