Fetus in Fetu

The term Fetus-in-fetu (FIF), was coined by Willis and first described by Johann Friedrich Meckel in the 18^th century. It is an extremely rare anomaly of monochorionic diamniotic  twins in which a malformed fetus resides in the body of its normal sibling during development¹.

Maternal care for (suspected) fetal abnormality and damage, unspecified, not applicable or unspecified. O35. 9XX0.

FIF occurs in about 1 in 500,000 live births. There have been fewer than than 200 cases reported in medical literature, most of which have been diagnosed after birth, either  in the neonatal period or in infancy. The prenatal diagnosis was first reported in 1983 and only a few cases of antenatal diagnosis of fetus in fetu have been published until now².

There are two prevailing theories that have been put forth for the development of FIF. One theory is that FIF is a highly differentiated form of teratoma.The other is the “parasitic twin” theory in which a parasitic, malformed fetus forms inside the body of its host twin and shares a common blood supply due to anastomoses of the vitelline circulation. Developmentally, the FIF goes through the embryological stage of the primitive streak, which is why FIF often has a vertebral body or column  and organs that are arranged around a central axis. Along with differences in zygosity, the absence of vertebral structures can help  differentiate FIF from a fetiform teratoma. In FIF, the parasitic fetus is genetically identicial to its host, whereas a fetiform teratoma can be homozygous in some loci but heterozygos to its host³. The parasitic fetus is usually covered by a membrane and derives its blood supply from the host fetus. FIF is usually malformed likely due to pressure and mass effect  exerted by the host organs on the  developing structures.

Willis (1953) emphasised the definition of FIF as a mass containing a vertebral axis along with other organs or limbs. However, a review of literature showed that in about 9% of cases of FIF, no vertebral column was found even on pathological examination. In these cases, features of advanced stage organogenesis have been present⁴.

Although the monozygotic twin theory is generally accepted, it may not be sufficient to explain the occurrence of multiple fetuses-in-fetu and its association with teratomas⁵.

Fetus in fetu is rarely associated with other structural or genetic abnormalities.

Recurrence risk is extremely low.

Ultrasound is the first-line tool in diagnosing FIF. Prenatally, FIF presents as a complex, well circumscribed intrafetal mass which is usually detected in the second or the third trimester⁶. Commonly, the mass contains a fluid‐filled sac with  solid elements or bony structures  within it. Internal calcifications are commonly present. The mass is usually surrounded by a membrane analogous to amniotic sac and amniotic fluid has been confirmed in some cases as the source of the surrounding fluid. This fluid can be mistaken for ascites⁷. The blood supply to the parasitic mass is usually from  a single feeding vessel which originates from the abdominal aorta or other regional vessels. Almost all FIF cases are anencephalic but they may have a vertebral column and budding limbs (91% and 82.5%, respectively). Lower limbs are usually more developed than the upper ones. The external genitalia are often identified. A true placenta is usually absent. In FIF, the blood supply source is usually from a vascular pedicle originating from the abdominal aorta or other regional vessels. Typically, FIF is not highly vascular on color Doppler unlike other abdominal tumors. Fetal MRI may be considered when ultrasound is not confirmatory, or if the management of the pregnancy will change based on the findings^8,9.

Eighty percent of FIF are found  in the retroperitoneum.  Other locations reported include scrotum, neck, mediastinum,  mouth and within the intracranial cavity. A single parasitic fetus has been reported in 89% of all cases, whereas an unusual patient had 11 parasitic fetuses⁸.

The main differential diagnosis of FIF is teratoma. FIF should be differentiated from a teratoma because of there is a higher potential for malignant trasformation with teratoma.  Teratoma is much more common than FIF and most commonly seen in the sacrococcygeal or head and neck regions, whereas fetus-in-fetu cases are typically located retroperitoneally^8,10.

Willis, in 1953,  established  criteria to differentiate these two conditions: FIF usually contains a vertebral axis with organs and limbs arranged around it, whereas a  teratoma is an accumulation of pluripotent cells in which there is neither organogenesis nor vertebral segmentation. While this distinction provides general guidance to the differential diagnosis, review of the literature showed that in about 9% of cases of fetus in fetu, a vertebral column was not found even on pathological examination⁴, despite the presence of highly developed organogenesis.

In general, it is very difficult to differentiate these two conditions because they have many similar features. Teratomas generally are (a) enclosed in connective tissue; (b) broadly attached to the surrounding tissue; and (c) capable of independent growth or malignant behavior. Commonalities between the two diagnoses can include location of the mass and the presence of highly differentiated tissue elements. The concurrence of both pathologies has been reported in some cases^10,11.

In addition, FIF may be confused with meconium pseudocyst and neuroblastoma.

Fetal meconium pseudocyst is a rare complication of meconium peritonitis that is caused by the intestinal perforation. Ascites and calcifications with are commonly seen with meconium pseudocyst with peritonitis⁸. (See the chapters on meconium pseudocyst and meconium peritonitis in the Abdomen section of VISUOG for more information).

Congenital neuroblastoma is the most common neoplasm among infants and the organs affected can include: skin, liver, adrenals or bone. Some cases of neuroblastoma are detected in the third trimester. The typical features of neuroblastoma include a mass containing microcalcifications. Hemorrhage may be present in some cases⁸.

Fetuses with FIF should have repeat ultrasound evaluations. Large masses may cause abdominal distention, hydronephosis,  and require caesarean delivery to prevent abdominal dystocia. Risks associated with FIF include hemorrhage, infection, mass effects, and pleuro-peritoneal inflammation due to the leaking of sac contents¹¹. Growth of the fetus should be monitored closely since the parasitic mass may slow fetal growth. Based on our experience, we would suggest revaluation of the fetus every two weeks.

During pregnancy, patients with FIF are typically scanned frequently to monitor growth and to detect mass effect, including compression of adjacent organs including the kidney and ureter. Delivery can be vaginal with cesaren delivery reserved for the usual obstetric indications.

Neonatal evaluation after delivery should be directed by the pediatric team in conjunction with pediatric surgery. Further imaging studies are typically performed in preparation for surgical excision of the FIF. Surgical treatment involves complete excision of the mass along with the surounding membrane to minimize the risk of malignant recurrence. Such an approach can restore the normal anatomy and physiology of the host fetus as well as decrease cancerous potential^5,8.

Although fetus-in-fetu is generally considered a benign disorder, there may be potential for malignant recurrence.

After surgical excision, patients should be monitored by imaging techniques and biomarkers, such as Alpha-fetoprotein (AFP) and Human Chorionic Gonadotropin (hCG) for a minimum follow-up period of 2 years in order to detect malignant recurrence.  Most of previous reports showed favorable outcome after the parasitic twin has been resected^8,10.

The long-term prognosis for fetuses with FIF is excellent.

1. Willis RA. The borderland of embryology and pathology 2nd ed. Washinton DC: Butterworths. 1962; 442-462.
2. Hoeffel CC, Nguyen KQ, Phan HT, Truong NH, Nguyen TS, Tran TT, Fornes P. Fetus in fetu: a case report and literature review. Pediatrics 2000;105:1335-1344.
3. Greenberg JA, Clancy TE. Fetiform Teratoma. Rev Obstet Gyencol 2008;1:95-96.
4. Gonzalez-Crussi F.  Extragonadal teratomas (Atlas of tumor pathology) Washington, DC: Armed Forces Institute of Pathology; 1982. 
5. Gilbert-Barness E, Opitz JM, Debich-Spicer D, Mueller T, Arnold SR, Quintero R. Fetus-in-fetu form of monozygotic twinning with retroperitoneal teratoma. Am J Med Genet A. 2003;120A:406–12.
6. Ruffo G, Di Meglio L, Di Meglio LD, Sica C, Resta A, Cicatiello R. Fetus-in-fetu: two case reports. J Matern Fetal Neonatal Med. 2019;32:2812–19.
7. Smith Z, Linthavong OF.  A fatal case of fetus-in-fetu. Pediatrics; 2018: 142, abstract 232.
8. Prescher LM, Butler WJ, Vachon TA, Henry MCC, Latendresse T,  Ignacio RC. Fetus in fetu: Review of the literature over the past 15 years. J Pediatr Surg Case Rep. 2015;3: 554-562.
9. Has R, Kalelioglu IH, Corbacioglu A, Demirbas R, Yuksel A, Yavuz E. Prenatal sonographic diagnosis of fetus in fetu. J Ultrasound Med. 2013; 32:2212-14.
10. Ji, Y., Chen, S., Zhong, L. Jiang X, Jin S, Kong F, Wang Q, Li C, Xiang B. Fetus in fetu: two case reports and literature review. BMC Pediatr 2014;14: 88.
11. Narayanasamy JN, Nallusamy MA, Baharuddin ND. Fetus-in-fetu: a pediatric rarity. J Surg Case Rep. 2014;2014:rju001.

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