Keywords
craniopharyngioma - ectopic - recurrence
Introduction
Although craniopharyngiomas are a benign histological entity, they have a high tendency
to recur at the same site even after an attempt to resect completely. However, it
can recur at ectopic sites very rarely. Tumor seeding along the surgical tract or
along the cerebrospinal fluid (CSF) pathways has been reported, which can result in
ectopic recurrence. There exists particularly high risk for cystic tumors. Before
the present case, 60 ectopic recurrent craniopharyngiomas have been reported up until
2016. The frontal lobe is the most common site of ectopic recurrence (23 cases).[1] In our case, recurrence was seen in an extra-axial parasagittal location that has
not been reported so far. Protection of the whole surgical bed and cautious manipulation
of the tumor is required to prevent seeding of tumor. It should be emphasized that
long-term radiologic surveillance is very important, even in patients undergoing complete
resection.[2]
[3]
Case History
A 12-year-old girl underwent right pterional craniotomy and gross total excision of
craniopharyngioma occupying the sellar region with suprasellar extension in January
2014 ([Fig. 1]). On histopathologic examination (HPE), it was proven to be adamantinomatous type
of craniopharyngioma. Postoperatively, the patient received radiotherapy and was on
hormonal replacement therapy as she developed panhypopituitarism. During her follow-up
visits in October 2016, she complained of headache. Clinical evaluation did not reveal
any visual deficits or any other focal deficits. A non-contrast computer tomographic
scan of her brain ([Fig. 2a]) revealed postcraniotomy status in the right frontal region with ventriculoperitoneal
(VP) shunt in situ. A well-defined hypodense area with a linear hyperdense septum
at its inferior aspect and irregular discontinuous peripheral hyperdense rim, in an
extra-axial, parasagittal location in the right frontal region measuring approximately
43 × 31 × 41 mm in size was visualized. No significant mass effect was seen. Contrast-enhanced
magnetic resonance imaging revealed a well-defined extra-axial lesion in the right
frontal region in a parasagittal location broad-based toward falx cerebri along its
anterior aspect. It was heterogeneously hyperintense on T2WI/FLAIR/T1WI ([Fig. 2b, c]). Few thin septae were seen within. Mural thickening with altered signal intensity
was seen in its anterior aspect suggestive of solid component, which revealed postcontrast
enhancement ([Fig. 2d]). Areas of magnetic susceptibility were seen within the lesion suggestive of calcification/hemorrhagic
products. Medially, the lesion was causing mild contra lateral displacement of the
falx cerebri. A midline shift of 7 mm was seen. On all other sides, it was causing
compression of the brain parenchyma with mild displacement of frontal horn of the
right lateral ventricle. Widening of sella with poor visualization of the pituitary
gland was seen. The patient underwent redo craniotomy and resection of the lesion
([Fig. 2e]). HPE of the resected lesion confirmed craniopharyngioma, and complex squamous epithelium
and stellate reticulum were seen. Microcyst and wet keratin were present with fibrous
stroma ([Fig. 2f]). Postoperative recovery was uneventful. She was continued on hormonal replacement
therapy, and after 1-year follow-up, there has been no recurrence of the lesion.
Fig. 1 (a) Preoperative T2 axial MRI showing heterogenous intensity lesion in sellar and suprasellar
region. (b) Preoperative T1 saggital magnetic resonance hypointense lesion in sellar and suprasellar
region. (c) Preoperative postcontrast saggital image showing enhancing solid component with
cystic area. (d) Postoperative (first surgery) saggital image showing GTR of the tumor. (e) Postoperative (first surgery) coronal image showing GTR of tumor.
Fig. 2 (a) NCCT showing well-defined, extra-axial, hypodense lesion with discontinuous rim
of calcification in right frontal region with mass effect. (b) T2 coronal MRI shows heterogeneously hyperintense lesion in parasagittal location
in right frontal region. (c) T1 sagittal MRI shows heterogeneously hyperintense lesion in extra-axial location
in right frontal region. (d) T1 sagittal postcontrast MRI showing heterogeneously enhancing solid area within
lesion. (e) Intraoperative image of the tumor cavity. (f) HPE 40x. Complex squamous epithelium with stellate reticulum. Microcyst and wet
keratin are present with fibrous stroma.
Discussion
Craniopharyngiomas are partially cystic tumors of the sellar region thought to arise
from remnants of Rathke's pouch and craniopharyngeal duct, and are benign lesions
per se. However, they can behave aggressively. It can spread to the adjacent areas
to involve important structures around the sellar region due to which complete removal
of the lesion may be very difficult. Tumor cells may remain behind if resection is
not performed adequately and can give rise to recurrence of tumor at local as well
as ectopic sites.[1]
[4]
Although recurrence at local site is common after gross total resection (GTR) of craniopharyngiomas,
ectopic recurrence occurs very rarely. The incidence of ectopic recurrence is difficult
to estimate as there are only a few reported cases. Before this case, 60 ectopic recurrent
craniopharyngiomas have been reported up until 2016.[5] There are two proposed theories for ectopic recurrence. The more common of the two
is direct implantation of tumor cells along the operative tract. The second theory
is the dissemination of tumor cells through CSF to ectopic location. Nomura et al
were able to confirm tumor seeds in CSF following surgery, and two separate ectopic
lesions were attributed to both mechanisms in their case. Out of the 60 cases, 33
tumors were located in the previous surgical routes and 27 were disseminated along
the cerebrospinal fluid pathway, which was almost equal (surgical tract 55%, CSF 45%).
All reported cases underwent surgery.[1]
[3]
[5]
[6]
[7] Ectopic recurrence can occur over a wide range of time after resection (1 month–26
years), with a median of 4 years. Equal prevalence was seen in male and female patients
(43% female, 57% male).[8] Children and adult patients were equally affected (27 vs. 24 cases). Male children
were affected predominantly (62%).[1]
The frontal lobe is the most common site of ectopic recurrence (23 cases). Epidural
and sylvian fissures are also common sites where implantation via surgical route is
the predominant mechanism. Location of ectopic recurrent craniopharyngioma in the
posterior fossa, spinal cord, cerebellopontine angle, and prepontine cisterns was
strictly associated with CSF contamination by tumor cells.[9] Extra-axial parasagittal location in the frontal region has not been reported before
this case.[1] A variety of techniques in surgery have been proposed to prevent recurrence. However,
these techniques may not always be successful. It was found that most reported ectopic
recurrent tumors had some cystic component that was also present in primary tumor.
Presence of cystic component in primary lesion is a major deciding factor for ectopic
recurrence after surgery of primary tumor.[10] The reason for this could be the higher chance of the cystic part to break easily
during surgical manipulation with release of its contents into the surrounding areas/CSF.
In our case too, the ectopic tumor had cystic component.[2]
[3] Vascular endothelial growth factor and its receptor are reported to be significantly
more expressed for ectopic recurrences than for the primary lesion. Tumor cells showed
positive immune-histochemical staining of up to 33%, whereas in the primary tumor
neither vascular endothelial growth factor nor its receptor could be detected on tumor
cells. However, the role of angiogenesis in ectopic recurrence of craniopharyngioma
has yet to be established.[1]
[11] There is a need for more research to determine the exact cause of ectopic recurrence
of craniopharyngioma.[1] Extra caution needs to be exercised while operating on cystic craniopharyngioma
to avoid spillage of its contents. Some authors approve the use of cotton for isolation
of the tumor and aspiration of cystic contents prior to dissection of capsule. Long-term
clinical and radiologic follow-up of the patients is recommended.[2]
[3]
Elliott et al reported about the treatment of 31 cases of ectopic recurrence. Twenty-two
patients underwent GTR that provided good disease control as seen on follow-up visits.
In this series, the underlying factors for subtotal resection of ectopic recurrences
included recurrence involving the brainstem and deep white matter as well as significant
medical comorbidities contraindicating extensive surgical resection. If the recurrence
is primarily cystic and in a surgically accessible region of the brain, GTR remains
the primary modality of treatment as in our case. However, where GTR is not feasible,
gamma knife radiotherapy, intracavitary irradiation, or chemotherapy with bleomycin
or interferon can be alternative modalities of treatment.[1]
[5]
[12] Ectopic recurrence of craniopharyngioma via CSF/surgical tract is a rare possibility
that needs to be addressed during surgery of primary tumor. It is important to remove
primary lesion in toto. Cystic tumors need special attention during removal because
of their high recurrence rate.
