Craniopharyngeal Canal and Its Spectrum of Pathology

Discussion

The CPC is a rare, well-corticated defect of the midline sphenoid body extending from the floor of the sella turcica to the roof of the nasopharynx.¹⁴ To our knowledge, our study is the largest series of CPCs since the advent of cross-sectional imaging. On the basis of quantitative and qualitative features, CPCs can be classified into 3 types: small incidental canals (type 1); medium-sized canals with ectopic pituitary tissue (type 2); and large canals containing cephaloceles (type 3A), tumors (type 3B), or both (type 3C). Identification and classification of CPCs have prognostic and therapeutic implications. Type 1 small incidental canals are benign but may be found in patients with other craniofacial or neural congenital anomalies. Type 2 medium-sized canals and type 3A large canals with cephaloceles are associated with ectopic adenohypophysis and possible pituitary dysfunction. Type 3 large CPCs containing tumors and/or cephaloceles often contain ectopic pituitary tissue within the nasopharynx; thus, care should be taken during surgery to avoid iatrogenic hypopituitarism and/or CSF leak. Compared with the previous division of small benign CPCs¹⁴ or large CPCs with associated nasopharyngeal masses and craniofacial malformations,⁴ our classification provides a more nuanced characterization of the CPC with the inclusion of medium-sized type 2 canals and subdivision of large type 3 canals.

From our data, a nasopharyngeal mass should raise the suspicion for a type 3 CPC, and pituitary dysfunction may suggest a type 2 or 3 CPC. CT is sufficient to characterize type 1 CPCs, unless there is suspicion for associated craniofacial congenital anomalies. MR imaging, however, is the best for evaluation of ectopic adenohypophysis in type 2 CPCs and cephalocele and/or tumor in type 3 CPCs due to its superior contrast resolution.

The CPC is postulated to arise from an error in the normal development of the pituitary gland (Fig 5). The pituitary gland originates from a single embryologic neuroectodermal adherence formed by fusion of the roof of the stomodeum (adenohypophysis anlage) and floor of the diencephalon (neurohypophysis anlage).¹⁶ At approximately the fourth week of gestation, the forebrain grows rostrocaudally and mesoderm proliferates ventrolaterally around the neuroectodermal adherence, causing the adherence to migrate dorsally and form an invagination, called the adenohypophyseal (Rathke) pouch.^16,17 During the fifth and sixth weeks of gestation, the adenohypophyseal pouch elongates, forming a narrow stalk between it and the stomodeum.¹⁸ At approximately the sixth to seventh weeks of gestation, the cartilaginous sphenoid skull base develops, obliterating this adenohypophyseal stalk.^18,19 The sphenoid cartilage is composed of 2 paired presphenoid and 2 paired postsphenoid cartilages. The presphenoid cartilages fuse and later form the anterior sphenoid body, and the postsphenoid cartilages fuse to form the basisphenoid cartilage, which later becomes the posterior sphenoid body and sella turcica.²⁰ Defective fusion of the postsphenoid cartilages results in nonobliteration of the stalk between the adenohypophyseal pouch and the stomodeum and a residual canal extending from the sella turcica to the pharynx, named the CPC.

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Fig 5.

Embryology of the normal pituitary gland. A, At 3–4 weeks of gestation, the neuroectodermal adherence develops at a point of contact between the diencephalon (neurohypophyseal anlage) and roof of the stomodeum (adenohypophyseal anlage). B, At 4–5 weeks, the neuroectodermal adherence migrates dorsally forming the adenohypophyseal (Rathke) pouch, while the diencephalon migrates dorsal to the stomodeum to assume the position of the future neurohypophysis. The adenohypophyseal pouch elongates forming a stalk at its ventral aspect at 5–6 weeks (not shown). C, At 6–7 weeks, the postsphenoid cartilage develops, which results in obliteration of the adenohypophyseal stalk. D, In this illustration of the infant pituitary gland and sella, a dotted line traces the path of the potential CPC, which is believed to arise from nonobliteration of the adenohypophyseal stalk. The spheno-occipital synchondrosis (illustrated in blue) does not close until approximately age 16 years and mimics the CPC in children. Graphic illustrations used with permission from Amirsys.

Two case series from the mid-20th century proposed that the CPC is merely a remnant of a vascular channel. Arey¹⁴ came to this conclusion when, after examining the sphenoid bone of 17 embryonic specimens for persistence of a CPC containing pituitary tissue, he only found channels for blood vessels. Lowman et al²¹ radiographically identified 2 complete CPCs in 400 neonate sphenoid bone specimens, but when he histologically analyzed the specimens, he found only vascular channels without evidence of “squamous or ciliated epithelium.” Both authors erroneously concluded that the absence of evidence for the pituitary origin of the CPC suggests that it does not arise from the embryologic pituitary.

Subsequent studies make a strong case for the pituitary origin. Kjaer and Fischer-Hansen¹ used modern immunohistochemistry to demonstrate adenohypophyseal tissue within the CPC of 6 fetuses with holoprosencephaly or anencephaly. Moreover, Kjaer and Fischer-Hansen noted that the postsphenoid bone is nearly always malformed in holoprosencephaly and invariably malformed in anencephaly, supporting an association between malformation of the cartilaginous sphenoid skull base and persistence of the CPC. Hori et al³ evaluated nasopharyngeal pituitary tissue of fetal specimens and demonstrated adenohypophyseal tissue in a CPC. These authors also performed a meta-analysis showing that 24 of 27 ectopic pituitary adenomas in the literature occurred in either the sphenoid sinus or the clivus. Hori et al³ believed this evidence for the persistence of pharyngeal pituitary tissue into adulthood; however, one could more convincingly propose, given the nonaggressive nature of pituitary adenomas, that the bony location of these ectopic adenomas supports pituitary tissue within a CPC rather than in the pharynx. The same conclusion can be made from the craniopharyngioma and adenomas in our series and case reports of ectopic intrasphenoid pituitary neoplasms in the literature.^2,12,13

The characteristics of our type 1 small incidental CPCs are similar to those of the meta-analysis performed by Arey.¹⁴ Of 8338 skulls in 11 studies, 35 CPCs were identified, yielding a prevalence of 0.42%. Each canal extended from the sella turcica to the basal surface of the sphenoid bone, was surrounded by “compact” bone, and measured < 1.5 mm. These features are comparable to our type 1 canals, which were delimited by cortical bone and measured 0.7–1.1 mm in AP diameter. Small CPCs were first systematically evaluated by Landzert (who coined the term craniopharyngeal canal) in 1868. He identified a complete bony sphenoid canal the width of a bristle in 10 (10%) of 100 anatomic specimens from infants up to 8 months old.¹⁴ A study in 1903 showed similar prevalence (18/200) in infants younger than 3 months old.¹⁴ Comparing these data with Arey's frequency of 0.42% raises the question of whether some CPCs obliterate in early childhood. To our knowledge, no studies have investigated this matter.

An in vivo type 2 medium-sized CPC with ectopic pituitary tissue was first reported in 1949 by Wilkerson and Cayce,²² in which a 19-year-old woman had a 3–5 mm diameter canal at the base of the sphenoid discovered during choanal atresia surgery. The canal was radiographed during extensive probing, and the patient subsequently experienced hypothyroidism and secondary amenorrhea. This development is not surprising given the presence of ectopic adenohypophysis in all type 2 CPCs in our series. Two recent case reports discuss medium-sized CPCs with ectopic pituitary tissue. One had an associated hypothalamic hamartoma, measured > 1.5 mm in diameter (exact measurement not provided), and had inferior ectopic adenohypophysis on MR imaging.¹¹ Currarino et al⁴ reported the other medium-sized CPC in their article on “large craniopharyngeal canals.” One of their 2 cases described a male infant with a 3-mm diameter CPC containing mildly displaced adenohypophysis (as demonstrated in the figures) but no pituitary dysfunction. This patient also had congenital anomalies, including cleft lip and palate, hypertelorism, and orbital hypoplasia. Type 2 CPCs are important to recognize not only for their apparent association with congenital abnormalities but also for the detection of related pituitary dysfunction. In our series, 2 of 7 type 2 CPCs had pituitary dysfunction. We postulate the cause to be ectopic pituitary tissue, as our type 3A large CPCs with cephaloceles and more displaced pituitary tissue had a higher rate of pituitary deficiency (4/6) than the type 2 canals.

A case of type 3A large CPC containing cephalocele and ectopic pituitary tissue was first described by Klinkosch in 1764, in which a neonate had a 5-mm wide passage extending through the middle of the sphenoid that contained prolapsed dura and an ectopic pituitary gland.¹⁴ Recent case reports of large CPCs with cephaloceles containing ectopic pituitary tissue describe canals measuring 10–13 mm in diameter.^8,9,23,24 One patient presented with recurrent meningitis (as in our series), and 2 patients had colobomas, believed to result from stretching of the optic nerves into the cephalocele.^23⇓–25 Three of 4 large CPCs in the literature that were identified before surgery had pituitary dysfunction, reflecting our 75% prevalence in large canals.^9,23 Hughes et al⁸ described 2 patients with large CPCs and cephaloceles who presented with suspected iatrogenic hypopituitarism after resection of nasopharyngeal “masses.” This finding underscores the importance of recognizing cephaloceles and ectopic pituitary tissue in type 3A CPCs to avoid CSF leak and/or pituitary resection during nasopharyngeal mass surgery.

Fewer than 25 cases of ectopic pituitary adenomas are reported within the sphenoid sinus, presumed to originate within type 3B CPCs. Most of these lesions presented due to mass effect (as in 1 of our 2 cases) or ectopic hormone secretion.^2,26 Reports of infrasellar craniopharyngiomas are rarer, with at least 5 reported in the modern literature.^{13,27⇓⇓–30} An infrasellar location separate from the sella turcica is important to recognize because it indicates that the craniopharyngioma originated within a type 3B CPC rather than invading the skull base inferiorly from a sellar origin.

Dermoids, teratomas, and gliomas are uncommon lesions of the nasopharynx.^31,32 Nasopharyngeal teratoma can be associated with duplication of the adenohypophysis, as in our case.³³ The epignathus type of teratoma is a large neoplasm that fills the oral cavity and has been reported in association with a CPC.⁵ Nasopharyngeal glioma is a rare entity composed of heterotopic neuroglial tissue. Although there are reported cases of nasopharyngeal gliomas associated with midline skull base defects, none are explicitly associated with CPCs or extend intracranially as our cases did.³² As in type 3 CPCs with cephalocele, identifying intracranial extension of a dermoid, teratoma, or glioma into a type 3 CPC is important for surgical planning to avoid inadvertent CSF leak and potential meningitis.

Limitations of this series were its relatively small size and retrospective nature. In addition, because many of the cases were referred for evaluation from outside institutions, we had no control of the quality or protocol of the imaging examinations and completeness of the clinical data.