Solid Tumor Residents

8/13/2019 Solid Tumor Residents

http://slidepdf.com/reader/full/solid-tumor-residents 1/58

Childhood Solid Tumors

Alexandra Walsh, MD

Resident Lecture1.26.12



Pediatric versus Adult Cancers

PEDIATRIC ADULTIncidence 17.6 per 100,000 538.8 per 100,000

Risk Factors Uncommon Common

Outcomes 75-80% overall survival <60%

Biology Embryonic: derived from non-ectodermal embryonal tissue

Carcinomas: derivedfrom epithelial tissue

NCI, SEER data



Percentage Distribution of

Childhood Cancers

Cancer Research UK, 2004



Cancer in Children

Cancer Children Adults

Acute Leukemia 28% 2.3%

CNS tumors 21% 1.6%

Lymphomas 11% 4.3%Neuroblastoma 7.5% 0%

Wilms’ tumor 6% 0%

Soft tissuesarcoma

6% <0.5%

OS and Ewing’ssarcoma

5% <0.5%

Retinoblastoma 3% 0%

Others 12.5% >90%



Childhood Cancers

Cancer Children

Acute Leukemia 28%

CNS tumors 21%

Lymphomas 11%

Neuroblastoma 7.5%

Wilms’ tumor 6%

Soft tissue sarcoma 6%

OS and Ewing’s sarcoma 5%

Retinoblastoma 3%

Others 12.5%

Abdominal tumors

Soft tissue tumors

Bone tumors

Eye tumors

61% ofchildhoodcancers are “solid tumors”



Case #1 HPI/PMH

3 yo female presents to PMD secondary to a “lump in the belly” that her mom felt while

bathing her the night before Child has been well

No fever, URI symptoms, N/V/D/C,

abdominal pain, urinary complaints orswelling anywhere else

PMH unremarkable



Case #1 PE

Afebrile, stable vital signs

Alert, active, playful 3 yo

Shoddy cervical lymphadenopathy

Heart regular rate and rhythym

Lungs clear 6 x 5 cm firm, smooth, non-tender abdominal

mass in the right quadrant, not crossing midline,margins well defined



Case #1 Labs WBC 6000

40% segs, 60% lymphs(ANC 2400)

Hgb 12 Hct 36

Plts 180,000

Normal CMPincluding BUN,creatinine

Normal LDH, uricacid

HVA, VMA Normal

AFP, B-HCG Normal

Urinalysis 2+ blood



CT Scan of Abdomen



Wilms Tumor 5-6% of childhood cancers

5th most common cancer overall and 2nd mostcommon abdominal malignancy

Occurs most commonly in children 2-5 yo

Arises from primitive metanephric blastema

Typically occurs sporadically but can occur incertain syndromes/ congential defects Beckwith-Wiedemann Syndrome Denys-Drash syndrome WAGR syndrome



Beckwith-Wiedemann Syndrome

Congenital disorder of growth regulation

1/14,000 children

Macrosomia, macroglossia, neonatalhypoglycemia, abdominal wall defects, earanomalies, visceromegaly

May be associated with hemi-hypertrophy

4-21% of patients develop cancer

Wilms tumor (43%) and Hepatoblastoma (12%)

Q4 month abdominal u/s until age 8



Wilms Tumor Associated

Syndromes Familial tumors- associated with 2 loci

WT1: primary gene implicated indevelopment of Wilms

Located at 11p13

Deletions noted in WAGR (Wilms, Aniridia, GUanomalies, Retardation)

Missense WT1 mutations in Denys Drash(gonadal dysgenesis, nephropathy)



Wilms Tumor

Presentation: Often asymptomaticincrease in size of abdomen

Labs: Usually normal

May have anemia secondary to hemorrhageinto the tumor

Microscopic hematuria



Wilms Tumor

Imaging: CT scan or ultrasound

Must evaluate contralateral kidney

Can metastasize to liver and lungs

Staging and histology of tumor importantfor prognosis

Overall survival rate of 90% (Stage IV,unfavorable histology has 17% overall survivalrate)



Wilms’ Tumor Treatment/Outcome



Case #2 HPI/PMH

3 yo male presents to PMD secondary to low-grade fever, fussiness, and decreased POintake over the past 2-3 weeks

Several pound weight loss

Irritable and over the past few days wants tobe held all the time and does not want towalk

No URI symptoms, no N/V/D/C, no sickcontacts

No significant PMH



Case #2 PE

Temp 100.8, P 130, R 25

Irritable, difficult to console, pale, ill-appearing 3 yo

Shoddy cervical lymphadenopathy

Tachycardia with II/VI SEM

Lungs CTA bilaterally

6 x 5 cm firm, fixed, irregularly shaped, right-sidedabdominal mass that extends beyond the midline



Case #2 Labs

WBC 4000 40% segs, 60%

lymphs (ANC2400)

Hgb 9

Hct 27

Plts 95,000

Retic 0.4

Normal CMP includingBUN, creatinine

elevated LDH, normaluric acid

AFP, B-HCG Normal

Urinalysis

Normal HVA, VMA Elevated



CT Scan of Abdomen



Neuroblastoma

7-10% of childhood cancers

50% diagnosed before 2 yo, 90% by 5 yo Arises from neural crest tissue of the

sympathetic ganglia or adrenal medulla

“Small round blue cell” malignancy

Must be differentiated from Ewings sarcoma(PNETs), rhabdomyosarcoma, lymphoma



Neuroblastoma Post-ganglionic sympathetic neuroblasts

(primitive, pluripotent)

Often constitutional symptoms: fever, irritability,

weight loss

Other symptoms based on primary site

Cervical: neck mass, Horner’s syndrome

Thoracic: Superior vena cava syndrome Paraspinous: cord compression

Abdominal: fullness, pain, obstruction

Metastatic disease: marrow, bone, liver, skin



Neuroblastoma

Elevated VMA, HVA,elevated ferritin, LDH, Abnormal blood counts ifmarrow involvement

< 18 mo tend to have low

stage, curable disease(70-90% survival)

> 18 months tend to havemetastatic disease (<15% survival)

Unique features: Stage4S, opsoclonus-myoclonus, raccoon eyes



Neuroblastoma Origin



Neuroblastoma IV-S

Infants with small primary tumors (stage I or II)

Distant metastases:

Liver Skin (blueberry muffin)

Bone marrow

NO BONE METS

Excellent prognosis with minimal or no therapy



Case #3 HPI/PMH 3 yo male presents to PMD secondary to

intermittent vomiting typically in the morningand irritability over the past couple of weeks

Crying more, waking up at night, and hishead seems to be hurting

Over past few days, he seems to be weakand is falling more

No fever, URI symptoms

No significant PMH



Case #3 PE/Labs

Afebrile, vitals stable

Fussy, somewhat lethargic 3 yo

Normal heart and lungs

Abdomen soft, NT/ND, active BS, no HSM or masses

Papilledema, CN II-XII normal, Normal motor

strength and sensation. Ataxic gait, dysmetria onfinger to nose

CBC, CMP normal



CT Scan/MRI of Head



Brain Tumors

Most common solidtumor in childhood(25% of all

childhood cancers) Tumors tend to be

infratentorial(posterior fossa) inyoung patients andsupratentorial inolder patients



Brain Tumors

Treatment consists of resection if possible,chemotherapy,+/- craniospinal radiation in

tumors with high probability of neuroaxisdissemination (≥ 3 yo)

Prognosis variable depending on location,

grade of tumor, resectability



Case #4 HPI/PMH

15 yo male presents with L knee pain ofapproximately 1 month duration

Originally began when he fell on his kneewhile being tackled playing touch-footballwith friends

+ swelling above the knee that seems to be

getting worse

No fever, no redness or warmth to the area

PMH unremarkable



Case #4 PE/Labs

Afebrile, vitals signs stable

Healthy appearing 15 yo in NAD Mass palpated involving L distal femur, no

effusion, warmth, erythema noted

Normal CBC

Elevated alkaline phosphatase and LDH



X-Ray, MRI of Knee



Bone Tumors

Signs of bone tumor include pain at site(often following minor trauma), mass, andfracture at area of bone destruction

Osteosarcoma and Ewing sarcoma aremost common types

Outcomes variable depending on whetheror not metastases present at diagnosisand location



Osteosarcoma Ewing Sarcoma

% of BoneTumors 60% 30%

PeakOccurrence

Adolescents Adolescents

Sex Males > Females Males > Females

Race African Americans > Caucasians Primarily Caucasians

Location

Metaphysis of Distal Femur >Proximal Tibia > Humerus

Pelvis > Diaphysis ofFemur > Tibia > Humerus

Imaging Appearance

Sunburst Appearance Onion-skin or Lamellated

Treatment Chemotherapy & Surgery Chemo then Surgery +/-Radiation & Chemo



Case #5 HPI/PMH

6 month old WF presents to herpediatrician for evaluation of fussiness andvomiting.

She has been on zantac for GERD.

PMH: term SVD, immunizations UTD

FH: colon cancer and colon polyps inmaternal family members

SH: lives with family; only child



Case #5 PE/Labs

Vital signs stable; afebrile

PE notable for hepatomegaly

Abdominal u/s reveals multilobular mass in rightlobe of liver measuring 7.6 x 10.9 cm.

CT scans without evidence of metastatic disease.

Labs: AST mildly elevated 96 T bili 1.1 (direct bilirubin 0.3) CBC notable for mild anemia AFP 2300 (<15)



CT Scan



Hepatoblastoma

Malignant liver tumors account for 1.1% of all childhoodcancers (1.5 cases/million children under age 15 yearly)

Hepatoblastoma accounts for 2/3rds

Usually occurs in first 4 yrs of life.

More common in males

Outcome is linked to stage of disease

Associated with prematurity

Occurs in association with several cancer geneticsyndromes.



Genetic Syndromes leading to

Hepatoblastoma Beckwith-Wiedemann

Reports of Li-Fraumeni (TP53) and trisomy

18

Familial adenomatous polyposis (FAP):germline mutation of APC gene

(chromosome 5q21.22) which is a tumorsuppressor gene. Associated also with colorectal cancer and

hepatocellular carcinoma



Case 6: HPI/PMH

16 mo WM who has been tilting his headwhen trying to look at objects.

Appetite has been normal. Rest of ROS isnegative.

Pediatrician referred to ophthalmology

who noted a lesion in the left eye ondilated exam.

PMH/FH: unremarkable



Case continues

MRI of brain confirmslesion in left eye (1.1 x

0.7 x 1.4 cm).

Exam under anesthesiaconfirms left eye lesionand revealed very smalllesion in right eye.



Retinoblastoma

Malignant tumor of the embryonic neuralretina

Most common intraocular tumor of childhood

Approx 3% of all childhood cancers

1/15,000 live births per year in US- estimated200 new diagnosis per year (20-30% are

bilateral) Median age at diagnosis is 2 yrs (90% of

cases are diagnosed before age 5)



Retinoblastoma presentation

Leukocoria

Strabismus

Lack of pain unless secondary glaucoma orinflammation.

Diagnosis is made by ophthalmologic andradiographic evaluation with pathologicconfirmation usually not needed.

Labs are usually normal



Hereditary Retinoblastoma

Usually presents with bilateraldisease/mutifocal tumors and at a youngerage (median age at dx is 11 mos).

RB1 gene Tumor suppressor gene on 13q14

RB protein- molecular switch controlling

passage thru G1 check point between G1 andentry into S phase

Vital for cell division/proliferation



RB1 mutations

Germline mutation- 90% risk of developingRB and 50% risk of passing mutation tooffspring

Genetic testing can identify mutations in 80-90% of individuals

Screening: Fundoscopic exam 1-2 wks after birth and every 2

weeks until 3 months of age. Then space out andcontinue exams until 4-5 yrs.

Yearly MRI from 6 mos to 5 yrs to screen for pineal

tumors



Treatment

90% overall 5 year survival Metastatic disease associated with a poor

prognosis

Trilateral retinoblastoma: Primary RB of pineal and parasellar sites Usually seen in familial disease Usually fatal

Mgmt: Local therapy- enucleation, cyrotherapy,

thermotherapy

Radiotherapy

Systemic chemotherapy



Presented to PMD with 3-day history ofswelling in R neck

Dx’d with sialthiothiasis and rx’d augmentin bid, sethim up see ENT if no improvement

11/24 saw ENT who agreed with diagnosis butobtained CT scan because it was not responding toantibiotics

Increased dose of augmentin

11/26 CT scan Large mass in R maxillary, ethmoid and extrachonal orbit

12/4 CT instatrac and MRI done

Case #7



PE: T 96.4, HR 76, BP 120/57,RR 20,

GEN: pleasant, oriented HEENT:+proptosis of R eye, withsubjunctival hemorrhage, EOMI,

large mass over R max sinus,large palpable mass in Rsupraclavicular area,nonerythematous, somewhat

tender, very firm CV, LUNG, LYMPH, ABD exams

unremarkable

LABS: CBC wnl, UA 10.3, LDH

1379

Case #7



Soft tissue sarcoma

Sarcoma: malignant tumor ofmesenchymal cell origin

Rhabdomyosarcoma: arises from immaturemesenchymal cells that are committed toskeletal muscle lineage (55-60%)

Non-RMS STS: Histology other than RMS (40-55%)



Rhabdomyosarcoma



RMS Treatment



Childhood Cancers

Cancer Children

Acute Leukemia 28%

CNS tumors 21%

Lymphomas 11%

Neuroblastoma 7.5%

Wilms’ tumor 6%

Soft tissue sarcoma 6%

OS and Ewing’s sarcoma 5%

Retinoblastoma 3%

Others 12.5%

Abdominal tumors

Soft tissue tumors

Bone tumors

Eye tumors

61% ofchildhoodcancers are “solid tumors”



The parents of a child who was diagnosed at birth with Beckwith-Wiedemann

syndrome bring in the baby for his 2-month evaluation. They ask about future health

problems and his prognosis now that his omphalocele has been repaired.

Of the following, the child is MOST at risk for

1. acute lymphocytic leukemia

2. astrocytoma

3. Hodgkin disease

4. Rhabdomyosarcoma5. Wilms tumor



A 2-year-old girl presents for evaluation of fussiness, low-grade fever, and what her

parents describe as "growing pains." On physical examination, you palpate a

nontender mass deep in the right periumbilical area and note mild purple

discoloration of the eyelids.

Of the following, the MOST likely diagnosis is

1. Hepatoblastoma

2. Hirschsprung disease

3. Intussusception4. Neuroblastoma

5. Wilms tumor

Solid Tumor Residents

Documents

Transcript of Solid Tumor Residents