oral medicine Editor: JAMES W. LITTLE, D.M.D., M.S.D. Chairman and Professor Department of Oral Diagnosis and Oral Medicine University of Kentucky Lexington, Kentucky 40506

Cheilitis granulomatosa (Melkersson- Rosenthal syndrome)

J. J. Zecha, D.M.D.,” L. vma Dijk, D.M.D.,” nncl H. N. Hadders, M.D.,‘” GroGzgen, The Netherlands

STATE TJNIVERSITY OF GRONINGEN

An oligosymptomatic manifestation of the Melkersson-Rosenthal syndrome is de- scribed. The importance of serial sections of the tissue specimen is emphasized. Satis- factory postoperative results mere obtained.

A spontaneously occurring, recurrent, and finally permanent swelling of one or both lips, without an evident cause, is the characteristic feature of a disease with which the name Niescher is connected. In 1945 Miescher’ published his article entitled : “iiber essentielle granulomatijse Macrocheilie (Cheilitis Granu- lomatosa) .” Initially Miescher’s cheilitis granulomatosa was considered as a separate entity. Today, because of a great similarity in clinical and microscopic features, most authors consider the disease as part of the Melkersson-Rosenthal syndrome.2, :I The characteristic signs of this syndrome are : facial swelling, facial nerve paresis, and plicated or fissured tongue. The facial swelling is usually con- fined to one lip and/or one cheek but may also affect the forehead, eyelids, nose, or chin. Intraoral manifestations may occur as swellings of the tongue, buccal mucosa, gingiva, and palatal mucosa. The swelling may vary from soft to firm- elastic and usually has a normal aspect. Sometimes it may be erythematous; acute inflammatory signs are absent. In some instances the labial swelling is as- sociated with herpetiform eruptions.

A recurrent, mostly unilateral paralysis of the facial nerve preceding or fol-

*Oral Surgeon, Department of Oral Surgery. **Professor of Pathology, Department of Oral Pathology.

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Cheilitis granulonzatosa 455

Fig. 1. A 24-year-old woman with a pronounced swelling of the lower lip.

lowing the development of the facial swelling has been reported in 20 to 30 per cent of the cases.” Secretory disturbances of salivary, lacrimal, and nasal glands may occur. Some patients complain of impaired taste and hearing. Other cranial nerves, such as the trigeminal nerve (trigeminal neuralgia), may also be involved in the disease. A migraine type of headache has been reported as well. Meanwhile, it has been shown that an impressive number of other abnormalities also belong to the syndrome. These abnormalities are particularly of a neurologic nature, al- though ophthalmologic, otorhinolaryngologic, and visceral disorders may occur simultaneously.* Patients with this syndrome are usually between the second and fourth decades of life. Males and females are equally affected. The etiology is unknown; an allergic base or a disturbance of the regulation of vasomotor nerves has been suggested.

It appears from the literature that the Melkersson-Rosenthal syndrome is probably not as rare as is often believed. However, it is striking that the syn- drome is frequently not recognized as such. The fact is that the characteristic signs of the disease are often seen in incomplete form and the typical microscopic picture (formations of epithelioid cells with multinucleated giant cells of the Langhans type) is not always present.

In the following case report these problems are demonstrated and discussed.

CASE REPORT

A healthy 24-year-old woman was referred to the Department of Oral Surgery because of a rather suddenly occurring swelling of the lower lip of varying size (Fig. 1). The swelling began about 7 weeks prior to presentation and was accompanied by a slight tingling to burn- ing sensation. The lip mucosa tended to fissure and to crust slightly. The cosmetic aspect of the enlarged lip was particularly distressing to her. She had no other complaints, and the medical history was noncontributory.

Extraoral and intraoral examination

The lower lip, particularly on the left and on the oral aspect, was enlarged. There were several marked fissures. The swelling of the lip was not tender on palpation. It was diffuse- soft to firm-elastic in consistency. The color was normal. There were no palpable lymph nodes.

The mucosa of cheeks and palate showed no abnormalities. The labial gingiva of the lower

456 Zecha, van Dijk, and Hadders Oral Surg. October, 1976

Fig. B. The tongue shows a deepened median fissure and a geographic tongue.

front teeth was retracted and hyperemic, probably as a result of the traction of the enlarged lower lip. The tongue showed a deepened median fissure and on the dorsum there were atrophic areas surrounded by a slightly raised, white margin consistent with a geographic tongue (Fig. 2). The dentition was in good condition. Radiographic examination of the teeth and jaws re- vealed no significant findings. The clinical diagnosis was “edematous swelling of the lower lip.”

Course and management

At re-examination 1 week later the swelling of the lower lip and the fissure in the tongue were unchanged. However, the aspect of a geographic t,ongue had disappeared.

A biopsy of the lower lip was taken. The microscopic diagnosis was “chronic nonspecific inflammation of the lip.”

Initially treatment consisted of administration of antibiotics. Because no ef%‘ect was ob- served, antihistaminic therapy was instituted to exclude any allergic causes. The antihistaminic therapy had no effect on the ever-changing swelling of the lower lip. It was decided to end medical treatment and to await further developments. The clinical conduct and the lack of therapeutic results suggested a case of cheilitis granulomatosa as described by Miescher. After 3 months the patient still had the same complaints. For cosmetic reasons surgical correction of the lower lip was decided upon. Preoperatively the elliptical lines of excision were ac- curately marked with Bonney’s blue. Under local anesthesia a wedge-shaped excision reaching to the orbicularis oris muscle was carried out, followed hy primary wound closure. Healing was uneventful.

Pathologic findings

The excision of the lower lip measured 44 by 9 by 8 mm. Perpendicular to the long axis, seven tissue blocks were prepared. The microscopic features in all sections of the seven tissue

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Fig. 5. The characteristic granulomatous formations in cheilitis granulomatosa are clearly seen. (Magnification, x50.)

blocks were identical. In and beneath the epithelium there mere scattered formations of mononuclear inflammatory cells. The connective tissue under the epithelium was edematous. This edema was less pronounced in the deeper layers. Near the basis some muscle tissue was found. Between this and the epithelium several formations of cell infiltrates were seen, partially in a perivascular arrangement. These cell infiltrates consisted mostly of lymphocytes, but plasma cells and various numbers of histiocytes and epithelioid cells were also encountered. It was striking that most cell infiltrates contained multinucleated giant cells of the Langhans type. These giant cells were partially surrounded by epithelioid cells. This picture is consistent with the diagnosis of cheilitis granulomatosa (Figs. 3 and 4).

On the basis of these findings, it was decided to revise the biopsy specimen. Serial sections were prepared. To our surprise, some of these sections also revealed the above-described microscopic features.

Neurologic examination

No abnormalities were found. , particularly, the function of the facial nerve was undis- turbed.

laboratory examination

Blood and urine values mere within normal limits.

Follow-up

Two years after the operation the cosmetic result of the lip correction was satisfactory (Fig. 5). The gingiva, which formerly was retracted and hyperemic, recovered spontaneously. No recurrence of the swelling was noted.

458 Zecha, va?b Dijk, and Haddem Oral Surg. October, 1976

Fig. 4. A detail of Fig. 3 shams many lymphocytes, plasma cells, histioeytes, epithelioid cells, and multinucleated giant cells of the Langhans type. (Magnification, x200.)

DISCUSSION

The characteristic features of the Melkersson-Rosenthal syndrome are hardly ever seen in complete form.” This is why initially the possibility of cheilitis gran- ulomatosa (Melkersson-Rosenthal syndrome) was not considered in our patient. It has been shown that a sudden swelling of a lip without any evident cause, to- gether with a fissured tongue, strongly indicates an oligosymptomatic manifesta- tion of the svndrome.‘, 4, R In our patient the tongue shows only a deepened median fissure as described by Gorlin and Pindborg” ; multiple fissures are absent. Rauch” has reported geographic tongues in two of his twenty cases of Melkersson- Rosenthal syndrome. In view of the frequent solitary occurrences of a geographic tongue, there is no evidence that this lesion is seen more often in the Melkersson- Rosenthal syndrome than in the general population. At the same time, the geo- graphic tongue often appears to be associated with cases of fissured tongue.

Microscopically, there is edema and a diffuse chronic inflammatory cell in- filtrate under the epithelium. More deeply, epithelioid cells and multinucleated giant cells, partially of the Langhans type, are observed. This finding strongly suggests cheilitis granulomatosa, but also sarcoidosis ( Besnier-Boeck-Schaumann’s disease) .2 Therefore, the clinical information is indispensable to the pathologist for diagnosing the case correctly. The granulomatous changes, however, are not always prcsenf.l, i, R In such instances only a chronic nonspecific inflamma-

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Cheilitis yrawulon~atosa 459

Fig. 5. The lower lip 2 years after surgical correction.

tory infiltrate is seen. This was the case in some sections of the biopsy specimen of the described patient. A biopsy taken at another moment or at a different place may reveal the typical granulomatous changes. Therefore, serial sections of the biopsy specimen are necessary and sometimes a repeated deep biopsy is required.

There is no sufficient evidence to consider the Melkersson-Rosenthal SW-

drome as part of Besnier-Boeck-Schaumann’s disease (sarcoidosis) because the characteristic sarcoidal changes in the lungs and bone have never been observed in the Nclkersson-Rosenthal syndrome.*

A labial swelling may have many causes, for instance, an acute alveolar abscess, a trauma, or an insect bite. When no obvious cause can be traced, one has to consider the following possibilities : Quincke’s edema (angioneurotir c&ma), erysipelas, Asher’s syndrome, and cheilitis granulomatosa.

Quincke’s edema is characterized by a transient and shifting clinical course. The swollen area has the aspect of a real edema and is usually pale. The condition responds well to the administration of ant,ihistamines. In the Rlelkersson-Rosen- thal syndrome the swelling is not shifting, it does not disappear completely, and antihistaminic therapy has no favorable effect.

Erysipclas, a strcptococcal infection of the skin, is always accompanied by ordinary inflammatory symptoms and surrounded by an elevated wall, contrary to the Melkersson-Rosenthal syndrome.

Ashcr’s syndrome is characterized by swellin g of the eyelids resulting in hlc~~ha.rochalasis, swelling of thr lips (the upper lip is often doubled), ant1 non- toxic goiter.

The lack of a well-defined etiology has contributed to varied treatments of cheilitis granulomatosa. Antibiotic, antiphlogistic, and antihistaminic therapy as well as radiotherapy have been applied with little or no s~~ccess.~~ !I Corticostc-

raids have proved effective in some instances2 The best results, however, are obtained by broad wedge-shaped excisions of the oral side of the affected lip.!‘-‘I It is essential that the underlying gland tissue be completely removed. Primary wound closure is carried out without undermining the wound edges. In this way inward rotation of the protuberant lip is achieved, producing a good cosmetic result.

460 Zecha, vnn Dijk, and Hadders Oral Surg. October, 1976

SUMMARY

A case is reported of a 24year-old woman with an oligosymptomatic mani- festation of the Melkersson-Rosenthal syndrome (cheilitis granulomatosa and a deepened median fissure of the tongue).

The histopathologic picture-inflammatory infiltrates with epithelioid cells and giant cells of the Langhans type-is not always characteristic of the disease. A biopsy taken at another moment or at a different place may reveal the typical granulomatous changes. The importance of serial sections of the tissue specimen is pointed out.

A satisfactory result after surgery is obtained; 2 years postoperatively the proportions of the lip are still normal.

REFERENCES

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Miescher, G. : iiber essentielle granulomatiise Macrochvilie (Cheilitis granulomatosa), Dermatologica (Basel) 91: 57-85, 1945. Hornstein, 0. : Klinische und histologische Untersuchungen iiber “Cheilitis granulomatosa” (Mieschrr) bzw. Melkersson-Rosenthal-Svndrom. Hautarzt 6: 433-447. 1955. Raueh, S:: New Gesichtspunkte zum Melkersson-Rosenthal-Synclrom, Schweiz. Med. Wochenschr. 98: 1743-1750, 1968. gtava, Z.: Das Melkersson-Rosenthal-Syndrom, in Hornstein, O., editor: Entziindliche und systemische Erkankungen der Mundschleimhaut, Stuttgart, 1974, Georg Thieme Verlag, pp. 99.108. Gorlin, R. J., and Pindborg, J. J.: Syndromes of the Head and Neck. New York, 1964, McGrawHill Book Company, Inc., pp. 358-365. Hornstein, 0. : Probleme der Cheilitis granulomatosa (Miescher) in gutachtlicher Sicht, Hautarzt 13: 302-309, 1962. Hamminga, II., and Doormaal, T. A. J. van: Het syndroom van Melkersson-Rosenthal, Ned. Tijdschr. Geneeskd. 97: 27-29, 1953. Woerdeman, M. J. : Het syndroom van Melkersson-Rosenthal, Ned. Tijdschr. Geneeskd. 99: 3335.3342, 1955. Miescher, G. , and Storck, I-I.: 5 Falle van Cheilitis granulomatosa, Drrmatologica (Basel) 102: 351-356, 1951. Findlay, G. H.: Idiopathic Enlargements of the Lips: Cheilitis Granulomatosa, Asher’s Syndrome and Double Lip, Hr. J. Dermatol. 66: 129-138, 1954. Klasen, H. J.: Tc dikko en dubbcle lippen. Ned. Tijdschr. Geneeskd. 115: 408-413, 1971.

Rep&t requests to: 5. 5. Zecha

Kliniek voor Mondheelkunde, Academisch Ziekenhuis Oostersingel 59 Groningen, The Netherlands