Skin metastases of glioblastoma in the absence of intracranial progression are associated with a shift towards a mesenchymal immunophenotype: report of two cases

Abstract

Glioblastoma multiforme (GBM) is the most malignantastrocytic tumour. Extra-neural spread is exceedingly rare,and usually develops at the time of intracranial progressionfollowing a surgical procedure [2–4]. Less frequently,metastases are a consequence of spontaneous tumour trans-dural extension or haematogenous spread. Here, wedescribe two unusual cases of GBM in which scalpmetastases appeared in the absence of intracranial diseaseprogression.Case 1A 48-year-old woman who presented with headache,speech disturbances and left facio-brachial paresis under-went magnetic resonance imaging (MRI), which revealed alarge right fronto-parietal mass with peripheral enhance-ment (Fig. 1a). The patient underwent gross total removalof the tumour, and a histopathological diagnosis of GBMwas made. Using immunohistochemistry, the tumour cellswere shown to co-express GFAP (intensely) and vimentin(less extensively). EGFR was positive in all tumour cellsand YKL-40 showed a faint cytoplasmic positivity in about30% of cells (Fig. 3). Conformal radiotherapy and adjuvanttemozolomide (TMZ) followed surgery. After 12 cycles,and in the absence of intracranial disease recurrence,the patient presented with a 2-cm scalp metastasis, closeto, but not contiguous with the surgical scar (Fig. 1b).A complete removal was performed and the diagnosis ofGBM was confirmed. Histologically, the metastasisshowed an infiltrating growth pattern dispersed intofibrotic tissue and consisted of a neoplastic population oflarge pleomorphic cells with a high mitotic index andstrong positivity for vimentin, while the GFAP stainingwas less diffuse than in the intracranial tumour. More-over, when compared with the primary lesion, EGFR wasnegative in the neoplastic cells, whereas a diffuse, intenseYKL-40 immunoreactivity was found (Fig. 3). The patientunderwent focal radiotherapy; 4 months later, an MRIrevealed distant intracranial progression in the righttemporal lobe. The patient received second-line chemo-therapy but soon the progressive intracranial disease ledto the patient’s death.Case 2A 53-year-old woman presented with a 1-month history ofspeech disturbances and facio-brachio-crural right motordeficit and underwent MRI, which showed a left frontalmass with contrast enhancement (Fig. 2a). She underwentcraniotomy with partial resection of the mass, and a diag-nosis of GBM was made. Immunohistochemistry showed adiffuse and intense GFAP reactivity with vimentin co-expression in a few GFAP-positive areas; EGFR positivitywas diffuse, whereas YKL-40 showed weak and focalexpression (Fig. 3). The patient underwent radiotherapyand standard TMZ treatment, and a partial response with a