Rathke's cleft cyst: From history to molecular genetics.

A Rathke's cleft cyst (RCC) is a remnant of the embryologic Rathke's pouch and a common pituitary lesion. A true RCC is lined with ciliated cuboidal or columnar epithelia with occasional goblet cells and squamous metaplasia. A RCC is frequently diagnosed incidentally through magnetic resonance imaging and computed tomography of the brain or pituitary gland. Presentation can range from an asymptomatic clinical picture to a rapidly progressive disease. RCC are located most often in the sellar and suprasellar regions and a careful differential diagnosis is crucial, especially to exclude craniophryngioma. Recent studies illuminate novel molecular mechanisms and markers for understanding the pathogenesis of RCC. PROP-1, a paired-like homeodomain transcription factor, controls pituitary ontogeny and its high expression induces RCCs. Both transgenic mouse models and immunohistochemical analysis of human RCCs indicate that the leukemia inhibitory factor is involved in pathogenesis. The expression of cytokeratins 8 and 2 in RCCs, but not in craniopharyngiomas, and the presence of beta-catenin mutations in many craniopharyngiomas, but not in RCCs, help with the differential diagnosis. For asymptomatic and small RCCs, observation is appropriate, with serial magnetic resonance imaging and hormonal investigation depending on the patient's clinical status. Surgical resection may be required for symptomatic RCC and recurrence rates are generally low. For patients with a recurrence, stereotactic radiosurgery is an effective approach with low risk.