What's Your Diagnosis: Smoker With Oral Lesions

HISTORY A 34-year-old man is seen for routine annual physical examination. Heavy smoker. No oral symptoms, no oral trauma. Denies recent weight loss, hematochezia, and fatigue. PHYSICAL EXAMINATION General appearance: looks slightly older than stated age because of increased skin wrinkling and slight grayish cast to face. Yellowish spots on buccal mucosa and oral vestibule, as shown. Although the areas on the tongue suggest candidal infection, scraping of the spots on the buccal mucosa with a tongue blade does not remove any of the yellow areas, nor induce bleeding. Chest examination: normal. No abdominal masses, distention, or tenderness. No rectal masses. Stool is brown; fecal occult blood test is negative. What's your diagnosis? Answer on next page , ANSWER: ORAL SEBACEOUS GLANDS (FORDYCE GRANULES) The lesions shown constitute ectopic intraoral sebaceous glands known as Fordyce granules or Fordyce spots.1,2  These histologically normal structures are quite prominent in some healthy persons, particularly when, as here, they are densely clustered. They have a predilection for the retromolar area but can appear anywhere on the buccal mucosa or elsewhere, including the mucosa of the oral vestibule inferior to the gingiva. Fordyce granules are found in a small number of children and in at least 1% of adults, more often in men than women. Data cited on prevalence among adults range wildly upward to 95%.2 SMOKER’S FACE The premature aging of this patient’s face might have resulted from excess sun exposure or from tobacco abuse. A constellation of features, including wrinkling and graying, is present in most persons who have smoked heavily for many years.3,4  The diagnostic value of these observations of “smoker’s face” lies not so much in uncovering a concealed habit as in the educational value to patients: knowing that cigarettes cause an immediate cosmetic detriment may motivate behavioral change more than does fear of disease in a future that may be dismissed as remote. Perhaps such a strategy would be effective with teenagers and young adults, two groups of Americans among whom tobacco use persists even if at a reduced level. Smoking in these groups has not approached the zero rate that one would desire purely from a health perspective. INTACT EPITHELIUM, VARIABLE APPEARANCE One key to the recognition of Fordyce granules is their sparing of the overlying epithelium, which thus remains smooth, intact and shiny—that is, not whitehead (pimple)-like, to use a morphologic analogy from the skin. This contrasts with the roughening that occurs in such epithelial disorders as carcinoma in situ, or with retained food matter that might mimic a Fordyce granule. The mucosal surface of a Fordyce granule may bulge a little to form a small hemisphere. Colors range from brilliant yellow, verging on yellow-orange, to nearwhite. These colors all contrast vividly with the red-pink background oral mucosa. Most Fordyce granules are pinhead-sized, although data show a size range from 0.8 to 3 mm.5  In the case of one aged patient, a Fordyce spot that was gray-white, solitary, and 4 mm across suggested intraoral lymphoid follicle. The smoothness of the patient’s lesion made the prospect of a sebaceous neoplasm arising from the gland less likely. FEAR OF ORAL CANCER Fordyce granules are sometimes mistaken for early oral squamous cell carcinoma or leukoplakia. Their large numbers provide a substantial clue to the diagnosis, particularly in concert with the other morphologic features cited above. One can usually reassure patients with such findings that, based on the history and physical examination, they do not have squamous cell carcinoma of the mouth and that there is no need for technologic or laboratory investigation. If a patient has risk factors for oral cancer— such as smoking, alcohol abuse, or use of chewing tobacco— counseling to stop these practices may have a slightly better chance of success after a scare about consequences. Yet we know that fear is a poor motivator of behavioral change. If either you or the patient requires a second opinion to be confident that there is no incipient neoplasia (for example, if there is an area of erythroplasia6 ), consultation with an oral diagnosis specialist or other dentist can be helpful. A POSSIBLE COLON CANCER CONNECTION Although the presence of neoplasms of sebaceous origin has long been recognized as part of a rare hereditary colon cancer syndrome—Muir-Torre syndrome—a report of a connection with the more common hereditary nonpolyposis colon cancer (HNPCC) has just been electronically published.5  The source is an Italian group that had previously published impressive research with unique methodology on increased oral vascular markings as potential indicators of HNPCC.7  Their work was accompanied by a cautiously excited editorial by Dr Lynch, whose eponym connotes the commonest HNPCC.8  That editorial was titled “Diagnosing Lynch Syndrome: Is the Answer in the Mouth?” Great excitement arises because Lynch syndrome accounts for a substantial minority of cases of colorectal cancer that adds up to many thousands per year worldwide and includes a disproportionate number of colorectal cancer deaths in younger adults. The discovery of a marker could focus prevention and early detection efforts. The Italian researchers cited complex scientific bases for a hypothesis that Fordyce granules are much more common in persons with Lynch syndrome. They then compared members of multiple affected kindreds with a variety of matched normal controls. In their series, Fordyce granules were found in 13 of 15 persons with Lynch syndrome and a personal history of colon cancer, and only 6 of 630 controls.5  There was also a difference in usual locale: in the controls, the retromolar area and the upper lip vermilion border were typically affected, whereas the lower gingival and vestibular oral mucosa were favored in persons with Lynch syndrome and a personal history of colon cancer. These results must be considered highly preliminary. As the authors themselves note, they include only unpublished data about two other critical groups in whom the prevalence of Fordyce granules need to be compared: persons with Lynch syndrome who have not had colon cancer, and persons who have had sporadic non-HNPCC colon cancer. The prevalence in these groups, and the extension of the investigation to other countries and other populations, will help determine whether the sign is dependable, and exactly what it means. If a solid link is ultimately proved, it would provide a first physical sign of Lynch syndrome. That would enormously help to guide which persons, other than those having multiple relatives with colon cancer, need to be referred for the complex and imperfect technologic screening for what is known as microsatellite instability and—if the results and the judgment of the geneticist or gastroenterologist so dictate—for more frequent colonoscopy starting at a much earlier age. How all this relates to Muir-Torre syndrome remains very murky at this moment. The index photograph was taken long ago, and by another physician, so I do not know the current status of this patient. If he were under my care, I would arrange an office visit to ask, face-to-face, about any possible family history of colon cancer. Because the molecular abnormality apparently can also occur as a mutation, I would also consider consulting with a geneticist or oncologist with expertise in cancer genetics. ANOTHER FORDYCE The Fordyce eponym is also applied to innocent scrotal hemangiomas, a few of which can be found in many healthy men older than 30 years. Fordyce spots of the scrotum carry a pathologic significance only for young boys, in whom they are an important sign of Fabry disease. Although it is an aberrant vascular proliferation in the skin that sometimes relates at least semiotically to an internal disorder, this scrotal finding would appear to have nothing except the name in common with all the above considerations in the mouth and the gut.  Schneiderman H. Oral sebaceous glands (Fordyce granules): a finding sometimes mistaken for oral cancer, and an extraordinary new hypothesis. CONSULTANT. 2005;45:895-899. REFERENCES: 1. Lewis MA, Lamey PJ. Clinical Oral Medicine. Boston: Wright; 1883:52-53. 2. Gier RE. Yellow conditions of the oral mucosa. In: Wood NK, Goaz PW, eds. Differential Diagnosis of Oral and Maxillofacial Lesions. 5th ed. St Louis: Mosby; 1997:225-226. 3. Model D. Smoker’s face: an underrated clinical sign? Br Med J. 1985;291: 1760-1762. 4. Soffer A. Smokers’ faces: who are the smokers? Chest. 1986;86:622. 5. De Felice C, Parrini S, Chitano G, et al. Fordyce granules and hereditary nonpolyposis colorectal cancer syndrome. Gut. 2005. May 6;doi:10.1136/gut. 2005.064881. [Epub ahead of print.] 6. Mashberg A, Feldman IJ. Clinical criteria for identifying early oral and oropharyngeal carcinoma: erythroplasia revisited. Am J Surg. 1988;156:273-275. 7. De Felice C, Latini G, Bianciardi G, et al. Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome. Gut. 2003;52:1764-1767. 8. Roy HK, Lynch HT. Diagnosing Lynch syndrome: is the answer in the mouth? Gut. 2003;52:1665-1667.