—  SPECIALTY CONFERENCE  —

Neuropathology

Case 3 - Malignant Glioneuronal Tumor

Suzanne Powell
The Methodist Hospital
Houston, TX


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Clinical History:
A 71-year-old man presented with a 4-week history of word finding difficulty. An initial screening head CT followed by an MRI scan revealed a large ring-enhancing mass of the left temporal lobe that abutted the dura. The patient was referred to a tertiary care hospital where craniotomy and surgical resection of the mass were performed.


Case 3 - Slide 1
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Case 3 - Figure 1
MRI coronal section showing ring-enhancing temporal lesion abutting dura
Case 3 - Figure 2
Cytologic touch imprint preparation showing hypercellularity and nuclear pleomorphism
Case 3 - Figure 3
medium power: glial component with vascular proliferation and necrosis

Case 3 - Figure 4
medium power: small cell component with focal multinucleated cells
Case 3 - Figure 5
medium power: small cell component with mitotic activity
Case 3 - Figure 6
low power: small cell component and adjacent gliotic brain tissue

Case 3 - Figure 7
low power: GFAP negative tumor cells with occasional reactive astrocytes within and in adjacent gliotic brain tissue
Case 3 - Figure 8
low power: Synaptophysin positive neoplastic small cells
Case 3 - Figure 9
high power: marked nuclear pleomorphism in large apparently glial cells with mitoses

Case 3 - Figure 10
high power: GFAP immunoreactive large pleomorphic cells
Case 3 - Figure 11
high power: Synaptophysin immunoreactive large multinucleated neoplastic cells


Differential Diagnosis:
The clinical differential diagnosis of a solitary contrast-enhancing mass in an older adult patient is broad, but the most common etiologies are metastatic carcinoma, glioblastoma, and primary central nervous system large B-cell lymphoma; other entities to keep in mind are demyelinating pseudotumor and cerebral abscess.

The misdiagnosis of demyelinating pseudotumor as diffuse glioma is one of the most common serious diagnostic errors in surgical neuropathology, which can lead to the inappropriate administration of CNS irradiation and/or chemotherapeutic intervention, both of which can have deleterious side effects.

Final Diagnosis:
Malignant glioneuronal tumor

Discussion:
This case is an example of one of the emerging tumor types: a malignant glioneuronal tumor. Recently, several new entities have been described in this group of neoplasms including histologic patterns of relatively low grade tumors that include: rosette-forming glioneuronal tumor, glioneuronal tumor with neuropil-like islands and papillary glioneuronal tumor. This neoplasm, however, represents a malignant glioneuronal tumor characterized by marked nuclear pleomorphism, brisk mitotic activity, vascular proliferation and necrosis, in addition to glial and neuronal differentiation as revealed by GFAP and synaptophysin immunoreactivity.

Malignant glioneuronal tumors are considered to be rare lesions. A wide range of diverse morphologies can be seen in high-grade diffuse glioma, and mixed glioneuronal phenotypic expression in this category is increasingly recognized and under intense investigation. Several case reports have described malignant glioneuronal tumors that were unclassifiable according to the existing schemas.

Histologically, the majority of these tumors resemble one of the common malignant glioma subtypes, with glioblastoma-like features being the most common. Neuronal differentiation can be detected reliably by immunostaining that demonstrates individual cells expressing neuronal markers. In some cases, neuronal differentiation can not be appreciated until immunostained. "Malignant" cells are often felt to be of glial origin.

The biological behavior of malignant glioneuronal tumors is uncertain probably because these tumors have remained largely unidentified. In a clinicopathological study on large series of this entity, gross total surgical resection proved to be an independent and significant predictor of survival. However, more experience and further systemic analyses are required to confirm these findings and to solidify this tumor as a new pathological entity.

Oncologic neuropathology remains a dynamic, evolving field in which novel tumor types and subtypes of clinical importance continue to be recognized and characterized.

Take Home Points
  • The clinical differential diagnosis of a solitary contrast-enhancing mass in an older adult patient is broad, but the most common etiologies are metastatic carcinoma, glioblastoma, and primary central nervous system large B-cell lymphoma; other entities to keep in mind are demyelinating pseudotumor and cerebral abscess.

  • The misdiagnosis of demyelinating pseudotumor as diffuse glioma is one of the most common serious diagnostic errors in surgical neuropathology, which can lead to the inappropriate administration of CNS irradiation and/or chemotherapeutic intervention, both of which can have deleterious side effects.

  • A wide range of diverse morphologies that can be seen in high-grade diffuse glioma, and mixed glioneuronal phenotypic expression in this category is increasingly recognized and under investigation.

  • The evaluation of CNS neoplasms increasingly relies on the interpretation and integration of panels comprised of several phenotypic markers rather than on single antibodies.

  • Oncologic neuropathology remains a dynamic, evolving field in which novel tumor types and subtypes of clinical importance continue to be recognized and characterized.

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