Fetus-in-Fetu:

An Unusual Cause for Abdominal Mass in Infancy

JAY L. GROSFELD, M.D., DONALD S. STEPITA, M.D., WALTER E. NANCE, M.D., Ph.D., CATHERINE G .PALMER, Ph.D.

Fetus-in-fetu is an unusual cause of retroperitoneal abdominal mass in infants, which most likely arises from inclusion of a monozygotic, diamniotic twin. This entity is distinguished from teratoma by its embryological origin, its unusual location in the retroperitoneal space, its invariable benignity, and by the presence of vertebral organization with limb buds and well-developed organ systems. Diagnosis is made radiographically by the finding of a diminutive vertebral column on a plain abdominal film. The treatment of choice is total excision with special attention being given to the fetus' blood supply which may be directly from the host's superior mesenteric vessels. A well-documented example of this unusual entity that occurred in a six-week old infant male is presented.

From the Section of Pediatric Surgery, Department of Surgery and the Department of Medical Genetics, Indiana University School of Medicine and the James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
6 lbs, 14 oz at birth. Labor was of two hours duration and delivery was uneventful. The baby's Apgar scores at one and five minutes were both 10. The mother was a 22-year-old, gravida-2, para-2, and abortus-0. There was no history of twinning or teratomas in either parents' families. In the neonatal period, the infant was completely asymptomatic and showed a normal growth and developmental pattern. At six weeks of age, during a routine pediatric examination, a right-sided abdominal mass was palpated and the child was referred for evaluation. On admission, the infant appeared healthy and in no acute distress. He weighed 9 lbs, 15 oz and the blood pressure was 85/60, pulse rate 120/min, respiratory rate was 30/min and temperature was 98.6 F. Significant physical findings were limited to the abdomen. On the right side, a large, round, firm, and fixed mass was easily palpable. It extended from the upper flank to the linea alba and down to the iliac crest. It was nontender and did not transilluminate. The abdomen was not obviously distended. Bowel sounds were normal and rectal examination was unremarkable. Chest x-ray was normal. Erect, recumbent and lateral, plain abdominal x-rays demonstrated bone densities consistent with a well organized fetal spine in the right abdomen (Fig. 1). Well-formed long bone densities were also observed. These findings were considered diagnostic of fetus-in-fetu. The hemoglobin was 9.9gm, hematocrit was 28%, and white blood cell count was 11,700/mm3 with 15% polymorphonuclear leukocytes, 80% lymphocytes, 4% monocytes, and 1% eosinophiles. Urinalysis, blood urea nitrogen, and serum electrolyte values were normal. A coagulation profile showed the prothrombin time, partial thromboplastin time, and fibrinogen level to be normal. Peripheral blood smear demonstrated a microcytic hypochromic anemia typical of iom deficiency. Urinary chorionic gonadotropins were normal. Twenty-four hour urinalysis for 17-ketosteroids and 17-hydroxy-corticosteroids were also within the normal range.

TETUS-IN-FETU is a rare cause of abdominal mass in r infancy which should be carefully differentiated from the more common, retroperitoneal teratoma. The distinction between these entities has been a subject of considerable controversy. The purpose of this report is to present evidence that fetus-in-fetu is an unusual abberation of monozygotic twinning; whereas, teratoma is an embryonic neoplasm with distinct malignant potential.
Case Report
A 6-week-old, white male was referred to the James Whitcomb Riley Hospital for Children on 12/20/72 with an abdominal mass. The infant was a product of a full term pregnancy and weighed

Submitted for publication August 28, 1973. Supported by HEW Maternal and Child Health Project #924 and awards from the John A. Hartford Foundation, Ind., and the James Whitconb Riley Memorial Association. Reprint requests: Jay L. Grosfeld, M.D., James Whitcomb Riley Hospital for Children, 1100 West Michigan Street, Indianapolis, Indiana 46202.

80

Vol. 180 * No. 1

FETUS-IN-FETU

81

Operative Findings An operation was performed through a large transverse supraumbilical incision. The ascending colon, cecum and appendix were stretched over a large right retroperitoneal mass. The right kidney was displaced anteromedially and the mass was in intimate contact with the under surface of the liver and posterior retroperitoneum. After dividing the peritoneal attachments, a firm retroperitoneal mass enveloped by a semi-transparent sac-like capsule was encountered. This was mobilized down to a stalk that entered the paravertebral musculature adjacent to the upper lumbar vertebra near the base of the mesentery. The capsule was incised and a bi-lobed feti-form structure was noted. The umbilical cord was contiguous with this stalk. When the stalk was severed to remove the sac and fetus, arterial bleeding was encountered. These vessels were appropriately suture ligated. The vascular stalk did not appear to anastamose with any of the surrounding mesenteric vessels. The mass was removed en-toto and the abdomen closed in layers in the usual fashion. The postoperative course was uneventful and the patient was discharged on the seventh postoperative day. One month later, the boy weighed 10 lbs, 2 oz and was in good health. Six months postoperatively, the infant continued in good health and weighed 16 lbs, 8 oz.

FIG. 2. Photograph of the specimen showing the fetus-in-fetu to be anencephalic. Limb buds are apparent as well as a patent omphalomesenteric duct.
tions were seen coming off the superior limb buds. A patent omphalomesenteric duct was noted and the fetus was taken to the X-ray Department where a contrast study of the bowel demonstrated relatively well-developed bowel in what appeared to be the mid-gut (Fig. 3). The bowel contained soft green, inspissated material. A spleen, pancreas, and adrenal gland were also identified. The lower part of the fetus demonstrated lower limb buds and radiographically showed a boney pelvis. Each lower limb bud showed a primitive femur, tibia, fistula, and primitive foot and phalanges. Hair was noted on the back of the inferior segwas an

Pathological Examination Gross examination of the fetus showed it to be anencephalic. Two upper limb buds were noted (Fig. 2). Finger-like projec-

ment. There

imperforate

anus

and is

was

hind-gut had not fully developed. A complete vertebral column was

present. A small area with what appeared to be brain tissue was also identified. Microscopic evaluation demonstrated normal histological features of jejunum, ileum and proximal colon. A small fragment of pelvic tissue resembling primitive prostatic acini among fibromuscular stroma was also noted. Skin sections showed hyperkeratosis with follicular plugging. Large numbers of hair follicles, sweat glands, and sebaceous glands were seen in the dermis. The gastroduodenal region and adjacent pancreatic tissue containing acini and islet cells were identified. The adrenal gland demonstrated normal cortex and a few medullary cells. The vertebral column showed irregular cartilagenous arches of focal bone formation. The bone marrow showed active hematopoesis. A few ganglia, nerve segments, and some pigment bearing choroid were identified. In the central canal of the vertebral area, neuroglial tissue containing nerve cells and ependymal lining was found. Nerve roots and telangectasis of local capillaries were seen. Sections of the skull and brain showed highly vascular nervous tissue including glial areas, astrocytes, ependymal lining, meninges and a well-formed choroid plexus.

obvious that the

Genetic Studies

FIG. 1. Abdominal radiograph demonstrating the presence of the vertebral column and long bones of the included fetus-in-fetu.

Chromosome studies were performed on fibroblasts cultured from the fetus and on leukocytes and fibroblasts from the normal infant. Both subjects had a 46 XY karyotype with no evidence of mosaicism. Staining of the preparations with quinacrine mustard revealed heteromorphic flourescent markers on chromosome #3 and #21 in both preparations. C-banding showed no other polymorphic variants. Histo-compatibility typing was performed on

82

GROSFELD AND OTHERS

Ann. Surg. * July 1974

FIG. 3. Contrast study of the primitive gut, obtained by injection of dilute barium through the patent omphalomesenteric duct. Skeletal structures can also be seen.

cultured fibroblasts from the infant and fetus using a technique developed by Krieger and Biegel.1 Both fibroblast lines demonstrated the HL-AL and W19 antigens at the first sublocus and the HL-A5 and HL-A2 antigens at the second sublocus.

Discussion
The great born are of

majority of abdominal masses in the newrenal origin. Wedge et al.'6 found hydro-

nephrosis and multicystic kidney to be the most common with enterogenous duplication and genital (ovarian cysts or hydrocolpos) lesions occurring less frequently. Neuroblastoma is the most common neoplasm in the neonate. Teratomas rarely arise in the retroperitoneal area in the neonate and account for less than 5% of retroperitoneal masses in all age groups. Retroperitoneal teracauses

regions. The distinction between fetus-in-fetu and teratomas has been a subject of considerable controversy. Willis believed that the two conditions could be clearly resolved by clinical and pathologic criteria.17 He regarded teratomas as a discordant congregation of pluripotential cells that demonstrate no vertebrate segmentation or systematic organogenesis. Lacking a primary organizer, embryonic tissues that compose a teratoma cannot pass through an organized primitive streak stage which endows the developing organism with its fundamental vertebrate pattern. In addition, teratomas occur in many extraretroperitoneal locations and have definite malignant potential. In contrast, Lord'4 observed that the fetus-in-fetu is almost always retroperitoneal in location, is benign in nature, and possesses a vertebral skeleton and often an appropriate arrangement of other organs and limbs with respect to this skeletal axis. The present case meets all of the accepted criteria for a fetus-in-fetu. As in other well documented cases, reported by Lord,14 Gross and Clatworthy,5 Janovski8 and Farris and Bishop,' the fetus was located in the retroperitoneal area, had a basic vertebral column, and in addition had anatomic, radiographic and histologic evidence of other welldeveloped organ systems. A recent report by Kakizoe and Tahara9 described a fetus-in-fetu in the scrotal sac of a full term Japanese infant. This unusual location suggests migration of the fetus along with normal descent of the testes from the retroperitoneal area to the scrotal sac. Kimmel et al10 reported a case in which multiple fetal masses were found in the cranial cavity of a hydrocephalic infant. Since not all of the fetal masses had organized axial skeletons, the validity of this finding as an infallible criteria for distinguishing teratomas from fetus-in-fetu is open to question. Because of this uncertainty and the similar histologic findings, some authors, such as Lewis12 and Warkany15 have questioned whether a clear distinction can be made between the two conditions. Recent observations, however, and the findings in the present case suggest that fetus-in-fetu and teratomas may have quite different embryological origins. Fetus-in-fetu is widely believed to represent an aberration of monozygotic twinning in which the parasitic fetus becomes included in the autosite (host). Genetic and cytogenetic studies, however, have previously been performed only in the case described by Grant and Pearn.4 In their report, the typing results of the fetus and host were identical for eight blood group systems. Chromosome studies revealed an XY karyotype in both subjects, but a structural variation in the short arm of

tomas, however, are far more common than fetus-in-fetu. Teratomas may also occur in the anterior mediastinum, testes, ovary, liver, cervical, presacral, and sacrococcygeal

Vol. 180 * No. l

FETUS-IN-FETU

an A group chromosome was noted in the fetus but not the host. In the present case, sufficient blood could not be obtained from the fetus for genotyping. Monozygosity, however, is supported by the finding of identical histocompatibility types and identical male karyotypes which, on detailed analysis with chromosomal banding techniques, were found to include two normal polymorphic marker chromosomes. In contrast to the origin of fetus-in-fetu, Linder and Power have recently provided compelling genetic evidence for the parthenogenic (reproduction by development of an unfertilized gamete) origin of ovarian teratomas from post-meiotic germinal cells of the host.13 These authors found that tumors derived from patients who were heterozygous for genetically determined enzyme variants frequently showed expression of only one of the two genes and concluded that the tumors must have been derived from cells in which meiotic segregation had occurred. Whether a similar mechanism is applicable teratomas in males or to non-gonadal teratomas is uncertain. In the present case, the host and fetus were identical and heterozygous for histocompatibility type, and two chromosomal markers. In addition, both possessed a single X and Y chromosome and could not have arisen from a single post meiotic cell. Thus, the available genetic evidence clearly indicates that fetusin-fetu differs from some teratomas in its embryologic origin. Whether all teratomas are pathogenically homogeneous remains uncertain. Certain teratomas, most notably those of the sacrococcygeal area, are known to occur more frequently in twins and are associated with a family history of twinning.6 Early sex chromatin studies of teratomas suggested that they were often discordant with the chromosomal sex of the patient.7 More recent data, however, employing karyotype analysis have not shown such striking differences.3 The present instance and previous reports demonstrate fetus-in-fetu to be an axial vertebrate organism with limb buds and various stages of development and organ system differentiation. The majority of the specimens are anencephalic, with some cases showing evidence of cranial bone anlage and neural tissue. This suggests that caudal growth from the primitive streak procedes in a relatively normal manner; however, cephalad growth from Henson's node is inhibited. Janovski described a Japanese boy in whom a 2.0 cm tumor was noted at age three months.8 No treatment was given. At five years of age, the tumor had increased in size but caused no symptoms. At laparotomy, a retroperitoneal fetus-in-fetu with its blood supply derived from two branches of the superior mesenteric artery was found. The mass was excised, however, the patient died of retroperitoneal hemorrhage and pulmonary com-

83 plications. Gross and Clatworthy5 described a case of twin fetus-in-fetu in which one obtained its blood supply from the base of the mesentery where its vessels communicated with the superior mesenteric artery and vein. In the present case, we could not grossly demonstrate any communication to the superior mesenteric vessels. An angiogram, which might have been more informative, was not performed. Careful control of the blood supply to the fetus-in-fetu, however, is of obvious importance. In four of the eight cases reviewed by Lord, there was a vascular network between the fetus and host.41 In agreement with previous reports, however, no true placental tissue was observed on histologic examination in the present case. The absence of a functioning placenta was confirmed by the infant's normal urinary chorionic gonadotropin levels prior to surgery. While most cases have been diagnosed in young infants, Galatius-Jensen et al. and Himore (as quoted by Lord) reported instances in teenagers 17- and 15-yearsold, respectively.2'14 Of further interest is an article from the Sunday Chicago Tribune (November 3, 1922) which reported a case of fetus-in-fetu from the medical examiner's office in Springfield, Massachusetts. This was observed during an autopsy of an aged man killed by an automobile. A male infant weighing five or six pounds, fully formed, with the exception of the head, was found in the abdomen. The baby within the abdomen had one arm slightly shriveled, but the other was nearly perfect as was the remainder of the body. The diagnosis of fetus-in-fetu is based simply on the observation of a vertebral column in an abdominal mass on plain abdominal x-ray. The treatment of choice for fetus-in-fetu is operative removal. The key points in the procedure are adequate transperitoneal exposure and careful control of the vascular supply to the fetus which may be derived from the superior mesenteric artery. Operative excision should be done to confirm a benign diagnosis and to obviate the potential effects of continued compression on surrounding structures, as well as the danger of infection, infarction, or hemorrhage. Regarding the latter, Himore's case (as described by Lord) demonstrated hemorrhage and rupture of the sac wall of the included fetus into the gastrointestinal tract of a child who ultimately died.14
Acknowledgments

We gratefully acknowledge the aid of D. Krieger and A. Biegel in performing the HLA-typing.

References
1. Farris, J. M., and Bishop, R. C.: Surgical Aspects of Abnormal Twinning. Surgery, 28:443, 1950. 2. Galatius-Jensen, F., Rah, D. H., Uhm, I. K. and Thorborg, J.: Foetus in Foetu. Br. J. Radiol., 38:305, 1965.

84

GROSFELD AND OTHERS

Ann. Surg. * July 1974

3. Galton, M., Benirschke, K., Baker, M. C. and Atkin, N. B.: Chromosomes of Testicular Teratomas. Cytogenetics, 5:261, 1966. 4. Grant, P. and Pearn, J. H.: Foetus-in-Foetu. Med. J. Aust., 1:1016, 1969. 5. Gross, R. E. and Clatworthy, Jr., H. W.: Twin Fetuses-inFetu. J. Pediatr., 38:502, 1951. 6. Hickey, R. C. and Layton, J. W.: Sacrococcygeal Teratoma: Emphasis on Biologic History and Eary Therapy. Cancer, 7:1031, 1954. 7. Hunter, W. F. and Lennox, B.: The Sex of Teratomata. Lancet, 2:633, 1954. 8. Janovski, N. A.: Fetus-in-Fetu. J. Pediatr., 61:100, 1962. 9. Kakizoe, T. and Tahara, M.: Fetus-in-Fetu Located in the Scrotal Sac of a Newborn Infant: A Case Report. J. Urol., 107:506, 1972. 10. Kimmel, D. L., Moyer, E. K., Peale, A. R., Winbome, L. W.

11.
12.

13.

14.

15.
16.
17.

and Gotwals, J. E.: A Cerebral Tumor Containing Five Human Fetuses. Anat. Ree., 106:141, 1950. Krieger, D. A. and Biegel, A. D.: HL-A Typing of Human Skin Fibroblasts: The Use of Fibroblasts in HL-A Cell Panel. (In press) Lewis, R. H.: Foetus-in-Fetu and Retroperitoneal Teratoma. Arch. Dis. Child., 36:220, 1961. Linder, D. and Power, J.: Further Evidence for Post-meiotic Origin of Teratomas in the Human Female. Ann. Hum. Genet. (Lond.), 34:21, 1970. Lord, J. M.: Intra-abdominal Foetus-in-Foetu. J. Path. Bact., 72:627, 1956. Warkany, J.: Congenital Malformations. Chicago, Yearbook Medical Publishers, 1245, 1971. Wedge, J. W., Grosfeld, J. L. and Smith, J. P.: Abdominal Masses in Neonates; 63 Cases. J. Urol., 106:770, 1971. Willis, R. A.: The Borderland of Embryology and Pathology. London, Butterworth, Inc., 147 and 442, 1958.