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

Case Presentation Mother reports the child has had a long history of constipation and she gives him extra water and a high fiber diet to no avail Mother reports the child has had a long history of constipation and she gives him extra water and a high fiber diet to no avail He has been fussy for the last three days He has been fussy for the last three days Yesterday he began vomiting nonbilious nonbloody emesis x 2 Yesterday he began vomiting nonbilious nonbloody emesis x 2 His last BM was two days ago His last BM was two days ago He is otherwise well He is otherwise well

Case Presentation PMH: FT, uncomplicated pregnancy and delivery PMH: FT, uncomplicated pregnancy and delivery Mother is 20yo G2P2 Mother is 20yo G2P2 Medication: polyethylene glycol (for constipation) Medication: polyethylene glycol (for constipation) FH: 4yo sister is healthy FH: 4yo sister is healthy

Case Presentation O/E: O/E: VS T 36.8 HR 110 RR 38 BP 111/65 Wt: 9.3 kg VS T 36.8 HR 110 RR 38 BP 111/65 Wt: 9.3 kg Gen: well-appearing and playful, well hydrated Gen: well-appearing and playful, well hydrated Skin: no rash, no lesions Skin: no rash, no lesions HEENT: Normocephalic; EOMI, PERRL, sclera nonicteric, TMs pearly and translucent; oropharynx benign HEENT: Normocephalic; EOMI, PERRL, sclera nonicteric, TMs pearly and translucent; oropharynx benign

Case Presentation Nodes: no cervical, axillary, inguinal adenopathy Nodes: no cervical, axillary, inguinal adenopathy CV: RRR, nl S1/S2, no m/r/g CV: RRR, nl S1/S2, no m/r/g Lungs: clear breath sounds bilaterally Lungs: clear breath sounds bilaterally Abdomen: soft, tenderness diffusely along left side, no rebound, no guarding, palpable mass in LLQ, normal bowel sounds Abdomen: soft, tenderness diffusely along left side, no rebound, no guarding, palpable mass in LLQ, normal bowel sounds Extr: warm and well perfused Extr: warm and well perfused

Case Presentation Differential Dx: Differential Dx: – Constipation – Wilm’s tumor – Neuroblastoma – Splenomegaly – Multicystic kidney disease – Renal tumor Clear cell sarcoma Clear cell sarcoma Rhabdoid tumor Rhabdoid tumor Mesoblastic nephroma Mesoblastic nephroma Renal cell carcinoma Renal cell carcinoma Renal medullary cancer Renal medullary cancer

Case Presentation Studies: KUB: bowel gas is distributed primarily along the right side of the abdomen; no obstruction; minimal stool seen in the colon KUB: bowel gas is distributed primarily along the right side of the abdomen; no obstruction; minimal stool seen in the colon US: large mass eminating from the left kidney, fully encapsulated US: large mass eminating from the left kidney, fully encapsulated

Case Presentation

Diagnosis: Diagnosis: Wilm’s Tumor

Wilm’s Tumor and Neuroblastoma Venée Tubman, MD Children’s Hospital Boston HEARTT

Wilm’s Tumor (WT) Wilm’s tumor is the most common renal malignancy in pediatrics Wilm’s tumor is the most common renal malignancy in pediatrics Amongst Americans, more common in African Americans Amongst Americans, more common in African Americans Slightly more common in females, bilateral disease more common in females Slightly more common in females, bilateral disease more common in females

WT: Associated Syndromes Syndrome are associated with mutations or deletions in WT1/FWT1/FWT2/p53 genes Syndrome are associated with mutations or deletions in WT1/FWT1/FWT2/p53 genes Beckwith-Wiedeman syndrome: macrosomia, macroglossia, omphalocele, large kidneys, hemihypertrophy Beckwith-Wiedeman syndrome: macrosomia, macroglossia, omphalocele, large kidneys, hemihypertrophy 5-10% of children will develop WT 5-10% of children will develop WT WAGR: WT, aniridia, GU anomalies, mental retardation WAGR: WT, aniridia, GU anomalies, mental retardation Denys-Drash: male pseudohermaphrodite and renal disease Denys-Drash: male pseudohermaphrodite and renal disease

WT: Pathology Approximately 7% of cases have bilateral disease Approximately 7% of cases have bilateral disease Most tumors are enclosed by renal capsule or intrarenal pseudocapsule Most tumors are enclosed by renal capsule or intrarenal pseudocapsule Tumor can contain a mixture of cells: Tumor can contain a mixture of cells: – blastemal cells – stromal cells – epithelial cells High degree of anaplasia associated with poor outcomes High degree of anaplasia associated with poor outcomes

WT: CLINICAL PRESENTATION Many cases present with an abdominal mass discovered by the parents during bath or changing time Many cases present with an abdominal mass discovered by the parents during bath or changing time Associated findings: abdominal pain (30%), hematuria (12-25%), hypertension (25%) Associated findings: abdominal pain (30%), hematuria (12-25%), hypertension (25%) Firm, nontender mass which does not cross the midline Firm, nontender mass which does not cross the midline Examine carefully given risk of capsular rupture Examine carefully given risk of capsular rupture Examine for associated anomlaies Examine for associated anomlaies

WT: EVALUATION KUB/US KUB/US If available, CT (chest/abdomen) If available, CT (chest/abdomen) Labs: chemistries, LFTs, urinalysis Labs: chemistries, LFTs, urinalysis

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

WT: STAGING International Society of Pediatric Oncologists (SIOP) (Europe): staging is determined after chemotherapy is initiated for 4-6 weeks Stage 1: fully resected and encapsulated Stage 1: fully resected and encapsulated Stage 2: beyond renal capsule but fully resected Stage 2: beyond renal capsule but fully resected Stage 3: extends into abdomen Stage 3: extends into abdomen Stage 4: hematogenous spread Stage 4: hematogenous spread Stage 5: bilateral renal disease Stage 5: bilateral renal disease

WT: TREATMENT Resection is the mainstay of treatment, but without chemotherapy there is a high rate of recurrence Resection is the mainstay of treatment, but without chemotherapy there is a high rate of recurrence Stage 1 or 2: 18 weeks of vincristine and dactinomycin Stage 1 or 2: 18 weeks of vincristine and dactinomycin Stage 3: 24 weeks of vincristine, doxorubicin, and dactinomycin; and radiation to the flank Stage 3: 24 weeks of vincristine, doxorubicin, and dactinomycin; and radiation to the flank Stage 4: 24 weeks of chemotherapy with radiation to flank and lungs Stage 4: 24 weeks of chemotherapy with radiation to flank and lungs

WT: OUTCOMES Response rate of 90% with chemotherapy and resection Response rate of 90% with chemotherapy and resection Best prognosis is under 2 years and stage 1 disease Best prognosis is under 2 years and stage 1 disease 15% recurrence rate if histology is favorable; 50% recurrence if anaplasia is present 15% recurrence rate if histology is favorable; 50% recurrence if anaplasia is present Complications are largely related to chemotherapy Complications are largely related to chemotherapy

NEUROBLASTOMA

NEUROBLASTOMA (NB) Represents a variety of tumors including neuroblastoma, ganglioneuroma, ganglioneuroblastoma Represents a variety of tumors including neuroblastoma, ganglioneuroma, ganglioneuroblastoma Tumors arise from primitive sympathetic ganglion cells Tumors arise from primitive sympathetic ganglion cells Characterized by variable location, histology and behavior Characterized by variable location, histology and behavior Most common extracranial solid tumor in children, accounting for 8% to 10% of all childhood cancers Most common extracranial solid tumor in children, accounting for 8% to 10% of all childhood cancers Prevalence is about 1 case per 7,000 live births Prevalence is about 1 case per 7,000 live births

NB: PATHOLOGY Small blue round cell tumor Small blue round cell tumor MYCN oncogene is activated in neoplastic cell lines MYCN oncogene is activated in neoplastic cell lines Associated with advanced disease and poor outcome Associated with advanced disease and poor outcome

NB: CLINICAL Can occur anywhere along the sympathetic nervous system: adrenal (40%), abdomen (25%), thoracic (15%), cervical (5%) Can occur anywhere along the sympathetic nervous system: adrenal (40%), abdomen (25%), thoracic (15%), cervical (5%) Majority of tumors are diagnosed prior to age 5 Majority of tumors are diagnosed prior to age 5 Hepatomegaly Hepatomegaly Single, large left supraclavicular LN is highly suggestive Single, 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, obstruction – Thoracic: incidental, Horner’s syndrome – Paravertebral: oncologic emergency

NB: CLINICAL Cathecolamine secretion causes hypertenison Cathecolamine secretion causes hypertenison Opsoclonus-myoclonus: dancing eyes, jerking movements, ataxia Opsoclonus-myoclonus: dancing eyes, jerking movements, ataxia Metastasizes to lymph nodes, bone marrow, bone, dura, orbits, liver, skin Metastasizes to lymph nodes, bone marrow, bone, dura, orbits, liver, skin

NB: Diagnosis An unequivocal pathologic diagnosis is made from: An unequivocal pathologic diagnosis is made from: – tumor tissue – increased urine (or serum) catecholamines or metabolites – bone marrow aspirate contains unequivocal tumor cells AND increased urine or serum catecholamines

NB: EVALUATION Excess cathecolamines cause urinary secretion of homovanillic acid (HVA), vanillylmandelic acid (VMA) and dopamine Excess cathecolamines cause urinary secretion of homovanillic acid (HVA), vanillylmandelic acid (VMA) and dopamine CT scan brain, chest, abdomen CT scan brain, chest, abdomen Bone marrow aspirate Bone marrow aspirate

NB: STAGING International Neuroblastoma Staging System Stage 1: Localized tumor Stage 1: Localized tumor Stage 2A: Unilateral tumor with incomplete resection; identifiable lymph node negative for tumor. Stage 2A: Unilateral tumor with incomplete resection; identifiable lymph node negative for tumor. Stage 2B: Unilateral tumor with complete or incomplete resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor. Stage 2B: Unilateral tumor with complete or incomplete resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor. Stage 3: Tumor infiltrating across midline involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement. Stage 3: Tumor infiltrating across midline involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement. Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S. Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, 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, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors). 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 nucleated bone marrow cells are tumors).

NB: Treatment Surgery, chemotherapy, radiation Surgery, chemotherapy, radiation Low risk disease may warrant surgery alone Low risk disease may warrant surgery alone Multiple chemotherapy regimens can be used for intermediate arisk Multiple chemotherapy regimens can be used for intermediate arisk Radiation, chemotherapy, bone marrow transplant regimens have 15% survival for high risk disease Radiation, chemotherapy, bone marrow transplant regimens have 15% survival for high risk disease

NB: Outcomes Prognosis depends on age, stage, histology, DNA content, presence of MYCN mutation Prognosis depends on age, stage, histology, DNA content, presence of MYCN mutation Good outcomes are suggested by: Good outcomes are suggested by: Age less than 18 months without MYCN amplification Age less than 18 months without MYCN amplification Stage 4S Stage 4S