Fetal abdomen: Differential diagnosis of abnormal echogenicity and calcification

INTRODUCTION — Prenatal ultrasound examination may detect echogenic masses and calcifications related to fetal abdominal or retroperitoneal organs and/or the peritoneal cavity. These findings may be transient or persistent. They may have no significant consequences, or they may impact prenatal and/or postnatal management.

This topic will describe several causes of abnormal echogenicity and calcification of the fetal abdomen that may be detected during a prenatal ultrasound examination. Fetal echogenic bowel is reviewed in detail separately. (See "Fetal echogenic bowel".)

GENERAL DIAGNOSTIC APPROACH — The identification of a fetal abdominal abnormality should prompt a detailed fetal survey to look for additional abnormalities and a review of the maternal history. Fetal diagnosis can often be made after the following assessments of the abnormality:

●Location

●Echogenicity (eg, bright as bone, heterogeneous)

●Type of calcification, if present (focal or scattered)

●Arterial and venous supply, if any

●Presence of associated abnormalities

●Evolution over time

When additional information is needed because of uncertainty or because this information may affect pregnancy management, magnetic resonance imaging can be helpful.

DIFFERENTIAL DIAGNOSIS OF ABNORMAL ECHOGENICITY

Gastric pseudo-mass

●Ultrasound appearance – In the second and third trimesters, discrete echogenic areas 4 to 12 mm in diameter may be seen in the fetal stomach (image 1) [1].

●Significance – The increased echogenicity represents swallowed debris (eg, red cells, meconium, skin cells) that has aggregated to form a pseudo-mass [1,2]. Relatively poor gastric peristaltic activity early in the second trimester may account for this finding, which resolves over time and is not associated with adverse neonatal outcome.

Echogenic bowel

●Ultrasound appearance – Specific criteria exist for diagnosis of echogenic bowel: The bowel should be as bright as adjacent bone; the usual standard for comparison is the iliac wing (image 2). Echogenicity can be diffuse or focal. It is uniform over a well-defined area that does not shadow and located primarily in the lower abdomen and pelvis. When making the diagnosis, it is important that a relatively low frequency transducer (3 to 5 MHz) is used because higher frequency transducers can simulate the appearance of echogenic bowel [3].

●Significance – Echogenic bowel is the most common etiology of an echogenic mass visualized in the fetal abdomen in the second trimester, with an incidence of 0.5 to 1.0 percent in a general obstetric population [4-7]. It can be a marker for underlying pathology, including cystic fibrosis, chromosomal abnormalities, intraamniotic bleeding, congenital infection, gastrointestinal atresia, and growth restriction, as well as fetal demise. Many cases diagnosed in the second trimester resolve over time. In over 80 to 90 percent of fetuses with an isolated sonographic finding of echogenic bowel, no etiology is identified antepartum, and the neonate (including the bowel) is normal at birth. However, when present with other abnormalities, the likelihood of an underlying pathologic condition increases. Second-trimester echogenic bowel, including obstetric work-up for underlying disorders, is discussed in more detail separately. (See "Prenatal genetic evaluation of the fetus with anomalies or soft markers", section on 'Approach to the evaluation of the fetus with "soft markers" and no structural anomalies'.)

In the third trimester, echogenic bowel is a common and a normal finding since the colon contains meconium, which can be echogenic. The visualized echogenicity should follow the expected path of the colon.

Echogenic abdominal mass

●Ultrasound appearance – Enteric duplication cysts are typically anechoic, since they contain mucoid fluid, but can present as an echogenic abdominal mass. Two sonographic signs suggestive of enteric duplication are (1) peristalsis involving the cyst/mass and (2) the "double-wall" sign (an inner hyperechoic rim and an outer hypoechoic layer reflecting the mucosa-submucosa and muscularis propria, respectively [8,9]). Most gastric duplications appear as a cystic noncommunicating structure located on the greater curve of the stomach near the pylorus (image 3).

●Significance – Enteric duplication cysts are benign, rare anomalies that arise during early embryonic development. They are most frequently found in the proximal small intestine, although they can also occur in the esophagus, stomach, and colon. There are two general types: those that are adjacent to the lumen (having lost communication to the gastrointestinal wall) and those that are tubular and communicate directly with the lumen. In a systematic review, the majority of fetal gastrointestinal cysts were enteric duplication cysts (77 percent), followed by mesenteric cysts (12 percent) and omental cysts (0.9 percent) [10]. (See "Endoscopic ultrasound for the characterization of subepithelial lesions of the upper gastrointestinal tract", section on 'Duplication cysts' and "Lower gastrointestinal bleeding in children: Causes and diagnostic approach", section on 'Gastrointestinal duplication cyst'.)

In up to one-third of cases, additional fetal structural abnormalities are noted, particularly of the spine and gastrointestinal tract [11], so a thorough evaluation of the spine and gastrointestinal tract should be performed, including identification of communication with the gastrointestinal tract, dilated bowel loops, and evidence of perforation.

Monthly follow-up ultrasound examinations are performed to document any change in size or development of calcifications and to assess for bowel obstruction/perforation, which is the most common complication. Cyst resolution is also possible [10]. Most cases can be expectantly managed until term and can be delivered in a hospital without a level III nursery [12].

Echogenic liver lesions (noncalcified)

●Ultrasound appearance – Most solid liver masses are hypoechoic, but echogenic masses also occur.

●Significance – The differential diagnosis of intrahepatic echogenic masses includes benign neoplasms such as hemangioma, mesenchymal hamartoma, adenoma, and focal nodular hyperplasia and malignant neoplasms, such as hepatoblastoma and metastatic neuroblastoma.

When an intrahepatic echogenic lesion is visualized, it is important to document lesion vascularity, portal vein patency, and any signs of hydrops. In cases of discrete, small, uniform, noncalcified lesions with no associated abnormalities, sonographic follow-up is recommended to document change, if any, in the above findings. Any substantial increase in size and/or change in vascularity should prompt close follow-up.

Vascular hepatic lesions such as hemangiomas, hemangioendotheliomas, and hepatoblastomas can act as vascular reservoirs, leading to anemia, high output cardiac failure, and hydrops [13-17]. Doppler assessment of the fetal middle cerebral artery peak systolic velocity is the best tool for predicting fetal anemia in at-risk pregnancies. (See "RhD alloimmunization in pregnancy: Management", section on 'Assess for severe anemia using MCA-PSV in fetuses at risk'.)

Hemangioma

●Ultrasound appearance – Hemangiomas are well-defined echogenic liver lesions (image 4). In utero, they typically appear avascular on color Doppler sonography, and rarely contain calcifications unless large vascular spaces with arteriovenous shunting are present. (See "Hepatic hemangioma".)

●Significance – Hemangiomas up to 12 cm have been described antenatally [18]. With lesions this large, substantial morbidity can occur from congestive cardiac failure, thrombocytopenia, anemia, or intraabdominal hemorrhage due to rupture.

Maternal glucocorticoid treatment to reduce the size of the lesion in utero has been described in case reports, with varying success [17,19,20]. Both steroids and interferon alpha have been used to treat these lesions in infants [21,22]. When medical treatment fails, surgery may be required postnatally, but spontaneous regression of hemangiomas has been documented.

In a review of imaging data from over 93,000 fetuses, 6 had large hepatic hemangiomas (5 to 10 cm in size); 5 had solitary lesions (4 in right lobe and 1 in left lobe) and 1 had lesions in both lobes [23]. On postnatal contrast-enhanced computed tomography, all lesions showed the contrast filling peripherally to centrally, with enhancement strongest at the periphery. Following postnatal treatment with oral propranolol, with or without dexamethasone or interventional therapy with the medical sclerosant pingyangmycin, all lesions decreased in size, with calcification plaques appearing six months after treatment, and all had good outcomes. (See "Infantile hemangiomas: Management".)

Mesenchymal hamartoma

●Ultrasound appearance – Mesenchymal hamartomas are usually multicystic, but solid and mixed echogenic tumors have been described. They arise from the inferior pole of the liver; large draining veins and a dilated proximal abdominal aorta may be observed [24].

●Significance – Mesenchymal hamartomas are composed of connective tissue, hepatocytes, and biliary elements arranged in a disorderly fashion. They do not communicate with the biliary tree and do not contain bile.

They usually have a benign course unless they are very large and compressing vital organs [25]. For example, ascites can occur if the upper intestinal tract is compressed and obstructed by the mass, and large hamartomas may be associated with hydrops due to compression of the inferior vena cava. Rarely, they have been associated with placental mesenchymal dysplasia (placentomegaly with grapelike vesicles); the combination has a poor prognosis [26].

Maternal serum alpha-fetoprotein may be elevated [27].

Gallbladder echogenicity

●Ultrasound appearance – Echogenic material in the expected location of the fluid-filled gallbladder in the fetal right upper quadrant suggests gallstones or gallbladder sludge (image 5) [28-32]. Echogenic foci that cast an acoustic shadow are more likely to be stones than sludge.

●Significance – Fetal gallstones are usually an incidental finding at third-trimester ultrasound performed for another indication.

In one series of 26 fetuses with echogenic material in the gallbladder, gestational age at the time of diagnosis ranged from 28 to 42 weeks, with a mean of 32 weeks [30]. The echogenic foci were associated with distal shadowing in eight fetuses (30 percent), comet-tail artifact in nine (35 percent), and no distal artifact in nine (35 percent). Postnatal follow-up was available in 17 cases. No hemolytic anemias, other predisposing risk factors, or clinical sequelae associated with biliary tract disease were identified in any of the infants. In nine infants, the echogenic foci resolved. In three cases, the foci persisted, but none of the children became symptomatic at up to 4.5 years follow-up.

In a review of approximately 200,000 obstetric sonograms, 34 fetuses had cholelithiasis (median gestational age 35 weeks [range 22 to 38 weeks]) [33]. Eight fetuses underwent postnatal imaging, and four had persistent cholelithiasis. There was one case of in utero demise. Two patients had structural anomalies (renal and cardiac) by sonogram. A subset of 17 patients was followed long term (range 3 to 20 years), and none developed clinical sequelae from cholelithiasis. The authors concluded that no child developed postnatal clinical sequelae related to cholelithiasis identified in utero and that fetal cholelithiasis can be managed expectantly without follow-up imaging in asymptomatic patients.

Suprarenal echogenicity — It is important to determine if echogenicity in the renal area is adrenal or renal or represents an extralobar pulmonary sequestration. The most common causes of suprarenal echogenicity are adrenal hemorrhage, neuroblastoma, extralobar pulmonary sequestration, and exophytic renal tumor. Less common lesions include adrenal adenoma, adrenal carcinoma, adrenal hyperplasia, duplication of the renal system, Wilms tumor, congenital mesoblastic nephroma (CMN), lymphatic malformations, and mesenteric and enteric duplication cysts [34,35].

Adrenal hemorrhage

●Ultrasound appearance – An echogenic mass is seen in the adrenal region. It is typically uniform with a central cystic portion, right-sided or bilateral.

●Significance – An echogenic solid-appearing suprarenal mass may represent a recent adrenal hemorrhage. The key to the diagnosis is lack of internal blood flow and change in appearance over serial ultrasound examinations, which will show development of a hypoechoic central region followed by a more cystic appearance and decrease in size [36,37]. Calcifications may develop in degenerated or necrotic tissue.

The right adrenal gland is involved in 75 percent of cases, possibly due to the relatively shorter adrenal vein [38]. Hypoxia and increased intravascular pressure have been postulated as causes of adrenal hemorrhage in utero, but the etiology is not well understood [38].

A systematic review found that most fetal adrenal hemorrhages persist prenatally and the majority regress or resolve postnatally [39]. Postnatal follow-up in fetuses with presumed adrenal hemorrhage is important since differentiation from neuroblastoma prenatally may be difficult in the latter stages [38]. In the systematic review, only one case out of the 16 suspected neuroblastomas was confirmed to have microscopic islets of neuroblastoma on pathology [39]. (See 'Neuroblastoma' below.)

Neuroblastoma

●Ultrasound appearance – Neuroblastoma is usually detected in the mid to late third trimester. The mass can be cystic, solid, or of mixed echogenicity (image 6) [40,41] and may be calcified along its rim. It is frequently on the right side and displaces the adjacent kidney inferiorly and laterally [42]. Hydrops and metastases to liver and placenta have been reported [43]. Presence of liver metastasis supports the diagnosis.

●Significance – Neuroblastoma is the most common neoplasm of the fetal adrenal gland. Spontaneous regression occurs in up to 40 percent of cases, but peripheral calcification may persist. Fetal magnetic resonance imaging is useful for detailed anatomic characterization of the tumor and extent of disease [44]. Differential diagnosis includes adrenal hemorrhage, extralobar pulmonary sequestration (discussed below), duplex collecting system with dysplastic changes, mesoblastic nephroma, retroperitoneal teratoma, liver tumor, and splenic cyst [45].

Possible maternal symptoms include hypertension and tachycardia, which result from elevated catecholamines and correlate with a more advanced stage of disease [46]. (See "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma", section on 'Prenatal diagnosis' and "Epidemiology, pathogenesis, and pathology of neuroblastoma" and "Treatment and prognosis of neuroblastoma".)

Subdiaphragmatic extralobar pulmonary sequestration

●Ultrasound appearance – Subdiaphragmatic extralobar pulmonary sequestration is typically uniform with left-sided echogenicity. Approximately 10 to 15 percent of extralobar pulmonary sequestrations occur below the diaphragm, with a 4:1 left-sided predominance (image 7). Features that help distinguish extralobar pulmonary sequestration from neuroblastoma are that sequestration is left-sided while neuroblastoma is more likely to be right-sided, sequestration is likely to be detected in the second trimester while neuroblastoma is usually identified in the third trimester, and sequestration is more echogenic than neuroblastoma [42]. Visualization of a feeding vessel arising from the thoracic aorta and extending below the diaphragm to the mass strongly favors the diagnosis of sequestration.

●Significance – An extralobar pulmonary sequestration is a nonfunctioning mass of lung tissue located outside the normal lung and with its own visceral pleura and anomalous blood supply. Most, but not all, are located above the diaphragm. Extralobar pulmonary sequestration accounts for approximately 25 percent of cases of bronchopulmonary sequestration and is likely to be associated with other congenital anomalies. When extralobar, pulmonary sequestration may be within the leaves of the diaphragm (in approximately 1 percent of cases) or in a suprarenal subdiaphragmatic location [47]. Many cases regress during gestation or postnatally, but some progress, and hydrops may develop. The affected newborn is usually asymptomatic but sometimes presents with respiratory distress. (See "Bronchopulmonary sequestration: Prenatal diagnosis and management" and "Bronchopulmonary sequestration".)

Renal echogenicity

Dysplastic kidneys

●Ultrasound appearance – Increased echogenicity of one or both renal fossae suggests the possibility of dysplastic kidney(s). Increased echogenicity is relative to the surrounding structures and presumably due to abundant fibrous tissue or numerous tissue interfaces from tiny cysts. Amniotic fluid volume may be normal, decreased, or absent, depending on the extent of renal involvement.

●Significance – Cystic kidney disease is one of the major causes of end stage renal disease in children and adults.

A detailed description of the prenatal diagnosis, differential diagnosis, and management of cystic kidney disease can be found separately. (See "Prenatal sonographic diagnosis of cystic kidney disease".)

Congenital mesoblastic nephroma

●Ultrasound appearance – CMN is the most common primary renal neoplasm in utero. The most common presentation of CMN is a unilateral solid mass with homogeneous, slightly hyperechoic echogenicity (compared with normal renal parenchyma), located near the renal hilum, and involving the renal sinus [48]. The tumor lacks a well-defined capsule and moves with the renal parenchyma when fetal breathing movements are present. Occasionally, however, CMN appears as a hypoechogenic tumor with an echogenic rim ("Ring sign") [49]. It is an angiomatous tumor and arteriovenous shunts may be present. Vascularity is assessed with color and spectral Doppler [50].

●Significance – A highly vascular solid mass identified later in pregnancy that is not clearly separate from the kidney is likely to be a mesoblastic nephroma. The differential diagnosis of a solid renal mass includes compensatory hypertrophy with absence of the contralateral kidney and crossed-fused ectopia. An adrenal mass (eg, neuroblastoma (see 'Neuroblastoma' above) or adrenal hemorrhage (see 'Adrenal hemorrhage' above)) may give the impression of an enlarged kidney, as can tumors arising from nearby organs [51]. Magnetic resonance imaging can be helpful for assessing the origin of the abdominal mass if ultrasound is not conclusive [52,53].

While CMN is more common than Wilms tumor in the fetus [54,55], it is not possible to differentiate these tumors based on prenatal ultrasound findings. Both tumors may appear as unilateral, single, solid masses arising from the kidney. Bilateral tumors are usually Wilms tumors; in a study evaluating the outcome of renal tumors in the first seven months of life, 37 out of 39 bilateral tumors were Wilms tumors [56]. By comparison, CMN can have hypoechoic cavitary portions from necrosis or hemorrhage and shows infiltration into the renal tissue, whereas Wilms tumor has a pseudocapsule. (See "Presentation, diagnosis, and staging of Wilms tumor".)

CMN is commonly associated with hydrops and polyhydramnios due to arteriovenous shunting. Additional congenital anomalies are rare and have consisted primarily of genitourinary abnormalities, but a few cases of associated gastrointestinal malformations, polydactyly, hydrocephalus, and Beckwith-Wiedemann syndrome have also been reported [57].

DIFFERENTIAL DIAGNOSIS OF CALCIFICATION

Solitary or multifocal calcification in bowel

Enteroliths

●Ultrasound appearance – Enteroliths appear as shadowing foci within a dilated loop of bowel.

●Significance – Enteroliths are intestinal calculi that can be caused by inspissated meconium related to bowel obstruction (associated findings might include echogenic bowel, dilated loops of bowel, and polyhydramnios [58]) or in association with a cloacal malformation where there is a mixing of urine and meconium.

Cloacal malformation

●Ultrasound appearance – A loop of bowel containing calcifications and located in the midabdomen/pelvis is a marker for cloacal malformation (image 8).

●Significance – Cloacal malformation occurs exclusively in phenotypic females, with an incidence of 1 in 50,000 births. Failure of the urorectal septum to reach the perineum results in formation of a single perineal opening that serves as the outlet for urine, genital secretions, and meconium. The mixture of meconium and urine results in enteroliths. Urinary tract abnormalities (reflux, ureteral ectopia, bladder duplication, urinary tract obstruction), gastrointestinal obstruction, and genital abnormalities (duplication or atresia of uterus and vagina, ambiguous genitalia) are frequently present, as well as abnormalities of the bony pelvis and vertebrae. Oligohydramnios is common [59,60]. (See "Body stalk anomaly and cloacal exstrophy: Prenatal diagnosis and management".)

Peritoneal calcification — When calcifications are visualized in the fetal peritoneum, the initial consideration is whether they are scattered or outlining the liver (suggestive of meconium peritonitis) or associated with a mass (suggestive of meconium pseudocyst).

Meconium peritonitis

●Ultrasound appearance – The diagnosis of meconium peritonitis is based on visualization of scattered calcifications throughout the peritoneum, often outlining bowel and/or liver (image 9). At times, however, only a focal calcification with shadowing is seen (image 10). Calcifications can be visualized after 18 weeks of gestation [61].

●Significance – Meconium peritonitis is a sequelae of in utero small bowel perforation with extrusion of meconium intraperitoneally, resulting in a sterile chemical peritonitis. Serial sonographic evaluation of the fetus with meconium peritonitis is indicated and includes documentation of the site, size, and location of calcifications, and assessment for additional abnormalities, such as dilated or echogenic bowel loops, meconium pseudocyst, ascites, and signs of hydrops.

Delivery at a center with a level III nursery and pediatric surgical facilities is suggested due to the potential for postnatally diagnosed fetal anomalies. Meconium peritonitis has been associated with cystic fibrosis with meconium ileus and gastrointestinal abnormalities, including ileal or jejunal atresia, volvulus, microcolon, intussusception, Meckel's diverticulum, fetal appendicitis, and imperforate anus. Rare cases have been associated with severe maternal disease [62-64]. Magnetic resonance can be particularly helpful in cases where the cause of the meconium peritonitis is not found by ultrasound. For example, microcolon can be easily diagnosed by magnetic resonance; the level of obstruction is also easily identifiable [65]. (See "Cystic fibrosis: Overview of gastrointestinal disease", section on 'Meconium ileus'.)

Although a 2013 retrospective review found no significant differences in outcome between inborn and outborn newborns ultimately diagnosed with meconium peritonitis or between prenatally and postnatally diagnosed cases, the study was limited because of small numbers, and the outcomes of outborn fetuses and those not sent to the center for treatment could not be assessed [66].

Meconium pseudocyst

●Ultrasound appearance – A meconium pseudocyst is a well-defined hypoechoic heterogeneous mass surrounded by an echogenic calcified wall (image 11). Associated findings may include ascites, polyhydramnios, and dilated bowel [67,68].

●Significance – Meconium pseudocysts occur when meconium that has extruded from a bowel perforation becomes walled off by adhesions between bowel, omentum, and peritoneum. Management is the same as with meconium peritonitis.

Hepatic calcification — Calcifications in the fetal liver are a relatively common finding, identified in 1 in 1750 second-trimester ultrasound examinations [69]. The site, size, and distribution of the lesions are major factors in determining outcome and management. The presence of an associated liver, abdominal, or retroperitoneal mass, as well as the association with ascites, impacts diagnosis and prognosis.

Subcapsular — Punctate echogenic lesions on the surface of the liver usually represent peritoneal calcifications; meconium peritonitis is the most common source (see 'Meconium peritonitis' above). Isolated subcapsular calcifications can be due to emboli from the portal or hepatic veins [70].

Intrahepatic

●Ultrasound appearance – Single or multiple calcifications may be observed in the liver parenchyma (image 12). In one series of 14 fetuses with hepatic calcifications, 12 fetuses had one or two calcified foci, one fetus had four scattered foci, and one had diffuse calcification of the liver as well as peritoneal and intestinal calcifications [69].

●Significance – When intrahepatic calcifications are visualized, it is important to evaluate for:

•An associated hepatic mass.

•Normal hepatic blood flow (by Doppler). Thrombosis or thromboembolism of hepatic or portal vein can result in abnormal blood flow with infarction or ischemia and subsequent fibrosis and calcification [71].

•Signs of fetal infection (eg, ventriculomegaly, intracranial calcifications, ascites [72]). Multiple calcifications usually present.

•Fetal structural or growth abnormalities.

In the majority of cases in which isolated hepatic calcific deposits are detected, no underlying abnormality is found, and the finding is of no clinical consequence [70,73]. Follow-up sonography typically shows stability or regression of the liver calcification, and no further work-up is required. In small case series, however, intrahepatic calcifications have also been associated with fetal aneuploidy and/or serious anatomic malformations in other organ systems [69,74]. The work-up of one fetus with multiple liver calcifications revealed maternal parvovirus B19 infection [74].

Calcified liver masses are rare and sometimes malignant. The two most common tumors are hepatoblastoma, which appears as a heterogeneous mass with coarse or punctate calcifications [75], and metastatic neuroblastoma, which most commonly originates in the adrenal gland. (See 'Neuroblastoma' above.)

Hepatoblastoma has been associated with Beckwith-Wiedemann syndrome, which may be suspected prenatally because of macrosomia and polyhydramnios. (See "Beckwith-Wiedemann syndrome".)

SUMMARY AND RECOMMENDATIONS

●General diagnostic approach – (See 'General diagnostic approach' above.)

•The identification of echogenic or calcified lesions in the fetal abdomen should prompt a detailed survey for additional findings and review of the maternal history. In utero diagnosis can often be made with careful evaluation of the lesion location, echotexture, associated calcifications, additional findings, and evolution over time.

•Depending on the specific diagnosis, fetal abdominal pathology may have a benign prognosis or may result in complications such as hydrops fetalis and bowel obstruction with or without in utero perforation (refer to topic text).

•Due to varied causes of echogenic or calcified lesions in the abdomen, follow-up ultrasound is almost always required. In rare cases, fetal magnetic resonance may be helpful to confirm a rare or difficult diagnosis.