Clinical records Melanotic neuroectodermal tumour of infancy By P.
KARMA,
O.
RASANEN
(Oulu)
and J. KARJA (Kuopio) SINCE Krompecher (1918) first described this tumour not more than 102 cases have been reported (Elomaa et al., 1973; Ostrander and Hayward, 1974). The rarity of the tumour is in contrast to the multitude of its names, which reflect the divergent opinions concerning its histogenesis. Of about 25 terms the most commonly used have been retinal anlage tumour, melanotic ameloblastoma, pigmented epulis, melanotic progonoma, and the nowadays widely accepted melanotic neuroectodermal tumour of infancy proposed by Borello and Gorlin (1966). Because the records of this rare benign tumour principally seen in the jaw are still scanty and its nature controversial, we believe it justified to present a further case and to discuss the specific features and especially the histogenesis of a tumour not too familiar to otolaryngologists.
Report of a case A 7-month-old boy, born after normal pregnancy and delivery, had a swelling in the upper alveolar ridge, that had grown rapidly since it was first noticed by his mother two weeks earlier. Physical examination revealed a firm painless tumour, diameter 1 -5 cm, covered by normal mucosa, anteriorly at d 51 region. Both jaws were still toothless. Otherwise the findings were normal. Roentgenologically, there was a sharply defined translucency resembling a cyst at d 51 region. Operation under general anesthesia revealed, immediately under the mucoperiosteum, a decidual central incisor attached to a bluish, firm tumour which filled the smooth-walled cavity in the alveolar process. The cavity consisted of anterior and posterior compartments partly separated by a bony septum. The posterior compartment extended underneath the palatal mucoperiosteum where the dislocated germ of the permanent central incisor was found attached to the tumourous mass. The tumour with both dentes was easily removed, and recovery was uneventful. Histologically, the tumour (Fig. 1) was non-encapsulated and made up of fibrous connective tissue with scattered pseudo-alveolar slits and openings of various forms and sizes throughout. The vasculature was rather scanty. In addition to relatively large stromal fibroblasts with pale nuclei, the rather cellular tumour contained three kinds of tumourous cells: pigmented, 'lymphocytelike' and spindle-shaped (Fig. 2a and 2b). The pigmented cells were large and variously shaped, most often cuboidal. The relatively abundant cytoplasm contained numerous small pigment granules (Fig. 3), which stained positively for 973
P. Karma, O. Rasanen and J. Karja
FIG. I.
can be seen at General view of the tumour. The germ of permanent central incisor (arrow) 50. x tion magnifica staining, HE tumour. the of periphery the lower
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Clinical records
FIG. 2a. The stroma is very cellular. In addition to fibroblasts there are pigmented cells principally around pseudo-alveoli, lymphocyte-like cells scattered throughout, and here and there some spindle-shaped cells. HE staining, magnification x 200.
melanin (Fontana) and negatively for iron (Turnbull). These cells principally lined the pseudo-alveolar structures but were also seen within them, as well as here and there outside them as small clusters in the stroma. The second type of cells were smaller, but had large hyperchromatic nuclei and very scanty cytoplasm resembling lymphocytes (Fig. 2a). These cells were seen within the pseudoalveoli and also, scattered and in clusters, elsewhere in the stroma. The third and rarest type of cells resembled the former in their hyperchromasia, but were spindle-shaped and had fibrillar extensions of varying length occasionally forming a kind of fibrillar network (Fig. 4). These cells were seen throughout the tumour but with varying density. No mitoses were seen. The germ of the permanent central incisor was separated from the tumour proper by a dense connective tissue zone (Fig. 1). It was devoid of cells typical of 975
P. Karma, O. Rasanen and J. Karja
FIG. 2b. The same view as in Fig. 2a with cobalt filter leaving only melanin-pigmented cells unfiltered. HE staining, magnification x 200.
the tumour and there was no sign of melanin, even in the epithelial cells of the enamel organ. The histopathological diagnosis was melanotic neuroectodermal tumour of \ infancy. The boy has now been followed up for 8 years without any sign of recurrence. Except for the missing d 11, his gingivo-alveolar and dental status is normal both physically and roentegenologically. Comment
Melanotic neuroectodermal tumour of infancy is seen during the first year • of life, most often during the first six months. There is no sex predilection. 75 of the 102 reported cases were in the maxilla, predominantly anteriorly, eight in ; 976
Clinical records
FIG. 3. Detailed view of Fig. 2 area showing large cells with melanin-pigmented granules. Pigmented cells line the pseudo-alveolus but are also seen within it. HE staining, magnification X 200, cobalt filter.
the mandible and 19 elsewhere (Elomaa et al., 1973): anterior fontanelle region (10), epididymis (3), temporal bone (2), zygoma (1), shoulder (1), thigh (i), and mediastinum (1). Typically the tumour presents a firm painless mass reaching a diameter of some centimeters within a few months. It is usually covered by normal gingival mucosa and is sometimes bluish-black in colour. When large, it may interfere with feeding. Histologically, the tumour is distinguished by its melanin-containing pigmented cells, and the typical microscopic patterns described above. Roentgenologically it presents a cystic translucency with displacement of possible 977
P. Karma, O. Rasanen and J. Karja
FIG. 4. Spindle-shaped cells having hyperchromatic nuclei and fibrillar extensions. HE staining, magnification X 800.
teeth in the affected area. Although the recurrences reported in 15 per cent of cases (Ostrander and Hayward, 1974) are probably due to incomplete removal, conservative removal of the tumour of the developing infant jaw is the treatment of choice. The histogenesis of the tumour is still enigmatic. Mummery and Pitts (1926), on the basis of the tumour's location in the jaw and its close association with dental elements, presumed an odontogenic origin. This formerly widely accepted (Tiecke and Bernier, 1956; Willis, 1962) theory cannot however, explain the occurrence of the tumour outside the jaw and the accompanying absence of dental elements (Borello and Gorlin, 1966). Halpert and Patzer (1947), assuming 978
Clinical records that pigmented cells were ciliary and smaller non-pigmented neuroblastic, believed the tumour to be of retinal anlage origin. Their theory, however, is not embryologically acceptable. Stowens' (1957) speculations that the tumour represents an atavism of sensory neuroectodermal development have not found support, either. Although many authors have found tumour structures to resemble neural elements morphologically (Halpert and Patzer, 1947; Stowens, 1957; Misugi et al., 1965), it has been difficult to identify them by ordinary neural stains. Borello and Gorlin (1966), however, found in their case high urinary levels of vanilmandelic acid, a characteristic of various tumours derived from neural crest cells. Consequently they suggested that the tumour was of neural crest origin, a theory that Koudstaad et al. (1968), with their comparative enzyme histochemical methods, confirmed, and which is now the most widely accepted. In our case, there were elements of a permanent incisor at the periphery of the tumour. However, they were separated by a fibrous connective tissue band from the tumour proper and contained neither cells resembling tumour cells nor any sign of melanin. Intra-operatively this incisor was found immediately under the palatal mucoperiosteum posteriorly, giving the impression of dislocation which was still more evident with the decidual incisor anteriorly. Bearing in mind that the tumour occasionally occurs outside the jaw and is then without dental elements, we cannot regard the presence of dental elements at the tumour site to be more than coincidental. Thus our case is not contradictory to a neural crest origin, which we accept as the most reliable theory of the histogenesis of these rare benign tumours. Summary The characteristics and especially the histogenesis of melanotic neuroectodermal tumour of infancy are discussed and a case of our own is documented. REFERENCES BORELLO, E. D. and GORLIN, R. J. (1966) Cancer 19, 196. ELOMAA, M., SAINIO, P., CALONIUS, P. E. B. and HIETANEN, J. (1973) Proceedings
of the Finnish Dental Society 69, 227. HALPERT, B. and PATZER, R. (1947) Surgery 22, 837. KOUDSTAAD, J., OLDHOFF, J., PANDERS, A. K. and HARDONK, M. J. (1968) Cancer
22, 151. KROMPECHER, E. (1918) Beitraege zur Pathologischen Anatomie und Allgemeinen Pathologie 64,165. MISUGI, K., OKAJIMA, H., NEWTON, W. A. Jr., KMETZ, D. R. and DELORIMIER, A. A.
(1965) Cancer 18, 447. MUMMERY, J. and PITTS, A. T. (1926) British Dental Journal 47, 12. OSTRANDER, R. B. and HAYWARD, J. R. (1974) Journal of Oral Surgery 32, 626. STOWENS, D. (1957) Journal of Pathology and Bacteriology 73, 43. TIECKE, R. W. and BERNIER, J. L. (1956) Oral Surgery 9, 1197. WILLIS, R. A. (1962) The Borderland of Embryology and Pathology, Butterworths, London, pp. 272-275. Department of Otolaryngology, University of Oulu, SF-90220 OULU 22, Finland.
979 5B
KARMA,
O.
RASANEN
(Oulu)
and J. KARJA (Kuopio) SINCE Krompecher (1918) first described this tumour not more than 102 cases have been reported (Elomaa et al., 1973; Ostrander and Hayward, 1974). The rarity of the tumour is in contrast to the multitude of its names, which reflect the divergent opinions concerning its histogenesis. Of about 25 terms the most commonly used have been retinal anlage tumour, melanotic ameloblastoma, pigmented epulis, melanotic progonoma, and the nowadays widely accepted melanotic neuroectodermal tumour of infancy proposed by Borello and Gorlin (1966). Because the records of this rare benign tumour principally seen in the jaw are still scanty and its nature controversial, we believe it justified to present a further case and to discuss the specific features and especially the histogenesis of a tumour not too familiar to otolaryngologists.
Report of a case A 7-month-old boy, born after normal pregnancy and delivery, had a swelling in the upper alveolar ridge, that had grown rapidly since it was first noticed by his mother two weeks earlier. Physical examination revealed a firm painless tumour, diameter 1 -5 cm, covered by normal mucosa, anteriorly at d 51 region. Both jaws were still toothless. Otherwise the findings were normal. Roentgenologically, there was a sharply defined translucency resembling a cyst at d 51 region. Operation under general anesthesia revealed, immediately under the mucoperiosteum, a decidual central incisor attached to a bluish, firm tumour which filled the smooth-walled cavity in the alveolar process. The cavity consisted of anterior and posterior compartments partly separated by a bony septum. The posterior compartment extended underneath the palatal mucoperiosteum where the dislocated germ of the permanent central incisor was found attached to the tumourous mass. The tumour with both dentes was easily removed, and recovery was uneventful. Histologically, the tumour (Fig. 1) was non-encapsulated and made up of fibrous connective tissue with scattered pseudo-alveolar slits and openings of various forms and sizes throughout. The vasculature was rather scanty. In addition to relatively large stromal fibroblasts with pale nuclei, the rather cellular tumour contained three kinds of tumourous cells: pigmented, 'lymphocytelike' and spindle-shaped (Fig. 2a and 2b). The pigmented cells were large and variously shaped, most often cuboidal. The relatively abundant cytoplasm contained numerous small pigment granules (Fig. 3), which stained positively for 973
P. Karma, O. Rasanen and J. Karja
FIG. I.
can be seen at General view of the tumour. The germ of permanent central incisor (arrow) 50. x tion magnifica staining, HE tumour. the of periphery the lower
974
Clinical records
FIG. 2a. The stroma is very cellular. In addition to fibroblasts there are pigmented cells principally around pseudo-alveoli, lymphocyte-like cells scattered throughout, and here and there some spindle-shaped cells. HE staining, magnification x 200.
melanin (Fontana) and negatively for iron (Turnbull). These cells principally lined the pseudo-alveolar structures but were also seen within them, as well as here and there outside them as small clusters in the stroma. The second type of cells were smaller, but had large hyperchromatic nuclei and very scanty cytoplasm resembling lymphocytes (Fig. 2a). These cells were seen within the pseudoalveoli and also, scattered and in clusters, elsewhere in the stroma. The third and rarest type of cells resembled the former in their hyperchromasia, but were spindle-shaped and had fibrillar extensions of varying length occasionally forming a kind of fibrillar network (Fig. 4). These cells were seen throughout the tumour but with varying density. No mitoses were seen. The germ of the permanent central incisor was separated from the tumour proper by a dense connective tissue zone (Fig. 1). It was devoid of cells typical of 975
P. Karma, O. Rasanen and J. Karja
FIG. 2b. The same view as in Fig. 2a with cobalt filter leaving only melanin-pigmented cells unfiltered. HE staining, magnification x 200.
the tumour and there was no sign of melanin, even in the epithelial cells of the enamel organ. The histopathological diagnosis was melanotic neuroectodermal tumour of \ infancy. The boy has now been followed up for 8 years without any sign of recurrence. Except for the missing d 11, his gingivo-alveolar and dental status is normal both physically and roentegenologically. Comment
Melanotic neuroectodermal tumour of infancy is seen during the first year • of life, most often during the first six months. There is no sex predilection. 75 of the 102 reported cases were in the maxilla, predominantly anteriorly, eight in ; 976
Clinical records
FIG. 3. Detailed view of Fig. 2 area showing large cells with melanin-pigmented granules. Pigmented cells line the pseudo-alveolus but are also seen within it. HE staining, magnification X 200, cobalt filter.
the mandible and 19 elsewhere (Elomaa et al., 1973): anterior fontanelle region (10), epididymis (3), temporal bone (2), zygoma (1), shoulder (1), thigh (i), and mediastinum (1). Typically the tumour presents a firm painless mass reaching a diameter of some centimeters within a few months. It is usually covered by normal gingival mucosa and is sometimes bluish-black in colour. When large, it may interfere with feeding. Histologically, the tumour is distinguished by its melanin-containing pigmented cells, and the typical microscopic patterns described above. Roentgenologically it presents a cystic translucency with displacement of possible 977
P. Karma, O. Rasanen and J. Karja
FIG. 4. Spindle-shaped cells having hyperchromatic nuclei and fibrillar extensions. HE staining, magnification X 800.
teeth in the affected area. Although the recurrences reported in 15 per cent of cases (Ostrander and Hayward, 1974) are probably due to incomplete removal, conservative removal of the tumour of the developing infant jaw is the treatment of choice. The histogenesis of the tumour is still enigmatic. Mummery and Pitts (1926), on the basis of the tumour's location in the jaw and its close association with dental elements, presumed an odontogenic origin. This formerly widely accepted (Tiecke and Bernier, 1956; Willis, 1962) theory cannot however, explain the occurrence of the tumour outside the jaw and the accompanying absence of dental elements (Borello and Gorlin, 1966). Halpert and Patzer (1947), assuming 978
Clinical records that pigmented cells were ciliary and smaller non-pigmented neuroblastic, believed the tumour to be of retinal anlage origin. Their theory, however, is not embryologically acceptable. Stowens' (1957) speculations that the tumour represents an atavism of sensory neuroectodermal development have not found support, either. Although many authors have found tumour structures to resemble neural elements morphologically (Halpert and Patzer, 1947; Stowens, 1957; Misugi et al., 1965), it has been difficult to identify them by ordinary neural stains. Borello and Gorlin (1966), however, found in their case high urinary levels of vanilmandelic acid, a characteristic of various tumours derived from neural crest cells. Consequently they suggested that the tumour was of neural crest origin, a theory that Koudstaad et al. (1968), with their comparative enzyme histochemical methods, confirmed, and which is now the most widely accepted. In our case, there were elements of a permanent incisor at the periphery of the tumour. However, they were separated by a fibrous connective tissue band from the tumour proper and contained neither cells resembling tumour cells nor any sign of melanin. Intra-operatively this incisor was found immediately under the palatal mucoperiosteum posteriorly, giving the impression of dislocation which was still more evident with the decidual incisor anteriorly. Bearing in mind that the tumour occasionally occurs outside the jaw and is then without dental elements, we cannot regard the presence of dental elements at the tumour site to be more than coincidental. Thus our case is not contradictory to a neural crest origin, which we accept as the most reliable theory of the histogenesis of these rare benign tumours. Summary The characteristics and especially the histogenesis of melanotic neuroectodermal tumour of infancy are discussed and a case of our own is documented. REFERENCES BORELLO, E. D. and GORLIN, R. J. (1966) Cancer 19, 196. ELOMAA, M., SAINIO, P., CALONIUS, P. E. B. and HIETANEN, J. (1973) Proceedings
of the Finnish Dental Society 69, 227. HALPERT, B. and PATZER, R. (1947) Surgery 22, 837. KOUDSTAAD, J., OLDHOFF, J., PANDERS, A. K. and HARDONK, M. J. (1968) Cancer
22, 151. KROMPECHER, E. (1918) Beitraege zur Pathologischen Anatomie und Allgemeinen Pathologie 64,165. MISUGI, K., OKAJIMA, H., NEWTON, W. A. Jr., KMETZ, D. R. and DELORIMIER, A. A.
(1965) Cancer 18, 447. MUMMERY, J. and PITTS, A. T. (1926) British Dental Journal 47, 12. OSTRANDER, R. B. and HAYWARD, J. R. (1974) Journal of Oral Surgery 32, 626. STOWENS, D. (1957) Journal of Pathology and Bacteriology 73, 43. TIECKE, R. W. and BERNIER, J. L. (1956) Oral Surgery 9, 1197. WILLIS, R. A. (1962) The Borderland of Embryology and Pathology, Butterworths, London, pp. 272-275. Department of Otolaryngology, University of Oulu, SF-90220 OULU 22, Finland.
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