—  SPECIALTY CONFERENCE  —

Neuropathology

Case 2 - Desmoplastic Non-Infantile Ganglioglioma

Tarik Tihan and Maher Alsughayer
UCSF School of Medicine
San Francisco, CA, and
King Hussein Cancer Center
Amman , Jordan


Click on each slide thumbnail image for an enlarged view


Clinical Summary
A 6-year-old boy presented with a history of unsteady gait and left arm weakness of one month duration that was progressive in nature. There was no other significant medical history. Physical examination revealed horizontal nystagmus, loss of coordination on the left side and left upper extremity weakness with atrophy. Preoperative CT and MRI scans were ordered, which showed a large right cerebral contrast-enhancing mass lesion with a cystic component. Craniotomy with resection of the mass were performed.


Case 2 - Figure 1 - Pre-operative axial contrast-enhanced CT scan
Case 2 - Figure 2 - Pre-operative axial non-contrast T1-weighted MRI
Case 2 - Figure 3 - Pre-operative axial T2-weighted MRI



Case 2 - Figure 4 - Pre-operative axial FLAIR MRI
Case 2 - Figure 5 - Pre-operative axial contrast-enhanced T1-weighted MRI
Case 2 - Figure 6 - Pre-operative coronal contrast-enhanced T1-weighted MRI



Case 2 - Figure 7 - H&E, medium magnification appearance
Case 2 - Figure 8 - H&E, epithelioid component
Case 2 - Figure 9 - H&E, epithelioid component



Case 2 - Figure 10 - H&E, ganglion-like cells in a desmoplastic glial background
Case 2 - Figure 11 - H&E, eosinophilic granular bodies
Case 2 - Figure 12 - Immunohistochemical stain for Collagen Type IV



Case 2 - Figure 13 - Immunohistochemical stain for GFAP
Case 2 - Figure 14 - Immunohistochemical stain for Neurofilament


Diagnosis
Desmoplastic Non-Infantile Ganglioglioma

Discussion
Desmoplastic supratentorial neuroepithelial neoplasms of infancy typically occur within the first 18 months of life, and are characterized by a prominent desmoplastic stroma and a divergent neuroepithelial tumor cell population. Such tumors with predominantly astrocytic phenotype were initially described by Taratuto et al. [14], while those with both glial and neuronal features were considered under the Desmoplastic Infantile Ganglioglioma (DIG) diagnosis by Vandenberg et al. [16]. Both of these neoplasms have been considered within the same spectrum of neoplasms [1, 10]. These infantile neoplasms are well recognized, and more than 100 cases have been reported to date.

Tumors with the typical radiological and histological features of DIG are extremely rare in the non-infantile population [3, 7, 8, 9, 12, 15, 17]. Kuchelmeister et al. first described the entity of desmoplastic non-infantile ganglioglioma (DNIG) in one adolescent and one adult patient [7]. Reports of unusual "desmoplastic" pediatric tumors can also be considered in this category [5].

The correct diagnosis of a desmoplastic ganglion cell tumor is paramount because these neoplasms may appear aggressive radiologically and histologically, and may be mistaken for a "malignant" glioma [2]. Even though the infantile tumors with similar features have an excellent prognosis and the non-infantile cases reported to date seem to have a very favorable outcome, long term prognosis of the non-infantile tumors and treatment options beyond surgery are still unclear.

DNIG is an exceedingly rare tumor, and the information from 11 patients form our opinion on the characteristics of this entity [3, 5, 7, 8, 9, 12, 13, 15, 17]. Patients with DNIG commonly present with significant neurologic deficits, seizures, or hemiparesis. The tumor typically involves the cerebral hemisphere. The pertinent imaging features include a large cystic and solid mass, and contrast enhancement in the solid component. Grossly, the tumors have large cysts containing small amounts of fluid. Some tumors can be attached to the adjacent parenchyma. The main histological features are the abundance of desmoplasia that gives the tumor a fibroblastic rather than a neuroepithelial character. Almost all cases of DNIG reported to date displayed large ganglionic cells resembling mature neurons, but it is possible that some examples may be predominantly of astrocytic phenotype, similar to some infantile tumors. Eosinophilic granular bodies, and perivascular lymphocytic infiltrates can be seen in some tumors. Despite the presence of gemistocytic cells in all tumors, the epithelioid cells with loose papillary pattern seen in our case has not been reported.

DIG and DNIG have numerous common and rare disparate features. The similarities are noted in the clinical presentation, the radiographic characteristics, and the profound desmoplasia. Histologically, there are more commonalities than the simple presence of desmoplasia. The fundamental differences between DIG and DNIG seem to be the age of onset and the rare histological features such as epithelioid and papillary architecture peculiar to some of the non-infantile examples. These features, like the age at presentation, may be of little or no consequence, or less likely, may be indicators of different etiological or pathogenetic process. Another intriguing aspect of DNIG is reflected in the case presented by Jay et al. [5]. These authors demonstrate an increasingly desmoplastic neoplasm with an extraordinary degree of neuronal differentiation and overlapping features between DIG and PXA. This case along with other reports of glioneuronal tumors with overlapping, or 'hybrid' features point to the possibility of a precursor cell with variable differentiation pathways [4, 6, 11]. The presence of DNIG in nature is clear, yet a separate pathologic entity from DIG is highly debatable. The importance of this case study is to document the clinicopathological features and comparison with cases published to date in order to aid future studies that can address the questions on the origin of these neoplasms.

A review of desmoplastic gangliogliomas in the non-infantile age group

Reference Age (yr) Sex Location Treatment Follow-up Outcome
Galatioto et al. [3] 17 M Temporal GTR, No adjuvant therapy N/A N/A
Jay et al. [5] 11 F Temporal GTR, 2nd Sx, 9 months AWD
Kuchelmeister et al. case#1 [7] 15 M Parietooccipital GTR, No adjuvant therapy N/A N/A
Kuchelmeister et al. case#2 25 M Occipital GTR, No adjuvant therapy N/A N/A
Marti et al. [8] 19 M Parietotemporal GTR, 2nd Sx N/A N/A
Onguru et al. [9] 14 M Parietooccipital GTR, No adjuvant therapy N/A N/A
Pommepuy et al. [12] 12 F Parietooccipital GTR, No adjuvant therapy 13 years NED
Rout et al. case#4 [13] 6 F Frontoparietal STR, RT 9 months NED
Torres et al. [15] 5 M Parietal GTR, No adjuvant therapy 1 year NED
Torres et al. [15] 7 F Parietal GTR, No adjuvant therapy 1 year NED
Woesler et al. [17] 14 M Temporal GTR, No adjuvant therapy 2 years NED

References

  1. de Chadarevian JP, Pattisapu JV, Faerber EN: Desmoplastic cerebral astrocytoma of infancy. Light microscopy, immunocytochemistry, and ultrastructure. Cancer 66:173-179, 1990.

  2. Duffner PK, Burger PC, Cohen ME, Sanford RA, Krischer JP, Elterman R, Aronin PA, Pullen J, Horowitz ME, Parent A, et al.: Desmoplastic infantile gangliogliomas: an approach to therapy. Neurosurgery 34:583-589; discussion 589, 1994.

  3. Galatioto S, Gullotta F: Desmoplastic non-infantile ganglioglioma. J Neurosurg Sci 40:235-238, 1996.

  4. Hirose T, Scheithauer BW: Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma. Acta Neuropathol (Berl) 95:649-654, 1998.

  5. Jay V, Edwards V, Rutka J, Mosskin M, Hwang P, Resch L: Unique desmoplastic cerebral tumor in a patient with complex partial seizures. Pediatr Dev Pathol 1:234-242, 1998.

  6. Komori T, Scheithauer BW, Parisi JE, Watterson J, Priest JR: Mixed conventional and desmoplastic infantile ganglioglioma: an autopsied case with 6-year follow-up. Mod Pathol 14:720-726, 2001.

  7. Kuchelmeister K, Bergmann M, von Wild K, Hochreuther D, Busch G, Gullotta F: Desmoplastic ganglioglioma: report of two non-infantile cases. Acta Neuropathol (Berl) 85:199-204, 1993.

  8. Marti A, Almostarchid B, Maher M, Saidi A: Desmoplastic non-infantile ganglioglioma. Case report. J Neurosurg Sci 44:150-154, 2000.

  9. Onguru O, Celasun B, Gunhan O: Desmoplastic non-infantile ganglioglioma. Neuropathology 25:150-152, 2005.

  10. Paulus W, Schlote W, Perentes E, Jacobi G, Warmuth-Metz M, Roggendorf W: Desmoplastic supratentorial neuroepithelial tumours of infancy. Histopathology 21:43-49, 1992.

  11. Perry A, Giannini C, Scheithauer BW, Rojiani AM, Yachnis AT, Seo IS, Johnson PC, Kho J, Shapiro S: Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature. Am J Surg Pathol 21:763-771, 1997.

  12. Pommepuy I, Delage-Corre M, Moreau JJ, Labrousse F: A Report of a Desmoplastic Ganglioglioma in a 12-year-old Girl with Review of the Literature. J Neurooncol, 2005.

  13. Rout P, Santosh V, Mahadevan A, Kolluri VR, Yasha TC, Shankar SK: Desmoplastic infantile ganglioglioma--clinicopathological and immunohistochemical study of four cases. Childs Nerv Syst 18:463-467, 2002.

  14. Taratuto AL, Monges J, Lylyk P, Leiguarda R: Superficial cerebral astrocytoma attached to dura. Report of six cases in infants. Cancer 54:2505-2512, 1984.

  15. Torres LF, Reis Filho JS, Netto MR, de Noronha L, Alessio AB, de Carvalho Neto A: [Infantile desmoplastic ganglioglioma: a clinical, histopathological and epidemiological study of five cases]. Arq Neuropsiquiatr 56:443-448, 1998.

  16. VandenBerg SR, May EE, Rubinstein LJ, Herman MM, Perentes E, Vinores SA, Collins VP, Park TS: Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis. J Neurosurg 66:58-71., 1987.

  17. Woesler B, Kuwert T, Kurlemann G, Morgenroth C, Probst-Cousin S, Lerch H, Gullotta F, Wassmann H, Schober O: High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient. Neurosurg Rev 21:31-35, 1998.