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Cheilitis glandularis: A re-evaluation
Journal of the American Academy of Dermatology
Reed et al
tions to toxins and venoms of common marine organisms. Cutis 23:450-454, 1979. 1 t. Black S, Humphrey JH, Niven JSF: Inhibition of Mantoux reaction by direct suggestion under hypnosis. Br Med J 1:1649-1652, 1963. 12. Dvorak HF, Mihm MC, Dvorak AM, et al: Morphology of delayed hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest 31:111-130, 1974.
III II
13. Allen AC: Persistent "insect bites" (dermal eosinophilic granulomas) simulating lymphoblastomas, histiocytoses, and squamous cell carcinomas. Am J Patho124"367-387, 1948. 14. Bemstein H, Shupack J, Ackerman AB: Cutaneous psuedolymphoma resulting from antigen injections. Arch Demaatol 110:756-757, 1974.
I
Cheilitis glandularis: A re-evaluation Robert A. Swerlick, M.D.,*'** and Philip H. Cooper, M.D.*.*** Charlottesville, VA Cheilitis glandularis (CG) has been attributed to hyperplasia of labia/salivary glands. We studied labial biopsy specimens of five patients with clinical CG and compared their salivary tissue with that seen in patients without CG. The labial glands from patients with CG did not differ in size, depth, or histologic appearance from those seen in the controls. They showed little or no inflammation and no hyperplasia. We also reviewed forty-eight cases of CG described in the literature. The accompanying photonficrographs nearly always depicted normal-appearing labial salivary glands. The case histories and clinical descriptions suggested that many examples of CG were manifestations of actinic cheilitis, whereas others may have been unusual presentations of atopic or factitious cheilitis. We believe CG represents an unusual reaction pattern in response to chronic irritation of the lips and is unrelated to labial salivary gland hyperplasia. (J AM ACAD DERMATOL10:466-472, 1984.)
Volkman, ~ in 1870, used the term cheilitis glandularis (CG) to describe a disorder affecting five patients who suffered from deep, suppurative inflammation involving the lower lip. He observed mucopurulent discharge from apparently dilated orifices of salivary ducts and, in addition, severe "catarrhal" inflammation of the mucous memFrom the Departments of Dermatology* and Pathology,*** University of Virginia. Accepted for publicationJuly 11, 1983. Reprint requests to: Dr. Philip H. Cooper, Departmentof Pathology, Box 214, University of Virginia Medical Center, Charlottesville, VA 22908/804-924-5127. **Presently a memberof the faculty of the Department of Dermatology, University of Oklahoma, Oklahoma City, OK.
466
branes of the mouth and pharynx. The presence of inflamed pharyngeal "glands" suggested to Volkman that the disorder of the lips was due to similar inflammation of labial glands. During the subsequent 40 years, additional patients were described with the designation CG, each with a swollen lower lip, prominent salivary duct orifices, and varying degrees of inflammation. 2-7 In one instance, only the upper lip was involved, z Sutton s was the first to suggest the existence of a "slight" form of CG,8 subsequently labeled " C G simplex" by Puente and A c e v e d o ) Their criteria consisted of a slightly enlarged, projecting lower lip with small red points that corresponded to salivary duct openings. Inflammation was minimal or absent.
Volume 10 Number 3 March, 1984
The existence of CG as a clinical entity was, thus, established, and additional patients were described. 10--20 Sutton s postulated, in 1914, that a "congenital a d e n o m a t o u s " enlargement of the labial salivary glands caused the lip enlargement of CG. Puente and A c e v e d o ~ also believed there was enlargement of labial salivary glands in CG. Others subsequentty offered a similar interpretation, 13"1~'~-2~ e m p l o y i n g the terms "hyperplasia" or "hyp e r t r o p h y " to describe the purportedly abnormal salivary tissue. Histologic comparisons with a control series of normal salivary glands were never made, however. B e t w e e n 1978 and 1983, five patients believed to fit within the clinical spectrum of CG were presented to the weekly teaching conference of the Department of Dermatology, University of Virginia Medical Center. A biopsy specimen of the lip was obtained as part of the diagnostic evaluation in each instance. The salivary glands present in the biopsy specimens did not appear to be grossly enlarged or abnormal, an observation similar to that of Woodburne and Philpott.12 We questioned whether salivary gland enlargement was responsible for the clinical appearance of patients with C G , whether the diagnosis of CG rested on a s o u n d histologic basis, and, indeed, whether CG represented a specific clinicopathologic entity. W e present our five patients with clinical CG, record the number and size of the salivary glands in their biopsy specimens, and compare these observations with data derived from a series of control specimens. We review and attempt to reclassify the nature of the cheilitis described in prior reports of CG. CASE REPORTS Case 1 A 62-year-old white man was referred to the University of Virginia Dermatology Clinic with a 1-year history of a swollen lower Lip. He was redheaded as a youth and had spent many years working outdoors. Examination revealed an everted lower lip with a whitish, hyperkeratotic surface. There were approximately one dozen small openings in the crust that exuded mucoid material when the lip was gently squeezed (Fig. I). The patient had severe actinic dam-
Cheilitis glandularis 467
Fig. 1. Case I. Enlarged, keratotic lower lip. With gentle pressure, beads of fluid appeared at prominent orifices of labial salivary glands. age of the skin of his face, neck, and arms. The biopsy specimen of the lip showed marked actinic damage, telangiectasia, hyperkeratosis, a small lichenoid actinic keratosis, and four normal-appearing salivary glands that ranged in maximal dimension from 0.7 to 4.0 mm (Fig. 2).
Case 2 A 34-year-old white woman was referred to the University of Virginia Dermatology Clinic with an 8month history of sweliing and cracking of the lower lip. She described a mucoid discharge from her lips and awoke in the mornings with them stuck together. At examination, the patient had a bulky lower lip with prominent, palpable salivary glands. She was treated with a wedge resection of the lower lip. Histologic examination showed hyperkeratosis, par',dceratosis, welldeveloped actinic elastosis, and twenty-seven normalappearing salivary glands that ranged from 0.4 to 3.1 mm in maximal dimension (Fig. 3). Case 3 A 14-year-old black girl was referred to the University of Virginia Dermatology Clinic with a 3-month history of swelling and crusting of the lower lip. She had crusting of both lips, much more marked on the lower, which was also everted and approximately twice normal size (Fig. 4). Mucopurulent material could be expressed through the crust when the lip was gently squeezed. The clinical impression was CG apostematosa. The biopsy specimen showed an inflammatory crust, parakeratosis, sparse lymphocytic infiltrate, and three normal-appearing salivary glands that ranged
468
Journal o f tile
Swerlick and Cooper
i
American Academy of Dermatology
!
: 4
,.;~7~
Fig. 2. Case 1. Biopsy specimen of lower lip. There are three salivary glands in this field. In photomicrographs, their outlines do not contrast markedly with adjacent connective tissue and skeletal muscle. The glands are 1.4, 2.3, and 4.0 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) in maximal dimension from 1.0 to 2.1 mm. The patient was noted to have a flattened 'affect, and subsequent questioning disclosed a history of multiple adjustment problems at home and at school. Case 4 An 18-year-old white young woman was referred to the University of Virginia Dermatology Clinic because of a 3-month history of an enlarged lower lip. She was annoyed with nodularity of the inner surface of her lower lip and complained that her lips were stuck together each morning upon awakening. Examination revealed a mildly enlarged lower lip that exuded beads of clear fluid when gently squeezed. The biopsy specimen showed parakeratosis and five normal-appearing salivary glands, 0.5 to 2,7 mm in maximal dimension. Case 5 A 16-year-old white girl came to the University of Virginia Dermatology Clinic with a l-year history of scaling and swelling of the lips, more marked on the upper lip. The patient also had a history of asthma, severe hay fever, and sinusitis. In addition to scaliness and enlargement, the upper lip had multiple small, cystlike structures that, when squeezed, produced beads of clear fluid. In spite of involvement of the upper lip, the clinical impression was CG. Biopsy of the upper lip showed marked acute inflammation. The
specimen was 0.2 mm in maximal thickness and contained no salivary gland tissue. MATERIALS AND M E T H O D S We reviewed a consecutive series of wedge excision specimens of the lower lip removed for squamous cell carcinoma in order to obtain ten specimens in which sections from at least one block contained one or more minor salivary glands. A series of mucoceles from the lower lip was similarly reviewed. We tabulated the following data: (1) the age and sex of each patient; (2) the number of salivary glands per section; (3) the maximal dimension of each gland, as measured with an ocular micrometer to the nearest 0.1 mm; and (4) the minimum depth of the most superficially located gland in each section, measured vertically from the surface of the mucosa to the superficial border of the gland. In addition, we noted the presence of acinar atrophy, duct ectasia, and inflammatory cell infiltrates in the glandular stroma. RESULTS Study o f fourteen wedge excisions was required in order to obtain ten examples that contained at least one section with salivary tissue (Fig. 5). T h e ten patients ranged in age from 55 to 71 years; all were men. A total o f twenty-six slides from the ten
Volume 10 Number 3 March, 1984
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~ _~.~:~
Fig. 3. Case 2. Biopsy specimen of lower lip.,The three salivary glands in this field are 1.2, 1.7, and 2.4 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) specimens contained salivary gland tissue. The number of glands per slide ranged from one to fourteen, and eighty-five glands were evaluated. The mean maximal dimension of the glands was 2.1 mm (range, 0.3 to 7.5; median, 1.7; SD, + 1.3). The depth of the most superficially located gland was measurable in twenty-one of the twenty-six slides and ranged from 0.5 to 3.0 mm (mean, 1.2; median, 0.9). Ten consecutive specimens of mucoceles contained one or more normal salivary glands. The patients ranged in age from 15 to 69 years. There was an equal number of male and female patients. The slides contained from one to twelve glands, and a total of fifty-four glands were evaluated. Their mean maximal dimension was 2.2 mm (range, 0.7 to 4.7; median, 1.9; SD, _ 1.2). The minimal depth was evaluable in nine of the ten specimens and ranged from 0.5 to 2.1 mm (mean, 1.2; median, 1.2). Minor degrees of lymphoplasmacytic infiltrate were seen in a minority of glands in both the wedge excision and mucocele specimens. There was prominent acinar atrophy in three of the wedge excision specimens, but it was our impression that the stroma was expanded to compensate for the loss of acinar tissue and that the overall dimension of the involved glands was not clearly reduced. Duct ectasia was not obvious in any specimen.
Fig. 4. Case 3. Swelling and marked crusting of both
lips, more marked on the lower lip. COMMENT The normal lip contains numerous salivary glands with ducts that open on the mucosal surface. If the everted lip is wiped dry, small drops of clear fluid develop at each of these ductal openings. 21 Labial salivary glands have been described as being about the size of small peas .22 After the significant shrinkage caused by processing, individual glands in our controls were as large as 7.5 mm, and our data also indicated a wide variation in size. It is not surprising, therefore, that clusters of these structures, as depicted by Sicher, 2a are easily palpated in normal individuals.
Journal of the 470
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American Academy of Dermatology
Fig. 5. A field from one of the control specimens (wedge excision of lower lip for squamous cell carcinoma). There are five closely arranged labial salivary glands in this field, separated by delicate fibrous bands. They measure 1.3, 2.0, 2.4, 2.8, and 3.1 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) There was no measurable difference between the size o f the labial salivary glands observed in our patients with clinical CG and the size of those seen in the control specimens. Woodburne and Philpott '2 expressed the same opinion in 1950, without the aid of control specimens. Moreover, the glands in our patients with clinical CG appeared histologically normal and had a grouped arrangement similar to that seen in the controls. Their minimal depth (range, 0.6 to 1.8 mm) was also similar to that observed in the control specimens. The sizes of purportedly enlarged salivary glands illustrated in prior reports of CG also appear to have been within the range of normal. Hyperplasia or hypertrophy of salivary tissue was not documented, and inflammatory cell infiltrates within the glands themselves were characteristically sparse and nonspecific or absent. One possible exception to the foregoing is the report of Weir and Johnson, ~8 who described three members of one family with the clinical presentation of CG who did have glands that appeared grossly enlarged. Histologically, there was considerable inflammatory infiltrate and edema within the substance of glandular tissue. These patients also had prominent duct ectasia and two had mucoceles.
Other examples of macrocheilia thought to be due to salivary gland enlargement are also poorly documented.2'l-28 Most appear to represent persistent lip swelling after an episode of trauma, 24''-'6 chronic lip biting, 25 lip enlargement associated with sarcoidal granulomas and facial palsies (Melkersson-Rosenthal syndrome), 26 or acute swelling of the lips and eyelids resulting in blepharochalasis and persistent lip swelling (Asher's syndrome). '-'~ Evidence of glandular enlargement in these reports is again based upon illustrations of salivary glands that appear to be no larger than those found in our controls. "6-'-'~ After reviewing descriptions of forty-eight patients with CG published since 1870, we believe that many can be classified into one of three basic categories. The largest group apparently developed CG on the basis of marked, chronic sun and wind exposure. 7,,,~,,t,t3,1,a,t6,t9,2o These individuals tended to be fair-skinned and had premature actinic damage of their skin as well as their lips. W e observed similar actinic damage in Patients 1 and 2. The development of squamous cell carcinoma of the lip is not unexpected in this subset of patients.'~ A second group of patients with CG also had
Volume 10 Number 3 March, 1984
histories that suggested a coexistent atopic diathesis.~.:~-.~.8.~:3 Patients with atopic dermatitis have been noted to have a predilection for developing cheilitis. 29 Authors of early reports of patients with CG commented on the presence of eczema,a,4 asthma, 1'~ or mouth breathing and inflammation of mucous membranes, 1'5'8 suggesting the presence of chronic hay fever and rhinorrhea as observed in Patient 5. Perhaps the constant drying of the lips produced by mouth breathing in atopic patients can act as an irritant capable of causing cheilitis with the clinical appearance of CG. In some patients, both atopy and chronic sun exposure seem to have contributed to the cheilitis. 8.t'~ A third group of patients with clinical CG actually have factitious cheilitis, ~~ as exemplified by Patient 3. Irritation of the lips in these individuals develops from excessive or inadequate wetting, lip biting, or other unusual manipulations. They have a history of emotional problems or a stressful environment and may suffer from personality disorders. a~ The use of a lip biopsy has been advocated to separate patients with factitious cheilitis frorn those with CG,'~~ but our study indicates that such a procedure is not helpful. In our view, CG represents an unusual clinical presentation of cheilitis that develops after chronic exposure to one or more irritants. Much of the enlargement of the lip can be attributed to edema, hyperemia, hyperkeratosis, and crusting that develop in response to chronic actinic exposure, repeated drying, factitious manipulations, or any other stimulus that can function as a chronic irritant. Even mild swelling of the lip causes eversion that tends to exaggerate the appearance of an enlarged lip. Secondary inflammation of the substance of the lip would enhance the swelling. Saliva exiting the salivary duct openings may protect against excessive irritation locally, thus minimizing the hyperkeratosis and crust in these areas. The resultant defects in the labial surface create the impression that the ductular orifices are dilated. The management of clinical CG depends upon the nature of the irritation. Obvious actinic changes should be treated with appropriate cryosurgery, vermilionectomy, chemosurgery, or topical chemotherapy? ~ The recognition of patients with underlying atopic disease or psychologic dis-
Cheilitis glandularis
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turbances depends on clinical history and observation. Individuals with scarring of the lips may require surgical debulking to restore a more norreal structure. Biopsy examination of the enlarged lip may rarely document an intrinsic sialadenitis, extrasalivary inflammation, or some other pathologic process. Its use, however, to demonstrate salivary gland hyperplasia in order to render a diagnosis of CG appears to be without basis. REFERENCES
1. Volkman R: Einige ffille yon cheiIitis glandularis apostematosa (myxadenitis labialis). Virchows Arch [Pathol Anat] 50:142-144, 1870. 2. Unna PG: [/ber Erkrankungen der schleimdriisen des mundes. Monatsschr Prakt Dermatol 11:317-321, 1890. 3. Purdon HS: Four cases of cheilitis glandularis. Br J Dermatol 5:23, 1893. 4. Fox H: Cheilitis glandularis. J Cutan Dis 27:229, 1909. 5. Sutton RL: Cheilitis glandularis apostematosa (with case report). J Cutan Dis 27:151-154. 1909. 6. Schamberg: Cheilitis glandularis. J Cutan Dis 29:449, 1911. 7. Wise: Cheilitis glandularis. J Cutan Dis 29:504-505, 1911. 8. Sutton RL: The symptomatology and treatment of three common diseases of the vermilion border of the lip. Int Clin (series 24) 3:123-128, 1914. 9. Puente JJ, Acevedo A: Queilitis glandularis. Rev Med Latinoam 12:671-679, 1927. i0. Wendlberger J: Cheilitis glandularis simplex (Acevedo) mit beginnender maligner degeneration. Osterr Dermatol Ges Ztbl Haul Gesehl 57:648, 1938a. 11. Van Dyck LS: Cheilitis glandularis. Arch Dermatol Syph 46:753, 1942. 12. Woodburne AR, Philpott OS: Cheilitis glandularis: A manifestation of emotional disturbance. Arch Dermatol Syph 62:820-828, 1950. 13. Everett FG, Holder TD: Cheilitis glandularis apostematosa. Oral Surg 8:405-413, 1955. 14. Wendlberger J: Cheilitis glandularis strnptex (famili~ires vorkommen). Wien Kiln Wochenschr 69:542-544; 1957. 15. Michalowski R: Cheilitis glandularis, heterotopic salivary glands and squamous cell carcinoma of the lip. Br J Dermatol 74:445-449, 1962. 16. Schweich L: Cheilitis glandularis simplex (Puente and Acevedo). Arch Dermatol 89:301-302, 1964. 17. Doku HC, Shklar G, McCarthy PL: Cheilitis glandularis. Oral Surg 20:563-571, 1965. 18. Weir TW, Johnson WC: Cheilitis glandularis. Arch Dermatol 103:433-437, 1971. 19. Oliver ID, Pickett AB: Cheilitis glandularis. Oral Surg 49:526-529, 1980. 20. Burwell RK: Cheilitis glandularis. J Assoc Milit De,'m 8:71-72, 1982. 21. Brand RW, lsselhard DE: Anatomy of orofaciat structures, ed. 2. St. Louis, 1982, The C. V. Mosby Co., p. 285. 22. Gray H: The digestive system, in Goss CM, editor:
472 Swerliek a~7d Cooper
23. 24.
25. 26.
27.
Gray's anatomy, ed. 26. Philadelphia, 1954, Lea & Febiger, p. 1246. Sicher H: Oral anatomy, ed. 3. St. Louis, 1960, The C. V. Mosby Co., p. 205. Lindenberger I: A case of macrochelia due to enlargement of the mucous glands of the lip. JAMA ,14:959, 1905. Hatton EH: Adenoma o f mucous glands of the mouth and macrochelia. J A M A 75:1176-1177, 1920. Conway H: Macrochelia due to hyperplasia of the labial salivary glands: Operative correction. Surg Gynecol Obstet 66:1024-1031, 1938. Findlay GH: Idiopathic enlargement of the lips: Cheilitis granulomatosis, Ascher's syndrome and double lip. Br J Dermatol 66:129-138, 1954.
Journal of the American Academy of Dermatology
28. McCarthy PL, Shklar G: Adenomatosis oris. Arch Dermatol Syph 70:293-297, 1954. 29. Rook A: The lips, in Rook A, Wilkinson DS, Ebling FJG, editors: Textbook of dermatology, ed. 3. Oxford, 1979, Blackwell Scientific Publications, vol. 2, p. 1905. 30. Savage J: Localized crusting as an artefact. Br J Dermatol 99:573-574, 1978. 31. Crotty CP, Dicken CH: Factitious lip crusting. Arch Dermatol 117:338-340, 1981. 32. Thomas JR III, Greene SL, Dicken CH: Factitious cheilitis. J AM ACAD DERMATOL 8:368-372, 1983. 33. Goette DK: Topical chemotherapy with 5-fluorouracil. J AM ACAD DERMATOL4:633-649, 1981.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the JOURNALOF THEAMERICANACADEMYOFDERbIATOLOGYare available to subscri'bers (only) for the 1984 issues from the Publisher at a cost of $53.50 ($65.00 international) for volume I0 (January-June) and volume i 1 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 30 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.
Reed et al
tions to toxins and venoms of common marine organisms. Cutis 23:450-454, 1979. 1 t. Black S, Humphrey JH, Niven JSF: Inhibition of Mantoux reaction by direct suggestion under hypnosis. Br Med J 1:1649-1652, 1963. 12. Dvorak HF, Mihm MC, Dvorak AM, et al: Morphology of delayed hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest 31:111-130, 1974.
III II
13. Allen AC: Persistent "insect bites" (dermal eosinophilic granulomas) simulating lymphoblastomas, histiocytoses, and squamous cell carcinomas. Am J Patho124"367-387, 1948. 14. Bemstein H, Shupack J, Ackerman AB: Cutaneous psuedolymphoma resulting from antigen injections. Arch Demaatol 110:756-757, 1974.
I
Cheilitis glandularis: A re-evaluation Robert A. Swerlick, M.D.,*'** and Philip H. Cooper, M.D.*.*** Charlottesville, VA Cheilitis glandularis (CG) has been attributed to hyperplasia of labia/salivary glands. We studied labial biopsy specimens of five patients with clinical CG and compared their salivary tissue with that seen in patients without CG. The labial glands from patients with CG did not differ in size, depth, or histologic appearance from those seen in the controls. They showed little or no inflammation and no hyperplasia. We also reviewed forty-eight cases of CG described in the literature. The accompanying photonficrographs nearly always depicted normal-appearing labial salivary glands. The case histories and clinical descriptions suggested that many examples of CG were manifestations of actinic cheilitis, whereas others may have been unusual presentations of atopic or factitious cheilitis. We believe CG represents an unusual reaction pattern in response to chronic irritation of the lips and is unrelated to labial salivary gland hyperplasia. (J AM ACAD DERMATOL10:466-472, 1984.)
Volkman, ~ in 1870, used the term cheilitis glandularis (CG) to describe a disorder affecting five patients who suffered from deep, suppurative inflammation involving the lower lip. He observed mucopurulent discharge from apparently dilated orifices of salivary ducts and, in addition, severe "catarrhal" inflammation of the mucous memFrom the Departments of Dermatology* and Pathology,*** University of Virginia. Accepted for publicationJuly 11, 1983. Reprint requests to: Dr. Philip H. Cooper, Departmentof Pathology, Box 214, University of Virginia Medical Center, Charlottesville, VA 22908/804-924-5127. **Presently a memberof the faculty of the Department of Dermatology, University of Oklahoma, Oklahoma City, OK.
466
branes of the mouth and pharynx. The presence of inflamed pharyngeal "glands" suggested to Volkman that the disorder of the lips was due to similar inflammation of labial glands. During the subsequent 40 years, additional patients were described with the designation CG, each with a swollen lower lip, prominent salivary duct orifices, and varying degrees of inflammation. 2-7 In one instance, only the upper lip was involved, z Sutton s was the first to suggest the existence of a "slight" form of CG,8 subsequently labeled " C G simplex" by Puente and A c e v e d o ) Their criteria consisted of a slightly enlarged, projecting lower lip with small red points that corresponded to salivary duct openings. Inflammation was minimal or absent.
Volume 10 Number 3 March, 1984
The existence of CG as a clinical entity was, thus, established, and additional patients were described. 10--20 Sutton s postulated, in 1914, that a "congenital a d e n o m a t o u s " enlargement of the labial salivary glands caused the lip enlargement of CG. Puente and A c e v e d o ~ also believed there was enlargement of labial salivary glands in CG. Others subsequentty offered a similar interpretation, 13"1~'~-2~ e m p l o y i n g the terms "hyperplasia" or "hyp e r t r o p h y " to describe the purportedly abnormal salivary tissue. Histologic comparisons with a control series of normal salivary glands were never made, however. B e t w e e n 1978 and 1983, five patients believed to fit within the clinical spectrum of CG were presented to the weekly teaching conference of the Department of Dermatology, University of Virginia Medical Center. A biopsy specimen of the lip was obtained as part of the diagnostic evaluation in each instance. The salivary glands present in the biopsy specimens did not appear to be grossly enlarged or abnormal, an observation similar to that of Woodburne and Philpott.12 We questioned whether salivary gland enlargement was responsible for the clinical appearance of patients with C G , whether the diagnosis of CG rested on a s o u n d histologic basis, and, indeed, whether CG represented a specific clinicopathologic entity. W e present our five patients with clinical CG, record the number and size of the salivary glands in their biopsy specimens, and compare these observations with data derived from a series of control specimens. We review and attempt to reclassify the nature of the cheilitis described in prior reports of CG. CASE REPORTS Case 1 A 62-year-old white man was referred to the University of Virginia Dermatology Clinic with a 1-year history of a swollen lower Lip. He was redheaded as a youth and had spent many years working outdoors. Examination revealed an everted lower lip with a whitish, hyperkeratotic surface. There were approximately one dozen small openings in the crust that exuded mucoid material when the lip was gently squeezed (Fig. I). The patient had severe actinic dam-
Cheilitis glandularis 467
Fig. 1. Case I. Enlarged, keratotic lower lip. With gentle pressure, beads of fluid appeared at prominent orifices of labial salivary glands. age of the skin of his face, neck, and arms. The biopsy specimen of the lip showed marked actinic damage, telangiectasia, hyperkeratosis, a small lichenoid actinic keratosis, and four normal-appearing salivary glands that ranged in maximal dimension from 0.7 to 4.0 mm (Fig. 2).
Case 2 A 34-year-old white woman was referred to the University of Virginia Dermatology Clinic with an 8month history of sweliing and cracking of the lower lip. She described a mucoid discharge from her lips and awoke in the mornings with them stuck together. At examination, the patient had a bulky lower lip with prominent, palpable salivary glands. She was treated with a wedge resection of the lower lip. Histologic examination showed hyperkeratosis, par',dceratosis, welldeveloped actinic elastosis, and twenty-seven normalappearing salivary glands that ranged from 0.4 to 3.1 mm in maximal dimension (Fig. 3). Case 3 A 14-year-old black girl was referred to the University of Virginia Dermatology Clinic with a 3-month history of swelling and crusting of the lower lip. She had crusting of both lips, much more marked on the lower, which was also everted and approximately twice normal size (Fig. 4). Mucopurulent material could be expressed through the crust when the lip was gently squeezed. The clinical impression was CG apostematosa. The biopsy specimen showed an inflammatory crust, parakeratosis, sparse lymphocytic infiltrate, and three normal-appearing salivary glands that ranged
468
Journal o f tile
Swerlick and Cooper
i
American Academy of Dermatology
!
: 4
,.;~7~
Fig. 2. Case 1. Biopsy specimen of lower lip. There are three salivary glands in this field. In photomicrographs, their outlines do not contrast markedly with adjacent connective tissue and skeletal muscle. The glands are 1.4, 2.3, and 4.0 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) in maximal dimension from 1.0 to 2.1 mm. The patient was noted to have a flattened 'affect, and subsequent questioning disclosed a history of multiple adjustment problems at home and at school. Case 4 An 18-year-old white young woman was referred to the University of Virginia Dermatology Clinic because of a 3-month history of an enlarged lower lip. She was annoyed with nodularity of the inner surface of her lower lip and complained that her lips were stuck together each morning upon awakening. Examination revealed a mildly enlarged lower lip that exuded beads of clear fluid when gently squeezed. The biopsy specimen showed parakeratosis and five normal-appearing salivary glands, 0.5 to 2,7 mm in maximal dimension. Case 5 A 16-year-old white girl came to the University of Virginia Dermatology Clinic with a l-year history of scaling and swelling of the lips, more marked on the upper lip. The patient also had a history of asthma, severe hay fever, and sinusitis. In addition to scaliness and enlargement, the upper lip had multiple small, cystlike structures that, when squeezed, produced beads of clear fluid. In spite of involvement of the upper lip, the clinical impression was CG. Biopsy of the upper lip showed marked acute inflammation. The
specimen was 0.2 mm in maximal thickness and contained no salivary gland tissue. MATERIALS AND M E T H O D S We reviewed a consecutive series of wedge excision specimens of the lower lip removed for squamous cell carcinoma in order to obtain ten specimens in which sections from at least one block contained one or more minor salivary glands. A series of mucoceles from the lower lip was similarly reviewed. We tabulated the following data: (1) the age and sex of each patient; (2) the number of salivary glands per section; (3) the maximal dimension of each gland, as measured with an ocular micrometer to the nearest 0.1 mm; and (4) the minimum depth of the most superficially located gland in each section, measured vertically from the surface of the mucosa to the superficial border of the gland. In addition, we noted the presence of acinar atrophy, duct ectasia, and inflammatory cell infiltrates in the glandular stroma. RESULTS Study o f fourteen wedge excisions was required in order to obtain ten examples that contained at least one section with salivary tissue (Fig. 5). T h e ten patients ranged in age from 55 to 71 years; all were men. A total o f twenty-six slides from the ten
Volume 10 Number 3 March, 1984
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~ _~.~:~
Fig. 3. Case 2. Biopsy specimen of lower lip.,The three salivary glands in this field are 1.2, 1.7, and 2.4 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) specimens contained salivary gland tissue. The number of glands per slide ranged from one to fourteen, and eighty-five glands were evaluated. The mean maximal dimension of the glands was 2.1 mm (range, 0.3 to 7.5; median, 1.7; SD, + 1.3). The depth of the most superficially located gland was measurable in twenty-one of the twenty-six slides and ranged from 0.5 to 3.0 mm (mean, 1.2; median, 0.9). Ten consecutive specimens of mucoceles contained one or more normal salivary glands. The patients ranged in age from 15 to 69 years. There was an equal number of male and female patients. The slides contained from one to twelve glands, and a total of fifty-four glands were evaluated. Their mean maximal dimension was 2.2 mm (range, 0.7 to 4.7; median, 1.9; SD, _ 1.2). The minimal depth was evaluable in nine of the ten specimens and ranged from 0.5 to 2.1 mm (mean, 1.2; median, 1.2). Minor degrees of lymphoplasmacytic infiltrate were seen in a minority of glands in both the wedge excision and mucocele specimens. There was prominent acinar atrophy in three of the wedge excision specimens, but it was our impression that the stroma was expanded to compensate for the loss of acinar tissue and that the overall dimension of the involved glands was not clearly reduced. Duct ectasia was not obvious in any specimen.
Fig. 4. Case 3. Swelling and marked crusting of both
lips, more marked on the lower lip. COMMENT The normal lip contains numerous salivary glands with ducts that open on the mucosal surface. If the everted lip is wiped dry, small drops of clear fluid develop at each of these ductal openings. 21 Labial salivary glands have been described as being about the size of small peas .22 After the significant shrinkage caused by processing, individual glands in our controls were as large as 7.5 mm, and our data also indicated a wide variation in size. It is not surprising, therefore, that clusters of these structures, as depicted by Sicher, 2a are easily palpated in normal individuals.
Journal of the 470
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Fig. 5. A field from one of the control specimens (wedge excision of lower lip for squamous cell carcinoma). There are five closely arranged labial salivary glands in this field, separated by delicate fibrous bands. They measure 1.3, 2.0, 2.4, 2.8, and 3.1 mm in maximal dimension. (Hematoxylin-eosin stain; x 16.) There was no measurable difference between the size o f the labial salivary glands observed in our patients with clinical CG and the size of those seen in the control specimens. Woodburne and Philpott '2 expressed the same opinion in 1950, without the aid of control specimens. Moreover, the glands in our patients with clinical CG appeared histologically normal and had a grouped arrangement similar to that seen in the controls. Their minimal depth (range, 0.6 to 1.8 mm) was also similar to that observed in the control specimens. The sizes of purportedly enlarged salivary glands illustrated in prior reports of CG also appear to have been within the range of normal. Hyperplasia or hypertrophy of salivary tissue was not documented, and inflammatory cell infiltrates within the glands themselves were characteristically sparse and nonspecific or absent. One possible exception to the foregoing is the report of Weir and Johnson, ~8 who described three members of one family with the clinical presentation of CG who did have glands that appeared grossly enlarged. Histologically, there was considerable inflammatory infiltrate and edema within the substance of glandular tissue. These patients also had prominent duct ectasia and two had mucoceles.
Other examples of macrocheilia thought to be due to salivary gland enlargement are also poorly documented.2'l-28 Most appear to represent persistent lip swelling after an episode of trauma, 24''-'6 chronic lip biting, 25 lip enlargement associated with sarcoidal granulomas and facial palsies (Melkersson-Rosenthal syndrome), 26 or acute swelling of the lips and eyelids resulting in blepharochalasis and persistent lip swelling (Asher's syndrome). '-'~ Evidence of glandular enlargement in these reports is again based upon illustrations of salivary glands that appear to be no larger than those found in our controls. "6-'-'~ After reviewing descriptions of forty-eight patients with CG published since 1870, we believe that many can be classified into one of three basic categories. The largest group apparently developed CG on the basis of marked, chronic sun and wind exposure. 7,,,~,,t,t3,1,a,t6,t9,2o These individuals tended to be fair-skinned and had premature actinic damage of their skin as well as their lips. W e observed similar actinic damage in Patients 1 and 2. The development of squamous cell carcinoma of the lip is not unexpected in this subset of patients.'~ A second group of patients with CG also had
Volume 10 Number 3 March, 1984
histories that suggested a coexistent atopic diathesis.~.:~-.~.8.~:3 Patients with atopic dermatitis have been noted to have a predilection for developing cheilitis. 29 Authors of early reports of patients with CG commented on the presence of eczema,a,4 asthma, 1'~ or mouth breathing and inflammation of mucous membranes, 1'5'8 suggesting the presence of chronic hay fever and rhinorrhea as observed in Patient 5. Perhaps the constant drying of the lips produced by mouth breathing in atopic patients can act as an irritant capable of causing cheilitis with the clinical appearance of CG. In some patients, both atopy and chronic sun exposure seem to have contributed to the cheilitis. 8.t'~ A third group of patients with clinical CG actually have factitious cheilitis, ~~ as exemplified by Patient 3. Irritation of the lips in these individuals develops from excessive or inadequate wetting, lip biting, or other unusual manipulations. They have a history of emotional problems or a stressful environment and may suffer from personality disorders. a~ The use of a lip biopsy has been advocated to separate patients with factitious cheilitis frorn those with CG,'~~ but our study indicates that such a procedure is not helpful. In our view, CG represents an unusual clinical presentation of cheilitis that develops after chronic exposure to one or more irritants. Much of the enlargement of the lip can be attributed to edema, hyperemia, hyperkeratosis, and crusting that develop in response to chronic actinic exposure, repeated drying, factitious manipulations, or any other stimulus that can function as a chronic irritant. Even mild swelling of the lip causes eversion that tends to exaggerate the appearance of an enlarged lip. Secondary inflammation of the substance of the lip would enhance the swelling. Saliva exiting the salivary duct openings may protect against excessive irritation locally, thus minimizing the hyperkeratosis and crust in these areas. The resultant defects in the labial surface create the impression that the ductular orifices are dilated. The management of clinical CG depends upon the nature of the irritation. Obvious actinic changes should be treated with appropriate cryosurgery, vermilionectomy, chemosurgery, or topical chemotherapy? ~ The recognition of patients with underlying atopic disease or psychologic dis-
Cheilitis glandularis
471
turbances depends on clinical history and observation. Individuals with scarring of the lips may require surgical debulking to restore a more norreal structure. Biopsy examination of the enlarged lip may rarely document an intrinsic sialadenitis, extrasalivary inflammation, or some other pathologic process. Its use, however, to demonstrate salivary gland hyperplasia in order to render a diagnosis of CG appears to be without basis. REFERENCES
1. Volkman R: Einige ffille yon cheiIitis glandularis apostematosa (myxadenitis labialis). Virchows Arch [Pathol Anat] 50:142-144, 1870. 2. Unna PG: [/ber Erkrankungen der schleimdriisen des mundes. Monatsschr Prakt Dermatol 11:317-321, 1890. 3. Purdon HS: Four cases of cheilitis glandularis. Br J Dermatol 5:23, 1893. 4. Fox H: Cheilitis glandularis. J Cutan Dis 27:229, 1909. 5. Sutton RL: Cheilitis glandularis apostematosa (with case report). J Cutan Dis 27:151-154. 1909. 6. Schamberg: Cheilitis glandularis. J Cutan Dis 29:449, 1911. 7. Wise: Cheilitis glandularis. J Cutan Dis 29:504-505, 1911. 8. Sutton RL: The symptomatology and treatment of three common diseases of the vermilion border of the lip. Int Clin (series 24) 3:123-128, 1914. 9. Puente JJ, Acevedo A: Queilitis glandularis. Rev Med Latinoam 12:671-679, 1927. i0. Wendlberger J: Cheilitis glandularis simplex (Acevedo) mit beginnender maligner degeneration. Osterr Dermatol Ges Ztbl Haul Gesehl 57:648, 1938a. 11. Van Dyck LS: Cheilitis glandularis. Arch Dermatol Syph 46:753, 1942. 12. Woodburne AR, Philpott OS: Cheilitis glandularis: A manifestation of emotional disturbance. Arch Dermatol Syph 62:820-828, 1950. 13. Everett FG, Holder TD: Cheilitis glandularis apostematosa. Oral Surg 8:405-413, 1955. 14. Wendlberger J: Cheilitis glandularis strnptex (famili~ires vorkommen). Wien Kiln Wochenschr 69:542-544; 1957. 15. Michalowski R: Cheilitis glandularis, heterotopic salivary glands and squamous cell carcinoma of the lip. Br J Dermatol 74:445-449, 1962. 16. Schweich L: Cheilitis glandularis simplex (Puente and Acevedo). Arch Dermatol 89:301-302, 1964. 17. Doku HC, Shklar G, McCarthy PL: Cheilitis glandularis. Oral Surg 20:563-571, 1965. 18. Weir TW, Johnson WC: Cheilitis glandularis. Arch Dermatol 103:433-437, 1971. 19. Oliver ID, Pickett AB: Cheilitis glandularis. Oral Surg 49:526-529, 1980. 20. Burwell RK: Cheilitis glandularis. J Assoc Milit De,'m 8:71-72, 1982. 21. Brand RW, lsselhard DE: Anatomy of orofaciat structures, ed. 2. St. Louis, 1982, The C. V. Mosby Co., p. 285. 22. Gray H: The digestive system, in Goss CM, editor:
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23. 24.
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Gray's anatomy, ed. 26. Philadelphia, 1954, Lea & Febiger, p. 1246. Sicher H: Oral anatomy, ed. 3. St. Louis, 1960, The C. V. Mosby Co., p. 205. Lindenberger I: A case of macrochelia due to enlargement of the mucous glands of the lip. JAMA ,14:959, 1905. Hatton EH: Adenoma o f mucous glands of the mouth and macrochelia. J A M A 75:1176-1177, 1920. Conway H: Macrochelia due to hyperplasia of the labial salivary glands: Operative correction. Surg Gynecol Obstet 66:1024-1031, 1938. Findlay GH: Idiopathic enlargement of the lips: Cheilitis granulomatosis, Ascher's syndrome and double lip. Br J Dermatol 66:129-138, 1954.
Journal of the American Academy of Dermatology
28. McCarthy PL, Shklar G: Adenomatosis oris. Arch Dermatol Syph 70:293-297, 1954. 29. Rook A: The lips, in Rook A, Wilkinson DS, Ebling FJG, editors: Textbook of dermatology, ed. 3. Oxford, 1979, Blackwell Scientific Publications, vol. 2, p. 1905. 30. Savage J: Localized crusting as an artefact. Br J Dermatol 99:573-574, 1978. 31. Crotty CP, Dicken CH: Factitious lip crusting. Arch Dermatol 117:338-340, 1981. 32. Thomas JR III, Greene SL, Dicken CH: Factitious cheilitis. J AM ACAD DERMATOL 8:368-372, 1983. 33. Goette DK: Topical chemotherapy with 5-fluorouracil. J AM ACAD DERMATOL4:633-649, 1981.
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