Neurol Med Chir (Tokyo) 50, 495¿498, 2010

Large Hypothalamic Hamartoma With Calcification and Cystic Components in an Adult —Case Report—

Shinya YAMAGUCHI,SatoshiO.SUZUKI*, Yoshihiro MATSUO,ToshioUESAKA, Koichiro MATSUKADO,KentaMASUI*,andToruIWAKI*

Department of , Hamanomachi Hospital, Fukuoka; *Department of Neuropathology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka

Abstract A 24-year-old female presented with an unusual case of hypothalamic hamartoma manifesting as sei- zure. Neuroimaging findings were atypical, showing the large tumor (maximum diameter, 50 mm) with a cystic component and calcification. Surgery was performed and histological examination demonstrat- ed heterotopia. Hamartoma should be considered in the differential diagnosis of a suprasellar, non-en- hanced mass attached to the . Excessive unnecessary surgery should be avoided, and in- traoperative pathological examination may lead to enhanced assessment and better outcomes. Key words: adult-type hypothalamic hamartoma, seizure, heterotopia, calcification, cystic component

Introduction initiated from the hypothalamic hamartoma and diffuse to the hypothalamus.8,11,27) Other types of surgeries have Hypothalamic hamartoma is a non-neoplastic, congenital varying outcomes,1,4,12,20,23,26,27) but morbidity is considered mass consisting of heterotopic neural tissue that common- high because of the position of the tumor. ly manifests as gelastic seizures and/or precocious puberty Here, we report a case of a large hypothalamic hamarto- in infants. Patients typically present with developmental ma in an adult with atypical neuroimaging and physical disturbances because of uncontrollable seizures. Comput- features. ed tomography (CT) and magnetic resonance (MR) imaging usually show hypothalamic hamartomas as small Case Report (diameter, 10–30 mm) round masses3) that are connected to the hypothalamus, with almost identical signal intensity A 24-year-old female was admitted to a hospital because of to that of brain parenchyma, with clear demarcation, sudden loss of consciousness and a tonic-clonic seizure. and no contrast enhancement.2,3,6,7,14,23,25,27,29) Hypothalam- She showed no signs of developmental disturbances, led a ic hamartomas do not usually develop or calcifica- normal life, worked as a clerk in a bookstore, and was en- tions.3,6,22) Morphologically, pedunculated types of gagedtobemarried.Shehadbeentreatedfordepression5 hypothalamic hamartomas are typically associated with years prior to the current episode but had been stabilized precocious puberty, whereas sessile types of hypothalamic with medication. Neuroimaging examination detected a hamartomas are associated with seizures.6,10,27,28) suprasellar mass, and the patient was subsequently Precocious puberty in patients with hypothalamic referred to our hospital. hamartoma is treated using a luteinizing hormone-releas- On admission, her state of consciousness was clear. She ing hormone analogue.9,10,24) Hypothalamic hamartoma is showed bitemporal light sensitivity depression on auto- considered to be epileptogenic5,12,18,23,27) and is likely to matic static perimetry. Neither pituitary endocrine dys- cause gelastic seizures. Other secondary lesions may also function nor elevation in luteinizing hormone or follicle- assume epileptogenic properties13) that cause various stimulating hormone levels was observed. The patient and types of seizure patterns. Seizures may be controlled by her father had polycystic kidneys, but her current kidney medication, but surgical treatment must be considered for function was normal. We administered valproic acid (400 uncontrollable seizures. Endoscopic disconnection be- mg/day) as an anticonvulsant. tween the hypothalamic hamartoma and the hypothala- Radiography demonstrated expansion of the sella turci- mus is based on the hypothesis that epileptic waves are ca (Fig. 1). CT revealed a large suprasellar mass with a cys- tic component and a high density lesion (Fig. 2A), but Received August 12, 2009; Accepted November 18, 2009 without enhancement by contrast material (Fig. 2B). MR

495 496 S. Yamaguchi et al.

Fig. 1 Radiograph showing expansion of the .

Fig. 3 (A) Coronal T1-weighted magnetic resonance (MR) im- age showing the obscure border between the tumor and the hypothalamus, and no enhancement by gadolinium. (B) Sagit-

tal T1-weighted MR image showing a normal and stalk enhanced by gadolinium, and a cystic component in

the rostroventral part of the tumor (arrow). (C) Sagittal T1- weighted MR image after surgery showing the ventral portion of the tumor was removed.

Fig. 2 Computed tomography scans, showing (A) a large suprasellar tumor containing a small high-density region, and (B) no enhancement by contrast material. imaging showed the tumor as an isointense mass com- paredwithgraymatteronT1-weighted imaging and as an iso- to hyperintense mass on T2-weighted imaging, which was not enhanced by gadolinium. The boundary between the hypothalamus and the tumor appeared obscure (Fig. 3A). The pituitary stalk and gland were compressed caudally, and a cystic component was present within the tumor (Fig. 3B). Angiography showed the bilateral arterial segments C2 through A1 were elongated by tumor com- pression. No tumor stain was visible, but an aneurysm was detected at the bifurcation of the left posterior com- Fig. 4 Intraoperative photographs, showing (A) the tumor (ar- municating artery. rows) resembling cerebral cortical tissue and the olfactory Surgery was performed via an interhemispheric ap- nerve (arrowheads), (B) the right side of the tumor strongly com- proach. The tumor appeared to consist of cerebral cortical pressing the A1 and optic nerve (arrows), and (C) the final opera- tissue (Fig. 4A). Both the optic nerves were strongly com- tive view of partial removal of the tumor under neuronaviga- pressed (Fig. 4B). The border between the tumor and the tional guidance. optic nerves was clear. Intraoperative pathological exami- nation indicated non-neoplastic neural tissue. We could not confirm involvement of the chiasma and optic tract be- turbances, we achieved the maximum possible decrease in cause of the size of the tumor. On the basis of the condi- the tumor mass under neuronavigational guidance (Figs. tion of the optic nerves, we thought that the optic chiasma 3C and 4C). The final histological diagnosis was neural and tract were cranio-dorsally compressed by the tumor. heterotopia (Fig. 5). Exercising the greatest care not to worsen the visual dis- The patient tolerated general anesthesia, recuperated

Neurol Med Chir (Tokyo) 50, June, 2010 Large Hypothalamic Hamartoma in an Adult 497

Calcification in hypothalamic hamartoma was previously unknown. Calcification is basically a nonspecific degener- ative change in old lesions that may have occurred due to various causes. The minerals in the plasma adhere to the tissue via osteopontin or osteonectin. Calcifications are observed in old infarcts or in other degenerative changes in the brain.13,15) Macrophages secrete osteopontin,30) and infiltrate into lesions where ischemic or other inflammato- ry changes occur and initiate the calcification process. In the present case, calcification was seen to be complete, and the underlying mechanisms are difficult to elucidate. However, we think that a similar mechanism, via os- teopontin or osteonectin, may be responsible in this case. Fig. 5 Photomicrograph of the tumor showing mature neural A case of thalamic hamartoma with calcification has been tissue with no abnormal , glial proliferation, or des- reported.16) Moreover, certain cases25) of formation in moplasia, but some spotted calcifications. Hematoxylin and hypothalamic hamartomas are known. The mechanism of eosin stain, original magnification ×60. cyst formation is considered to involve ischemic change followed by liquefactive necrosis. A large hypothalamic well, and recovered from her visual field defect. Since the hamartoma that could cause circulation disturbances may procedure, the patient has not experienced any recurrence show the presence of calcification and cyst formation. of seizure, and no growth of the residual tumor has been Hypothalamic hamartoma should not be excluded based detected. on the neuroimaging findings of calcification or cystic components. Discussion Treatment of the present case needed to consider the di- agnosis, seizure activity, and visual disturbances. Hypothalamic hamartoma is commonly observed as a and solid-type craniopharyngioma were also considered small round mass with clear demarcation. The diameter of as differential diagnoses because of the neuroimaging hypothalamic hamartoma ranges between 5 and 50 mm findings. Non-neoplastic neuronal tissue was confirmed but is generally approximately 10–30 mm.3) Eight hypotha- by intraoperative pathological diagnosis which lead to the lamic hamartomas treated by gamma knife surgery ranged minimum invasiveness of the treatment. from 8 to 22 mm,17) and 14 hypothalamic hamartomas The seizure for which the patient was admitted was the treated by surgery because of uncontrollable seizure meas- first attack. Hypothalamic hamartomas have better prog- ured 10–42 mm.27) Some childhood cases of relatively large nosesinadultsthaninchildren.Assessmentof14adult- hypothalamic hamartoma have also been reported.14,19,20) type hypothalamic hamartomas manifesting as seizures in In our case, the hypothalamic hamartoma was relatively adulthood found that patients with adult-type hypothalam- large, with a maximum diameter of 50 mm. ic hamartomas showed milder abnormal behaviors and Neuroimaging examination of hypothalamic hamarto- fewer learning disabilities than those showed by pediatric ma typically reflects the findings of neural heterotopia. CT patients.21) Manyofthepatientswereabletowork,marry, shows hypothalamic hamartomas as isodense, non-en- and lead normal lives. Their seizures were easy to control hanced masses with absence of calcification and cyst for- with medication and because of their high level of social mation.6,7,22) MR imaging shows hypothalamic hamarto- and cognitive function, such patients can treated by mas as isointense masses on T1-weightedimagingandiso- minimally invasive surgery or drug therapy. Our patient to hyperintense masses on T2-weighted imaging, without manifested with seizure in adulthood, so we expected enhancement by gadolinium.2,3,6,7,14,23,25,27,29) A possible satisfactory seizure control with medication. reason is that the blood vessels of the hypothalamic hamar- Removal of a tumor only for seizure control is consi- toma retain the blood-brain barrier. The pituitary gland deredtohavehighmorbidity.1,4,12,20,23,26,27) Since visual dis- and stalk are relatively easy to identify on MR imaging turbance was also present, we performed partial removal with contrast medium, even if compressed by a large of the tumor, with excision of as much tumor tissue as pos- hypothalamic hamartoma.6) Hypothalamic hamartoma sible. The optic nerves were strongly compressed by the must be differentiated from low-grade glioma and solid- tumor. We could not confirm the condition of the optic type craniopharyngioma. Solid-type craniopharyngioma chiasma and tract because of the tumor size. We predicted appears as a relatively hypointense mass on T1-weighted that these components were compressed cranio-dorsally imaging compared with hypothalamic hamartoma. in the direction of the optic nerve. We performed partial The presence of calcifications and cyst formation com- removal of the tumor under neuronavigation guidance to monly contradicts the diagnosis of hypothalamic hamarto- reduce the compression on the optic nerve, chiasma, and ma.3,6,22) However, in the present case, a cystic component tract. The patient achieved full recovery from her visual was present on CT and MR imaging, and a high density disturbance after surgery. Intraoperative electroen- area, suspected of being calcification, was observed in the cephalography would have been ideal for understanding hypothalamic hamartoma on CT. Furthermore, histologi- the mechanism of the seizure in this case, but the partial cal examination confirmed the presence of calcification. destruction of the tumor may enable this patient to live

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Acta Neuropathol 105: 259–264, 2003 Address reprint requests to: Shinya Yamaguchi, M.D., Department 14)GuibaudL,RodeV,Saint-PierreG,PracrosJP,ForayP, of Neurosurgery, Hamanomachi Hospital, 3–5–27 Maiduru, Tran-Minh VA: Giant hypothalamic hamartoma: an unusual Chuou–ku, Fukuoka 810–8539, Japan.

Neurol Med Chir (Tokyo) 50, June, 2010