244 Patología Revista latinoamericana Volumen 51, núm. 4, octubre-diciembre, 2013

Revista latinoamericana Informe de caso

Patología 2013;51:244-247

Unusual case of radiotherapy induced sclerosing meningiomaMartha L Tena-Suck,1 Ulises García-González2

1 Departamento de Neuropatología.2 Servicio de Neurocirugía. Instituto Nacional de Neurología y Neurocirugía, México.

Correspondence to: Martha L Tena Suck M.D. Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía. Insurgentes Sur 3788, colonia La Fama, CP 14269, E-mail: mlte-nasuck@gmail.com

Received: March 2013.Accepted: September 2013.

This article must be quoted: Tena-Suck ML, García-González U. Unusual case of radiotherapy induced sclerosing meningioma. Patología Rev Latinoam 2013;51:244-247.

www.revistapatologia.com

RESUMEN

Presentamos un caso raro de un hombre de 50 años que desarrolló un meningioma esclerosante asociado con radioterapia. El tumor inicial fue un meningioma de tipo fibroblástico grado I de acuerdo con la OMS de 10 años de evolución. El paciente se presentó con síntomas de masa cerebral ocupativa, clínica y radiológicamente correspondió a un meningioma. Se realizó estudio transoperatorio el cual fue muy difícil de realizar el extendido, observándose aisla-das células meníngeas con colágena de fondo. Histológicamente se observó un tumor formado por nidos y bandas irregulares de colágena densa con ocasionales células de aspecto meningotelial entremezclada en esta lesión densamente colagenizado. Por IHQ las células aisladas fueron positivas para queratina 8/18, EMA, vimentina, s-100. Laminina, metaloproteinasa 9 fueron positivas en las áreas esclerosantes y las células periféricas y astrocitos atrapados fueron PGAF positivas. La p53 fue positiva en las células meningoteliales y el índice mib1 fue de 5%. El meningioma hialini-zado es una lesión muy rara y se asocia con cambios postradiación. Por lo general se presentan cambios hialinizados asociados con meningioma y no sustitución total del tumor primario. El tratamiento es resección quirúrgica completa.

Palabras clave: tumores esclerosantes, meningioma esclerosante, immunohistoquímica, post-radioterapia.

ABSTRACT

We report a 50 years-old male who developed a sclerosing menin-gioma due the radiotherapy treatment of a fibroblastic meningioma grade I according WHO classification, more than one decade after. The patient presented with symptoms of space occupying lesion which clinically and radiological features were considered as me-ningioma. Crush intraoperatory pap smears showed a meningeal cell and collagen background. On histopathology, the lesion was composed of extensive non-calcifying collagenous whorls of varying size that formed sclerosing areas, while interposed tumor cells are sparse. Tumors cells were positive-expression to S-100, vimentin, EMA, p-53, keratins 8, 18. Laminin and metalloproteinase 9 were positive in sclerosing areas and in brain invasion and glial fibrillary acidic protein was positive in peritumoral location and trapped cells between tumor. The mib-1 labelling index was 5%. Sclerosing changes have been a rare presentation in meningioma, generally has been in focal or areas of sclerosing stroma. Sclerosing me-ningioma is a benign lesion for which surgical removal is the most advantageous treatment.

Ked words: sclerosing tumors, sclerosing meningioma, immuno-histochemistry, post-radiotherapy.

Sclerosing meningioma (SM) is a rare subtype of meningioma with differences in the histol-ogy and it has not so far been recognized by WHO classification.1-4 The most conspicuous

histological finding is the extensive collagen deposi-tion, so called ‘sclerosis’ with intermingled small cells population, those cells can be spindle or round cells with a clear cytoplasm giving a ‘fried egg’ appearance and those have been seen in pleomorphism, mitotic activity, brain invasion and necrosis.2-4 SM is a benign lesion for which surgical removal is the most advanta-geous treatment.

245Patología Revista latinoamericana Volumen 51, núm. 4, octubre-diciembre, 2013

Unusual case of radiotherapy induced sclerosing meningioma

CASE REPORT

50 years-old male with a history of head trauma; with a fracture of the left temporal bone and the skull base 15 years ago. He was diagnosed with fibroblastic meningioma in the right temporal lobe at the age of 40 years with incomplete resection and he received postoperative three-dimensional conformal radiotherapy. He was considered “disease-free” for nearly ten years. Recently he presented again with se-vere headaches, nausea and vomiting. CT and MRI showed right parieto-temporal tumor that was considered as me-ningioma recurrence (Figure 1a). On examination, he had no neurodeficit, he was underwent surgery with complete tumor resection. Crush intraoperatory pap smears analysis showed a meningeal cell and collagen background (Figure 1b and 1c). Histologically the tumor was composed of few meningothelial cells with clear appearance in perivascular distribution. Most of the part of the tumor was formed by

collagen bands, density and vague collagenous whorls and dense eosinophilic hailing material with varying degrees collagen (Figure 1d). Osseous metaplasia and calcospherites immersed in collagenous matrix (Figure 1e). The vessels were numerous with irradiation changes. Brain infiltration was observed as necrotic collagenous material irradiated in normal brain parenchyma (Figure 1F). Reactive and pleo-morphic astrocytes were observed (Figure 2a). Tumor cells exhibited positive immunoreactivity for EMA (Figure 2b), vimentin (Figure 2c), p35, neurofilament, NSE and cytoke-ratin were negative. MIB-1 (Ki-67) labeling index ranged of 5% was obtained. GFAP was positive in atypical astrocytes trapped in meddle of the tumor (Figure 2d). EVGF, laminin (Figure 2e) and metalloproteinase 9 (Figure 2f) were strong positive in the hyalinized stroma near to vessels and brain invasion. The patient was biopsied only of the initial injury, and he was never tumor resection performed because he refused such surgery so radiation therapy was given.

Figure 1. (a) MRI showed right parieto-temporal enhancement mass and hydrocephalus. (b) The crushed smear was haemorrhagic background with in (v) observed isolated and occasional eosinophilic cells and collagenous material deposition (h&Ex400). (d) The tumors showed that the most of the part of the tumor was formed by collagen bands, density and vague collagenous whorls and dense eosinophilic hailing material with varying degrees collagen. (e) Osseous metaplasia and calcospherites immersed in collagenous matrix. And (f) showed that the vessels were numerous with irradiation changes.

246 Patología Revista latinoamericana Volumen 51, núm. 4, octubre-diciembre, 2013

Tena-Suck ML and García-González U

DISCUSSION

Sclerosing meningioma is a rare entity that intraoperative analyses are difficult to realize. In our case the intraope-rative study was conducted by crushed smear, it not easy to spread abroad and cytological smear. The background was hemorrhagic and with eosinophilic collagenous mate-rial deposition, with occasional meningothelial cells were observed. No intraoperative diagnosis mas made.

Radiation is widely used for the treatment of menin-giomas even after gross total resection and especially after subtotal excision.2,7 Because sub lethal doses of radiation are capable of activating growth factor recep-tors and pro-survival signalling pathways, they have the potential to increase cell proliferation and resistance.6,7,9 The enhance of tumor cell migration and invasion in cells that received a sub lethal dose it is through the up regulation of proteolyses molecules (including uPA).6-9 The uPA-uPAR system is known to interact with several molecules on the cell surface (e.g., integrins, vitronec-tin, caveolin and G protein-coupled receptor) and also

to be involved in other cell signalling processes.5-7 As a result of this cascade, various growth factors are induced (e.g., βFGF, VEGF, HGF), cell migration and binding of integrins and other adhesion receptors to their ECM ligands, through the up regulation of secreted proteases, such as matrix metalloproteinases and plasminogen activators (uPA).5-7

Immnunoexpression of EVGF, EVGFR, βFGF, p53 and mib1 index mildly elevated in some areas of this tumor suggests that those changes are due to radiation. They may be changes suggestive malig-nancy but changes are radiotherapy. Sub lethal doses of radiation cause DNA damage and the production of reactive oxygen species, which in turn, trigger the activation of wild-type p53, ataxia telangiectasia mu-tated and other regulatory proteins including growth factor receptors like the ERBB family of receptors. Subsequently, several signalling pathways, such as MEK1/2/ERK1/2, JUN and PI3K/AKT enhance their activity and regulate cell survival, growth and other properties of tumour cells.5

Figure 2. (a) Brain Infiltration was observed as necrotic collagenous material irradiated in normal brain parenchyma. (b) Tumor cells exhibited positive immunoreactivity to EMA in meningoendothelial cells, (c) vimentin positive cells, (d) GFAP was positive in atypical astrocytes. (e) Laminin and metalloproteinase 9 (f) were strong positive in the hyalinized tumor stroma and in vessels in brain tissue.

247Patología Revista latinoamericana Volumen 51, núm. 4, octubre-diciembre, 2013

Unusual case of radiotherapy induced sclerosing meningioma

Atypical and reactive astrocytes may have been related to the production and distribution of the collagen with no inflammatory response and irradiation toxicity.3,4 Invasion to the extracranial portion might be associated with laminin and MMP-9 expression.5-7

Recognition of this meningioma variant is important in the differential diagnosis of meningioma versus other fibrous tumors of the meninges, including: solitary fibrous tumors of the meninges, and all sclerosing fibrous tumor and variant of epithelioid fibrosarcoma, neurinoma, li-posarcoma, and unusual forms of desmoplastic gliomas and chondroid tumors.1 Diffuse sclerosing variant of papillary carcinoma of the thyroid Brain metastases has been reported.

Desmoplastic gliomas are usually positive for GFAP and negative for EMA and cytokeratin.1

Idiopathic sclerosing inflammation injury is insidious and relentless course that makes distinction from neoplasia clinically difficult including Hodgkin disease. Some case s of meningiomas has been published.

The diagnosis of sclerosing meningioma is not easy to do neither clinic, radiological, histopathology or by cytomorphologic pap smears. In this case the small menin-gothelial cells in perivascular localization with malignant appearance immerse in collagenized stroma are difficult to interpreting and have been increased mistakes in the diagnosis.

Conclusions; we report a rare case of completely hiali-nizated meningioma after radiation with atypical features, ten year after primary fibroblastic meningioma resection.

REFERENCES

1. Perry A, Louis DN, Scheithahuer BW, Budka H, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Ed. WHO press. 3rd ed. Chapter meningiomas. pp164-180.

2. Haberler C, Jarius C, Lang S, Rössler K, et al. Fibrous meningeal tumours with extensive non-calcifying collage-nous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma. Neuropathol Appl Neurobiol 2002;28:42-47.

3. Im SH, Chung CK, Cho BK, Kim MK, Chi JG. Sclerosing me-ningioma: clinicopathological study of four cases. J Neurooncol 2004;68:169-175.

4. Kim NR, Im SH, Chung CK, Suh YL, et al. Sclerosing meningio-ma: immunohistochemical analysis of five cases. Neuropathol Appl Neurobiol 2004;30:126-135.

5. Mandriota SJ, Seghezzi G, Vassalli JD, Ferrara N, et al. Vascular endothelial growth factor increases urokinase re-ceptor expression in vascular endothelial cells. J Biol Chem 1995;270:9709-9716.

6. Park CM, Park MJ, Kwak HJ, Lee HC, et al. Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signal-ing pathways. Cancer Res 2006;66:8511-8519.

7. Wild-Bode C, Weller M, Rimner A, Dichgans J, Wick W. Suble-thal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma. Cancer Res 2001;61:2744-2750.