Constipation and Asymmetric Rectal Tone in a 10-month-old Girl

A 10-month-old girl presents to the primary care office for follow-up of worsening constipation.Over approximately 3 weeks, her mother reports a transition from daily soft stools to hard and round stools every other day. She had been seen for this 2 days previously in the pediatrician’s office and the night before in urgent care. An abdominal radiograph in urgent care had demonstrated a normal gas pattern and sigmoidal colonic stool burden. Rectal stimulation completed once in urgent care and one home glycerin suppository were both tried with no resultant stool by the time she presented to the pediatrician’s office. Caregivers have also attempted frequent abdominal massages, prune juice, and dark corn syrup over the previous 3 weeks.In the pediatrician’s office now, the mother reports that the patient has been eating less than usual, is intermittently fussier, and is having night awakenings with crying. She is voiding normally and acting at baseline between episodes of fussiness. She drinks standard antireflux formula per parental choice, which they are mixing appropriately, and eats other age-appropriate infant foods.Past medical history is significant for a full-term healthy birth with normal growth and development. At 6 months, there was parental concern that she preferred her right leg for weight bearing when held in the standing position by caregivers, with an “out-turned” left leg. Examination at that time was unremarkable, with normal Barlow and Ortolani maneuvers at that and all prior visits. A hip/pelvis radiograph was without sign of developmental hip dysplasia nor other abnormality. Approximately 2 weeks before this presentation for constipation, the parents brought up motor concerns while in a physician’s office for an otitis media follow-up. At that time, the parents noted the patient was not yet pulling to a stand and did not like to crawl or scoot, although she was observed to do so in the office. She again had a normal examination and parents were reassured regarding a mild gross motor milestone delay, with plans to monitor.Returning to her current presentation for constipation, on examination her temperature is 99.7°F, and she is 9 kg with normal weight gain along the 50th percentile curve. Her abdomen, palpated between crying episodes, is soft, and without organomegaly or palpable masses. The external rectal examination is normal and there is no stool in the rectal vault. There is increased tone palpated on the pelvic floor during digital rectal examination at approximately 7:00 to 8:00 (if 12:00 is ventral and 6:00 dorsal) and in-office osteopathic manipulative treatment is attempted to relax this, which the patient tolerates well. She is discharged with a plan for once daily suppositories and a laxative. Follow-up is scheduled for 2 days later.At the appointment 2 days later, the patient is beginning to pass small amounts of stool. Her general examination is unchanged, and she is again irritable. No stool is palpated during the rectal examination. She is admitted for bowel cleanout with abdominal radiograph to be performed before the cleanout. To the pediatrician’s and mother’s surprise, “no significant rectosigmoidal stool” is visualized on the film.Concern over previously reported abnormal lower extremity use, slightly delayed gross motor milestones, and historical constipation without radiologic evidence lead to further imaging and the diagnosis.An MRI of the lumbar spine and pelvis demonstrates a large heterogeneous mass arising from “either the pre-sacral space or less likely the anterior sacrum” measuring greater than 5 cm in diameter but also extending laterally through the left obturator foramen and cephalad to L4-S1, with signs of nodal and hepatic metastases. The rectum is displaced anteriorly. The urinary bladder is also displaced anteriorly and superiorly and is distended with moderate bilateral hydroureteronephrosis.The patient is admitted to the local pediatric oncology unit. α Fetoprotein (AFP) is elevated to 118,322 ng/mL, and β-human chorionic gonadotropin (β-HCG) is normal. She undergoes ultrasound-guided percutaneous biopsy of the pelvic mass, resulting in the histologic diagnosis of a yolk sac tumor.Yolk sac tumors are a histologic type of malignant germ cell tumor. Germ cell tumors are relatively rare, accounting for 3% to 5% of all childhood malignancy. (1) They arise from defects in the primordial germ cells, which explains the many different histological features they may demonstrate. There is a bimodal age of distribution amongst children with germ cell tumors, with one peak before age 3 years and another occurring during adolescence into young adulthood. (2) In infants and children, the most common type of extragonadal germ cell tumor is the sacrococcygeal teratoma. Often, patients with these tumors may be treated for bowel obstruction or constipation, and rectal examination may identify a mass or mass effect, as in this case. (3) Rarely a presacral mass is associated with anorectal malformation and sacral vertebral bony defect, called Currarino syndrome. (4)Of sacrococcygeal teratomas, up to 35% have malignant components. The yolk sac component is the most common of these malignant elements and produces AFP but not β-HCG. Notably, AFP is used as a tumor marker in yolk cell tumors but is also elevated at birth, falling during infancy. Other types of germ cell tumor include seminomas, arising in the testes, and dysgerminomas, arising in the ovaries. These tumors are negative for AFP, occasionally positive for β-HCG, and typically arise in adolescents and young adults. Choriocarcinoma (AFP negative and β-HCG strongly positive) arises from the chorion placenta, most commonly in pregnant teenagers. Embryonal carcinoma (AFP and β-HCG both occasionally positive) occurs in the ovaries and testes and is typically associated with other germ cell tumor types. (2)Malignant germ cell tumor should be considered for any midline tumor, with extracranial presentation being most common in the gonads, sacrococcyx, retroperitoneum, or mediastinum. (2) Sacrococcygeal tumors usually present within the first 3 years of age but may present around the time of birth or even be noted antenatally on ultrasound. Female patients are more likely to have these tumors by a ratio of 3 or 4 to 1. (5) Sacrococcygeal tumors typically present with pain on sitting, bowel/bladder dysfunction, or lower extremity dysfunction. Approximately 20% of patients may have distant metastases, which often involves lungs but also liver, brain, and bone. (2)Typically, patients with yolk cell tumors undergo surgical resection before chemotherapy, although neoadjuvant chemotherapy may be used before resection in those with locally advanced and/or metastatic disease. Chemotherapy regimens are derived from regimens used by Einhorn and Donohue in the 1970s for the treatment of men with disseminated testicular germ cell tumors. As such, platinum-based chemotherapy is critical for the treatment of pediatric germ cell tumors, and cisplatin or carboplatin are typically combined with bleomycin and etoposide. Pediatric intergroup data demonstrates an 89% overall survival amongst children younger than 12 years with malignant extragonadal germ cell tumors on platinum-based chemotherapy, although that number falls to 54% for those 12 years old or older. (1) The UK Children’s Cancer Study Group demonstrates an 87.8% 5-year event-free survival but notes that site, stage, and AFP level correlate to prognostic significance in patients between 0 and 16 years old with sacrococcygeal germ cell tumors treated with neoadjuvant chemotherapy. (6)Upon admission to the oncology unit, CT scan is performed and the patient is found to have bilateral lung metastases with right upper lobe pulmonary embolism. Tumor biopsy is consistent with sacrococcygeal yolk sac tumor. She is started on Children’s Oncology Group (COG) protocol AGCT0132, off study, and receives cisplatin, etoposide, and bleomycin for Induction Cycle 1. Per protocol, she is intermediate risk and surgical resection is indicated only if, after multiple cycles, she continues to have residual tumor with elevation of tumor markers. Given her pulmonary embolism, she is started on enoxaparin and continues this for 1 week before stopping it in the setting of decreasing platelet counts resulting from her chemotherapy.After 4 cycles of cisplatin, etoposide, and bleomycin, CT scan at approximately 3 months postdiagnosis demonstrates significant reduction of her primary pelvic/sacral tumor and decreased size and number of lung and liver metastases. AFP has decreased but remains elevated. She undergoes primary surgical tumor resection with plans for an additional 2 cycles of postoperative chemotherapy.During additional chemotherapy, her AFP begins rising, and she has CT scan imaging concerning for progressive metastasis. Previous research indicates that some patients with refractory germ cell tumors and poor outcomes with conventionally dosed chemotherapy can benefit from high-dose chemotherapy that necessitates autologous stem-cell rescue. (7) Her protocol is transitioned accordingly. Her first of 3 planned courses of this therapy is complicated by intermittent neutropenic fevers with multiple identified respiratory viruses. Later, CT scan identifies concern for new fungal nodules, and she is treated with voriconazole. Most recently, local tumor recurrence in the pelvis is surgically removed, but follow-up CT scan shows new rectal and liver metastases. The family obtains a second opinion with recommendation of transition to comfort care, but wishes to move forward with another new chemotherapy regimen. Ultimately, the patient transitions to hospice care and dies at age 22 months.