Keywords
Rathke's cleft cyst - pituitary abscess - transphenoidal surgery
Introduction
Pituitary abscesses are rare, accounting for 0.27 to 0.6% of pituitary lesions.[1]
[2] Pituitary abscess associated with a Rathke's cleft cyst (RCC) is even rarer and
only around 60 cases have been published to date.[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
Primary pituitary abscess occurs in normal pituitary tissue, without an underlying
structural cause. Pituitary abscesses developing on the background of a preexisting
sellar lesion or following pituitary surgery are named secondary pituitary abscesses,
such as in the case we describe.[12] While radiological findings of a pituitary abscess may be nonspecific, intracranial
extension is most unusual; here, we describe the course of such an abscess associated
with an RCC that gave rise to peculiar radiological findings leading to diagnostic
challenges.
Case Report
A previously fit and well 31-year-old man presented to his local hospital with 1-week
history of generalized severe headache. Brain computed tomography (CT) was reported
as negative for acute intracranial pathology, notably without any evidence of sinus
infection.
He represented 5 weeks later with worsening headache and blurring of vision. He also
reported recent onset of erectile dysfunction and reduced libido. He had no polyuria
or polydipsia. Neuroophthalmic assessment revealed asymmetric bitemporal field defects,
the left worse than the right, with slightly reduced left best corrected visual acuity
(BCVA) of 6 of 9. This was consistent with an asymmetric compression of the optic
chiasm. The left visual acuity continued to deteriorate over the subsequent days to
6 of 18. Systemically, he was well without pyrexia or hemodynamic instability. Pituitary
function tests showed hypogonadotropic hypogonadism and mild hyperprolactinemia (538mU/L,
73–407). His other pituitary function was intact. His C-reactive protein (CRP) was
normal (2mmol/L) and erythrocyte sedimentation rate (ESR) was mildly elevated (29mm/h).
Further brain CT revealed a large area of hypodensity centered on the left thalamus/basal
ganglia, and subsequent magnetic resonance imaging (MRI) with contrast showed a medium
size pituitary cyst with suprasellar extension and two contiguous tandem cysts with
thick enhancing walls along the left optic tract ([Fig. 1]). The sellar/suprasellar cyst was compressing the optic chiasm and the lateral cysts
along the left optic tract were causing perilesional edema of the adjacent brain parenchyma.
These imaging characteristics were consistent with high-grade optic pathway glioma
with extension into the thalamus.
Fig. 1 Preoperative imaging. (A) CT plain imaging, axial view showing hypodensity/edema in left basal ganglia region,
tracking along visual radiation (white arrow). (B) Gadolinium-enhanced T1-weighted imaging, sagittal view, showing multi-septate edge
enhancing lesion arising from the sella (white arrow) and a second smaller contiguous cyst at the superior/posterior aspect. (C) Gadolinium-enhanced T1-weighted imaging, axial view showing multi-septate edge enhancing
lesion extending along the left optic tract (white arrow) in contact with the suprasellar component of the pituitary cyst. (D) T2-weighted imaging, axial view showing edema around the abscess (white arrow). CT, computed tomography.
The Pituitary Multidisciplinary Team (MDT) discussion recommended biopsy of the presumed
high-grade tumor. Surprisingly, the intraoperative findings during the endoscopic
transsphenoidal biopsy were in keeping with an abscess, rather than a tumor. Frank
pus was drained from the pituitary fossa, without evidence of solid tissue consistent
with tumor ([Fig. 2]). The pus was evacuated and the cyst wall was sampled for biopsy. Empiric antibiotics
were started intraoperatively and intraoperative histological examination showed epithelium
with reactive atypia ruling out a malignant tumor. Initial culture grew a highly sensitive
Staphylococcus aureus.
Fig. 2 Intraoperative photographs. (A) Pus filled the sphenoid sinus following dural sellotomy. (B) Following aspiration of the pus, the cyst wall was dissected of the dura.
The formal histological examination revealed a heavily inflamed cyst lined by cuboidal
epithelium in the vicinity of anterior pituitary gland tissue ([Fig. 3A]), with focally prominent cilia typical for RCC ([Fig. 3B]). There were regions of suppuration in the lumen of the cyst ([Fig. 3C]). Squamous metaplasia and mild reactive atypia were seen in places, reflective of
secondary changes to the inflammation ([Fig. 3D]). The overall appearances were consistent with an inflamed RCC with abscess formation
([Fig. 3]).
Fig. 3 Histology of the specimen. (A) Histology illustrates a benign cyst with acute-on-chronic inflammation (white asterisk) in the vicinity of atrophic/fibrotic anterior pituitary gland tissue (black asterisk). (B) The cyst epithelium is focally ciliated (black arrow) and acutely inflamed by infiltrating neutrophils (white arrow). Underneath, there is a dense chronic inflammatory infiltrate. (C) Focally, the epithelium is eroded by inflammation (black arrow), and purulent material is seen in the cyst lumen (white arrow). (D) The epithelium shows squamous metaplasia and mild reactive atypia in places (white asterisk), as secondary changes to the inflammation.
Septic screen that included skin examination, blood cultures, cardiac ultrasound,
CT chest/abdomen/pelvis, and orthopentogram revealed no source of infection. The postoperative
period was uncomplicated with good clinical improvement and normalization of vision.
A standard course of 6 weeks of intravenous (IV) antibiotics (ceftriaxone) was administered.
Pituitary function at follow-up showed ongoing hypopituitarism (adrenocorticotrophic
hormone [ACTH], thyroid stimulating hormone [TSH], and gonadotrophin deficiency).
Repeat imaging 6 weeks after surgery showed no recurrence of the sellar cyst and significant
reduction in the size of the two presumed abscesses along the left optic tract. The
3-month postoperative imaging demonstrated almost complete resolution of the abscess.
Discussion
RCCs are benign lesions developing between the anterior and posterior pituitary gland
from remnants of the embryological Rathke's pouch.[14]
A preexisting pituitary lesion, such as adenoma, RCC, or craniopharyngioma, is considered
a risk factor for developing a pituitary abscess.[6] However, they only make up a small percentage of all pituitary abscesses.[10]
[15] There have been around 60 reported cases of RCC associated abscess. Only one-third
of them are single case reports of patients presenting acutely without prior knowledge
of pituitary disease.[1]
[3]
[4]
[6]
[7]
[8]
[9]
[11]
[12]
[13]
[15]
[16]
[17]
[18]
[19]
[20]
[21] One case involved a patient with previously known RCC for which they had not yet
had surgery.[5] Several other cases were presentations of secondary pituitary abscess in patients
previously operated on for their RCC.[2]
[3] Interestingly, in a review of 6,832 patients who had undergone transsphenoidal surgery
for pituitary disease, 23 later presented with pituitary abscess (0.3%), and 8 of
them had RCC removal as the primary operation.[2]
The clinical and radiological presentations of pituitary abscess associated with RCC
have been widely variable in the literature to date, making preoperative diagnosis
challenging.[12]
[16]
[17] Most have been described in females, with a median age within the fourth decade
of life,[3] and only a handful of cases involving pediatric populations.[7]
[8]
[11]
[17] The clinical presentation in our case of headache, visual disturbance with associated
manifestations of hypopituitarism is not uncommon. In a recent literature review of
pituitary abscess associated with RCC, headache occurred in 70% of patients, visual
disturbance in 35%, and hypopituitarism in 80%.[3] Septic manifestations, such as fever with raised CRP and white cell count, were
reported in only 30%; therefore, the lack of these in our case report is not unexpected.[3]
[12]
Risk factors associated with an increased risk of abscess development within an RCC
are previous surgical or irradiation treatment for the RCC, as well as immunosuppression.[2]
[3]
[12]
[14]
[18] The majority, however, occurs spontaneously, as with our patient.[3]
[12] Furthermore, other sites of infection predisposing to abscess formation in an RCC
have been linked. Such cases include local spread from the sphenoid sinus, direct
translocation of infection locally from meningitis or thrombophlebitis,[6]
[11]
[19] or hematogenous spread from a distant nidus of infection.[3]
[20] However, most cases do not have evidence of preceding infection elsewhere, and the
abscesses are cryptogenic.[11]
[12]
It has been hypothesized that RCC abscesses develop from direct contact with the sphenoid
sinuses, due to proximity to the sella and from similar pathogens causing chronic
sinusitis.[3]
[22] Given that most cases do not have radiological evidence of sinusitis or anatomical
sinusal defect, spread via the venous drainage system that supplies both the sphenoid
sinus and the pituitary gland has been suggested.[14]
A unique finding of our case is the extension of the abscess along the optic pathway
and the associated radiological appearances. We speculate that the abscess originated
in the sella and extended to the left optic tract by contiguous spread. Most pituitary
MRI protocols do not include sequences specific to infection, such as diffusion-weighted
imaging (DWI), and their sensitivity in identifying pituitary abscess may be limited.[12] However, a review[23] of MRIs of 51 patients with a pituitary abscess, suggested that 96% of cases had
MR evidence of local invasion to at least one adjacent structure. Despite this, there
was no case demonstrating such extensive spread into the optic pathway. Moreover,
a correct diagnosis of pituitary abscess was made in two-thirds of cases preoperatively
due to what they found to be more “typical” MRI findings within this group. These
included iso- or hypointensity on T1-weighted imaging (59% of cases), iso- or hyperintensity
on T2-weighted imaging (76.5% of cases), disappearance of the posterior pituitary
bright spot (86% of cases), and ring enhancement postgadolinium injection in 82%.
Similarly, of all the reported cases of RCC-associated abscess to date, none describes
such as an extensive course of abscess spread, nor mentions of optic pathway or basal
ganglia involvement, making our case unique. The MRI appearance and the spread of
the lesion in our patient led to the initial radiological diagnosis of high-grade
optic glioma. Interestingly, there was evidence of restricted diffusion on DWI on
the MRI head which has been previously thought to be present in cases of pituitary
abscess.[14]
The provisional diagnosis of a pituitary abscess was made intraoperatively when purulent
material was found in the pituitary fossa and empiric antibiotic treatment commenced
immediately. The histological examination confirmed findings typical for RCC that
had undergone inflammatory changes, without evidence of neoplasia. Almost all previously
reported cases showed histological appearances of RCC with or without evidence of
inflammation.[1]
[7]
[18]
[19]
[20] Of those who had more nonspecific histology, the diagnosis was made with the combination
of radiological, intraoperative, histological, and microbiological findings.[3]
[12]
Surgical drainage of the pituitary abscess is the treatment of choice aiming to treat
the infection and to obtain samples for microbiological and histological examination.[3]
[14] Empiric antibiotics should be administered once pus is confirmed intraoperatively,
followed by a prolonged targeted antibiotic course, if the responsible organism is
identified. The transsphenoidal route is the approach of choice for the sellar abscess[15] but cannot be used for drainage of the cysts along the optic tract. In our case,
we elected to treat the intraparenchymal abscesses medically with antibiotics because
of their relatively small size; the risks associated with a needle aspiration through
a bur hole in this deep-seated location, the fact that we had already obtained pus
sample and equally importantly, and the fact that the vision improved following aspiration
of the sellar abscess. Needle aspiration of the contiguous abscesses would have been
considered in this case, only if medical management had failed. Despite treatment,
the rate of recurrence of abscesses among these patients is high in reported cases
with at least 18 patients of the 60 reported cases developing reaccumulation of the
abscess after initial surgical drainage.[1]
[4]
[9]
[11]
[14]
[17]
[19]
[21] Most of these reaccumulated within 6 months after the operation and some relapsed
multiple times, one patient requiring five surgeries to drain the abscess.[11]
Postoperative improvement of endocrine and visual deficits following treatment of
infected RCC has been reported at 66 and 75%, respectively.[3] Our patient had rapid visual improvement but did not recover any pituitary function.
Close follow-up will be needed, given the rate of recurrence.
Conclusion
Abscess in an RCC with extension along the optic pathway has not been previously described.
This case is unique in that respect and the atypical findings on imaging posed diagnostic
challenges. The intraoperative findings and pathological review led to the correct
diagnosis and management.
