RADIOLOGIC-PATHOLOGIC CORRELATIONS IN AN EARLYRECURRENT DYSPLASIC SQUAMO-PAPILLARY

CRANIOPHARYNGIOMA

D. Haba1, G. Dumitrescu2, A. Indrei3, V. Mogos4, M. Grigoras5, L. Foia6, D. Mihaila7, A. Varna7, I. Poeata8

1Department of General and Dental Radiology, 3Department of Anatomy and Embryology,4Department of Endocrinology, 6Department of Biochemistry, "Gr. T. Popa" University ofMedicine and Pharmacy, 5Department of Radiology, "Sf. Spiridon" Emergency Hospital

7Department of Pathology, "Sf. Maria" Children Emergency Hospital 2Department ofPathology, 8IIIrd Clinic of Neurosurgery, "Prof. dr. N. Oblu" Emergency Hospital,

Iasi, Romania

AbstractCraniopharyngioma is part of a spectrum of suprasellar cystic neoplasms, with two

distinct clinicopathological entities: most are adamantinomatous tumors occurring moreoften in children and young adults, and radiographically are calcified, while papillary formdevelops more often in adults, lacks calcification, and have a better outcome.

In this report we describe clinical, CT and MRI features, together withhistopathological findings of an early recurrent papillary craniopharyngioma. Reviewing theCT and MRI findings and microscopic specimens of both the initial and the recurredcraniopharyngioma, we identified the rapid relapse of the solid tumoral component andcorrelate it with low-grade basal cell dysplasia of the epithelial component that evolves fromsmall patchy foci to more extensive areas in length and width. While low-grade basal celldysplasia is not clearly malignant, once the pathologist sees these cellular changes in apapillary cranyopharyngioma, he must note them in his report as basal cell dysplasia couldbe the cause of an early tumoral recurrence. Although low-grade basal cell dysplasia insquamo-papillary craniopharyngioma is uncommon, when such a diagnosis is established,the radiologist must pay attention to MRI characteristic findings of the solid part (maximumdiameters, enhancing aspects, shape, and location) and compare them with those from theprevious data.

Keywords: squamo-papillary craniopharyngioma, MRI, CT, MIB-1, diabetesinsipidus.

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Case Reportdoi: 10.4183/aeb.2010.111

*Correspondence to: Danisia Haba MD, PhD, Department of General and Dental Radiology, "Gr. T.Popa" University of Medicine and Pharmacy, Ateneului Street nr. 2, Iasi, Romania 70309, Tel 0040-721696133, Email: dhaba@hotmail.com

Acta Endocrinologica (Buc), vol VI, no. 1, p. 111-122, 2010

INTRODUCTION

Craniopharyngioma is a rare epithelial tumor occurring in the sellar region,comprising 3% of all intracranial tumors. Although its origin is not firmlyestablished, it is generally thought to be derived from remnants of Rathke's pouch.Despite their benign histological nature, craniopharyngiomas may behaveaggressively and recur even after apparent complete surgical removal.

Tumor recurrence is one of the most fearful complications in patients operatedfor a craniopharyngioma because of strong adverse consequences on survival andquality of life. Recurrence rates from 5% to 57% have been reported in large seriesof craniopharyngiomas (1-4). The variability of the reported recurrence rates isattributable to various factors, such as different definitions of recurrence (clinical orneuroradiological), extent of resection, administration or not of radiation therapypostoperatively, and the tumor growth potential.

The present report describes the clinical, radiological, and histopathologicalfeatures of an early recurrent squamo-papillary craniopharyngioma in order todelineate possible factors of recurrence.

CASE REPORT

First AdmissionIn September 2006 a 37-year-old unmarried man was referred to Endocrine

department with a history of polyuria, polydipsia, anorexia, marked asthenia,bifrontal progressive headache associated with retroorbital pain, and slowlyprogressive diminution of vision in both eyes over the previous two months. He hadlost 12 kg over the same period. The patient was informed about the diagnostic andtreatment procedures and gave his informed written consent. The institutional ethicscommittee approved the study protocol.

Physical examination revealed marked hypotension (75/40 mm Hg).Endocrinological examination (Table 1) showed low serum concentrations of freethyroxine (fT4=0.70 ng/dL), luteinizing hormone (LH=0.5 mlU/mL) andtestosterone levels (1.6 ng/mL), whereas plasma prolactin (PRL) level and thyroidstimulating hormone (TSH) levels were normal. Serum cortisol level was decreased(4.75 μg/dL), but the ACTH stimulation test revealed secondary hypoadrenalismwith increased levels of plasma cortisol at 50.9 μg/dL.

Urinary osmolarity was low and did not rise even after water deprivation test,certifying diabetes insipidus. Testicular ultrasonography identified reduced volume,with intense hypoechogen echostructure. Left kidney could not be identified.Ultrasonography of the thyroid gland revealed a normal thyroid volume withhypoechogene echostructure. Ophthalmologic examination showed normal fundus.Plain skull X-ray described a sella turcica with an ovalar contour.

Magnetic resonance imaging (MRI) of the head was made with a 1.5 T MR

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system. The sequences employed were axial and coronal T2 fast spin echosequences and axial, coronal and sagittal T1 sequences obtained before and afterintravenous gadolinium (20 mL 0.1 mmol/L). A fast saturation (FS) pulse wasadded to the axial and coronal contrast-enhanced T1-weighted sequences. Enhancedcoronal, axial and sagittal T1WI FS showed a sharply delineated noncalcified,mixed solid-cystic ovalar lesion. The cystic part presented high signal intensity onT2 weighted images (Fig. 1a) and began from sella turcica to suprasellar region.The tissue component of the lesion is in close contact with the right side wall of thecyst and showed hyposignal intensity on T2 and isosignal intensity on T1 weightedimages without contrast (Fig. 1a,b). Postcontrast T1-weighted images (T1WI)showed an inhomogeneous high signal intensity solid part of the tumor with anirregular shape due to multiple papilliferous cauliflower-like extensions inside thecystic component. This solid part began at the superior edge of sella turcica andextended to the suprasellar area predominantly on the anterior and right lateral wallof the cystic part (Fig. 1c). Maximum diameters of the entire tumour were 53 mmcephalo-caudal/ 38 mm antero-posterior / 36 mm transverse. The lesion compressedthe optic chiasm and came into contact with the internal wall of the right internalcarotid artery. There weren't any calcifications or necrosis. The lesion enlargedsella turcica and compressed almost totally the pituitary gland, extendingpredominantly in suprasellar cistern. Its superior pole blocked foramen Monroe onthe right side and caused triventricular hydrocephalus. Through the mass effect thelesion compressed the right lateral ventricle and moved the midline structures to theleft. MR imaging established the diagnosis of sellar and suprasellar mixedcraniopharyngioma with triventricular hydrocephalus.

Based on the combination of clinical, biochemical, and radiographic data, adiagnosis of panhypopituitarism and diabetes insipidus due to a craniopharyngioma

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1a 1b 1c

Fig. 1. Craniopharyngioma. Precontrast coronal MRI T2WI (a) and T1WI demonstrated mixed tumorin the suprasellar cistern with a cystic part (*) presenting high signal intensity on T2 weighted images(a). The solid part (¢) of the lesion was in close contact with the right side wall of the cyst and showedhyposignal intensity on T2 and isosignal intensity on T1 weighted images (b). Enhanced sagittal T1WI(c) showed sellar mixed solid cystic ovalar mass with suprasellar extension and triventricularhydrocephalus. The tumor showed an inhomogeneous high signal intensity solid part with an irregularshape due to multiple papilliferous cauliflower-like extensions (¢}) inside the cystic component.

was made. He started hormonal substitution therapy with oral drugs (prednisone 7.5mg / day and LThyroxine 50 μg/day). As his visual acuity diminished and hisheadache became more prominent and diffuse, in November 2006 the patient wasreferred to the Neurosurgery Department.

First Operation and Histopathological FindingsThe patient underwent a right frontotemporal craniotomy and subtotal removal

of the tumor was achieved. Grossly, the tumor featured both solid and cysticcomponents. Histologic sections 5-μm thick, were prepared from 10% formalin-fixed, paraffin-embedded tissues. All sections were stained with hematoxylin andeosin and studied by light microscopy. We used the classic histopathologicaltechnique on tissue specimens. Immunohistochemical stains for the nuclearproliferation marker Ki-67 (DAKO, Denmark) were performed on 5-μm thick,formalin-fixed, paraffin-embedded tissue sections using the EnVision techniquewith diaminobenzidine as a chromogen and standard manual methods. Onmicroscopic examination, the solid part of the tumor expressed papillary sheets of

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Figure 2. Craniopharyngioma pathology. a) Papillary architecture with mature squamousepithelium forming pseudopapillae and an anastomosing myxomatous fibrovascular stroma withrare microvessels and small number of chronic inflammatory cells. (HE, ob.x4, oc.x10); b) Areaof low-grade basal cell dysplasia (HE, ob.x20, oc.x10) ; c) Area of low-grade basal cell dysplasiawith MIB-1 immunoreactivity not only in peripheral basal cell, but also in intermediate cells(MIB-1 immunoreactivity, ob.x10, oc.x10).

2a 2b 2c

Figure 3. Non contrast postoperativeCT demonstrated residual mixedtumor in the suprasellar cistern witha solid portion (¢) seen as a smallsoft-tissue isodense masssurrounding the cystic component(*) and being more prominent inanterior and right lateral walls of thecyst (a). The primarily cysticcomponent presented an extensioninto the third ventricle,subarachnoidian hemorrhage(black*) in the posterior part of thecystic component of the tumor, indilated occipital horns of the lateralventricles, and beneath the rightfronto-temporal bone (b).

3a 3b

well-differentiated squamous epithelial cells lining on prominent cores of highlyvascularized and edematous fibrous stroma with numerous neutrophils,lymphocytes and macrophages. No cytologically atypical features were noted (Figs.2a-c). First specimens showed areas of typical papillary pattern (Fig. 2 a), but withseveral foci of apparent proliferation of basal cells, composing a zone 3 to 4 cellsdeep. The basal layer showed a slightly disorderly pattern and basal cells variedsomewhat in size and shape. The nuclei stained darkly and showed rare normalmitotic figures. The normal histological pattern of the lining stratified squamousepithelium again became apparent above this layer (Fig. 2 b).

Early postoperative computer tomography without contrast performed using asingle slice CT with a slice thickness of 3mm for soft tissue images, demonstratedan inhomogeneously mixed tumor in the suprasellar cistern with a solid portion seenas a small soft-tissue isodense mass surrounding the cystic component and beingmore prominent in anterior and right lateral walls of the cyst (Fig. 3a). The primarilycystic component presented an extension into the third ventricle (Fig. 3b). There isalso a small subarachnoidian hemorrhage in the posterior part of the cysticcomponent of the tumor, and in dilated occipital horns of the lateral ventricles, andbeneath the right frontotemporal bone. There were no visible calcifications in oraround the tumor viewed on bone windows. The maximum diameters of the entirelyactual tumor were 20 mm cranio-caudal/ 25mm antero-posterior/ 25 mm transverse,but there was a marked reduction of the solid part as its thickness was 5 mm. CTimages were interpreted as postoperative residual craniopharyngioma.

First Postoperative CourseThe patient was well postoperatively. He did not develop any new

neurological deficit. No postoperative radiation therapy was given. Postoperativeendocrinological assessment in February 2007 (Table 1) revealed lower serumconcentrations of testosterone and cortisol levels (0.3 ng/ml, and 30 μg/dlrespectively), whereas free thyroxine (T4) showed more elevated serumconcentrations (1 ng/dl). Prostatic serum antigen (PSA) level was normal (0.1μg/ml; N<4 μg/ml). Hormone replacement therapy was administered (testosteroneundecanoate 1,000 mg in two administrations every six weeks, than 1,000 mg every3 months; Levothyroxine 50 μg/day; Desmopressin 0.2 mg/day; Prednisone 7.5mg/d) and a new re-evaluation after 6 months was established.

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Hormone Normal range Sept 2006 Feb 2007 Sept 2007 Aug 2008fT4 0.8-2.0 ng/dL 0.7 1 1.0 0.72

LH 1.0-13.8 mUI/mL 0.5 - 0.3 0.2Testosterone 2.0-6.9 ng/mL 1.6 0.3 3.1 1.2

PRL 0.94-20.94 ng/mL 3.1 - 11.4 35.8TSH 0.4-3.45 mUI/L 1.3 - 1.7 0.92Plasma cortisol 50-250 μg/dL 47.5 30 - -

Table1. Endocrinological evaluation

In September 2007 the patient carried out a new clinical, biological andtherapeutic re-evaluation, under treatment, (Table 1) showing almost normalthyroid functions (TSH = 1.7 μUI / ml, FT4 = 1 ng/dl). Testosterone levelsincreased (3.1 ng/dL) under treatment with testosterone undecanoate. MRIidentified a mixed solid-cystic tumor that established an intimate contact with theright sylvian artery (Fig. 4). The lesion was about 20/23/25 mm in diameters. Thetumour was in close relation with to the wall of III ventricle and its superior polecompressed the inferior part of the right frontal lobe. Supratentorial hydrocephalusdecreased from the previous examination. The MRI control examination with 3 mmthin sections postcontrast, centred on sella turcica and suprasellar region with T1WIfat suppression signal (T1FS) showed an important recurrence of the solid part ofthe tumour as well as the presence of a very small cystic component. The lesiondeveloped predominantly in the suprasellar region. Though the greatest diametersof entirely lesion were smaller than at the first MRI examination, the maximumdiameters of the solid part were increased in size since the last examination.Hormone supplementation included the administration of Testosterone undecanoate1,000 mg every 3 months; L Thyroxine 100 μg/day; Desmopressin 0.2 mg/day;Prednisone 7.5 mg/day).

Second Operation and Histopathological FindingsSince the patient's status worsened as the headache became diffuse, visual

acuity in both eyes decreased, and diabetes insipidus remained persistent, in August2008 a new MR imaging was made and revealed a T2WI inhomogeneoushyposignal tissue component which had increased. Around the solid part there wasa large cystic component so the entire lesion extended under the frontal lobe whereit exerted a small mass effect (Fig. 5). T1 WI showed posterior and left extensiontoward the lateral wall of III ventricle, causing a moderate increase of it, and

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4 5

Fig. 4. Precontrast coronal MRI T2WIdemonstrated a residual mixed tumor in thesuprasellar cistern with a solid portion (¢) seen asa small soft-tissue hyposignal mass surroundedby a small cystic (*) component (Sept 2007).

Fig. 5. Precontrast coronal MRI T2WI revealedthe recurrence of the mixed sellar and suprasellartumour (Aug 2008).

ambient cistern. A lot of fluid accumulated in and expanded the cystic componentwhich occupied the sella turcica, right laterosellar and retrosellar spaces and pushedthe solid component to the superior part of the tumor which seems to be in contactwith the frontal lobe with a minimal dural thickening at periphery of the lesion. Atthe same time endocrinological re-evaluation (Table 1) showed hypopituitarism,with low serum free thyroxine (T4), luteinizing hormone (LH) and testosteronelevels (0.72 ng/mL; 0.2 mlU/ml; 1.2 ng/ml respectively), whereas serum prolactin(PRL) level were higher and thyroid stimulating hormone (TSH) level was normal.

The patient was readmitted over 22 months postoperatively in the Neurosurgerydepartment. The neurosurgeons reopened old scar and made a subtotal resection of thetumour. The recurred tumor presented also areas of typical papillary pattern, but smallpatchy areas revealed basal low-grade dysplasia with complete loss of the normalparallel arrangement of the basal cells, with many cells lying in haphazard groups andorientation. There was a fairly marked proliferation of these basal cells so that theyextend approximately one-third of the way through the epithelium. Within the basalcells, there is a moderate variation in cell and nuclear size and shape, with increasedchromaticity of many of the nuclei. No frank tumor giant cells are present. Somenormal mitotic figures are scattered throughout, but no abnormal mitoses are noted.Squamous epithelial cells were present on the luminal surface of the dysplastic basalcells. Neovascularization and marked inflammatory infiltrate were seen beneath thedysplastic epithelium. Some other folds presented an abrupt transformation of typicalcraniopharyngiomatous epithelium into tongues or islands of squamous moderatedysplastic epithelium invaginated in highly vascularized fibrous core (Fig. 6 a) withouttypically craniopharingiomatous epithelium. The nervous tissue from the vicinity of thetumor presented pilocytic gliosis and small islands of tumor epithelial component.Proliferative activity of both specimens (initial and recurrent tumor) was determinedusing an immunohistochemical method with monoclonal antibody MIB-1.Considerable variation of the MIB-1 labeling indices (3-10%) was found between the

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Figure 6. Craniopharyngioma a) Papillary folds with abrupt transition from typicalcraniopharyngiomatous epithelium into tongues or islands of squamous moderate dysplasticepithelium invaginated in highly vascularized fibrous core, that contained also a marked inflammatoryreaction including lymphocytes, plasma cells, and small aggregates of foamy histiocytes (HE, ob.x4,oc.x10). b) Tongues of neoplasic epithelium with low-grade basal cell dysplasia exhibited higher Ki-67 LI compared with previous specimen (MIB-1 immunoreactivity, ob.x20, oc.x10)

6a 6b

different areas of the initial tumor, the highest values being encountered in small areasof dysplastic epithelium (Fig. 2 c). Recurrent tumor had higher Ki-67 LIs than itsprimary counterpart, especially in dysplastic areas where there was an enhancedexpression of proliferative index Ki-67 (over 20%). In all dysplastic areas, MIB-1immunoreactivity was seen in basal cells, but also in the intermediate cells (Fig. 6 b).The final diagnosis was squamo-papillary cranipharyngioma with dysplastic areas.

DISCUSSION

Craniopharyngiomas are considered to be histologically benign neoplasms.According to the World Health Organization Classification of Nervous Tissue Tumors,craniopharyngiomas are grade I tumors, but with a recognized infiltrative growth pattern(5). The sellar and suprasellar localization of craniopharyngiomas make them locallyaggressive. Craniopharyngiomas are often difficult to excise surgically, and they have ahigh recurrence rate. Many authors tried to establish predictive factors of recurrence andclinical outcome in craniopharyngioma patients, but the results are controversial.Predictors of poor prognosis include large tumor size, young age, severe hydrocephalus,hypopituitarism, and subtotal excision (1). On the other hand, Eldevik et al. couldn'tfind any histologic or radiologic characteristics to predict tumor recurrence (2). MRimages can realize the differentiation between squamous papillary andadamantinomatous craniopharyngiomas. Typical features of a squamous-papillarycraniopharyngioma include a predominantly solid or mixed solid-cystic spherical tumorin a suprasellar location in adults. The solid tumor parts have an inhomogeneous butintense enhancement, with small necrotic areas. The tumor cysts contain a watery liquidthat is hypointense on T1-weighted images and hyperintense on T2-weighted images.The adamantinous craniopharyngioma is a cystic or predominantly cystic lobulatedtumor, often observed in an intrasellar / suprasellar location in children. On precontrastT1- weighted images show typically single or multiple hyperintense cysts with thinperipheral enhancing rims. On T2-weighted images, these cysts are either hypointenseor hyperintense because they contain various amounts of cholesterol, triglycerides,methemoglobin, protein, and desquamated epithelium. The solid tumor part enhancesinhomogeneously on T1-weighted images, suggesting the possibility of small necroticareas. The hypointense areas within the solid tumor parts on T2- weighted imagesrepresent areas with deposits of hemosiderin and keratin nodules (6). In our case, MRimages correlates well with histopathological findings as the solid component had acauliflower-like aspect well identified on enhancing sections and papillary architecturewith mature squamous epithelium forming pseudopapillae on histopathologicalsections.

Several reports have attempted to provide evidence for two distincthistological subtypes that differ in their clinical behavior. Traditional descriptions

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of craniopharyngioma have focused on the adamantinomatous type, characterizedhistologically by a complex epithelial pattern with lobules, cystic spaces, andperipherally palisading cells. Keratin nodules ("wet keratin") and calcifications arewell-recognized diagnostic hallmarks. In 1984, Giangaspero et al. (7) reported, forthe first time, six patients with a new tumor variant and attempted to distinguish itas a clinicopathological entity. The histopathologic appearance of the less commonpapillary craniopharyngiomas is different. It is a well-circumscribed lesioncomposed of cores of fibrovascular stroma lined by well-differentiated squamousepithelium that mimics squamous papilloma. Unlike adamantinomatouscraniopharyngiomas, papillary craniopharyngiomas lack the peripheral palisadingof cells, the stellate reticulum, "wet" keratinization, microcalcification, microcysticdegeneration, and xanthogranulomatous inflammation with cholesterol clefts. Thisconstellation of histologic features was named papillary craniopharyngioma, andcorresponded to Kahn's adult type (8). So, craniopharyngioma is now classified intotwo major histologic types according to the microscopic pattern of the epithelium:adamantinomatous and squamous papillary form, which are considered to beclinically, genetically, and pathologically distinct entities (3, 4, 9, 10).

There is some debate about the prognosis of craniopharyngiomas based onhistopathological aspects. Adamantinomatous craniopharyngiomas are consideredto have a poor prognosis because of recurrences, but squamous papillary type isreported to behave in a less aggressive manner, being associated with a goodfunctional postoperative outcome and lower recurrence rate (11). Both Adamson etal. (12) and Kahn et al. (8) found no recurrences in patients with squamouspapillary craniopharyngiomas and emphasized that the recurrence of these tumorshas never been reported. On the contrary, Russel and Rubinstein stated that highlypapillary architecture in the epithelial formations of craniopharyngiomas was anunusual feature seldom seen in their experience and, when seen, was associatedwith aggressive brain invasion (13). Weiner et al. argued that both squamouspapillary and adamantinomatous tumors can recur when subtotally resected as therecurrence of craniopharyngiomas is more dependent on extent of surgical resectionthan on histopathological pattern (3).

Aside of sign and symptoms, we described MRI aspects together withhistopathological features and immunostaining findings of a low-grade basal celldysplasia in an early recurrent papillary craniopharyngioma. Reviewing the MRimages and microscopic specimens of both the initial and the recurredcraniopharyngiomas. In our case, MR images correlates well with histopathologicalfindings as the solid component had a cauliflower-like aspect well identified onenhancing sections and papillary architecture with mature squamous epitheliumforming pseudopapillae on histopathological sections. Also, we could see the rapidprogression of the solid tumoral component and the evolution of low-grade basalcell dysplasia from small patchy areas to more extensive in length and width.

Some investigators tried to correlate the proliferative potential ofcraniopharyngiomas with clinical outcomes by analyzing the immunostaining for

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MIB-1, the cell cycle nuclear antigen Ki-67. Low MIB-1 labeling indices (LIs)observed in the majority of tumors are in concordance with the slow growth and low-grade invasiveness associated with craniopharyngiomas. However, unlike otherintracranial neoplasms, where Ki-67 LIs have been useful in predicting tumor behavior,a clear relationship could not be demonstrated between MIB-1 immunoreactivity,morphological features and clinical outcomes in adults or children withcraniopharyngiomas (14, 15).

Our case showed a close relationship between the proliferation activity of thetumour, assessed by means of Ki-67 LI, and the risk of relapse as the mean Ki-67increased from first resected craniopharyngioma (7%) to recurrent papillarycraniopharyngioma (20%). Nishi and coworkers stated that a MIB-1 LI greater than7% is a useful predictor of regrowth/recurrence of craniopharyngiomas (15) and thisresult was introduced in OMS Revised Classification of Nervous System Tumours(5). Losa et al. (1) showed that the presence of a strong inflammatory reaction anddiabetes insipidus at presentation were independently associated with high Ki-67LIs. The authors took in discussion the possible hypothesis thatcraniopharyngiomas with a high proliferative index might induce a stronginflammatory reaction. On the other hand, they stated that diabetes insipidus couldbe a surrogate marker for an infiltrating and more aggressive tumor behavior (1).

Our patient presented with diabetes insipidus, too. On the other side, we identifiedmarked inflammatory infiltrate, mainly with lymphocytes, in fibrous cores. Theneoplastic epithelium expressed high values for Ki67 LIs for both specimens (initial andrecurred tumor), especially in small foci of basal cell dysplasia. So, we do not agree withthe conclusion of Losa et al. since for epithelial tumors the association of basal celldysplasia with inflammation and high Ki-67 is a well known aspect.

We analyzed the number and morphology of intratumoral vessels of resectedspecimens because some reports established that angiogenesis has prognosticsignificance in predicting the recurrence of craniopharyngiomas (17). Microscopicexamination of first resected specimens revealed some fibrous papillae with abundantvascularization. Second resected specimens showed marked vascularization of allintratumoral fibrous cores. Therefore, we discussed the possibility that markedangiogenesis could be the factor for early recurrence. Due to dysplastic aspects of thetumor, we raised the hypothesis that dysplasia could be also the cause of the earlyrecurrence of the squamo-papillary craniopharyngioma. It can be also taken intoconsideration the possibility of a de novo development in the future of a squamouscarcinoma because basal cell dysplasia is strongly implicated as a precursor of epithelialcancers and can be found adjacent to the foci of cancerous transformation (18).

In our case, dysplastic changes, however, became progressively more marked overthe course of the following years, but no frank anaplasia was present at the time of lastobservation. As the later course of events strongly suggests highly suspicioushistopathological findings, we take into consideration the question if dysplasia incraniopharyngiomas can be the forerunner of frank anaplasia and of progress to thedevelopment of a carcinoma. Malignant transformation in craniopharyngiomas, although

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extremely rare, does exist. The literature consists mostly of isolated case reports (19-23).The mechanism for malignant transformation in craniopharyngiomas is currentlyunknown. It was suggested a causal relationship between radiation therapy andmalignant transformation of craniopharyngiomas because 7 cases of reportedcarcinomas developed after administration of multiple courses of radiotherapy forrecurrent craniopharyngiomas (20, 21). De novo malignancy in craniopharyngiomas iseven more unusual, but also has an ominous prognosis (22).

In our case, the presence of basal cell dysplasia within areas showing features of atypical papillary craniopharyngioma supports the fact that a carcinoma can arise de novofrom an underlying craniopharyngioma without previous administration ofradiotherapy. But as not all dysplasia progresses to malignancy, nor does all cancer arisein preexisting dysplastic changes.

Four features of this case, however, must be stressed at this point:a. In the presented case, MR images correlate with histopathological findings as

the solid component had a cauliflower-like aspect on enhancing sections and a papillaryarchitecture with mature squamous epithelium forming pseudopapillae onhistopathological sections.

b. Although low-grade basal cell dysplasia in craniopharyngiomas is uncommon,pathologists should be aware of its occurrence as it may represent a possible causative factor forearly relapse. We propose the evolutive follow-up of the histopathological andimmunohistochemical aspects of a squamo-papillary craniopharyngioma not only for possibleoccurrence of dysplastic features, but also for its possible transformation in a carcinoma.

c. When a diagnosis of squamo-papillary craniopharyngioma is made, theradiologist must follow-up especially the solid part of the tumor concerning itsmaximum diameters, enhancing aspects, shape, location and compare them with thosefrom the previous images in order to identify an early relapse. It is also very importantto make the same protocols for each evaluation and if possible on the equipment withthe same magnetic field intensity.

d. This case imposes a multidisciplinary approach between the neuroradiologist,neuropathologist, endocrinologist and neurosurgeon in order to evaluate the squamo-papillary craniopharyngiomas with dysplastic features for an appropriate management.

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