Adult Extrarenal Wilms Tumor Occurring in the Uterus: A Case Report and Review of the Literature.

Renal Wilms tumor is one of the most common malignant, solid, extracranial tumors of children.[1] Most cases occur in the first 5 years of life. Its occurrence in adult patients is rare. Extrarenal Wilms tumor (EWT) is a rare lesion that occurs at a variety of sites. Occurrence within the uterus has been the subject of 5 previous case reports.[2-6] All previous reports occurred in young patients, ranging in age from childhood to early adulthood. The oldest patient was 22 years of age.[4] The present case is unusual in 2 respects, namely, its occurrence in the uterus and its presentation outside the usual pediatric age range. Although adult EWT has been the topic of occasional case reports,[7] the occurrence of this tumor in the uterus of a middle-aged patient brings with it special considerations in terms of the histopathologic differential diagnosis.

REPORT OF A CASE

A 42-year-old woman presented with a pedunculated necrotic mass extending through the cervical os. After an initial polypectomy, the patient was lost to follow-up. She presented 6 months later with a history of severe vaginal bleeding. A necrotic tumor was noted within the upper vagina. An abdominal computed tomographic scan showed the presence of a lobulated pelvic mass arising from the right lower uterine segment, with left lateral displacement of the bladder. There was no evidence of a renal neoplasm, hydronephrosis, or metastatic disease. In addition, there was no evidence to suggest the presence of an ovarian tumor The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and subtotal resection of the tumor In view of the incomplete surgical resection of the tumor, the patient was referred for radiotherapy. However, she died 1 year after diagnosis from uncontrollable local tumor spread and vaginal bleeding.

PATHOLOGIC FINDINGS

The initial polypectomy specimen consisted of an irregular polypoid mass measuring 77 x 62 x 60 mm (Figure 1). The cut surface revealed a glistening mucoid appearance, with extensive hemorrhage. Sixteen blocks of tumor were taken. The definitive resection specimen consisted of a uterus measuring 110 x 87 x 68 mm and weighing 290 g, with a tumor originating in the right lower uterine segment. The collective volume of the tumor tissue was 145 x 135 x 30 mm. A further 16 blocks were taken from the definitive resection specimen. Invasion through the uterine wall and infiltration of the cervix to the inferior resection margin were evident.

[ILLUSTRATION OMITTED]

Multiple histologic sections of the tumor (in excess of 1 per centimeter of tumor) showed the presence of necrotic tissue admixed with epithelial structures and focal aggregates of undifferentiated blastemal tissue (Figure 2). These elements were set in a background of abundant edematous, loosely textured primitive mesenchyme. The epithelial component consisted of ductular structures of varying caliber lined by pseudostratified, columnar to cuboidal basaloid cells with hyperchromatic nuclei and brisk mitotic activity. Fetal-type glomeruloid structures were distributed throughout the lesion (Figure 3). The blastemal component comprised small cells with hyperchromatic, rounded nuclei surrounded by a small amount of basophilic cytoplasm. These cells displayed brisk mitotic activity. There was no evidence of anaplasia.

[ILLUSTRATIONS OMITTED]

Undifferentiated, spindle-shaped cells formed the predominant mesenchymal component. These cells possessed spindled, hyperchromatic nuclei set in pale eosinophilic cytoplasm. Present within this primitive mesenchyme were several straplike rhabdomyoblasts (Figure 4). A small island of primitive cartilage was also noted. Neither ectodermal nor endodermal components were identified in the sections examined.

[ILLUSTRATION OMITTED]

Transmural extension through the wall of the right lower uterine segment and invasion of the upper endocervix were confirmed. Vascular invasion was also identified.

COMMENT

Certain criteria should be fulfilled before a lesion can be regarded as an adult EWT. The histologic structure of the primary neoplasm, which must be in an extrarenal location, should confirm the presence of primitive blastemal components and provide evidence of abortive or embryonic tubular or glomeruloid structures. In addition, there must be no evidence of a renal Wilms tumor or teratoma, and the patient should be older than 15 years.[8] The present case fulfills these criteria for an adult EWT. Histologic examination confirmed triphasic differentiation, with representation of blastemal tissue, mesenchyme, and epithelium. The latter was represented by primitive tubules, rosettes, and numerous distinct embryonic glomeruli. In addition, heterologous elements in the form of immature cartilage and rhabdomyoblasts were present.

Wilms tumor occurring in the kidney is thought to arise from aberrant differentiation of persistent metanephric mesenchyme.[9] Although the exact histogenesis of EWT is unclear, origin from persistent embryonic nests of primitive renal anlage is favored. Mesonephric remnants may give rise to tumors occurring in the retroperitoneum, gonads, and the inguinal region, whereas the remains of the pronephros may account for those tumors occurring more cranially (mediastinum and the chest wall). After establishment of an aberrant "rest" of nephrogenic tissue, ultimate malignant transformation most likely results from a genetic event.[9] Roberts et al[10] found that 2 (25%) of 8 EWTs expressed Wilms tumor 1 (WT1) gene messenger RNA, as detected by RNA-RNA in situ hybridization using a 35S-labeled probe derived from a cloned WT1 gene. This relates to the finding that WT1 is highly expressed in renal Wilms tumor Additional postulated origins of EWT include derivation from primitive or undifferentiated mesenchymal cells[11] and development from teratomas.[22]

With regard to those tumors occurring in the female genital tract, the most plausible histogenetic theory relates to the occurrence of primitive nephrogenic rests. The close relationship between the mullerian ducts, which fuse to form the uterus, and the mesonephros during embryologic life supports this proposed origin.[4] Remnants of implanted mesonephric duct tissue, derived during mullerian duct fusion, may account for the origin of uterine or cervical EWT.

The differential diagnosis of EWT includes metastatic Wilms tumor, embryonal rhabdomyosarcoma, immature teratoma, and malignant mixed mullerian tumor (MMMT). Metastatic Wilms tumor is excluded by confirming the absence of Wilms tumor in the kidneys. Although the skeletal muscle differentiation in the mesenchymal component of heterologous EWT may arouse suspicion of a possible embryonal rhabdomyosarcoma, this tumor fails to demonstrate the epithelial structures characteristic of Wilms tumor.

Although this lesion could conceivably represent an immature teratoma, a teratoma occurring in the uterus remains an exceedingly rare neoplasm. One reported case of an immature teratoma admixed with a grade 1 endometrial adenocarcinoma was characterized by an admixture of squamous and mucinous epithelium, cartilage, bone, dental tissue, and a conspicuous immature neuro-epithelial component.[13] A diagnosis of immature teratoma was considered unlikely in our case in view of the lack of distinct ectodermal-derived structures and the absence of primitive neuroepithelial tissue. In addition, MMMT is an important differential diagnostic consideration. These tumors exhibit an admixture of malignant epithelial and mesenchymal tissue, with the latter occasionally demonstrating heterologous differentiation. Glomeruloid structures are, however, not a feature of this neoplasm, and furthermore, MMMTs usually present in an older (postmenopausal) patient population. In view of these features, we consider this tumor not to represent a MMMT, but there remains no absolute way of excluding this possibility.

Despite the absence of anaplastic histologic features, the patient died of local spread, supporting the contention that adult Wilms tumors tend to behave more aggressively than their pediatric counterparts even in extrauterine locations. The delayed presentation of the patient both with primary and residual clinical disease may, however, have contributed to the poor prognostic outcome depicted in this case.

We thank Mike Lanesman and Guy Hall for their invaluable assistance in photography.

References

[1.] Charles AK, Vujanic GM, Berry PJ. Renal tumours of childhood. Histopathology. 1998;32:293-309.

[2.] Bittencourt AL, Britto JF, Fonseca LE. Wilms' tumor of the uterus: the first report of the literature. Cancer. 1981;47:2496-2499.

[3.] Bell DA, Shimm DS, Gang DL. Wilms' tumor of the endocervix. Arch Pathol Lab Med. 1985;109:371-373.

[4.] Comerci JT Jr, Denhy T, Gregori CA, Breen JL. Wilms' tumor of the uterus: a case report. J Reprod Med. 1993;38:829-832.

[5.] Benatar B, Wright C, Freinkel AL, Cooper K. Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp. Int J Gynecol Pathol. 1998; 17:277-280.

[6.] Constanzi G, Massarelli G, Bosincu L. Su un tumore embrionario dell'utero e degli annessi: Wilms extra-renale o una nuova neoplasia? Arch Ital Anat Istol Patol. 1970;44;27-38.

[7.] Fukutomi Y, Shibuya C, Yamamoto S, et al. Extrarenal Wilms' tumor in the adult patient. Am J Clin Pathol. 1988;90:618-622.

[8.] Babaian RJ, Skinner DG, Waisman J. Wilms' tumor in the adult patient: diagnosis, management, and review of the world literature. Cancer. 1980;45: 1713-1719.

[9.] Arkovitz MS, Ginsburg HB, Eidelman J, Greco MA, Rauson A. Primary extrarenal Wilms' tumor in the inguinal canal: case report and review of the literature. J Pediatr Surg. 1996;31:957-959.

[10.] Roberts DJ, Haber D, Sklar J, Crum CP. Extrarenal Wilms' tumors: a study of their relationship with the classical Wilms' tumor using expression of WT1 as a molecular marker. Lab Invest. 1993;68:528-536.

[11.] Thompson MR, Emmanuel IG, Campbell MS, et al. Extrarenal Wilms' tumors. J Pediatr Surg. 1973;8:37-41.

[12.] Ward SP, Dehner LP. Sacrococcygeal teratoma with nephroblastoma (Wilms' tumor): a variant of extragonadal teratoma in childhood: a histologic and ultrastructural study. Cancer. 1974;33:1355-1363.

[13.] Ansah-Boateng Y, Wefls M, Poole DR. Coexistent immature teratoma of the uterus and endometrial adenocarcinoma complicated by gliomatosis peritonei. Gynecol cncol. 1985;21:106-110.

Accepted for publication January 31, 2001.

From the Department of Anatomical Pathology, School of Pathology, University of the Witwatersrand, and the South African Institute for Medical Research, Johannesburg, Republic of South Africa (Drs Muc and Grayson). Dr Grobbelaar is a part-time consultant in obstetrics and gynecology, Yoosuff Dadoo and Leratong Hospitals, Krugersdorp, South Africa, and a full-time consultant in private practice at Krugersdorp Hospital, Krugersdorp, South Africa.

Reprints: Ronald S. Muc, BSc, MBBCh(Wits), FCPath(SA), Department of Anatomical Pathology, South African Institute for Medical Research, PO Box 1038, Johannesburg 2000, South Africa (e-mail: ronaldm@ mail.saimr.wits.ac.za).