Congenital Abnormalities of the Sellar and Parasellar Regions

1. Congenital Abnormalities of the Sellar and Parasellar Regions Division of Neuroradiology Department of Radiology University of North Carolina at Chapel Hill

2. Purpose • To present the imaging appearances of congenital diseases arising in the sellar and suprasellar regions • To demonstrate how the embryological correlations of the pituitary gland with the adjacent structures facilitate the correct interpretation of sellar and parasellar congenital abnormalities

3. Embryology The pituitary gland consists of two embryological and functionally distinct divisions: • Adenohypophysis (pars anterior, pars intermedia and pars tuberalis) • Neurohypophysis (median eminence, infundibular stem and pars posterior)

4. Embryology • Development of the pituitary gland begins in the 4th week of life with inductive signals from the diencephalon initiating the formation of Rathke's pouch • Rathke’s pouch has been considered as a diverticulum of the epithelium lining of the stomodeum but recent evidence indicates it is a derivative of neural ectoderm from the anterior neural ridge

5. Embryology • By the 8th week of life, the primitive adenohypophysis separates from the oral cavity and primitive pituitary cells undergo rapid proliferation with differentiation into specialized hormone lines • Adenohypophysis consists of: pars anterior or distalis, pars intermedia (rudimentary in humans) and pars tuberalis (along the stalk)

6. Embryology • Neurohypophysis originates from a neuroectodermal evagination of tissue in the diencephalic floor which grows to the stomodeal roof. An extension of the 3rd ventricle (the infundibular recess), persists in the neuroectodermal diverticulum of the forebrain • Neurohypophysis is divided into median eminence, infundibular stem and pars posterior

7. Embryology Figure 1A. 6-week embryo shows the dual origin of the gland from Rathke's pouch and from diencephalic floor (infundibulum) (used with permission). Sadler, T., Susceptible periods during embryogenesis of the heart and endocrine glands. Environ Health Perspect, 2000; 108: 555

8. Embryology Figure 1B. Pituitary at 11 weeks of life. The gland is formed and a cleft persists between pars intermedia and pars anterior. The craniopharyngeal canal closes and occasionally the adenohypophysis remains in the nasopharynx (used with permission). Sadler, T., Susceptible periods during embryogenesis of the heart and endocrine glands. Environ Health Perspect, 2000; 108: 555

9. Embryology Figure 1C. Pituitary gland at 16 weeks of life. The gland acquires an ‘adult’ configuration and the craniopharyngeal canal closes (used with permission). Sadler, T., Susceptible periods during embryogenesis of the heart and endocrine glands. Environ Health Perspect, 2000; 108: 555

10. Embryology • Regulation of pituitary embryogenesis involves a cascade of genes expressed during the 4th week of life in the diencephalon initiating formation of Rathke‘s pouch and later a combined expression of multiple genes throughout the stomodeal epithelium required for morphogenesis of the pouch and proliferation and differentiation of hormone specific cells

11. Newborn Pituitary Gland • In neonates the pars anterior and pars posterior are both uniformly bright on the T1 images • At birth the pituitary gland may also be globular in shape • This appearance likely reflects the hormonal surges that occur perinatally • The signal intensity and size of the pituitary gland becomes similar to older children’s appearance by two months of age

12. Newborn Pituitary Gland Figure 2. Sagittal non-contrast T1 image shows pituitary gland at 5 days of age. Until 2 months of age, the pituitary gland is uniformly bright

13. Abnormal Separation of Ectoderm and Neuroectoderm

14. Transsphenoidal Encephalocele • It is an “occult” encephalocele characterized by a bone defect in ethmoid or sphenoid bone • Usually diagnosed later than other forms of encephaloceles • Hypothalamus, pituitary gland, 3rd ventricle, optic nerves and chiasm may be located in the encephalocele sac • Typical clinical presentation: nasal obstruction, difficulty feeding and failure to thrive

15. Transsphenoidal Encephalocele A B Figure 3. Sagittal post-Gd T1 (A) and T2 (B) images show herniation of a CSF-filled sac (white arrows) through a bone defect in the body of the sphenoid. The neurohypophysis (black arrow) is also noted. Agenesis of the corpus callosum (C/o of Dr. A. Rossi).

16. Congenital AbnormalitiesDevelopment of the Hypothalamo-Pituitary Axis

17. Hypoplastic Pituitary Gland • Pituitary hypoplasia is a congenital disorder involving the adenohypophysis, neurohypophysis and often the stalk • Patients with pituitary hypoplasia survive with hormonal replacement but pituitary aplasia is incompatible with life • Pituitary dwarfism due to deficiency of growth hormone is a common clinical presentation

18. Hypoplastic Pituitary Gland A B Figure 4. Coronal (A) and sagittal (B) T1 images show small pituitary gland and stalk.

19. Pituitary and Hypothalamic Hypoplasia Figure 5. Sagittal T1 image shows hypoplastic pituitary gland (black arrow), hypothalamus and optic chiasm (white arrow).

20. Ectopic Neurohypophysis • It is characterized by a “bright spot” along median eminence of hypothalamus or along stalk which may be tiny or absent • Adenohypophysis and sella may be small • Frequently associated with growth hormone deficiency (pituitary dwarfism) • Associated adenohypophysis dysfunction may be related to absent infundibulum • Associated midline CNS abnormalities: (septo-optic dysplasia, lobar holoprosencephaly, olfactory bulb anomalies)

21. Ectopic Neurohypophysis A B Figure 6. Pre- (A) and post-Gd (B) sagittal T1 images show “bright spot” in tuber cinereum of the hypothalamus

22. Ectopic Neurohypophysis with Thin Stalk Figure 7. Sagittal T1 image shows ectopic neurohypophysis (black arrow) in tuber cinereum and hypoplastic pituitary stalk (white arrow).

23. Duplicated Pituitary Gland • Rare congenital disorder due to duplication of primitive stomodeal structures • Two sellae, lateral stalks and glands are present • Mammillary bodies are fused with tuber cinereum, thickening of 3rd ventricle floor (hamartoma?) • Basilar artery shows lack of longitudinal fusion • Anterior 3rd ventricle may be duplicated • Possible association with CN I and II hypoplasia • Pituitary-related symptoms are rare • Associations: craniofacial clefting, oral midline tumors, dysgenesis of corpus callosum, Dandy-Walker spectrum

24. Duplicated Pituitary Gland A B Figure 8. Post–Gd coronal (A) and axial (B) T1 images show two stalks (arrows), pituitary glands and sellae.

25. Tuber Cinereum Hamartoma • It is a congenital malformation characterized by heterotopia of gray matter in the region of the mammillary bodies or tuber cinereum • Round non-enhancing pedunculated or sessile mass, contiguous with tuber cinereum; isointense to gray matter on T1 and slightly T2 bright • Isosexual precocious puberty due to LHRH and/or gelastic seizures • Common associations: congenital facial/cerebral midline abnormalities, visceral anomalies, digital malformations • Differential diagnosis: hypothalamic astrocytoma, hystiocytosis, germ cell tumor

26. Tuber Cinereum Hamartoma A B C Figure 9. Post–Gd T1 (A), T2 (B) sagittal, and post-Gd T1 axial (C) images. A mass is seen between the infundibulum and mammillary bodies, hyperintense to gray matter on T2. The mass appears similar to the brain parenchyma on T1 and shows no enhancement (courtesy of Dr. A. Osborn).

27. Tuber Cinereum Hamartoma A B Figure 10. Post–Gd sagittal T1 (A) and T2(B)images show a large tuber cinereum hamartoma that is T1 isointense and T2 bright (courtesy of Dr. A. Osborn).

28. Optic Infundibular Hypoplasia • Disorder of midline prosencephalic development (6th weeks of life) • Overlaps with septo-optic dysplasia but septum pellucidum is present • Optic chiasm/optic nerves are hypoplastic • Pituitary hypoplasia, thin stalk, ectopic neurohypophysis may be present

29. Optic Infundibular Hypoplasia A B C Figure 11. Sagittal T1 (A), coronal T2 (B) and T1 (C). A: Hypoplastic pituitary gland, stalk, optic chiasm and hypothalamus. B: Hypoplastic optic nerves. C: Ectopic neurohypophysis (arrow).

30. Congenital DisordersDevelopment of the Adenohypophysis

31. Persistent Craniopharyngeal Canal A B Figure 12. Sagittal T1 (A) and coronal T1 (B) images. The craniopharyngeal canal is patent. The adenohypophysis is within the canal (arrow) and extends into the nasopharynx (arrowhead) (C/o of Dr. M. Michel)

32. Persistent Craniopharyngeal Canal A B Figure 13. Sagittal T1 MR (A) and axial CT (B) images. A: The adenohypophysis (arrow) is in a persistent craniopharyngeal canal. B: Shows persistence of a craniopharingeal canal (arrowhead) (C/o Dr. K. Marsot-Dupuch).

33. Rathke’s Cleft Cyst • Non-neoplastic cyst arising from remnants of squamous epithelium of Rathke’s cleft • Non-enhancing non-calcified intra or supra-suprasellar cyst • Variable cyst content: mucous (T1 bright) serous (T1 dark) and possible blood products (T2 dark)

34. Rathke’s Cleft Cyst A B Figure 14. Pre- (A) and post-Gd (B) T1 weighted images show an intrasellar mass (black arrow) that is bright compared to normal pituitary gland (white arrow). Location (middle 1/3 of gland) and signal intensity strongly suggest a Rathke’s cleft cyst

35. Rathke’s Cleft Cyst Figure 15. Axial T2 image shows intrasellar mass with fluid level (arrow) a typical feature of Rathke’s cleft cyst; the differential diagnosis includes a hemorrhagic pituitary adenoma.

36. Craniopharyngioma • Benign dysontogenetic epithelial tumor arising from cell remnants of Rathke’s pouch • Complex mass, with inhomogeneous enhancement of solid components • Calcifications: very common • T1 signal varies with cyst contents • Bimodal age distribution (5-15 y; > 50)

37. Craniopharyngioma A B Figure 16. Sagittal post-Gd T1 (A) and coronal T2 (B) images show an enhancing suprasellar mass (arrows) with complex appearance.

38. Craniopharyngioma A B Figure 17. Coronal (A) and sagittal (B) post-Gd T1 images show a suprasellar cystic mass (white arrows). A solid enhancing nodule is noted (black arrow) and the rim also enhances (small white arrows).

39. Pars Intermedia Cyst • These cysts arise in the pars intermedia of the adenohypophysis which is rudimentary in humans • They are usually less than 3 mm in diameter • They are located between the pars anterior and pars posterior

40. Pars Intermedia Cyst A C B Figure 18. Sagittal pre- (A) and post-Gd (B) T1 images and (C) axial T2 image show nonenhancing cyst (arrows) between the pars anterior and pars posterior.

41. Miscellaneous

42. Dermoid • Intracranial dermoids are ectodermal inclusion cysts that originate from midline inclusion of surface ectoderm during the 3rd-5th weeks of life at the time of closure of the neural tube • Common intracranial locations: frontonasal, sellar and parasellar regions, posterior fossa and ventricles • Dermoids are T1 bright due to presence of lipids and cholesterols and may rupture with spreading of fat droplets along the CSF containing spaces resulting in aseptic meningitis

43. Dermoid Figure 19. Sagittal T1 image shows a well-defined bright midline suprasellar mass (arrows).

44. Teratoma • Teratomas are composed of tissues from the three embryonic germ layers • The majority of teratomas are supratentorial in the region of the optic chiasm and in the pineal gland • They are midline tumors containing fat, soft tissue and calcifications • Classified as mature, immature and malignant • Occasionally they present in newborns as holocranial tumors

45. Teratoma A B Figure 20. Sagittal non-contrast T1 (A) and axial fat-suppressed T2 (B) images show a heterogeneous suprasellar mass (arrows) due to presence of calcifications and fat.

46. References Barkovich, A., Pediatric Neuroimaging. 3rd edition ed. 2000, New York: Raven Press. Chen, C., D. David, and A. Hanieh, Morning glory syndrome and basal encephalocele. Childs Nerv Syst, 2004(20): p. 87-90. Chong, B. and T. Newton, Hypothalamic and pituitary pathology. The Radiology Clinics of North America, 1993. 31(5): p. 1147-1183. Dietrich, R., et al., Normal MR appearance of the pituitary gland in the first two years of life. AJNR, 1995. 16: p. 1413-1419. Gray, H., Gray’s Anatomy. 37th edition ed. 1989, New York, Churchill Livingstone. Osborn, A., Diagnostic Imaging. Brain. 2004, Salt Lake City: Amirsys. Sadler, T., Susceptible periods during embryogenesis of the heart and endocrine glands. Environ Health Perspect., 2000. 108: p. 555-561. Shroff, M., et al., Basilar artery duplication associated with pituitary duplication: a new finding. AJNR, 2003(24): p. 956-961.