A Case of Mistaken Identity

Yavini Reddy MBCHB(UCT), DCH(SA),DipHIVMan(SA) Paediatric Registrar UKZN Zohra Bibi Banoo MBBCH (Wits), DCH (SA), FCP (SA), Paediatric Critical Care Fellow UKZN

Case Discussion
Baby NG was an eight month old female who was referred to the Pediatric Surgical team at Inkosi Albert Luthuli Central Hospital for the workup of a right abdominal mass that was present since birth. Baby NG presented to the local clinic with flu-like symptoms one month prior to being referred. The abdominal mass was an incidental finding that prompted referral. Baby NG was born with a weight of 2.9kg to an HIV uninfected mum. At initial examination she was clinically wasted with a weight of 5kg which was underweight for age according to the Welcome Classification. She was neither pale nor jaundiced. There were no skin lesions present. There was a palpable firm abdominal mass in the right upper quadrant extending to the right iliac fossa and across the midline. The upper border of the mass was accessible. There was no bruit heard over the mass. She was normotensive with a blood pressure of 96/48mm Hg and she was not in congestive cardiac failure. Her neurological examination was normal. The clinical differential diagnosis for this mass in order of probability included: Neuroblastoma Nephroblastoma Lymphoma Congenital Mesoblastic Nephroma Teratoma The initial biochemical workup for this abdominal mass included tumour markers: BHCG and alpha-fetoprotein which were normal. Her LDH was also within normal limits. An abdominal ultrasound showed a large heterogeneous mass extending from the right retroperitoneum with internal calcification and no significant vascular changes with it, however attenuation of the right renal artery was suspected. The ultrasound findings of this mass was suggestive of a neuroblastoma. To further delineate this mass a CT scan was ordered which confirmed a large 9 X 10.6 X 11.8cm heterogeneous retroperitoneal mass crossing the midline to the left with areas of calcification within. The right kidney was displaced laterally and anteriorly and the liver was diplaced superiorly. There was decreased enhancement of the right kidney compared to the left suggesting compression of the renal artery. CT findings were again

suggestive of a neuroblastoma.

Initial scans showing the large heterogeneous mass extending across the midline. Further workup for the mass included a fine needle aspiration: the results were suggestive of a ganglioneuroblastoma. A standardized neuroblastoma chemotherapeutic protocol was initiated for tumour debulking prior to any surgical intervention. The patient subsequently developed hypertension and initially required a single antihypertensive agent for blood pressure control. Five days later baby NG developed respiratory distress in the ward and was transferred to the PICU for ventilatory support for suspected nosocomial pneumonia.

Initial CXR showing cardiomegaly and opacification of the right lung fields In PICU there were many challenges in the management of Baby NG. She developed uncontrolled hypertension requiring 4 antihypertensive agents for her BP control. She also developed a hypertensive cardiomyopathy. CXR showed cardiomegaly and echogram confirmed a dilated left ventricle with borderline systolic function and a fractional shortening of 28%. There was no evidence of hypertensive retinopathy. However doppler studies were not suggestive of renal artery stenosis. Urinary catecholamines were also negative. Chemotherapeutic agents were continued in an attempt to decrease the tumour size, however due to its immunosuppressive effects Baby NG developed a varicella zoster infection, CMV pneumonitis and polymicrobial nosocomial infections which made weaning off the ventilator prolonged. Due to the large nature of the mass, she developed feed intolerance and this further compromised her nutritional status. She was successfully extubated 5 weeks later and was transferred back to the paedatric surgical team for continuation of chemotherapy. There was no visible shrinkage of the abdominal mass on repeat CT scan despite chemotherapy.

Repeat CT scan 8 weeks later showing no visible shrinkage in tumour size despite chemotherapy. The patient was taken to theatre 2 months later for resection. Intra-operative findings were that of a large retroperitoneal mass displacing the kidney, inferior vena cava and aorta with involvement of the right kidney. The mass weighed 1.227kg. A right nephrectomy was performed with removal of the tumour. Post surgery she was readmitted to the PICU but no ventilatory support was required and the antihypertensive medications were weaned off. Histology results revealed a teratoma with immature and mature components. The mature components included bone, muscle, fat, cartilage, skin, bronchial and intestinal epithelium. At follow up one month later she was still normotensive and repeat ultrasound showed no residual tumour. The follow up echo demonstrated good left ventricular contractility with fractional shortening of 42%. Baby NG is to be followed up yearly with abdominal ultrasound and tumour markers to look for tumour recurrence.

Approach to the Diagnosis of a Pediatric Abdominal Mass

The above case illustrates a rare case of an abdominal mass presenting as a teratoma. Patients presenting with an abdominal mass require a good history and an astute clinical examination combined with good radiological and pathology services for an accurate diagnosis. Important features on history include age, associated symptoms and signs such as anorexia, failure to thrive, hypertension, jaundice, feed intolerance and haematuria. Descriptive features of the mass should include Site Tenderness

Size and shape Surface and edge Consistency Mobility Pulsatility Accessibility above the mass

The above clinical findings lend itself to some working diagnosis as to the origin of the mass. Due to the limited scope of this article, the differential for hepatosplenomegaly has not been included. Initial investigations should include: Ultrasound which is a widely available and reliable imaging modality that can be used as an initial screening tool to identify the organ of origin and consistency of the mass. CT scan or MRI can further elucidate details of the mass including the relations to other important organs, vascular involvement and metastasis. Fine needle Aspiration under ultrasound guidance is useful but can be misleading. Tumour markers are an important facet in the determination of the organ of origin Histology post resection may be required for definitive diagnosis as in the index patient.

Diagnostic Algorithm
I have approached the differential diagnosis using renal versus extrarenal as renal masses are the most common cause. This can be further subdivided into benign and non benign.
Multicystic Dyplastic Kidneys Autosomal Recessive Polycystic Kidney Disease Congenital Mesoblastic Nephroma Multiloculated Cystic Renal Tumour

Benign

Renal

Maligna nt

Wilms Tumour Renal Cell Carcinoma Rhabdoid tumour Renal lymphoma

Benign

Extrarenal

Adrenal: Adrenocortical adenoma Liver: Haemangioendothelioma Biliary Tree: Cloledochal Cyst Pancreas: Pseudocyst Pelvis: Hydrocolpos Ovarian Cyst Germ Cell: Teratoma Bowel: Merconium pseudocyst Duplication cysts Intussusception Tuberculosis LN

Malignant

Adrenal :Neuroblastoma Adrenocortical carcinoma Liver: Hepatoblastoma Embryonal sarcoma Pancreas: Pancreatoblastoma Pelvis: Rhabdomyosarcoma, Bowel : Lymphoma

A discussion of teratoma, neuroblastoma and nephroblastoma will precede discussion of the structured approach as outlined in the table above. 1.Germ cell tumour Teratoma
Teratomas are interesting but uncommon lesions, occurring in 1 in 35,000-40,000 live births.1 Teratomas arise from postmeiotic germ cells and have components of all 3 embryonic layers. These tissues are always foreign to the location in which they are found. There is abnormal differentiation of fetal germ cells from the yolk sac with normal migration resulting in gonadal tumours and abnormal migration resulting in extragonadal tumours. Teratomas may be classified as mature or immature depending on the presence of immature neuroectodermal elements within the tumor. Most benign teratomas are composed of mature cells but may contain up to 25% of immature elements. Sacrococcygeal teratomas account for the majority of cases (45-65%). The next most common locations are: gonadal (10-35%), mediastinal (10-12%), retroperitoneal(3-5%), cervical (3-6%), presacral (3-5%), and central nervous system (2-4%).1 The most frequent abdominal teratomas are gonadal teratomas, retroperitoneal teratomas and gastric teratomas. Other rare sites include liver, kidney, intestine, bladder, uterus, mesentery and abdominal wall. Gonadal Teratoma

Mature teratomas are the most common germ cell tumour found in children with no significant malignant potential. It usually presents as an abdominal mass . The occurrence of bilateral ovarian involvement is < 10%. 1 Treatment is removal of the teratoma with some preservation of ovarian tissue. Mature teratomas Retroperitoneal Teratomas Retroperitoneal teratomas occur with equal frequency between males and females. They usually occur outside the pelvis in a an abdominal mass which may result in vomiting and constipation due to compression. Chest and abdominal xrays may provide evidence of calcification or bony structures within the tumour. In addition to ultrasound, a CT scan may be useful to determine the relationship of the tumor to other retroperitoneal structures and distinguish it from a primary renal or adrenal tumor. Serial assessment of serum markers such as raised B HCG and AFP have important diagnostic and prognostic value. Retroperitoneal teratomas should be surgically removed. The vast majority are benign and require no further treatment. Patients with malignant lesions and those with high grade immature elements should be treated with cisplatinbased chemotherapy Gastric Teratomas

These are rare lesions occurring most frequently in male infants. The tumour may present as a mass with complications of haematemesis or vomiting due to gastric outlet obstruction. They are usually benign and should be surgically excised.

2.Adrenal Tumours Neuroblastoma Neuroblastoma is the most common extracranial solid tumour in infants and children. Incidence is 1:10000 births and 30% of all cases occur in the first year of life. 4 These tumours arise from primordial neural crest cells, and can occur in the adrenal medulla or anywhere along the sympathetic ganglia most notably in the retroperitoneum and posterior mediastinum. Neuroblastomas refer to poorly differentiated tumour whereas ganglioneuroma is its well differentiated benign counterpart. Biochemical markers include neuron specific enolase (NSE), ferritin and lactate dehydrogenase. Intra-abdominal neuroblastomas often present as an asymptomatic firm fixed mass detected incidentally during a routine clinic visit. Haematogenous metastasis is often present at diagnosis. Painless subcutaneous nodules with distinct bluish discoloration in infants are called blueberry-muffin like spots.

Elevation of urinary cathecholamine metabolites (homovanillic acid and vanillylmandelic) is used as diagnostic screening. Calcification can often be detected on radiographs. Ultrasound is helpful to confirm the solid nature of the tumour. CT scan provides details on tumour consistency, extent of local disease and distant organ involvement. A large peri-renal mass with calcification is characteristic of neuroblastoma. Diagnosis is confirmed histologically. The usual modality of treatment include surgery, chemotherapy and radiotherapy Wilms Tumour This is the most common paediatric renal tumour, accounting for 6% of all malignancies with an incidence of 1:10000 children.4 It tends to occur between the ages of 1 and 7 years. Various congenital anomalies are known to be associated with Wilms tumour: aniridia, hemihypertrophy, genitourinary tract abnormalities, BeckwithWiedermann Syndrome, and Denys Drash Syndrome.5 Most children present with an asymptomatic abdominal mass. Gross or macroscopic haematuria is found in up to 25% of patients, and hypertension may be present due to an increase in renin secretion by the tumour or from a displaced kidney or renal artery.6 On examination a large smooth and firm nontender, immobile mass that does not cross the midline is palpated. Wilms tumour spreads by contiguous invasion of adjacent organs or by extension into the renal vein and inferior vena cava. Distant spread is most commonly to the lung and liver. CTscan of the abdomen defines the anatomic location and the the presence of bilateral renal involement.. Depending on the staging of the lesions management options include chemotherapy, radiotherapy and surgical excision.

3.Renal Masses
Two thirds of abdominal masses in the neonate are renal in origin and most are benign.2 Benign masses include: a. Hydronephrosis Common causes of hydronephrosis are unilateral uteropelvic junction obstruction(UPJO), vesicoureteral reflux, uterovesicular junction obstruction and the presence of posterior urethral valves.

UPJO is the commonest cause of prenatally diagnosed hydronephrosis. Ultrasound findings are typically limited to the dilation of the renal pelvis without ureteral or bladder abnormalities.2 Vesicoureteral reflux (VUR) is caused by an abnormal insertion of the distal ureter into the bladder. Renal cortical thinning and increased cortical echogenicity can also be seen on ultrasound. 2 Uterovesicular junction obstruction (UVJO) is a cause of neonatal hydronephrosis . Ultrasound findings include a distal dilated ureter. 2 Posterior urethral valves are caused by a malformation in the posterior urethra in boys. Ultrasound reveals a trabeculated thick walled bladder often with diverticula. A voiding cystourethrogram demonstrating the valve leaflets or a filling defect is often needed to confirm the diagnosis.2 b. Multicystic Dyplastic Kidneys (MCDK) This is a renal cystic abnormality that is more commonly unilateral with a male predominance. MCDK is believed to occur secondary to high grade stenosis of the uteropelvic junction. On ultrasound, multiple round anechoic structures of varying sizes are seen.3 Surgery is indicated in patients with complications such as hypertension and infection c. Autosomal Recessive Polycystic Kidney Disease (ARPKD) This is a genetic condition resulting from ectasia, dilatation and elongation of the renal tubules. May be associated with biliary duct ectasia. Kidneys can have a variable phenotypic and sonographic appearance. Treatment is supportive with renal and hepatic monitoring. d. Congenital Mesoblastic Nephroma (CMN) This is the most common abdominal neoplasm in the neonate. 2 Typically presents at three months with an abdominal mass. It is believed to be generally benign with some malignant potential that may warrant nephrectomy. Ultrasound findings include a large solid renal mass with heterogenous echogenicity.3 Further evaluation of the mass and adjacent structures should be done with CT or MR imaging to exclude metastasis. e. Multiloculated Cystic Renal Tumour (MCRT) This is a septated, cytic tumour of the kidney that usually presents as a large mass in children between 3 months and 2 years of age with a slight male predominance. CT scan confirms the diagnosis and treatment is with surgical excision.

f. Angiomyolipomas These are benign neoplasms with components of fat, vascular and smooth muscle tissue. This is common in patients with tuberous sclerosis. Malignant tumours include : a. b.Renal Cell Carcinoma Abdominal pain or haematuria and less commonly a palpable mass are the most common presentations. It can sometimes be radiologically difficult to differentiate from a Wilms tumour and usually presents in the advanced stage requiring a nephrectomy.

c. Rhabdoid tumour of the kidney It is one of the most aggressive and lethal of the paediatric tumours. The median age of presentation is 15 months. Common presentations include an abdominal mass, hypertension, fever and haematuria. Surgery, radiotherapy and chemotherapy are recommended however the survival rate is only 2025%.3 d. Renal Lymphoma This usually develops secondary to extranodal spread of lymphoma and is usually successfully treated with chemotherapy.

4.Extrarenal masses
4.1Liver a.Hepatic haemangioendotheliomas These are the most common symptomatic tumour in infants under 6 months.7 They present with a palpable mass, congestive heart failure and thrombocytopaenia and jaundice. It can be diagnosed on ultrasound and spontaneous regression is usually seen if uncomplicated. b. Hepatoblastoma (HB) This is the most common liver tumor in children that usually presents between the ages of 1 and 3 years with a palpable abdominal mass and raised AFP levels.3 Beckwith-Wiedemann Syndrome and familial adenomatous polyposis are associated with an increased risk for HB. c. Embryonal sarcoma (ES) This is a rare tumor of the liver, occurring in older children with normal serum AFP levels and a palpable abdominal mass. Constitutional symptoms, such as pain, fever, or jaundice may be present.

4.2 Biliary Tract

a. Choledochal cysts are congenital malformations of the biliary system and are usually treated surgically.

4.3 Pancreas
a. Pancreatic pseudocysts develop as a sequela from an episode of pancreatits and the diagnosis is generally made clinically by elevation of the serum amylase and lipase levels or by an appropriate history.

4.4 Pelvis
a.Hydrocolpos and Hydrometrocolpos Blood or fluid is contained in a dilated proximal vagina because of a distal vaginal obstruction. Treatment is with correction of the underlying problem. b.Neonatal ovarian cysts These are most likely due to in utero exposure to maternal hormones and treatment for large cysts is often surgical. c.Rhabdomyosarcoma (RMS) is one of the most common malignant solid tumors of childhood, ranking fourth behind CNS neoplasms, NB, and Wilms tumor. 8 The genitourinary tract is the second most common site of RMS, behind the head and neck. Treatment is with surgical excision.

4.5Bowel a. Meconium pseudocyst This can result from an inflammatory reaction following perforation of the intestines during fetal life, which causes a chemical peritonitis. b. Enteric duplication cysts can occur anywhere along the bowel on the mesenteric side and can act as a lead point for intussusception. c. Mesenteric cyst is also in the differential for a cystic mass in the abdomen. d. Intussusception Often colicky abdominal pain in a young child, associated with blood in the stools suggests the possibility of an intussusception. Intussusceptions occur in younger children, typically 5 months to 2 years of age.1 4,6Lymph Nodes

a. Lymphoma
Lymphomas have a wide range of cell types and histological patterns. Non Hodgkins Lymphoma (NHL), Malignant B cell lymphomas and Hodgkins

lymphoma can all present with an abdominal mass at initial diagnosis. Usually associated with systemic signs such as weight loss, night sweats and pyrexia. There is a higher incidence of all lymphomas but particularly NonHodgkins Lymphoma in patients with advanced HIV. Treatment is with a combination of chemotherapy and radiotherapy.

b. Abdominal Tuberculosis
This is an important differential in view of the high incidence of tuberculosis and HIV in South Africa. Abdominal tuberculosis results from haematogenous spread or secondary spread due to swallowed bacilli from pulmonary disease. The infection spreads from the intestinal mucosa to the mesenteric glands potentially causing periadenitis and peritonitis. The clinical manifestations include ascites, gastrointestinal tract disease and palpable nodes. Deep palpation may reveal masses due to enlarged glands in the right iliac fossa, centrally or along both sides of the spine.

Summary
The differential diagnosis of an abdominal mass is extensive but the combination of good clinical examination and radiological studies can assist in making a definitive diagnosis.

References
1.Adkins ES. Teratomas and other germ cell tumours. May 2008. Available at www.emedicine.medscape.com/article/939938 2. Pinto E., Guinard J.P.: Renal masses in the neonate. Biol Neonate 1995 68. 175-184. 3.Milla SS, Lee EY, Buonomo C, Bramson RT. Ultrasound evaluation of paediatric abdomoninal masses. Ultrasound Clinics 2007 July; 2(3):541-559. 4. Gurney J.G., Severson R.K., Davis S., et al. Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type. Cancer 1995; 75 : 2186-2195. 5 Coppes M.J., Egeler R.M., Genetics of Wilms' tumor. Semin Urol Oncol 1999; 17 : 2-10. 6.Kim S, Chung DH. Paediatric Solid Malignancies: Neuroblastoma and Wilms Tumour. Surgical Clinics of North America 2006 April; 86(2):469-487 7. Selby D.M., Stocker J.T., Waclawiw M.A., et al: Infantile hemangioendothelioma

of the liver. Hepatology 1994 ;20. 39-45. 8. Agrons G.A., Wagner B.J., Lonergan G.J., et al: Genitourinary rhabdomyosarcoma in children: radiologicpathologic correlation. Radiographics 1997;17. 919-937. 9. Vasavada P.: Ultrasound evaluation of acute abdominal emergencies in infants and children. Radiol Clin North Am 2004;42. (2): 445-456.