- Email: [email protected]
The presence of Candida albicans in hereditary benign intraepithelial dyskeratosis
The presence of Candida albicans in hereditary benign intraepithelial dyskeratosis An ultrastructural
observation
Ezedin M. Sadeghi, D.D.S., M.S., * and Carl J. Witkop, D.D.S., Milwaukee, Wis., and Minneapolis, Minn. DIVISION HUMAN
OF PATHOLOGY, AND
ORAL
MARQUETTE
GENETICS,
UNIVERSITY
UNIVERSITY,
SCHOOL
OF MINNESOTA,
MS., **
OF DENTISTRY, SCHOOL
AND
DIVISION
OF
OF DENTISTRY
Specimens taken from the buccal mucosa of two patients with hereditary benign intraepithelial dyskeratosis (HDID) were studied by transmission electron microscopy. The uttrastructure of epithelial tissue in HBID was previously reported. Discovery of Candida albicans in this lesion was an accidental finding. The literature on the subject was reviewed and the ultrastructural features of Candida albicans were described.
C
hronic mucocutaneous candidiasis is or may be a prominent clinical feature associated with a number of endogenous or iatrogenic abnormalities. If one disregards candidiasis associated with debilitating conditions such as blood dyscrasias’ or carcinomatosis and iatrogenic alterations of mucosal flora by antibiotics and antineoplastic drugs, 2-4 these underlying abnormalities classically fall into three major categories: (1) abnormalities of the immune system,5-11 (2) endocrinopathies involving particularly parathyroid and adrenal deficiencies,12-i7 or (3) combined, autoimmuneendocrinopathies. 18-21However, with the exception of disorders associated with thymic dysgenesis, such as Swiss-type agammaglobulinemia in which both the thymus-dependent cellular immunity system and the immunoglobulin-antibody system are deficient,22-24 dysplasia of the thymus without agammaglobulinemia (Nezelof-Allibone syndrome), and the third and fourth branchial pouch syndrome of DiGeorge,25s 26the exact nosologic classification of specific Candida-related entities is vague. The literature strongly suggests that many of the cases described as only immune deficiency-associated or as only endocrinopathy-associated are *Assistant Science. **Professor
342
professor,
Division
and Chairman,
of Pathology/Department
Division
of Human
of Basic
and Oral Genetics.
in reality various aspects of an autoimmune-endocrinopathy syndrome.26 Numerous cases of candidiasis occur without known underlying general abnormalities. This type of candidiasis has been the particular concern of investigations of oral “leukoplakia.“27-32 In a majority of these studies, the “leukoplakias” investigated were defined on clinical criteria only as “a white patch, not less than 5 mm. in diameter, which cannot be removed by rubbing and which cannot be classified as any other diagnosable disease.“36 Most of these studies showed a significantly higher frequency of Candidu organisms in speckled leukoplakia (erythematous patches between white ones) than in other types of leukoplakia.27, 32,33 With few exceptions, the frequency of Candida in other types of leukoplakias was not significantly different than the frequency in normal mucosa. Several studies addressed the problem of whether cellular atypia is associated more frequently with lesions containing Candida than with those not containing the organism.27-33 While the criteria for cellular atypia and histologic methods differed, three studies found that 40 to 56 percent of Candida -involved leukoplakias showed atypia and 53 to 67 percent of leukoplakias with atypia were invaded by Candida. 28, 30*31 The problem with these studies is that they do not clearly distinguish whether tissues with cellular atypia are prone to inva003Cb4220/79/100342+05$00.50/0
0
1979 The C. V. Mosby Co.
Volume 48 Number 4
C. albicans in hereditary benign intraepithelial
dyskerutosis
343
Fig. 1. Section from upper region of spinous layer and superficial layer showing intracellularly located Candidn organisms (crrrows). (Toluidine blue stain. Magnification, X400.)
sion by the organisms or whether cellular atypia results from the invasion of Candida. Further, Cawsonzs found Cundida present in only two well-differentiated oral carcinomas out of sixty examined and in none of twenty-seven examples of lichen planus. However, Cundidu was found in six out of ten dyskeratotic lesions. HEREDITARY BENIGN INTRAEPITHELIAL DYSKERATOSIS (HBID)
This report presents evidence for Cundidu invasion associated with hereditary benign intraepithelial dyskeratosis. HBID was first described by Von Sallmann and Paton and Witkop and associates.“” The ocular lesions consist of gelatinous-appearing plaques overlying a hyperemic bulbar conjunctivae most prominently found on the perilimbal bulbar conjunctiva. The oral lesions were asymptomatic and varied from a white delicate opalescent membrane to rough, shaggy, folded plaques most prominently involving the buccal and labial mucosa, floor of the mouth, and side of the tongue. Histologically, the epithelium was increased in thickness due to hyperplasia of the middle and upper prickle-cell layer of large vacuolated cells. Throughout
the layers were numerous round dyskeratotic cells best visualized in Papanicolaou-stained sections. “Cellwithin-cell”- type bodies reminiscent of the corps ronds of Darier’s disease were frequent.35’ M THEPRESENTSTUDY
Biopsies of buccal mucosa lesions were obtained from two patients, a 16-year-old boy and a 22-year-old woman, for an electron microscopic study previously reported. 37 At the time of biopsy, both patients were experiencing a severe flare of their ocular disease. They had photophobia, tearing, and itching of the eyes so severe that they confined themselves to dimly lit rooms during daytime hours. The technique for the preparation of the electron microscopic sections was described in our first report.37 Specimens prepared for electron microscopy were cut, stained with toluidine blue, and examined by light microscopy. Sections from the upper region of the spinous layer and superficial layer showed some intracellularly located elements compatible with Cundida albicans (Fig. 1). Electron microscopic sections from the upper region of the stratum spin&urn and superficial layer showed the presence of fungal elements in both patients
CM surg.
October,1979
Fig. 2. This electron micrograph illustrates &e presence of fungat cetis in the upper spinous cell layer. One of these fungal cells demonstratebranching. (Magnification, ~4,000.)
(Fig‘ 2). Hyphae were present intracellularly, some demonstrating branching [Fig. 2). Yeast cells were found penetrating the keratinocyte membrane (Fig. 3). Fungal cells were not observed within round dyskeratotic cells but were seen in their vicinity (Fig. 3). The yeast cell wall was homogeneous with moderate electrodensity. The cell membrane was situated immediately beneath the cell wall and had an electron-dense trilaminar unit membrane structure and occasionally showed small in~cytopla~mic invaginations. Mitochondria were well developed with parallel cristae (Fig. 4), Occasionally, inflammatory elements, particularly mast ceils, could be found in the connective tissue below the basal-cell layer. The fine structure of these fungal eiements was identical to those previously described for C. afbicarrs. 38-40 DISCUSSON Within recent years many investigators have tried to categorize oral candidiasis.28, 2e, 4o* 41 In order to
achieve a reasonable classification of this condition, one must study the pathogenicity of C. ~1~~~~~. a feature which has never been indisputably estabiished. Many factors related to the pathogenicity of C. albicans have been suggested: defective celular immunity,t7 immune det5ciencney,5-‘1endocrinopathy,i~-~~ iatrogenic factors such as antibiotic therapy,3 use of antineoplastic drugs for patients with cancer,4 and lack of anticandidal factors in the serum of patients with chronic candid~asis.~ F~he~ore, it has been suggested that the defective epithelium may act as a predisposing factor for the overgrowth of C. albicuns. 43Since epithelial tissue of the oral mucosa of patients with I-IBID is dyskeratotic, it may offer a special milieu for C* albicans, as the organism has been shown to be capable of using keratin as its sole source of nitrogen.44 The finding of Candida organisms in the oral tissues of two patients with I-IBID at a time when they were experiencing severe ocular lesions suggests that these organisms may be associated with the vernal exacerba-
Volume 48 Number 4
C. albicans in hereditary benign intraepithelial
dyskeratosis
Fig. 3. E lectron micmgraph showing a fungal cell in the process of penetration of the epithelial cell mc:mbrane Part of a round dyskeratotic cell can be observed at the upper part of the section. (Magnification, X 8 ,0001.)
4. n his is a high-magnification view of a fungal cell. Cell wall (CW), cell membrane (CM), mito char rdria and ribosomes (R) can be identified in this electron micrograph. (Magnification, X35,ooo.)
345
346
Sadrghi und Witkop
tion of the eye lesions observed in this disease. The present study was primarily initiated to describe the ultrastructure of hereditary benign intraepithelial dyskeratosis. The discovery of C. albicans was an incidental finding which has not been formerly reported. The significance of this observation remains to be demonstrated by further epidemiologic and histologic studies of this condition. REFERENCES
5
6. 7. 8. 9. 10.
Il.
Bodey, G. P.: Fungal Infection Complicating Acute Leukemia, J. Chron. Dis. 19: 667-687, 1966. Hultin, M.: Candidos och Antibiotica, Svensk. Tandliik Tidskr. 47: 441-451, 1954. Giunchi, G.: Candidosis Following Antibiotic Therapy, Sci. Med. Ital. 6: 580-628, 1958. Bottomley, W. K., Perlin, E., and Koss, Cl. R.: Antineoplastic Agents and Their Oral Manifestations, ORAL SURG. 44: 527534, 1977. Chilgren, R. A., Quie, P. Cl., Meuwissen, H. J., a&Hong, R.: Chronic Mucocutaneous Candidiasis, Deficiency of Delayed Hypersensitivity and Selective Local Antibody Defect, Lancet 2: 688-693, 1967. Chilgren, R. A., Hong, R., and Quie, P. Cl.: Candida-Serum Interaction in Six Patients With Chronic Candidiasis, Fed. Proc. 26: 699, 1967. (Abst.) Canales, L., Louro, J. M., Middlemas, R. O., III, and South, M. A.: Immunological Observations in Chronic Mucocutaneous Candidiasis, Lancet 2: 567-571, 1969. Kirkpatrick, C. H.: Chronic Mucocutaneous Moniliasis With Impaired Delayed Hypersensitivity, Clin. Exp. Immunol. 6: 375-385, 1970. Kirkpatrick, C. H., Rich, R. R., and Bennett, J. E.: Chronic Mucocutaneous Candidiasis: Model Building in Cellular Immunity, Am. bit. Med. 74: 955-978, 1971. Amman. A. J., and Hong, R.: Cellular Immunodeficiency Disorders. In Stiehm, E. R., and Fulginiti, V. A. (editors): Immunologic Disorders in Infants and Children, Philadelphia, 1973, W. B. Saunders Company. Mylarniemi, S., and Perheentupa, J.: Oral Findings in the Autoimmune Polyendorcinopathy-Candidiasis Syndrome (APECS) and Other Forms of Hypoparathyroidism, ORAL SURG. 45: 721-729,
1978.
12. Thorpe, E. S., and Handley, H. E.: Chronic Tetany and Chronic Mycelial Stomatitis in a Child Aged Four and One-Half Years, Am. J. Dis. Child. 38: 328-338, 1929. 13. Gass, J. D.: The Syndrome of Keratoconjunctivitis, Superficial Moniliasis, Idiopathic Hypoparathyroidism and Addison’s Disease, Am. J. Ophthalmol. 54: 660-674, 1962. 14. Genant, H. K.: Addison’s Disease and Hypoparathyroidism (Schmidt’s Syndrome), Metabolism 16: 189--194, 1967. 15. Blizzard. R. M.. and Gibbs, J. H.: Candidiasis: Studies Pertaining to its Association With Endocrinopathies and Pernicious Anemia, Pediatrics 42: 231-237, 1968. 16. Golonka, J. E., and Goodman, A. D.: Coexistence of Primary Ovarian Insufficiency, Primary Adrenocortical Insufficiency and Idiopathic Hypoparathyroidism, J. Clin. Endocrinol. 28: 79-82, 1968. 17. Hermans, P. E., Ulrich, J. A., and Merkowitz, H.: Chronic Mucocutaneous Candidiasis as a Surface Expression of DeepSeated Abnormalities, Am. J. Med. 47: 503-519, 1969. 18. Wuepper, K. D., and Fudenberg, H. H.: Moniliasis, “Autoimmune” Polyendocrinopathy, an Immunologic Family Study, Clin. Exp. Immunol. 2: 71-82, 1967. 19. Hermans, P. E., and Ritts, R. E.: Chronic Mucocutaneous Candidiasis: Its Association With Immunologic and Endocrine Abnormalities, Minn. Med. 53: 75-80, 1970. 20. Perheentupa, J., and Hiekkala, H.: Twenty Cases of the Syndrome of Autoimmune Endocrinopatby and Candidiasis, Acta Paediatr. Stand. 62: 1 I@lll, 1973.
Oral Surg. October, 1979 21. Richman, R. A.: Candidiasis and Multiple Endocrinopathies, Arch. Dermatol. 111: 625-627, 1975. 22. Glanzmann, E., and Riniker, P.: Essentielle Lymphocytophthise: Ein Neues Krankheitsbild aus der Sauglingspathologie. Ann. Paediatr. 175: l-32, 1950. 23. Freycon, F., Jeune, M., Larbre, F., and Germain. D.: L’aplaaie Lymphoplasmocytose au Nourisson Avec Alymphocytose et Hypogammaglobulinemie, J. Med. Lyon 42: 147-192, 196 1. 24. Peterson, R. D., Cooper, M. D., and Good, R. A.: The Pathogenesis of Immunologic Deficiency Diseases. Am. J. Med. 38: 579604, 1965. 25. DiGeorge, A. M.: Discussion, J. Pediatr. 67: 907-908, 1965. 26. Gorlin, R. J., Pindborg, J. J., and Cohen, M. M., Jr.: Syndromes of the Head and Neck, ed. 2, New York, 1976, McGraw-Hill Book Co. 27. Jepsen, A., and Winther, J. E.: Mycotic Infection in Oral Leukoplakia, Acta Odontol. Stand. 23: 239-256, 1965. 28. Cawson, R. A.: Chronic Oral Candidosis and Ieukoplakia, ORAL SURG. 22: 582-591,
1966.
29. Cawson, R. A., and Lehner, R.: Chronic Hyperplastic Candidiasis-Candidal Leukoplakia, Br. J. Dermatol. SO: 9- 16, 1968. 30. Renstrup, G.: Occurrence of Candida in Oral Leukoplakias, Acta Pathol. Microbial. Stand. B 78: 421-424. 1970. 31. Roed-Petersen, B., Renstrup, G., and Pindborg, J. J.: Candida in Oral Leukoplakia. A Histologic and Exfoliative Cytologic Study, Stand. J. Dent. Res. 78: 323-328, 1970. 32. Dafiary, D. K., Mehta, F. S., Gupta, P. C.. and Pindborg, J. J.: The Presence of Candida in 723 Oral Leukoplasias Among Indian Villagers, Stand J. Dent. Res. 80: 75-79. 1972. 33. Pindborg, J. J., Jelst, O., Renstrup, G., and Roed-Peterson, B.: Studies in Oral Leukoplakia. A Preliminary Report on the Period Prevalence of Malignant Transformation in Leukoplakia Based on a Follow-up Study of 248 Patients, J. Am. Dent. Assoc. 75: 767-771, 1968. 34. Von Sallmann, L., and Paton, D.: Hereditary Benign Intraepithelial Dyskeratosis I. Ocular Manifestations. Am. Med. Assoc. Arch. Ophthalmol. 63: 421-429, 1960. 35. Witkop, C. J., Jr., Shankle, C. M., Graham, J. B., Murray, M. R., Rucknagel, D. L.. and Byerly, B. H.: Hereditary Benign Intraepithehal Dyskeratosis II. Oral Manifestations and Hereditary Transmission, Arch. Pathol. 70: 696-71 I, 1960. 36. Witkop, C. J., Jr., and Gorlin, R. J.: Four Hereditary Mucosal Syndromes, Arch. Dermatol. 84: 762.771, 1961. 37. Sadeghi, E. M., and Witkop, C. J., Jr.: Ultrastructural Study of Hereditary Benign Intraepithelial Dyskeratosis. ORAL SURG. 44: 567-577, 1977. 38. Cawson, R. A., and Rajasingham, K. C.: Ultrastructural Features of the Invasive Phase of Can&da a/&am, Br. J. Dermatol. 87: 435-443, 1972. 39. Mohamed, A. M. H.: Ultrastructural Aspects of Chronic Oral Candidosis, J. Oral Pathol. 4: 18@194, 1975. 40. Montes, L. F., and Wilborn, W. H.: Ultrastructural Features of Host-Parasite Relationship in Oral Candidiasis, J. Bacterial. 96: 1349-1356, 1968. 41. Lehner, T.: Oral Candidosis, Dental Pratt. 17: 209-216, 1960. 42. Roth, F. J., Jr., and Goldstein, M. I.: Inhibition of Growth of Pathogenic Yeasts by Human Serum, J. Invest. Dermatol. 36: 383-387, 1961. 43. Maibach, H. J., and Kligman, A. M.: The Biology of Experimental Human Cutaneous Monoliasis, Arch. Dermatol. 85: 233-257, 1962. 44. Kapica, L., and Blank, F.: Growth of Candida albicuns on Keratin as Sole Source of Nitrogen, Dermatologica 115: 8 1- 105, 1957.
Reprint
requesrs to:
Dr. Ezedin M. Sadeghi Division of Pathology Marquette University School of Dentistry 604 N. Sixteenth St. Milwaukee, Wis. 53233
observation
Ezedin M. Sadeghi, D.D.S., M.S., * and Carl J. Witkop, D.D.S., Milwaukee, Wis., and Minneapolis, Minn. DIVISION HUMAN
OF PATHOLOGY, AND
ORAL
MARQUETTE
GENETICS,
UNIVERSITY
UNIVERSITY,
SCHOOL
OF MINNESOTA,
MS., **
OF DENTISTRY, SCHOOL
AND
DIVISION
OF
OF DENTISTRY
Specimens taken from the buccal mucosa of two patients with hereditary benign intraepithelial dyskeratosis (HDID) were studied by transmission electron microscopy. The uttrastructure of epithelial tissue in HBID was previously reported. Discovery of Candida albicans in this lesion was an accidental finding. The literature on the subject was reviewed and the ultrastructural features of Candida albicans were described.
C
hronic mucocutaneous candidiasis is or may be a prominent clinical feature associated with a number of endogenous or iatrogenic abnormalities. If one disregards candidiasis associated with debilitating conditions such as blood dyscrasias’ or carcinomatosis and iatrogenic alterations of mucosal flora by antibiotics and antineoplastic drugs, 2-4 these underlying abnormalities classically fall into three major categories: (1) abnormalities of the immune system,5-11 (2) endocrinopathies involving particularly parathyroid and adrenal deficiencies,12-i7 or (3) combined, autoimmuneendocrinopathies. 18-21However, with the exception of disorders associated with thymic dysgenesis, such as Swiss-type agammaglobulinemia in which both the thymus-dependent cellular immunity system and the immunoglobulin-antibody system are deficient,22-24 dysplasia of the thymus without agammaglobulinemia (Nezelof-Allibone syndrome), and the third and fourth branchial pouch syndrome of DiGeorge,25s 26the exact nosologic classification of specific Candida-related entities is vague. The literature strongly suggests that many of the cases described as only immune deficiency-associated or as only endocrinopathy-associated are *Assistant Science. **Professor
342
professor,
Division
and Chairman,
of Pathology/Department
Division
of Human
of Basic
and Oral Genetics.
in reality various aspects of an autoimmune-endocrinopathy syndrome.26 Numerous cases of candidiasis occur without known underlying general abnormalities. This type of candidiasis has been the particular concern of investigations of oral “leukoplakia.“27-32 In a majority of these studies, the “leukoplakias” investigated were defined on clinical criteria only as “a white patch, not less than 5 mm. in diameter, which cannot be removed by rubbing and which cannot be classified as any other diagnosable disease.“36 Most of these studies showed a significantly higher frequency of Candidu organisms in speckled leukoplakia (erythematous patches between white ones) than in other types of leukoplakia.27, 32,33 With few exceptions, the frequency of Candida in other types of leukoplakias was not significantly different than the frequency in normal mucosa. Several studies addressed the problem of whether cellular atypia is associated more frequently with lesions containing Candida than with those not containing the organism.27-33 While the criteria for cellular atypia and histologic methods differed, three studies found that 40 to 56 percent of Candida -involved leukoplakias showed atypia and 53 to 67 percent of leukoplakias with atypia were invaded by Candida. 28, 30*31 The problem with these studies is that they do not clearly distinguish whether tissues with cellular atypia are prone to inva003Cb4220/79/100342+05$00.50/0
0
1979 The C. V. Mosby Co.
Volume 48 Number 4
C. albicans in hereditary benign intraepithelial
dyskerutosis
343
Fig. 1. Section from upper region of spinous layer and superficial layer showing intracellularly located Candidn organisms (crrrows). (Toluidine blue stain. Magnification, X400.)
sion by the organisms or whether cellular atypia results from the invasion of Candida. Further, Cawsonzs found Cundida present in only two well-differentiated oral carcinomas out of sixty examined and in none of twenty-seven examples of lichen planus. However, Cundidu was found in six out of ten dyskeratotic lesions. HEREDITARY BENIGN INTRAEPITHELIAL DYSKERATOSIS (HBID)
This report presents evidence for Cundidu invasion associated with hereditary benign intraepithelial dyskeratosis. HBID was first described by Von Sallmann and Paton and Witkop and associates.“” The ocular lesions consist of gelatinous-appearing plaques overlying a hyperemic bulbar conjunctivae most prominently found on the perilimbal bulbar conjunctiva. The oral lesions were asymptomatic and varied from a white delicate opalescent membrane to rough, shaggy, folded plaques most prominently involving the buccal and labial mucosa, floor of the mouth, and side of the tongue. Histologically, the epithelium was increased in thickness due to hyperplasia of the middle and upper prickle-cell layer of large vacuolated cells. Throughout
the layers were numerous round dyskeratotic cells best visualized in Papanicolaou-stained sections. “Cellwithin-cell”- type bodies reminiscent of the corps ronds of Darier’s disease were frequent.35’ M THEPRESENTSTUDY
Biopsies of buccal mucosa lesions were obtained from two patients, a 16-year-old boy and a 22-year-old woman, for an electron microscopic study previously reported. 37 At the time of biopsy, both patients were experiencing a severe flare of their ocular disease. They had photophobia, tearing, and itching of the eyes so severe that they confined themselves to dimly lit rooms during daytime hours. The technique for the preparation of the electron microscopic sections was described in our first report.37 Specimens prepared for electron microscopy were cut, stained with toluidine blue, and examined by light microscopy. Sections from the upper region of the spinous layer and superficial layer showed some intracellularly located elements compatible with Cundida albicans (Fig. 1). Electron microscopic sections from the upper region of the stratum spin&urn and superficial layer showed the presence of fungal elements in both patients
CM surg.
October,1979
Fig. 2. This electron micrograph illustrates &e presence of fungat cetis in the upper spinous cell layer. One of these fungal cells demonstratebranching. (Magnification, ~4,000.)
(Fig‘ 2). Hyphae were present intracellularly, some demonstrating branching [Fig. 2). Yeast cells were found penetrating the keratinocyte membrane (Fig. 3). Fungal cells were not observed within round dyskeratotic cells but were seen in their vicinity (Fig. 3). The yeast cell wall was homogeneous with moderate electrodensity. The cell membrane was situated immediately beneath the cell wall and had an electron-dense trilaminar unit membrane structure and occasionally showed small in~cytopla~mic invaginations. Mitochondria were well developed with parallel cristae (Fig. 4), Occasionally, inflammatory elements, particularly mast ceils, could be found in the connective tissue below the basal-cell layer. The fine structure of these fungal eiements was identical to those previously described for C. afbicarrs. 38-40 DISCUSSON Within recent years many investigators have tried to categorize oral candidiasis.28, 2e, 4o* 41 In order to
achieve a reasonable classification of this condition, one must study the pathogenicity of C. ~1~~~~~. a feature which has never been indisputably estabiished. Many factors related to the pathogenicity of C. albicans have been suggested: defective celular immunity,t7 immune det5ciencney,5-‘1endocrinopathy,i~-~~ iatrogenic factors such as antibiotic therapy,3 use of antineoplastic drugs for patients with cancer,4 and lack of anticandidal factors in the serum of patients with chronic candid~asis.~ F~he~ore, it has been suggested that the defective epithelium may act as a predisposing factor for the overgrowth of C. albicuns. 43Since epithelial tissue of the oral mucosa of patients with I-IBID is dyskeratotic, it may offer a special milieu for C* albicans, as the organism has been shown to be capable of using keratin as its sole source of nitrogen.44 The finding of Candida organisms in the oral tissues of two patients with I-IBID at a time when they were experiencing severe ocular lesions suggests that these organisms may be associated with the vernal exacerba-
Volume 48 Number 4
C. albicans in hereditary benign intraepithelial
dyskeratosis
Fig. 3. E lectron micmgraph showing a fungal cell in the process of penetration of the epithelial cell mc:mbrane Part of a round dyskeratotic cell can be observed at the upper part of the section. (Magnification, X 8 ,0001.)
4. n his is a high-magnification view of a fungal cell. Cell wall (CW), cell membrane (CM), mito char rdria and ribosomes (R) can be identified in this electron micrograph. (Magnification, X35,ooo.)
345
346
Sadrghi und Witkop
tion of the eye lesions observed in this disease. The present study was primarily initiated to describe the ultrastructure of hereditary benign intraepithelial dyskeratosis. The discovery of C. albicans was an incidental finding which has not been formerly reported. The significance of this observation remains to be demonstrated by further epidemiologic and histologic studies of this condition. REFERENCES
5
6. 7. 8. 9. 10.
Il.
Bodey, G. P.: Fungal Infection Complicating Acute Leukemia, J. Chron. Dis. 19: 667-687, 1966. Hultin, M.: Candidos och Antibiotica, Svensk. Tandliik Tidskr. 47: 441-451, 1954. Giunchi, G.: Candidosis Following Antibiotic Therapy, Sci. Med. Ital. 6: 580-628, 1958. Bottomley, W. K., Perlin, E., and Koss, Cl. R.: Antineoplastic Agents and Their Oral Manifestations, ORAL SURG. 44: 527534, 1977. Chilgren, R. A., Quie, P. Cl., Meuwissen, H. J., a&Hong, R.: Chronic Mucocutaneous Candidiasis, Deficiency of Delayed Hypersensitivity and Selective Local Antibody Defect, Lancet 2: 688-693, 1967. Chilgren, R. A., Hong, R., and Quie, P. Cl.: Candida-Serum Interaction in Six Patients With Chronic Candidiasis, Fed. Proc. 26: 699, 1967. (Abst.) Canales, L., Louro, J. M., Middlemas, R. O., III, and South, M. A.: Immunological Observations in Chronic Mucocutaneous Candidiasis, Lancet 2: 567-571, 1969. Kirkpatrick, C. H.: Chronic Mucocutaneous Moniliasis With Impaired Delayed Hypersensitivity, Clin. Exp. Immunol. 6: 375-385, 1970. Kirkpatrick, C. H., Rich, R. R., and Bennett, J. E.: Chronic Mucocutaneous Candidiasis: Model Building in Cellular Immunity, Am. bit. Med. 74: 955-978, 1971. Amman. A. J., and Hong, R.: Cellular Immunodeficiency Disorders. In Stiehm, E. R., and Fulginiti, V. A. (editors): Immunologic Disorders in Infants and Children, Philadelphia, 1973, W. B. Saunders Company. Mylarniemi, S., and Perheentupa, J.: Oral Findings in the Autoimmune Polyendorcinopathy-Candidiasis Syndrome (APECS) and Other Forms of Hypoparathyroidism, ORAL SURG. 45: 721-729,
1978.
12. Thorpe, E. S., and Handley, H. E.: Chronic Tetany and Chronic Mycelial Stomatitis in a Child Aged Four and One-Half Years, Am. J. Dis. Child. 38: 328-338, 1929. 13. Gass, J. D.: The Syndrome of Keratoconjunctivitis, Superficial Moniliasis, Idiopathic Hypoparathyroidism and Addison’s Disease, Am. J. Ophthalmol. 54: 660-674, 1962. 14. Genant, H. K.: Addison’s Disease and Hypoparathyroidism (Schmidt’s Syndrome), Metabolism 16: 189--194, 1967. 15. Blizzard. R. M.. and Gibbs, J. H.: Candidiasis: Studies Pertaining to its Association With Endocrinopathies and Pernicious Anemia, Pediatrics 42: 231-237, 1968. 16. Golonka, J. E., and Goodman, A. D.: Coexistence of Primary Ovarian Insufficiency, Primary Adrenocortical Insufficiency and Idiopathic Hypoparathyroidism, J. Clin. Endocrinol. 28: 79-82, 1968. 17. Hermans, P. E., Ulrich, J. A., and Merkowitz, H.: Chronic Mucocutaneous Candidiasis as a Surface Expression of DeepSeated Abnormalities, Am. J. Med. 47: 503-519, 1969. 18. Wuepper, K. D., and Fudenberg, H. H.: Moniliasis, “Autoimmune” Polyendocrinopathy, an Immunologic Family Study, Clin. Exp. Immunol. 2: 71-82, 1967. 19. Hermans, P. E., and Ritts, R. E.: Chronic Mucocutaneous Candidiasis: Its Association With Immunologic and Endocrine Abnormalities, Minn. Med. 53: 75-80, 1970. 20. Perheentupa, J., and Hiekkala, H.: Twenty Cases of the Syndrome of Autoimmune Endocrinopatby and Candidiasis, Acta Paediatr. Stand. 62: 1 I@lll, 1973.
Oral Surg. October, 1979 21. Richman, R. A.: Candidiasis and Multiple Endocrinopathies, Arch. Dermatol. 111: 625-627, 1975. 22. Glanzmann, E., and Riniker, P.: Essentielle Lymphocytophthise: Ein Neues Krankheitsbild aus der Sauglingspathologie. Ann. Paediatr. 175: l-32, 1950. 23. Freycon, F., Jeune, M., Larbre, F., and Germain. D.: L’aplaaie Lymphoplasmocytose au Nourisson Avec Alymphocytose et Hypogammaglobulinemie, J. Med. Lyon 42: 147-192, 196 1. 24. Peterson, R. D., Cooper, M. D., and Good, R. A.: The Pathogenesis of Immunologic Deficiency Diseases. Am. J. Med. 38: 579604, 1965. 25. DiGeorge, A. M.: Discussion, J. Pediatr. 67: 907-908, 1965. 26. Gorlin, R. J., Pindborg, J. J., and Cohen, M. M., Jr.: Syndromes of the Head and Neck, ed. 2, New York, 1976, McGraw-Hill Book Co. 27. Jepsen, A., and Winther, J. E.: Mycotic Infection in Oral Leukoplakia, Acta Odontol. Stand. 23: 239-256, 1965. 28. Cawson, R. A.: Chronic Oral Candidosis and Ieukoplakia, ORAL SURG. 22: 582-591,
1966.
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Dr. Ezedin M. Sadeghi Division of Pathology Marquette University School of Dentistry 604 N. Sixteenth St. Milwaukee, Wis. 53233