Preterm Infant of Diabetic Mother with a Retrorectal Mass: A Troubling Tail Tale.

A 934-g preterm female infant is born via cesarean delivery at 27 6/7 weeks’ gestation because of preeclampsia superimposed on chronic hypertension and premature rupture of membranes to a 23-year-old gravida 3, para 0-1-1-1 woman. The maternal medical history is significant for poorly controlled diabetes mellitus type 1, chronic hypertension, bipolar disorder, and atypical seizures. She is followed by maternal-fetal medicine specialists and has undergone multiple prenatal ultrasonographic fetal evaluations that indicate intrauterine growth restriction and a distended stomach, but no obvious malformation had been identified. At delivery, the infant requires minimal resuscitative efforts, is placed on noninvasive respiratory support with nasal continuous positive airway pressure, and transferred to the NICU. Physical examination reveals a right-sided partial cleft lip without cleft palate and bilateral rocker-bottom feet. A discrete 2 × 2 cm fluctuant bulge covered by intact skin devoid of sinus, hyperpigmentation, or hair tuft to suggest stigmata of spinal dysraphism is palpable in the sacral region. The initial radiograph shows absent osseous sacral elements in addition to a distended stomach and proximal duodenum. A double-bubble sign prompts the suspicion for duodenal obstruction (Fig 1). Abdominal radiography performed after air insufflation once again shows gastric and proximal duodenal distention but no gas in the distal bowel, consistent with duodenal atresia or critical stenosis.Further imaging confirms absent cardiovascular malformations or other skeletal abnormalities. Exploratory laparotomy, performed on the first postnatal day to relieve the duodenal obstruction, reveals an annular pancreas causing duodenal stenosis and intestinal malrotation without the evidence of volvulus that requires primary duodenoduodenostomy and Ladd procedure.The lumbosacral ultrasonographic evaluation demonstrates a blunted end of the distal spinal cord, compatible with caudal dysgenesis, and a nondescript sacral region mass. Magnetic resonance imaging (MRI) is recommended for further evaluation. MRI of the lumbosacral spine with intravenous gadolinium contrast reveals a hypoplastic and dysmorphic S1 vertebral body with agenesis of the remainder of the sacrum. Abrupt truncation of the spinal cord at the thoracolumbar junction is again consistent with caudal regression syndrome. A lobulated 1.9 × 1.6 × 1.6–cm midline posterior pelvic floor cystic mass in the expected region of the sacrum exhibits a thin peripheral enhancing rim and internal enhancing components that are hypointense on T1-weighted and hyperintense on T2-weighted images. The septated cystic mass abuts the rectum (Fig 2).With concern for sacrococcygeal teratoma versus tailgut cyst, pediatric surgery is consulted. En bloc resection of the retrorectal mass is achieved using a posterior sagittal approach at the age of 15 weeks. An excised 2.5 × 1.4 × 1.0–cm cystic soft tissue mass shows a multiloculated gross appearance. The largest cystic space on the cut surface measures 0.9 cm and is distended with white pasty material. Histopathologically, the cystic spaces are lined by squamous, transitional, and columnar epithelia interspersed with goblet cells. The intercystic space is composed of fibrocollagenous and some adipose tissue with discontinuous pericystic mural bundles of smooth muscle (Fig 3). No heterologous elements suggestive of sacrococcygeal teratoma are detected. Pathology findings confirm the presumptive MRI diagnosis of tailgut cyst. After appropriate weight gain for 2 months, the patient is deemed safe to be discharged and followed by pediatrics and pediatric surgery on an outpatient basis. Karyotype shows 46,XX normal female constitution. Chromosomal microarray analysis reveals interstitial gain of chromosome 2 within 2p22.3{arr[GRCh37] 2p22.3(32160722_32330144)x3}, a variant of unknown clinical significance. None of the 3 genes involved are known to be associated with the phenotype of our patient.Preterm infant of a diabetic mother (IDM) with tailgut cyst and caudal regression syndrome, along with annular pancreas and small intestinal malrotation.In the setting of an IDM with cystic presacral lesions, exclusion of spinal dysraphism is imperative. Cystic sacrococcygeal teratomas, retrorectal epidermoid cysts, dermoid cysts, and anal gland cyst are other considerations in the differential diagnosis. Hence, a presacral mass can pose both a diagnostic and evaluation conundrum, especially in IDM.Pregestational breakdown in glucose homeostasis is among the most potent human teratogens. An undue uterine metabolic milieu alters the embryonic and fetoplacental development and affects neonatal morbidity, congenital anomalies, and mortality. (1)(2) We describe herein an extremely low gestational age newborn of a mother with pregestational diabetes with the paradigmatic anomalies seen in an IDM, along with a subcutaneous mass in the sacral region and upper gastrointestinal (GI) obstruction. Imaging disclosed a nonenhancing lobulated cystic mass in the sacral region that abutted the rectum and had no meningeal communication, consistent with a tailgut cyst. The resected retrorectal mass proved to be a tailgut cyst on histopathologic examination. (3) Furthermore, the preterm infant was found to have small intestinal malrotation and duodenal obstruction due to an annular pancreas during exploratory laparotomy. With refinements in imaging modalities, tailgut cysts are increasingly being identified, predominantly in middle-aged women, but are seldom reported in neonates, and unreported in the setting of IDM. The GI anomalies in our patient have rarely been reported in IDM. (4)(5)In utero exposure to a hyperglycemic milieu during blastogenic, embryonic, and fetoplacental development in the setting of pregestational/inadequately controlled diabetes is a well-known cause of congenital malformations, neonatal morbidity, and mortality. (1)(2) An unfavorable intrauterine environment during the first 8 weeks of gestation, a critical period for organogenesis, signals developmental malprogramming. Although the precise mechanisms for diabetes-induced teratogenicity are uncertain, the variable phenotypic expression of diabetic embryopathy suggests that teratogenicity is multifactorial. (6) One of the proposed mechanisms is the oxidative stress-induced homeostatic imbalance in the expression of apoptotic and antiapoptotic genes. (6) Caudal dysgenesis syndrome is a salient developmental abnormality with the highest relative frequency among infants with diabetic embryopathy, (1) a defect in the current case. Although our patient manifested some of the well-known abnormalities of IDM, the tailgut cyst and GI tract anomalies, the often-associated annular pancreas and small intestinal malrotation, are worth special mention.Tailgut cysts, otherwise known as retrorectal cystic hamartomas, are a rare type of retrorectal/presacral or perineal multicystic lesion that arises from the embryologic remnant of the postanal hindgut. (3) Similar to all other vertebrates, the tail forms during the embryonic phase of human development, reaching a maximum dimension at 35 days’ gestation. The postanal embryonic hindgut extends into the developing tail, a temporary embryonic structure called tailgut. However, by 8 weeks’ gestation, the human tail undergoes programmed apoptotic regression, ensuring its evanescence. If tailgut epithelia persist due to failed regression, the accrual of their secretions and exfoliation over time result in a growing tailgut cyst with consequent clinical manifestation. There is a strong predilection for female patients, with a ratio of 5:1. Tailgut cyst may become overt at any age, but usually between 30 and 60 years, and only occasionally diagnosed in the prenatal and immediate neonatal periods. (7)(8)(9)Tailgut cysts are either detected as an incidental finding during radiologic evaluation for unrelated indications or due to compressive effect by impinging upon adjacent anatomic structures. (10) Analogous to reported cases of neonatal diagnosed tailgut cyst, a directly observed mass in the sacral region preceded the diagnostic imaging. We speculate that accelerated secretory/desquamative activity of the lining epithelia led to earlier detectability of a sacral mass. Moreover, an absent sacrum, as part of caudal dysgenesis syndrome, unshielded and made the retrorectal mass singularly conspicuous.As in the current case, MRI is the best imaging modality to evaluate the presence of tailgut cysts due to its superior ability to assess soft tissues in multiple planes. (10) On MRI, an uncomplicated tailgut cyst will appear hypointense on T1-weighted and hyperintense on T2-weighted images (Fig 2). A defining clue of tailgut cyst is its multilocular appearance with internal septa. Histopathologic examination of the excised specimen provides a definitive diagnosis. (3) Tailgut cysts are typically multiloculated, the variably sized spaces containing mucoid material and/or squamous debris. The distinctive histologic findings of the tailgut cyst include the tailgut-derived epithelia, including squamous, columnar, and transitional, ciliated columnar, and goblet cells; absent ganglion cells; or heterotopic ectodermal and mesodermal derivatives. (3)Presumably, an unfavorable in utero environment that interfered during the crucial period of robust apoptotic tail regression may have led to residual vestiges of tailgut epithelium. Concurrent with the tailgut cyst, our patient had other classic manifestations of IDM. Of the altered developmental programming seen in IDM, gene expression abnormality is a salient one. (1)(11) Sonic hedgehog (SHH) signaling pathway regulates several essential aspects of embryonic patterning and development. (11) Complex molecular and cytologic mechanisms are required for the primitive gut tube to differentiate and transform into a highly complex absorptive, secretory, and excretory 3-dimensional organ. Causation of structural malformations typically includes genetic and environmental factors. SHH mis-signaling plays a role in pancreatic abnormalities (12); intestinal looping; hindgut, right, and left-right axis determination; and sacral agenesis. (13) Conceivably, a rarified in utero environment altered SHH signaling with manifest phenotypic abnormalities in our patient, including tailgut cyst formation.Known complications of tailgut cyst include infection, fistula formation, and malignant transformation. The treatment of choice for neonatal tailgut cysts is en bloc surgical excision, even in asymptomatic patients. Of the various surgical routes for retrorectal/presacral mass resection, the choice needs to be adjusted based on the size and location of the mass as well as the clinical setting. As in our case, a posterior approach is recommended for small uncomplicated cysts to prevent a recurrence. Hitherto, we are aware of a single reported case of a 12-year-old girl with sacral agenesis who presented with a voluminous tailgut cyst. (14)We document a preterm newborn female IDM with a palpable multiloculated tailgut cyst in the setting of caudal dysgenesis, annular pancreas, and intestinal malrotation. The differential diagnoses of a retrorectal/presacral mass are diverse, chiefly in IDM. The diagnosis of a neonatal tailgut cyst, which is distinctly infrequent, relies on a combination of clinical examination, radiographic imaging, and high index of suspicion. A categorical diagnosis is established only after histopathologic examination of the completely resected specimen. Early identification of a tailgut cyst and excision are warranted to prevent potential infectious and neoplastic complications.