- Email: [email protected]
Firm swelling on the anterior maxillary gingiva of an infant
JADA d ia g n o s in g o r a l d i s e a s e
Firm swelling on the anterior maxillary gingiva of an infant D. John Webb, DDS William B. Wescott, DMD, MS
A
^
1
l
■ ' ■ *
K '
Ralph W. Correll, DDS
6-day-old w h ite fem ale was brought to the dental clinic after the parents and pediatrician noted a mass in the maxilla at birth (Fig 1,2). The patient was able to breast-feed satisfactorily; how ever, there was some difficulty initiating attachment to the nipple. Tbe vaginal, full-term delivery had been normal and no other disease was evident. There was no parental history of medical problems. Clinical examination showed a 2.5 cm firm, nodular, exophytic mass attached to the maxillary anterior alveolar crest. No fluctuance was evident and no teeth were seen in the mass or the immediately adjacent area. The lesion emanated from a narrow stalk along the crest of the ridge and had not shown appreciable growth since birth. Radiographic examination showed no teeth in the mass and no bone erosion. An excisional biopsy was done, remov ing the lesion at the base of the stalk. An elliptical defect remained and was closed primarily with chromic sutures. The sur gical site healed uneventfully with no evidence of recurrence 6 months after re moval. Diagnosis
,
y
.
Gross exam ination of the formalin-fixed specimen showed a firm, smooth, glistening nodule with a light pink surface. The cut sur face was gray-white and homogeneous. Micro scopic examination of sections from the lesion disclosed u n ifo r m stra tifie d squam ous epithelium, with absence of rete pegs, overly ing a collection of large, closely packed, round to polyhedral cells with pale, eosinophilic granular cytoplasm (Fig 3). A thin zone of con nective tissue separated this mass of cells from the epithelium; however, it did not appear en capsulated. The cytoplasm was finely granular and the small, round, or ovoid cell nuclei were generally eccentrically placed. The scanty stroma showed delicate collagen fibrils and numerous blood vessels. Mitotic activity was not seen. On the basis of these findings, the gingival mass was diagnosed as a congenital granular cell epulis (congenital epulis).
Characteristics The congenital granular cell epulis (congenital epulis of the newborn, congenital granular cell
epulis, congenital granular cell myoblastoma, and gingival granular cell tumor) is an un common lesion of the newborn that is not con sidered to be a true neoplasm. From the cases reported in the literature, the congenital epulis is found about nine times more frequently in females than in males and in the maxilla about twice as often as in the mandible. Clinically, the lesions have the same coloration as the adjacent gingiva, yet in a few cases have appeared reddened. The gingival mass may arise from a pedicle or may have a broad attachment. Larger lesions may interfere with feeding and may compromise breathing. Approximately 164 instances of “congenital epulis” have been reported since Neumann’s description.1 A number of theories have been suggested that include origin from odon togenic, fibroblastic, myoblastic, histiocytic, mesenchymal, or neurogenic tissues or cells. It has also been suggested that the lesion is not neoplastic and arises as the result of either trauma, inflammatory, degenerative, or other processes. A review of the various theories, their proponents, and their findings was pre sented by Fuhr and Krogh.2 Because of the close histologic similarity between the con genital epulis and the granular cell myo blastoma, it is understandable why the lesion was named congenital granular cell myo blastoma. As this terminology was not univer sally accepted, many preferred to use the name “congenital epulis of the newborn.” Another source of confusion has been the grouping of cases of congenital epulis of the newborn and reporting them along w ith granular cell myoblastomas. Although the existence of the granular cell myoblastoma has been known for many years, its exact histogenesis has been the subject of controversy. Fust and Custer3 proposed the term granular cell neurofibroma rather than granular cell myoblastoma, suggesting that the tumors de veloped from nerve tissue. They also stated that there was no essential difference between those that occur in the tongue or in other sites and that they all were of neural origin; how ever, they did exclude four cases of so-called congenital epulis from their series. Even though the histologic pattern was similar, they were unable to demonstrate nerve compo nents. Then in 1952, these same authors listed the differences between congenital epulis and granular cell myoblastoma.4 They found a more uniform histologic structure in congeni tal epulis, along w ith absence of pseudoepitheliom atous hyperplasia, absence of neural components, a prominent vascular component, a higher incidence in infants and in females, and a characteristic location in the anterior incisor region of the maxilla or man dible. They concluded that the congenital epulis was a distinct entity and histologically was an “embryonal” hamartoma of a super numerary tooth bud implying arrested devel opment at an early stage.
One of two lesions present at birth in a female infant was the first to be subjected to ultramicroscopic observations in 1971.5 The lesion was found to be similar to the adult granular cell tumors previously described and no basic morphologic differences between the granular cell tumors and the congenital epulis could be found. Several distinct types of granules have been identified.6'9Miller and others,10in a review of the ultrastructural studies on granular cell tumors, agreed with others that the granules represented lysosomes at various stages.7'9 Their findings of autophagic vacuoles, myelin figures, and oval dense bodies with eccentri cally placed vacuoles were characteristic of stages in lysosomal degradation. They also noted that the number of phagolysosomes present was inversely proportional to the number of other cytoplasmic organelles, a finding previously described in granular cell epulis.11'12 A morphologically similar type of granular cell has been identified in sites of pre vious trauma.13 The neurogenic theory of origin for granular cell tumor (myoblastoma), particularly from Schwann cells, has gained additional support in recent years. In 44 cases of granular cell tumor reported by Bangle,14,15 32 of the tumors were intimately associated with peripheral nerves and one was confined within a segment of a small peripheral myelinated nerve in the buccal mucosa. After studying five granular cell tumors using histochemical procedures a n d e le c tro n m ic ro s c o p y , F ish e r an d W echsle r8 c o n c lu d e d that the fin d in g s strongly indicated a neural derivation of the le sions and their histogenesis from Schwann cells. Giunta and Adelman16 reported a granu lar cell tumor of the lower lip that was inti mately associated with a peripheral nerve. Further evidence for a neural tissue origin has been shown in recent years using S-100 protein, which is a nervous system-specific protein first isolated from bovine brain by Moore.17 In the central nervous system, S-100 protein is found principally in neurons and pe ripherally in Schwann cells of myelinated and unmyelinated nerves and satellite cells of dor sal roots and autonomic ganglia.18 It has also been found in the adrenal medulla, melano cytes, melanocytic nevi, Langerhans cells, interdigitating dendritic cells of the paracortex of ly m p h nodes, an d in chondrocytes. Schwannomas and neurofibromas contain cells positive for S-100 protein. Nakasato and colleagues19 showed localiza tion of a nervous system-specific protein in three cases of granular cell myoblastoma. Nerve bundles running through the lesion were stained specifically both in the Schwann cells and in the “granular” endoneurial cells. Peripheral nerve and an acoustic schwannoma used for control material also showed positive staining for S-100 protein, whereas muscle cells, fibroblasts, blood vessels, and tumor JADA, Vol. 109, August 1984 ■ 307
Fig 1 ■ C linical appearance of congenital granular cell epulis.
Fig 2 ■ Multilobed mass attached to m axillary gingiva.
O’Brien21suggested that the natural history of congenital epulis is to undergo resolution in the absence of trauma or infection, and this represents further evidence against the neo plastic nature of the lesion. Generally, these lesions are surgically re moved within a few hours or days after the birth of the infant. Larger lesions interfere with nursing and may even compromise breathing. Because the congenital epulis reacts in such a benign manner, “the line of resection should be close to it and err on the side of leaving tumor tissue if this is necessary to avoid dam age to tooth buds”.22 General anesthesia may be preferred to prevent movement and to avoid damage to developing teeth. Although the tumor extended to the margins of the specimen in some cases, there was no recurrence.11,23In contrast to the granular cell tumor, a malignant counterpart of congenital granular cell epulis has not been described.22
Summary
Fig 3 ■ Large, closely packed cells with eosino p h ilic granular cytoplasm.
cells of leiomyomas were not positive. In another report, all tumor cells in ten granular cell tumors stained intensely with antiserum to S-100. These findings further support the pro posed origin of granular cell tumors from Schwann cells. In a recent report, Lifshitz and colleagues20 examined a congenital granular cell epulis for S-100 protein to further define this lesion and its differences from granular cell tumor. Immunocytochemical staining with antiserum to S-100 protein of a congenital lesion in a female infant showed no localization within tumor cells. A few isolated cells in pericapillary locations in the lesion were strongly posi tive. In the same report, the granular cell tumors included in the study showed cyto plasm and nuclei positively stained. Their findings provide additional evidence that the histogenesis of congenital granular cell epulis and granular cell tumor is different. They also suggest that the congenital epulis may arise from mesenchymal cells. These findings are consistent with other reports.11,12 The clinical behavior of the congenital epulis is also different from that of granular cell tumors. Active growth of the congenital epulis apparently stops at birth in most cases and in some infants with several lesions there has been spontaneous regression of small le sions after surgical removal of larger ones. 308 ■ JADA, Vol. 109, August 1984
A female infant with a congenital granu lar cell epulis on the maxillary gingiva has been described. This is consistent with the most common clinical presenta tion of this lesion. The similarities and differences of this lesion are compared with granular cell tumor. The publication of this series is coordinated by the Veterans Administration Dental Education Center, West Los Angeles VA Medical Center, Los Angeles, and is supported in part by the Veterans Administra tion and by the American Dental Association. The opinions and assertions contained herein are those of the authors and are not to be construed as official or necessarily representing the views of the Veterans Administration. Dr. Webb is associate chief, division of oral and maxillofacial surgery, Harbor/UCLA Medical Center, Torrance; and assistant professor, School of Den tistry, University of California, Los Angeles. Dr. Wescott is director, Veterans Administration Dental Edu cation Center, West Los Angeles Veterans A dm inis tration Medical Center, Los Angeles; professor, de partment of oral diagnosis, radiology, and pathology, Loma Linda University School of Dentistry; and ad ju nct professor, departm ent of oral diagnosis, medicine, and pathology, School of Dentistry, U ni versity of California, Los Angeles. Dr. Correll is as sociate director, Veterans Administration Dental Education Center; and clinical assistant professor, department of pathology, University of Southern Cal ifornia School of Dentistry, Los Angeles. Address re quests for reprints to Dr. Wescott, VA Dental Educa tion Center (161), West Los Angeles VA Medical Cen ter, Los Angeles, 90073. 1. Neumann, E. Ein fall von congenitaler epulis. Arch Heilkunde 12:189-190, 1871. 2. Fuhr, A.H., and Krogh, P.H. Congenital epulis of
the newborn: centennial review of the literature and report of case. J Oral Surg 30:30-35, 1972. 3. Fust, J.A., and Custer, R.P. On the neurogenesis of so-called granular cell myoblastoma. Am J Clin Path 19:522-535,1949. 4. Custer, R.P., and Fust, J.A. Congenital epulis. Am J Clin Pathol 22:1044-1045, 1952. 5. Kay, S.; Elzay, R.P.; and Willson, M.A. Ultrastructural observations on a gingival granular cell tumor (congenital epulis). Cancer 17:674-680, 1971. 6. Sobel, H.J., and others. Granular cell myo blastoma. A n electron microscopic and cytochemical study illustrating the genesis of granules and aging of myoblastoma cells. Am J Pathol 65:59-78,1971. 7. Aparacio, S.R., and Lumsden, C.E. Light- and electron-microscopic studies on the granular cell myoblastomas of the tongue. J Pathol 97:339-355, 1969. 8. Fisher, E.R., and Wechsler, H. Granular cell myoblastoma— a misnomer. Electron microscopic and histochemical evidence concerning its Schwann cell derivation and nature (granular cell schwan noma). Cancer 15:936-954, 1962. 9. Whitten, J.B. The fine structure of an intraoral granular-cell myoblastoma. Oral Surg 26:202-213, 1968. 10. Miller, A.S., and others. Oral granular-cell tumors— report of twenty-five cases with electron m i croscopy. Oral Surg 44:227-237,1977. 11. Lack, E.E., and others. Gingival granular cell tumors of the newborn (congenital ‘epulis’): a clinical and pathologic study of 21 patients. Am J Surg Pathol 5:37-46, 1981. 12. Lack, E.E., and others. Gingival granular cell tumor of the newborn (congenital ‘epulis’): ultrastructural observations relating to histogenesis. H um Pathol 13:686-689,1982. 13. Sobel, H.J., and others. Reactive granular cells in sites of trauma. Am J Clin Pathol 61:223-234,1974. 14. Bangle, R., Jr. A morphological and histo chemical study of the granular-cell myoblastoma. Cancer 5:950-965, 1952. 15. Bangle, R., Jr. An early granular-cell myo blastoma confined within a small peripheral myeli nated nerve. Cancer 6:790-793, 1953. 16. G iunta, J.L., and A d e lm an, L.S. A n oral granular-cell tumor of neural origin. J Oral Med 34:106-108,1979. 17. Moore, B.W. A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 19:739-744,1965. 18. Stefansson, K., and Wollman, R.L. S-100 pro tein in granular cell tumors (granular cell myoblas tomas). Cancer 49:1834-1838, 1982. 19. N ak azato , Y ., and others. Im m u n o h is tochemical localization of S-100 protein in granular cell myoblastoma. Cancer 49:1624-1628,1982. 20. Lifshitz, M.S.; Flotte, T.J.; and Greco, M.A. Congenital granular cell epulis. Immunohistochemical and ultrastructural observations. Cancer 53:1845-1848, 1984. 21. O ’Brien, F.V., and Pielou, W.D. Congenital epulis: its natural history. Arch Dis Child 46:559-560, 1971. 22. Chamberlain, J.W. Congenital epulis (granular cell myoblastoma). J Pediatric Surg 2:158-163, 1967. 23. Freedman, G.L.; Hooley, J.R.; and Gordon, R.C. Congenital epulis of the newborn: report of two cases. J Oral Surg 26:61-64, 1968.
Firm swelling on the anterior maxillary gingiva of an infant D. John Webb, DDS William B. Wescott, DMD, MS
A
^
1
l
■ ' ■ *
K '
Ralph W. Correll, DDS
6-day-old w h ite fem ale was brought to the dental clinic after the parents and pediatrician noted a mass in the maxilla at birth (Fig 1,2). The patient was able to breast-feed satisfactorily; how ever, there was some difficulty initiating attachment to the nipple. Tbe vaginal, full-term delivery had been normal and no other disease was evident. There was no parental history of medical problems. Clinical examination showed a 2.5 cm firm, nodular, exophytic mass attached to the maxillary anterior alveolar crest. No fluctuance was evident and no teeth were seen in the mass or the immediately adjacent area. The lesion emanated from a narrow stalk along the crest of the ridge and had not shown appreciable growth since birth. Radiographic examination showed no teeth in the mass and no bone erosion. An excisional biopsy was done, remov ing the lesion at the base of the stalk. An elliptical defect remained and was closed primarily with chromic sutures. The sur gical site healed uneventfully with no evidence of recurrence 6 months after re moval. Diagnosis
,
y
.
Gross exam ination of the formalin-fixed specimen showed a firm, smooth, glistening nodule with a light pink surface. The cut sur face was gray-white and homogeneous. Micro scopic examination of sections from the lesion disclosed u n ifo r m stra tifie d squam ous epithelium, with absence of rete pegs, overly ing a collection of large, closely packed, round to polyhedral cells with pale, eosinophilic granular cytoplasm (Fig 3). A thin zone of con nective tissue separated this mass of cells from the epithelium; however, it did not appear en capsulated. The cytoplasm was finely granular and the small, round, or ovoid cell nuclei were generally eccentrically placed. The scanty stroma showed delicate collagen fibrils and numerous blood vessels. Mitotic activity was not seen. On the basis of these findings, the gingival mass was diagnosed as a congenital granular cell epulis (congenital epulis).
Characteristics The congenital granular cell epulis (congenital epulis of the newborn, congenital granular cell
epulis, congenital granular cell myoblastoma, and gingival granular cell tumor) is an un common lesion of the newborn that is not con sidered to be a true neoplasm. From the cases reported in the literature, the congenital epulis is found about nine times more frequently in females than in males and in the maxilla about twice as often as in the mandible. Clinically, the lesions have the same coloration as the adjacent gingiva, yet in a few cases have appeared reddened. The gingival mass may arise from a pedicle or may have a broad attachment. Larger lesions may interfere with feeding and may compromise breathing. Approximately 164 instances of “congenital epulis” have been reported since Neumann’s description.1 A number of theories have been suggested that include origin from odon togenic, fibroblastic, myoblastic, histiocytic, mesenchymal, or neurogenic tissues or cells. It has also been suggested that the lesion is not neoplastic and arises as the result of either trauma, inflammatory, degenerative, or other processes. A review of the various theories, their proponents, and their findings was pre sented by Fuhr and Krogh.2 Because of the close histologic similarity between the con genital epulis and the granular cell myo blastoma, it is understandable why the lesion was named congenital granular cell myo blastoma. As this terminology was not univer sally accepted, many preferred to use the name “congenital epulis of the newborn.” Another source of confusion has been the grouping of cases of congenital epulis of the newborn and reporting them along w ith granular cell myoblastomas. Although the existence of the granular cell myoblastoma has been known for many years, its exact histogenesis has been the subject of controversy. Fust and Custer3 proposed the term granular cell neurofibroma rather than granular cell myoblastoma, suggesting that the tumors de veloped from nerve tissue. They also stated that there was no essential difference between those that occur in the tongue or in other sites and that they all were of neural origin; how ever, they did exclude four cases of so-called congenital epulis from their series. Even though the histologic pattern was similar, they were unable to demonstrate nerve compo nents. Then in 1952, these same authors listed the differences between congenital epulis and granular cell myoblastoma.4 They found a more uniform histologic structure in congeni tal epulis, along w ith absence of pseudoepitheliom atous hyperplasia, absence of neural components, a prominent vascular component, a higher incidence in infants and in females, and a characteristic location in the anterior incisor region of the maxilla or man dible. They concluded that the congenital epulis was a distinct entity and histologically was an “embryonal” hamartoma of a super numerary tooth bud implying arrested devel opment at an early stage.
One of two lesions present at birth in a female infant was the first to be subjected to ultramicroscopic observations in 1971.5 The lesion was found to be similar to the adult granular cell tumors previously described and no basic morphologic differences between the granular cell tumors and the congenital epulis could be found. Several distinct types of granules have been identified.6'9Miller and others,10in a review of the ultrastructural studies on granular cell tumors, agreed with others that the granules represented lysosomes at various stages.7'9 Their findings of autophagic vacuoles, myelin figures, and oval dense bodies with eccentri cally placed vacuoles were characteristic of stages in lysosomal degradation. They also noted that the number of phagolysosomes present was inversely proportional to the number of other cytoplasmic organelles, a finding previously described in granular cell epulis.11'12 A morphologically similar type of granular cell has been identified in sites of pre vious trauma.13 The neurogenic theory of origin for granular cell tumor (myoblastoma), particularly from Schwann cells, has gained additional support in recent years. In 44 cases of granular cell tumor reported by Bangle,14,15 32 of the tumors were intimately associated with peripheral nerves and one was confined within a segment of a small peripheral myelinated nerve in the buccal mucosa. After studying five granular cell tumors using histochemical procedures a n d e le c tro n m ic ro s c o p y , F ish e r an d W echsle r8 c o n c lu d e d that the fin d in g s strongly indicated a neural derivation of the le sions and their histogenesis from Schwann cells. Giunta and Adelman16 reported a granu lar cell tumor of the lower lip that was inti mately associated with a peripheral nerve. Further evidence for a neural tissue origin has been shown in recent years using S-100 protein, which is a nervous system-specific protein first isolated from bovine brain by Moore.17 In the central nervous system, S-100 protein is found principally in neurons and pe ripherally in Schwann cells of myelinated and unmyelinated nerves and satellite cells of dor sal roots and autonomic ganglia.18 It has also been found in the adrenal medulla, melano cytes, melanocytic nevi, Langerhans cells, interdigitating dendritic cells of the paracortex of ly m p h nodes, an d in chondrocytes. Schwannomas and neurofibromas contain cells positive for S-100 protein. Nakasato and colleagues19 showed localiza tion of a nervous system-specific protein in three cases of granular cell myoblastoma. Nerve bundles running through the lesion were stained specifically both in the Schwann cells and in the “granular” endoneurial cells. Peripheral nerve and an acoustic schwannoma used for control material also showed positive staining for S-100 protein, whereas muscle cells, fibroblasts, blood vessels, and tumor JADA, Vol. 109, August 1984 ■ 307
Fig 1 ■ C linical appearance of congenital granular cell epulis.
Fig 2 ■ Multilobed mass attached to m axillary gingiva.
O’Brien21suggested that the natural history of congenital epulis is to undergo resolution in the absence of trauma or infection, and this represents further evidence against the neo plastic nature of the lesion. Generally, these lesions are surgically re moved within a few hours or days after the birth of the infant. Larger lesions interfere with nursing and may even compromise breathing. Because the congenital epulis reacts in such a benign manner, “the line of resection should be close to it and err on the side of leaving tumor tissue if this is necessary to avoid dam age to tooth buds”.22 General anesthesia may be preferred to prevent movement and to avoid damage to developing teeth. Although the tumor extended to the margins of the specimen in some cases, there was no recurrence.11,23In contrast to the granular cell tumor, a malignant counterpart of congenital granular cell epulis has not been described.22
Summary
Fig 3 ■ Large, closely packed cells with eosino p h ilic granular cytoplasm.
cells of leiomyomas were not positive. In another report, all tumor cells in ten granular cell tumors stained intensely with antiserum to S-100. These findings further support the pro posed origin of granular cell tumors from Schwann cells. In a recent report, Lifshitz and colleagues20 examined a congenital granular cell epulis for S-100 protein to further define this lesion and its differences from granular cell tumor. Immunocytochemical staining with antiserum to S-100 protein of a congenital lesion in a female infant showed no localization within tumor cells. A few isolated cells in pericapillary locations in the lesion were strongly posi tive. In the same report, the granular cell tumors included in the study showed cyto plasm and nuclei positively stained. Their findings provide additional evidence that the histogenesis of congenital granular cell epulis and granular cell tumor is different. They also suggest that the congenital epulis may arise from mesenchymal cells. These findings are consistent with other reports.11,12 The clinical behavior of the congenital epulis is also different from that of granular cell tumors. Active growth of the congenital epulis apparently stops at birth in most cases and in some infants with several lesions there has been spontaneous regression of small le sions after surgical removal of larger ones. 308 ■ JADA, Vol. 109, August 1984
A female infant with a congenital granu lar cell epulis on the maxillary gingiva has been described. This is consistent with the most common clinical presenta tion of this lesion. The similarities and differences of this lesion are compared with granular cell tumor. The publication of this series is coordinated by the Veterans Administration Dental Education Center, West Los Angeles VA Medical Center, Los Angeles, and is supported in part by the Veterans Administra tion and by the American Dental Association. The opinions and assertions contained herein are those of the authors and are not to be construed as official or necessarily representing the views of the Veterans Administration. Dr. Webb is associate chief, division of oral and maxillofacial surgery, Harbor/UCLA Medical Center, Torrance; and assistant professor, School of Den tistry, University of California, Los Angeles. Dr. Wescott is director, Veterans Administration Dental Edu cation Center, West Los Angeles Veterans A dm inis tration Medical Center, Los Angeles; professor, de partment of oral diagnosis, radiology, and pathology, Loma Linda University School of Dentistry; and ad ju nct professor, departm ent of oral diagnosis, medicine, and pathology, School of Dentistry, U ni versity of California, Los Angeles. Dr. Correll is as sociate director, Veterans Administration Dental Education Center; and clinical assistant professor, department of pathology, University of Southern Cal ifornia School of Dentistry, Los Angeles. Address re quests for reprints to Dr. Wescott, VA Dental Educa tion Center (161), West Los Angeles VA Medical Cen ter, Los Angeles, 90073. 1. Neumann, E. Ein fall von congenitaler epulis. Arch Heilkunde 12:189-190, 1871. 2. Fuhr, A.H., and Krogh, P.H. Congenital epulis of
the newborn: centennial review of the literature and report of case. J Oral Surg 30:30-35, 1972. 3. Fust, J.A., and Custer, R.P. On the neurogenesis of so-called granular cell myoblastoma. Am J Clin Path 19:522-535,1949. 4. Custer, R.P., and Fust, J.A. Congenital epulis. Am J Clin Pathol 22:1044-1045, 1952. 5. Kay, S.; Elzay, R.P.; and Willson, M.A. Ultrastructural observations on a gingival granular cell tumor (congenital epulis). Cancer 17:674-680, 1971. 6. Sobel, H.J., and others. Granular cell myo blastoma. A n electron microscopic and cytochemical study illustrating the genesis of granules and aging of myoblastoma cells. Am J Pathol 65:59-78,1971. 7. Aparacio, S.R., and Lumsden, C.E. Light- and electron-microscopic studies on the granular cell myoblastomas of the tongue. J Pathol 97:339-355, 1969. 8. Fisher, E.R., and Wechsler, H. Granular cell myoblastoma— a misnomer. Electron microscopic and histochemical evidence concerning its Schwann cell derivation and nature (granular cell schwan noma). Cancer 15:936-954, 1962. 9. Whitten, J.B. The fine structure of an intraoral granular-cell myoblastoma. Oral Surg 26:202-213, 1968. 10. Miller, A.S., and others. Oral granular-cell tumors— report of twenty-five cases with electron m i croscopy. Oral Surg 44:227-237,1977. 11. Lack, E.E., and others. Gingival granular cell tumors of the newborn (congenital ‘epulis’): a clinical and pathologic study of 21 patients. Am J Surg Pathol 5:37-46, 1981. 12. Lack, E.E., and others. Gingival granular cell tumor of the newborn (congenital ‘epulis’): ultrastructural observations relating to histogenesis. H um Pathol 13:686-689,1982. 13. Sobel, H.J., and others. Reactive granular cells in sites of trauma. Am J Clin Pathol 61:223-234,1974. 14. Bangle, R., Jr. A morphological and histo chemical study of the granular-cell myoblastoma. Cancer 5:950-965, 1952. 15. Bangle, R., Jr. An early granular-cell myo blastoma confined within a small peripheral myeli nated nerve. Cancer 6:790-793, 1953. 16. G iunta, J.L., and A d e lm an, L.S. A n oral granular-cell tumor of neural origin. J Oral Med 34:106-108,1979. 17. Moore, B.W. A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 19:739-744,1965. 18. Stefansson, K., and Wollman, R.L. S-100 pro tein in granular cell tumors (granular cell myoblas tomas). Cancer 49:1834-1838, 1982. 19. N ak azato , Y ., and others. Im m u n o h is tochemical localization of S-100 protein in granular cell myoblastoma. Cancer 49:1624-1628,1982. 20. Lifshitz, M.S.; Flotte, T.J.; and Greco, M.A. Congenital granular cell epulis. Immunohistochemical and ultrastructural observations. Cancer 53:1845-1848, 1984. 21. O ’Brien, F.V., and Pielou, W.D. Congenital epulis: its natural history. Arch Dis Child 46:559-560, 1971. 22. Chamberlain, J.W. Congenital epulis (granular cell myoblastoma). J Pediatric Surg 2:158-163, 1967. 23. Freedman, G.L.; Hooley, J.R.; and Gordon, R.C. Congenital epulis of the newborn: report of two cases. J Oral Surg 26:61-64, 1968.