Hepatic mesenchymal hamartoma (HMH) are rare liver tumors, that appear most frequently in young children under age two (85%) and rarely in newborns (15%). Such tumors are non-malignant growths on the liver that develop in the mesenchymal tissue; etiological analysis ascribes HMH to abnormal mesodermal development in the portal tract (1), where mesenchymal tissue overgrowth takes place that, in turn, leads to the formation of the hamartoma. The exact cause of HMH is unknown. Histological analysis is essential in HMH diagnosis, as well as in being able to distinguish it from other liver tumors.

Neonates report excellent HMH prognosis, with very little recurrence after surgical resection. However, long-term follow-up is necessary to monitor potential complications. Given the broad, heterogeneous, and complex nature of both clinical and histopathological differential diagnoses, close attention to diagnostic features—especially microscopic findings—is essential.

A 16-day-old female newborn, whose prenatal ultrasounds revealed the presence of an abdominal mass. Subsequent images confirmed the cystic mass with an apparently mesenteric location; suggestive of mesenteric cystic lymphangioma versus peritoneal inclusion cyst; MRI revealed a cystic lesion that apparently involved the retroperitoneum, along with suspected intraperitoneal extension occupying the pelvis and part of the abdominal cavity, displacing the intestinal loops; another suggested lymphatic vascular malformation, less likely a cystic teratoma. Surgical laparotomy isolated a large smooth-surfaced intraperitoneal cyst with serous content that covered 60% of abdominal cavity, originating at free edge of hepatic segment V. Additional tests revealed elevated levels of alpha-fetoprotein.

Pathology lab described the 138 g, 12 cm × 7.5 cm × 5.5 cm surgical specimen as an ovoid cystic mass, of rubbery, soft tissue, of overall light-yellow color. Specimen discharged a yellow serous fluid; multiloculated internal cavity possessed a smooth internal surface. Histological examination pinpointed a mainly cystic disordered arrangement of mesenchyme, bile ducts and hepatic parenchyma; loose connective tissue surrounded cysts; towards the periphery, a few hepatocyte cords and some bile ducts were present. Moderate active chronic inflammation and small amounts of bile pigment also appeared (Figure 1).

Figure 1. Figure 1. A), B) and C) show us loose mesenchymal components with prominent vascularization. On figure C and D, beneath the mesenchymal components, there is hepatic parenchyma with well-formed bile ducts. Figures E, F G and H represent hepatic parenchyma with active chronic inflammation. (Hematoxylin & eosin)

Only at the time of histopathological analysis was the diagnosis of this rare cystic hepatic lesion—HMH—established.

HMH are rare liver tumors, that appear most frequently in young children under age two (85%) and rarely in newborns (15%), is the most common benign hepatic lesion in the first years of life. Etiological analysis describes HMH to abnormal mesodermal development in the portal tract. The exact cause of HMH is unknown; attributed to anomalies of embryonic development, in which excessive growth of mesenchymal tissue occurs and subsequent C19MC overexpression in stromal cells causes tumorigenesis. Others suggest that HMH arise from true neoplasms involving chromosome 19q. Among the debated theories, there exists a link between HMH and placental lesions: mesenchymal stem villous hyperplasia, thrombosis, transient honeycombed multicystic placental enlargement (1). Others claim that HMH can be reactive, originating in blood supply alteration that leads to ischemia and cystic change. There are no indications that the condition is hereditary, and it does not generally increase risk of developing liver cancer. Documented links exist between HMH and polycystic kidney, congenital liver fibrosis, Beckwith-Weidman Syndrome, biliary atresia, congenital heart diseases and biliary hamartoma.

Because HMH is usually asymptomatic, discovery occurs only incidentally. Some patients have exhibited elevated alpha-fetoprotein levels, and symptoms such as abdominal distention, vomiting, or hepatomegaly. In neonates, rapid tumor enlargement may be the cause of liver compression, respiratory distress, ileus or abdominal compartment syndrome (2), which could be lethal and linked to non-immune hydrops (3) and intrauterine death. Preoperative complications, such as hemorrhage or rupture, may result in shock; surgical interventions could include cystic drainage and obliteration, marsupialization, tumor resection. MHM occurs most frequently in the right lobe (75%) but may rarely involve both lobes.

Cysts measuring from a few millimeters to around 6 cm in diameter (range, 4-30), having a smooth, shiny lining (3). In the case described herein, the cyst was unusually large (12 cm) for a neonatal abdomen.

Histological HMH features include disorganized proliferation of mesenchymal tissue elements, cyst formation, and varying degrees of fibrosis; cysts are bile duct-like or mesenchymal; usually lined by a single layer variable cell in size and shape, some may contain mucin; cell linings may contain endothelia, cuboidal bile duct epithelia or neither one (3). Another common feature is myxoid fibrous connective tissue septa, which are widely variable and contain small bile ducts and blood vessels, often accompanied by portal tract hyperplasia. There are often thick fibrous capsules encircling the lesion. Adjacent liver tissue can be compressed, atrophic or fibrotic. Characteristically, cystic structures do not communicate directly with the biliary tree. Multiples case reports rarely mention presence of bile pigment: however, it was present in this case.

In the pediatric population, the most described types of hepatic tumors include infantile hepatic hemangioendothelioma, focal nodular hyperplasia, regenerative nodular hyperplasia, hepatic adenoma, and HMH (4,5). Differential diagnosis can be difficult, especially when tumor is made up of mesenchymal stromal elements and when fibrosis is prominent. Neonates report excellent HMH prognosis, with very little recurrence after surgical resection. However, long-term follow-up is necessary to monitor potential complications.

HMH is a rare benign liver tumor, and it is extremely uncommon in neonates. Its etiology remains unknown, although associations with placental lesions have been reported. In neonatal cases, consideration should be given to associated syndromes, potentially informative laboratory findings, a broad range of clinical differential diagnoses, and a thorough histological analysis—particularly with close attention to the distinctive microscopic features of the neonatal liver.

Pontificia Universidad Javeriana and Hospital Universitario San Ignacio in Bogotá, Colombia, financed this report.

No author has any potential or actual interests relevant to the topics discussed in this manuscript.

Cordoba and Beltran participated in the case design, literature review, and writing of the manuscript, and viewed and approved the final version. Dr. Martinez participated in the summary of medical record, histological analysis and has seen and approved the final version.

Dr. Olaya-C participated in the summary of medical record, histological analysis and in support and review of the entire process; she has seen and approved the final version.

The ethics committee approved this study (FM-CIE-0616-23); informed consent was not requested, because the case does not contain patient identifiers.

The authors declare that the clinical data are no available for ethical reasons.