Incidence

• Cancer is 2^nd most common cause of death in children aged 1-14 – 10%. (Accidents #1 – 42%)
• Leukemia accounted for ~33% of all cancers in children in the US in 1985.
• CNS tumors was second with ~20%.
• They are followed by: lymphomas, neuroblastoma, Wilms tumor, Bone cancer, rhabdomyosarcoma
• Overall survival from all malignancies has increased from 28% in 1960 to 67.5% in 1986.
• From 1975-1995, mortality due to leukemia dropped by 50%. In the same time period, mortality due to brain tumors changed very little.
• In 2005, leukemia accounts for about one third of all cancers in children under age 15 and one fourth of cancers occurring before age 20. Of about 2,800 children (ages 0-14) who will develop leukemia in 2005, about 78% (2,200) will be diagnosed with acute lymphocytic leukemia (ALL). Most of the remaining children will be diagnosed with acute myelogenous leukemia (AML). Chronic leukemias are rare in children. (leukemiafoundation.org).

Childhood tumors have their own separate natural behavior

• A disproportion between histologic findings and behavior exist in many cases.

1.     Hemangioma – appears invasive, but does no behave aggressively and often regresses

2.     Neuroblastoma – may regress even after mets

3.     Spitz nevus is a benign melanocytic proliferation in children (histo almost identical to malignant melanoma in adults)

Comparisons between Children and adults with cancer :

Pediatrics                                                        Adults

1^o sites                                 connective tissues,

hematopoietic tissues                        Visceral Organs

Histology                              Sarcomas, Leukemias                           Carcinomas

Stage at diagnosis Disseminated                                                       Local/Regional

Response to therapy            very good                                               less

5 yr survival                         >60%                                                       <50%

prevention                            NO                                                          YES (80%)

Benign Tumors

Hemangiomas

• MOST COMMON TUMOR IN INFANCY
• Benign proliferation of blood vessels
• Usually affects skin of face and scalp
• Can be disseminated and involve multiple organs
• Can cause local damage
• Grows rapidly
• May regress

Lymphangiomas

• cystic lesions of the neck, axilla, mdiastinum, and retroperitoneum
• lymphatic channels with variable lymphoid tissue involvement
• tough to manage and excise

Fibromatoses

• Collagen and fibroblasts with a variety of presentations and histologic appearances
• Composed of bland-spindled fibroblasts
• Tend to recur and be locally aggressive
• May regress
• There is a rare and potentially malignant form

Ø  Congenital Fibrosarcoma

Ø  12p13 and 15q25-26 rearrangements

Langerhans Cell Histiocytosis

• proliferation of Langerhans Histiocytes which are CD1a and S100 protein positive
• contain Birbeck granules by electron microscopy
• prognosis depends on age and extent of disease

Ø  fatal – disseminated infantile form

Ø  intermediate prognosis – multiple bone lesions w/ or w/o visceral lesions

• associated with Diabetes insipidus because of hypothalamic involvement (KNOW!)
• Called Hans-Schuller Christian

Germ Cell Tumors

• Gonadal or Midline

1)     in children and infants, Ovary>sacrococcygeal>testis

• Germ cell tumors give rise TO A VARIETY of tumors depending of LINE OF DIFFERENTIATION
• Prepubertal tumors are limited to:

1)     teratomas – consists of 3 germlines (endo-, ecto-, mesoderm)

2)     yolk sac tumors (malignant)

Ovarian Germ Cell Tumors

• MOST COMMON TYPE – Mature teratoma (benign)
• 15% are composed of immature teratoma (has malignant potential) or yolk-sac/teratoma mixed (malignant)

Sacrococcygeal germ cell tumors

• also a common tumor of infancy
• 33% have immature or yolk sac components
• usually not aggressive and occur before 4 mths of age

Testicular Germ Cell Tumors

• MOST COMMON TYPE – Pure yolk Sac
• Findings:

1)     Schiller-Duval Bodies

2)     Hyaline globules

3)     Alpha-fetoprotein

• Remember that a seminoma only occurs in POST-pubertal males

Malignant Tumors of Infancy and Childhood

Hematopoietic Tumors

Leukemia

• THE MOST COMMON MALIGNANCY OF CHILDHOOD (33% of all malignancies)
• Acute lymphoblastic leukemia (ALL) is more common than Acute Myoblastic Leukemia (AML)
• Most ALL are of B cell linage
• When you have a T cell ALL it is the leukemic part of T cell lymphoblastic lymphoma
• MOST COMMON LEUKEMIA IN CHILDHOOD = early pre-B cell acute lymphoblastic leukemia (65%)
• Prognostic Factors

1)     CD10 positive

2)     TEL-AML gene fusion t(12;21)

3)     Hyperdiploidy with > 50 chromosomes

Lymphoma

• 10% of pediatric tumors are lymphomas

Brain Tumors

• 2^nd MOST COMMON TUMOR OF CHILDHOOD
• In the first year of life, supratentorial tumors are more common

1)     Teratomas

2)     Choroid Plexus Tumors

• In the ages of 1-8, infratentorial tumors or posterior fossa tumors are more common

1)     Medulloblastoma (#1)

2)     Juvenile Pilocytic Astrocytoma

3)     Ependymoma

• Over 8 years of age the tumors become more adult-like and have an adult-like distribution (supratentorial)

Wilms Tumor

• MOST COMMON TUMOR AT BIRTH
• Accounts for 90-95% of renal tumors in childhood
• Mesenchymal origin with connective tissue and epithelial components
• Clinical Presentation of Wilms Tumor

1)     silent abdominal mass in a healthy child – most common

2)     rarely present after 5 years

3)     abdominal pain in 25-30%

4)     Hematuria (Gross or microscopic)

5)     Anemia, fever

• Must be distinguished from polycystic kidney, hydronephrosis, and other renal tumors
• High rate of recovery
• About 10% are bilateral
• GROSS

1)     Large, pale and firm with distortion of kidney and adjacent structures

2)     Gray to yellow, soft and gelatinous

3)     Can show cystic degeneration, hemorrhage, calcification

• MICRO: Classic triphasic histologic pattern
• GROWTH

1)     direct extension through capsule and into renal pelvis

2)     Hematogenous mets

• usually lung and lymph nodes
• rarely to bone
• PROGNOSIS

Ø  Dependent on stage of disease and histology

Staging of Wilms Tumor:

Stage I             Confined to Kidney, completely resected

Stage II            extends beyond kidney, completely resected

Stage III           residual confined to abdomen

Stage IV          Hematogenous metastases

Stage V           Bilateral; substage most advanced tumor

Histology and Stage               2 year survival

Favorable Histology and …

Stage I                   97.2%

Stage II                  92.8%

Stage III                 88.4%

Stage IV                83.5%

Unfavorable Histology and …

Stage I-III              71.5%

Stage IV                55.2%

Other renal tumors

Congenital Mesoblastic nephroma

• benign c.t. tumors usually appears in the 1^st month of life

Clear Cell sarcoma

Rhabdoid Tumor

Nephroblastomatosis

Neuroblastoma and Ganglioneuroma: spectrum of tumors that arise from the neuroepithelium

Neuroblastoma

• Behavior

Ø  usually inexorable growth with widespread mets particularly to liver and bone

Ø  HIGHEST RATE OF SPONTANEOUS REGRESSION OF ALL HUMAN TUMORS

Ø  Best prognosis if appears in 1^st year of life

Ø  Matures to a ganglioneuroma (benign) – a tumor of ganglion cells

• Clinical

Ø  tumor of young children; usually <5 years

Ø  Primary tumor

1)     abdominal mass or pain,

2)     RDS,

3)     dysphagia,

4)     cord paralysis,

5)     bowel or bladder dysfunction,

6)     more

Ø  Metastatic disease

1)     hepatomegaly, lymphadenopathy, bone pain, periorbital ecchymoses, more

Ø  Paraneoplastic syndromes

1)     VIP syndrome – chronic watery diarrhea and abdominal distension

2)     Opsonoclonus – myoclonus or cerebellar ataxia syndrome

3)     Excessive catecholamine release – HTN, headaches, flushing, sweating, tachy, palps.

• Neuroblastoma Morphology

Ø  Composed of neuroblasts and neuropils

Ø  Primary sites

1)     Adrenal medulla

2)     Sympathetic chain

3)     Retroperitoneal paraganglia

4)     Organ of Zuckerkandl

Ø  GROSS

1)     initial: localized and encapsulated

2)     variable

Ø  MICRO

1)     Undiferentiated: undifferentiated cells w/ large nuclei, thin rim of cytoplasm, neuropil absent, may require EM or histochemistry to id

2)     Poorly differentiated: less than 5% differentiated cells

3)     Differentiating: over 5% of differentiated cells, with enlarged nuclei, large single nucleolus…

4)     Metastases: lymph nodes, bone, bone marrow, liver, skin

Ganglioneuroblastoma

• mixture of neuroblastomatous and ganglioneuromatous elements
• majority of tumor is ganglioneuroma
• there are subtypes

Ganglioneuroma (Benign Tumor)

• posterior mediastinum is most common site
• GROSS
• HISTO

1)     mature ganglion cells

2)     Schwann cells, fibroblsts, collagen

3)     Often infiltrated by lymphocytes and plasma cells

• Prognosis

Ø  adrenal primaries have poorer prognosis; thoracic primaries have better prognosis

Ø  patients < 1 year do well

Stage of Disease – Evans Staging

Stage I           Tumor confined to organ of origin

Stage II          contiguous extension beyond organ of origin, does not cross midline

Stage III         contiguous extension across midline, regional lymph nodes, bilateral extension of

midline tumors

Stage IV         Remote disease, bone marrow, lymph nodes, soft tissue, skin

Stage IVS      Small/resectable primary w/ disseminated disease confined to bone marrow, skin,

liver; may not involve bone

Ø  Stage I & II – 80-90% survival, surgery alone

Ø  Stage III & IV – 20-40% 2 year survival, radiation and chemotherapy

Ø  Stage IVS

• frequent spontaneous regression of disease
• usually infants
• tumors tend to be hyperdiploid; single copy of N-myc

Cytogenetics, nuclear DNA content, and N-myc oncogene amplification

Favorable (usually differentiating)

-        normal chromosome 1

-        near triploid

Unfavorable (usually undifferentiated tumor)

-        marker chromosome 1

-        near diploid/tetraploid

-        N-myc amplification

Hepatoblastoma

• Primary tumor of liver
• Usually present in the first 2 years of life
• Two types: Hepatocellular and mixed
• Most important prognostic factor – resectability

Rhabdomyosarcoma

• Special Features

1.     MOST COMMON SOFT TISSUE SARCOMA IN CHILDHOOD

2.     Can arise anywhere

3.     18% have disseminated disease at time of diagnosis

• Embryonal rhabdomyosarcoma

Ø  Clinical

1)     average age 3-5 years

2)     males> Females

3)     primary sites: head and Neck, orbit, GU tract, biliary tract, extremities (virtually everywhere!)

Ø  GROSS

1)     sarcoma botyroids

2)     deep seated tumors

Ø  MICRO

1)     not uniform

2)     Classic: solid sheets of uniform dark cells with little discernible cytoplasm

• Alveolar rhabdomyosarcoma

Ø  Clinical

1)     older children (10-12 years)

2)     Males> Females

3)     Primary Sites: extremities, head and neck, orbit

Ø  GROSS

1)     up to 10 cm mass,

2)     mucoid surface

Ø  MICRO

1)     Nests of cells surrounded by septa of collagenous connective tissue

Ø  Metastases: lung, regional lymph nodes, bone, liver, brain

• Prognosis of rhabdomyosarcomas

Ø  overall survival – 70% if localized disease

Ø  after relapse, 5 year survival – 17%

Ø  Histo: embryonal variants do better that alveolar variants

Ø  Primary Site: orbital or GU primaries do better than extremity or parameningeal primaries

Tags: Alpha-fetoprotein, Atelectasis, Bilateral hypoplasia, Bone cancer, Bronchogenic, Bronchopulmonary Dysplasia, Canalicular Period, Choroid plexus tumors, Clear Cell sarcoma, Congenital Lobar Emphysema, Congenital Mesoblastic nephroma, Germ Cell Tumors, Hans-Schuller Christian, Hemangioma, Hematogenous, Hematopoietic Tumors, hematuria, Hepatobiliary, Hyaline globules, Hyaline Membrane disease, hyaline membranes, Hypoplastic lung, Langerhans Cell Histiocytosis, Leukemia, Lymphangiectasis, lymphoma, lymphomas, malformation syndromes, Neonatal Pulmonary Disease, Nephroblastomatosis, neuroblastoma, pneumonia, Pseudoglandular period, Rhabdoid Tumor, rhabdomyosarcoma, sacrococcygeal teratoma, Schiller-Duval Bodies, Spitz nevus, Terminal Sac Period, unilateral hypoplasia, Wilms tumor

This entry was posted on Friday, June 26th, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.