According to Bonnin and Rubinstein, astroblastomas are defined histologically by the presence of astroblastic pseudorosettes and prominent perivascular hyalinization . However, pseudorosettes may also be observed in otherwise conventional astrocytomas, glioblastoma multiforme, embryonal neoplasms (PNET) and ependymomas . We agree that designation of astroblastoma should not be solely based on the these microscopic structural features but a constellation of clinical, radiological and histological findings as illustrated in the current case.
Mierau et al demonstrated two morphologically distinct cell types in astroblastoma . These two types of cells display an unusual organizational relationship namely: more primitive cells appeared nesting within the cytoplasm of the differentiated cells. The authors hypothesized that the more differentiated cells served as "nurse cells" for the maturing population. Both types of cells are nicely illustrated in this tumor.
To the best of our knowledge, this is the second published case on astroblastoma with rhabdoid morphology in the English literature. In Bannykh et al's article, the main emphasis is made on the radiological aspect . Histologically, the rhabdoid tumor cells in their case report are arranged in perivascular pattern and solid sheets. Prominent hyalinization of the vessel wall is shown. However, convincing pseudovascular rosettes with broad base cytoplasmic processes are not demonstrated. The tumor cells are positive for GFAP and vimentin. They are negative for EMA. Necrosis and mitotic figures are frequent. We concur with Bannykh's interpretation but we believe that more typical histological, immunohistochemical and ultrastructural features are illustrated in our current case and hence provide further evidence for the existence of this peculiar variant of astroblastoma.
A long list of differential diagnosis should be considered once rhabdoid cells are encountered in CNS tumor. Rhabdoid cells are regarded as tumor cells with eccentrically placed nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. In addition, globular eosinophilic cytoplasmic inclusions are easily appreciated. These inclusions represent whorls of intermediate filaments as confirmed by ultrastructural study. In the central nervous system, these tumor cells are typically observed in atypical teratoid/rhabdoid tumor (AT/RT). Occasionally, rhabdoid cells may also be seen in meningioma, glioma, melanoma, rhabdomyosarcoma and metastatic carcinoma.
Atypical teratoid/rhabdoid tumors occur mostly in children under the age of three but a small number of cases are reported in adult . Morphologically, the tumors are usually heterogeneous with neuroectodermal, mesenchymal and epithelial differentiation. The rhabdoid cells usually account for only a small proportion of the tumor. Mitotic figures are brisk and the proliferation activity is high (up to 100% as demonstrated with immunohistochemical marker Ki-67 [MIB-1]) . The tumor cells show a broad spectrum of immunohistochemical reactivity. They are consistently positive for EMA and vimentin and may have co-expression of GFAP, synaptophysin and cytokeratin. Occasionally, the tumor may consist of only rhabdoid cells arranged in sheets as in our case with no other lineage of morphologic differentiation found . However, the low mitotic activity, relatively low tumor proliferation rate and the presence of other features more specific for astroblastoma in this case are not supportive for the diagnosis of AT/RT. In addition, the preservation of INI1 protein expression in the current tumor speaks strongly against the diagnosis of AT/RT in which this protein is expected to be lost.
Rhabdoid papillary meningioma is an uncommon aggressive subtype of meningioma. It consists of rhabdoid tumor cells arranged in sheets and pseudopapillary pattern. This subtype typically presents as a recurrent rather than primary de novo case. In addition to immunoreactivity towards EMA, the tumor cells may show focal positivity for S-100 protein, cytokeratin and GFAP . Despite the morphological and immunohistochemical overlap between this kind of tumor and astroblastoma, our case is regarded as an astroblastoma because of the primary rather than recurrent presentation and its non-dural based location. In addition to the clinical history and site of tumor, hyalinized vessels, perivascular pseudorosettes and stromal hyalinization are not reported in rhabdoid meningioma. Furthermore, the diagnostic ultrastructural features of meningioma, namely interdigitating cytoplasmic processes and frequent intercellular tight junctions, are not identified in our case.
Another important differential diagnosis is ependymoma, especially the unusual type giant cell ependymoma . This tumor consists of single or multinucleated tumor cells arranged in sheets. Perivascular pseudorosettes and pseudopapillary areas are prominent. By immunohistochemistry, the tumor cells are positive for GFAP, S-100 protein and EMA with a characteristic dot-like pattern with EMA, representing the intracytoplasmic microlumina. Interestingly, this EMA staining pattern is also appreciated in our case. According to Hasselblatt, although this pattern is highly sensitive for ependymoma, it may also be observed in glioblastomas, fibrillary astrocytomas, and oligodendrogliomas which may be suggestive of aberrant ependymal differentiation. On the other hand, EMA with ring-like pattern is considered as more specific for ependymoma . This pattern is absent in our case. In contrast to the present case, ependymoma is expected to be located within the ventricle or in periventricular area but not the cerebral cortex. In addition, our case possesses a clean rather than fibrillary background that is expected in an ependymoma. Furthermore, the foot processes in the perivascular pseudorosette of ependymoma should be long and indistinct rather than short and broad as seen in this case. Finally, ultrastructural ependymal differentiation as characterized by cilia, intracytoplasmic mircolumina and long zonular adherens are not identified in our case.
Other possible differential diagnoses encompassing glioma, melanoma, rhabdomyosarcoma and metastatic carcinoma are excluded in our case due to the divergent immunohistochemical reactivity detected in the tumor cells with various lineage markers and negative staining pattern with other specific markers including HMB-45, actin and desmin.
Apart from the unusual rhabdoid appearance in the tumor cells, all the histopathological features typical for astroblastoma are present in this case. These features include pseudopapillary arrangement, astroblastic pseudorosettes, perivascular hyalinization and calcifications, absence of fibrillary background and a pushing tumor border. This diagnosis is also well supported by the age of presentation, anatomical location and radiological features of the tumor.
Survival for patients with astroblastoma is variable and depends of multiple factors including completeness of excision, histological grade and radiosensitivity. Bonnin and Rubinstein classified astroblastomas into low grade and high grade forms. Focal or multifocal regions of high cellularity with loss of typical papillary architecture, presence of anaplastic nuclear features, elevated mitotic indices (>5 per 10 HPF), endovascular proliferation and pseudopalisading necrosis correspond to the high grade group . Our current case displays some but not all of the high grade features namely high cellularity and presence of anaplastic nuclear features. However, Lau et al has reported a low grade astroblastoma that recurs in a short follow-up period after complete excision . On the other hand, long term survival has been reported in completely resected high grade astroblastoma treated with post-operative adjuvant therapy . Astroblastoma appears to be radiosensitive but no definite chemotherapy are available. Therefore the optimal protocol for adjuvant therapy remains to be established. Whilst complete surgical excision seems more achievable in view of its superficial location and well-circumscription, the tumor in this case is unfortunately incompletely excised in an attempt for critical cortical function preservation.
In summary, this article reported an astroblastoma with rhabdoid feature which is rarely described in the English literature. We believe that on top of the unusual tumors with rhabdoid cells, astroblastoma should also be considered in the list of differential diagnosis though its prognostic implication awaits further exploration.
We would like to thank Dr. Colin Smith, Senior Lecturer in Pathology (Neuropathology) of University of Edinburgh for his expert opinion in this case.
Contributed by Yuen Shan FAN, FRCPA, Philip C.W. LUI, FRCPA, Fiona K.Y. TAM, MBBS, Kwan Ngai HUNG, FRCS(Ed), Ho Keung NG, FRCPath, Suet Yi LEUNG, FRCPath