EPIGNATHUS, DOUBLE PITUITARY A N D AGENESIS O F CORPUS CALLOSUM PATRICIA M. BALEAND R. D. K. REYE Institute of Pathology, Royal Alexandra Hospital for Children, Camperdown, N.S. W. 2050, Australia
PLATES LXV AND LXVI DUPLICATION of the pituitary is a rare lesion, reports of only three human cases having been found (Ahlfeld, 1880; Morton, 1957; Bainborough and Hase, 1958). This report describes two additional cases discovered at necropsy in the last 5 yr, in neonates from unrelated families. Each infant had a combination of double pituitary, epignathus and anomalies of the head characterised by widening or separation of midline structures. CASEREPORTS The pertinent features are listed in the table. Neither mother remembered any drug or unusual food taken during the first 2 mth of pregnancy. In case 1 the mother was hospitalised at 7 mth for premature rupture of the membranes. Later she described intermittent loss of brownish and clear fluid per vaginum from the 6th wk of gestation. Other features of the pregnancy were poor weight gain, vomiting, colds, and poor foetal movements. The mother of case 2 was well throughout pregnancy, with no haemorrhage, infection or other illness. At birth, each infant had a large skin covered tongue-like mass of tissue projecting from the hard palate out through the mouth (fig. 1). Both infants were cyanosed, and displayed decreased limb tone. In case 2 the rooting reflex was absent and the fists were unusually clenched, with overlapping fingers. Each child died in respiratory arrest during the 1st day of life. Pathology At necropsy each infant had pulmonary interstitial haemorrhage. The lungs were normally lobed and all other organs and tissues below the neck, including the adrenal glands, were normal. The anomalies were confined to the head and neck and are listed in the table. In each case the two hypophyses lay side by side in separate fossae (fig. 2), separated by a central bar of bone and cartilage about 0.5 cm wide. The pituitary glands were not weighed before fixation but each appeared about 3 to average size, so that the total amount of tissue may have been more than normal for each infant. Microscopically each had an anterior and posterior part and stalk. In each infant the palatine epignathus was large, considerably reducing the oral and nasopharyngeal cavities. In case 1 it was a single polypoid mass (fig. 3). In case 2, the main epignathus had smaller projections from its base (fig. 4), the smallest containing a tooth and the two larger being soft and pedunculated. One of the latter had a second attachment to the midline of the lower alveolar margin, where there was a conical elevated mass, 0.7 cm diameter, containing three tooth buds. Microscopically the palatine epignathi had a covering of skin with many pilo-sebaceous follicles. Each had a fibro-adipose core containing a little striated muscle toward the base.
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Received 30 Dec. 1975; accepted 13 Feb. 1976. J. PATH.-VOL.
120 (1976)
161
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PATRICIA M. BALE AND R. D . K. REYE
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Closer to the base there were sero-mucinous glands, cysts lined by ciliated epithelium, cartilage, bone, small islands of adamantine epithelium, cavities lined by ameloblasts and stratum intermedium of tooth germs. In case 1 there were also foci of melanin close to cuboidal epithelium. The most posterior part of the mass in this case extended into the basisphenoid which was displaced upwards and backwards. In case 2 the anterior third of the tongue was tripartite (fig. 5).
TABLE Clinical and pathological features of infants with epignathi and double pituitaries Case 2. 1st child H ydramnios
M.
24 hr
Morton’s case. M. 3 days 1st child Uterine bleeding 1st mth
Gestation, birth weight
Case I. F. 6 hr 5 siblings alive and well Loss of amniotic fluid since 6 weeks: pregnant 37 wk. large baby ”
Pathological features Epignathus: Size Attachments
To upper alveolar ridge and
To wide philtrum of uppec lip
Hypertelorism
Hypertelorism 3.6 cm Optic nerves 17 mm apart
Right choanal atresia 1 cm from anterior nares
...
Central nasal groove Right choanal atresia 3 cm from anterior nares Wide mandible and lips
“
Ears low, small, curled
Trifid tongue Ears low, dimpled lobules
...
Case, Sex, Age at death Family history Pregnancy
Face
6x5x4cm
basisphenoid
38 wk, 3.3 kg 5.5 x 2.5 x 1.5 cm
and length of hard palate one tag to a I cm projection mid lower gum
38 wk
To nasal septum, between cleft palate Bar of tissue from roof to floor of mouth Optic nerves 17 mm apart (normal 10 mm)
... ...
Double ” mandible and lower lip Bifid tongue
...
Wide cribriform plate Mammillary bodies 1 cm apart
35 cm Wide sutures (I cm) Wide cribriform plate Wide tuber cinereum
Pituitaries
2 pituitaries each with stalk
2 pituitaries each with stalk
2 pituitaries each with stalk Pharyngeal pituitaries
Corpus callosum
Absent Anterior and intermediate commissures and septum lucidum also absent. Fornix present.
Absent Anterior and intermediate commissures and septum lucidum also absent. Fornix. absent.
Thyroid and larynx
Small isthmus
Absent isthmus
Head circumference Cranium
35.6 cm
...
...
...
(Absent olfactory tracts)
Notched epiglottis
The absent corpus callosum (fig. 6) was associated in case 1 with a small posterior cranial fossa, low tentorium and mildly hypoplastic cerebellum (weight of cerebellum and brain-stem 14.4 g) but the vermis was present. The olfactory bulbs and uncal gyri were present in both patients.
DISCUSSION These cases are very similar to the one described by Morton (1957), showing epignathi, duplication of the pituitary and abnormal stomatodaeal structures. An additional feature of the present cases is the absence of corpus callosum and of midline commissures in both brains. Morton’s case differed in that the olfactory tracts were absent and the brain was said to be otherwise normal though the corpus callosum was not mentioned. Other features in the present cases were wide cribriform plates, a central groove in the saggital plane of the nose, unilateral choanal atresia and low ears. Morton found accessory pharyngeal adenohypophyseal masses, which were not noted in our first case but could have been missed. In case 2 a small focus of probable adenohypophysis was found in one of several blocks from the root of the epignathus.
DOUBLE PITUITARY
163
The epignathi in our cases are regarded as maldevelopmental over-growths rather than true teratomas, as although tissues from all three embryonic layers were present, all were normal to the oro-nasal region, and not necessarily neoplastic. Morton interpreted the widened lips and mandible, supernumerary central incisor teeth, bifid anterior half of tongue and bar of tissue connecting roof and floor of mouth, as duplication of the stomatodaeal structures. The presence in our cases of tooth germs in the midline near the posterior part of the epignathi, at the level of molar teeth, tends to support Morton’s theory of at least partial duplication of the stomatodeum. He considered that this could not have been caused simply by failure of union of embryonic masses, but must have resulted from duplication of the prochordal plate and anterior end of notochordal process at about the 15th to 16th day, with formation of two Rathke’s pouches. The mother of his patient had uterine bleeding at this stage of pregnancy. Double pituitary may evidently occur as an isolated anomaly, as Ahlfeld (1880) and Bainborough and Hase (1958) did not mention epignathus or absent corpus callosum in their patients, and in a case of double pituitary in a dog, the corpus callosum can be seen in the illustrations and epignathus was not mentioned (Cozens and Mawdesley-Thomas, 1966). Double pituitary alone is compatible with life, as the example of Bainborough and Hase (1958) was an incidental finding in a 26-yr-old woman with a broad forehead dying in Addisonian crisis with tuberculosis of both adrenal glands. It is possible that the triad of double pituitary, absent corpus callosum and epignathus need not be fatal, as each of these conditions on its own is compatible with life. Not only has double pituitary been found in an adult with no relevant symptoms (Bainborough and Hase, 1958) but absence of the corpus callosum may also be an incidental necropsy finding (Loeser and Alvord, 1968). Finally, large epignathi are surgically resectable. Successful excision and later reconstructive surgery has been described by Rintala and Ranta (1974) in a neonate with large epignathi of upper and lower jaws similar to those in our case 2. The child also had a bipartite tongue and radiological deformity of the sphenoid bone. On recent examination there is hypertelorism, and the pituitary cannot be visualised radiologically. The corpus callosum and septum pelucidum in a pneumoencephalogram appear normal. The patient has developed spastic attacks, a somewhat abnormal electro-encephalogram and retardation, perhaps a result of cardiac arrest during surgery (Rintala, personal communication 1975). The possibility of double pituitary cannot yet be excluded in this living 3-yr-old child. SUMMARY Two infants from unrelated families died on the 1st day of life with epignathus, duplication of the entire pituitary, infundibulum and sella, and widening or separation of midline structures of the head including absent corpus callosum. We suggest that some infants surviving surgery for large epignathi may have relatively symptomless absent corpus callosum or double pituitary.
164
PATRICIA M. BALE AND R. D. K. REYE
REFERENCES F. 1880. Die Missbildungen des Menschen, Grunow, Leipzig, part 1, p. 73. AHLFELD, BAINBOROUGH, A. R., AND HASE,S. 1958. Double hypophysis. Canad. Med. Ass. J., 79,912. L. E. 1966. Reduplication of the pituitary in a dog. COZENS, D., AND MAWDESLEY-THOMAS, Veterinary Record, 78, 474. LOESER, J. D., AND ALVORD, E. C. JR1968. Agenesis of the corpus callosum. Bruin,91,553. MORTON, W. R. M. 1957. Duplication of the pituitary and stomatodaeal structures in a 38-week male infant. Arch. D. Childh., 32, 135. RINTALA, A. E. 1975. Personal communication. RINTALA, A., AND RANTA,R. 1974. Separate epignathi of the mandible and the nasopharynx with cleft palate: case report. Brit. J. Plastic Surg., 27, 103.
BALEA N D REYE
PLATE LXV DOUBLE PITUITARY
FIG. 1.-Case 2, showing hypertelorism, deep wide philtrum of upper lip, and epignathus which attaches to upper alveolar margin.
FIG.2.-Case
FIG. 3.-Case 1. Epignathus bisected longitudinally, showing adipose tissue in distal third and mucous cysts below centre.
1. Base of skull showing wide cribriform plate above, and two pituitaries, each with stalk, one on either side of a midline bony bar.
BALEA N D REYE
PLATELXVl DOUBLE PITUITAKY
FIG.4.
FIG.5.
FIG.4.-Case 2. Mouth, showing the main epignathus reflected upwards and the lower lip downwards, to reveal a conical projection from the lower alveolar margin, and a wide frenulum. The cord ioining upper to lower epignathi has been cut and is not shown, but the two other projections from the upper epignathus are seen. The tongue is not seen. FIG.5.-Case
2. The tongue, with trifid tip.
FIG.6.-Case 2. Coronal slices of cerebrum to show the absent corpus callosuni, with Probst's bundle on each side. Septum lucidum, pillars of the fornix and anterior and intermediate commissures are also absent.
FIG.6.
PLATES LXV AND LXVI DUPLICATION of the pituitary is a rare lesion, reports of only three human cases having been found (Ahlfeld, 1880; Morton, 1957; Bainborough and Hase, 1958). This report describes two additional cases discovered at necropsy in the last 5 yr, in neonates from unrelated families. Each infant had a combination of double pituitary, epignathus and anomalies of the head characterised by widening or separation of midline structures. CASEREPORTS The pertinent features are listed in the table. Neither mother remembered any drug or unusual food taken during the first 2 mth of pregnancy. In case 1 the mother was hospitalised at 7 mth for premature rupture of the membranes. Later she described intermittent loss of brownish and clear fluid per vaginum from the 6th wk of gestation. Other features of the pregnancy were poor weight gain, vomiting, colds, and poor foetal movements. The mother of case 2 was well throughout pregnancy, with no haemorrhage, infection or other illness. At birth, each infant had a large skin covered tongue-like mass of tissue projecting from the hard palate out through the mouth (fig. 1). Both infants were cyanosed, and displayed decreased limb tone. In case 2 the rooting reflex was absent and the fists were unusually clenched, with overlapping fingers. Each child died in respiratory arrest during the 1st day of life. Pathology At necropsy each infant had pulmonary interstitial haemorrhage. The lungs were normally lobed and all other organs and tissues below the neck, including the adrenal glands, were normal. The anomalies were confined to the head and neck and are listed in the table. In each case the two hypophyses lay side by side in separate fossae (fig. 2), separated by a central bar of bone and cartilage about 0.5 cm wide. The pituitary glands were not weighed before fixation but each appeared about 3 to average size, so that the total amount of tissue may have been more than normal for each infant. Microscopically each had an anterior and posterior part and stalk. In each infant the palatine epignathus was large, considerably reducing the oral and nasopharyngeal cavities. In case 1 it was a single polypoid mass (fig. 3). In case 2, the main epignathus had smaller projections from its base (fig. 4), the smallest containing a tooth and the two larger being soft and pedunculated. One of the latter had a second attachment to the midline of the lower alveolar margin, where there was a conical elevated mass, 0.7 cm diameter, containing three tooth buds. Microscopically the palatine epignathi had a covering of skin with many pilo-sebaceous follicles. Each had a fibro-adipose core containing a little striated muscle toward the base.
+
~~
Received 30 Dec. 1975; accepted 13 Feb. 1976. J. PATH.-VOL.
120 (1976)
161
L
PATRICIA M. BALE AND R. D . K. REYE
162
Closer to the base there were sero-mucinous glands, cysts lined by ciliated epithelium, cartilage, bone, small islands of adamantine epithelium, cavities lined by ameloblasts and stratum intermedium of tooth germs. In case 1 there were also foci of melanin close to cuboidal epithelium. The most posterior part of the mass in this case extended into the basisphenoid which was displaced upwards and backwards. In case 2 the anterior third of the tongue was tripartite (fig. 5).
TABLE Clinical and pathological features of infants with epignathi and double pituitaries Case 2. 1st child H ydramnios
M.
24 hr
Morton’s case. M. 3 days 1st child Uterine bleeding 1st mth
Gestation, birth weight
Case I. F. 6 hr 5 siblings alive and well Loss of amniotic fluid since 6 weeks: pregnant 37 wk. large baby ”
Pathological features Epignathus: Size Attachments
To upper alveolar ridge and
To wide philtrum of uppec lip
Hypertelorism
Hypertelorism 3.6 cm Optic nerves 17 mm apart
Right choanal atresia 1 cm from anterior nares
...
Central nasal groove Right choanal atresia 3 cm from anterior nares Wide mandible and lips
“
Ears low, small, curled
Trifid tongue Ears low, dimpled lobules
...
Case, Sex, Age at death Family history Pregnancy
Face
6x5x4cm
basisphenoid
38 wk, 3.3 kg 5.5 x 2.5 x 1.5 cm
and length of hard palate one tag to a I cm projection mid lower gum
38 wk
To nasal septum, between cleft palate Bar of tissue from roof to floor of mouth Optic nerves 17 mm apart (normal 10 mm)
... ...
Double ” mandible and lower lip Bifid tongue
...
Wide cribriform plate Mammillary bodies 1 cm apart
35 cm Wide sutures (I cm) Wide cribriform plate Wide tuber cinereum
Pituitaries
2 pituitaries each with stalk
2 pituitaries each with stalk
2 pituitaries each with stalk Pharyngeal pituitaries
Corpus callosum
Absent Anterior and intermediate commissures and septum lucidum also absent. Fornix present.
Absent Anterior and intermediate commissures and septum lucidum also absent. Fornix. absent.
Thyroid and larynx
Small isthmus
Absent isthmus
Head circumference Cranium
35.6 cm
...
...
...
(Absent olfactory tracts)
Notched epiglottis
The absent corpus callosum (fig. 6) was associated in case 1 with a small posterior cranial fossa, low tentorium and mildly hypoplastic cerebellum (weight of cerebellum and brain-stem 14.4 g) but the vermis was present. The olfactory bulbs and uncal gyri were present in both patients.
DISCUSSION These cases are very similar to the one described by Morton (1957), showing epignathi, duplication of the pituitary and abnormal stomatodaeal structures. An additional feature of the present cases is the absence of corpus callosum and of midline commissures in both brains. Morton’s case differed in that the olfactory tracts were absent and the brain was said to be otherwise normal though the corpus callosum was not mentioned. Other features in the present cases were wide cribriform plates, a central groove in the saggital plane of the nose, unilateral choanal atresia and low ears. Morton found accessory pharyngeal adenohypophyseal masses, which were not noted in our first case but could have been missed. In case 2 a small focus of probable adenohypophysis was found in one of several blocks from the root of the epignathus.
DOUBLE PITUITARY
163
The epignathi in our cases are regarded as maldevelopmental over-growths rather than true teratomas, as although tissues from all three embryonic layers were present, all were normal to the oro-nasal region, and not necessarily neoplastic. Morton interpreted the widened lips and mandible, supernumerary central incisor teeth, bifid anterior half of tongue and bar of tissue connecting roof and floor of mouth, as duplication of the stomatodaeal structures. The presence in our cases of tooth germs in the midline near the posterior part of the epignathi, at the level of molar teeth, tends to support Morton’s theory of at least partial duplication of the stomatodeum. He considered that this could not have been caused simply by failure of union of embryonic masses, but must have resulted from duplication of the prochordal plate and anterior end of notochordal process at about the 15th to 16th day, with formation of two Rathke’s pouches. The mother of his patient had uterine bleeding at this stage of pregnancy. Double pituitary may evidently occur as an isolated anomaly, as Ahlfeld (1880) and Bainborough and Hase (1958) did not mention epignathus or absent corpus callosum in their patients, and in a case of double pituitary in a dog, the corpus callosum can be seen in the illustrations and epignathus was not mentioned (Cozens and Mawdesley-Thomas, 1966). Double pituitary alone is compatible with life, as the example of Bainborough and Hase (1958) was an incidental finding in a 26-yr-old woman with a broad forehead dying in Addisonian crisis with tuberculosis of both adrenal glands. It is possible that the triad of double pituitary, absent corpus callosum and epignathus need not be fatal, as each of these conditions on its own is compatible with life. Not only has double pituitary been found in an adult with no relevant symptoms (Bainborough and Hase, 1958) but absence of the corpus callosum may also be an incidental necropsy finding (Loeser and Alvord, 1968). Finally, large epignathi are surgically resectable. Successful excision and later reconstructive surgery has been described by Rintala and Ranta (1974) in a neonate with large epignathi of upper and lower jaws similar to those in our case 2. The child also had a bipartite tongue and radiological deformity of the sphenoid bone. On recent examination there is hypertelorism, and the pituitary cannot be visualised radiologically. The corpus callosum and septum pelucidum in a pneumoencephalogram appear normal. The patient has developed spastic attacks, a somewhat abnormal electro-encephalogram and retardation, perhaps a result of cardiac arrest during surgery (Rintala, personal communication 1975). The possibility of double pituitary cannot yet be excluded in this living 3-yr-old child. SUMMARY Two infants from unrelated families died on the 1st day of life with epignathus, duplication of the entire pituitary, infundibulum and sella, and widening or separation of midline structures of the head including absent corpus callosum. We suggest that some infants surviving surgery for large epignathi may have relatively symptomless absent corpus callosum or double pituitary.
164
PATRICIA M. BALE AND R. D. K. REYE
REFERENCES F. 1880. Die Missbildungen des Menschen, Grunow, Leipzig, part 1, p. 73. AHLFELD, BAINBOROUGH, A. R., AND HASE,S. 1958. Double hypophysis. Canad. Med. Ass. J., 79,912. L. E. 1966. Reduplication of the pituitary in a dog. COZENS, D., AND MAWDESLEY-THOMAS, Veterinary Record, 78, 474. LOESER, J. D., AND ALVORD, E. C. JR1968. Agenesis of the corpus callosum. Bruin,91,553. MORTON, W. R. M. 1957. Duplication of the pituitary and stomatodaeal structures in a 38-week male infant. Arch. D. Childh., 32, 135. RINTALA, A. E. 1975. Personal communication. RINTALA, A., AND RANTA,R. 1974. Separate epignathi of the mandible and the nasopharynx with cleft palate: case report. Brit. J. Plastic Surg., 27, 103.
BALEA N D REYE
PLATE LXV DOUBLE PITUITARY
FIG. 1.-Case 2, showing hypertelorism, deep wide philtrum of upper lip, and epignathus which attaches to upper alveolar margin.
FIG.2.-Case
FIG. 3.-Case 1. Epignathus bisected longitudinally, showing adipose tissue in distal third and mucous cysts below centre.
1. Base of skull showing wide cribriform plate above, and two pituitaries, each with stalk, one on either side of a midline bony bar.
BALEA N D REYE
PLATELXVl DOUBLE PITUITAKY
FIG.4.
FIG.5.
FIG.4.-Case 2. Mouth, showing the main epignathus reflected upwards and the lower lip downwards, to reveal a conical projection from the lower alveolar margin, and a wide frenulum. The cord ioining upper to lower epignathi has been cut and is not shown, but the two other projections from the upper epignathus are seen. The tongue is not seen. FIG.5.-Case
2. The tongue, with trifid tip.
FIG.6.-Case 2. Coronal slices of cerebrum to show the absent corpus callosuni, with Probst's bundle on each side. Septum lucidum, pillars of the fornix and anterior and intermediate commissures are also absent.
FIG.6.
