Brain Pathology Case of the Month - January 2005

FINAL DIAGNOSIS:   PRIMITIVE NEUROECTODERMAL TUMOR (PNET) SHOWING MULTILINEAL DIFFERENTIATION

DISCUSSION:

The differential diagnosis of this extremely unusual CNS tumor rests between PNET with multilineal differentiation and germ cell tumor. A diagnosis of atypical teratoid / rhabdoid tumor is not tenable, because the tumor contains mature tissues and does not comprise the polymorphic small cells of the atypical teratoid / rhabdoid tumor, which characteristically show focal immunoreactivities for a range of epithelial and mesenchymal markers [11]. A diagnosis of mature teratoma seems pragmatic, because of the presence of tissues derived from different cell lineages. Furthermore, the development of a PNET in a teratoma is an uncommon, but well recognized, phenomenon [9]. However, the cerebellum would be a very unusual site for a CNS germ cell tumor; nearly all are suprasellar or pineal [8]. In contrast, more than 90% of CNS PNETs arise in the cerebellum, and the question of whether a PNET (medulloblastoma) could differentiate into such diverse mature tissues then arises.

The medulloblastoma, with its capacity for neuroepithelial differentiation along neuronal or glial lines, is considered to be the archetypal PNET [8]. This differentiation occasionally manifests as a neuronal (ganglionic) or astrocytic morphophenotype, but is more usually expressed as immunoreactivity for a neuronal marker or GFAP [6]. In addition to neuroepithelial differentiation, PNETs can show evidence of differentiation along other embryonic lines. The current WHO classification recognizes the medullomyoblastoma and melanotic medulloblastoma as examples of this phenomenon [8], and there are reports of children with cerebellar PNETs that contain myeloid and epithelial elements (+ / - melanin producing cells), or cartilage [1, 2, 7]. In addition, one tumor from a series of three childhood medullomyoblastomas contained a "teratoma", with mature tissue from all three germ layers including cartilage, hair follicles and sweat glands [5], and another cerebellar tumor from a boy aged 5 years combined what was described as a medulloblastoma and mature teratoma [4].

We hypothesized that if this cerebellar tumor is a PNET with multilineal differentiation its cells might show a cytogenetic abnormality more consistent with this diagnosis than with a diagnosis of germ cell tumor. An isochromosome 17q (i17q) is present in about one third of medulloblastomas [3, 6], but is not characteristic of intracranial germ cell tumors [10]. Our FISH results are compatible with the presence of an i17q in both the small cell and mature components of the tumor, providing support for a diagnosis of PNET with multilineal differentiation. The case suggests that PNETs have a more diverse repertoire of differentiation than previously recognized.

REFERENCES:

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  11. Rorke, L.B., R.J. Packer, and J.A. Biegel, Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: Definition of an entity. J Neurosurg, 85(1): 56-65, 1996.

Contributed by Azzam Ismail, MD, Jayne M. Lamont, PhD, Deborah A. Tweddle, MBChB, PhD, Andrew D. Pearson, MD, Steven C. Clifford, PhD, David W. Ellison, MD, PhD

International Society of Neuropathology