Wilms Tumor Presents a Classic Histologic Triphasic Pattern - Lab Report Example

Topic:  Wilms Tumor Definition Wilms’ tumor is otherwise known as nephroblastoma, birch – hirschfield tumor, renal embryoma, and mixed tumor of the kidney. It is the most common malignancy of the kidneys with mixed histology that usually affects children ages 2 – 5 years old, and rarely in adults. In Wilms’ tumor, the embroyonal renal tissue of a child remains dormant instead of maturing into glomeruli and nephron. Wilms’ tumor is one of the most common types of cancer in the childhood. The tumor affects about 1 in 10,000 children and can affect one or both kidneys. In 1899, a medical paper on kidney tumors of the children was written by a German doctor named Max Wilms, and subsequently named the condition after him (Paulino 1; Mowell, what). Description Wilms’ tumor presents a classic histologic triphasic pattern that is composed of three elements: (1) epithelial, (2) blasternal, and (3) stromal. Anasplastic changes characterizes about 3 – 7% of Wilms tumor and presents an unfavorable histology as well as predicts poor outcome if these changes are diffusely present throughout the tumor. Wilms’ tumor is more common in African American race (Paulino 3). The intrinsic distortion of the collecting system of the calyces that is caused by the presence of solid extrarenal mass is diagnostic of Wilms’ tumor (Vicente 49). (Source: Sodal 2003) (Triphasic Pattern, University of Washington 2007) In the United States, about 500 new cases of Wilms’ tumor are diagnosed each year. This accounts for about 5% to 6% of all childhood cancers in the U.S. This tumor is slightly more common in girls than in boys. It affects only one kidney in most cases (Aetna InteliHealth). Wilms’ tumor occurs in many forms, it can be sporadic in 95%, familial in 1 – 2%, and associated with a syndrome in about 2%. The following syndromes predisposes Wilms’ tumor. These are WAGR (Wilms, aniridia, genitourinary malformation and mental retardation), Beckwith-Wiedemann Syndrome (gigantism, macroglossia, pancreas cell hyperplasia, BWS), and Denys-Drash Syndrome (male pseudohermaphrodite, nephropathy and Wilms tumor, DDS). Moreover, in 10% of cases, the sporadic type of Wilms’ tumor is associated with isolated malformations of genitourinary systems namely: hypospadia, cryptorchidism and renal fusion. In about 5 – 10% of cases, bilateral synchronous tumors of the kidneys are seen. Thus, for children who have a high risk of developing Wilms’ tumor, routine abdominal ultrasound screening every six months up to eight years of age is recommended (Vicente 2007).    Causes and Symptoms Alteration of genes that is responsible for the normal development of genitourinary system is considered to have caused Wilms’ tumor. The tumor will develop when the malignant kidney cells go out of control and develops into a mass that is firm, grayish or tan in color. Wilms’ tumor is observed to be smooth and fairly round. Consequently, as the tumor will grow larger, the tumor changes the kidneys’ shape and appearance. This tumor appears firm and a smooth lump in the abdomen of a child when it grows into a large size is noted. It has a potential to metastasize out to the neighboring organs such as the lungs and liver with no proper treatment (Aetna InteliHealth). Wilms’ tumor was originally thought to have developed after the two – hit model developed for retinoblastoma. In connection with this, the tumor is stated to be heritable. An individual becomes at risk for multiple tumors when first mutation would occur before the union of the sperm and egg. This is called as constitutional or germline mutation. Consequently, it was reported that nonhereditary Wilms’ tumor would develop following two zygotic mutations in a single cell. The aforementioned is called as somatic mutation. Several gene mutations are believed to have been involved in the overall pathogenesis of Wilms’ tumor (Vicente). Wilms’ tumor is believed to have contained a loss of heterozygosity (LOH) in 50% of cases. Loss of heterozygosity (LOH) is a mechanism that is believed to inactivate the tumor – suppressor gene where a loss of whole portions of chromosome is noted. Children associated with WAGR shows deletion of the short arm in the chromosome 11 band 11 (11p13) although with a normal 11p15 region. The region of deletion is termed as WT1 gene, a tumor suppressor gene forming a complex with p53, a tumor suppressor gene. It is known that in all WAGR syndrome cases, WT1 is deleted. For a normal nephroblasts differentiation, the important association of WT1 mutation and WAGR syndrome with intralobar nephrogenic rests immediately suggests that WT1 expression is necessary (Vicente). The presenting clinical manifestations of Wilms’ tumor are: large abdominal or flank mass associated with abdominal pain, asymptomatic hematuria, occasionally fever, body malaise, loss of weight, anemia, left varicocele (obstructed left renal vein), and hypertension. In addition, a child may also have hematuria, decreased appetite, constipation, stomach pain, nausea, and vomiting (Mayo Clinic Staff). Diagnosis Diagnostic Studies The following are diagnostic studies that should be performed to determine Wilms’ tumor: (1) CBC count, (2) Chemistry profile, including kidney function tests and routine measurements of electrolytes and calcium, (3) Urinalysis, (4) Coagulation studies, and Cytogenetics studies. The results of cytogenetic studies may reveal a deletion in 11p13,duplication of the paternal allele 11p15, and mutational analysis of the WTI gene (Paulino 5). Imaging Studies (1) Renal ultrasonography – this includes dynamic imaging of the renal vein and interior vena cava. (2) CT scanning includes: (a) Abdominal scanning helps in determining tumor origin, lymph node involvement, involvement of bilateral kidneys, major blood vessel invasion, and metastasis of the liver. (b) Chest CT (3) Four-field chest radiography – depicts metastasis to the lungs. It was reported that whole –lung radiation must be given with positive lung lesion on chest radiography. Procedures Histopathologic disease confirmation is essential. For staging of the disease, lymph node biopsy sample must be obtained. Treatment Wilms tumor has become a paradigm for multimodal treatment of malignant solid tumor in the children. Treatment for Wilms’ tumor would depend on the staging of the tumor. There are three types of treatment used in Wilms’ tumor. These are: surgery, radiation, and chemotherapy. Surgery is performed for treatment and staging purposes and to establish the need of therapy. To determine the extent of the disease, it is important that biopsy of the lymph nodes must be performed. Treatments for Wilms disease would depend on the disease staging, cell type histology, age of patient, and health of the patient in general. Tumor staging by National Wilms’ Tumor Study Group: Stage I – tumor is limited in the kidney and resected completely. If a child has favorable tumor histology, the probable treatment will be surgery followed by chemotherapy (Vincristine; Dactinomycin); however, if a child has an unfavorable tumor, treatment would still be surgery followed by radiation therapy in addition with chemotherapy (Vicente 49; Mowell, treatment). Stage II – tumor would extend beyond the kidney and is excised completely. Favorable tumor histology is probably treated with nephrectomy and chemotherapy while unfavorable tumor is treated with nephrectomy followed by radiation therapy in addition with chemotherapy (Vicente 49; Mowell, treatment). Stage III - residual non-hematogenous tumor that is confined to the abdomen. Both the favorable and the unfavorable tumors are treated with surgery followed by radiation therapy plus chemotherapy. Biopsy followed by chemotherapy with or without radiation will be performed in cases when the tumor is located near the organs and blood vessels making it too large remove. Chemotherapeutic agents used are Vincristin, Dactinomycin, and Doxorubin (Paulino 6; Vicente 49). Stage IV – hematogenous metastasis. The child with favorable or unfavorable tumor histology will receive radiation therapy in addition with chemotherapy after the surgery (Paulino 6; Vicente 49). Stage V – bilateral tumors. During this stage, the possibility of removing both kidneys is remote. The physician will take out a portion of a cancer in both kidneys and the lymph nodes around the kidneys are removed to ascertain whether they contain cancer cells. Following the procedure, chemotherapy and/or radiation therapy is routinely performed surgery (Paulino 6; Vicente 49). Prognosis Stage Relapse-Free Survival, % Overall Survival, % I 92 98 II 85 96 III 90 95 IV 80 90 (Source: Paulino 8) With the current multimodality therapy, about 80-90% of children with a diagnosis of Wilms tumor survives. On the other hand, the overall rate of survival for patients with favorable histology of the tumors will have at least 80% overall rate of survival at 4 years following the initial diagnosis, even in patients diagnosed to have stage IV disease. A survival rate of 70 –80% was reported in patients with synchronous bilateral tumors, while a 45 – 50% rate of survival was reported in patients with metasynchronous tumors. After retrieval of therapy, it was reported that the prognosis of patients who have a relapse is poor with only 30 – 40% of survival rate (Paulino 8). Prevention “There is no way to prevent Wilms tumor” (Aetna Intellihealth). References Mayo Clinic Staff. Wilms Tumor. 07 Sept 2007. Mayo Clinic. 25 March 2008 < http://www.mayoclinic.com/health/wilms-tumor/DS00436/DSECTION=2> Mowell, Betsy. Wilmstumour dot com. 07 Feb 2007. Cure Search Wilms’ Initiative. 25 March 2008 Paulino, Arnold. “Wilms Tumor.” Medscape Journal 19 Dec 2006: 1 – 11. Sodal, Gunnar. The Operating Theater at Haydom Lutheran Hospital. Jan 2003. Haydom Lutheran Hospital 25 March 2008 Solid Malignancies of Childhood. 31 Oct 2007. 25 March 2008 University of Washington Medicine Pathology Database. Vicente, Humberto. Pediatric Surgery Handbook. Oct 2007. Pediatric Surgery Handbook. 25 March 2008 University of Puerto Rico Wilms’ Tumor. 08 Feb 2008. Aetna Intellihealth. 25 March 2008 < http://www.intelihealth.com/IH/ihtIH/WSIHW000/9339/24568.html#prevent> Read More