Case PresentationCase Presentation

9 mo M presents to clinic with a chief compliant 9 mo M presents to clinic with a chief compliant of vomitingof vomiting

Case PresentationCase Presentation

• Mother reports the child has had a long Mother reports the child has had a long history of constipation and she gives him extra history of constipation and she gives him extra water and a high fiber diet to no availwater and a high fiber diet to no avail

• He has been fussy for the last three daysHe has been fussy for the last three days• Yesterday he began vomiting nonbilious Yesterday he began vomiting nonbilious

nonbloody emesis x 2nonbloody emesis x 2• His last BM was two days agoHis last BM was two days ago• He is otherwise wellHe is otherwise well

Case PresentationCase Presentation

• PMH: FT, uncomplicated pregnancy and PMH: FT, uncomplicated pregnancy and deliverydelivery

• Mother is 20yo G2P2Mother is 20yo G2P2• Medication: polyethylene glycol (for Medication: polyethylene glycol (for

constipation)constipation)• FH: 4yo sister is healthyFH: 4yo sister is healthy

Case PresentationCase Presentation

• O/E:O/E:• VS T 36.8 HR 110 RR 38 BP 111/65 Wt: 9.3 kgVS T 36.8 HR 110 RR 38 BP 111/65 Wt: 9.3 kg• Gen: well-appearing and playful, well Gen: well-appearing and playful, well

hydratedhydrated• Skin: no rash, no lesions Skin: no rash, no lesions • HEENT: Normocephalic; EOMI, PERRL, sclera HEENT: Normocephalic; EOMI, PERRL, sclera

nonicteric, TMs pearly and translucent; nonicteric, TMs pearly and translucent; oropharynx benignoropharynx benign

Case PresentationCase Presentation

• Nodes: no cervical, axillary, inguinal Nodes: no cervical, axillary, inguinal adenopathyadenopathy

• CV: RRR, nl S1/S2, no m/r/gCV: RRR, nl S1/S2, no m/r/g• Lungs: clear breath sounds bilaterallyLungs: clear breath sounds bilaterally• Abdomen: soft, tenderness diffusely along left Abdomen: soft, tenderness diffusely along left

side, no rebound, no guarding, palpable mass side, no rebound, no guarding, palpable mass in LLQ, normal bowel soundsin LLQ, normal bowel sounds

• Extr: warm and well perfusedExtr: warm and well perfused

Case PresentationCase Presentation• Differential Dx:Differential Dx:– ConstipationConstipation– Wilm’s tumorWilm’s tumor– NeuroblastomaNeuroblastoma– SplenomegalySplenomegaly– Multicystic kidney diseaseMulticystic kidney disease– Renal tumorRenal tumor

• Clear cell sarcomaClear cell sarcoma• Rhabdoid tumorRhabdoid tumor• Mesoblastic nephromaMesoblastic nephroma• Renal cell carcinomaRenal cell carcinoma• Renal medullary cancerRenal medullary cancer

Case PresentationCase Presentation

Studies:Studies:

• KUB: bowel gas is distributed primarily along KUB: bowel gas is distributed primarily along the right side of the abdomen; no obstruction; the right side of the abdomen; no obstruction; minimal stool seen in the colonminimal stool seen in the colon

• US: large mass eminating from the left kidney, US: large mass eminating from the left kidney, fully encapsulatedfully encapsulated

Case PresentationCase Presentation

Case PresentationCase Presentation

• Diagnosis:Diagnosis:

Wilm’s TumorWilm’s Tumor

Wilm’s Tumor and Wilm’s Tumor and NeuroblastomaNeuroblastoma

Venée Tubman, MDVenée Tubman, MDChildren’s Hospital BostonChildren’s Hospital Boston

HEARTTHEARTT

Wilm’s Tumor (WT)Wilm’s Tumor (WT)

• Wilm’s tumor is the most common renal Wilm’s tumor is the most common renal malignancy in pediatricsmalignancy in pediatrics

• Amongst Americans, more common in African Amongst Americans, more common in African AmericansAmericans

• Slightly more common in females, bilateral Slightly more common in females, bilateral disease more common in femalesdisease more common in females

WT: Associated SyndromesWT: Associated Syndromes

• Syndrome are associated with mutations or Syndrome are associated with mutations or deletions in WT1/FWT1/FWT2/p53 genesdeletions in WT1/FWT1/FWT2/p53 genes

• Beckwith-Wiedeman syndrome: macrosomia, Beckwith-Wiedeman syndrome: macrosomia, macroglossia, omphalocele, large kidneys, macroglossia, omphalocele, large kidneys, hemihypertrophyhemihypertrophy• 5-10% of children will develop WT5-10% of children will develop WT

• WAGR: WT, aniridia, GU anomalies, mental WAGR: WT, aniridia, GU anomalies, mental retardationretardation

• Denys-Drash: male pseudohermaphrodite and Denys-Drash: male pseudohermaphrodite and renal diseaserenal disease

WT: PathologyWT: Pathology

• Approximately 7% of cases have bilateral diseaseApproximately 7% of cases have bilateral disease• Most tumors are enclosed by renal capsule or Most tumors are enclosed by renal capsule or

intrarenal pseudocapsuleintrarenal pseudocapsule• Tumor can contain a mixture of cells:Tumor can contain a mixture of cells:– blastemal cellsblastemal cells– stromal cellsstromal cells– epithelial cellsepithelial cells

• High degree of anaplasia associated with poor High degree of anaplasia associated with poor outcomesoutcomes

WT: CLINICAL PRESENTATIONWT: CLINICAL PRESENTATION

• Many cases present with an abdominal mass Many cases present with an abdominal mass discovered by the parents during bath or discovered by the parents during bath or changing timechanging time

• Associated findings: abdominal pain (30%), Associated findings: abdominal pain (30%), hematuria (12-25%), hypertension (25%)hematuria (12-25%), hypertension (25%)

• Firm, nontender mass Firm, nontender mass which does not cross the which does not cross the midlinemidline

• Examine carefully given risk of capsular ruptureExamine carefully given risk of capsular rupture• Examine for associated anomlaies Examine for associated anomlaies

WT: EVALUATIONWT: EVALUATION

• KUB/USKUB/US• If available, CT (chest/abdomen)If available, CT (chest/abdomen)• Labs: chemistries, LFTs, urinalysisLabs: chemistries, LFTs, urinalysis

WT: STAGINGWT: STAGING

National Wilm’s Tumor Study National Wilm’s Tumor Study (US): staging is (US): staging is determined before chemotherapy is initiateddetermined before chemotherapy is initiated

WT: STAGINGWT: STAGING

International Society of Pediatric Oncologists International Society of Pediatric Oncologists (SIOP) (SIOP) (Europe): staging is determined after (Europe): staging is determined after chemotherapy is initiated for 4-6 weekschemotherapy is initiated for 4-6 weeks

• Stage 1: fully resected and encapsulatedStage 1: fully resected and encapsulated• Stage 2: beyond renal capsule but fully resectedStage 2: beyond renal capsule but fully resected• Stage 3: extends into abdomenStage 3: extends into abdomen• Stage 4: hematogenous spreadStage 4: hematogenous spread• Stage 5: bilateral renal diseaseStage 5: bilateral renal disease

WT: TREATMENTWT: TREATMENT

• Resection is the mainstay of treatment, but Resection is the mainstay of treatment, but without chemotherapy there is a high rate of without chemotherapy there is a high rate of recurrencerecurrence

• Stage 1 or 2: 18 weeks of vincristine and Stage 1 or 2: 18 weeks of vincristine and dactinomycindactinomycin

• Stage 3: 24 weeks of vincristine, doxorubicin, Stage 3: 24 weeks of vincristine, doxorubicin, and dactinomycin; and radiation to the flankand dactinomycin; and radiation to the flank

• Stage 4: 24 weeks of chemotherapy with Stage 4: 24 weeks of chemotherapy with radiation to flank and lungsradiation to flank and lungs

WT: OUTCOMESWT: OUTCOMES

• Response rate of 90% with chemotherapy and Response rate of 90% with chemotherapy and resectionresection

• Best prognosis is under 2 years and stage 1 Best prognosis is under 2 years and stage 1 diseasedisease

• 15% recurrence rate if histology is favorable; 15% recurrence rate if histology is favorable; 50% recurrence if anaplasia is present50% recurrence if anaplasia is present

• Complications are largely related to Complications are largely related to chemotherapychemotherapy

NEUROBLASTOMANEUROBLASTOMA

NEUROBLASTOMA (NB)NEUROBLASTOMA (NB)• Represents a variety of tumors including Represents a variety of tumors including

neuroblastoma, ganglioneuroma, neuroblastoma, ganglioneuroma, ganglioneuroblastomaganglioneuroblastoma

• Tumors arise from primitive sympathetic ganglion Tumors arise from primitive sympathetic ganglion cellscells

• Characterized by variable location, histology and Characterized by variable location, histology and behaviorbehavior

• Most common extracranial solid tumor in Most common extracranial solid tumor in children,children,accounting for 8% to 10% of all childhood cancersaccounting for 8% to 10% of all childhood cancers

• Prevalence is about 1 case per 7,000 live birthsPrevalence is about 1 case per 7,000 live births

NB: PATHOLOGYNB: PATHOLOGY

• Small blue round cell tumorSmall blue round cell tumor

• MYCN oncogene is activated in neoplastic cell linesMYCN oncogene is activated in neoplastic cell lines• Associated with advanced disease and poor outcomeAssociated with advanced disease and poor outcome

NB: CLINICALNB: CLINICAL• Can occur anywhere along the sympathetic nervous Can occur anywhere along the sympathetic nervous

system: adrenal (40%), abdomen (25%), thoracic system: adrenal (40%), abdomen (25%), thoracic (15%), cervical (5%)(15%), cervical (5%)

• Majority of tumors are diagnosed prior to age 5Majority of tumors are diagnosed prior to age 5• HepatomegalyHepatomegaly• Single, large left supraclavicular LN is highly suggestiveSingle, large left supraclavicular LN is highly suggestive• Presentation depends on location of tumor:Presentation depends on location of tumor:– Fixed, firm abdominal mass: LE edema, abdominal pain, Fixed, firm abdominal mass: LE edema, abdominal pain,

obstructionobstruction– Thoracic: incidental, Horner’s syndromeThoracic: incidental, Horner’s syndrome– Paravertebral: oncologic emergencyParavertebral: oncologic emergency

NB: CLINICALNB: CLINICAL

• Cathecolamine secretion causes hypertenisonCathecolamine secretion causes hypertenison• Opsoclonus-myoclonus: dancing eyes, jerking Opsoclonus-myoclonus: dancing eyes, jerking

movements, ataxiamovements, ataxia• Metastasizes to lymph nodes, bone marrow, Metastasizes to lymph nodes, bone marrow,

bone, dura, orbits, liver, skinbone, dura, orbits, liver, skin

NB: DiagnosisNB: Diagnosis

• An unequivocal pathologic diagnosis is made An unequivocal pathologic diagnosis is made from:from:– tumor tissue tumor tissue – increased urine (or serum) catecholamines or increased urine (or serum) catecholamines or

metabolites metabolites – bone marrow aspirate contains unequivocal bone marrow aspirate contains unequivocal

tumor cells AND increased urine or serum tumor cells AND increased urine or serum catecholamines catecholamines

NB: EVALUATIONNB: EVALUATION

• Excess cathecolamines cause urinary secretion Excess cathecolamines cause urinary secretion of homovanillic acid (HVA), vanillylmandelic of homovanillic acid (HVA), vanillylmandelic acid (VMA) and dopamineacid (VMA) and dopamine

• CT scan brain, chest, abdomenCT scan brain, chest, abdomen• Bone marrow aspirateBone marrow aspirate

NB: STAGINGNB: STAGINGInternational Neuroblastoma Staging SystemInternational Neuroblastoma Staging System• Stage 1: Localized tumorStage 1: Localized tumor• Stage 2A: Unilateral tumor with incomplete resection; identifiable lymph node Stage 2A: Unilateral tumor with incomplete resection; identifiable lymph node

negative for tumor.negative for tumor.• Stage 2B: Unilateral tumor with complete or incomplete resection; with ipsilateral Stage 2B: Unilateral tumor with complete or incomplete resection; with ipsilateral

lymph node positive for tumor; identifiable contralateral lymph node negative for lymph node positive for tumor; identifiable contralateral lymph node negative for tumor.tumor.

• Stage 3: Tumor infiltrating across midline involvement; or unilateral tumor with Stage 3: Tumor infiltrating across midline involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement.involvement.

• Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S.or other organs except as defined by Stage 4S.

• Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors).nucleated bone marrow cells are tumors).

NB: TreatmentNB: Treatment

• Surgery, chemotherapy, radiationSurgery, chemotherapy, radiation• Low risk disease may warrant surgery aloneLow risk disease may warrant surgery alone• Multiple chemotherapy regimens can be used Multiple chemotherapy regimens can be used

for intermediate ariskfor intermediate arisk• Radiation, chemotherapy, bone marrow Radiation, chemotherapy, bone marrow

transplant regimens have 15% survival for transplant regimens have 15% survival for high risk diseasehigh risk disease

NB: OutcomesNB: Outcomes

• Prognosis depends on age, stage, histology, Prognosis depends on age, stage, histology, DNA content, presence of MYCN mutationDNA content, presence of MYCN mutation

• Good outcomes are suggested by:Good outcomes are suggested by:• Age less than 18 months without MYCN Age less than 18 months without MYCN

amplificationamplification• Stage 4S Stage 4S