Warty dyskeratoma of the oral mucosa Correlated
light and ekctron
J. Robert Newland,
DEPARTMENT OF PATHOLOGY SCIENCE CENTER AT HOUSTON
and George S. Leventon. D.D.S.,
M.S., Houston, OF TEXAS
A warty dyakeratoma arising from the palatal mucoaa of a 36year-old man was studied by light and electron microscopy. The ultrastructural features of this lesion were compared with those of the lesions of Darier’a disease. Histologic sections showed a keratin-filted depression of the epithelial surface, auprabaaal clefting, and acantholytic, dyakeratotic grains and corps ronda. Electron microscopic examination revealed a decrease in the number of intact attachment sites on the surfaces of the epithelial cells adjacent to the auprabaaal cleft. Acantholytic grains within the cleft contained dense bands of tonofilamenta and were devoid of attachment sites. Corps ronda within the stratum granuloaum appeared as dyakeratotic vacuolated cells. Warty dyskeratomaa and the lesions of Darier’a disease are clinically distinct, but the acantholytic and dyakeratotic cells characteristic of both show many ultrastructural similarities. (ORAL
arty dyskeratoma is a focal acantholytic dyskeratosis’ that commonly occurs on the skin of the scalp, face, and neck. Lesions arising on the oral mucosa are rare, and only twelve examples have been reported previously.2-‘0 Warty dyskeratomas are histologically similar to the lesions of Darier’s disease, but their clinical presentation is different and the precise relationship between the two diseases is uncertain. The purpose of this report is to describe the light and electron microscopic appearance of a warty dyskeratoma arising on the oral mucosa and to compare the ultrastructural features of this lesion with those of Darier’s disease. CASE REPORT
A 36-year-oldwhite manwasreferred for evaluationof an asymptomaticlesionof unknownduration arisingfrom the left palatal gingiva (Fig. 1). Clinical examination revealeda well-circumscribed,slightly elevatedlesionwith a keratotic surface.A local anestheticwasgiven, and the lesionwasexcised. Histologic
The biopsyspecimenwasbisectedandhalf wasplacedin 10%neutral buffered formalin for routine light microscopy. The remaining half was fixed in 2% glutaraldehyde, postfixed in 1% osmiumtetroxide, dehydrated in graded alcohols,and embeddedin Epon. Thin sectionswere cut with a diamondknife, stainedwith uranyl acetateandlead 176
1. Clinical photograph showing a well-circumscribed,slightly elevated,keratotic lesionof the left palatal mucosa.
citrate, and examinedwith a ZeissEM9 S transmission electron microscope. Light microscopicfindings. The lesionconsistedof a nodularfragmentof parakeratinizedpalatal mucosawith a deep,keratin-filled defect extending through the stratum spinosum(Fig. 2). A suprabasalcleft was presentwithin the epithelium adjacent to the defect. Submucosalvilli lined with a singlelayer of basalepithelialcellsformedthe baseof the cleft (Fig. 3). Acantholytic celb werescattered within the cleft (Fig. 3), and corps ronds, each with
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Fig. 2. Photomicrographof the lesionillustrated in Fig. 1, showinga thickenedepithelialsurfacewith a keratin-filled depression and a suprabasalcleft. (Hematoxylin and eosinstain, magnification,X100.)
abundantcytoplasmand a pyknotic nucleusencircledby a distinct halo, were encounteredin the epithelium at the junction of the stratum spinosumand stratum granulosum (Fig. 4). Electron microscopicfindings. Elongatedbasalepithelial cells lining the submucosalvilli were attached to the underlying basallamina by well-formedhemidesmosomes (Fig. 5). Microvilli extended from the apical and lateral surfacesof eachbasalcell. Adjacent cells werejoined by desmosome-tonofilament complexesalongtheir lateral cell surfaces.Intact desmosometonofilament complexeswere absent on the apical surfaces of the basal cells, but hemidesmosomes consistingof plaquelike thickeningsof the cytoplasmic membranewith attached tonofilament bundleswere occasionallyseen(Fig. 6). Each basalcell containeda large, centrally located nucleuswith coarsely clumpedchromatin and an indented nuclear membrane. Prominentnucleoliwerecommonlyseen.The cytoplasmof thesecellscontaineddense,perinuclearbandsof tonofilamentsand numerousribosomesand polyribosomes.Other organelleswere lessconspicuousand consistedof a few cisternaeof rough endoplasmicreticulum and scattered mitochondria. Elongatedacantholytic grains with irregular cytoplasmic outlines and numerous microvilli were identified within the cleft (Fig. 7). Desmosome-tonofilament complexeswere not present,and hemidesmosomes were seen only rarely. The cytoplasm of these acantholytic cells containeddensebandsof tonofilamentswith a few interspersedvacuoles. Many did not contain nuclei. When
present,nucleiwere usuallysmallerthan thoseof adjacent basal cells. In addition to the’ epithelial grains, a few erythrocytesand scatteredcellular debriswerealsopresent within the cleft. The roof of the suprabasalcleft was formed by elongatedparabasalcellswhich werelesscloselyapposedthan cellshigher in the stratum spinosum.There wereno intact desmosome-tonofilament complexeson their surfacesadjacent to the cleft; however,a few residualhemidesmosomes were present(Fig. 8, inset). Each cell containeda large, oval nucleus with coarsely clumped chromatin and a distinct nucleolus.Their cytoplasmwasfilled with bundles of tonotilaments,and a few containedscatteredvacuoles. Dyskeratotic corps ronds were distinctly round and appearedto beseparatedfrom adjacentepithelialcellsby a narrow clear zone (Fig. 9). Attachment siteswere inconspicuous.Nuclei, which were smallerthan thoseof neighboringcells,weresurroundedby numerousvacuoleswhich displacedcytoplasmic tonofilament bundles toward the periphery of the cell. DISCUSSION Warty dyskeratomas are common cutaneous lesions,but oral mucosal involvement is unusual. The clinical features of the twelve reported cases are summarized in Table I. The oral mucosal lesion presented in this report displayed all the histologic features of a warty dyskeratoma: thickening of the epithelial surface
Fig. 3. Higher-powerphotomicrographof the suprabasalcleft showinga submucosal villus lined with a singlelayer of basalepithelialcells.An acantholyticgrain (arrow) canbeseenwithin the cleft. (Hematoxylin and eosinstain. Magnification, x450.)
Fig. 4. Higher-powerphotomicrographof the stratumgranulosumshowinga corpsrond (arrowj separated from the neighboringepithelial cellsby a narrow clear zone. The corpsrond containsa pyknotic nucleus surroundedby a distinct perinuclearhalo. (Hematoxylin and eosinstain. Magnification, x450.)
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Warty dyskeratoma of oral mucosa 179
Fig. 5. An electron micrograph of a portion of a submucosal villus showing elongated basal cells attached to the underlying connective tissue. The basal cells contain oval nuclei and dense bundles of perinuclear tonofilaments. Their apical surfaces display numerous microvilli, but intact desmosome-tonofilament complexes cannot be seen. (Magnification, X4,200.)
kg. 6. An electron micrograph of the apical surface of a basal epithelial cell showing several hemidesmosomes (urrows~. (Magnification, X 10,000.)
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Fig. 7. An electronmicrographof an acantholytic grain within the suprabasal cleft. The cytoplasm is filled with dense bands of tonofiiaments and scattered vacuoles. The surface of the grain is devoid of desmosome-tonofilament complexes.(Magnification, ~3,500.)
with a central, keratin-filled depression, a suprabasal cleft beneath the depression, submucosal villi lined with a single layer of basal epithelial cells projecting into the cleft, and the presence of acantholytic, dyskeratotic grains and corps ronds. When viewed with the electron microscope, hemidesmosomes consisting of an attachment plaque with associated tonofilament bundles were seen on the surfaces of the epithelial cells adjacent to the cleft. The presence of these altered attachment sites suggested that the acantholysis seen with the light microscope was the result of a defect in the desmosometonofilament complexes joining the affected cells. Since the desmosomal attachment plaque and tonofilaments were intact, the defect appeared to be localized in the region of the intercellular contact layer. The dyskeratosis seen in the affected epithelial cells resulted from the accumulation of dense bands of tonofilaments within their cytoplasm. In the basal and parabasal epithelial cells adjacent to the cleft, tonofilaments tended to aggregate in dense bands around the nucleus of each cell, whereas in the epithelial grains tonofilaments completely filled the cytoplasm, obscuring other cytoplasmic constituents. In the corps ronds, tonofilament bundles were displaced toward the periphery of the cytoplasm by numerous perinuclear vacuoles. The zone of vacuoles in the
corps ronds corresponded to the perinuclear halo seen by light microscopy. Similar vacuoles were distributed randomly between the tonofilament bundles in the cytoplasm of epithelial grains. It was not possible to determine the exact nature of these vacuoles, but they resembled dilated cistemae of endoplasmic reticulum. The ultrastructural changes seen in the cells of the warty dyskeratoma presented here were strikingly similar to the alterations described in the cells of the lesions of Darier’s disease.“-” On the basis of electron microscopic observations, two mechanisms have been proposed to account for the acantholysis seen in the lesions of Darier’s disease. The first suggests that the initial defect leading to loss of cellular attachment is separation of tonofilament bundles from the attachment plaque of the desmosome-tonofllament complex followed by the dissolution of the intercellular contact layer. *it12 The second suggests that the loss of the intercellular contact layer precedes detachment of the tonofilaments.‘3, I5 The presence of hemidesmosomes with intact tondilament bundles on the cells of the lesion presented in this report indicates that the second mechanism produces the acantholysis seen in warty dyskeratoma. The development of epithelial grains and corps ronds in warty dyskeratomas appears to follow the
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8. An electron micrograph of parabasalcells in the stratum spinosumforming the roof of the suprabasalcleft. They contain large irregular nuclei and numerousbundlesof tonofilaments.(Magnification, X4,200.) The surfacesof the parabasalcells adjacent to the cleft display severalhemidesmosomes. (Inset magnification, X10,000.)
sequence of development proposed by Gottlieb and Lutzner14 for grains and corps ronds in the lesions of Darier’s disease. Those authors suggest that vacuolated basal and parabasal cells adjacent to the suprabasal cleft were precursors of both grains and corps ronds. During the formation of grains, these precursor cells lost their attachments to neighboring cells and began premature synthesis of keratin. As the number of cytoplasmic tonofilaments increased, vacuoles became less conspicuous. In corps rond precursors, cytoplasmic vacuoles continued to develop around the nucleus, compressing the tonofilament bundles into a ring at the periphery of the cytoplasm. The cause of warty dyskeratoma is not known. Cutaneous lesions have been associated with the pilosebaceous apparatus, and the development of oral mucosal lesions from ectopic sebaceous glands has been propoxd3 However, Fordyce’s granules could not be demonstrated in histologic sections of the warty dyskeratoma presented in the current study. The use of tobaccos and local trauma’ have also been implicated as contributing factors in the development of oral lesions, but our patient did not use tobacco in any form; nor did he have a history of intraoral trauma. It is of interest that nine of the previously reported oral warty dyskeratomas and the
lesion presented here occurred on attached mucosa adjacent to teeth on the left side of the mouth. Right-handed people are known to cause abrasion of teeth on the left side of their mouths by brushing improperly. It is possible that the incorrect use of a toothbrush with hard bristles could cause oral warty dyskeratomas. Previous reports did not mention specific toothbrushing habits, and our patient denied using a hard toothbrush. By light microscopy, warty dyskeratomas and the lesions of Darier’s disease are similar. Roth show hyperkeratosis, suprabasal clefting, and the formation of epithelial grains and corps ronds. This histologic similarity has prompted some investigators to consider warty dyskeratomas and the lesions of Darier’s disease to be variants of the same disease.1*6 Ackerman’ proposed a method of classification of these lesions based on their number and suggested the term focal acantholytic dyskeratosis to describe them. Focal acantholytic dyskeratoses could present clinically as solitary lesions, such as warty dyskeratomas, or as multiple lesions like those seen in Darier’s disease. However, this concept is controversial. The clinical presentation of warty dyskeratomas and the lesions of Darier’s disease are distinctly different. Warty dyskeratomas appear as solitary lesions, and they do not show any genetic pattern of
Newland and Leventon
Oral Surg. August, 1984
Fig. 9. An electronmicrographof a corpsrond in the stratum granulosum.It containsa pyknotic nucleus surroundedby vacuoleswhich displacethe tonofilament bundlestoward the periphery of the cytoplasm. (Magnification, ~7,200.)
features of warty dyskeratomas of the oral mucosa
1. GorlinandPeterson’ 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
Tomich and Burkes’ Tomich and Burkesj Tomich and Burkes3 Anneroth and Isaccson4 Guinta et aL5 Guinta et aLs Basu andMoss6 Harrist et al.’ Danforth and Greet? Patibanda9 Dixey and Fayio
45/M 49/M 61/M 61/M 74/F 51/F 33/F
49/F 74/F 65/M 53/M 36/M
transmission. In contrast, Darier’s disease presents clinically as multiple mucocutaneous lesions that show an autosomal dominant mode of genetic transmission. Other investigators, emphasizing these clinical differences, consider the two diseases to be totally unrela&d4 This study does not demonstrate conclusively that the warty dyskeratoma is an isolated form of Darier’s disease, but our findings do show that the ultrastruo tural features of the acantholytic and dyskeratotic cells characteristic of both are remarkably similar.
Left hard palate Left mandibular ridge Left mandibular ridge Left hard palate Left hard palate Left buccal mucosa Anterior hard palate Left hard palate Left hard palate Left maxillary ridge Left mandibular ridge Mandibular gingiva
Verrucous nodule Keratotic depression Keratotic papule Keratotic depression Verrucous papule White-gray nodule Gray-white papule Umbilicated papule Verrucous papule Corrugated white lesion Elevated white patch White-gray nodule
REFERENCES 1. Ackerman AB: Focal acantholytic dyskeratosis. Arch Dermato1 106: 702-706, 1972.
2. Gorlin RJ, PetersonWC: Warty dyskeratoma: a notecon3. 4. 5. 6.
cernina its occurrence on the oral mucosa. Arch Dermatol 95: 292-293, 1967. Tomich CE, Burkes EJ: Warty dyskeratoma (isofated dyskeratosis folhcularis) of the oral mucosa. ORAL SURG 31: 7% 808, 1971. Anneroth G, Isacsson G: Warty dyskeratoma. Acta Derm Venereal 55: 227-232. 1975. Guinta JL, Gomez LSA, Greer RO: Oral focal acantholytic dyskeratosis (warty dyskeratoma): reportof twocases. ORAL SURG 39: 474-478, 1975. Basu MK, Moss N: Warty dyskeratoma: a note concerning its
Volume 58 Number 2 occurrence on the oral mucosa, and its possible pathogenesis. Br J Oral Surg 17: 57-61, 1979. 1. Harrist TJ, Murphy GF, Mihm MC: Oral warty dyskeratoma. Arch Dermatol 116: 929-93 1, 1980. 8. Danforth RA, Green TL: Oral warty dyskeratoma. ORAL SURG
11. 12. 13. 14.
Patibanda R: Warty dyskeratoma of the oral mucosa. ORAL 52: 422-424, 198 1. Dixey RJ, Fay JT: Oral warty dyskeratoma: literature review and report of a case. J Oral Surg 39: 378-380, 1981. Charles A: An electron microscopic study of Darier’s disease. Dermatologica 122: 107-l 15, 1961. Caulfield JB, Wilgram GF: An electron microscopic study of dyskeratosis and acantholysis in Darier’s disease. J Invest Dermatol 41: 57-65, 1963. Mann PR, Haye KR: An electron microscopic study on the acantholytic and dyskeratotic processes in Darier’ disease. Br J Dermatol 82: 561-566, 1970. Gottlieb SK, Lutzner MA: Darier’s disease: an electron microscopic study. Arch Dermatol 107: 225-230, 1973. SURG
of oral mucosa
15. Biagini G, Costa AM, Laschi R: An electron microscopic study of Darier’s disease. J Cutan Path01 2: 47-49, 1975. 16. Sato A, Anton-Lamprecht I, Schnyder UW: Ultrastructure of dyskeratosis in morbus Darier. J Cutan Path01 4: 173-184, 1911.
17. Miller RL, Bernstein ML, Arm RN: Darier’s disease of the oral mucosa: clinical case report with ultrastructural evaluation. J Oral Pathol 11: 79-89. 1982. Reprint
Dr. J. Robert Newland Department of Pathology Dental Branch University of Texas Health Science Center P. 0. Box 20068 Houston, TX 77225