Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 7-2

Five-Year-Old Girl

MARINA CATALLOZZI

HISTORY OF PRESENT ILLNESS

A 5-year-old female was well until 2 days prior to presentation when she developed emesis and fever. On the day of presentation she had two bouts of nonbloody, nonbilious emesis and continued to have fever as high as 103°F. The patient pointed to the periumbilical area when describing her pain. Her parents also reported that she has had ear pain and a sore throat for the past 3 days. They deny cough, dysuria, and frequency. She has had a good appetite and no weight loss. The parents reported that about six months ago the patient had an episode of abdominal pain. Her primary care physician reportedly felt stool in the abdomen and started her on prune juice which she stopped using regularly.

MEDICAL HISTORY

Birth history was normal with no complications at delivery or birth. She had mild asthma but no hospitalizations. Three years prior, she was exposed to tuberculosis and had a positive tuberculin skin test. She was treated with isoniazid for 9 months.

PHYSICAL EXAMINATION

T 39°C; RR 24/min; HR 119 bpm; BP 106/65 mmHg

Weight 22.9 kg, 70th percentile; Height 120 cm, 70th percentile

Physical examination revealed an alert, well nourished, and interactive child. There was no conjunctival pallor. The tonsils were 2+ bilaterally with mild erythema of the posterior pharynx. There was shotty cervical lymphadenopathy with enlarged superior cervical lymph nodes that were mobile and nontender. The lungs were clear and there was an I/IV systolic ejection murmur at the left lower sternal border. The abdominal examination revealed normal bowel sounds. On palpation, the abdomen was nontender, but a firm mass was felt in the periumbilical region and left upper quadrant. The mass had sharp borders, was approximately 6 cm × 4 cm, and was slightly mobile. Rectal examination revealed good rectal tone and the rectal vault was full of stool which was negative for occult blood. She was a Tanner I female with no inguinal lymphadenopathy. Her neurologic examination was normal.

DIAGNOSTIC STUDIES

Laboratory analysis revealed 11 500 WBCs/mm3 with 2% band forms, 62% segmented neutrophils, 24% lymphocytes, and 9% monocytes. The hemoglobin was 14.3 g/dL and the platelet count was 251 000/mm3. Electrolytes, blood urea nitrogen, creatinine, calcium, magnesium, and phosphorus were normal. Liver function tests were normal. The uric acid was 5.3 mg/dL and the lactate dehydrogenase, 747 U/L. The abdominal radiograph revealed a large amount of stool.

COURSE OF ILLNESS

A fleets enema was given with good results, but the mass was still palpable. Abdominal MRI suggested a diagnostic category (Figure 7-2). Biopsy of the mass confirmed the diagnosis.

Image

FIGURE 7-2. Abdominal MRI.

DISCUSSION CASE 7-2

DIFFERENTIAL DIAGNOSIS

The finding of an abdominal mass in a child is an important one that can be attributed to causes as varied as bladder distention and life-threatening malignancies. The age of the patient, history, physical examination, and specific laboratory and imaging studies are crucial to arriving at the correct diagnosis. Children younger than 5 years are the group in which abdominal masses are most commonly identified, and the majority of abdominal masses that are identified in childhood by physical examination are secondary to organomegaly.

In neonates, retroperitoneal masses that arise from the genitourinary system are the most common and include hydronephrosis, multicysticpolycystic kidneys, mesoblastic nephroma, and renal vein thrombosis which is seen in infants of diabetic mothers or with severe hydration. Other possible etiologies include pelvic masses such as an ovarian cyst or hydrometrocolpos which presents with a suprapubic mass and vomiting as a result of hydronephrosis from obstruction of the ureters. Gastrointestinal etiologies include intestinal duplication, malrotation, and sacrococcygeal teratoma. Bladder distention, often as a consequence of posterior urethral valves, can also be common in the neonatal period. Hydronephrosis and multicysticpolycystic disease make up as much as a large percentage of the abdominal masses in neonates.

In infants, the most common malignant solid tumor is neuroblastoma. In childhood, Wilms tumor is the most common childhood abdominal malignancy. The classic presentation is that of an asymptomatic child whose parent notes an abdominal mass while bathing the child. Over half of Wilms tumor is seen before 5 years of age. Neuroblastomas that arise in the abdomen often cross the midline and more than half are seen within the first 2 years of life. The tumor can produce catecholamines and can therefore be clinically associated with tachycardia, hypertension, and skin flushing. The variability of the site of the primary tumor makes the clinical presentation variable, but constitutional symptoms such as fever and weight loss often occur. Other retroperitoneal masses seen in infants in children include rhabdomyosarcoma, lymphoma, Ewing sarcoma, and germ cell neoplasm. There are several liver lesions that can cause abdominal masses in this age group including benign solid tumors, malignant tumors, vascular lesions, and cystic hepatobiliary disease. There are also lesions of the stomach (carcinoma, leiomyosarcoma, fibrosarcoma), small bowel (duplication, Meckel, lymphoma), and colon (fecal mass also common in this age group), and omentum that can cause abdominal masses in this age group.

Adolescents can have many of the etiologies of abdominal masses that are seen in infants and children, but there are some diagnoses that are more common, pelvic masses in particular. Hematocolpos may not be clinically evident until menarche. Ovarian cystic lesions are common and the majority of these lesions are benign, with teratomas as the most common lesion of this type. Malignant ovarian lesions include germ cell tumors, dysgerminomas, choriocarcinomas, and gonadoblastomas. In the retroperitoneal region, renal cell carcinoma occurs most commonly at 14 years of age and presents with flank pain and hematuria.

Physical examination is the most important aspect of early detection of abdominal masses in children. Studies have shown that the majority of malignant abdominal masses in children could be palpated on initial examination.

DIAGNOSIS

MRI of the abdomen (Figure 7-2) revealed a 6 cm × 4.5 cm multiloculated mass arising from the left adrenal gland. There were no other retroperitoneal masses. During recovery, the biopsy of the tumor revealed ganglioneuroma. Metaiodobenzylguanidine (MIBG) scan was negative, confirming that the tumor was entirely a ganglioneuroma. The patient was started on a chemotherapy protocol to reduce the size of the mass before resection. The diagnosis is abdominal ganglioneuroma.

INCIDENCE AND EPIDEMIOLOGY OF GANGLIONEUROMAS

There is a spectrum of neuroblastoma tumors that includes ganglioneuromas, neuroblastomas, and ganglioneuroblastoma that arise from neural crest cells. Unlike neuroblastomas, ganglioneuromas are benign and differentiated tumors. Although the incidence of ganglioneuromas is not known, they are most common in children and young adults. They are usually found in the posterior mediastinum and retroperitoneum, and generally arise from the adrenal medulla. Much like pheochromocytomas, which are tumors of chromaffin cells of the adrenal medulla and adrenergic ganglia, adrenal ganglioneuromas can secrete epinephrine and norepinephrine giving rise to endocrinologic symptoms. There have been reports of malignant transformation of ganglioneuromas to neuroblastoma as well as mixed tumors with pheochromocytoma.

CLINICAL PRESENTATION

Ganglioneuromas are more commonly seen in children 5 years of age and older. Apart from the mass effect of any abdominal mass, ganglioneuromas can secrete catecholamines and present with the paraneoplastic syndrome seen with pheochromocytomas. Hypertension is the most concerning sign, and symptoms can include perspiration, tremor, nausea, vomiting, diarrhea, and other manifestations of Cushing syndrome. Because ganglioneuromas can be associated with neurofibromatosis type I or von Recklinghausen disease, clinical manifestations of this disease (such as axillary freckling and café au lait spots) may be noted.

DIAGNOSTIC APPROACH

Evaluation of an adrenal mass should include studies to detect ganglioneuroma, pheochromocytoma, and neuroblastoma.

Abdominal imaging. The initial study is usually an abdominal radiograph to exclude gastrointestinal obstruction. Some clinicians next obtain an ultrasound to determine the organ of origin and identify cysts, hemorrhage, and calcification. MRI may be used in lieu of ultrasound for clearer visualization of the adrenal gland. Additional imaging of the head, spine, or chest may be indicated to exclude metastatic disease.

Complete blood count. Pancytopenia indicates bone marrow involvement due to malignancy. Isolated anemia suggests either chronic illness or hemorrhage into the mass.

Electrolytes, calcium, phosphorus, uric acid, and lactate dehydrogenase. Abnormalities in these studies are seen with tumor lysis syndrome.

Urine HVA and VMA. In any patient with an adrenal mass, spot urine for homovanillic acid (HVA) and vanillylmandelic acid (VMA) should be obtained to detect neuroblastoma or pheochromocytoma.

Other studies. Plasma concentrations of normetanephrines or metanephrines (4-fold and 2.5-fold) above the upper reference limits indicate a pheochromocytoma with 100% specificity. MIBG scanning helps to rule out neuroblastoma.

TREATMENT

Treatment of abdominal ganglioneuroma is dependent on the patient’s clinical manifestations. In general, resection is curative. If the patient has endocrinologic manifestations, these should be stabilized medically prior to surgical resection.

SUGGESTED READINGS

1. Squires RH. Abdominal masses. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB, eds. Pediatric Gastrointestinal Disease. 3rd ed. Hamilton: B.C. Decker, Inc; 2000:150-163.

2. Golden CB, Feusner JH. Malignant abdominal masses in children: quick guide to evaluation and diagnosis. Pediatr Clin North Am. 2002;49:1369-1392.

3. Waguespack SG, Bauer AJ, Huh W, Ying AK. Endocrine tumors. In: Pizzo PA, Poplack DG. eds. Principles and Practices of Pediatric Oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2010.

4. Pacak K, Linehan WM, Eisenhoffer G, et al. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Internal Med. 2001;134:315-329.

5. Celik V, Unal G, Ozgultekin R, et al. Adrenal ganglioneuroma. Br J Surg. 1996;83:263.

6. Meyer S, Reinhard H, Ziegler K, et al. Ganglianeuroma: radiological and metabolic features in 4 children. Pediatr Hematol Oncol. 2002;19(7):501.