Fordyce spots

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2].

Synonyms and keywords: Fordyce granules; Fordyce disease; Fordyce bodies.

Overview

Fordyce spots (also termed Fordyce granules, or Fordyce disease), are visible sebaceous glands that are present in most individuals. They appear on the genitals and/or in the mouth. They appear as small, painless, raised, pale, red or white spots or bumps 1 to 3 mm in diameter that may appear on the scrotum, shaft of the penis or on the labia, as well as the inner surface (retromolar mucosa) and vermilion border of the lips of the face. They are not associated with any disease or illness, nor are they infectious but rather they represent a natural occurrence on the body. No treatment is therefore required, unless the individual has cosmetic concerns. Persons with this condition sometimes consult with a dermatologist because they are worried they may have a sexually transmitted disease (especially genital warts) or some form of cancer.

Classification

Sebaceous glands are normal adnexal structures of the dermis but may also be found ectopically within the mouth, where they are referred to as Oral Fordyce Granules or ectopic sebaceous glands. On the foreskin they are called Tyson's glands, not to be confused with hirsuties coronae glandis.

When they appear on the penis, they are also called penile sebaceous glands.

When seen as a streak of individual glands along the interface between the skin of the lip and the vermilion border, the terms Fox-Fordyce disease and Fordyce's condition have been used.

Signs and symptoms

On the shaft of the penis, Fordyce spots are more visible when the skin is stretched, and may only be noticeable during an erection. The spots can also appear on the skin of the scrotum.

Oral Fordyce granules appear as rice-like granules, white or yellow-white in color. They are painless papules (small bumps), about 1–3 mm in greatest dimension. The most common site is along the line between the vermilion border and the oral mucosa of the upper lip, or on the buccal mucosa (inside the cheeks) in the commissural region, often bilaterally. They may also occur on the mandibular retromolar pad and tonsillar areas, but any oral surface may be involved. There is no surrounding mucosal change. Some patients will have hundreds of granules while most have only one or two.

Occasionally, several adjacent glands will coalesce into a larger cauliflower-like cluster similar to sebaceous hyperplasia of the skin. In such an instance, it may be difficult to determine whether or not to diagnose the lesion as sebaceous hyperplasia or sebaceous adenoma. The distinction may be moot because both entities have the same treatment, although the adenoma has a greater growth potential. It should be mentioned that sebaceous carcinoma of the oral cavity has been reported, presumably arising from Fordyce granules or hyperplastic foci of sebaceous glands.

In some persons with Fordyce spots, the glands express a thick, chalky discharge when squeezed.

Causes

Normally, sebaceous glands are only found in association with a hair follicle.

They appear to be more obvious in people with greasy skin types, with some rheumatic disorders, and in Hereditary nonpolyposis colorectal cancer. In the latter, the most common site for Fordyce spots is the lower gingiva (gums) and vestibular mucosa.

Differentiating Fordyce spots drom other diseases

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic
Diseases involving oral cavity and other organ systems
Behcet's disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels
Crohn's disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh ≤1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles

Diagnosis

Large numbers of lobules coalescing into a definitely elevated mass may be called benign sebaceous hyperplasia, and occasional small keratin-filled pseudocysts may be seen and must be differentiated from epidermoid cyst or dermoid cyst with sebaceous adnexa. The pathologist must be careful to differentiate such lesions from salivary neoplasms with sebaceous cells, such as sebaceous lymphadenoma and sebaceous adenoma, and their malignant counterparts sebaceous lymphadenocarcinoma and sebaceous carcinoma.

Oral Fordyce granules are usually not biopsied because they are readily diagnosed clinically, but they are often seen as incidental findings of mucosal biopsies of the buccal, labial and retromolar mucosa. The granules are similar to normal sebaceous glands of the skin but lack hair follicles and almost always lack a ductal communication with the surface. The glands are located just beneath the overlying epithelium and often produce a local elevation of the epithelium. Individual sebaceous cells are large, with central dark nuclei and abundant foamy cytoplasm. The surrounding stroma may contain occasional chronic inflammatory cells because of trauma with adjacent teeth.

Physical examination

Gallery

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Prognosis

Fordyce spots are completely benign, and require no treatment. Often their presence is considered normal anatomic variants rather than a true medical condition.

Treatment

Vaporising laser treatments such as CO₂ laser or electro desiccation have been used with some success in diminishing the appearance of this condition if they are of cosmetic concern, despite the fact that most doctors consider this a normal physiological phenomenon and advise against treatment.

Success varies per patient, but some have found relief from pulsed dye Lasers, a laser normally used to treat sebaceous gland hyperplasia, which is similar to Fordyce spots. Treatment with pulsed dye lasers is expensive, but may be less likely to scar than other methods.

No treatment is required for oral Fordyce granules, except for cosmetic removal of labial lesions if the individual wishes it. Inflamed glands can be treated topically with clindamycin. When surgically excised they will not recur. Neoplastic transformation is very rare but has been reported.

Epidemiology

This variation of normal anatomy is seen in the majority of adults. It is estimated about 80% of people have oral Fordyce spots, but seldom are granules found in large numbers. They are not usually visible in children, and tend to appear at about age 3, then increasing during puberty and become more obvious in later adulthood. They are more prominent in males. Examples reported in a cancer screening represent approximately 1% of adults.

History

They are named after an American dermatologist, John Addison Fordyce.