FIF is extremely rare pathology (1/500,000 live births) [4], in which a malformed fetus is located in the body of its twin. The liberal definition of FIF was proposed by Gonzalez-Crussi [5], who defined FIF as ‘high organotypic development and presence of a vertebral axis with arrangement of tissue around this axis’. In most cases, there is a single parasitic twin. But rarely, more than 1 parasitic twin is observed in the host body. To our knowledge, the maximum number of FIF previously documented was 11 [6]. Studies of genetic markers, such as blood group, sex chromosome constitution, protein polymorphisms, and DNA marker, suggested that host infants and their fetiform mass are genetically identical [6, 7].
Eighty-nine percent of FIF lesions were noted before 18 months of ages [3]. Most FIF are located retroperitoneally along the ventral midline [8], while other rare reported sites include the cerebral ventricles [9], liver, pelvis [10], scrotum [11, 12], and mediastinum [2]. Although FIF is a benign condition, the mass may compress the surrounding organs and tissue. Therefore, symptoms of FIF are primarily due to its mass effect such as abdominal distension, feeding difficulty, emesis, jaundice or pressure effects on the renal or respiratory system. Compression of the lung by the mass may explain the dyspnea in our first patient. After the surgical procedure, the boy had no further significant symptom and did well.
To qualify as an FIF, one of the following characteristics must be present: a mass enclosed within a distinct sac, partially or completed covered by skin, grossly recognizable anatomic features and attached to the host by a pedicle containing a few relatively large blood vessels [13]. The two FIFs in our report fulfilled the criteria for being FIF and not a teratoma. Ultrasonography and plain radiography can be used to achieve a diagnosis of FIF. Computed tomography scan and magnetic resonance imaging can give a more accurate diagnosis and defines the relation of the FIF with the other intra-abdominal structures [14]. In both our patients, computed tomography revealed that the mass contained irregularly shaped structures resembling a gestational sac in the middle stages of a pregnancy. The imaging played an important role in our ability to make a preoperative diagnosis.
FIF is usually overlooked in the differential diagnosis of a newborn abdominal calcification. In some cases, FIF may be confused with meconium peritonitis, which is commonly associated with calcifications [15]. Other causes of calcifications include neuroblastoma, adrenal hemorrhage, and viral infection. It is also important to differentiate between a retroperitoneal teratomas and a retroperitoneal FIF because the former have more than 10% malignancy rate. In contrast, FIF is almost always benign. Until now, only one case of malignant FIF has been reported [16]. Clinically, FIF can be differentiated from teratoma by the presence of vertebral bodies and limbs. The presence of vertebral bodies not only means that the FIF passed the primary stage of gastrulation, but also may reflect its derivation from a primitive streat. The formation of the primitive streak normally starts during the 3rd week, together with gastrulation that will lead to the notochord formation and subsequently to the vertebral column and segmental axis. Therefore, FIF likely arises from a zygote at a primitive-streak stage and fetiform mass develops to a certain degree in a manner similar to normal fetal development [7]. In contrast, teratoma consists of pluripotent cells, without organogenesis or vertebral segmentation [17]. In both our patients, pathologic examination showed vertebral column with cartilage within the mass, further supporting the diagnosis of FIF.
As described above, many authors agree that FIF corresponds to a monochorionic, monozygotic twin contained with the host [18, 19]. In the study of Miura et al [7], the investigators demonstrated that host infants and their fetus shared the same genotypes, further supporting the monozygotic theory. These findings also confirmed a separate etiology for FIF as compared to teratoma. However, our knowledge of early molecular and genetic events that regulate embryo development and organogenesis is rudimentary. The possible association between FIF and highly differentiated teratoma is still controversial. Some investigators hypothesized that FIF represents a well-differentiated and highly organized teratoma [20]. In other words, FIF and teratoma may share a causal/pathogenetic mechanism. There are several observable phenomena support the teratoma theory. First, FIF are observed in the same sites as teratomas, including retroperitoneum and ovaries [1]. Second, FIF can be associated with a teratoma [21]. Retroperitoneal teratoma formation after FIF resection has also been reported [16]. A simple monozygotic (monochorionic, diamniotic) twin theory may be difficult to explain these phenomena. Third, there have been many reports of invertebrate teratomas containing well-developed fetiform structures, including brain-like tissue with ependymal-lined ‘ventricles’ and spinal cord with a central canal [22]. As there are many similarities at the histological level, and considerable overlap between FIF and teratomas, establishing the true nature of FIF is of great interesting.
The recommended treatment for FIF is surgical excision. Because the final diagnosis of FIF is not made until pathological analysis, all parts of the mass should be removed to prevent malignant recurrence. Postoperative follow-up with screening for the tumor markers β-HCG and AFP is often used and is further supported on the basis of malignant recurrence of FIF. The detection of raised CEA levels generally indicates advanced malignant disease. Therefore, the raised CEA level in our first patient is of great concern. Whether this association of abnormal CEA level is a manifestation of the FIF or an incidental finding is unclear based on our case. Further studies are needed to establish the significant of this phenomenon.