The coexistence of IHH and HMH is rare, and there have been no reports of PMD associated with these two pathologies. The patient described in our report was well for some time after birth and received regular follow-up. However, at the age of 9 months, the rapid growth of IHH and HMH caused abdominal distension and poor oral intake. The combination of propranolol therapy for IHH and partial tumorectomy for HMH resulted in extensive tumor volume reduction without post-surgical regrowth. Although the etiology of IHH, HMH, and PMD has not yet been fully elucidated, their simultaneous occurrence in our patient suggests that some common etiological mechanisms underlie the three pathologies.

It has been previously speculated that HMH could contain hemangiomatous elements. However, to the best of our knowledge, the coexistence of IHH and HMH has been reported only six times in the literature (Table 1) [4,5,6,7]. All patients were female. They presented with symptoms such as abdominal compartment syndrome from rapid tumor growth and required interventions including cyst puncture and tumorectomy. One patient died of heart failure despite treatment and another required liver transplantation (LT). In two cases, IHH developed after HMH resection, whereas in the other four cases, IHH and HMH occurred simultaneously. The possible common pathogenic mechanisms have not been sufficiently discussed in the literature.

Table 1 Reports on the coexistence of infantile hepatic hemangioma (IHH) and hepatic mesenchymal hamartoma (HMH)

Moreover, our patient was also diagnosed with PMD. There have been reports of HMH associated with PMD [8,9,10,11]. HMH and PMD have similar histologies, including mesenchymal tissue growth with myxoid changes, and it is speculated that the pathogenetic origin is the same. Kitano et al. postulated that thrombin in placental vessels might embolize the fetal liver, resulting in mesenchymal hamartoma via a reactive response to ischemia [10]. They also considered that HMH could have metastasized from the PMD in utero.

More recently, it has been suggested that HMH and PMD could be caused by ABM. First, a mixed cell population consisting of normal and androgenetic (complete paternal uniparental disomy) cells was identified in the PMD placenta [13, 14]. The presence of ABM was later confirmed in HMH associated with PMD [11]. Reed, et al. have conjectured that ABM may cause PMD and HMH through at least two mechanisms. First, androgenetic cells greatly increase the likelihood of recessive traits with a genome-wide paternal uniparental disomy. Second, androgenetic cells may influence some phenotypes associated with paternal uniparental disomy through abnormal expression of paternally imprinted genes. However, ABM was not detected in our patient, and thus, other genetic factors might also be involved.

Hemangiomas (liver and skin) in neonates have been associated with PMD [14] and placental hemangiomas [15, 16]. Although the pathogenesis of infantile hemangioma is poorly understood, some researchers have hypothesized that its origin is embolization of placental chorionic villous mesenchymal core cells [2]. In addition, hypoxia seems to be involved in the development of both infantile hemangioma and HMH [17]. Impaired placental circulation due to PMD may create a hypoxic fetal environment, leading to the development of IHH and HMH.

In our patient, the combination of propranolol therapy for IHH and tumorectomy for the two largest HMH lesions diminished the progressive abdominal distension during infancy. Three years after the surgery, the HMH showed no regrowth, and the IHH was gradually regressing. Still, the optimal treatment and prognosis for our patient remain unclear. IHH is known to regress over time [2, 17] and should be expected to improve in the future. For HMH, there is a risk of malignant transformation to undifferentiated embryonal sarcoma, and complete resection is preferred [3]. However, the HMH was diffusely distributed in both hepatic lobes in our patient, and complete resection was impossible without LT. Treatment options included sequential tumorectomy with follow-up or LT. Because HMH containing-hemangioma components are considered more likely to regress [3], complete resection may become possible over time. ABM, which is often associated with PMD and HMH, was not observed in this patient. Loss of heterozygosity associated with ABM has been reported to increase the predisposition to malignancy. In such cases, pre-emptive LT may be more appropriate than follow-up [18]. For our patient, no ABM is present, and further follow-up is required with close attention to the potential for malignant HMH transformation.

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