Heterologous tissue elements in meianotic neuroectodermal tumor of infancy

P, J. Slootweg Department of Pathology, University Utrecht, the Netherlands

Hospital

Slootweg PJ: Heteroiogous elements in meianotic neuroectodermal tumor of infancy. J Oral Pathol Med 1992; 21; 90-2. Two cases of meianotic neuroectodermal tumor of infancy (MNTI) contained highly cellular stromal areas consisting of spindle cells exhibiting mitotic activity. In one case, single spindle cells exhibited the same immunohistochemical profile as tumor cells forming part of the epithelial component. In the other case woven bone was formed in a dense fibroblastic stroma. These tumor parts were judged to be heterologous tissue elements that also may be observed in other kinds of neuroectodermal ttimors and that reflect the potential of the neural crest to differentiate into various mesenchymal tissue types.

The derivation of meianotic neuroectodermal tumor of infancy (MNTI) from neural crest cells was initially proposed because of the elaboration of high levels of vanillylmandelic acid by the tumor cells (1) and subsequently supported by histologic, immunohistochemical and ultrastructural data (2). Neuroectodermal tumors in general may exhibit heterologous tissue elements as melanocytes, skeletal muscle, cartilage and bone which is explained by the divergent differentiation pathways that neural crest cells may follow (3, 4) and which includes maturing into various mesenchymal cell types. Therefore one would expect that such heterologous elements may also be found in cases of MNTI and in fact, rhabdomyoblastic differentiation as well as presence of muscle-specific proteins in MNTI tumor cells has been observed (5-7). In the present paper two cases are reported in which mesenchymal differentiation of the MNTI cells contributed to the morphogenesis of the stromal tumor parts.

ation including two tooth germs attached to the lesion resulted in a permanent cure, follow-up time being over 20 yr. Paraffin embedded material from this patient was still available. Additional slides were cut and immunohistochemistry was performed with the following antisera and dilutions: antivitnentin 1:5 (Dako), atiti-polykeratin 1:200 (Dako), anti S-100 1: 1000 (Dako), anti-J-NSE l;200 (Dako), anti-synaptophysin 1:5 (Boehringer), anti-NKI-C3 1:5 (Eurodiagnostics) and using the indirect PAP-method.

Key words: immunohistochemistry: jaws, neoplasms: meianotic neuroectodermal tumor of infancy, P, J, Slootweg, Dept, Pathology H04,312, University Hospital, Postbox 85500, 3508,,GA Utrecht, the Netherlands Accepted for publication August 24, 1991

Results Light microscopy

Stnall and large tumor cells could be discerned in both cases. The small cells had an irregularly cotitoured hyperchromatic nucleus and a small rim of deeply eosinophiiic cytoplasm. They were arranged in clusters of varying size and lacked any pigmentation. The large cells had centrally placed vesicular nuclei with distinct nucleoli and ample weakly eosinophiiic cytoplasm sometimes containing granu-

Patients and methods

Two cases of MNTI were available for analysis. Case I was a 15-month-old child with the tutnor located in the maxilla. Only slides and a pathology report were available, data on sex and followup lacking. Case 2 was a 3-month-old boy with a maxillary tumor. Enucle-

Fig, 1. Case 2. Micrograph shows stnall dark as well as large pale tumor cells, the latter exhibiting vesicular nuclei. Large tumor cells are lying in clusters as well as single. H & E, x300.

Heterologous tissue in MNTI

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was formed in areas of maximal stromal cellularity (Figs. 2, 3). Slides of Case 2 only contained tumor tissue, thus making analysis of the growth pattern not possible. Case 1 however showed ample uninvolved tissue. In some areas, there was a clear demarcation between tumor and adjacent jaw bone. At other sites, the border between tumor and surrounding tissue was less distinct. Extensive invasive growth however was not observed (Fig. 4). immunoiiistochemistry

PC Fig. 2. Case I. Micrograph shows nests and strands of pigmented epithelium with intervening highly cellular fibroblastic tissue. In these latter areas, deposition of plexiform bone can be observed, H & E , x 37,5,

lar brown tnelanin pigment. These large cells sometimes surrounded the clusters of small cells. Moreover these cells were observed as single cells in the stromal tumor parts where they exhibited a spindle-eell appearance with cytoplasmic exterisions. Mitotic figures were seen in the small as well as the large cells but were more numerous iti the latter. The stroma varied in ccllularity but cell-rich areas prevailed. In these cellrich areas the strotnal cells exhibited sometimes large vesicular nuclei with prominent nucleoli similar to the nuclei

of the above described large pigmented tumor cells and as some stromal spindle-cells had also ample eosinophiiic cytoplasm while more classical fibroblastlike stromal cells had cytoplasmic melanin pigment, it was often impossible to distinguish tumor cells from stromal cells (Fig, 1), Also in the stromal parts, mitoticfigurescould easily be identified. Focally the stroma adjacent to tumor nests exhibited hyalinization. All the above tnentioned histologic features were seen in Case 1 as well as Case 2. Only in Case 1, woven bone

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Fig. 3. Higher magnification frotn Fig. 2 in which the formation of plexiform bone in fibroblastic strorna is more clearly displayed. H & E, x 300.

Immunohistochemical findings only apply for Case 2. The small cells were positive for synaptophysin and J-NSE. The large cells exhibited positivity for vimentin, polykeratin, J-NSE and NKIC3. Stromal cells were invariably positive for vimentin but there were also spindle cells in the stromal areas that were positive for J-NSE. There were no cells exhibiting positivity for S-100. Discussion Neuroectodermal tumors may contain heterologous tissue elements originating through mesenchymal differentiation of the neural crest cells from which these tumors are derived (3, 4). In MNTI, ultrastructurally proven presence of rhabdomyoblasts and immunohistochemically demonstrated presence of tumor cells containing muscle-specific proteins are interpreted as examples of this divergent differentiation of neuroectodermal cells and as additional evidence for its derivation from the neural crest (5-7). Supportive although less firm evidence for mesenchymal differentiation of MNTI cells, in this case fibroblastic, comes from the observation that these tumors may contain plump spindleshaped cells occassionally containing melanin (8), The present observations indicate that a mesenchymally directed differentiation pathway may contribute to the morphogenesis of the stromal tumor elements as a gradual transition from large pigmented tumor cells lying in clusters to single spindle-shaped cells intermingled with ordinary fibroblasts was seen in both cases. The presence of the same mitotic activity in clustered as well as single cells was interpreted as additional evidence for the satne neoplastic nature of both single and clustered cells whereas the similarity in im-

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SLOOTWEG 2, DouROV N, MAYER R , MARTELAERE F DE, GODART S, G E P T S W , M A U R U S R .

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f.^. 4. C / Low po _r rog.-.ph _Lows rcl t onsh p between MNTI nd t surround ings. At the upper side, demarcation between tumor and adjacent jaw bone is clearly visible. At other sites, especially where tumor abuts on pulpal side of neighbouring tooth germ, the border between tumor and adjacent tissue is less distinct. Bony trabeculae are present distributed among entire tumor tissue. H & E, x 7.5.

munohistochemical profile between single and clustered cells in Case 2 supported their common source. The formation of bone in Case 1 was also interpreted as evidence for mesenchymal differentiation of the neuroectodermal tumor cells. Neural crest cells may form bone (4) and the demarcation between tumor and surrounding jaw bone made the possibility of this bone being due to remodelling activity in preexistent jaw bone engulfed by tumor unlikely.

Both MNTI cases serve to show the multipotentiality of the neural crest cells resulting in a diversity in phenotypic characteristics expressed in tumors thereof. References 1. BoRELLO ED, GoRLiN RJ. Melanotic neuroectodermal tumor of infancy - a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vanilmandelic acid. Cancer 1966; 19: 196-206,

neuroectodermal tumors (MNT) of infancy: intermediate filament, neuroendocrine and melanoma associated antigen profile. Modern Pattiotogy 1989; 2: 109 A (Abstract). 6, RoA J, ARAYA J , GONZALES S, GARRI-

DO C, Peripheral pigmented neuroectodermal tumor of infancy with rhabdomyoblastic differentiation, Pathot Res Pract 1990; 186: 403-7. 7,

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Heterologous tissue elements in melanotic neuroectodermal tumor of infancy.

Two cases of melanotic neuroectodermal tumor of infancy (MNTI) contained highly cellular stromal areas consisting of spindle cells exhibiting mitotic ...
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