Renal and urinary system

Question 1

Wilms tumor (AKA: nephroblastoma)

Answer 1

*mutation in the tumor suppressor gene WT-1 or P53
*syndromic association is seen in a minority of patients:
-WAGR syndrome: germline WT-1 mutation: Wilms tumor, Aniridia, Genital abnormalities, mental Retardation
-Beckwith-Weidmann syndrome: germline WT-2 mutation,
neonatal hypoglycemia
macroglossia
macrosomia
ear abnormalities
midline abdominal defects (gastroschisis, omphalocele)
*CF:
-most children present at age 2-5 and almost never after age 10
-abdominal mass, no other symptoms usually
-a minority of patients have hematuria or abdominal tenderness
Dx:
-abdominal imaging to localize the mass to the kidney and decide whether it is surgically resectable
-chest and pelvic imaging to rule out metastasis
-biopsy for definitive diagnosis
pathology:
gross: large, solitary, tan mass in the kidney
microscopic: triphasic morphology
- glandular epithelium (rental tubules, and/or glomeruli)
-blastema (small hyperchromatic blue cells arranged in sheets, cords, or nodules)
-stroma
-the presence of anaplasia (enlarged hyperchromatic nuclei, atypical mitotic figures) is a poor prognostic sign
*DDx:
Neuroblastoma
-it’s another renal tumor
-maybe associated with elevated catecholamines and hypertension
-microscopically, the tumor shows endocrine features: rosette architecture, salt and pepper nuclei
Tr. and outcomes:
*excellent prognosis with surgery plus chromo and/or radiation therapy
* 5-year survival is 90%
*risk of tumor spillage during surgery
*risk of secondary malignancies in adulthood after radiation therapy
*Mutations in tumor suppressor genes and protooncogenes are often implicated in oncogenesis. Normally, tumor suppressor genes such as TP53, RB, and BRCA1/2 inhibit proliferation of damaged cells. Hereditary or acquired loss-of-function mutations of both alleles of a gene allow the development of malignancy (two-hit hypothesis). Proto-oncogenes are involved with normal cellular growth and development. A gain-of-function mutation converts a proto-oncogene into an oncogene that enables unchecked cellular proliferation. Only one mutated oncogene is required to promote oncogenesis.
*Vincristine is a chemotherapeutic agent used to treat Wilms tumors and many other malignancies. Vincristine binds to microtubules in the M phase of mitosis, preventing the formation of spindles. In addition to causing bone marrow suppression like most chemotherapeutics, vincristine can also cause peripheral neuropathy and neuralgias.