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Oral squamous cell carcinoma in a young person with candidosis endocrinopathy syndrome: a case report
Int. Z Oral Maxillofac. Surg. 1997; 26."42-44 Printed in Denmark. All rights reserved
Copyright 9 Munksgaard 1997 tntemationa]Jouma]of
Oral& MaxillofacialSurgery ISSN 0901-5027
Oral squamous cell carcinoma in a young person with
N. A. Firth 1, J. F. O'Grady ~, P. C. Reade 1 1School of Dental Science, The University of Melbourne, Melbourne, Australia; 2(former address) Peter McCallum Cancer Institute, Melbourne, Australia.
candid0sis end0crin0pathy syndrome: a case report N. A. Firth, J. F O'Grady, P. C Reade: Oral squamous cell carcinoma in a young person with candidosis endocrinopathy syndrome: a case report. Int. J. Oral Maxillofac. Surg. 1997; 26: 42-44. 9 Munksgaard, 1997 Abstract. Candidosis endocrinopathy syndrome is a rare condition characterized by mucocutaneous candidosis and multiple endocrinal abnormalities. This case reports a patient with the syndrome who also developed an oral mucosal squamous cell carcinoma at the age of 21.
Candidosis endocrinopathy syndrome (CES) is defined as chronic mucocutaneous candidosis ( C M C ) occurring in conjunction with one or more autoimmune endocrinopathies, most frequently hypoparathyroidism and/or Addison's disease 1,4,5,8,2~ Oral candidosis is often the initial feature in this rare condition 19,2~ Other immunologically related diseases associated with CES include diabetes mellitus, chronic lymphocytic thyroiditis, pernicious anaemia and ovarian failure1,4, 8. Candidosis in CES occurs generally in the first few years of life, while endocrine disorders may not appear until 10-15 years o f age el. This sequence, however, can be reversed. Multiple organ-specific autoantibodies are found in patients with CES and in their unaffected relatives. CES can have an autosomal recessive m o d e of inheritance or arise spontaneously 19. Complications reportedly associated with CES include achlorhydria (without pernicious anaemia), malabsorption, vitiligo 3'5, keratoconjunctivitis, corneal ulceration, cataracts 4, enamel hypo-
plasia 13,14,18,2s, alopecia, cystic fibrosis and juvenile cirrhosis 21. The purpose of this paper is to present a case in which a young adult patient with established CES developed an oral mucosal squamous cell carcinoma ( O M S C C ) without exposure to the c o m m o n risk factors. The concomitant occurrence of CES and O M S C C has not been previously reported. Case report A 21-year-old unmarried Caucasian female consulted her local medical practitioner with an acute, painful swelling involving all of the left cheek. This was associated with mild trismus. Assuming an inflammatory origin, the patient was treated with antimicrobial medication but this had no effect. The swelling slowly subsided, but because of continuing concern, the patient consulted her physician, with whom she had a long association. Her medical history included autoimmune hypoparathyroidism diagnosed at 2 years of age, pernicious anaemia diagnosed when she was 8 years old, Addison's disease since the age of 16, premature ovarian failure and mucocutaneous candidosis involving the oral mucosa and finger nails. Medications included dexamethazone (0.75 mg daily), flu-
Key words: carcinoma; candidosis; endocrinopathy; oral. Accepted for publication 20 November 1996
cortisone acetate (0.1 mg daily), calcitrol, conjugated oestrogens (Premarin | Ayerst Labs, Parramatta NSW, Australia) and medroxyprogesterone acetate, hydroxocobalamin and nystatin mouthwash. She had no allergies. She did not smoke and rarely consumed alcoholic beverages. On examination approximately one month after the onset of oral symptoms, the patient had angular cheilitis and generalized enamel hypoplasia. Oral hygiene was good. The oral mucosa was generally erythematous and a clinical diagnosis of oral candidosis was made. An exophytic lesion with ulceration, which occupied most of the left cheek mucosa and extended to the commissure was present. The lesion did not involve the depth of either the mandibular or maxillary buccal sulci, nor did it extend to the retromolar region. The lesion measured approximately 4.5• cm (Fig. 1). On palpation, the lesion was acutely tender, indurated and infiltrated deep into the substance of the cheek. Neck examination revealed no palpable lymph nodes. Smears stained with Periodic acid Schiff~ showed Candida hyphae. The histopathology of a biopsy of the left cheek mucosal lesion was reported to be well-differentiated OMSCC and clinically staged as T4N0. The patient was assessed in a multidisciplinary clinic (the Head & Neck Unit, Peter McCal-
Candidosis endocrinopathy syndrome and oral carcinogenesis
Fig. 1. Clinical photograph Of the patient's left cheek mucosa (reflected in a mirror) showing OMSCC. Enamel hypoplasia of molars and premolars can be seen.
lum Cancer Institute) where it was decided to use 60 Gy (in 30 increments) external beam, accelerated hyperfractionated megavoltage radiotherapy (MVT) to the left face and 50 Gy (in 25 increments) to the left neck. Mucositis was moderate during MVT treatment. Clinical resolution of the lesion occurred during treatment. The patient received oral ketoconazole (200 mg/day) during the period of radiotherapy. The post-MVT phase was made more difficult due to several episodes of acute pseudomembranous candidosis, despite continuous prophylactic use of nystatin oral drops. Each episode was treated successfully, however, with amphotericin B (10 mg) lozenges. In order to reduce the risk of dental caries, custom-made fluoride carriers were provided for use with Orofluor | (Colgate Oral Care Co., Mt Waverley, Australia) neutral gel. When reviewed 10 months after her initial presentation, there was no evidence of recurrent tumour in the cheek and there were no enlarged cervical lymph nodes from clinical examination. A moderate degree of xerostomia was present, but dental caries was not evident. The patient continued to comply with topical fluoride therapy. Eighteen months after presentation, despite care by the patient, a number of carious lesions developed necessitating the extraction of teeth from the upper and lower left quadrants. Ketoconazole, which had been reinstituted, was ceased following acute liver problems. Twenty-four months after presentation multiple erythematous patches developed in sites other than the primary lesion, including tongue and palate. After 30 months there was little change to the areas of erythroplakia. Carious breakdown of the dentition on the left side had continued. Both maxillary and mandibular teeth have been extracted without-complications developing such as osteoradionecrosis. Currently the patient is re-
viewed every six months and when reviewed 60 months after her initial work-up, she was considered to be free of squamous cell carcinoma (SCC). Discussion
Intra-oral cancer in young adults is uncommon. There is, however, some evidence indicating an increased likelihood of occurrence in immunocompromised individuals6'12'29, including transplant recipients 7'1~ and patients with the acquired immunodeficiency syndrome (AIDS) 25. Cases have been reported in patients with Fanconi's anaemia 23 and dietary deficiencies 11,15,3~ Frequently the aetiological factors most frequently associated with O M S C C in older adults (smoking and alcohol consumption) are absent in the younger group of patients 24, as they were in this case. It is likely that the patient in this case had an immunological defect. A n u m b e r of immunological abnormalities have been found in patients with CMC, but there is no consistent type. Most frequently, abnormalities are those affecting the, cell-mediated system, but neutrophil and monocyte defects have also been found 21'22. As some of the cellular responses improve after treatment of candidosis, it is likely that not all observed mechanisms are intrinsic 17. The precise association of immunological abnormalities with development of OMSCC is unclear. Recent studies have reported an increased prevalence of SCC involving the lips and premalignant lesions such as leukoplakia and dysplasia in
43
immunosuppressed groups of patients e.g. renal-transplant recipients 7. Risk factors other than immunosuppression such as smoking and, in the case of lip cancer, sun exposure also have a role 7. A possible additional factor is the presence of Candida and its implication in the transformation of leukoplakia into carcinoma 9 by acting as a promoter of carcinogenesis as demonstrated in an animal model 16. Regarding treatment of this patient's candidosis, ketoconazole during M V T was only moderately helpful in controlling the candidosis and when the drug was ceased and nystatin drops used, post-MVT acute pseudomembranous candidosis rapidly developed. Interestingly, this was quickly controlled with amphotericin B lozenges, suggesting that the latter medication is of greater benefit than nystatin, in the form of oral drops at least. No detectable change in the cutaneous lesions occurred. Itraconazole (100 mg/day) has been demonstrated to be effective in controlling candidal infections in one CES patient 2 and this agent or fluconazole should be considered. A case in which SCC, involving the vermilion of the upper lip, developed in a patient with C M C - t h y m o m a syndrome, has been reported 22. The case reported here is unusual in that O M S C C has not been reported in patients with CES. The role of candidosis in the aetiology of O M S C C in immunosuppressed individuals remains unresolved, however, persistent antimicrobial therapy of oral candidosis is indicated in patients with CES. References
1. BLIZZARD RM, GIBBS JH. Candidiasis: studies pertaining to its association with endocrinopathies and pernicious anaemia. Pediatrics 1968: 42: 231-7. 2. DEPADOVA-ELDERSM, DITRECM, KANTOR GR. Candidiasis endocrinopathy syndrome. Treatment with itraconazole. Arch Dermatol 1994: 130: 19-22. 3. FISHERM, FITZPATRICKTB. Candidiasis, vitiligo, thyroid disease and autoimmunity. Arch Dermatol 1970: 102: 110-2. 4. Hiaas JM, WELLSRS. Chronic mucocutaneous candidiasis: associated abnormalities of iron metabolism. Br J Dermatol 1972:86 (suppl): 88-102. 5. HOWANITZ N, NORDLUND JL, LERNER AB, BRYSTRYNJ-C. Antibodies to melanocytes. Arch Dermatol 1981: 117: 7058. 6. JENKINS VK, RAY P, ELLIS H, GRIFFITHS
44
Firth et aL
CM, PERRY RR, OLSON MH. Lymphocyte response in patients with head and neck cancer. Arch Otolaryngol 1976: 102: 59(~600. 7. KING GN, HEALY CM, GLOVER MT, KWAN JT, WILLIAMS DM, LEIGH IM, WORTHINGTON HV, THORNHILL MH. Increased prevalence of dysplastic and malignant lip lesions in renal-transplant recipients. New Engl J Med 1995: 332: 1052-7. 8. KIRKPATRICK CH, RICH RR, BENNETT JE. Chronic mucocutaneous candidiasis: model building in cellular immunity. Ann Int Med 1971: 74: 955-78. 9. KROGH P, HOLMSTRUP P, THORN J J, VEDTOFTE P, PINDBORGJJ. Yeast species and biotypes associated with oral leukoplakia and lichen planus. Oral Surg Oral Med Oral Pathol 1987: 63:48 54. 10. LEE YW, GISSERSD. Squamous cell carcinoma of the tongue in a nine-year-old renal transplant survivor. A case report with a discussion on the risk of development of epithelial carcinomas in renal transplant survivors. Cancer 1978: 41: 16. 11. MARSHALL J, GRAHAM S, METTLIN C, SrmDD D, SWANSONM. Diet in the epidemiology of cancer. Nutr Cancer 1982: 3: 145-9. 12. MERRICK YR, JENSEN H. Carcinoma of the floor-of the mouth in a young patient: a case report and review of the literature. J Laryngol Otol 1979: 93: 937~42. 13. MYLLARNIEMI S, PERHEENTUPA J. Oral findings in the autoimmnne polyendocrinopathy-candidosis syndrome (APECS) and other forms of hypoparathyroidism. Oral Surg Oral Med Oral Pathol 1978: 45: 721-9. 14. NALLYFE Idiopathic juvenile hypoparathyroidism with superficial moniliasis. Oral Surg Oral Med Oral Pathol 1970: 30: 356-65.
15. NOTANI PN, SANGHVILD. Role of diet in the cancers of the oral cavity. Ind J Cancer 1976: 13:156 60. 16. O'GRADY JF, READE PC. Candida Albicans as a promotor of oral mucosal neoplasia. Carcinogenesis 1992: 13:783 6. 17. PETERSONPY, SEMOR, BLUMENSCHEING, SWELSTADJ. Mucocutaneous candidiasis, anergy and a plasma inhibitor of cellular immunity: reversal after amphotericin B therapy. Clin Exp Immunol 1971: 9: 595602. 18. PISANTYS, GAREUNI~LA. Familial hypoparathyroidism with candidiasis and mental retardation. Oral Surg Oral Med Oral Pathol 1977: 44: 374-83. 19. PORTERSR, SCULLYC. Candidiasis endocrinopathy syndrome. Oral Surg Oral Med Oral Pathol 1986: 61: 573-8. 20. PORTER SR, SCULLY C, GREENSPAN D. Primary and secondary immnnodeficiencies. In: JONES JH, MASON DK, eds.: Oral Manifestations of Systemic Disease, 2nd ed. London: Bailliere-Tinddall, 1990: 131 2. 21. PRICE ML, McDONALD DM. Candida endocrinopathy syndrome. Clin Exp Dermatol 1984: 9: 105-9. 22. ROTHBERG MS, EISENBUD L, GRIBOEF S. Chronic mucocutaneous candidiasis-thymoma syndrome. Oral Surg Oral Med Oral Pathol 1989: 68: 411-3. 23. SARNA G, TOMASULOP, LOTZ M J, BUBINAK JE SHULMAN NR. Multiple neoplasms in two siblings with a variant form of Fanconi's anemia. Cancer 1975: 36:1029 33. 24. SANKARANARAYANANR, NAJEEB MOHODEEN M, KRISHNANNAIR M, PADMANABHAS TK. Aetiology of oral cancer in patients <30 years of age. Br J Cancer 1989: 59: 439-40. 25. SILVERMANS, MIGLIORATI CA, LOZADANtm E GI~ENSPAND, CONANTMA. Oral
findings in people with or at high risk for AIDS: A study of 375 homosexual males. J Am Dent Assoc 1986: 112: 187-92. 26. SUTPHIN A, ALBRIGHT F, McLuNE DJ. Five cases (three in siblings) of idiopathic hypoparathyroidism associated with moniliasis. J Clin Endocrinol 1943: 3: 625-34. 27. TRENCE DL, MORLEY JE, HANDWERGER BS. Polyglandular autoimmune syndromes. Am J Med 1984: 77:107 16. 28. WALLSWG, SOAMESJV. Dental manifestations of autoimmune hypoparathyroidism. Oral Surg 1993: 75: 452-4. 29. WANEBO H J, JUN MY, STRONG EW, OETTGEN H. T cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg 1975: 130: 445-51. 30. WINs DM, ZIEGLER RG, PICKLE LN, GRIDLEY G, BLAT WJ, HOOVERRN. Diet in the etiology of oral and pharyngeal cancer among women from Southern United States. Cancer Res 1984: 44: 1216 22. 31. WHITAKER J, LANDING BH, ESSELBORN VM, WILLIAMSRR. Syndrome of familial juvenile hypoadrenocorticism, hypoparathyroidism and superficial moniliasis. J Clin Endocrinol 1956: 16: 1274-87.
Address: Dr N. A. Firth School of Dental Science The University of Melbourne 711 Elizabeth Street Melbourne, Victoria 3000 Australia
Copyright 9 Munksgaard 1997 tntemationa]Jouma]of
Oral& MaxillofacialSurgery ISSN 0901-5027
Oral squamous cell carcinoma in a young person with
N. A. Firth 1, J. F. O'Grady ~, P. C. Reade 1 1School of Dental Science, The University of Melbourne, Melbourne, Australia; 2(former address) Peter McCallum Cancer Institute, Melbourne, Australia.
candid0sis end0crin0pathy syndrome: a case report N. A. Firth, J. F O'Grady, P. C Reade: Oral squamous cell carcinoma in a young person with candidosis endocrinopathy syndrome: a case report. Int. J. Oral Maxillofac. Surg. 1997; 26: 42-44. 9 Munksgaard, 1997 Abstract. Candidosis endocrinopathy syndrome is a rare condition characterized by mucocutaneous candidosis and multiple endocrinal abnormalities. This case reports a patient with the syndrome who also developed an oral mucosal squamous cell carcinoma at the age of 21.
Candidosis endocrinopathy syndrome (CES) is defined as chronic mucocutaneous candidosis ( C M C ) occurring in conjunction with one or more autoimmune endocrinopathies, most frequently hypoparathyroidism and/or Addison's disease 1,4,5,8,2~ Oral candidosis is often the initial feature in this rare condition 19,2~ Other immunologically related diseases associated with CES include diabetes mellitus, chronic lymphocytic thyroiditis, pernicious anaemia and ovarian failure1,4, 8. Candidosis in CES occurs generally in the first few years of life, while endocrine disorders may not appear until 10-15 years o f age el. This sequence, however, can be reversed. Multiple organ-specific autoantibodies are found in patients with CES and in their unaffected relatives. CES can have an autosomal recessive m o d e of inheritance or arise spontaneously 19. Complications reportedly associated with CES include achlorhydria (without pernicious anaemia), malabsorption, vitiligo 3'5, keratoconjunctivitis, corneal ulceration, cataracts 4, enamel hypo-
plasia 13,14,18,2s, alopecia, cystic fibrosis and juvenile cirrhosis 21. The purpose of this paper is to present a case in which a young adult patient with established CES developed an oral mucosal squamous cell carcinoma ( O M S C C ) without exposure to the c o m m o n risk factors. The concomitant occurrence of CES and O M S C C has not been previously reported. Case report A 21-year-old unmarried Caucasian female consulted her local medical practitioner with an acute, painful swelling involving all of the left cheek. This was associated with mild trismus. Assuming an inflammatory origin, the patient was treated with antimicrobial medication but this had no effect. The swelling slowly subsided, but because of continuing concern, the patient consulted her physician, with whom she had a long association. Her medical history included autoimmune hypoparathyroidism diagnosed at 2 years of age, pernicious anaemia diagnosed when she was 8 years old, Addison's disease since the age of 16, premature ovarian failure and mucocutaneous candidosis involving the oral mucosa and finger nails. Medications included dexamethazone (0.75 mg daily), flu-
Key words: carcinoma; candidosis; endocrinopathy; oral. Accepted for publication 20 November 1996
cortisone acetate (0.1 mg daily), calcitrol, conjugated oestrogens (Premarin | Ayerst Labs, Parramatta NSW, Australia) and medroxyprogesterone acetate, hydroxocobalamin and nystatin mouthwash. She had no allergies. She did not smoke and rarely consumed alcoholic beverages. On examination approximately one month after the onset of oral symptoms, the patient had angular cheilitis and generalized enamel hypoplasia. Oral hygiene was good. The oral mucosa was generally erythematous and a clinical diagnosis of oral candidosis was made. An exophytic lesion with ulceration, which occupied most of the left cheek mucosa and extended to the commissure was present. The lesion did not involve the depth of either the mandibular or maxillary buccal sulci, nor did it extend to the retromolar region. The lesion measured approximately 4.5• cm (Fig. 1). On palpation, the lesion was acutely tender, indurated and infiltrated deep into the substance of the cheek. Neck examination revealed no palpable lymph nodes. Smears stained with Periodic acid Schiff~ showed Candida hyphae. The histopathology of a biopsy of the left cheek mucosal lesion was reported to be well-differentiated OMSCC and clinically staged as T4N0. The patient was assessed in a multidisciplinary clinic (the Head & Neck Unit, Peter McCal-
Candidosis endocrinopathy syndrome and oral carcinogenesis
Fig. 1. Clinical photograph Of the patient's left cheek mucosa (reflected in a mirror) showing OMSCC. Enamel hypoplasia of molars and premolars can be seen.
lum Cancer Institute) where it was decided to use 60 Gy (in 30 increments) external beam, accelerated hyperfractionated megavoltage radiotherapy (MVT) to the left face and 50 Gy (in 25 increments) to the left neck. Mucositis was moderate during MVT treatment. Clinical resolution of the lesion occurred during treatment. The patient received oral ketoconazole (200 mg/day) during the period of radiotherapy. The post-MVT phase was made more difficult due to several episodes of acute pseudomembranous candidosis, despite continuous prophylactic use of nystatin oral drops. Each episode was treated successfully, however, with amphotericin B (10 mg) lozenges. In order to reduce the risk of dental caries, custom-made fluoride carriers were provided for use with Orofluor | (Colgate Oral Care Co., Mt Waverley, Australia) neutral gel. When reviewed 10 months after her initial presentation, there was no evidence of recurrent tumour in the cheek and there were no enlarged cervical lymph nodes from clinical examination. A moderate degree of xerostomia was present, but dental caries was not evident. The patient continued to comply with topical fluoride therapy. Eighteen months after presentation, despite care by the patient, a number of carious lesions developed necessitating the extraction of teeth from the upper and lower left quadrants. Ketoconazole, which had been reinstituted, was ceased following acute liver problems. Twenty-four months after presentation multiple erythematous patches developed in sites other than the primary lesion, including tongue and palate. After 30 months there was little change to the areas of erythroplakia. Carious breakdown of the dentition on the left side had continued. Both maxillary and mandibular teeth have been extracted without-complications developing such as osteoradionecrosis. Currently the patient is re-
viewed every six months and when reviewed 60 months after her initial work-up, she was considered to be free of squamous cell carcinoma (SCC). Discussion
Intra-oral cancer in young adults is uncommon. There is, however, some evidence indicating an increased likelihood of occurrence in immunocompromised individuals6'12'29, including transplant recipients 7'1~ and patients with the acquired immunodeficiency syndrome (AIDS) 25. Cases have been reported in patients with Fanconi's anaemia 23 and dietary deficiencies 11,15,3~ Frequently the aetiological factors most frequently associated with O M S C C in older adults (smoking and alcohol consumption) are absent in the younger group of patients 24, as they were in this case. It is likely that the patient in this case had an immunological defect. A n u m b e r of immunological abnormalities have been found in patients with CMC, but there is no consistent type. Most frequently, abnormalities are those affecting the, cell-mediated system, but neutrophil and monocyte defects have also been found 21'22. As some of the cellular responses improve after treatment of candidosis, it is likely that not all observed mechanisms are intrinsic 17. The precise association of immunological abnormalities with development of OMSCC is unclear. Recent studies have reported an increased prevalence of SCC involving the lips and premalignant lesions such as leukoplakia and dysplasia in
43
immunosuppressed groups of patients e.g. renal-transplant recipients 7. Risk factors other than immunosuppression such as smoking and, in the case of lip cancer, sun exposure also have a role 7. A possible additional factor is the presence of Candida and its implication in the transformation of leukoplakia into carcinoma 9 by acting as a promoter of carcinogenesis as demonstrated in an animal model 16. Regarding treatment of this patient's candidosis, ketoconazole during M V T was only moderately helpful in controlling the candidosis and when the drug was ceased and nystatin drops used, post-MVT acute pseudomembranous candidosis rapidly developed. Interestingly, this was quickly controlled with amphotericin B lozenges, suggesting that the latter medication is of greater benefit than nystatin, in the form of oral drops at least. No detectable change in the cutaneous lesions occurred. Itraconazole (100 mg/day) has been demonstrated to be effective in controlling candidal infections in one CES patient 2 and this agent or fluconazole should be considered. A case in which SCC, involving the vermilion of the upper lip, developed in a patient with C M C - t h y m o m a syndrome, has been reported 22. The case reported here is unusual in that O M S C C has not been reported in patients with CES. The role of candidosis in the aetiology of O M S C C in immunosuppressed individuals remains unresolved, however, persistent antimicrobial therapy of oral candidosis is indicated in patients with CES. References
1. BLIZZARD RM, GIBBS JH. Candidiasis: studies pertaining to its association with endocrinopathies and pernicious anaemia. Pediatrics 1968: 42: 231-7. 2. DEPADOVA-ELDERSM, DITRECM, KANTOR GR. Candidiasis endocrinopathy syndrome. Treatment with itraconazole. Arch Dermatol 1994: 130: 19-22. 3. FISHERM, FITZPATRICKTB. Candidiasis, vitiligo, thyroid disease and autoimmunity. Arch Dermatol 1970: 102: 110-2. 4. Hiaas JM, WELLSRS. Chronic mucocutaneous candidiasis: associated abnormalities of iron metabolism. Br J Dermatol 1972:86 (suppl): 88-102. 5. HOWANITZ N, NORDLUND JL, LERNER AB, BRYSTRYNJ-C. Antibodies to melanocytes. Arch Dermatol 1981: 117: 7058. 6. JENKINS VK, RAY P, ELLIS H, GRIFFITHS
44
Firth et aL
CM, PERRY RR, OLSON MH. Lymphocyte response in patients with head and neck cancer. Arch Otolaryngol 1976: 102: 59(~600. 7. KING GN, HEALY CM, GLOVER MT, KWAN JT, WILLIAMS DM, LEIGH IM, WORTHINGTON HV, THORNHILL MH. Increased prevalence of dysplastic and malignant lip lesions in renal-transplant recipients. New Engl J Med 1995: 332: 1052-7. 8. KIRKPATRICK CH, RICH RR, BENNETT JE. Chronic mucocutaneous candidiasis: model building in cellular immunity. Ann Int Med 1971: 74: 955-78. 9. KROGH P, HOLMSTRUP P, THORN J J, VEDTOFTE P, PINDBORGJJ. Yeast species and biotypes associated with oral leukoplakia and lichen planus. Oral Surg Oral Med Oral Pathol 1987: 63:48 54. 10. LEE YW, GISSERSD. Squamous cell carcinoma of the tongue in a nine-year-old renal transplant survivor. A case report with a discussion on the risk of development of epithelial carcinomas in renal transplant survivors. Cancer 1978: 41: 16. 11. MARSHALL J, GRAHAM S, METTLIN C, SrmDD D, SWANSONM. Diet in the epidemiology of cancer. Nutr Cancer 1982: 3: 145-9. 12. MERRICK YR, JENSEN H. Carcinoma of the floor-of the mouth in a young patient: a case report and review of the literature. J Laryngol Otol 1979: 93: 937~42. 13. MYLLARNIEMI S, PERHEENTUPA J. Oral findings in the autoimmnne polyendocrinopathy-candidosis syndrome (APECS) and other forms of hypoparathyroidism. Oral Surg Oral Med Oral Pathol 1978: 45: 721-9. 14. NALLYFE Idiopathic juvenile hypoparathyroidism with superficial moniliasis. Oral Surg Oral Med Oral Pathol 1970: 30: 356-65.
15. NOTANI PN, SANGHVILD. Role of diet in the cancers of the oral cavity. Ind J Cancer 1976: 13:156 60. 16. O'GRADY JF, READE PC. Candida Albicans as a promotor of oral mucosal neoplasia. Carcinogenesis 1992: 13:783 6. 17. PETERSONPY, SEMOR, BLUMENSCHEING, SWELSTADJ. Mucocutaneous candidiasis, anergy and a plasma inhibitor of cellular immunity: reversal after amphotericin B therapy. Clin Exp Immunol 1971: 9: 595602. 18. PISANTYS, GAREUNI~LA. Familial hypoparathyroidism with candidiasis and mental retardation. Oral Surg Oral Med Oral Pathol 1977: 44: 374-83. 19. PORTERSR, SCULLYC. Candidiasis endocrinopathy syndrome. Oral Surg Oral Med Oral Pathol 1986: 61: 573-8. 20. PORTER SR, SCULLY C, GREENSPAN D. Primary and secondary immnnodeficiencies. In: JONES JH, MASON DK, eds.: Oral Manifestations of Systemic Disease, 2nd ed. London: Bailliere-Tinddall, 1990: 131 2. 21. PRICE ML, McDONALD DM. Candida endocrinopathy syndrome. Clin Exp Dermatol 1984: 9: 105-9. 22. ROTHBERG MS, EISENBUD L, GRIBOEF S. Chronic mucocutaneous candidiasis-thymoma syndrome. Oral Surg Oral Med Oral Pathol 1989: 68: 411-3. 23. SARNA G, TOMASULOP, LOTZ M J, BUBINAK JE SHULMAN NR. Multiple neoplasms in two siblings with a variant form of Fanconi's anemia. Cancer 1975: 36:1029 33. 24. SANKARANARAYANANR, NAJEEB MOHODEEN M, KRISHNANNAIR M, PADMANABHAS TK. Aetiology of oral cancer in patients <30 years of age. Br J Cancer 1989: 59: 439-40. 25. SILVERMANS, MIGLIORATI CA, LOZADANtm E GI~ENSPAND, CONANTMA. Oral
findings in people with or at high risk for AIDS: A study of 375 homosexual males. J Am Dent Assoc 1986: 112: 187-92. 26. SUTPHIN A, ALBRIGHT F, McLuNE DJ. Five cases (three in siblings) of idiopathic hypoparathyroidism associated with moniliasis. J Clin Endocrinol 1943: 3: 625-34. 27. TRENCE DL, MORLEY JE, HANDWERGER BS. Polyglandular autoimmune syndromes. Am J Med 1984: 77:107 16. 28. WALLSWG, SOAMESJV. Dental manifestations of autoimmune hypoparathyroidism. Oral Surg 1993: 75: 452-4. 29. WANEBO H J, JUN MY, STRONG EW, OETTGEN H. T cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg 1975: 130: 445-51. 30. WINs DM, ZIEGLER RG, PICKLE LN, GRIDLEY G, BLAT WJ, HOOVERRN. Diet in the etiology of oral and pharyngeal cancer among women from Southern United States. Cancer Res 1984: 44: 1216 22. 31. WHITAKER J, LANDING BH, ESSELBORN VM, WILLIAMSRR. Syndrome of familial juvenile hypoadrenocorticism, hypoparathyroidism and superficial moniliasis. J Clin Endocrinol 1956: 16: 1274-87.
Address: Dr N. A. Firth School of Dental Science The University of Melbourne 711 Elizabeth Street Melbourne, Victoria 3000 Australia