Wilms' tumor in a 51-year-old patient: An extremely rare case and review of the literature

Abstract

Wilms tumor or nephroblastoma is a common kidney malignant tumor in childhood, accounting for ~5% of all pediatric tumors. At present, reports on Wilms' tumor occurring in adults, particularly at ages >30 years, are extremely rare. The majority of the cases of adult Wilms' tumor are closely associated with chemotherapy. Furthermore, in rare cases, Wilms' tumor is characterized by three classic types of cells, namely blastemal, stromal and epithelial cells. We herein report a case of Wilms' tumor with three classic types of cells on histological examination in a 51 year-old male patient who had received prior chemotherapy. The patient promptly underwent radical nephrectomy and remains alive. A review of previously presented cases of adult Wilms' tumor from PubMed database was also performed.

Introduction

Wilms' tumor or nephroblastoma, named by the German surgeon Carl Max Wilhelm Wilms' in the 19th century, is the second most common intra-abdominal tumor in young children, with a peak incidence between 2 and 5 years. The incidence of Wilms' tumor in adults is extremely low, and the total cases presented to date account for <1% (1). However, the precise number of cases of Wilms' tumor in adults remains unknown, as a significant number of cases are either insufficiently documented or misdiagnosed. The stage-for-stage prognosis in adults is poorer compared with that in children. Due to the improved practicable treatments, the survival of adult patients has improved significantly from <30 to >90% (2). To the best of our knowledge, 9 cases of adult Wilms' tumor were previously published (Table I) and our patient, aged 51 years, is the second oldest patient reported to date. A radical nephrectomy was performed with subsequent chemotherapy. The present study was approved by the Ethics Committee of Peking University Shenzhen Hospital (Shenzhen, China) and written informed consent was obtained from the patient regarding the publication of his clinicopathological data.

Table I.

Reported cases of adult Wilms tumor.

Case	First author/Refs.	Year	Age (years), gender	Main complaint	Size (cm)	Localization	Microscopic characteristics	Immunohistochemical staining
1	Huang/(3)	2015	20, female	Left flank pain and back pain	6.4×6.2	Left kidney, lower pole	Triphasic pattern of blastemal, epithelial and stromal components	Vimentin+, CD99+, CD117+, WT1+
2	Varma/(4)	2006	48, male	Flank pain and hematuria	11×10	Right kidney, upper pole	Highly cellular, comprising epithelial, blastemal and stromal elements	No description
3	Thevendran/(5)	2010	37, female	Left flank mass	9.5×14.2	Right kidney, upper pole	Triphasic tumor composed of epithelial, blastematous and stromal elements	WT1+
4	Morabito/(6)	2014	38, male	Abominal pain and macroscopic hematuria	10	Right kidney	Triphasic cellular pattern with undifferentiated blastemal cells and cells differentiating toward epithelial and stromal lineages	Vimentin+, desmin+, WT1+
5	Patnayak/(7)	2012	19, male	Low backache and colicky left loin pain	15×10	Right kidney	Monomorphous tumor cells presenting as nests, islands and sheets, with intervening necrosis and lymphoid collections	S-100+, CD117+, NSE+
6	Guo/(8)	2011	54, male	Low backache and colicky left loin pain	2.5×2.3	Right kidney	Triphasic pattern of blastemal, epithelial, and stromal components	WT1+
7	Masuda/(9)	2004	22, male	Right flank pain	4.2×1.8	Right kidney, upper pole	Predominantly epithelial histology	No description
8	Seifert/(10)	2012	26, female	Fever	12	Left kidney,	Primarily undifferentiated blastemal cells	PAN-CK+, vimentin+,
9	Present case	2015	51, male	Identified on checkup examination	4.0×4.5	Left kidney, upper pole	Undifferentiated blastemal cells differentiating to various degrees and epithelial and stromal lineages in different proportions	WT1+

WT1, Wilms' tumor 1 antibody; NSE, neuron-specific enolase; PAN-CK, pancytokeratin.

Case report

A 51 year-old man was diagnosed with a left kidney tumor on routine examination and was admitted to the Department of Urology of Peking University Shenzhen Hospital (Shenzhen, China) for further evaluation. The patient had no urinary or respiratory symptoms and had not undergone previous surgery. The general examination revealed no significant findings. The patient had a heart rate of 88 beats/min, a blood pressure of 118/67 mmHg, a temperature of 36.8°C and a respiratory rate of 22 breaths/min.

Laboratory examination revealed a haemoglobin level of 11.3 g/dl, and a white blood cell count of 6.86×10⁹/l, with 59.8% granulocytes. The glucose level was 4.98 mmol/l, the blood urea nitrogen was 7.95 mmol/l and the serum creatinine was 79.2 µmol/l. The liver function tests and serum electrolyte levels were normal. Urine examination revealed several erythrocytes per high-power field. The chest X-ray, renal function tests, cardiovascular and neurological investigations were largely normal. The non-contrast computed tomography (CT) scan of the kidneys revealed a 4.0×4.0×4.5-cm round hypodense mass [39 Hounsfield units (HU)] arising from the upper pole of the left kidney (Fig. 1A). The contrast-enhanced CT revealed a heterogeneously enhanced lesion (51 HU) (Fig. 1B).

Figure 1.

Renal computed tomography (CT) scan. (A) A round hypodense mass (39 HU), sized 4.0×4.0×4.5-cm was identified in the upper pole of the left kidney (non-contrast CT). (B) The mass was heterogeneously enhanced (51 HU) on contrast-enhanced CT.

The patient underwent left radical nephrectomy and macroscopically the tumor was a well-encapsulated mass that did not appear to invade neighboring tissue. The microscopic examination identified blastemal cells, undifferentiated or differentiated to various degrees, and epithelial and stromal lineages in different proportions (Fig. 2A). However, the most typical characteristic was the presence of undifferentiated blastemal cells. On immunohistochemical staining, Wilms' tumor 1 antibody (WT1) was found to be positive (Fig. 2B) and the renal neoplasm was confirmed as Wilms' tumor. Positron emission tomography-CT revealed no metastases. Chemotherapy was performed regularly and there was no evidence of cancer on medical examination at the 2-year follow-up (11).

Figure 2.

Results of pathological and immunohistochemical examination. (A) Blastemal cells undifferentiated and differentiated to various degrees, with different proportions of epithelial and stromal lineages (magnification, ×400). (B) Positive immunohistochemical staining with Wilms' tumor 1 antibody (magnification, ×400).

Discussion

Nephroblastoma, also referred to as Wilms' tumor, is a embryonal neoplasm originating from nephrogenic blastemal cells, which replicates the histology of the kidneys and usually exhibits various patterns of differentiation (12). Approximately one in every 7,000 children suffer from this disease (12). There are no gender differences and Wilms' tumor occurs in equal frequency in both kidneys. The mean age is 35 and 45 months for males and females, respectively, and 98% of the cases occur at ages <10 years (12). Wilms' tumor has also been reported in adults, but it is extremely rare (13). The most common main complaints are local pain and painless hematuria, but in children a palpable mass is more common (14). The tumor is often detected by abdominal palpation, CT and ultrasound scan (15). Compared with pediatric counterparts, adult patients with advanced clinical stage exhibit metastatic manifestations more frequently (10 vs. 29%, respectively) (12). The prognosis of adult Wilms' tumor is worse compared with that in the pediatric population, and there is no detailed explanation for that phenomenon to date. Approximately 5% of Wilms' tumors are associated with an unfavorable outcome and are recognized pathologically as having unfavourable histology, mainly due to the presence of nuclear anaplasia (12).

In pediatric patients as well as in adults, Wilms' tumors present as triphasic embryonic kidney tumors, and their histological appearance has the characteristics of marked structural diversity (5). Although, classic Wilms' tumor consists of three types of cells (blastemal, stromal and epithelial), the presence of all three types is uncommon in the same case (16). The presence of blastemal cells is the predominant histological component of Wilms' tumors, and it appears in distinctive patterns. Blastemal cells exhibit scant cytoplasm and are very small, mitotically active, with rotund and overlapping nuclei containing coarsely distributed chromatin and evenly small nucleoli (17). An epithelial component is present in several Wilms' tumors, and this feature may be represented by primitive structures merely recognizable as tubular formations. Other Wilms' tumors are composed of papillary and tubular elements that are easily recognized, recapitulating normal stages of nephrogenesis (18). Various stromal patterns may occur and cause diagnostic difficulties when there is lack of blastemal and epithelial differentitation. The common undifferentiated RCC has been divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC (19,20). To the best of our knowledge, various undifferentiated tumors in adults should be considered in the differential diagnosis, particularly when the carcinoma is predominantly monophasic.

From a genetics aspect, ~10% of Wilms' tumors develop in association with one of several well-characterized dysmorphic syndromes. The molecular events of adult Wilms' tumorigenesis have not been fully elucidated (21). However, similar to other tumor genes, the location of Wilms' tumor may be detected by cytogenetic analysis of DNA from the patients whose abnormalities were genetically determined, enabling the prediction of a number of chromosomal disruptions significantly associated with phenotypic abnormalities. The constitutional loss of band 13 of the short arm of chromosome 11 (11p13 or WT1) was significantly associated with adult Wilms' tumors (22). The deletion of genetic material from chromosome 11p13 was clearly associated with tumorigenesis, indicating that some critical deletions may involve the tumor suppressor genes. The candidate genes were entirely selected from the deleted regions of chromosome 11p13 and the target gene WT1 or 11p13 was isolated and cloned (23). The sequence analysis demonstrated that 11p13 acts as a transcriptional regulator whose protein product significantly affects specific DNA motifs (23). However, the accurate function of the WT1 protein remains unknown. Recent research suggests that patterns of WT1 expression may play an extremely significant role in cell differentiation of the metanephric stem, which may explain the finding of associated genitourinary abnormalities. The gene for Beckwith-Wiedemann syndrome has been localized to the chromosome 11p15 and named WT2, but the precise genetic mechanism has not yet been fully elucidated (24). Efforts to identify the precise genetic event at this locus have identified the presence of clusters of imprinted genes. At the locus, a preferential deletion of its maternal allele in several cases of Wilms' tumor reveals that genomic imprinting is associated with the pathogenesis of certain neoplasms (24). Furthermore, additional genetic loci are involved in familial Wilms' tumor in patients carrying WT1 and WT2. A proportion of patients with nephroblastoma usually have a positive family history of identical tumors. It remains unclear whether the aberration of genes results in Wilms' tumor or other tumors. Therefore, this issue requires further investigation.

There are currently no adequate treatment guidelines for adult Wilms' tumor (25). The pediatric regimen, which includes radical nephrectomy and adjuvant chemotherapy, with or without radiotherapy, is recommended for the treatment of the adult counterpart. However, there is limited information available for adult Wilms' tumor treatment if the initial chemotherapy fails or if the tumor recurs (25).

In the present case, our patient is the second oldest reported to date and he had received no prior chemotherapy. Furthermore, all three types of cells were histopathologically identified in the tumor. Therefore, we consider this to be an extremely rare case of adult Wilms' tumor.