epignathus,always a simple teratoma question mark

Ultrasound Obstet Gynecol 2003; 21: 397403Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.92

Epignathus: always a simple teratoma? Report of anexceptional case with two additional fetiforme bodies

N. SARIOGLU*, R. D. WEGNER, A. GASIOREK-WIENS, M. ENTEZAMI, J. SCHMOCK,A. HAGEN and R. BECKERDepartments of *Paidopathology and Human Genetics, Klinikum Rudolf Virchow, Humboldt University, Department of Obstetricsand Gynecology, Klinikum Benjamin Franklin, Free University of Berlin, Center of Prenatal Diagnosis and Gynecological Office, Berlin,Germany

KEYWORDS: epignathus; fetus parasitici; prenatal diagnosis; teratoma; ultrasound

ABSTRACT

We report on a case of a fetal epignathus combined withtwo fetus-like structures resembling acardius acranius.The anomaly was detected at 23 weeks of gestation andled to termination of pregnancy at 24 weeks. This isthe first description of epignathus with parasitic fetusesdetected prenatally. It shows that the boundary betweenfetal teratoma and multiple pregnancy in special casesmay be difficult to define. Copyright 2003 ISUOG.Published by John Wiley & Sons, Ltd.

INTRODUCTION

In general, it is easy to distinguish multiple pregnanciesfrom teratomas, which are the most frequent type of fetaltumor, occurring in different locations. A fetal teratomaoriginating from the base of the skull is called epignathus.It is a rare, benign, congenital teratoma1 that is notnormally associated with other anomalies2. It may developbidirectionally and involve intracranial structures1. Theprenatal diagnosis of fetal epignathus1,321 has beenreported previously and, at the beginning of the lastcentury22, there was a description of an epignathuswith parasitic fetuses diagnosed postnatally. To ourknowledge, this is the first description of a fetal teratomawith structures presenting the features of additionalfetuses.

CASE REPORT

A 24-year-old pregnant woman of Turkish origin wasreferred to our center for prenatal diagnosis at 24 + 0gestational weeks. The woman and her partner werecousins and their first child was healthy. The pregnancy

had been uneventful, although, because the couple lackedhealth insurance, they had not been seen by a gynecologistor midwife. The first scan of this pregnancy was performedat 23 + 6 weeks because of atypical enlargement ofthe maternal abdomen. This scan raised the suspicionof conjoined twins and, following a second scan in aspecialized institution, the patient was referred to ourtertiary center.

Ultrasound biometry revealed that the fetus wasappropriate for the gestational age of 24 + 0 weeks.Polyhydramnios was noted and the fetal stomach couldnot be seen. Arising from the fetal face was a tumormeasuring 119 77 93 mm adherent to which was afetiforme body (Figure 1). The parts of a second fetuswere seen attached to the facial tumor, and color Dopplerexamination revealed vessels connecting the epignathusand the appending fetal structure (Figure 2). This complexstructure contained bones (Figure 3) and exhibited limbs(Figure 4), raising the suspicion of the presence of anacranius acardius. There was no evidence of a fetal heador heart and an umbilical cord could not be demonstrated.

The couple declined fetal karyotyping. Followingcounseling by a geneticist and pediatric surgeon withthe support of an interpreter, the parents opted fortermination of the pregnancy. This was performed at24 + 4 gestational weeks by Cesarean section due to thelarge size of the tumor.

A male fetus with a weight of 885 g was delivered(Figure 5) and died immediately after. A large 290-g tumorprotruded from the fetal ethmoid bone. Histologicalanalysis of this tumor revealed the presence of skin,cartilage, bone, glandular, nervous and muscular tissue.A heart or head could not be demonstrated in thetumor, which was classified as epignathus. Apart from the

Correspondence to: Prof. R. Becker, Free University of Berlin, Klinikum Benjamin Franklin, Kurfurstendamm 199, D-10719 Berlin,Germany (e-mail: [email protected])

Accepted: 11 January 2003

Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. CASE REPORT

398 Sarioglu et al.

Figure 1 Oblique cross-section through the fetal head and the hugesolid tumor with the appending fetus-like structure. h, head; fp,fetus parasiticus; arrows, epignathus.

Figure 2 Color Doppler sonography of the fetal teratoma and theappending fetus parasiticus showing the connecting vessels betweenepignathus and fetus parasiticus. FH, fetal head; FP, fetusparasiticus; E, epignathus.

Figure 3 Sagittal section of the fetus parasiticus appending to theepignathus.

Figure 4 Oblique section of one pole of the fetus parasiticus with astructure resembling a fetal lower leg and foot.

craniopharyngeal teratoma, a missing terminal phalanxof digit 4 of the left hand was the only fetal anomaly.

The second, fetus-like, structure (heteropagus parasiti-cus), which had been detected at sonographic examina-tion, measured 100 55 30 mm and weighed 121 g. Itwas separated from the fetus/epignathus during Cesareansection. This structure contained four limbs and fragmentsof skull (Figures 6 and 7).

In addition there was a third, fetus-like, structure(heteropagus parasiticus) which had not been detectedat the sonographic examination. It weighed 40 g. Thisstructure contained two limbs, structures of pelvic bonesand a male genital organ (Figures 6 and 7).

The placenta showed no abnormalities with a normalumbilical cord containing one vein and two arteries. Therewas no additional placental tissue and no second umbilicalcord.

DISCUSSION

Fetal tumors are rare, the most frequent type beingteratomas2 which have an incidence of between 1 : 20 000and 1 : 40 000 live births23. Teratomas may presentin several locations. The rare form of fetal teratomaoriginating from the base of the skull is named epignathus.It presents with a frequency of < 1% of all congenitalteratomas (6/1253 (0.48%), Table 1).

Although teratomas may grow into the oral and nasalcavities and may extend intracranially, they usually

Table 1 Frequency of reported congenital teratomas andepignathus

Ref. Teratoma (n) Epignathus (n)

Carney et al. (1972)48 58 1Grosfeld et al. (1976)49 85 0Tapper and Lack (1983)23 254 1Chervenak et al. (1985)2 6 2Tharrington and Bossen (1992)50 850 2

Total 1253 6

Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 21: 397403.

Epignathus 399

Figure 5 Aspect of the fetus with the craniopharyngeal teratoma (epignathus) following termination of pregnancy at 24 + 4 gestationalweeks (middle). Demonstration of the two parasitic fetuses with the larger first fetiforme body appending the epignathus and the secondparasitic fetus which was found in the uterine cavity during Cesarean section (right). Reproduction of a drawing of a case examined by Baartde la Faille in 1875, published 190722 (left), Urban & Fischer Verlag.

protrude out of the mouth of the fetus or neonate. Interatomas originating from the oropharynx, malignantchanges have not been described7. Prenatal diagnosisis possible1,321; there have been several reports ofdiagnosis before 20 weeks1,4,6,15,16,21 and the earliestdiagnosis so far has been at 15 weeks1,6. Sonographicfeatures of fetal epignathus are the presence of cysticand solid components, commonly protruding out ofthe fetal mouth2,5,9,19. Accompanying symptoms areelevation of maternal serum alpha-fetoprotein16,21,24

and acute polyhydramnios2,4,7,15,19,25 reflecting impairedfetal swallowing. The differential diagnosis includescephalocele involving the oral cavity26.

In our case, early prenatal diagnosis of the lesionwas not possible since the pregnant woman visited agynecologist for the first time at 23 + 6 gestationalweeks. The oropharyngeal tumor was easily identifiedon ultrasound examination, as was the presence of onefetiforme body appending the tumor. The second smallerfetiforme body was not identified by sonography inspite of a thorough examination of the whole mass. Wetherefore hypothesize that this second fetiforme body wasalready disconnected from the teratoma and was hiddenat the back of the amniotic cavity, or was attached to theback of the tumor and became detached because of themanipulations during Cesarean section.

The outcome of affected newborns is usuallyunfavorable7 but depends on the size and location of the

tumor and the degree of intracranial spread6. Althoughlong-term survival is possible10,11,27,28, and indeed hasbeen documented in a case with no surgical intervention29,the tumors are generally not amenable to resection andinfants born with these lesions usually die secondaryto respiratory compromise19. A precondition of success-ful management is the availability of medical facilitiesimmediately after birth following prenatal diagnosis2,8,10.If the almost inevitable respiratory distress during thefirst minutes following birth can be avoided by a timelytracheostomy and intact fetomaternal circulation, theseinfants can survive with only minimal problems aftertumor resection10.

The etiology of epignathus still remains unclear. Themost common theory supposes that epignathus derivesfrom pluripotent cells in Rathkes pouch that grow ina disorganized manner30. While most tumors normallyconsist of parts of one germ layer only, teratomas presentwith parts of at least two, and normally three, germ layers.

In our case, the diagnosis of epignathus was basedon the involvement of three germ layers showing severaltissues and a tumor protruding from the oral cavity.Diagnostic problems arose from the two fetiforme bodiesconnected to the teratoma. They had no heart but theypresented clear differentiation of organs and resembledacardius acranius. Although they were part of andconnected to the oral tumor, both fetiforme bodies hadpassed stage 7 of germ layer development, implying


400 Sarioglu et al.

Figure 6 Skeletal preparation of the two fetiforme bodies with alizarin red (bone) and alcian blue (cartilage) staining (not to scale). On theleft is the smaller fetiforme body which was found in the amniotic cavity; on the right is the bigger fetiforme body appending the fetalteratoma. Black arrows, lower limbs; large white arrows, upper limbs; small white arrow, patella; X, cranium-like structure.

they had reached the 15th day of normal embryologicaldevelopment3133.

The phenomenon of gestation complicated by addi-tional structures with varying degrees of differentiationis extremely rare. There is only one similar case of epig-nathus with two fetiforme bodies dating back to 1875 andpublished in 190722 (Figure 5). Other perhaps comparablesituations have been described in two cases of sacro-coccygeal teratoma, one with a single fetiforme body34,another even with heartbeats33. One case, reported at24 weeks of gestation, was associated with an 8 15-cmteratoma freely moving in the amniotic sac18.

Fetal teratomas which arise from pluripotent cellsto form an unorganized conglomerate of matureand/or immature tissues, often with the tendency tobecome malignant, are usually readily distinguishablefrom monozygotic twins. In monoamniotic twins oracardius acranius, two umbilical cords are found aswell as communicating vessels on the placental surface.Incomplete separation of monozygotic twins leads to

conjoined twins; usually these forms are not combinedwith the appearance of a congenital tumor. Another rareform of twinning, fetus in fetu35, involves an incorporatedtwin inside an amniotic-like sac connected to its twin byan umbilical cord arising from the mesenteric vessel ofthe bearer. Normally, this form of twinning can clearlybe distinguished from teratomas because in fetus in fetuthere is a spine suggesting that it has passed the stageof primitive streak and groove development inducingmetameric differentiation32.

The etiology of the anomalies observed in the presentcase is obscure and thus open to speculation. Variouscauses might exist for the origin of teratomas or ofepignathus, for example chromosomal aberrations20,21,gene mutations (e.g. HLXB936) or anomalies of earlyembryonic development of unknown causes37. It mightbe assumed that the epignathus belonged to a groupof extragonadal tumors arising from locations wherethe attachment of conjoined twins has been observed37.It might also be speculated that the epignathus and


Epignathus 401

Figure 7 Demonstration of the two fetiforme bodies by x-ray (not to scale).

the two fetiforme bodies had a common origin i.e.an erroneous process of early embryonic development.Initially, incomplete conjoined twinning with unequaldivision of the blastula37 might have occurred resultingin the presence of a few totipotent cells in anunusual location. Embryonic development is a complexprocess requiring a precise spatiotemporal expression ofdevelopmental genes38. Unequal blastula division mightresult in aberrant exposure of these totipotent cells togrowth and differentiation factors from maternal orparacrine sources39, altering the expression of essentialgenes and of autocrine factors which finally results inabnormal development. In our case, derivatives of all threegerm layers were present, thus some products regulatingearly embryonic development must have reached theirtarget. Control of cell division and differentiation musthave been lost, however. Since many of the developmentalgenes code for both transcription factors and tumorsuppressors, a defect of such genes leads to loss of control

of cell regulation resulting in tumor growth, as occurs,for example, with PAX gene mutations40. This couldexplain the origin of the teratoma (epignathus). Assumingthat local areas of the epignathus were influenced bymore favorable environmental factors, regulating some ofthe developmental genes in a more normal manner, thiscould have resulted in the two fetiforme bodies with ahigher degree of general differentiation but neverthelesswith only partial development. In this context it is ofinterest to know that the occurrence of several teratomasof varying grades of differentiation in one fetus has beenobserved previously41.

In summary, we suggest that the development of theobserved fetiforme structures and the teratoma did notoccur independently of each other. The link might be aprimary event impairing the process of normal embryonicdevelopment. However, as mentioned above, other causesfor the present anomaly cannot be excluded. In particular,the consanguineous relationship of the parents opens up


402 Sarioglu et al.

the possibility of a recessive gene mutation segregating inthis family, although this explanation is less probable sincethe majority of developmental genes act in a dominantmanner.

Our case suggests that a strong distinction betweenteratoma as a simple tumor and a malformation likeours with fetiforme bodies does not exist. It supportsthe hypothesis33,42,43 that the boundary between rareforms of twinning like fetus in fetu44,45 or craniopagusparasiticus46 and extreme forms of fetal teratoma with anorganoid appearance is not as sharp as it normally seems.A priori there is no biological barrier beyond which ateratoma cannot develop47. A description like teratomapartim fetiformis alluding to the special composition ofthis form of neoplasm might be appropriate.

ACKNOWLEDGMENT

We thank Mrs Gisela Krantz for producing the photos ofthe autoptic specimen.

REFERENCES

1. Gull I, Wolman I, Har-Toov J, Amster R, Schreiber L, Less-ing JB, Jaffa A. Antenatal sonographic diagnosis of epignathusat 15 weeks of pregnancy. Ultrasound Obstet Gynecol 1999;13: 271273.

2. Chervenak FA, Isaacson G, Touloukian R, Tortora M,Berkowitz RL, Hobbins JC. Diagnosis and management of fetalteratomas. Obstet Gynecol 1985; 66: 666671.

3. Abendstein B, Auer A, Pumpel R, Mark E, Desch B, Tscharf J.Epignathus: prenatal diagnosis by sonography and magneticresonance imaging. Ultraschall Med 1999; 20: 207211.

4. Bruhwiler H, Muller MD, Rabner M. Ultraschalldiagnose einesEpignathus in der 17. SSW. Ultraschall in Med 1995; 16:238240.

5. Chervenak FA, Tortora M, Moay F, Hobbins JC. Antenatalsonographic diagnosis of epignathus. J Ultrasound Med 1984;3: 235237.

6. Clement K, Chamberlain P, Boyd P, Molyneux A. Prenataldiagnosis of an epignathus: a case report and review of theliterature. Ultrasound Obstet Gynecol 2001; 18: 178181.

7. Ekici E, Soysal M, Kara S, Dogan M, Gokmen O. Prenataldiagnosis of epignathus causing acute polyhydramnios. ActaObstet Gynecol Scand 1996; 75: 498501.

8. Gaucherand P, Rudigoz RC, Chappuis JP. Epignathus: clinicaland sonographic observations of two cases. Ultrasound ObstetGynecol 1994; 4: 241244.

9. Kang KW, Hissong SL, Langer A. Prenatal ultrasonographicdiagnosis of epignathus. J Clin Ultrasound 1978; 6: 330331.

10. Levine AB, Alvarez M, Wedgwood J, Berkowitz RL, Holz-man I. Contemporary management of a potentially lethal fetalanomaly: a successful perinatal approach to epignathus. ObstetGynecol 1990; 76: 962966.

11. Lodeiro JG, Feinstein SJ, McLaren RA, Shapiro SL. Antenataldiagnosis of epignathus with neonatal survival. A case report.J Reprod Med 1989; 34: 997999.

12. Papageorgiou C, Papathanasiou K, Panidis D, Vlassis G. Prena-tal diagnosis of epignathus in the first half of pregnancy: a casereport and review of the literature. Clin Exp Obstet Gynecol2000; 27: 6768.

13. Ramirez Robles LJ, Gomez Partida G, Trujillo Gomez JJ.Epignathus: ultrasonic diagnosis. Report of a case and reviewof the literature. Ginecol Obstet Mex 1999; 67: 512515.

14. Sevelda P, Amann G. Epignathus, eine seltene Dop-pelmibildung. Geburtshilfe Frauenheilkd 1985; 45: 572573.

15. Shouno H, Matsuo N, Miyabara S, Yamasaki M, Kuriyama K,Sugimori H. Intrauterine diagnosis of epignathus using ultra-sonic tomography. Asia Oceania J Obstet Gynaecol 1988; 14:199205.

16. Smart PJ, Schwarz C, Kelsey A. Ultrasonographic and biochem-ical abnormalities associated with the prenatal diagnosis ofepignathus. Prenat Diagn 1990; 10: 327332.

17. Smith NM, Chambers SE, Billson VR, Laing I, West CP,Bell JE. Oral teratoma (epignathus) with intracranial extension:a report of two cases. Prenat Diagn 1993; 13: 945952.

18. Tajani E, Gragnanielle G, Agostinelli D, Marolla C, Ianniru-berto A. Diagnosi ecografica di due rare malformazioni fetali.In Aggiornamenti 1981 in ecografia ostetricoginecologica. Cati-zone FA, Ianniruberto A, Bertagnoli L (eds). Novappia Editrice:Roma, 1981; 213216.

19. Teal LN, Angtuaco TL, Jimenez JF, Quirk JG. Fetal teratomas:antenatal diagnosis and clinical management. J Clin Ultrasound1988; 16: 329336.

20. Yapar EG, Ekici E, Gokmen O. Sonographic diagnosis ofepignathus (oral teratoma), prosencephaly, meromelia andoligohydramnios in a fetus with trisomy 13. Clin Dysmorphol1995; 4: 266271.

21. Schwartz S, Raffel LJ, Sun CC, Waters E. An unusual mosaickaryotype detected through prenatal diagnosis with duplicationof 1q and 19p and associated teratoma. Teratology 1992; 46:399404.

22. Schwalbe E. Morphologie der Missbildungen der Menschen undTiere. Verlag Gustav Fischer Jena, 1907.

23. Tapper D, Lack EE. Teratomas in infancy and childhood. A54-year experience at the Childrens Hospital Medical Center.Ann Surg 1983; 198: 398401.

24. Melchert F. Pranatale Diagnostik eines Epignathus. Gynakologe1979; 12: 7779.

25. Kaplan C, Perlmutter S, Molinoff S. Epignathus with placentalhydrops. Arch Pathol Lab Med 1980; 104: 374375.

26. Carlan SJ, Angel JL, Leo J, Feeney J. Cephalocele involving theoral cavity. Obstet Gynecol 1990; 75: 494495.

27. Bennett JP. A case of epignathus with long term survival. Br JPlast Surg 1970; 23: 360364.

28. Maeda K, Yamamoto T, Yoshimura H, Itoh H. Epignathus: areport of two neonatal cases. J Pediatr Surg 1989; 24: 395397.

29. Calderon S, Kaplan I, Gornish M. Epignathus: case report oflong-term survival with no surgery. Int J Oral Maxillofac Surg1991; 20: 322324.

30. Pavlin JE, OGorman A, Williams HB. Epignathus: a report oftwo cases. Ann Plast Surg 1984; 13: 452456.

31. Willis RA. The structure of teratoma. J Pathol Bacteriol 1935;40: 136.

32. Willis RA. The Borderland of Embryology and Pathology (2nd

edn). Butterworths: Washington, 1962; 442462.33. De Lagausie P, De Napoli Cocci S, Stempfle N, Truong QD,

Vuillard E, Ferkadji L, Aigrain Y. Highly differentiated ter-atoma and fetus-in-fetu: a single pathology? J Pediatr Surg1997; 32: 115116.

34. Ouimet A, Russo P. Fetus in fetu or not? J Pediatr Surg 1989;24: 926927.

35. Al-Baghdadi R. Fetus in fetu in the liver: case report and reviewof the literature. J Pediatr Surg 1992; 27: 14911492.

36. Kochling J, Karbasiyan M, Reis A. Spectrum of mutations andgenotype-phenotype analysis in Currarino syndrome.Eur JHumGenet 2001; 9: 599605.

37. Ashley DJB. Origin of teratomas. Cancer 1973; 2: 390394.38. Arthur W. The emerging conceptual framework of evolutionary

developmental biology. Nature 2002; 415: 757764.39. Diaz-Cueto L, Gerton GL. The influence of growth factors on

the development of preimplantation mammalian embryos. ArchMed Res 2001; 32: 619626.

40. Chi N, Epstein JA. Getting your Pax straight: Pax proteins indevelopment and disease. Trends Genet 2002; 18: 4147.


Epignathus 403

41. Hanquinet S, Damry N, Heimann P, Delaet MH, Perlmutter N.Association of a fetus in fetu and two teratomas: US and MRI.Pediatr Radiol 1997; 27: 336338.

42. Eng HL, Chuang JH, Lee TY, Chen WJ. Fetus in fetu: a casereport and review of the literature. J Pediatr Surg 1989; 24:296299.

43. Senyuz OF, Rizalar R, Selayir S, Oz F. Fetus in fetu or giantepignathus protruding from the mouth. J Pediatr Surg 1992;27: 14931495.

44. Bernal-Sprekelsen JC, Bernal-Cascales M. Fetus in fetu: einFallbericht einer extrem seltenen Ursache von Bauchtumorenbeim Saugling. Z Kinderchir 1990; 45: 317318.

45. Blumberg NA. Abdominal parasitic twin: an unusual cause ofduodenal obstruction. Br J Surg 1980; 67: 675676.

46. Aquino DB, Timmons C, Burns D, Lowichik A. Craniopagusparasiticus: a case illustrating its relationship to craniopagusconjoined twinning. Pediatr Pathol Lab Med 1997; 17:939944.

47. Alpers CE, Harrison MR. Fetus-in-fetu associated with anundescended testis. Pediatr Pathol 1985; 4: 3746.

48. Carney JA, Thompson DP, Johnson CL, Lynn HB. J PediatrSurg 1972; 7: 271282.

49. Grosfeld JL, Ballantine TV, Lowe D, Baehner RL. Benign andmalignant teratomas in children: analysis of 85 patients. Surgery1976; 80: 297305.

50. Tharrington CL, Bossen EH. Nasopharyngeal teratomas. ArchPathol Lab Med 1992; 116: 165167.


epignathus,always a simple teratoma question mark

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