Rathke cleft cysts (RCCs) are benign sellar and suprasellar lesions believed to develop
from remnants of the craniopharyngeal duct during embryogenesis. RCCs are usually
small and asymptomatic; however, when large, they can present with symptoms related
to mass effect on adjacent structures. In rare cases, RCCs have been reported to present
with symptoms of pituitary apoplexy—the sudden onset of headache and visual symptoms
due to hemorrhagic transformation or infarction of a pituitary lesion.[1] The coexistence of RCC and pituitary adenoma has been described in up to 2.1% of
patients with sellar lesions.[2] We report the case of two patients with clinical symptoms of pituitary apoplexy
and intraoperative findings of coexisting RCC and nonfunctional pituitary adenoma.
CASE REPORTS
Case 1
HISTORY, PRESENTATION, AND EXAMINATION
A 76-year-old woman experienced acute onset of headache, retro-orbital pain, double
vision, and a drooping left eyelid 3 weeks before presentation. She reported that
her initial symptoms had improved; however, she experienced another event 2 weeks
later with worsening headache and double vision. Her medical history was remarkable
for a coronary artery bypass graft and aortic valve replacement within a year of presentation;
thus, she had been treated with Coumadin (warfarin) and was undergoing anticoagulant
therapy during the onset of the symptoms.
Clinical examination of the patient demonstrated a left third nerve palsy and a partial
sixth nerve palsy, with limitation of gaze in all directions and significant ptosis.
A pituitary endocrinological laboratory work-up was found to be normal, with the exception
of a mildly elevated prolactin level of 26.7 ng/mL (normal = 2.8 to 20 ng/mL).
Magnetic resonance imaging (MRI) demonstrated a left-sided sellar mass displacing
the pituitary gland along with the infundibulum consistent with a pituitary adenoma
(Fig. [1]). A noncontrast head computed tomography (CT) scan obtained after her initial apoplectic
episode revealed a sellar hyperdensity consistent with hemorrhage.
Figure 1 Preoperative imaging of patient 1. (A) Axial CT image obtained preoperatively after
onset of headaches showing a mixed hyperdense sellar lesion. T1-weighted axial (B)
and sagittal (C) MRI demonstrating a hypointense lesion along the infundibulum consistent
with a pituitary adenoma.
OPERATIVE AND HISTOPATHOLOGICAL FINDINGS
Our diagnosis based on clinical and radiographic data was pituitary adenoma with two
episodes of pituitary apoplexy. Following discussion with her cardiothoracic surgeon,
the patient's anticoagulation therapy was withheld in the immediate perioperative
period. The patient subsequently underwent transsphenoidal resection, at which time
the tissue extracted was notable for adenoma and mucoid (RCC) tissues. Intraoperatively,
the sella turcica was found to be eroded, and, when the dura mater was opened, a hemorrhagic
pituitary mass was expressed. Additionally, a mucinous lesion was resected, consistent
with RCC. Pathological analysis confirmed the diagnosis of both nonfunctional hemorrhagic
pituitary adenoma and RCC–type epithelia and content conclusive for RCC (Fig. [2]).
Figure 2 Histopathology of tissue from patient 1. (A) Low-magnification view showing a cystic,
epithelium-lined lesion filled with mucinous material (left to center) surrounded
by cellular and hemorrhagic tissue. (B) High-magnification image showing the interface
of the RCC (upper right) and the adjacent pituitary adenoma. Formalin-fixed, paraffin-processed
sections stained with hematoxylin and eosin. Scale bar: 1 mm (A) and 0.1 mm (B).
POSTOPERATIVE COURSE
At 5-month follow-up examination, the patient was free of complaints and neurologically
intact; pituitary-related hormone levels were within normal limits. MRI showed complete
resection of the pituitary tumor.
Case 2
HISTORY, PRESENTATION, AND EXAMINATION
A 67-year-old man reported an acute onset of headaches 6 months before presentation.
He described the headaches to be constant and at the same level since onset. His medical
history was significant for atrial fibrillation, for which he was receiving anticoagulation
therapy with Coumadin (warfarin). His clinical examination was free of any focal neurological
deficits.
Endocrinological laboratory findings were consistent with a diagnosis of nonsecreting
adenoma. Preoperative MRI (Fig. [3]) displayed an 18 × 22.5-mm sellar mass in contact with the optic chiasm that appeared
to be an RCC, because the images showed an internal hypointense cystic lesion on T1-weighted
MRI with gadolinium enhancement.
Figure 3 Preoperative imaging of patient 2. Preoperative axial (A), sagittal (B), and coronal
(C) T1-weighted MRI with gadolinium enhancement displaying a sellar mass in contact
with the optic chiasm, consistent with an RCC. The image shows an internal hypointense
cystic lesion.
OPERATIVE AND HISTOPATHOLOGICAL FINDINGS
On the basis of the patient's clinical presentation and MRI studies, the operation
was performed via a transsphenoidal approach. After removal of the sellar floor bone
and opening of the dura, a hemorrhagic mucoid material bulged through the incision.
The mass was removed in total for pathological analysis. After removal of the specimen,
a second mass identified as a pituitary adenoma was visible; it was subsequently removed
with curettage. Histopathological analysis described a nonsecreting pituitary adenoma
and large amounts of colloid and mucoid material with simple ciliated and mucinous
columnar epithelium consistent with RCC (Fig. [4]).
Figure 4 Histopathology of tissue from patient 2. (A) Low-magnification view showing a fragment
of cellular tissue including a portion of the epithelial lining of the RCC and adjacent
pituitary adenoma (top) and a small portion of the voluminous mucoid cyst contents
(bottom). (B) High-magnification view of the simple ciliated and mucinous columnar
epithelium of the RCC surrounded by pituitary adenoma. Formalin-fixed, paraffin-processed
sections stained with hematoxylin and eosin. Scale bar: 1 mm (A) and 0.1 mm (B).
POSTOPERATIVE COURSE
The patient was readmitted on postoperative day 7 for recurrent epistaxis; he was
successfully treated with nasal packing and was discharged 3 days later. The patient's
anticoagulation therapy, which had been stopped before surgery, was resumed upon discharge
from the hospital. At the 1-month follow-up examination, results of the patient's
neurological examination were normal. He did not complain about constant headaches,
and his pituitary-related hormone levels were within normal limits.
DISCUSSION
RCCs have a wide spectrum of clinical manifestations and imaging features.[3]
[4]
[5]
[6] Although many cases of RCC are asymptomatic, if the cyst becomes large enough, patients
can present with symptoms from compression of the adjacent structures including headache,
visual deficits, and pituitary dysfunction.[7] It is rare for an RCC to present with pituitary apoplexy. Because RCCs have varied
T1- and T2-weighted MRI qualities, they may be indistinguishable from pituitary hemorrhage
on MRI. In a recent series of six patients with RCC presenting with apoplexy, all
patients had preoperative MRI consistent with hemorrhagic pituitary tumor; however,
only two patients were found to have hemorrhage at the time of surgery.[1]
RCCs rarely coexist with pituitary adenoma.[2]
[8] A review of 374 patients who underwent surgery for sellar or juxtasellar lesions
found concomitant RCC and pituitary adenoma in 8 patients (2.1%), all of whom presented
with symptoms from functional growth hormone or adrenocorticotrophic hormone-producing
adenomas.[2] Coexisting RCC and nonfunctional pituitary adenomas are even more rare.[5]
Our first case is unique in that the patient had both RCC and a nonfunctional pituitary
adenoma and presented with pituitary apoplexy. As in other reports, preoperative imaging
favored a diagnosis of hemorrhagic pituitary tumor, and the presence of the RCC was
only discovered at the time of surgery. The imaging of the second case indicated a
cystic component favoring an RCC and the diagnosis of hemorrhagic RCC was discovered
during surgery.
Of particular interest is that both individuals were taking Coumadin (warfarin) for
anticoagulation at the time of symptom onset. Although the patients' International
Normalized Ratio (INR) was not measured at the time of symptom onset, both patients
were compliant with their medication regime and thus the INR values were presumably
in the therapeutic range. Anticoagulation therapy may lead to spontaneous pituitary
hemorrhage in patients with pituitary adenomas as reported in three cases.[9]
[10]
[11] Pituitary adenomas have an increased risk of ischemic apoplexy as they compress
supplying vessels or outgrow effective blood supply.[12]
[13] Because of vascular pathology, hemorrhagic pituitary adenomas can be observed in
up to 25% of patients suffering from pituitary adenoma.[14] It is possible that anticoagulation therapy increases the likelihood of having a
symptomatic hemorrhagic event as our patients experienced.
Only a few cases of RCC and concomitant pituitary adenoma have been described. Symptomatic
RCC may present by compression of surrounding structures or by apoplexy of the pituitary
gland. Presentation may also occur with apoplexy of the RCC as our cases demonstrate.
Anticoagulation therapy precipitates pituitary adenomas and possibly RCCs to hemorrhage
and may increase the risk of symptomatic apoplexy. Our cases demonstrate the importance
of patient education and physician's alertness in patients with acute onset of headache
and history of pituitary adenoma or RCC.
ACKNOWLEDGMENT
The authors thank Kristin Kraus, M.Sc., for excellent editorial assistance in preparing
this paper.
