Index of suspicion.

Abstract

We invite readers to contribute case presentations and discussions. Please use the Submit and Track My Manuscript link on the Pediatrics in Review homepage: http://pedsinreview.aappublications.org.An 11-year-old girl presents to the emergency department (ED) with a 1-day history of severe abdominal pain. The patient characterizes the pain as episodic, cramping, and localized to the suprapubic area and right lower quadrant. The episodes occur approximately every 2 to 4 weeks, during which she experiences pain several times a day for 3 to 5 days. The pain self-resolves, and she is pain free between episodes. There are no alleviating or exacerbating factors. She reports associated nausea but no vomiting, diarrhea, constipation, or fever. The patient denies menarche.On presentation, she is tachycardic with a heart rate of 124 beats per minute. Other vital signs are normal. Her height is 1.67 m (>95th percentile) and weight is 59.3 kg (95th percentile). She appears to be in significant pain; she is lying on her side in a fetal position. There is diffuse abdominal tenderness, which is most notable over the suprapubic region, with no rebound or guarding. The abdominal examination findings are otherwise normal, with normal bowel sounds and no distention, masses, or organomegaly. Genitourinary examination findings are consistent with a sexual maturity rating of 2. The hymenal ring is open and intact without notches or tears. The breast sexual maturity rating is 3.Results of initial laboratory evaluation are as follows: white blood cells, 1500/μL (1.5 × 109/L); hemoglobin, 12 g/dL (120 g/L); and platelets, 256 × 103/μL (256 × 109/L). The urinalysis result is positive for trace ketones with 1 white blood cell, and no bacteria are seen on microscopic examination. A urine pregnancy test result is negative. Abdominal ultrasonography reveals a uterine mass. Additional evaluation and imaging studies reveal the diagnosis.A 9-year-old boy presents to the ED with a 12-hour history of epigastric pain and vomiting. The pain is intermittent, does not radiate, and has no exacerbating factors. The emesis is nonbloody and nonbilious. He had similar symptoms 3 weeks ago. There is no history of recent travel or sick contacts. His medical history is otherwise unremarkable. On further questioning, the parents report a poor appetite with a possible 8-lb weight loss during the preceding 3 months.The physical examination reveals a comfortable and well-appearing child. His vital signs are normal, and his body mass index is in the 50th percentile. The abdominal examination findings are significant for a 1- to 2-cm, poorly defined epigastric mass with hepatomegaly spanning 2 cm below the right costal margin. There is neither splenomegaly nor icterus. The remainder of the physical examination findings are unremarkable.Results of laboratory studies include the following: normal complete blood cell count; normal serum levels of electrolytes, bilirubin, albumin, amylase, lipase, and lactate dehydrogenase; alanine aminotransferase, 268 U/L (reference range, 0–41 U/L); aspartate aminotransferase, 330 U/L (reference range, 0–38 U/L); and alkaline phosphatase, 262 U/L (reference range, 39–117 U/L). The results of laboratory tests for hepatitis B, hepatitis A, hepatitis C, and, hepatitis E infections are negative. The results of the monospot test, as well as serologic tests for cytomegalovirus and Epstein-Barr virus, are negative. Abdominal imaging leads to the diagnosis.A 4-year-old girl presents with a 3-day history of left inguinal swelling that initially was the size of an olive but is progressively increasing in size. She has fever, pain, and redness of skin at the site. She has no weight loss, night sweats, bone pain, sick contacts, recent travel, trauma, or animal contacts. Her prenatal, natal, and postnatal history is unremarkable. Her immunizations are up to date.On physical examination she is in moderate distress attributed to pain and is afebrile. Her heart rate is 95 beats per minute, blood pressure is 101/65 mm Hg, and respiratory rate is 20 breaths per minute. Her weight is 22.7 kg and height is 115 cm, both greater than the 97th percentile, and her body mass index is 17.16 (75th percentile). She has left-sided inguinal swelling that measures 4 × 2 cm, extending into the left labia. The swelling is firm, tender, and nonfluctuant on palpation. It does not enhance on coughing and is non-reducible. The overlying skin is warm and erythematous, with no evidence of trauma or discharge. The rest of the physical examination findings are unremarkable.Results of laboratory evaluation are as follows: white blood cells, 16,800/μL (16.8 × 109/μL), with 67% neutrophils, 30% lymphocytes, and 3% monocytes; hemoglobin, 13.1 g/dL (131 g/L); hematocrit, 39.4% (0.39); and platelets, 298 × 103/μL (298 × 109/L). Ultrasonography reveals a confluent nodal mass in the left inguinal region suggestive of an abscess. Incision and drainage of the abscess are performed with lymph node excision, and she is discharged home with a prescription for oral clindamycin. Twelve days after discharge, a pathology report of the resected necrotic inguinal lymph nodes reveals the diagnosis.The patient was treated with ketorolac and morphine as needed for pain control. Pelvic magnetic resonance imaging (MRI) performed to further evaluate the uterine mass revealed a vaginal obstruction with hematocolpos with mild distention of the uterus (Figure 1). The cervix and ovaries were normal. Pelvic examination with the patient under general anesthesia revealed a transverse vaginal septum. She underwent surgical resection of the septum and evacuation of retained blood. Intraoperative vaginal ultrasonography confirmed complete evacuation of hematocolpos. Her pain resolved postoperatively.The differential diagnosis of abdominal pain in a girl of this age is vast but can be narrowed by classifying the pain as acute, chronic, or recurrent. The major organ systems to consider are the gastrointestinal, urologic, and gynecologic. This girl was experiencing recurrent abdominal pain, as such the differential diagnosis included constipation, peptic ulcer disease, urinary tract infection, dysmenorrhea, and ruptured ovarian cyst. Less common diagnoses would include inflammatory bowel disease, cyclic vomiting syndrome, kidney stones, heavy metal poisoning, ovarian torsion, and imperforate hymen with hematocolpos. The possibility of a functional abdominal pain disorder should be considered when an organic origin of pain is not detected on thorough evaluation. Certainly, many children with organic abdominal pain may also have a component of functional pain, which makes diagnosis and management more challenging.Embryologically, the vagina is formed from 2 evaginations that originate from the urogenital sinus and mullerian duct. A transverse vaginal septum results from failure of fusion and/or canalization of these evaginations. These septae may be located at various levels in the vagina; approximately 46% are found in the upper portion of the vagina, 35% to 40% in the middle portion, and 15% to 20% in the lower portion. Most septae are generally less than 1 cm in thickness and have fenestrations and therefore do not cause a complete obstruction.A girl born with a vaginal septum will have normal-appearing external female genitalia. Younger children may present with mucocolpos, whereas adolescents commonly present with hematocolpos. Ascending infection is also possible through a perforation or fenestration, leading to pyohematocolpos. Occasionally, a mass may be palpated on abdominal or rectal examination, which may lead to symptoms secondary to a mass effect on the urinary system, such as urinary retention or hydronephrosis.Hematocolpos is a condition where the vagina becomes distended with blood due to accumulation of menstrual products. Hematometra is a related condition that refers to a distended uterus filled with blood caused by large accumulation of menstrual products. The most common causes of hematocolpos and hematometra are imperforate hymen, vaginal agenesis (1:5000), and complete transverse vaginal septum (1:30,000–1:80,000). Vaginal agenesis is also known as mullerian aplasia or Mayer-Rokitansky-Kuster-Auser syndrome and refers to congenital absence of the vagina with variable cervical and uterine development. Symptoms secondary to hematocolpos or hematometra generally present at the time of menarche and include periodic lower abdominal pain and primary amenorrhea.Approximately 25% to 50% of females with uterine or vaginal anomalies will have an associated urologic anomaly, such as unilateral renal agenesis, horseshoe kidney, or abnormalities of the collecting system. Skeletal anomalies of the spine, ribs, and extremities are also associated with uterine or vaginal anomalies in 10% to 15% of cases.Definitive diagnosis is usually made by ultrasonography or pelvic MRI. Imaging is required to define the level and thickness of the septum. It is also important to differentiate between a high septum and a congenital absence of the cervix and to delineate any additional genitourinary abnormalities.Once the diagnosis is confirmed, the septum should be surgically excised with end-to-end anastomosis of vaginal mucosa. Endometriosis is a known complication of hematocolpos and often requires continued follow-up with a gynecologist. Although not completely understood, the endometriosis is presumed to be related to retrograde menstruation and implantation of endometrial cells.As stated earlier, uterine and vaginal anomalies have been associated with other congenital anomalies and therefore may require additional evaluation.The pathology report of the resected inguinal lymph nodes revealed Schiller-Duval body, which is pathognomonic for yolk sac tumor (Figure 2). The Schiller-Duval body consists of a central blood vessel surrounded by germ cells, which together lie in a cystic space surrounded by flattened germ cells. Further laboratory studies revealed a lactate dehydrogenase level of 410 IU/L and an AFP level of 16,766.3 ng/mL (16,766.3 μg/L). The patient underwent whole-body CT with contrast, which revealed a lobulated, rim-enhancing, precoccygeal mass suggestive of sacrococcygeal teratoma (SCT) (Figure 3). Lymphadenopathy most likely due to metastasis was found in the bilateral pelvic sidewalls, right external iliac, right paraspinal, left inguinal, and presacral regions. Soft tissue implants were noted within the bilateral gluteus maximus muscles. Mediastinal and bilateral hilar lymphadenopathy with multiple lung nodules were also detected (Figure 4). The culture from the pus drained yielded Staphylococcus aureus. Thus, our patient had acute lymphadenitis of a metastatic lymph node in the inguinal region.Acute lymphadenitis was high on the differential diagnosis. Isolated inguinal lymphadenopathy can be seen in lower-extremity suppurative infection, vector-born diseases (tularemia, plague, brucellosis, and cat-scratch disease), perineal infections, venereal disease, and malignant tumors. Among the malignant tumors, rhabdomyosarcomas and nonrhabdomyosarcomas, Hodgkin and non-Hodgkin lymphoma, and primary neuroblastoma have been reported to present with inguinal lymphadenopathy. Inguinal hernia was one of the differential diagnoses, but the mass did not enhance on coughing, had no audible bowel sounds on direct auscultation, and was firm on palpation.SCT is the most common germ cell tumor of childhood and comprises 40% of all germ cell tumors. They are seen in approximately 1 in every 27,000 live births and are more common in females in ratios of 3:1 to 4:1. Teratomas include components from all 3 embryonic layers: endoderm, mesoderm, and ectoderm. They may be classified as mature or immature on the basis of the presence of immature neuroectodermal elements within the tumor. The tumor was found to be malignant in 48% of girls and 67% of boys when they were older than 2 months at the time of the diagnosis of SCT compared with 7% in girls and 10% in boys when SCT was diagnosed in infants younger than 2 months. SCTs are more likely to recur when compared with teratomas in the ovary and at other sites.Fetal sacrococcygeal tumors may be diagnosed on prenatal ultrasonography, especially when located partly or entirely externally. Some fetuses may develop high-output cardiac failure, hydrops, and maternal mirror syndrome. Maternal mirror syndrome refers to the association of fetal and placental hydrops with preeclampsia. The edematous states of both fetus and mother mirror each other. Neonatal SCT can present as a visible lump or mass under the skin at the top of the buttocks crease. In infants and young children, a small SCT, if it is entirely inside the body, may not develop clinical manifestations for years, until it grows large enough to cause mass effects, such as pain and constipation, or until it begins to extend out of the pelvis. When not externally visible, even large teratomas may be missed because they are concealed within the bony pelvis.SCTs are classified according to their relative extent outside and inside the body by the American Academy of Pediatrics Surgical Section classification:CT of the abdomen and pelvis is essential for the staging of abdominal and pelvic tumors at the time of presentation. MRI can be substituted for CT, and if so, it should be used throughout therapy to maintain consistency in imaging studies.For benign SCTs, surgical resection is sufficient, where typically the coccyx is resected en bloc with the tumor to minimize risk of recurrence as the tumor lacks a capsule. For malignant SCTs, postsurgery platinum-based chemotherapy that consists of a combination of bleomycin, etoposide, and cisplatin is the most common first-line therapy used. Our patient underwent surgical resection of the tumor and is undergoing bleomycin, etoposide, and cisplatin chemotherapy.An ultrasonogram of the abdomen revealed a round heterogeneous structure in the left hepatic lobe. Serum uric acid, α-fetoprotein (AFP), and human chorionic gonadotropin levels were within normal limits. Abdominal computed tomography (CT) revealed multiple hepatic masses with necrotic areas.Histopathologic findings of an endoscopically ultrasonogram-guided biopsy were consistent with hepatocellular carcinoma (HCC). MRI of the abdomen revealed stage 3 disease, with extensive intra-abdominal metastasis without distant metastasis. The patient underwent an extended left hepatectomy (segments 2, 3, 4, and 8) and resection of the perihepatic and celiac lymph nodes. It was determined that the patient was not a candidate for liver transplantation. He was prescribed sorafenib, a chemotherapeutic agent. Approximately 18 months after the diagnosis was made, the patient died of complications of HCC.HCC is a primary malignant tumor of the liver, which may occur in multiple sites within the liver. It can metastasize to other abdominal structures and to the lungs.Primary liver tumors are uncommon in children and adolescents, accounting for approximately 0.5% to 2% of all neoplasms in these age groups. HCC is the second most common hepatic malignant tumor in children after hepatoblastoma. Annual incidence of HCC in children varies widely, depending on geographic location due to regional variations in exposure to hepatitis viruses. In low incidence regions, such as North and South America, Australia, and parts of Europe and the Middle East, the incidence is approximately 0.5 cases per million and is rare before the age of 15 years. However, in regions such as People’s Republic of China, Hong Kong, Sub-Saharan Africa, and Taiwan, where hepatitis B infection is prevalent, the incidence can be as high as 0.5 per 100,000 population.Most cases of HCC result from conditions that cause chronic liver disease, such as hepatitis B and C infections and cirrhosis. Less common causes associated with an increased risk of HCC are conditions causing long-term inflammation of the liver, such as autoimmune diseases of the liver, and some congenital diseases, such as hereditary tyrosinemia type 1, Wilson disease, type 1 glycogen storage disease, α1-antitrypsin deficiency, progressive familial intrahepatic cholestasis type 2, and hemochromatosis. Prolonged exposure to hepatic toxins, such as androgenic steroids in adolescent athletes and mycotoxins (aflatoxin B1 and ochratoxin A), which are contaminants of staple foods in tropical subsistence farming communities, has been linked to HCC.Patients with HCC may be asymptomatic in the early course of the disease but can present with right upper quadrant pain due to stretching of the Glisson capsule. Other symptoms may include jaundice, nausea, vomiting, diarrhea, anorexia, weight loss, and fever. Physical examination may reveal a tender, enlarged liver and icterus. In rare cases, paraneoplastic syndromes, manifested as hypoglycemia, erythrocytosis, hypercalcemia, or watery diarrhea, can occur. Complications are associated with extension of the tumor into hepatic or portal veins, resulting in arteriovenous shunting and gastrointestinal bleeding. As hepatic failure ensues, manifestations of coagulopathy, encephalopathy and ascites develop.Diagnostic evaluation involves laboratory and imaging studies. Elevated liver enzyme levels, abnormal liver function test results, and elevated serum AFP levels are common but not seen in all patients. Serum AFP levels do not correlate with the size or the stage of HCC, although an elevated AFP level can be used to gauge response to therapy. Abdominal ultrasonography can be used as an initial imaging modality. CT or MRI is used to delineate the tumor and assess for vascular invasion and extrahepatic metastasis. Final diagnosis is confirmed by image guided needle biopsy.The differential diagnosis of a child presenting with an epigastric mass and associated elevated liver enzyme levels can be limited primarily to liver conditions. Viral hepatitis is a systemic viral infection in which the predominant manifestation is that of hepatic injury. Ninety percent of cases of hepatitis are caused by hepatotropic viruses, which include hepatitis A to E. Ten percent of cases are due to other viruses, such as Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus, rubella, parvovirus, adenovirus, or enteroviruses. Tender hepatomegaly and jaundice may or may not be present. Two-thirds of children with hepatitis A present with jaundice, and there may be dark urine and pale stools. Marked elevation in aspartate aminotransferase and alanine aminotransferase levels is seen during acute infection, although these levels may be normal or mildly elevated in chronic infections. Viral serologic testing helps clinch the diagnosis.Primary liver tumors are uncommon in children. Of these, approximately two-thirds are benign, and one-third is malignant. In general, the most common clinical manifestation of pediatric liver neoplasms is an asymptomatic abdominal mass. Hemangiomas are the most frequently observed benign liver tumor in children and are usually incidental findings in asymptomatic patients.Hepatoblastoma is the most common pediatric liver malignant tumor (incidence of 0.9 per 1 million children) followed by HCC. Hepatoblastoma presents usually within the first 2 years of life, with more than 90% of children having elevated AFP levels. Occasionally, precocious puberty or virilization, secondary to excess androgen secretion, is seen. Other nonspecific features include weight loss, abdominal pain, loss of appetite, anemia, fever, vomiting, and jaundice. In contrast to HCC, hepatoblastoma arises in an otherwise healthy liver and is usually sensitive to chemotherapy. It occurs in association with Beckwith-Wiedemann syndrome and hemihypertrophy.A transitional liver cell tumor is a rare neoplasm that is found in older children. The tumor cells vary between those of classic hepatoblastoma and HCC, and much like HCC, response to chemotherapy is poor. Other primary liver malignant tumors, including liver sarcomas and choriocarcinoma, are extremely rare in children.HCC is an aggressive tumor that is usually detected at an advanced stage. The median survival after diagnosis is approximately 6 to 20 months.Treatment options for patients with HCC are dictated by the functional reserve of the liver. Only 10% to 20% of HCCs can be removed completely by surgery. The Milan criteria are applied to patients with cirrhosis and HCC when determining eligibility for hepatic transplantation. Transplant candidates should have a singular lesion less than 5 cm or up to 3 lesions smaller than 3 cm each with no extrahepatic manifestations and no vascular invasion.Other treatment modalities that have been used in adults are only relatively recently being used in children. Chemotherapy has not been used routinely for patients with advanced HCC; however, there are ongoing studies using multiple chemotherapeutic agents. Sorafenib tosilate (Nexavar), a receptor tyrosine kinase inhibitor that blocks tumor growth and has been reported by several studies to increase medial overall survival, is approved for patients with advanced and unresectable HCC.Avoidance of hepatotoxic agents and childhood vaccination against hepatitis B have been reported to reduce the future risk of HCC. In Taiwan on July 1, 1984, a mass hepatitis B vaccination program was launched, primarily aimed at immunizing newborn infants. Twenty years after the implementation of this program, there was an 85% parallel decrease of hepatitis B prevalence, as well as HCC and cirrhosis.Surveillance for HCC in selected groups of patients known to be at high risk for HCC, such as certain metabolic diseases or chronic liver diseases, may lead to prompt diagnosis and aggressive treatment.To view Suggested Reading lists for these cases, visit http://pedsinreview.aappublications.org and click on the “Index of Suspicion” link.