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Mucocutaneous pigmented spots and oral myxomas: The oral manifestations of the complex of myxomas, spotty pigmentation, and endocrine overactivity
oral medicine Editor: JAMES
W. LITTLE,
D.M.D.,
M.S.D.
School of Dentistry University of Minnesota 515 S.E. Delaware St. Minneapolis, Minn. 55455
Mucocutaneous pigmented spots and oral myxomas: The oral manifestations of the complex of myxomas, spotty pigmentation, and endocrine overactivity Cli’ord A. Cook, D.D.S., Bruce A. Lund. D.D.S., M.S., and J. Aidan Carney, M.D., Ph.D., F.R.C.P.I.. Rochester, Minn. THE SECTION OF ORAL AND MAXILLOFACIAL CLl’JlC AND MAYO FOUNDATION
SURGERY
AND
THE DEPARTMENT
OF PATHOLOGY,
MAYO
The complex of myxomas, spotty pigmentation, and endocrine overactivity is a recently recognized syndrome, transmitted as an autosomal dominant trait. The most serious component of the disorder is cardiac myxoma, which has caused the death of one fourth of the affected patients and serious disability in an equal number. It is, therefore, important to recognize patients at risk from the syndrome and, in particular, to test them for cardiac myxoma. Fortunately, in many patients the myxoma complex has a clearly visible marker: mucocutaneous pigmentation. Among 58 patients with the syndrome, spotty facial pigmentation was present in 38 (62%), and 29 (50%) of these also had pigmented spots on their lips, This type and distribution of pigmentation should be a clue to the possible presence of the complex of myxomas, spotty pigmentation, and endocrine overactivity, and patients thus affected should be referred for further investigation. Oral cavity myxoma(s) occurred in four patients with the syndrome. (ORAL SURC. ORAL MED. ORAL PATHOL. 1987;63:175-83)
M
anifestations of disorders of the oral cavity may be limited to the mouth. However, through blood, lymphatic, nerve, and other tissue pathways, the oral tissues maintain an intimate relationship with the remainder of the body and not infrequently are involved secondarily in various nonoral conditions. Importantly, oral findings may be the harbingers of a variety of serious systemic disorders. The characteristic mucocutaneous pigmentation of the PeutzJeghers syndrome is an example of this,’ and thickened lips and lumps on the anterior one third of the tongue (ganglioneuromatosis), a clue to the presence of medullary thyroid carcinoma or pheochromocyto-
ma or both (multiple endocrine neoplasia, type 2b),2 is another. In this article, we draw attention to a newly recognized group of oral findings that may signal a systemic disorder that includes a potentially lethal neoplasm: cardiac myxoma. The findings are components of a complicated condition involving visceral and soft tissue myxomas, spotty pigmentation of the skin, and endocrine overactivity.3 Recognition of the disorder was basedon findings in 40 patients, each of whom had two or more of the following conditions: ( 1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoid fibroadenoma, (4) spotty muco175
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Table
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I. Selected findings in three patients with oral myxoma(s) Reported by
Case
Location of lesion
I
Rees et al.*
Junction, right hard and soft palate
2
Atherton et al?
3
Tway et al.‘O
Hard palate and tongue Right hard palate
Right hard and soft palate (? recurrence)
Clinical
Pedunculated lesion with small area of ulceration
Smooth, bulky, nontender, submucosal mass
Spongy mass, 3.5 X 2 cm, commencing almost at free edge of soft palate and advancing to midportion of hard palate
cutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease,(6) testicular tumors, and (7) pituitary adenoma secreting growth hormone. The syndrome is inherited as an autosomal dominant trait.4, 5 The most serious component of the myxoma complex is cardiac myxoma, which has caused the death of one fourth of the patients and serious morbidity in an equal number.3 Therefore, it is important to recognize patients at risk from the complex of myxomas, spotty pigmentation, and endocrine overactivity in order to examine them for components of the syndrome, in particular to test them (and their primary relatives) for cardiac myxoma. In this article, we present details of the oral findings that may be clues to this serious heritable syndrome. MATERIALS
description
AND METHODS
The study group included 58 patients (25 male and 33 female): 40 patients previously described by Carney and coworkers,3 1 patient mentioned in the literature: 5 other patients described by Carney and associates,411 patients identified by McCarthy and associates,’ and 1 patient whose case was communicated to us (A. J. Edis-personal communication). The ages of the patients ranged from newborn to 58 years at the time of diagnosis of a condition that, in retrospect, was recognized as a component of the complex of myxomas, spotty pigmentation, and
--Gross findings White, shining mass, 2.5X1.5X1.2cm,witha slightly gelatinous cut surface Sessile, cream, dome-shaped lesion 6 X 5 X 2 mm (palate) Whitish, firm, polypoid mass, 3.5 X 2.5 X 1.5 cm; tan, uniform, cut surface with a single 4 mm cystic space containing clear fluid Circumscribed but encapsulated 2.5 cm tan mass with lobules of salivary gland attached; pearly gray, cut surface of formalin-fixed specimen exuded a clear, viscous, sticky fluid and featured bulging lobules separated by whitish septa and spaces filled with clear tenacious content
Original pathologic diagnosis Myxoid fibroma Myxoid neurofibroma Neurofibroma
Myxoma
-
endocrine overactivity. Cardiac myxoma(s) was present in 41 patients (71%); spotty skin pigmentation in 38 (66%); skin myxoma(s) in 24 (41%); primary pigmented nodular adrenocortical diseasein 19 (33%); myxoid mammary fibroadenoma(s) in 13 (22%); Cushing’s syndrome in 12 (2 1%); acromegaly or gigantism in 5 (9%); and testicular tumor(s) in 11 of the 25 male patients (44%). Twenty-one patients (36%) were members of eight families with the syndrome; one family had dominant inheritance of the condition.4 At the time of this report, 28 (48%) of the patients were well; 13 were alive with someof the foregoing conditions or complications of them, most frequently embolic sequelae of cardiac myxoma(s) (8 patients); and 17 had died, 14 (24%) of cardiac myxoma. The case histories and records of the 58 patients were scrutinized for facial and oral abnormalities. Through the courtesy of colleagues at other institutions, we had the opportunity to review the histologic slides of oral lesions in three of the reported cases.*-lo Tissues were fixed in 10% buffered formalin and embedded in paraffin. Sections were stained with combinations of the following stains or staining techniques: hematoxylin and eosin, mucicarmine, colloidal iron with and without prior digestion with testicular hyaluronidase, alcian blue at pH 1 and 2.5, Bodian, Gomori’s reticulin, and antibodies against S- 100 protein.
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Fig. 2. Bosselated external surface (right) of palatal myxoma. The cut surface (left) is glistening, whitish, and somewhat lobulated.
Fig. 1. Multiple, nonelevated, brown-black spots on face, vermilion borders, and right upper eyelid. There is a nodule (histologically, a myxoma) on the right lower eyelid. (From Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VLW. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine [Baltimore] 1985;64:270-83. By permission of the Williams & Wilkins Co.)
CASEREPORTS Case 1
A man, 34 years of age, became unconscious and suffered a stroke at the age cf 18 years after a blow to the right cheek. Some details of the case have been reported previously.* Examination revealed “lentiginosis, particularly abundant on the face, lips, and hands,” and black pigmentation of the right lacrimal caruncle. An apical systolic murmur was heard on one occasion. Echocardiographic and angiocardiographic findings were typical of left atria1 myxoma. Cardiac exploration confirmed the clinical impression, and the lesion was excised. At the age of 19 years, the patient was given a physical examination after an epileptic seizure, and an asymptomatic, nontender, palatal soft tissue lesion was found. The lesion was ulcerated focally, and the ulceration was thought to have occurred as the result of trauma during recent seizures. The mass was excised (Table I). At the ages of 22 and 25 years, the patient had developed single nodules on his left
upper and lower eyelids, respectively; these were excised and proved to be cutaneous myxomas. At the age of 33 years, the patient underwent a follow-up echocardiogram that revealed a new left atria1 myxoma; two tumors were found and excised. The patient’s mother, who was “heavily freckled,” had died of mammary carcinoma in her mid40s. His father and half siblings had no manifestations of the complex. Case 2
A male infant had pigmented skin lesions at birth. Some features of the case have been recorded previously.9 When the infant was 6 weeks old, four lesions in the roof of his mouth were treated with cautery without a biopsy being done. When he was between the ages of 2 and 8 years, multiple myxoid skin lesions were excised, including one behind an ear and another on the chin, On examination at the age of 10 years, he had myriad pigmented skin lesions with involvement of the vermilion border of both lips and the conjunctiva of the right eye. There was a single pigmented spot on the right buccal mucosa. An intermittent cardiac murmur was noticed. Echocardiographic examination showed a left atria1 myxoma, which was excised, as was a similar small right atria1 tumor. At the age of 13 years, the patient had a mass on the hard palate and a tongue nodule, which were resected (Table I). The patient died at the age of 14 years after an operation for removal of “recurrent” cardiac myxomas. As revealed in an autopsy, the adrenal glands had the characteristic microscopic features of primary pigmented nodular adrenocortical disease. The patient’s parents were heavily “freckled” and his two brothers were “freckled,” but they had not been tested for the complex. Case 3
The patient, a 29-year-old mother of three children, had sought medical attention at the age of 24 years becauseof
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February,1987 a “large growth in the roof of the mouth” that had been present for more than 5 years. No bony involvement was evident during a roentgenographic examination, and the mass was excised (Table I). The patient was otherwise asymptomatic, but a work-up before the excision of the oral tumor had revealed a cardiac murmur. This proved to be due to three cardiac myxomas, two in the left atrium and one in the right atrium; these were excised.“’ When the patient was 27 years old, a 2.5 cm myxoma that included a keratinous cyst was excised from her right upper arm. She also had a smaller mass (presumably a myxoma) on the left forearm, which was not excised. Sometime later, the patient felt “something in the roof of her mouth.” The lesion was not painful and did not affect speech or swallowing. When the lump was noticed by her dentist, he recommended that she visit the physician. An examination showed a palatal mass, and excision of the lesion was recommended. During a preoperative examination, a new left atria1 myxoma was discovered and subsequently excised. The palatal mass was excised 7 months later, when the patient was 29 years old (Table I). It was unclear whether the mass was a recurrence of the earlier palatal mass or a new lesion. At the time of the oral operation, an axillary mass was also removed; this proved to be two myxoid fibroadenomas in the tail of the breast. Photographs of the patient showed blotchy patches of pigmentation on the vermilion border of her lower lip. A sister of the patient had facial lentiginosis with involvement of the vermilion border of the lower lip.6 She also had “several large freckles on the inside of her lips and one or two on the buccal mucosa.” Peutz-Jeghers syndrome was tentatively diagnosed, and the alimentary tract was examined roentgenographically. At the age of 12 years, she experienced acute heart failure after a volleyball game. Subsequent cardiac tests disclosed a massin the left atrium, and the patient later died after an operation for removal of a cardiac myxoma. A son of the patient has facial lentiginosis with involvement of the vermilion border of his lips, and he has had a cutaneous myxoma. The results of a recent echocardiogram were normal. The patient’s parents and three surviving siblings have not been examined for the complex. Case 4 A 34-year-old woman3,4,” was examined at the Mayo Clinic in 1984 because of persistent headaches. She had had pigmented spots on her face since birth. The finding of an asymptomatic cardiac murmur when she was 24 years oid led to the discovery of separate left ventricular and left atria1 myxomas, which were successfully excised. On one occasion, she was told by a dermatologist that she had Peutz-Jeghers syndrome. When she was 25 years old, an asymptomatic mass was removed from her left breast; histologically, it was a multicentric myxoid fibroadenoma. Two skin lesions, microscopically identified as myxomas, were removed from her back the following year. Five years later, a pedunculated mass was excised from her right external auditory canal; histologically, this was a myxoma with an epithelial component that resembled trichofollicu-
loma. When she was 34 years old, additional regions of myxoid fibroadenomatosis were excised From both breasts. When the patient was examined at the Mayo Clinic, her heart and nervous system were normal. Her pituitaryadrenal functions were investigated, and the results were normal. A dental examination revealed an abscessedtooth, which was the cause of her headaches. Numerous small, dark brown, pigmented spots were present on the central part of her face, especially on the cheeks, nose, and upper lip, including the vermilion border. Similar single spots of dark pigmentation were present on the right buccal mucosa and on the conjunctiva of the right medial canthus. About 6 months after this evaluation, the development of symptoms, signs, and laboratory findings suggestive of Cushing’s syndrome was noted. In September 1985, a bilateral adrenalectomy was performed, and both glands showed gross and microscopic features of primary pigmented nodular adrenocortical disease. Examination of the patient’s primary relatives revealed that facial lentigines, which included involvement of the vermilion border of the lips, were present in three of the patient’s siblings, their mother, and a niece (who had no involvement of the vermilion borders of the lips).“ Cutaneous myxomas were present in two of the pigmented siblings and probably in their mother. One of these siblings had acromegaiy caused by a pituitary adenoma that produced growth hormone. The results of echocardiographic examinations of the patient’s affected siblings and niece were normal; the patient’s mother declined to be examined. RESULTS Facial and labial spotty pigmentation
Among the 58 patients, spotty facial pigmentation was present in 36 (62%), and 29 of these also had pigmented spots on the vermilion border(s) of their lips (Fig. 1). The pigmented skin spots were small (0.2 to 2 mm), brown to dark brown or black, round, irregularly shaped or jagged, nonelevated or slightly elevated, and consistent with lentigines. They were distributed characteristically around the mouth, around the eyes, often in butterfly array on the bridge of the nose and cheeks, and on the vermilion border of the lips. In at least two patients, the spots were evident at birth. They were most obvious during the late preteen years and the second decade of life; they tended to fade with age, but they were still visible in the fifth decade of life. Microscopic examination of four facial lesions showed lentigo in two casesand ephelis in two cases.The pigmentation on the vermilion border of the lips ranged from sharply outlined and black to irregularly outlined and blotchy brown. Three patients each had a single pigmented spot on their buccal mucosa, and one patient had multiple pigmented spots on her buccal mucosa.
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Fig. 3. Circumscribed but unencapsulated myxoma featuring irregularly shaped pale massesof hypocellular tissue separated by serpiginous empty spaces.(Hematoxylin and eosin stain. Magnification, x40.)
Fig. 4. Circumscribed but unencapsulated myxoma includes lobules of minor salivary gland. (Movat pentachrome stain. Magnification, X2.) Intraoral
myxomas
Four patients (7%) had six intraoral tumors, five of which were excised (Table I); they were on the palate in two, on the palate and the tongue in one, and on the tongue in one. One lesion may have been a recurrence of an earlier tumor that had been incompletely excised (Case 3). The ages of the patients at the time of resection ranged from 13 to 29 years. None of the tumors were painful or causeddysphagia or dysarthria. The overlying mucosa was normal,
except in one case in which it was ulcerated. The sizes of the excised lesions ranged from 0.6 X 0.5 X 0.2 cm to 3.5 X 2.5 X 1.5 cm (Fig. 2). Characteristically, the cut surface of the tumors was pearly gray and gelatinous and exuded clear, sometimes tenacious fluid. Histologically, the tumors were composed of mesenchymal cells, mutinous matrix, capillaries, collagen and reticulin fibers, and mast and inflammatory cells. Low-power microscopic examination revealed
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Fig. 5. Hypocellular tissue featuring collagen fibers separated by much acid mucopolysaccharide and containing scattered pale oval and round nuclei. A few lymphocytes and mast cells are present. (Hematoxylin and eosin stain. Magnification, x400.)
lobules, vaguely or distinctly outlined by fibrous septa, pools of basophilic or acidophilic ground substance,and irregularly shaped and collapsed cysts (Fig. 3). The tumors were circumscribed but unencapsulated. The initial tumor excised in Case 3 had a cyst that was lined with squamous epithelium and that contained clear fluid. The presumed recurrent tumor in this patient included lobules of minor salivary gland, and at its periphery the myxoma dissected into and between lobules of the gland (Fig. 4). The shape of the basic tumor cell, which resembled a fibroblast, varied from plump and polygonal to stellate; there were also many spindle cells (Fig. 5). The nuclei were pale and visualized with difficulty; many were round, but others were lobulated or irregular in shape or cleaved or spindle. Nucleoli were small and inconspicuous. The cells had a modest amount of poorly outlined cytoplasm that was faintly acidophilic and did not stain with antibodies to S-100 protein. A mutinous matrix formed the major component of the tumor and was present in abundance among the cells, capillaries, and collagen and other fibers. Histochemical techniques gave the following results: mucicarmine positivity, positive colloidal iron reaction, and complete or almost complete removal of this positivity by prior digestion with testicular hyaluronidase and positive alcian blue staining at pH 2.5 but no staining at pH 1.0. The results indicated the presenceof large amounts of proteoglycans in the
matrix. Thin-walled capillaries were scattered throughout the tumors and were conspicuous by virtue of there being few other structures or cells present (Fig. 6). Collagen and reticulin fibers ranged from being virtually absent to being present in a modest number; they did not stain with the Bodian technique. In some instances, the collagen fibers appeared to be produced in the tumors. Mast cells were scattered through all tumors, and there was often a sprinkling of chronic inflammatory cells. REVIEW OF THE LITERATURE Muttlple lentigines syndrome
The multiple lentigines syndrome is a complicated, multisystem disorder transmitted as an autosomal dominant trait with variable penetrance and expressivity. I2 Lentigines are small (0.1 to 2 mm) brown, dark brown, or black skin lesions, round or irregular in shape or jagged. They appear when persons are at an early age, do not increase in number with sun exposure, and tend to lighten with age. Microscopically, they feature a focal proliferation of typical melanocytes and increased melanin pigmentation of the basal layers; elongation of the rete pegs may be present, as may vertical narrow bands of melanin pigment that extend through all layers of the epidermis. Multiple lentigines syndrome may be associated with various visceral and somatic abnormalities; only those involving the heart will be mentioned here. Forney and coworkersI3 described a family with
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Fig. 6. Vaguely demarcated to well-demarcated hypocellular myxoma featuring numerous capillaries cut longitudinally and transversely. (Hematoxylin and eosin stain. Magnification, X64.)
lentigines (face and shoulders), cardiac anomalies, and other developmental anomalies. Three affected members of the family had congenital mitral insufficiency (probably mitral valve prolapse), conductive deafness, and skeletal anomalies. Multiple lentigines have also been reported with hypertrophic cardiomyopathy,‘4 and some patients with these conditions have had variable combinations of short stature, hypogonadism, and sensorineural deafness. Gorlin and coworkers’s introduced the acronym LEOPARD for this syndrome, referring to lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis,abnormalities of the genitals, retardation of growth, and deafness. The lentigines were most numerous on the face, neck, and upper part of the trunk. They did not involve mucosal surfaces. In 1973, Rees and associates8described a young man with lentiginosis and cardiac myxoma (Case 1). Subsequently, Atherton and associates9described a teenager with lentiginosis, cardiac myxoma, and cutaneous myxoid lesions (Case 2). Rhodes and associatesI recognized that the skin lesions were myxomas. In 1982, Schweizer-Cagianut and colleagues” described the association of Cushing’s syndrome, cardiac myxoma, and spotty skin pigmentation. Recently, we3gathered these and other reports and, supplementing them with our own cases,enunciated the complex of myxomas, spotty pigmentation, and endocrine overactivity.
Myxoma of oral soft tissues
Myxoma of the oral soft tissues is a rare lesion. Because of this, the tumor is not well defined, and additional casesmay have been reported under other designations, such as oral focal mucinosis or neurofibroma. The literature contains 25 casesor probable casesof the tumor.13-32 The 25 affected patients (11 male and 14 female) ranged in age from newborn (congenital tumor) to 72 years. The tumor was most common in the fourth decadeof life. It produced few symptoms; usually, it appeared in the form of a painless mass, and on a few occasions it caused difficulty with mastication. The locations most commonly affected were the palate and the gingiva; other locations included the cheek, the lip, the floor of the mouth, and the tongue. Examinations usually revealed a mass that felt cystic, fluctuant, or compressible, was well demarcated, and almost invariably was nonulcerated. The usual clinical diagnosis was that of a fibroma or a mucocele. Grossly, the sizes of the excised tumors ranged from 0.5 to 7 cm, and they were described as being circumscribed, whitish, shining, mucoid, gelatinous, or slimy. Microscopically, the lesions featured hypocellularity, myxoid stroma, numerous capillaries, and circumscription, but not encapsulation. The cells present were stellate to spindle-shaped and widely separated by the abundant ground substance. A variable number of collagen fibers were present in the tumors. The duration of follow-up ranged from 1 month to 13
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years, but it was usually less than 1 year. None of the tumors recurred. None of the patients had other unusual lesions; specifically, none had myxomas in other locations, mucocutaneous pigmented spots, or endocrine abnormalities. DISCUSSION
The most important component of the complex of myxomas, spotty pigmentation, and endocrine overactivity is cardiac myxoma. This tumor may be silent until it embolizes, not infrequently resulting in a stroke, or obstructs a cardiac valve, causing acute cardiac failure and, sometimes, death. These events underscore the necessity for the physician, the dentist, and the oral surgeon to be aware of the special markers of this myxoma complex, cutaneous and mucocutaneous, that may be clues to occult cardiac myxoma(s) . The most evident manifestation of the myxoma complex is facial mucocutaneous spotty pigmentation, characterized by the presence of many small, brown, round-to-irregular pigmented spots on the face (often in butterfly distribution across the bridge of the nose and on the cheeks), the vermilion borders of the lips, and the conjunctiva. The lesions may be present at birth, but they usually develop during the first decade of life, are maximally intense during the second and third decades,and tend to fade with age. The histologic features of the pigmented lesions of the vermilion borders of the lips have not been examined, but the spots are presumably lentiginous. The pigmented facial and labial lesions are similar to those of Peutz-Jeghers syndrome (mucocutaneous and oral pigmentation and intestinal hamartomatous polyposis).’ In fact, several patients with the myxoma complex, including two in this study, have been investigated for that syndrome. However, PeutzJeghers syndrome typically features prominent intraoral pigmented spots on the palate, the gingiva, and the buccal mucosa, findings that are uncommon in the syndrome under discussion. A further differential point is the infrequency of conjunctival pigmented spots in Peutz-Jeghers syndrome’ and their frequency in the complex of myxomas, spotty pigmentation, and endocrine overactivity.3 In the myxoma complex, myxomas have occurred in the heart, the skin, and the breast. It seems unlikely that four patients with this most unusual disorder had oral cavity myxoma, a very rare lesion, by pure chance. Because these oral myxomas were histologically similar to the cardiac and cutaneous myxomas, they are likely an integral part of the disorder-a further manifestation of the myxoma-
tous disorder. In the myxoma complex, the oral myxomas were asymptomatic, occurred in young patients (average age, 20 years), and had a predilection for the palate, limited to one side by the raphe in two patients. Because of its rarity and the absence of specific clinical characteristics, a preoperative diagnosis of myxoma of the oral cavity is unlikely. Most often, the lesion will be excised because it has been recognized as an indeterminate oral mass. Grossly, it may be confused with a mucocele because the tumor is often cystic and releasessubstantial amounts of clear fluid when transected. Microscopically, distinguishing it from focal mucinosis and myxoid neurofibroma may be difficult. The former tends to be very poorly delineated, whereas myxoma in the complex, although not encapsulated and at times penetrating as tongues into adjacent tissue, is, on the whole, circumscribed. The absence of neurites and S-100 protein distinguish oral cavity myxoma from myxoid neurofibroma. Although none of the reports of oral cavity myxoma in the literature mentioned any of the components of the myxoma complex and our review of the records of three Mayo Clinic patients with oral cavity myxoma revealed no elements of the syndrome among them, we think that certain patients with the tumor will likely have other specifically related conditions. We suggest that if oral myxoma is diagnosed in a young person, particularly if the lesion is multicentric or recurrent, consideration should be given to the possible presence of the myxoma complex and the patient should be referred for further evaluation, especially if the patient also has spotty mucocutaneous pigmentation. In the past, the significance of the telltale mucocutaneous pigmentation of the myxoma complex was not realized, and consequently some patients died of cardiac myxoma or were seriously disabled by it. We hope that this article will ameliorate this situation by providing dentists and oral surgeons with the information that will permit them to refer for medical evaluation patients who may have a silent, benign, curable, but potentially lethal neoplasm: cardiac myxoma. We thank D. J. Atherton, M.B., A. R. Rees, M.D., and K. P. Tway, M.D., for follow-up information concerning their patients.
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26. Tahsinogulu M, Cologlu AS, Kuralay T. Myxoma of the gingiva: a case report. Br J Oral Surg 1975;13:95-7. 27. Sakai Y, Horiuchi H, Takahashi S. Eight casesof myxofibroma appearing in the oral region. Shika Gakuho 1976;10:14717. 28. Swart JGN, van der Kwast WAM, Snow GB, van der Waal I. Possible myxoma of the floor of the mouth: report of case. J Oral Surg 1977;35:501-3. 29. Matsumura T, Hasegawa K, Isono K, Kawakatsu K. Congenital fibromyxoma: report of case. J Oral Surg 1977;35:3135. 30. Elzay RP, Dutz W. Myxomas of the paraoral-oral soft tissues. ORAL SURG ORAL MED ORAL PATHOL 1978;45:246-54.
31. Campos GM, Grandini SA, Lopes RA. Myxoma of the oral soft tissue. Tumori 1980;66:655-9. 32. Rapidis AD, Triantafyllou AG. Myxoma of the oral soft tissues. J Oral Maxillofac Surg 1983;41:188-92. Reprint requests to:
Dr J.A. Carney Department of Pathology Mayo Clinic Rochester, MN 55905
W. LITTLE,
D.M.D.,
M.S.D.
School of Dentistry University of Minnesota 515 S.E. Delaware St. Minneapolis, Minn. 55455
Mucocutaneous pigmented spots and oral myxomas: The oral manifestations of the complex of myxomas, spotty pigmentation, and endocrine overactivity Cli’ord A. Cook, D.D.S., Bruce A. Lund. D.D.S., M.S., and J. Aidan Carney, M.D., Ph.D., F.R.C.P.I.. Rochester, Minn. THE SECTION OF ORAL AND MAXILLOFACIAL CLl’JlC AND MAYO FOUNDATION
SURGERY
AND
THE DEPARTMENT
OF PATHOLOGY,
MAYO
The complex of myxomas, spotty pigmentation, and endocrine overactivity is a recently recognized syndrome, transmitted as an autosomal dominant trait. The most serious component of the disorder is cardiac myxoma, which has caused the death of one fourth of the affected patients and serious disability in an equal number. It is, therefore, important to recognize patients at risk from the syndrome and, in particular, to test them for cardiac myxoma. Fortunately, in many patients the myxoma complex has a clearly visible marker: mucocutaneous pigmentation. Among 58 patients with the syndrome, spotty facial pigmentation was present in 38 (62%), and 29 (50%) of these also had pigmented spots on their lips, This type and distribution of pigmentation should be a clue to the possible presence of the complex of myxomas, spotty pigmentation, and endocrine overactivity, and patients thus affected should be referred for further investigation. Oral cavity myxoma(s) occurred in four patients with the syndrome. (ORAL SURC. ORAL MED. ORAL PATHOL. 1987;63:175-83)
M
anifestations of disorders of the oral cavity may be limited to the mouth. However, through blood, lymphatic, nerve, and other tissue pathways, the oral tissues maintain an intimate relationship with the remainder of the body and not infrequently are involved secondarily in various nonoral conditions. Importantly, oral findings may be the harbingers of a variety of serious systemic disorders. The characteristic mucocutaneous pigmentation of the PeutzJeghers syndrome is an example of this,’ and thickened lips and lumps on the anterior one third of the tongue (ganglioneuromatosis), a clue to the presence of medullary thyroid carcinoma or pheochromocyto-
ma or both (multiple endocrine neoplasia, type 2b),2 is another. In this article, we draw attention to a newly recognized group of oral findings that may signal a systemic disorder that includes a potentially lethal neoplasm: cardiac myxoma. The findings are components of a complicated condition involving visceral and soft tissue myxomas, spotty pigmentation of the skin, and endocrine overactivity.3 Recognition of the disorder was basedon findings in 40 patients, each of whom had two or more of the following conditions: ( 1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoid fibroadenoma, (4) spotty muco175
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Table
Oral Surg. February, 1987
I. Selected findings in three patients with oral myxoma(s) Reported by
Case
Location of lesion
I
Rees et al.*
Junction, right hard and soft palate
2
Atherton et al?
3
Tway et al.‘O
Hard palate and tongue Right hard palate
Right hard and soft palate (? recurrence)
Clinical
Pedunculated lesion with small area of ulceration
Smooth, bulky, nontender, submucosal mass
Spongy mass, 3.5 X 2 cm, commencing almost at free edge of soft palate and advancing to midportion of hard palate
cutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease,(6) testicular tumors, and (7) pituitary adenoma secreting growth hormone. The syndrome is inherited as an autosomal dominant trait.4, 5 The most serious component of the myxoma complex is cardiac myxoma, which has caused the death of one fourth of the patients and serious morbidity in an equal number.3 Therefore, it is important to recognize patients at risk from the complex of myxomas, spotty pigmentation, and endocrine overactivity in order to examine them for components of the syndrome, in particular to test them (and their primary relatives) for cardiac myxoma. In this article, we present details of the oral findings that may be clues to this serious heritable syndrome. MATERIALS
description
AND METHODS
The study group included 58 patients (25 male and 33 female): 40 patients previously described by Carney and coworkers,3 1 patient mentioned in the literature: 5 other patients described by Carney and associates,411 patients identified by McCarthy and associates,’ and 1 patient whose case was communicated to us (A. J. Edis-personal communication). The ages of the patients ranged from newborn to 58 years at the time of diagnosis of a condition that, in retrospect, was recognized as a component of the complex of myxomas, spotty pigmentation, and
--Gross findings White, shining mass, 2.5X1.5X1.2cm,witha slightly gelatinous cut surface Sessile, cream, dome-shaped lesion 6 X 5 X 2 mm (palate) Whitish, firm, polypoid mass, 3.5 X 2.5 X 1.5 cm; tan, uniform, cut surface with a single 4 mm cystic space containing clear fluid Circumscribed but encapsulated 2.5 cm tan mass with lobules of salivary gland attached; pearly gray, cut surface of formalin-fixed specimen exuded a clear, viscous, sticky fluid and featured bulging lobules separated by whitish septa and spaces filled with clear tenacious content
Original pathologic diagnosis Myxoid fibroma Myxoid neurofibroma Neurofibroma
Myxoma
-
endocrine overactivity. Cardiac myxoma(s) was present in 41 patients (71%); spotty skin pigmentation in 38 (66%); skin myxoma(s) in 24 (41%); primary pigmented nodular adrenocortical diseasein 19 (33%); myxoid mammary fibroadenoma(s) in 13 (22%); Cushing’s syndrome in 12 (2 1%); acromegaly or gigantism in 5 (9%); and testicular tumor(s) in 11 of the 25 male patients (44%). Twenty-one patients (36%) were members of eight families with the syndrome; one family had dominant inheritance of the condition.4 At the time of this report, 28 (48%) of the patients were well; 13 were alive with someof the foregoing conditions or complications of them, most frequently embolic sequelae of cardiac myxoma(s) (8 patients); and 17 had died, 14 (24%) of cardiac myxoma. The case histories and records of the 58 patients were scrutinized for facial and oral abnormalities. Through the courtesy of colleagues at other institutions, we had the opportunity to review the histologic slides of oral lesions in three of the reported cases.*-lo Tissues were fixed in 10% buffered formalin and embedded in paraffin. Sections were stained with combinations of the following stains or staining techniques: hematoxylin and eosin, mucicarmine, colloidal iron with and without prior digestion with testicular hyaluronidase, alcian blue at pH 1 and 2.5, Bodian, Gomori’s reticulin, and antibodies against S- 100 protein.
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Fig. 2. Bosselated external surface (right) of palatal myxoma. The cut surface (left) is glistening, whitish, and somewhat lobulated.
Fig. 1. Multiple, nonelevated, brown-black spots on face, vermilion borders, and right upper eyelid. There is a nodule (histologically, a myxoma) on the right lower eyelid. (From Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VLW. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine [Baltimore] 1985;64:270-83. By permission of the Williams & Wilkins Co.)
CASEREPORTS Case 1
A man, 34 years of age, became unconscious and suffered a stroke at the age cf 18 years after a blow to the right cheek. Some details of the case have been reported previously.* Examination revealed “lentiginosis, particularly abundant on the face, lips, and hands,” and black pigmentation of the right lacrimal caruncle. An apical systolic murmur was heard on one occasion. Echocardiographic and angiocardiographic findings were typical of left atria1 myxoma. Cardiac exploration confirmed the clinical impression, and the lesion was excised. At the age of 19 years, the patient was given a physical examination after an epileptic seizure, and an asymptomatic, nontender, palatal soft tissue lesion was found. The lesion was ulcerated focally, and the ulceration was thought to have occurred as the result of trauma during recent seizures. The mass was excised (Table I). At the ages of 22 and 25 years, the patient had developed single nodules on his left
upper and lower eyelids, respectively; these were excised and proved to be cutaneous myxomas. At the age of 33 years, the patient underwent a follow-up echocardiogram that revealed a new left atria1 myxoma; two tumors were found and excised. The patient’s mother, who was “heavily freckled,” had died of mammary carcinoma in her mid40s. His father and half siblings had no manifestations of the complex. Case 2
A male infant had pigmented skin lesions at birth. Some features of the case have been recorded previously.9 When the infant was 6 weeks old, four lesions in the roof of his mouth were treated with cautery without a biopsy being done. When he was between the ages of 2 and 8 years, multiple myxoid skin lesions were excised, including one behind an ear and another on the chin, On examination at the age of 10 years, he had myriad pigmented skin lesions with involvement of the vermilion border of both lips and the conjunctiva of the right eye. There was a single pigmented spot on the right buccal mucosa. An intermittent cardiac murmur was noticed. Echocardiographic examination showed a left atria1 myxoma, which was excised, as was a similar small right atria1 tumor. At the age of 13 years, the patient had a mass on the hard palate and a tongue nodule, which were resected (Table I). The patient died at the age of 14 years after an operation for removal of “recurrent” cardiac myxomas. As revealed in an autopsy, the adrenal glands had the characteristic microscopic features of primary pigmented nodular adrenocortical disease. The patient’s parents were heavily “freckled” and his two brothers were “freckled,” but they had not been tested for the complex. Case 3
The patient, a 29-year-old mother of three children, had sought medical attention at the age of 24 years becauseof
178
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Surg.
February,1987 a “large growth in the roof of the mouth” that had been present for more than 5 years. No bony involvement was evident during a roentgenographic examination, and the mass was excised (Table I). The patient was otherwise asymptomatic, but a work-up before the excision of the oral tumor had revealed a cardiac murmur. This proved to be due to three cardiac myxomas, two in the left atrium and one in the right atrium; these were excised.“’ When the patient was 27 years old, a 2.5 cm myxoma that included a keratinous cyst was excised from her right upper arm. She also had a smaller mass (presumably a myxoma) on the left forearm, which was not excised. Sometime later, the patient felt “something in the roof of her mouth.” The lesion was not painful and did not affect speech or swallowing. When the lump was noticed by her dentist, he recommended that she visit the physician. An examination showed a palatal mass, and excision of the lesion was recommended. During a preoperative examination, a new left atria1 myxoma was discovered and subsequently excised. The palatal mass was excised 7 months later, when the patient was 29 years old (Table I). It was unclear whether the mass was a recurrence of the earlier palatal mass or a new lesion. At the time of the oral operation, an axillary mass was also removed; this proved to be two myxoid fibroadenomas in the tail of the breast. Photographs of the patient showed blotchy patches of pigmentation on the vermilion border of her lower lip. A sister of the patient had facial lentiginosis with involvement of the vermilion border of the lower lip.6 She also had “several large freckles on the inside of her lips and one or two on the buccal mucosa.” Peutz-Jeghers syndrome was tentatively diagnosed, and the alimentary tract was examined roentgenographically. At the age of 12 years, she experienced acute heart failure after a volleyball game. Subsequent cardiac tests disclosed a massin the left atrium, and the patient later died after an operation for removal of a cardiac myxoma. A son of the patient has facial lentiginosis with involvement of the vermilion border of his lips, and he has had a cutaneous myxoma. The results of a recent echocardiogram were normal. The patient’s parents and three surviving siblings have not been examined for the complex. Case 4 A 34-year-old woman3,4,” was examined at the Mayo Clinic in 1984 because of persistent headaches. She had had pigmented spots on her face since birth. The finding of an asymptomatic cardiac murmur when she was 24 years oid led to the discovery of separate left ventricular and left atria1 myxomas, which were successfully excised. On one occasion, she was told by a dermatologist that she had Peutz-Jeghers syndrome. When she was 25 years old, an asymptomatic mass was removed from her left breast; histologically, it was a multicentric myxoid fibroadenoma. Two skin lesions, microscopically identified as myxomas, were removed from her back the following year. Five years later, a pedunculated mass was excised from her right external auditory canal; histologically, this was a myxoma with an epithelial component that resembled trichofollicu-
loma. When she was 34 years old, additional regions of myxoid fibroadenomatosis were excised From both breasts. When the patient was examined at the Mayo Clinic, her heart and nervous system were normal. Her pituitaryadrenal functions were investigated, and the results were normal. A dental examination revealed an abscessedtooth, which was the cause of her headaches. Numerous small, dark brown, pigmented spots were present on the central part of her face, especially on the cheeks, nose, and upper lip, including the vermilion border. Similar single spots of dark pigmentation were present on the right buccal mucosa and on the conjunctiva of the right medial canthus. About 6 months after this evaluation, the development of symptoms, signs, and laboratory findings suggestive of Cushing’s syndrome was noted. In September 1985, a bilateral adrenalectomy was performed, and both glands showed gross and microscopic features of primary pigmented nodular adrenocortical disease. Examination of the patient’s primary relatives revealed that facial lentigines, which included involvement of the vermilion border of the lips, were present in three of the patient’s siblings, their mother, and a niece (who had no involvement of the vermilion borders of the lips).“ Cutaneous myxomas were present in two of the pigmented siblings and probably in their mother. One of these siblings had acromegaiy caused by a pituitary adenoma that produced growth hormone. The results of echocardiographic examinations of the patient’s affected siblings and niece were normal; the patient’s mother declined to be examined. RESULTS Facial and labial spotty pigmentation
Among the 58 patients, spotty facial pigmentation was present in 36 (62%), and 29 of these also had pigmented spots on the vermilion border(s) of their lips (Fig. 1). The pigmented skin spots were small (0.2 to 2 mm), brown to dark brown or black, round, irregularly shaped or jagged, nonelevated or slightly elevated, and consistent with lentigines. They were distributed characteristically around the mouth, around the eyes, often in butterfly array on the bridge of the nose and cheeks, and on the vermilion border of the lips. In at least two patients, the spots were evident at birth. They were most obvious during the late preteen years and the second decade of life; they tended to fade with age, but they were still visible in the fifth decade of life. Microscopic examination of four facial lesions showed lentigo in two casesand ephelis in two cases.The pigmentation on the vermilion border of the lips ranged from sharply outlined and black to irregularly outlined and blotchy brown. Three patients each had a single pigmented spot on their buccal mucosa, and one patient had multiple pigmented spots on her buccal mucosa.
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Fig. 3. Circumscribed but unencapsulated myxoma featuring irregularly shaped pale massesof hypocellular tissue separated by serpiginous empty spaces.(Hematoxylin and eosin stain. Magnification, x40.)
Fig. 4. Circumscribed but unencapsulated myxoma includes lobules of minor salivary gland. (Movat pentachrome stain. Magnification, X2.) Intraoral
myxomas
Four patients (7%) had six intraoral tumors, five of which were excised (Table I); they were on the palate in two, on the palate and the tongue in one, and on the tongue in one. One lesion may have been a recurrence of an earlier tumor that had been incompletely excised (Case 3). The ages of the patients at the time of resection ranged from 13 to 29 years. None of the tumors were painful or causeddysphagia or dysarthria. The overlying mucosa was normal,
except in one case in which it was ulcerated. The sizes of the excised lesions ranged from 0.6 X 0.5 X 0.2 cm to 3.5 X 2.5 X 1.5 cm (Fig. 2). Characteristically, the cut surface of the tumors was pearly gray and gelatinous and exuded clear, sometimes tenacious fluid. Histologically, the tumors were composed of mesenchymal cells, mutinous matrix, capillaries, collagen and reticulin fibers, and mast and inflammatory cells. Low-power microscopic examination revealed
180
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Cook, Lund, and Carney
Fig. 5. Hypocellular tissue featuring collagen fibers separated by much acid mucopolysaccharide and containing scattered pale oval and round nuclei. A few lymphocytes and mast cells are present. (Hematoxylin and eosin stain. Magnification, x400.)
lobules, vaguely or distinctly outlined by fibrous septa, pools of basophilic or acidophilic ground substance,and irregularly shaped and collapsed cysts (Fig. 3). The tumors were circumscribed but unencapsulated. The initial tumor excised in Case 3 had a cyst that was lined with squamous epithelium and that contained clear fluid. The presumed recurrent tumor in this patient included lobules of minor salivary gland, and at its periphery the myxoma dissected into and between lobules of the gland (Fig. 4). The shape of the basic tumor cell, which resembled a fibroblast, varied from plump and polygonal to stellate; there were also many spindle cells (Fig. 5). The nuclei were pale and visualized with difficulty; many were round, but others were lobulated or irregular in shape or cleaved or spindle. Nucleoli were small and inconspicuous. The cells had a modest amount of poorly outlined cytoplasm that was faintly acidophilic and did not stain with antibodies to S-100 protein. A mutinous matrix formed the major component of the tumor and was present in abundance among the cells, capillaries, and collagen and other fibers. Histochemical techniques gave the following results: mucicarmine positivity, positive colloidal iron reaction, and complete or almost complete removal of this positivity by prior digestion with testicular hyaluronidase and positive alcian blue staining at pH 2.5 but no staining at pH 1.0. The results indicated the presenceof large amounts of proteoglycans in the
matrix. Thin-walled capillaries were scattered throughout the tumors and were conspicuous by virtue of there being few other structures or cells present (Fig. 6). Collagen and reticulin fibers ranged from being virtually absent to being present in a modest number; they did not stain with the Bodian technique. In some instances, the collagen fibers appeared to be produced in the tumors. Mast cells were scattered through all tumors, and there was often a sprinkling of chronic inflammatory cells. REVIEW OF THE LITERATURE Muttlple lentigines syndrome
The multiple lentigines syndrome is a complicated, multisystem disorder transmitted as an autosomal dominant trait with variable penetrance and expressivity. I2 Lentigines are small (0.1 to 2 mm) brown, dark brown, or black skin lesions, round or irregular in shape or jagged. They appear when persons are at an early age, do not increase in number with sun exposure, and tend to lighten with age. Microscopically, they feature a focal proliferation of typical melanocytes and increased melanin pigmentation of the basal layers; elongation of the rete pegs may be present, as may vertical narrow bands of melanin pigment that extend through all layers of the epidermis. Multiple lentigines syndrome may be associated with various visceral and somatic abnormalities; only those involving the heart will be mentioned here. Forney and coworkersI3 described a family with
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Pigmented spots and myxomas 181
Fig. 6. Vaguely demarcated to well-demarcated hypocellular myxoma featuring numerous capillaries cut longitudinally and transversely. (Hematoxylin and eosin stain. Magnification, X64.)
lentigines (face and shoulders), cardiac anomalies, and other developmental anomalies. Three affected members of the family had congenital mitral insufficiency (probably mitral valve prolapse), conductive deafness, and skeletal anomalies. Multiple lentigines have also been reported with hypertrophic cardiomyopathy,‘4 and some patients with these conditions have had variable combinations of short stature, hypogonadism, and sensorineural deafness. Gorlin and coworkers’s introduced the acronym LEOPARD for this syndrome, referring to lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis,abnormalities of the genitals, retardation of growth, and deafness. The lentigines were most numerous on the face, neck, and upper part of the trunk. They did not involve mucosal surfaces. In 1973, Rees and associates8described a young man with lentiginosis and cardiac myxoma (Case 1). Subsequently, Atherton and associates9described a teenager with lentiginosis, cardiac myxoma, and cutaneous myxoid lesions (Case 2). Rhodes and associatesI recognized that the skin lesions were myxomas. In 1982, Schweizer-Cagianut and colleagues” described the association of Cushing’s syndrome, cardiac myxoma, and spotty skin pigmentation. Recently, we3gathered these and other reports and, supplementing them with our own cases,enunciated the complex of myxomas, spotty pigmentation, and endocrine overactivity.
Myxoma of oral soft tissues
Myxoma of the oral soft tissues is a rare lesion. Because of this, the tumor is not well defined, and additional casesmay have been reported under other designations, such as oral focal mucinosis or neurofibroma. The literature contains 25 casesor probable casesof the tumor.13-32 The 25 affected patients (11 male and 14 female) ranged in age from newborn (congenital tumor) to 72 years. The tumor was most common in the fourth decadeof life. It produced few symptoms; usually, it appeared in the form of a painless mass, and on a few occasions it caused difficulty with mastication. The locations most commonly affected were the palate and the gingiva; other locations included the cheek, the lip, the floor of the mouth, and the tongue. Examinations usually revealed a mass that felt cystic, fluctuant, or compressible, was well demarcated, and almost invariably was nonulcerated. The usual clinical diagnosis was that of a fibroma or a mucocele. Grossly, the sizes of the excised tumors ranged from 0.5 to 7 cm, and they were described as being circumscribed, whitish, shining, mucoid, gelatinous, or slimy. Microscopically, the lesions featured hypocellularity, myxoid stroma, numerous capillaries, and circumscription, but not encapsulation. The cells present were stellate to spindle-shaped and widely separated by the abundant ground substance. A variable number of collagen fibers were present in the tumors. The duration of follow-up ranged from 1 month to 13
182 Cook, Lund, and Carney
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years, but it was usually less than 1 year. None of the tumors recurred. None of the patients had other unusual lesions; specifically, none had myxomas in other locations, mucocutaneous pigmented spots, or endocrine abnormalities. DISCUSSION
The most important component of the complex of myxomas, spotty pigmentation, and endocrine overactivity is cardiac myxoma. This tumor may be silent until it embolizes, not infrequently resulting in a stroke, or obstructs a cardiac valve, causing acute cardiac failure and, sometimes, death. These events underscore the necessity for the physician, the dentist, and the oral surgeon to be aware of the special markers of this myxoma complex, cutaneous and mucocutaneous, that may be clues to occult cardiac myxoma(s) . The most evident manifestation of the myxoma complex is facial mucocutaneous spotty pigmentation, characterized by the presence of many small, brown, round-to-irregular pigmented spots on the face (often in butterfly distribution across the bridge of the nose and on the cheeks), the vermilion borders of the lips, and the conjunctiva. The lesions may be present at birth, but they usually develop during the first decade of life, are maximally intense during the second and third decades,and tend to fade with age. The histologic features of the pigmented lesions of the vermilion borders of the lips have not been examined, but the spots are presumably lentiginous. The pigmented facial and labial lesions are similar to those of Peutz-Jeghers syndrome (mucocutaneous and oral pigmentation and intestinal hamartomatous polyposis).’ In fact, several patients with the myxoma complex, including two in this study, have been investigated for that syndrome. However, PeutzJeghers syndrome typically features prominent intraoral pigmented spots on the palate, the gingiva, and the buccal mucosa, findings that are uncommon in the syndrome under discussion. A further differential point is the infrequency of conjunctival pigmented spots in Peutz-Jeghers syndrome’ and their frequency in the complex of myxomas, spotty pigmentation, and endocrine overactivity.3 In the myxoma complex, myxomas have occurred in the heart, the skin, and the breast. It seems unlikely that four patients with this most unusual disorder had oral cavity myxoma, a very rare lesion, by pure chance. Because these oral myxomas were histologically similar to the cardiac and cutaneous myxomas, they are likely an integral part of the disorder-a further manifestation of the myxoma-
tous disorder. In the myxoma complex, the oral myxomas were asymptomatic, occurred in young patients (average age, 20 years), and had a predilection for the palate, limited to one side by the raphe in two patients. Because of its rarity and the absence of specific clinical characteristics, a preoperative diagnosis of myxoma of the oral cavity is unlikely. Most often, the lesion will be excised because it has been recognized as an indeterminate oral mass. Grossly, it may be confused with a mucocele because the tumor is often cystic and releasessubstantial amounts of clear fluid when transected. Microscopically, distinguishing it from focal mucinosis and myxoid neurofibroma may be difficult. The former tends to be very poorly delineated, whereas myxoma in the complex, although not encapsulated and at times penetrating as tongues into adjacent tissue, is, on the whole, circumscribed. The absence of neurites and S-100 protein distinguish oral cavity myxoma from myxoid neurofibroma. Although none of the reports of oral cavity myxoma in the literature mentioned any of the components of the myxoma complex and our review of the records of three Mayo Clinic patients with oral cavity myxoma revealed no elements of the syndrome among them, we think that certain patients with the tumor will likely have other specifically related conditions. We suggest that if oral myxoma is diagnosed in a young person, particularly if the lesion is multicentric or recurrent, consideration should be given to the possible presence of the myxoma complex and the patient should be referred for further evaluation, especially if the patient also has spotty mucocutaneous pigmentation. In the past, the significance of the telltale mucocutaneous pigmentation of the myxoma complex was not realized, and consequently some patients died of cardiac myxoma or were seriously disabled by it. We hope that this article will ameliorate this situation by providing dentists and oral surgeons with the information that will permit them to refer for medical evaluation patients who may have a silent, benign, curable, but potentially lethal neoplasm: cardiac myxoma. We thank D. J. Atherton, M.B., A. R. Rees, M.D., and K. P. Tway, M.D., for follow-up information concerning their patients.
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Dr J.A. Carney Department of Pathology Mayo Clinic Rochester, MN 55905