Spontaneous malignant transformation of a supratentorial pilocytic astrocytoma

doi:10.1016/S1130-1473(10)70084-1

Neurocirugía

Volume 21, Issue 3, 2010, Pages 245-252

https://doi.org/10.1016/S1130-1473(10)70084-1 Get rights and content

Summary

Pilocytic astrocytoma (PA) is a circumscribed neoplasia considered as a grade I astrocytoma by the World Health Organization. Its most common location is the cerebellum and it develops during the first two decades of the life. Prognosis is mostly excellent if gross-total resection can be achieved, with 10-year survival rates of up to 80%. Anaplastic or malignant transformation (MT) can rarely occur and is usually related to previous radiation. Spontaneous MT has exceptionally been reported. Histological criteria for diagnosis of MT are unclear, so no consensus exists. We present an atypical case of MT of a frontal PA without previous radiotherapy in a 28 years old patient. Also, we review the literature about prognostic factors of PA and discuss histological features that are considered as anaplastic or malignant in the PA.

Resumen

El astrocitoma pilocítico es un tumor bien delimitado, que según la clasificación de la Organización Mundial de la Salud, se cataloga dentro del grupo de los astrocitomas de grado I. La localización más frecuente de esta neoplasia es el cerebelo y se manifiesta fundamentalmente en las dos primeras décadas. Siempre y cuando se consiga una resección total, el pronóstico es muy bueno, alcanzando una tasa de supervivencia del 80% a los diez años. De manera excepcional, puede haber casos de transformación anaplásica o maligna, normalmente asociados a radioterapia previa; se han descrito muy pocas situaciones de transformación espontánea. Existe mucha discusión a la hora de considerar los criterios de malignidad desde un punto de vista anatomopatológico. Presentamos un caso excepcional de transformación anaplásica de un astrocitoma pilocítico en un paciente de 28 años, al igual que revisamos los criterios pronósticos de esta neoplasia y discutimos los datos anatomopatológicos que se consideran de anaplasia o malignidad.

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Cited by (16)

Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient: Case Report and Review of the Literature
2020, World Neurosurgery
Citation Excerpt :
However, complete resection of the tumor is not always feasible if the tumor is located in the brainstem or hypothalamus. Occasionally, the tumor has recurred with malignant transformation, local recurrence, or multicentric or leptomeningeal dissemination.3,4 Investigation of the genetic profile including BRAF V600E and KIAA1549 is inevitable to confirm the correct diagnosis of PA.
Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported.
An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histologic examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was <1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, magnetic resonance imaging showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histologic findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed.
It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy. A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.
Cathepsin L silencing increases As<inf>2</inf>O<inf>3</inf> toxicity in malignantly transformed pilocytic astrocytoma MPA58 cells by activating caspases 3/7
2017, Experimental Cell Research
Citation Excerpt :
Despite this, in order to predict disease outcome and choose more aggressive treatments, it is very important to distinguish between PAs and PAs with anaplastic features [5]. Moreover, although surgical resection of PAs prolongs survival rates [3], some tumors recur with malignant transformation [2], in particular, those treated with radiation therapy [3,8,9]. PAs with anaplastic features demand more harsh radiotherapy and chemotherapy treatments [4,6], while new therapeutic modalities are also needed.
Low-grade, pilocytic astrocytomas are treated by resection, but additional therapy is necessary for those tumors with anaplastic features. Arsenic trioxide (As₂O₃) is emerging as an effective chemotherapeutic agent for treatment of malignant glioblastoma multiforme, where Cathepsin L silencing enables lower, less harmful As₂O₃ concentrations to achieve the desired cytotoxic effect. Here, we evaluated the effects of As₂O₃ combined with stable Cathepsin L shRNA silencing on cell viability/metabolic activity, and apoptosis in primary cultures of recurrent malignantly transformed pilocytic astrocytoma (MPA). These cells expressed high Cathepsin L levels, and when grown as monolayers and spheroids, they were more resistant to As₂O₃ than the U87MG glioblastoma cell line. Caspases 3/7 activity in MPA58 spheroids was not significantly affected by As₂O₃, possibly due to higher chemoresistance of primary biopsy tissue of less malignant astrocytoma versus the malignant U87MG cell line. However, As₂O₃ treatment was cytotoxic to MPA spheroids after silencing of Cathepsin L expression. While Cathepsin L silencing only slightly decreased the live/dead cell ratio in As₂O₃-treated MPA-si spheroids under our experimental conditions, there was an increase in As₂O₃-mediated apoptosis in MPA-si spheroids, as indicated by elevated caspases 3/7 activity. Therefore, Cathepsin L silencing by gene manipulation can be applied when a more aggressive approach is needed in treatment of pilocytic astrocytomas with anaplastic features.
Adult recurrent pilocytic astrocytoma: Clinical, histopathological and molecular study
2015, Neurochirurgie
Citation Excerpt :
Previously adult PA was thought to be a begin tumor, such as the paediatric PA [13,21,26,27]. Recently, a series of adult PA with malignant transformation and recurrence [28], as well as PA with unusual anaplastic pattern [21,29] were reported. In those previous studies the diagnosis of anaplastic adult cases of PA was mainly based on histopathology and imaging [5,10,21,30–32].
PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers.
We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor.
Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity.
Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses.
L’astrocytome pilocytique (AP) est une tumeur gliale de grade 1, survenant le plus souvent à un âge pédiatrique. Chez les adultes, en dépit de la similarité histologique, l’AP est de moins bon pronostic. Cette évolution défavorable est sous-tendue par un profil génétique spécifique. En effet, un grand nombre d’altérations moléculaires de valeurs diagnostiques, pronostiques et théranostiques seraient à l’origine de cette différence pronostique.
Dans cette étude, nous rapportons un cas de tumeur gliale infratentorielle chez un patient adulte de 58 ans. Les données d’imagerie et de neuropathologie suggèrent l’AP comme premier diagnostic. Deux ans après une résection complète, nous avons observé une récidive bifocale au siège initial de la tumeur avec une évolution rapide, accompagnée d’une deuxième localisation dans la région pinéale. Aussi bien la tumeur initiale que la récidive ont été explorées par techniques d’immunohistochimie (IHC), d’amplification et ligation multiplexes de sondes (MLPA) et d’hybridation in situ fluorescente (FISH).
Les données d’imagerie et neuropathologie suggèrent un diagnostic rare d’AP récidivant de l’adulte. Les analyses moléculaires par MLPA et FISH apportent la confirmation diagnostique en révélant la présence du gène de fusion KIAA1549:BRAF. D’autres altérations génétiques pouvant justifier l’agressivité de la tumeur ont également été détectées.
L’analyse moléculaire en matière d’AP de l’adulte s’avère complémentaire de l’histopathologie et de l’imagerie. En plus de sa valeur diagnostique connue, elle serait d’un grand apport pronostique. Elle devrait ainsi intégrer le protocole routinier du diagnostic des PA adultes.
Pilocytic astrocytoma. Presentation forms
2014, Revista Argentina de Radiologia
Nuestro objetivo fue mostrar y describir casos de astrocitomas pilocíticos (AP) supra e infratentoriales en sus formas típicas y atípicas de presentación en resonancia magnética y tomografía computada. Para ello, fueron seleccionados de nuestra casuística 32 pacientes: 24 tuvieron diagnóstico confirmado de AP por anatomía patológica y los 8 restantes mostraban gliomas de la vía óptica, por lo que el AP era el diagnóstico presuntivo más relevante. Veinte pacientes eran de sexo masculino y 12 de sexo femenino, con un rango etario entre los 10 meses y los 65 años. A todos se les pidió una resonancia magnética de cerebro con gadolinio, solo a 6 se les realizó difusión y espectroscopia, y en 6 también se llevó a cabo una tomografía computada.
Las localizaciones de los AP seleccionados (n = 32) fueron: vía óptica y región hipotálamo-quiasmática (n = 17), cerebelo (n = 7), tálamo (n = 6) y parénquima (n = 2).
En la resonancia magnética, la mayoría de los AP se presentaron como lesiones sólido-quísticas, iso-hipointensas en ponderación T1 e hiperintensas en ponderación T2 y mesencéfalo talámico, con realce poscontraste.
Cuatro pacientes presentaron características atípicas: 1 AP cerebeloso sólido con calcificaciones, 1 AP hipotalámico en un niño sin neurofibromatosis tipo 1 ni realce poscontraste, y 1 AP parenquimatoso en una mujer de 65 años.
Los AP son gliomas de grado I, según la clasificación de la Organización Mundial de la Salud. Sus localizaciones más frecuentes son la vía óptica, la región hipotálamo-quiasmática y la fosa posterior. Son tumores circunscriptos, sólido-quísticos, de baja celularidad y, en general, de lento crecimiento.
Our purpose is to illustrate and describe the typical and atypical imaging findings of supra and infratentorial pilocytic astrocytoma (PA) with computed tomography (CT) and magnetic resonance imaging (MRI). For this, 32 patients with PA from our case series were selected. Twenty-four patients had confirmed PA from histologic analysis. The remaining 8 patients presented optic pathway gliomas and PA was the most accurate presumptive diagnosis. All patients, 20 male and 12 female (age range 10 months-65 years), underwent unenhanced and enhanced MRI. Diffusion-weighted images and MR spectroscopy (MRS) were performed in 6 patients, and 6 patients underwent CT.
The locations of the PA selected (n = 32) were: optic pathway and hipotalamous-quiasmatic region (n = 17), cerebellum (n = 7), talamous (n = 6) and cerebral hemisphere (n = 2).
At MRI most PA appeared as solid-cystic masses, iso to hypointense in T1-weighted images and hyperintense in T2-weighted images and FLAIR, with post-contrast enhancement.
Four patients presented atypical characteristics: 1 solid cerebellum PA with calcifications, 1 hypothalamus PA in a child without NF1 with no contrast enhancement and 1 cerebral hemisphere PA in a 65 year old woman.
The PA are regarded as grade I tumors in the WHO classification. The optic pathway and the hypothalamic-quiasmatic region, as well as the posterior fossa are the most frequent locations. PA are typically well-circumscribed and solid-cystic lesions with low cellularity and slow growth.
Pilocytic astrocytoma with neoplastic gemistocytes undergoing spontaneous transformation to glioblastoma multiforme without prior radiotherapy
2011, Journal of Clinical Neuroscience
Citation Excerpt :
Using the WHO classification, features such as endothelial proliferation, palisading necrosis and multiple mitoses are indicators of malignant change but these tumours do not necessarily behave like a glioblastoma multiforme.2 This is based, in part, on the observation that these changes are not correlated with the same dismal outcome.2,6 This case demonstrates a patient with spontaneous malignant transformation without prior treatment with radiotherapy.
Pilocytic astrocytoma, the most common glioma of childhood, is considered a clinically benign tumour. Malignant transformation of this tumour is rare and thought to occur almost exclusively in the setting of prior radiotherapy. We describe a patient with mixed pilocytic and gemistocytic astrocytoma which transformed into a glioblastoma multiforme, leading to rapid deterioration and death of the patient, without prior radiotherapy.
Anaplastic Transformation of a Pilocytic Astrocytoma
2023, Canadian Journal of Neurological Sciences

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^☆: Otero-Rodríguez, A,; Sarabia-Herrero, R.; García- Tejeiro, M.; Zamora-Martínez, T.: Spontaneous malignant transformation of a supratentorial pilocytic astrocytoma. Neurocirugía 2010; 21: 245–252.

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Spontaneous malignant transformation of a supratentorial pilocytic astrocytomaTransformación maligna espontánea de un astrocitoma pilocítico supratentorial☆

Summary

Resumen

Int J Radiation Oncol Biol Phys

Mayo Clin Proc

Hum Pathol

Supratentorial lobar pilocytic astrocytomas: report of 45 operated cases, including 9 recurrences

Acta Neurochir (Wien)

Benign recurrence of a cerebellar pilocytic astrocytoma 45 years after gross total resection

Acta Neurochir (Wien)

Second surgery for recurrent pilocytic astrocytoma in children

Pediatr Neurosurg

Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents

J Clin Oncol

An unusual case of malignant pilocytic astrocytoma occurring in the eye

Virchows Arch

Late malignant recurrence of childhood cerebellar astrocytoma

Clin Neuropathol

Cerebral pilocytic astrocytoma

Cancer

Ascending central nervous spreading of a spinal astrocytoma

J Neurooncol

Development of anaplastic changes in low-grade astrocytomas of childhood

Neurosurgery

Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and review of the literature

Childs Nerv Syst

The proliferative potential of the pilocytic astrocytoma: the relation between MIB-1 labeling and clinical and neuro-radiological follow-up

J Neurooncol

J Neurooncol

Pilocytic astrocytomas in childr prognostic factors a retrospective study of 80 cases

Neurosurgery

Leptomeningeal dissemination of pilocytic astrocytoma at diagnosis in childhood Two cases report

Arq Neuropsiquiatr

Supratentorial pilocytic astrocytomas. A clinicopatholo- gic, prognostic, and flow cytometric study of 51 patients

Cancer

Juvenile pilocytic astrocitoma of the cerebrum in adults: A distinctive neoplasm with favorable prognosis

J Neurosurg

Astrocytomas of the cerebellum in children

J Neurosurg

Cellular proliferation in pilocytic and diffuse astrocytomas

J Neuropathol Exp Neurol

Age -related changes in diagnoses, histological features, and survival in children with brain tumors: 1930–1979 The Childhood Brain Tumor Consortium

Neurosurgery

Astrocytomas of the cerebellum. A comparative clinicopathologic study of pilocytic and diffuse astrocytomas

Cancer