Brain Pathology Case of the Month - August 2008

DIAGNOSIS   Pituitary gonadotroph adenoma with adamantinomatous craniopharyngioma


Nests of squamous cell epithelium have long been recognized to exist within the normal pituitary gland and are thought to represent remnants of the embryologic hypophyseal-pharyngeal duct. Luse and Kernohan investigated 1364 pituitary glands and found that 333 (24 percent) had nests of squamous epithelium (5). Of these 333 pituitary glands, only one had squamous nests outside of the pars tuberalis; in no case was there evidence of squamous epithelium distributed within the adenohypophysis. It has been suggested that these nests of squamous epithelium serve as the precursors for the development of adamantinomatous type craniopharyngiomas (7).

Several lines of evidence suggest that the squamoid nests found in this adenoma are not simply pre-existing squamous rests. First, the squamoid cell islands do not show the prototypical appearance of developmental squamous deposits of rests but have the morphological features of adamantinomatous craniopharyngioma with peripheral nuclear palisading and a focal stellate reticular appearance. Second, the squamoid epithelial cells are distributed randomly throughout the tumor suggesting that they have, in fact, developed in concert with the gonadotroph adenoma. They are not located at the edge of the tumor within preexisting pituitary stalk where they can often be found in normal pituitary glands. And thirdly, the positive immunostaining of the craniopharygioma for Ki-67 (Figure F) suggests that these cells are proliferating and are not quiescent embryologic remnants. Based on this line of reasoning, we believe that this case represents a neoplastic proliferation expressing gonadotrophic adenoma with adamantinomatous type craniopharyngioma.

There are rare case reports of craniopharyngioma coexisting alongside a pituitary adenoma with those reported cases being prolactinomas (1, 3, 9). In these cases the two components represented geographically separate mass lesions. In one case report, a patient with a large craniopharyngioma was shown to have a microprolactinoma. In that particular case the authors hypothesized that the prolactinoma may have arisen because of disruption of inhibitory dopaminergic signaling (3). In the case reported here, the component showing craniopharyngioma differentiation is small, multifocal and intimately admixed with the pituitary adenoma. Additionally the adenoma is gonadotrophic rather than a prolactinoma.

The pathogenesis of these two morphologically distinct appearing components of the tumor is not clear from the present study; however, several mechanisms can be hypothesized. One hypothesis is that this tumor is composed of two independent primary neoplasms; however, the intimate admixture of the two components makes this explanation unlikely. Alternatively, the two components of this tumor could have arisen from a common tumor stem cell through divergent differentiation. Activation of factors involved in normal embryonic development could have led to cells resembling primordial cells of Rathke's pouch that then could differentiate into the pars tuberalis (leading to craniopharyngioma development) and the pars distalis (leading to pituitary adenoma development). Pituitary cells with stem cell characteristics have been described in adults (2), and these cells also could be the source of the two coexisting pituitary tumors. Another theoretical mechanism could be divergent differentiation of one neoplasm into the other. Interestingly, normal adenohypophyseal cells have been documented to have plasticity in differentiation. Lactotrophs and somatotrophs can change their phenotype through transdifferentiation (8). This process can be adaptive as recruitment of cells of one type to secrete hormones of another cell type can meet increased physiological needs (6). A more frequently reported form of divergent differentiation in pituitary adenomas is the presence of ganglion cells found in some adenomas with neuronal differentiation (4).

Based on the data presented, we suggest that the nests of craniopharyngioma found in this pituitary adenoma represent islands of an unusual form of divergent differentiation in a pituitary adenoma.


  1. Asari J, Yamanobe K, Sasaki T, Yamao N, Kodama N (1987) A case of prolactinoma associated with craniopharyngioma. No Shinkei Geka.15(12):1313-8.
  2. Chen J, Hersmus N, Van Duppen V, Caesens P, Denef C, Vankelecom H (2005) The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics. Endocrinology.146(9):3985-98.
  3. Cusimano MD, Kovacs K, Bilbao JM, Tucker WS, Singer W (1988) Suprasellar craniopharyngioma associated with hyperprolactinemia, pituitary lactotroph hyperplasia, and microprolactinoma. Case report. J Neurosurg.69(4):620-3.
  4. Kontogeorgos G, Mourouti G, Kyrodimou E, Liapi-Avgeri G, Parasi E (2006) Ganglion cell containing pituitary adenomas: signs of neuronal differentiation in adenoma cells. Acta Neuropathol (Berl).112(1):21-8.
  5. Luse SA, Kernohan JW (1955) Squamous-cell nests of the pituitary gland. Cancer.8(3):623-8.
  6. Melmed S (2003) Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest.112(11):1603-18.
  7. Miller DC (1994) Pathology of craniopharyngiomas: clinical import of pathological findings. Pediatr Neurosurg.21 Suppl 1:11-7.
  8. Vidal S, Horvath E, Kovacs K, Lloyd RV, Smyth HS (2001) Reversible transdifferentiation: interconversion of somatotrophs and lactotrophs in pituitary hyperplasia. Mod Pathol.14(1):20-8.
  9. Wheatley T, Clark JD, Stewart S (1986) Craniopharyngioma with hyperprolactinaemia due to a prolactinoma. J Neurol Neurosurg Psychiatry.49(11):1305-7.

Contributed by Robert M. Sargis, MD, PhD; Robert L. Wollmann, MD, PhD; and Peter Pytel, MD

International Society of Neuropathology