Intraoral sebaceous hyperplasia

Intraoral sebaceous hyperplasia Diagnostic criteria Tom D. Daley, DDS, MSc, FRCD(C).(’ DEPARTMENT

OF PATHOLOGY,

UNIVERSITY

London, Ontario, OF WESTERN

Canada

ONTARIO

Surprisingly little is understood about the physiologic and pathologic processes that involve intraoral sebaceous glands. Neoplasms are rare. Hyperplasia of these glands is undoubtedly more common, but criteria for the diagnosis of intraoral sebaceous hyperplasia have not been established. These lesions are too often misdiagnosed as large “Fordyce granules” or, when very large, as sebaceous adenomas. On the basis of a series of 31 nonneoplastic sebaceous lesions and on published data, the following definition is proposed: intraoral sebaceous hyperplasia occurs when a lesion, judged clinically to be a distinct abnormality that requires biopsy for diagnosis or confirmation of clinical impression, has histologic features of one or more well-differentiated sebaceous glands that exhibit no fewer than 15 lobules per gland. Sebaceous glands with fewer than 15 lobules that form an apparently distinct clinical lesion on the buccal mucosa are considered normal, whereas similar lesions of other intraoral sites are considered ectopic sebaceous glands. Sebaceous adenomas are less differentiated than sebaceous hyperplasia. (ORAL

St-RG

ORAL

MED

ORAL

PATHOL

A

1992;74:343-7)

dvances have been made in the understanding of the function of somemucosal sebaceousglands, such as the meibomian glands of the eyelid that secrete lipids that are now known to stabilize the precorneal tear film.’ Research on the function and control of sebaceousglands of the skin has escalated considerably, in part because of the market for antiacne drugs.’ Yet despite the presenceof hundreds of sebaceousglands on the buccal mucosaof most people,*.” their function remains a matter of speculation with little, if any, interest directed to them. Pathologic changes in these intraoral glands are equally ignored except for rare reports that usually concern neoplasms.‘.’ The most common abnormality is undoubtedly sebaceoushyperplasia, a diagnosis that is difficult becauseof the lack of defined criteria and the tendency to misdiagnose these lesions as large Fordyce’s granules or, when very large, as sebaceous adenomas. As drugs that alter the sebaceousfunction of the skin become available to treat acne vulgaris, correspondingchangesin oral glands shouldbe anticipated. Because these changes may alter the morphologic “Associate Copyright

Professor. ’ 1993 by Mosby-Year

0030-4220/93/$1.00+.10

7/14/41443

Book,

Inc.

conditions of the sebaceousgland, it may be important to develop diagnostic criteria to permit a more accurate diagnosis of intraoral sebaceous hyperplasia, which could then be distinguished both from the normal range in size of intraoral sebaceousglands and from sebaceousadenoma. On the basis of a series of 31 nonneoplastic sebaceouslesions that range from simple sebaceous glands to markedly enlarged sebaceousstructures, and considering published data on intraoral sebaceous glands, as well as incorporating criteria developed in dermatopathology, this paper recommends criteria for the diagnosis of intraoral sebaceoushyperplasia. MATERIAL AND METHODS Thirty casesdiagnosed as sebaceousgland lesions, which included Fordyce’s granules and its many synonyms, were retrieved from the archives of the Oral Pathology Diagnostic Service, University of Western Ontario, London, Ontario, for the 15-year period from 1977 to 199 1 inclusive. One additional casewas included from the archives of University Hospital, London, Ontario. Lesions that involved major salivary glands were excluded. No sebaceousneoplasms of intraoral glands were found, and one case of steatocystoma simplex that had been reported elsewhere’ was excluded. Initially, a single hematoxylin 343

Fig. 1. IVormal sebaceous gland with sewn lobules. l.oi~ule count ix based on 5 pm tissue sections despite the i‘,~c: Ihat more lobules are undoubtedlq present in other plane\. Lobules :! and 3 arc scparaled 1~1 ;I pcrminativt: la>tzr thai exctenda hall’\zay to Ihe excretory duct. (flern~ltoli~lin-eoain stain:

and

original

niagnilication

eosin-stained

section

of each

and lobules counted.

A lobule.

tissue

detined

section.

5;ebocytes native

~\a:,

surrounded cells.

except

I

X50.

the

or

;I

focal

of :I 5 pnr

collection

IWO layer\

sehoqtcs

RESULTS

I\;I~ examined.

in the contcxt as

bq one where

cast

were

I)!

ot’ germi. in dircci

a duct (Fig. I ). Bilobed acini were counted as two lobules if the separating germinatilc layer extended more than halfway to the cxcretor! duct (Fig. 1 ). Casts that were clinically distinct and exhibited fewer than 20 lobules were sectioned at fi\,c levels, reexamined. and recounted to determine if the number of lobules initially counted wxs ;I maximunl. The tissue section with the maximum lobule count was used for analysis. No attempt \vas made to produce 3 threc-dimensional model that hould result in ;I higher lobule count. continuity

with

‘I‘ahlc I ii41\ pertinent inl‘ormation on lhc 31 cast\. Sixteen were diagnosed as sebaceous hypcrplasia ;IC.. cording to criteria developed (Fig. 2). F’ifteen GIW 1‘rom the Oral Pathology Diagnostic Service were found among 20.360 accessions. or :thout 1 cease in cvcry 2000. The mean age Eor patients with \cbaceouh hjpcrptasia wax 3X.3 yeara with ;I range from 22 to 70 >cars. There uere nine men and seven women. The solitar\ lesions, which were interpreted to be clinicall) abnormal. wcrc described a\ a\ymptonlatic. raised. w bite-to-yellow\. and round or oval (Fig. 3 ). On occaiion. ;I \L bite g!rcas>’ nlatcrial could bc expressed with applied prcksurc. Five. including the Lhrcc largebt, ocmrrcd

on t hc rctrornolar

huccal

mucous or i.estihule;

pad;

five

occurred

t\\o occurred

on the

on the gin--

OKAI. SUKGER~ OILYI M~~DICI~E Volume 7.5. Number 3

ORAL

Dale!

PATHOLOGY

Table I. Clinical diagnosis, lobule count, and final diagnosis of 31 nonneoplastic sebaceous lesions. (‘a.\ e

Clinical diagnosis (location)

L-

I 2 3 -I 5 6 7 x 9 I0 II I? I? I4 IS I6 I7 I8 I9 20 21 2’ 23 24 75 26 27

Lymphiod/lipid

tissue

Aphthous

ulcer

Papilloma Leukoplakia

(rmp) (ulm)

- (rmp) Verruciform Ectopic Sebaceous

granule

gland (hm)

Fordyce’s

granule

(g)

(am)

(g) (rmp)

(hm) granule

(atp)

(g)

Periodontal Scarred Incidental

abcess (g) parulis (g) tinding (rmp)

Infected

gingival

Unknown Nicotine

3)

(hm)

Fordyce’s granule Large Fordyce’s

Stomatitis I-ordyce’s

(Fig.

(atp)

(am) (hm)

H yperkeratosis

Lcukoplakia

(rmp)

sebaceous gland cyst (hm)

Sebaceous Trauma Keratin Fihroma

Distinct

(rmp)

xanthoma

Fordyce’s

--r---

nicotina granules (hm) irritation

cyst

(g)

(hm) (bm)

Incidental L*ichen

29

Incidental

finding

(bm)

30 31

Fordyce’s Sebaceous

granule glands

(hm) (hm)

giva; two on the maxillary alveolar mucosa; and one each on the upper lip mucosa and anterior tonsillar pillar. Six cases were diagnosed as ectopic sebaceous glands; four on the maxillary gingiva; and one each on the anterior tonsillar pillar and retromolar pad. The remaining nine were considered normal sebaceous glands of the buccal mucosa. DISCUSSION Large clinical studies have consistently shown that 70% to 80% of the population have sebaceousglands in the buccal mucosa. including the maxillary and mandibular buccal vestibules.2-” They occur in both sexesand all age groups, although lessoften in young children. Given this information, sebaceousglands of the buccal mucosa must surely be considered normal structures, even though their function is speculative at present. However, sebaceousglands are not charac-

Ski Sll sti SII Sll

151 60 42

Yes Yes

32 31

Yes

31

Ye5 Yes

28 25

Yes Yes

2.3 21 IE

Sfl Yfl

Ye5

21

St1

Yes Ye5

21 20

Sll Sll

Yes Yes

I9 18

sti SII

Ye5

IX

Yes YCS

I0 IO

Sl I Ix;

SII Sll SII

Yes Yes

9 6 IF

Ye5

3 2 IE

k,SG L:SG l:SCi ESG NSG NSG

9 s 5

No

s

Yes

3 3 I

unknw+n, maxillary

F,.hG

37 29

NO

No

SH. sebaceous hyperplasta: ESG, ectopic sebaceous gland: NSG, normal :sebaceous gland;--. cosa; (3~). :~nterror tonGlIar pillar. (rmp). retromolar pad, (ulm). upper lip mucos;~, (am).

COLl?l!

Yes

No Yes

finding (hm) planus (hm)

biopsies of

Yes YCi

No

(hm)

2x

lesion

intraoral

345

(g), gingiva: IE mcomplctc alveolar muc~x:~

NSG NSG NSG NW NSG N.\G NSG excision:

(bm !, bucwl

mu-

teristically found in any other intraoral site. Therefore the term ectupic can justifiably be applied to intraoral sebaceousglands found on the tonsillar pillars, the retromolar pad, the gingiva, the tongue, the alveolar mucosa, the palate, the labial mucosa, and the floor of the mouth.’ If it is accepted that intraoral sebaceousglands are normal, then excessiveenlargement of one or more of these glands should be considered “sebaceous hyperplasia.” Hyperplasia is defined as an abnormal increase in the number of normal cells in normal arrangement in a tissue.to For sebaceousglands this would be manifest as an increase in the number of cells per lobule, an increasein the number of lobules, or both. Counting cells, which is time consuming and often requires special equipment and statistical analysis, would be an impractical method for diagnostic histopathologists to readily assesssebaceoushyperplasia. On the other hand, data from this study indi-

346

DaleI,

cate that counting lobules in a routine tissue section is easy, fast, requires no special techniques. and is 21 reliable method to assesssebaceousgland enlargement. The critical number of lobules above which a diagnosisof sebaceoushyperplasia is appropriate is \c:i-\ difficult to determine becauseof the range in G/e ;,I sebaceousglands from person to person. and in the same person.‘.” Becauseof this wide variation. hotlr Miles’ and Sewerin’ were reluctant to recognire &I state of intraoral sebaceoushyperplasia. Miles stated that glands varied in size from I to “30 or so” lobule\ but large glands “could have as many as 10 lobules ” He described in his Fig. IO3 a lesion with 40 lobulcl with cystic degeneration of the duct, with the phraxl~ “very large sebaceousgland.” Sewerin stated that hc: did not “feel in a position to fix any upper limit to thy siLe of ‘normal’ sebaceous glands.” Hc ;~ccepteti glands that exceeded 2.4 mm in size a:, clinical]\ nor ma].’ Yet there exists white-to-yello\+ subepithelial 111s cules or papules that appear clinically as distinct :lhnormalities (Fig. 3) that require biopsy for diagnosis These lesions consist of numerous sebaceousgland lobules that exhibit normal maturation. They ;~rc unequivocally. clinically enlarged. The presenceof a clinical lesion on skin is ;I prcrcq uisite for the diagnosisof sebaceoushyperplasia.’ ‘. ’ This is necessarybecauselarge sebaceousglands thar do not produce a papule would not be clinically e\;~dent becauseof the keratinization and pigmentation of the overlying skin. However, in the oral cavit?, even normal sebaceousglands are clinically obvious under the nonkeratinized. usually nonpigmented epitheiiunl of the buccal mucosa. Even a small sebaceousgland may be interpreted by someclinician,. in the proper setting, as a lesion. Therefore the presence01’an apparently distinct clinical lesion alone is not suffcienl criteria for intraoral sebaceoushyperplasia. It ib ncc essaryto assigna value for the number of lobules hclow which a diagnosisof sebaceoushyperplasia ih in appropriate in spite of the clinical setting. ‘l-hi> method does not attempt to establish an upper limit for the number ol‘ lobules within the range of normal sebaceousglands, but it does establish a loucr limit for the number of lobules necessaryf‘ur a diagnosiso! sebaceoushyperplasia. Chambersi studied 100 histologic sections 01‘\cbaceousglands of the buccal mucosaand constructed three-dimensional modelsof two glands. His research showed that the oral glands varied from one IC) I o lobules. Margolis and Weidman” examined tihsuc sections of buccal mucosa from rime necropsiesand found sebaceousglands with as few as one lobule aI-

though “moat ut them” consistedof “two to four lobules.” Miles’ found sebaceousglands to have from one !O 70 “()I’ \,I’. iobules. Our studies showed a gap in iohulc number, between 10 and IX. On the basis of these data. ;I iimit oi’ Ii lobules was arhitrarill set, Thib is well ;Ibove the limit suggesLedby Chambers :Ind b\- Margoiis and Weidman, but within the limit \uggestcd h> jliles, \t ho wah reluctant IO recognize sebaceoushi pcrplasia. and within Ihc gap Loneof this
(‘rlteriott _i i’here must be no lewer than 15 normalls differentiating sebaceouslobules. L2’ith the IIX of these criteria, the 31 ases in c)ur jtudq can hc divided into specific categories. Sixteen axes pro examples of sebaceoushyperplasia because Ihey ?+credlslinct clinical lesionsand had more than 17 lobulch. thr numbers ranged from IX to 151. Six GISC~ wcrc di\l.rete lesionswith fewer than 15 lobules hut occurring III unusual oral sites. ‘These are diagnosed;I\I “zclopic sebaceousglands.” Se\;en casesthat occurred on tiic‘ buccal mucosaand had fewer than 15 lobule:, are interpreted as “normal sebaceousglands.” l-our 01‘these lesions\sere discrete clinically but had microscopii, ~~IXICCOLI~ glands that wcrc considered I$ithin the ~~~.rrma! range. Trio cases on the buccal mucosa in i~ur ,ludS had more than 1C lobules but \\ere no1 di\cretc clinical lesions. These two were
0~41

SLIK(;I:RY

Volume

M~;DICIILE

ORAL

75, Number

0~4~

Dales 347

P,ITI~OLO(;Y

3

of sebocytes that differentiate fully from the basal and parabasal layers of germinative cells.]‘, I2 Sebaceous adenomas contain sebocytes, basaloid germinative cells, and some intermediate cells in varying porportions per lobule, which show disorderly differentation to the point when some lobules may be predominently basaloid cells (Fig. 4). It follows then that sebaceous adenoma is a microscopic diagnosis. Therefore a very large lesion composed of orderly, differentiating sebaceous lobules that have only basal and parabasal germinative cells is sebaceous hyperplasia, not sebaceous adenoma. Batsakis and El-Naggar16 accurately stated that oral sebaceous lesions are most often hyperplastic-hype:rtrophic rather than neoplastic. CLINICAL

DIFFERENTIAL

DIAGNOSIS

A discrete yellow papule or macule may clinically resemble a number of lesions including verruciform xanthoma, xanthogranuloma, paraffinoma, abcess, lipoma, benign lymphoepithelial cyst, or epidermoid cyst. On gingiva or alveolar mucosa, sebaceous hyperplasia or ectopia may simulate a periodontal abcess, periapical abcess or ectopic salivary gland tissue. A spectrum of differential diagnoses is presented in Table I. REFERENCES I. Thody AJ. Shuster S. Control and function of glands. Physiol Rev 1989;69:383-416. 2. Halperin V, Kotas S, Jefferis KR, Huddleston SO, HBG. The occurrence of Fordyce spots, benign gtossitls. median rhomboid gtossitis, and fissured 2478 dental patients. ORAL SURC ORAL MED OR4L 1953:6:1072-7.

sehaceoJs Robinson migratory tongue in PATHOL

3. Mites AEW. Sebaceous glands in the lip and cheek mucosa of man. Br Dent J 1958;105:235-48. 4. Sewerin I. The sebaceous glands in the vermilion horder of the tips and in the oral mucosa of man. Acta Odontot Stand 1975;33(suppt 68):2-217. 5. Miller AS, McCrea MW. Sebaceous gland adenoma of the huccat mucosa: report of case. J Oral Surg 1968;26:593-5. 6. Ortian At. Satman L. Reddi T. Yamane GM. Chaudrv AP. Sebaceous adenoma of the oral mucosa. J Oral Med ‘I 987: 42:38-9. 7. Damm DD, O’Connor WN, White DK, Drummond JF, Morrow LW, Kenady DE. Intraoral sebaceous carcinoma. OR,~L SURG

OR?ZL

MED

ORAL

PATHOL

I99 1;72:709-I

I.

8. Ferguson JW, Geary CP, MacAlister AD. Case report: Sehaceous cell adenoma-Rare intraoral occurrence of a tumour which is a frequent marker of Terre’s syndrome. Pathology 1987;19:204-8. 9. Datey TD. The pathology of intraoral sebaceous glands: a review. J Oral Pathot Med (in press). IO. Dortand’s illustrated medical dictionary, 27th ed. Phitadelphia: WB Saunders Co, 1988:797. Il. Prioleau PG, Santa Cruz DJ. Sebaceous gland neoplasia. J Cutan Pathot t984;t 1:396-414. 12. Lever WF, Schaumburg-Lever G. Histopathology of the skin, 7th ed. Grand Rapids: JB Lippincott. 1990:596-7. 13. Chambers SO. The structure of Fordyce’s disease as demonstrated by wax reconstruction. Arch Dermatol Syphilot t928;t 8:666-72. 14. Margolis A, Weidman F. Statistical and histologic studies of Fordyce’s disease. Arch Dermatol Syphilot I92 I ;3:723-42. 15. Warnock GR, Jensen JL, Kratochvil FJ. Developmental diseases. In: Ellis GL, Auctair PL, Gnepp DR. Surgical pathotogy of the salivary glands. Philadelphia: WB Saunders, t991:18-20. 16. Batsakis JG. El-Naggar AK. Sebaceous lesions of the salivary glands and oral cavity. Ann Otol Rhino Larkngol 1990; 99:416-g. Reprim requests: Tom D. Daley, DDS, MSc. FRCD(C) Associate Professor Department of Pathology University of Western Ontario London, Ontario, Canada N6A 5Cl