Cancer Epidemiology and Pediatric Neoplasia p11-14

Clinical Manifestations of Neuroblastoma:

Test q: Common presentations of neuroblastoma in children include all of the following EXCEPT: Hypertension. (Other choices: Large abdominal mass, Blueberry muffin baby, Horner’s syndrome, Orbital metastases) Test q: A 2y/o child undergoes surgical resection of a neuroblastoma. All the following are common features of the tumor EXCEPT: Hypertension. (Other choices: catecholamines in urine, metastasis to skin, metastasis to periorbital bones.)

Neuroblastoma Stage IV S (Special): - Metastases limited to liver, skin, bone marrow - Patients usually 5% ganglion cells but still w/immature neuroblasts. (5% is cutoff – start calling it neuroblastoma)

Above: Ganglioneuroma – mature ganglion cells within a schwannian stroma. no immature neuroblasts, no neuropil. Schwannian stroma mixed with ganglion cells = totally benign

Above: Neuroblastoma Electron Microscopy. Neuroendocrine granules and microtubules are highly characteristic.

Test q: A 19F undergoes appendectomy. At surgery, a large yellow-gray mass (8cm) is found adjacent to the left adrenal gland. The tumor shows ganglia and Schwann cells but blastic cells are not seen. Diagnosis: Ganglioneuroma.

 Neuroblastoma Electron Microscopy, higher magnification.

NEUROBLATOMA PROGNOSTIC FACTORS: 1. Age and histology (Shimada scheme) 2. Stage 3. Location – abdominal worse than mediastinum, neck pelvis; adrenal primary worse than other sites (except IV S) 4. N-myc oncogene – aggressive tumors show amplification = worse prognosis. 5. Many others – see handout and Robbins text Test q: Of the following, which is the most important factor for neuroblastoma prognosis? Age of the patient (Other choices: tumor size, ratio of catecholamine metabolites in the urine, tumor calcification, and location of the primary tumor) Test q: All of the following features of neuroblastoma indicate a good prognosis EXCEPT: development outside the mediastinum. (Other choices: Absence of N-myc amplification, Presence of ganglion cell differentiation, Age under 2 years, and Stage IV S.) Test q: A 2y/o female presents w/a large abdominal mass involving the left kidney. Age is critical in determining the prognosis for this malignant tumor. Histology shows small blue cells and neuropil. What molecular abnormality is associated with this tumor? N-Myc amplification Test q: The mother of a 5y/o boy notices that his abdomen is enlarged. On phys exam, the physician palpates an ill-defined abdominal mass. An abdominal CT scan shows a 9-cm mass in the region of the right adrenal gland. The mass is removed and microscopically appears to be a neuroblastoma. Cytogenetic analysis of tumor cells shows many double minutes and homogeneously staining regions. Which of the following genes is most likely to have undergone alterations to produce these findings? N-MYC (transcription factor gene).

Wilms Tumor (Nephroblastoma): - Most common malignant kidney tumor in children - About 500 new cases per year in U.S. - Peak age 2-4 years, rarely congenital - Most are sporadic but also occurs in hereditary forms Conditions Associated with Wilms Tumor: - Aniridia (up to 33% will develop Wilms tumor) – see discussion of WT1 and WT2 genes in Robbins text - WAGR syndrome (Wilms tumor , aniridia, GU anom., retardation) - Drash syndrome (Wilms tumor, pseudohermaphroditism, nephrotic synd) - Beckwith-Weidemann syndrome (Exomphalos, macroglossia, gigantism) and Perlman’s syndrome (Wilms tumor, renal dysplasia, fetal gigantism, pancreatic endocrine hyperplasia, MCA, MR) - Hemihypertrophy (BWS) - GU anomalies, skin hamartoma, hemangiomas, malformed ears - Increased incidence in VRD, Bloom’s syndrome, trisomy 13 & 18, intersex anomalies Wilms Tumor Clinical Presentation - Typical history is abdominal mass noted by mother - Hematuria 5-10% - Sudden hemorrhage into Wilms tumor may cause anemia, HTN, rapidly increasing abdominal mass (Ramsey’s Triad) - Metastases to nodes, liver, lungs (different from neuroblastoma); bone metastases extremely rare (whereas neuroblastoma goes to bone all the time) Wilms tumor, 757 g, 22 month old female  Extremely well circumscribed and encapsulated. Tan, white, homogenous, can be huge. Unfavorable Histology in Wilms’ Tumors - About 5% of WT are unfavorable histology - Characterized histologically by increased nuclear anaplasia/hyperchromasia and by bizarre mitotic figures - UH tumors are more resistant to chemoTx, and have a worse prognosis if beyond stage 1 - Anaplasia correlates with p53 mutations Wilms Tumor Prognosis - Survival of low stage favorable histology >90% - Prognosis not as strikingly related to age as with neuroblastoma - Worse prognosis with extensive lung metastases or with UH beyond stage 1

Wilms Tumor w/Invasion of the Renal Pelvis, 900g, 13 Month old Female  Can have areas of focal degeneration – can extend into the renal pelvis.

 Wilms Tumor Microscopic from Robbins th 4 Edition. Classically a triphasic tumor (3 components) – cilia, mesechyma, and blastema. Wilm’s tumor, regardless of advances in treatment, looks the same today as 20 years ago. Pathology is the same.

Above: Wilms Tumor w/ Hemorrhage. 3 y/o Female

Wilms Tumor – Triphasic Pattern

Wilms Tumor – with Fetal Skeletal Muscle See skeletal muscle differentiation.

Wilms Tumor – Blastema and Stroma

Wilms Tumor – Blastema and Epithelium

Anaplasia in a Wilms’ tumor w/a bizarre mitotic figure Unfavorable histology. Predicts worse prognosis.

Test q: A 3y/o female is noted to have an abdominal mass by her mother. The child is anemic. Hematuria is NOT present. The surgically resected tumor shows small, round blue cells, primitive tubules, and spindled stroma. This description is most consistent with: Wilms tumor. Test q: A large abdominal tumor is removed from a 5y/o boy. On H&E sections, the tumor exhibits primitive blastoma, tubule formation, and loose stroma. This tumor is diagnosed as: Wilm’s tumor.