Wilms' tumor (redirected from Wilm's tumor)

Wilms' Tumor 

Definition

Wilms' tumor is a cancerous tumor of the kidney that usually occurs in young children. It is named for Max Wilms, a German surgeon (1867–1918) and is also known as a nephroblastoma.

Description

When an unborn baby is developing, the kidneys are formed from primitive cells. Over time, these cells become more specialized. The cells mature and organize into the normal kidney structure. Sometimes, clumps of these cells remain in their original, primitive form. If these cells begin to multiply after birth, they may ultimately form a large mass of abnormal cells. This is known as a Wilms' tumor.

Wilms' tumor is a type of malignant tumor. This means that it is made up of cells that are significantly immature and abnormal. These cells are also capable of invading nearby structures within the kidney and traveling out of the kidney into other structures. Malignant cells can even travel through the body to invade other organ systems, most commonly the lungs and brain. These features of Wilms' tumor make it a type of cancer that, without treatment, would eventually cause death. However, advances in medicine during the last 20 years have made Wilms' tumor a very treatable form of cancer.

Wilms' tumor occurs almost exclusively in young children. The average patient is about three years old, although cases have been reported in infants younger than six months and adults in their early twenties. Females are only slightly more likely than males to develop Wilms' tumors. In the United States, Wilms' tumor occurs in 8.3 individuals per million in white children under the age of 15 years. The rate is higher among African-Americans and lower among Asian-Americans. Wilms' tumors are found more commonly in patients with other types of birth defects. These defects include:

• absence of the colored part (the iris) of the eye (aniridia)
• enlargement of one arm, one leg, or half of the face (hemihypertrophy)
• certain birth defects of the urinary system or genitals
• certain genetic syndromes (WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome)

Causes and symptoms

The cause of Wilms' tumor is not completely understood. Because 15% of all patients with this type of tumor have other heritable defects, it seems clear that at least some cases of Wilms' tumor are due to an inherited alteration. A genetic defect known as WT1, the Wilms' tumor suppressor gene, has been identified in some patients on chromosome 11. It

Wilm's tumor.

(Illustration by Argosy, Inc.)

appears that the tendency to develop a Wilms' tumor can run in families. In fact, about 1.5% of all children with a Wilms' tumor have family members who have also had a Wilms' tumor. The genetic mechanisms associated with the disease are unusually complex; it is thought as of 2004 that the tumor develops because the defective WT1 gene fails to stop its growth. Other genes that have been linked to Wilms' tumor are located on chromosomes 16q, 7p15, and 17q12.

Some patients with Wilms' tumor experience abdominal pain, nausea, vomiting, high blood pressure, or blood in the urine. However, the parents of many children with this type of tumor are the first to notice a firm, rounded mass in their child's abdomen. This discovery is often made while bathing or dressing the child and frequently occurs before any other symptoms appear. Rarely, a Wilms' tumor is diagnosed after there has been bleeding into the tumor, resulting in sudden swelling of the abdomen and a low red blood cell count (anemia).

About 4-5% of Wilms' tumor cases involve both kidneys during the initial evaluation. The tumor appears on either side equally. When pathologists look at these tumor cells under the microscope, they see great diversity in the types of cells. Some types of cells are associated with a more favorable outcome in the patient than others. In about 15% of cases, physicians find some degree of cancer spread (metastasis). The most common sites in the body where metastasis occurs are the liver and lungs.

Researchers have found evidence that certain types of lesions occur before the development of the Wilms' tumor. These lesions usually appear in the form of stromal, tubule, or blastemal cells.

Diagnosis

Children with Wilms' tumor generally first present to physicians with a swollen abdomen or with an obvious abdominal mass. The physician may also find that the child has fever, bloody urine, or abdominal pain. The physician will order a variety of tests before imaging is performed. These tests mostly involve blood analysis in the form of a white blood cell count, complete blood count, platelet count, and serum calcium evaluation. Liver and kidney function testing will also be performed as well as a urinalysis.

Initial diagnosis of Wilms' tumor is made by looking at the tumor using various imaging techniques. Ultrasound and computed tomography scans (CT scans) are helpful in diagnosing Wilms' tumor. Intravenous pyelography, where a dye injected into a vein helps show the structures of the kidney, can also be used in diagnosing this type of tumor. Final diagnosis, however, depends on obtaining a tissue sample from the mass (biopsy), and examining it under a microscope in order to verify that it has the characteristics of a Wilms' tumor. This biopsy is usually done during surgery to remove or decrease the size of the tumor. Other studies (chest x rays, CT scan of the lungs, bone marrow biopsy) may also be done in order to see if the tumor has spread to other locations.

Treatment

In the United States, treatment for Wilms' tumor almost always begins with surgery to remove or decrease the size of the kidney tumor. Except in patients who have tumors in both kidneys, this surgery usually will require complete removal of the affected kidney. During surgery, the surrounding lymph nodes, the area around the kidneys, and the entire abdomen will also be examined. While the tumor can spread to these surrounding areas, it is less likely to do so compared to other types of cancer. In cases where the tumor affects both kidneys, surgeons will try to preserve the kidney with the smaller tumor by removing only a portion of the kidney, if possible. Additional biopsies of these areas may be done to see if the cancer has spread. The next treatment steps depend on whether/where the cancer has spread. Samples of the tumor are also examined under a microscope to determine particular characteristics of the cells making up the tumor.

Information about the tumor cell type and the spread of the tumor is used to decide the best kind of treatment for a particular patient. Treatment is usually a combination of surgery, medications used to kill cancer cells (chemotherapy), and x rays or other high-energy rays used to kill cancer cells (radiation therapy). These therapies are called adjuvant therapies, and this type of combination therapy has been shown to substantially improve outcome in patients with Wilms' tumor. It has long been known that Wilms' tumors respond to radiation therapy. Likewise, some types of chemotherapy have been found to be effective in treating Wilms' tumor. These effective drugs include dactinomycin, doxorubicin, vincristine, and cyclophosphamide. In rare cases, bone marrow transplantation may be used.

The National Wilms' Tumor Study Group (NWTSG) has developed a staging system to describe Wilms' tumors. All of the stages assume that surgical removal of the tumor has occurred. Stage I involves "favorable" Wilms' tumor cells and is usually treated successfully with combination chemotherapy involving dactinomycin and vincristine and without abdominal radiation therapy. Stage II tumors involving a favorable histology (cell characteristics) are usually treated with the same therapy as Stage I. Stage III tumors with favorable histology are usually treated with a combination chemotherapy with doxorubicin, dactinomycin, and vincristine along with radiation therapy to the abdomen. Stage IV disease with a favorable histology is generally treated with combination chemotherapy with dactinomycin, doxorubicin, and vincristine. These patients usually receive abdominal radiation therapy and lung radiation therapy if the tumor has spread to the lungs.

In the case of Stage II through IV tumors with unfavorable, or anaplastic, cells, then the previously-mentioned combination chemotherapy is used along with the drug cyclophosphamide. These patients also receive lung radiation therapy if the tumor has spread to the lungs. Another type of tumor cell can be present in Stages I through IV. This cell type is called clear cell sarcoma of the kidney. If this type of cell is present, then patients receive combination therapy with vincristine, doxorubicin, and dactinomycin. All of these patients receive abdominal radiation therapy and lung radiation therapy if the tumor has spread to the lungs.

As of 2004, there are significant differences between the treatment protocols of the NWTSG and its European counterpart, the Société Internationale d'Oncologie Pédiatrique (SIOP). Whereas American practice favors surgery followed by chemotherapy, European oncologists use preoperative chemotherapy and stage the tumor at the time of surgery rather than at the point of initial imaging studies.

Key terms

Biopsy — A procedure in which a small sample of tissue is removed, prepared, and examined with a microscope to determine the characteristics of the tissue's cells.

Blastemal — An immature material from which cells and tissues develop.

Cancer — A process where abnormal cells within the body begin to grow out of control, acquire the ability to invade nearby structures, and travel through the bloodstream in order to invade distant structures.

Malignant — Refers to cancer or cancer cells.

Sarcoma — A type of cancer that originates from connective tissue such as bone or muscle.

Stromal — A type of tissue that is associated with the support of an organ.

Tubule — Tissues and cells associated with the structures that connect the renal pelvis to the glomeruli.

Prognosis

The prognosis for patients with Wilms' tumor is quite good, compared to the prognosis for most types of cancer. One German study reported the overall five-year survival rate to be 89.5%. The patients who have the best prognosis are usually those who have a small-sized tumor, a favorable cell type, are young (especially under two years old), and have an early stage of cancer that has not spread. Modern treatments have been especially effective in the treatment of this cancer. Patients with the favorable type of cell have a long-term survival rate of 93%, whereas those with anaplasia have a long-term survival rate of 43% and those with the sarcoma form have a survival rate of 36%.

Prevention

There are no known ways to prevent a Wilms' tumor, although it is important that children with birth defects associated with Wilms' tumor be carefully monitored.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Wilms' Tumor (Nephroblastoma)." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Black, Timothy L. "Wilms' Tumor." In Dambro: Griffith's 5-Minute Clinical Consult. Philadelphia: J.B. Lippincott, 1999.

DeVita, Vincent J., et al., editors. "Wilms' Tumor." In Cancer: Principles and Practice of Oncology. Philadelphia: J. B. Lippincott Company, 2001.

Periodicals

Boglino, C., A. Inserra, S. Madafferi, et al. "A Single-Institution Wilms' Tumor and Localized Neuroblastoma Series." Acta Paediatrica Supplementum 93 (May 2004): 74-77.

Coppes, Max J., and Kathy Pritchard-Jones. "Principles of Wilms' Tumor Biology." Urologic Clinics of North America 27 (August 2000).

Emerson, R. E., T. M. Ulbright, S. Zhang, et al. "Nephroblastoma Arising in a Germ Cell Tumor of Testicular Origin." American Journal of Surgical Pathology 28 (May 2004): 687-692.

Glick, R. D., M. J. Hicks, J. G. Nuchtern, et al. "Renal Tumors in Infants Less Than 6 Months of Age." Journal of Pediatric Surgery 39 (April 2004): 522-525.

Neville, Holly L., and Michael L. Ritchey. "Wilms' Tumor." Urologic Clinics of North America 27 (August 2000).

Weirich, A., R. Ludwig, N. Graf, et al. "Survival in Nephroblastoma Treated According to the Trial and Study SIOP-9/GPOH with Respect to Relapse and Morbidity." Annals of Oncology 15 (May 2004): 808-820.

Organizations

American Cancer Society. 1515 Clifton Rd. NE, Atlanta, GA 30329. (800) 227-2345. http://www.cancer.org.

March of Dimes Birth Defects Foundation, National Office. 1275 Mamaroneck Ave., White Plains, NY 10605. http://www.modimes.org.

National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422-6237. 〈http://www.nci.nih.gov\〉.

National Wilms Tumor Study Group (NWTSG). Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P. O. Box 19024, Seattle, WA 98109-1024. (800) 553-4878. Fax: (206) 667-6623. http://www.nwtsg.org.

Other

Online Mendelian Inheritance in Man (OMIM). #194070. "Wilms Tumor 1; WT1." http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194070.

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tumor /tu·mor/ (too´mer)

1. swelling, one of the cardinal signs of inflammation; morbid enlargement.

2. neoplasm; a new growth of tissue in which cell multiplication is uncontrolled and progressive.

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adenomatoid odontogenic tumor  a benign odontogenic tumor with ductlike or glandlike arrangements of columnar epithelial cells, usually occurring in the anterior jaw region.

Askin's tumor  a malignant small-cell tumor of soft tissue in the thoracopulmonary region in children; one of the peripheral neuroectodermal tumors.

benign tumor  one lacking the properties of invasion and metastasis and showing a lesser degree of anaplasia than do malignant tumors; it is usually surrounded by a fibrous capsule.

Brenner tumor  a rare, usually benign, tumor of the ovary characterized by groups of epithelial cells lying in a fibrous connective tissue stroma.

brown tumor  a giant-cell granuloma produced in and replacing bone, occurring in osteitis fibrosa cystica and due to hyperparathyroidism.

Buschke-Löwenstein tumor  a large, destructive, penetrating, cauliflower-like mass on the prepuce, especially in uncircumcised males, and also in the perianal region.

carcinoid tumor  carcinoid.

carcinoma ex mixed tumor  carcinoma ex pleomorphic adenoma.

carotid body tumor  a chemodectoma of the carotid body, a firm, round mass at the bifurcation of the common carotid artery.

dermal duct tumor  a small, intradermal, papular, eccrine lesion occurring on the head and neck in older adults.

desmoid tumor  an unencapsulated locally invasive fibromatous tumor arising in the musculoaponeurotic tissue, usually the abdominal wall, and often resembling fibrosarcoma.

diarrheogenic tumor  VIPoma.

endodermal sinus tumor  yolk sac t.

erectile tumor  cavernous hemangioma.

Ewing's tumor  see under sarcoma.

false tumor  structural enlargement due to extravasation, exudation, echinococcus, or retained sebaceous matter.

feminizing tumor  a functional tumor that produces feminization in boys and men or precocious sexual development in girls, e.g., germinoma.

fibrohistiocytic tumor  a tumor containing cells resembling histiocytes and others resembling fibroblasts; often used to denote the most general meaning of benign or malignant fibrous histiocytoma.

functional tumor , functioning tumor a hormone-secreting tumor in an endocrine gland.

germ cell tumor  any of a group of tumors arising from primitive germ cells, usually of the testis or ovary.

giant cell tumor 

1. a bone tumor, ranging from benign to frankly malignant, composed of cellular spindle cell stroma containing multinucleated giant cells resembling osteoclasts.

2. a benign, small, yellow, tumor-like nodule of tendon sheath origin, most often of the wrist and fingers or ankle and toes, laden with lipophages and containing multinucleated giant cells.

glomus tumor 

1. a benign, blue-red, painful tumor involving a glomeriform arteriovenous anastomosis (glomus body).

2. chemodectoma.

glomus jugulare tumor  a chemodectoma involving the tympanic body (glomus jugulare).

granular cell tumor  a usually benign, circumscribed, tumor-like lesion of soft tissue, particularly of the tongue, composed of large cells with prominent granular cytoplasm; the histiogenesis is uncertain, but Schwann cell derivation is favored.

granulosa tumor , granulosa cell tumor an ovarian tumor originating in the cells of the membrana granulosa.

granulosa-theca cell tumor  an ovarian tumor composed of granulosa (follicular) cells and theca cells; either form may predominate.

heterologous tumor , heterotypic tumor one made up of tissue differing from that in which it grows.

hilar cell tumor  a rare benign neoplasm of the hilus of the ovary, histologically resembling Leydig cell tumor of the testis.

homologous tumor  one resembling the surrounding parts in its structure.

Hürthle cell tumor  new growth of the thyroid gland composed predominantly of Hürthle cells; it is usually benign (Hürthle cell adenoma) but may be locally invasive or metastasize (Hürthle cell carcinoma or malignant Hürthle cell tumor).

islet cell tumor  a tumor of the pancreatic islets; many secrete excessive amounts of hormones. Types include gastrinoma, glucagonoma, insulinoma, somatostatinoma, and VIPoma.

Krukenberg's tumor  carcinoma of the ovary, usually metastatic from gastrointestinal cancer, marked by areas of mucoid degeneration and by the presence of signet-ring–like cells.

Leydig cell tumor 

1. a usually benign, nongerminal tumor of the Leydig cells of the testis.

2. hilar cell t.

lipoid cell tumor of ovary  a usually benign ovarian tumor composed of eosinophilic cells or cells with lipoid vacuoles; it causes masculinization.

malignant tumor  one having the properties of invasion and metastasis and showing a high degree of anaplasia.

mast cell tumor  mastocytosis.

melanotic neuroectodermal tumor  a benign, rapidly growing, dark tumor of the jaw and occasionally of other sites; seen almost exclusively in infants.

mixed tumor  a tumor composed of more than one type of neoplastic tissue.

müllerian mixed tumor  a malignant mixed tumor of the uterus containing both endometrial adenocarcinoma and sarcomatous cells that may be either of uterine or extrauterine origin.

neuroendocrine tumor , neuroendocrine cell tumor any of a diverse group of tumors containing neurosecretory cells that cause endocrine dysfunction; most are carcinoids or carcinomas.

nonfunctional tumor , nonfunctioning tumor a tumor located in an endocrine gland but not secreting hormones.

odontogenic tumor  a lesion derived from mesenchymal or epithelial elements, or both, that are associated with the development of the teeth; it occurs in the mandible or maxilla, or occasionally the gingiva.

papillary tumor  papilloma.

pearl tumor , pearly tumor cholesteatoma.

peripheral neuroectodermal tumor  a primitive neuroectodermal tumor occurring outside of the central nervous system in a site such as the pelvis, a limb, or the chest wall.

phyllodes tumor  a large, locally aggressive, sometimes metastatic fibroadenoma in the breast, with an unusually cellular, sarcomalike stroma.

primitive neuroectodermal tumor  (PNET) proposed name for a heterogeneous group of neoplasms thought to derive from undifferentiated cells of the neural crest.

proliferating trichilemmal tumor  a large, solitary, multilobulated lesion of the hair follicle, occurring on the scalp, usually in middle-aged or older women; often confused with squamous cell carcinoma.

sand tumor  psammoma.

squamous odontogenic tumor  a benign odontogenic epithelial neoplasm occurring in the mandible or maxilla and believed to derive from transformation of the rests of Malassez.

stromal tumors  a diverse group of tumors derived from the ovarian stroma, many of which secrete sex hormones.

teratoid tumor  teratoma.

testicular tumor  a general term for any tumor of the testes; in adults these are almost always malignant germinomas, whereas in children many are yolk sac tumors or benign varieties such as teratomas or androblastomas.

theca cell tumor  a fibroid-like ovarian tumor containing yellow areas of lipoid material derived from theca cells.

turban tumor  a term used to describe the gross appearance of multiple cutaneous cylindromas of the scalp.

virilizing tumor  a functional tumor that produces virilization in girls and women or precocious sexual development in boys.

Warthin's tumor  adenolymphoma.

Wilms' tumor  a rapidly developing malignant mixed tumor of the kidneys, made up of embryonal elements, usually affecting children before the fifth year.

yolk sac tumor  a germ cell tumor that represents a proliferation of both yolk sac endoderm and extraembryonic mesenchyme; it produces α-fetoprotein and is usually in the testes.

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Wilms' tumor (vlms)

n.

A malignant renal tumor occurring in young children and composed of small spindle cells and other tissue. Also called adenomyosarcoma, embryoma of kidney, nephroblastoma, renal carcinosarcoma.

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Wilms' tumor

[vilms]

Etymology: Max Wilms, German surgeon, 1867-1918

a malignant neoplasm of the kidney occurring in young children before the fifth year in 75% of the cases. It is slightly more common among females than males and among African-American children than Caucasian children. The most frequent early signs are hypertension, a palpable mass, pain, and hematuria. Diagnosis can be established by an excretory urogram with tomography. The tumor, an embryonal adenomyosarcoma, is well encapsulated in the early stage, but it may extend into lymph nodes, the renal vein, or the vena cava and metastasize to the lungs or other sites. Removal of resectable tumors by transperitoneal nephrectomy is recommended. Radiotherapy is used before or after surgery or palliatively in inoperable cases. Chemotherapy combined with surgery and irradiation is proving highly effective. Also called adenomyosarcoma, nephroblastoma. See also kidney cancer.

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Wilms' tumor

a rapidly developing malignant mixed tumor of the kidneys, made up of embryonal elements, and occurring chiefly in young pigs and chickens; called also embryonal nephroma, nephroblastoma.

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Wilms' tumor

Nephroblastoma Oncology An embryonal renal tumor that arises in aberrant mesenchymal renal stem cell lines, coupled with loss of functioning tumor suppressor genes; WT comprises 92% of 1º childhood renal CAs–frequency: 1:10,000–the rest are sarcomas Clinical WT presents as a mass, often with HTN 60%, hematuria 24%, nephritis–Wilms' nephritis, serosal effusions–ascites, pleural effusions; 5% are bilateral; anaplasia connotes a poor prognosis. See WAGR syndrome.

Wilms' tumor staging

  I  CA in kidney only; can be completely removed by surgery

 II  CA spread to tissue near kidney, to blood vessels, or to the renal sinus–a part of the kidney through which blood and fluid enter and exit; CA can be completely removed by surgery

III CA has spread to tissues near the kidney; cannot be completely removed by surgery. CA may have spread to blood vessels or organs near the kidney or throughout the abdomen and/or to regional lymph nodes

IV CA spread to organs distant from kidney–eg, lungs, liver, bone, brain

 V CA in both kidneys