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Clear cell calcifying epithelial odontogenic tumor
Clear cell calcifying epithelial odontogenic tumor A case report
Andrea Schmidt-Westhausen 1, Hans Peter Philipsen 2, Peter A. Reichart 1 1Abteilung for zahnfirztliche Chirurgie/ Oralchirurgie Nord-Freie Universit&t Berlin, Germany and 2Oral Biology Unit, Faculty of Dentistry, University of Hong Kong, Prince Phillip Dental Hospital, Hong Kong
A. Schmidt- Westhausen, H P Philipsen, PA. Reichart." Clear cell calcifying epithelial odontogenic tumor. A case report. Int. J. Oral Maxillofac. Surg. 1992; 21: 47-49. Abstract. C l e a r cell v a r i a n t s o f o d o n t o g e n i c t u m o r s are rare. A case o f clear cell calcifying epithelial o d o n t o g e n i c t u m o r of the m a n d i b l e in a 38-year-old C a u c a s i a n m a l e is described. This case is c o m p a r e d to 8 previously r e p o r t e d cases. The origin o f clear cells in o d o n t o g e n i c t u m o r s is still u n k n o w n . E n bloc resection o f the t u m o r is r e c o m m e n d e d .
Clear cells are characteristic cellular c o m p o n e n t s o f the epithelial lining o f m o s t lateral p e r i o d o n t a l a n d gingival cysts in adults, or they m a y be f o u n d as clear-cell rests of the dental l a m i n a within the c o n n e c t i v e tissue wall o f these cysts H. W i t h considerably less frequency clear cells m a y occur in certain epithelial o d o n t o g e n i c t u m o r entities. I n fact, only 11 cases o f clear-cell t u m o r v a r i a n t s have been r e p o r t e d so far, 7 b e i n g clear-cell calcifying epithelial o d o n t o g e n i c t u m o r (CCCEOT) 1'2'3'8'13'14 a n d 3 clear-cell a m e l o b l a s t o m a (CCA) v a r i a n t s 9'12. In addition, clear-cell changes have been described in a calcifying o d o n t o g e n i c cyst ( C C C O C ) 1°. These t u m o r v a r i a n t s d e m o n s t r a t e a r a t h e r consistent " b i p h a s ic" histologic p a t t e r n with areas diagnostic of the t u m o r entity in question a n d o t h e r areas with conspicuous clear-cell c o m p o n e n t . It is n o t yet k n o w n w h e t h e r clear-cell v a r i a n t s of o d o n t o g e n i c tumors biologically b e h a v e differently f r o m the " m o t h e r t u m o r " a l t h o u g h the 2 cases of clinically aggressive C C A rep o r t e d by WALDRON et al.~2 m a y indicate t h a t such a possibility does exist. Prim a r y j a w t u m o r s of p u t a t i v e o d o n t o genie origin, c o m p o s e d principally o f clear cells, h a v e recently been described u n d e r the diagnosis o f clear-cell o d o n t o genie t u m o r ( C C O T ) 4.v. The clinical, r a d i o g r a p h i c a n d histological findings in a case o f C C C E O T are presented in this paper.
Case report A 38-year-old Caucasian male had for several months noticed a painless firm swelling slowly growing in the mandibular anterior
vestibule (44~31). The teeth in this region had been extracted some years previously. An orthopantomogram showed a radiolucency of 2.5 cm in diameter extending from the right mandibular canine to the left first incisor (Fig. 1). Ill-defined radiopacities were found in the cranial part of the cystic lesion. The mucosa overlying the lesion was intact. Incisional biopsy was taken resulting in the tentative diagnosis of CEOT. En bloc resection of the tumor-bearing area was performed under general anesthesia. The patient's postoperative course was uneventful and on examination 2 years later no sign of recurrence was found.
Histopathology The operation specimen was subjected to routine histological procedures and sections were stained with hematoxylin and eosin, van Gieson's connective tissue stain and PAS: Tumor tissue retrieved from formalin was postfixed in 1% osmium tetroxide and embedded in araldite. Ultrathin sections were examined in a JEOL 100 CX electron microscope. Examination in LM revealed strands, sheets and islands of proliferating epithelial tumor cells in a mature fibrous connective tissue stroma (Fig. 2). The cytoplasm of the polyhedral cells was eosinophilic and finely granular. The nuclei were generally uniform
Key words: calcifying epithelial odontogenic tumor; clear cells. Accepted for publication 2 October 1991
in size and shape but focal cell groups showed nuclear polymorphism, hyperchromatism and bi- and multinucleation (Fig. 3). Occasional mitotic figures were detected (Fig. 4). Cell necrosis was found centrally in some larger tumor islands. Rounded clear cells occurred as single or clustered components in a large number of tumor islands or sheets (Fig. 5). The clear cells appeared to develop from the CEOT tumor cells through continuous accumulation of initially PAS-positive material. In later stages the cytoplasm of the clear cells appeared empty. Occasionally, bridging between individual tumor cells could be demonstrated. Deposits of calcified material and amyloid-like substance were found in several areas of the tumor (Fig. 6). In TEM the cytoplasm of the clear cells contained remnants of tonofilaments, scattered clusters of ribosomes, a few profiles of endoplasmic reticulum but most cells appeared almost without detectable organelles. A search for rod- and racket-shaped structural Birbeck's granules was negative. Desmosomes were found between clear cells and between these and the tumor cells.
Discussion T h e n u m b e r a n d d i s t r i b u t i o n o f clear cells o b s e r v e d in the present case indicate
Fig. 1. Orthopantomogram showing a radiolucency between the mandibular right first premolar (44) and left first incisor (31). Diffuse radiopacities are seen in the central and cranial part of the lesion.
48
S c h m i d t - W e s t h a u s e n et aL Fig. 2. Low magnification of tumor invading bone. A solid area of tumor composed of odontogenic epithelial cells and clear cells is surrounded by dense collagenous tissue. A small island of calcification is seen in the upper part of the micrograph (arrow). H&E, x 60.
Fig. 3. Strands of epithelial cells with few clear cells showing hyperchromatic nuclei. H&E, x 100.
beck's granules which are cytoplasmic organelles characteristic of Langerhans' cells. Such granules, however, were not revealed in the present case. The ultrastructural findings in our case indicated that the clear cells were of epithelial origin and thus very likely originated from C E O T tumor cells through a possible degenerative process. Clear cells in odontogenic tumors may occur singly or in clusters giving a glandular configuration. If the latter occurs and if the clear cells numerically dominate the tumor tissue diagnostic problems m a y arise. The histopathology then mimics a clear-cell salivary gland t u m o r or even a metastatic renal cell carcinoma. Immunohistochemical and ultrastructural investigations may contribute to the correct diagnosis through a demonstration af glandular or non-glandular cellular characteristics. The small number of cases of clearcell containing odontogenic tumors published so far does not allow any conclusions to be drawn as to biological behaviour or prognosis of these tumors. As reported by WALDRON et al. 12 and HANSEN et al. 6 occurrence of the clear cells may prove to be a sign of increased tumor aggressiveness indicating a more radical surgical approach. The clinical course of the present case, which did not show recurrence after 2 years, suggests a particular aggressiveness is not always associated with the presence o f clear cells. Nevertheless en bloc resection of such tumors is strongly recommended.
Acknowledgements'. We are grateful to Dr. Dr. H. F. Behnsen for referring the case and to Prof. Dr. H. S. Koppang for confirmation of the histopathological diagnosis. We also thank Mr. J. Eckert for his excellent photography. Fig. 4. Tumor area consisting mainly of clear cells with glandular configuration. H& E, xl00.
that this tumor qualifies for the diagnosis of a clear-cell variant of C E O T with a histology consistent with that of the cases described previously 1'2'3'8'13'14.Transition between clear cells and C E O T tumor cells was evident throughout the tumor tissue. The true nature of clear cells in C C C E O T is still not known. Findings in the case presented here show, however, that clear cell changes may originate
from individual C E O T t u m o r cells as an accumulation of initially PAS-positive material. As the "ballooning" increases, the nucleus is displaced toward the cell periphery and the PAS-positivity is gradually lost. A rather in'teresting ultrastructural finding was reported by ASANO et al. 3 who, in clear cells occurring in a case of CEOT, demonstrated so-called Bir-
References
I. ABRAMSAM, HOWELLFV. Calcifying epithelial odontogenic tumors: report of four cases. JADA 1967: 74: 1231-40. 2. ANDERSONHC, KIM B, MINKOWITZ.Calcifying epithelial odontogenic tumor of Pindborg. Cancer 1969: 24:585 96. 3. ASANO M, TAKAHASHIT, KUSAMAK, et al. A variant of calcifying epithelial odontogenic tumor with Langerhans cells. J Oral Pathol Med 1990: 19: 430-4. 4. EVERSOLELR, BELTONCM, HANSENLS. Clear cell odontogenic tumor: Histochemical and ultrastructural features. J Oral Pathol 1985: 14:603 14.
Clear cell calciJj~ing epithelial odontogenic tumor 5. GREER RO, RICHARDSON JE Clear-cell
calcifying epithelial odontogenic tumor viewed relative to the Pindborg tumor. Oral Surg 1976: 42:775 9. 6. HANSEN LS, EVERSOLELR, GREEN TL, POWELL NB. Clear cell odontogenic tumor- a new histologic variant with aggressive potential. Head Neck Surg 1985: 8: I15 23. 7. KOPPANGHS, BANGG, HANSENLS, GILT~UVS MOE O, AKSDAL E. Hellzellinger odontogener Tumor. Kasuistischer Beitrag. Dtsch Z Mund Kiefer GesichtsChir i988: 12: 356-60. 8. KROLLSSO, PIND~ORGJJ. Calcifying epithelial odontogenic tumor. Arch Pathol. 1974: 98: 206-10.
9. MULLERH, S c o o r w m R Clear cell differentiation in an ameloblastoma. J Maxillofac Surg 1986: 14: 158-60. 10. NG KH, SIAR CH. Clear cell change in a calcifying odontogenic cyst. Oral Surg 1985: 60:417 19. 11. RASMVSSON LG, MAGNUSSON BC, BORRMANH. The lateral periodontal cyst. A histopathological and radiographic study of 32 cases. Br J Oral Maxillofac Surg 1991: 29: 54-7. 12. WALDRONCA, SMALLIA, SILVERMANH. Clear cell ameloblastoma- an odontogenic carcinoma. J Oral Maxillofac Surg 1985: 43: 70~17. 13. WALLACEJ. Calcifying epithelial odontogenic tumour ("Pindborg tumour"): A
49
case report. Br J Plast Surg 1974: 27: 28-30. 14. YAMAGUSHIA, KOKUBUJM, TAKAGI M, [SHIKAWA G. Calcifying epithelial odontogenic tumor: histochemical and electron microscopic observations on a case. Bull Tokyo Med Dent Univ 1980: 27: 129-35. Address:
A. Schmidt- Westhausen Abteilung fiir zahniirztliche Chirurgie/ Oralchirurgie-Nord Freie Universit& Berlin F6hrer St~ 15, D-IO00 Berlin 65 Germany
Andrea Schmidt-Westhausen 1, Hans Peter Philipsen 2, Peter A. Reichart 1 1Abteilung for zahnfirztliche Chirurgie/ Oralchirurgie Nord-Freie Universit&t Berlin, Germany and 2Oral Biology Unit, Faculty of Dentistry, University of Hong Kong, Prince Phillip Dental Hospital, Hong Kong
A. Schmidt- Westhausen, H P Philipsen, PA. Reichart." Clear cell calcifying epithelial odontogenic tumor. A case report. Int. J. Oral Maxillofac. Surg. 1992; 21: 47-49. Abstract. C l e a r cell v a r i a n t s o f o d o n t o g e n i c t u m o r s are rare. A case o f clear cell calcifying epithelial o d o n t o g e n i c t u m o r of the m a n d i b l e in a 38-year-old C a u c a s i a n m a l e is described. This case is c o m p a r e d to 8 previously r e p o r t e d cases. The origin o f clear cells in o d o n t o g e n i c t u m o r s is still u n k n o w n . E n bloc resection o f the t u m o r is r e c o m m e n d e d .
Clear cells are characteristic cellular c o m p o n e n t s o f the epithelial lining o f m o s t lateral p e r i o d o n t a l a n d gingival cysts in adults, or they m a y be f o u n d as clear-cell rests of the dental l a m i n a within the c o n n e c t i v e tissue wall o f these cysts H. W i t h considerably less frequency clear cells m a y occur in certain epithelial o d o n t o g e n i c t u m o r entities. I n fact, only 11 cases o f clear-cell t u m o r v a r i a n t s have been r e p o r t e d so far, 7 b e i n g clear-cell calcifying epithelial o d o n t o g e n i c t u m o r (CCCEOT) 1'2'3'8'13'14 a n d 3 clear-cell a m e l o b l a s t o m a (CCA) v a r i a n t s 9'12. In addition, clear-cell changes have been described in a calcifying o d o n t o g e n i c cyst ( C C C O C ) 1°. These t u m o r v a r i a n t s d e m o n s t r a t e a r a t h e r consistent " b i p h a s ic" histologic p a t t e r n with areas diagnostic of the t u m o r entity in question a n d o t h e r areas with conspicuous clear-cell c o m p o n e n t . It is n o t yet k n o w n w h e t h e r clear-cell v a r i a n t s of o d o n t o g e n i c tumors biologically b e h a v e differently f r o m the " m o t h e r t u m o r " a l t h o u g h the 2 cases of clinically aggressive C C A rep o r t e d by WALDRON et al.~2 m a y indicate t h a t such a possibility does exist. Prim a r y j a w t u m o r s of p u t a t i v e o d o n t o genie origin, c o m p o s e d principally o f clear cells, h a v e recently been described u n d e r the diagnosis o f clear-cell o d o n t o genie t u m o r ( C C O T ) 4.v. The clinical, r a d i o g r a p h i c a n d histological findings in a case o f C C C E O T are presented in this paper.
Case report A 38-year-old Caucasian male had for several months noticed a painless firm swelling slowly growing in the mandibular anterior
vestibule (44~31). The teeth in this region had been extracted some years previously. An orthopantomogram showed a radiolucency of 2.5 cm in diameter extending from the right mandibular canine to the left first incisor (Fig. 1). Ill-defined radiopacities were found in the cranial part of the cystic lesion. The mucosa overlying the lesion was intact. Incisional biopsy was taken resulting in the tentative diagnosis of CEOT. En bloc resection of the tumor-bearing area was performed under general anesthesia. The patient's postoperative course was uneventful and on examination 2 years later no sign of recurrence was found.
Histopathology The operation specimen was subjected to routine histological procedures and sections were stained with hematoxylin and eosin, van Gieson's connective tissue stain and PAS: Tumor tissue retrieved from formalin was postfixed in 1% osmium tetroxide and embedded in araldite. Ultrathin sections were examined in a JEOL 100 CX electron microscope. Examination in LM revealed strands, sheets and islands of proliferating epithelial tumor cells in a mature fibrous connective tissue stroma (Fig. 2). The cytoplasm of the polyhedral cells was eosinophilic and finely granular. The nuclei were generally uniform
Key words: calcifying epithelial odontogenic tumor; clear cells. Accepted for publication 2 October 1991
in size and shape but focal cell groups showed nuclear polymorphism, hyperchromatism and bi- and multinucleation (Fig. 3). Occasional mitotic figures were detected (Fig. 4). Cell necrosis was found centrally in some larger tumor islands. Rounded clear cells occurred as single or clustered components in a large number of tumor islands or sheets (Fig. 5). The clear cells appeared to develop from the CEOT tumor cells through continuous accumulation of initially PAS-positive material. In later stages the cytoplasm of the clear cells appeared empty. Occasionally, bridging between individual tumor cells could be demonstrated. Deposits of calcified material and amyloid-like substance were found in several areas of the tumor (Fig. 6). In TEM the cytoplasm of the clear cells contained remnants of tonofilaments, scattered clusters of ribosomes, a few profiles of endoplasmic reticulum but most cells appeared almost without detectable organelles. A search for rod- and racket-shaped structural Birbeck's granules was negative. Desmosomes were found between clear cells and between these and the tumor cells.
Discussion T h e n u m b e r a n d d i s t r i b u t i o n o f clear cells o b s e r v e d in the present case indicate
Fig. 1. Orthopantomogram showing a radiolucency between the mandibular right first premolar (44) and left first incisor (31). Diffuse radiopacities are seen in the central and cranial part of the lesion.
48
S c h m i d t - W e s t h a u s e n et aL Fig. 2. Low magnification of tumor invading bone. A solid area of tumor composed of odontogenic epithelial cells and clear cells is surrounded by dense collagenous tissue. A small island of calcification is seen in the upper part of the micrograph (arrow). H&E, x 60.
Fig. 3. Strands of epithelial cells with few clear cells showing hyperchromatic nuclei. H&E, x 100.
beck's granules which are cytoplasmic organelles characteristic of Langerhans' cells. Such granules, however, were not revealed in the present case. The ultrastructural findings in our case indicated that the clear cells were of epithelial origin and thus very likely originated from C E O T tumor cells through a possible degenerative process. Clear cells in odontogenic tumors may occur singly or in clusters giving a glandular configuration. If the latter occurs and if the clear cells numerically dominate the tumor tissue diagnostic problems m a y arise. The histopathology then mimics a clear-cell salivary gland t u m o r or even a metastatic renal cell carcinoma. Immunohistochemical and ultrastructural investigations may contribute to the correct diagnosis through a demonstration af glandular or non-glandular cellular characteristics. The small number of cases of clearcell containing odontogenic tumors published so far does not allow any conclusions to be drawn as to biological behaviour or prognosis of these tumors. As reported by WALDRON et al. 12 and HANSEN et al. 6 occurrence of the clear cells may prove to be a sign of increased tumor aggressiveness indicating a more radical surgical approach. The clinical course of the present case, which did not show recurrence after 2 years, suggests a particular aggressiveness is not always associated with the presence o f clear cells. Nevertheless en bloc resection of such tumors is strongly recommended.
Acknowledgements'. We are grateful to Dr. Dr. H. F. Behnsen for referring the case and to Prof. Dr. H. S. Koppang for confirmation of the histopathological diagnosis. We also thank Mr. J. Eckert for his excellent photography. Fig. 4. Tumor area consisting mainly of clear cells with glandular configuration. H& E, xl00.
that this tumor qualifies for the diagnosis of a clear-cell variant of C E O T with a histology consistent with that of the cases described previously 1'2'3'8'13'14.Transition between clear cells and C E O T tumor cells was evident throughout the tumor tissue. The true nature of clear cells in C C C E O T is still not known. Findings in the case presented here show, however, that clear cell changes may originate
from individual C E O T t u m o r cells as an accumulation of initially PAS-positive material. As the "ballooning" increases, the nucleus is displaced toward the cell periphery and the PAS-positivity is gradually lost. A rather in'teresting ultrastructural finding was reported by ASANO et al. 3 who, in clear cells occurring in a case of CEOT, demonstrated so-called Bir-
References
I. ABRAMSAM, HOWELLFV. Calcifying epithelial odontogenic tumors: report of four cases. JADA 1967: 74: 1231-40. 2. ANDERSONHC, KIM B, MINKOWITZ.Calcifying epithelial odontogenic tumor of Pindborg. Cancer 1969: 24:585 96. 3. ASANO M, TAKAHASHIT, KUSAMAK, et al. A variant of calcifying epithelial odontogenic tumor with Langerhans cells. J Oral Pathol Med 1990: 19: 430-4. 4. EVERSOLELR, BELTONCM, HANSENLS. Clear cell odontogenic tumor: Histochemical and ultrastructural features. J Oral Pathol 1985: 14:603 14.
Clear cell calciJj~ing epithelial odontogenic tumor 5. GREER RO, RICHARDSON JE Clear-cell
calcifying epithelial odontogenic tumor viewed relative to the Pindborg tumor. Oral Surg 1976: 42:775 9. 6. HANSEN LS, EVERSOLELR, GREEN TL, POWELL NB. Clear cell odontogenic tumor- a new histologic variant with aggressive potential. Head Neck Surg 1985: 8: I15 23. 7. KOPPANGHS, BANGG, HANSENLS, GILT~UVS MOE O, AKSDAL E. Hellzellinger odontogener Tumor. Kasuistischer Beitrag. Dtsch Z Mund Kiefer GesichtsChir i988: 12: 356-60. 8. KROLLSSO, PIND~ORGJJ. Calcifying epithelial odontogenic tumor. Arch Pathol. 1974: 98: 206-10.
9. MULLERH, S c o o r w m R Clear cell differentiation in an ameloblastoma. J Maxillofac Surg 1986: 14: 158-60. 10. NG KH, SIAR CH. Clear cell change in a calcifying odontogenic cyst. Oral Surg 1985: 60:417 19. 11. RASMVSSON LG, MAGNUSSON BC, BORRMANH. The lateral periodontal cyst. A histopathological and radiographic study of 32 cases. Br J Oral Maxillofac Surg 1991: 29: 54-7. 12. WALDRONCA, SMALLIA, SILVERMANH. Clear cell ameloblastoma- an odontogenic carcinoma. J Oral Maxillofac Surg 1985: 43: 70~17. 13. WALLACEJ. Calcifying epithelial odontogenic tumour ("Pindborg tumour"): A
49
case report. Br J Plast Surg 1974: 27: 28-30. 14. YAMAGUSHIA, KOKUBUJM, TAKAGI M, [SHIKAWA G. Calcifying epithelial odontogenic tumor: histochemical and electron microscopic observations on a case. Bull Tokyo Med Dent Univ 1980: 27: 129-35. Address:
A. Schmidt- Westhausen Abteilung fiir zahniirztliche Chirurgie/ Oralchirurgie-Nord Freie Universit& Berlin F6hrer St~ 15, D-IO00 Berlin 65 Germany