Presenting Signs and Prognostic Factors of Common Pediatric Malignancies

Educational Objectives

The goal of this program is to improve the management of common malignancies in children. After hearing and assimilating this program, the clinician will be better able to:

1. Elaborate on the age-related frequency of different pediatric cancers.

2. Recognize presenting features of common pediatric malignancies.

3. Anticipate and mitigate disease- and treatment-related complications of pediatric malignancies.

Summary

Common pediatric cancers by age: leukemia is among the most common in all age groups; 0 to 4 yr — central nervous system (CNS) tumors, neuroblastoma, kidney tumors, and retinoblastoma are most common; 5 to 9 yr — frequency of CNS tumors and lymphomas increase; neuroblastoma becomes less frequent; 10 to 14 yr — lymphoma, CNS, bone, and soft tissue tumors; 15 to 19 yr — tumor types become similar to adults; frequency of melanoma, adrenal cancer, thyroid cancer, and germ cell tumors increase; leukemia, lymphoma, and CNS tumors continue to be common

Wilms tumor (nephroblastoma): most common presentation is painless abdominal mass; other signs include hematuria, abdominal pain with or without hypertension or fever, anemia, and iron deficiency; treatment is chemotherapy, surgical resection, and radiation for patients with lymph node disease, positive margins, or tumor spillage; palpating the abdomen rarely causes tumor rupture; features portending poor prognosis include unfavorable histology and higher stage; ≥90% overall survival (OS) for stages I to III with favorable histology; ≈80% OS for stage IV; ≤50% OS with unfavorable histology

Neuroblastoma: derived from neural crest cells; most commonly affects children of younger age; locations include abdominal, intrathoracic, posterior mediastinal, cervical, and paraspinal; wide dissemination to bone, bone marrow, skin, liver, and lymph nodes; mass effect can cause abdominal pain, superior vena cava syndrome, Horner syndrome, or spinal cord compression; systemic symptoms include fever, irritability, diarrhea, weight loss, hypertension, and opsoclonus-myoclonus; metastatic disease can cause bone pain, limp, cytopenia, raccoon eyes, blueberry muffin rash, and hepatomegaly; stage 4S is a unique presentation in children age <1 yr with liver and skin involvement; may involve bone marrow (<10%); diagnostic tests include urine for homovanillic acid and vanillylmandelic acid; 123I-metaiodobenzylguanidine (MIBG) scan to evaluate disease burden

Treatment: infant with 4S disease — observation; others — surgery, chemotherapy, radiation, and 131I-MIBG therapy; stem cell transplantation and immunotherapy are reserved for patients with high-risk disease; children with low stage disease or 4S have ≥85% to 90% 5-yr OS

Pediatric liver tumors: hepatoblastoma typically affects children aged <5 yr; hepatocellular carcinoma affects children aged >10 yr; hepatoblastoma presents with abdominal pain, anorexia, vomiting, and icterus; α fetoprotein (AFP) is elevated in 90%; treatment is chemotherapy and surgical resection; some patients qualify for liver transplantation; risk features include metastatic disease at diagnosis, nonresectable tumor, low AFP at diagnosis, and small cell undifferentiated tumor on histology; >75% 5-yr OS for nonmetastatic disease and ≈20% for metastatic

Sarcomas: malignancies derived from embryonal mesoderm; histology does not necessarily reflect tissue of origin

Rhabdomyosarcoma: embryonal type has good prognosis; common sites include head and neck, parameningeal space, perineum, and anus; alveolar type has poor prognosis; common sites include axial trunk and retroperitoneum; metastasizes to lungs, bone and marrow, and lymph nodes; treatment with chemotherapy, surgical resection, and radiation; local control with surgery is of paramount importance

Osteosarcoma: most often presents as painful mass; more common in boys than girls; peak age of presentation is 15 yr; common tumor sites include appendicular skeleton (eg, humerus, femur, tibia); treatment with chemotherapy and complete surgical resection; limb-sparing surgery is preferred when possible; amputation when necessary; local control is critical; responds poorly to radiation

Ewing sarcoma: primarily affects children aged <20 yr; sites include lower extremity and axial skeleton (eg, pelvis, ribs, spine); systemic symptoms include fever and weight loss; treatment is chemotherapy, surgical resection, and radiation; 75% 5-yr OS for non-metastatic disease and <25% for patients with metastatic disease at diagnosis

Brain tumors: symptoms depend on location; include headache, nausea, vomiting, ataxia, diplopia, behavior change, seizures, and endocrinopathies; treatment is surgery, radiation, and chemotherapy; intrathecal chemotherapy has no role

Retinoblastoma (RB): usually presents with leukocoria or as a large intra-orbital mass; RB1 gene mutation has strong role in RB; in patients with bilateral RB, germline RB1 mutation is present in 100%; risk for osteosarcoma is increased if treated with radiation therapy; can be unilateral or bilateral; bilateral usually presents at age <1 yr; unilateral is more common and presents in older children

Treatment goal: maximal vision preservation; local therapy is preferred in patients with limited disease; enucleation is done for more extensive disease; systemic chemotherapy is for patients with advanced conditions

Acute leukemia: includes acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML); peak age of presentation 2 to 5 yr; slightly more common in boys; leukemic triad consists of fever, pallor, and bruising; other signs include bone and join pain, limp, hepatosplenomegaly, mediastinal mass T cell-ALL, variable degrees of anemia and thrombocytopenia, and variable white blood cell count, usually with circulating blasts

Acute lymphoblastic leukemia: treatment is systemic chemotherapy; intrathecal chemotherapy is given as prophylaxis for prevention of CNS involvement; CNS involvement is treated with intrathecal chemotherapy and radiation in some cases; phases of treatment include induction, consolidation, and maintenance; total duration of treatment ≈2.5 yr; >95% survival

Acute myelogenous leukemia: incidence is relatively constant throughout life; M3 subtype (acute promyelocytic) commonly presents with disseminated intravascular coagulation and coagulopathy; M7 is seen frequently in Down syndrome; treatment is intensive chemotherapy for ≈7 mo; retinoic acid and arsenic trioxide are used for treatment of acute promyelocytic leukemia; children with relapsed or refractory ALL or AML often require stem cell transplant

Hodgkin lymphoma: often presents with cervical or supraclavicular mass; usually has subacute presentation over several weeks; may have “B” symptoms (eg, fever, weight loss, night sweats); bloodwork may show anemia, lymphopenia, and elevated inflammatory markers; biopsy shows pathognomonic Reed-Sternberg cells; treatment is chemotherapy, radiation, and immunotherapy; surgery has no role; survival >95%; late side effects (eg, hyperthyroidism, cardiomyopathy, infertility) are common

Non-Hodgkin lymphoma: lymphoblastic lymphoma — 90% are T–lymphoblastic; mature B cell lymphomas — Burkitt lymphoma (BL) and diffuse large B-cell lymphoma; BL is the fastest growing cancer; endemic form is seen in Africa as jaw mass; always associated with Epstein-Barr virus; treatment is surgery, chemotherapy, immunotherapy, and radiation (for selected cases); prognosis in children is good

Tumor lysis syndrome: release of intracellular products from rapidly proliferating and dying tumor cells causes renal failure and severe metabolic derangement; hypocalcemia occurs secondary to hyperphosphatemia and binding of calcium; treatment is hyperhydration; allopurinol is given to inhibit xanthine oxidase and reduce production of uric acid; rasburicase is given when uric acid level is very high; symptomatic management of electrolyte abnormalities

Readings

Ishaq H and Patel BC. Retinoblastoma. StatPearls Publishing. 2021 Feb 25; DOI: https://www.ncbi.nlm.nih.gov/books/NBK545276/; Jamil A and Mukkamalla SKR. Lymphoma. StatPearls Publishing. 2021 Mar 7; DOI: https://www.ncbi.nlm.nih.gov/books/NBK560826/; Leslie SW et al. Wilms tumor. StatPearls Publishing. 2021 Feb 14; DOI: https://www.ncbi.nlm.nih.gov/books/NBK442004/; Mahapatra S and Challagundla KB. Neuroblastoma. StatPearls Publishing. 2020 July 17; DOI: https://www.ncbi.nlm.nih.gov/books/NBK448111/; Prater S and McKeon B. Osteosarcoma. StatPearls Publishing. 2021 Feb 20; DOI: https://www.ncbi.nlm.nih.gov/books/NBK549868/; Young G et al. Recognition of common childhood malignancies. Am Fam Physician. 2000 Apr 1;61(7):2144-2154.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Buhtoiarov was recorded at the 26th Annual Pediatric Board Review, held virtually from August 30 to September 4, 2020, and presented by the Cleveland Clinic Foundation. For information on future CME activities from this sponsor, please visit www.clevelandclinicmeded.com. Audio Digest thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD672202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.