Pigmented Lesions
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ADDISON'S DISEASE
Addison’s Disease (primary adrenal insufficiency) is a rare autoimmune endocrine disorder that leads to improper steroid hormone production. Recall, cortisol and aldosterone are fabricated in the adrenal cortex. Secondary adrenal insufficiency is caused by decreased production of adrenocorticotropic hormone (pituitary gland) or corticotropin-releasing hormone (hypothalamus). When stressed an inadequate production of adrenal hormones may lead to a potentially serious medical emergency (adrenal crisis). Adrenal insufficiency may also be triggered by infection (tuberculosis, histoplasmosis, coccidioidomycosis), medications (ketoconazole, rifampicin, phenytoin), sepsis, or trauma to the adrenal glands. Visual changes to the skin and oral mucosa are due to secondary melanocyte stimulation by increased levels of adrenocorticotropic hormone (ACTH) or β-lipotropin. The common clinical presentation includes:
- Brown macular pigmentation is usually seen in association with cutaneous bronzing.
- Weakness, weight loss, salt craving, nausea, vomiting, and hypotension.
- May cause behavioral changes (e.g. anxiety, depression, irritability).
Addison’s disease is confirmed using serological testing. Adrenal hormone levels will remain low after stimulation with synthetic ACTH. Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include melanosis visible within mucosa biopsy. Your differential diagnosis should include:
- Smoker’s melanosis.
- Normal ethnic pigmentation.
- Heavy metal deposition/argyrosis or amalgam tattoo.
- Drug-induced pigmentation.
- Peutz-Jeghers syndrome.
Treatment options include:
- Management of underlying adrenal insufficiency.
- Corticosteroid replacement therapy.
- Steroid cover may be required to prevent adrenal crisis.
AMALGAM TATTOO
Amalgam Tattoo refers to the discoloration seen in oral tissues where dental amalgam has been deposited. The common clinical presentation includes:
- Well differentiated gray, blue or black focal macule.
- Asymptomatic lesions with no indication of associated inflammation.
- May be visible radiographically.
Diagnosis is based on the lesion history, clinical presentation, and radiographic analysis only. If biopsied, microscopic findings may include:
- Fragments of metal within connective tissue.
- Metal staining of reticulin fibers.
- Particles may be surrounded by fibrous tissue.
- Granulomatous inflammation with a mixture of lymphocytes and plasma cells.
Your differential diagnosis should include:
- Melanoma.
- Vascular malformation.
- Nevus.
- Mucosal melanotic macule.
- Melanoacanthoma.
No treatment is required.
DRUG-INDUCED PIGMENTATION
Drug-induced pigmentation is a form of abnormal mucosal pigmentation that can be caused by several drugs, including cytotoxic agents, analgesics, anticoagulants, antimicrobials, antiretrovirals, metals, and antiarrhythmic. Pigmentation is caused by the accumulation of melanin, synthesis of new pigment (lipofuscin), or accumulation of iron (minocycline). The common clinical presentation includes:
- Macular mucosal discoloration (brown, gray, black).
- Most commonly seen on the palate and gingiva.
- Some medications can cause the discoloration of teeth (minocycline/tetracycline).
Diagnosis is based on the lesion history and clinical presentation only. Your differential diagnosis should include:
- Physiologic pigmentation.
- Smoker’s melanosis.
- Mucosal melanotic macule.
No treatment is required.
MELANOACANTHOMA
Melanoacanthoma is a rare but surprisingly fast growing cutaneous tumor presenting as a deeply pigmented benign proliferation of dendritic melanocytes and keratinocytes, usually associated with local trauma. The common clinical presentation includes:
- Smooth dark melanotic macules or slightly raised papules.
- Brown to blue-black.
- Most common in non-Caucasian patients and more common in women.
- History of trauma and/or local irritation.
- Can grow rapidly.
- Most commonly found on the buccal or labial mucosa.
- Asymptomatic.
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Scattered dendritic melanocytes within spongiotic and acanthotic epithelium.
- Increased number of melanocytes along basal layer.
Your differential diagnosis should include:
- Melanoma.
- Drug-induced pigmentation.
- Smoker’s melanosis.
- Mucosal melanotic macule.
- Nevus.
- Amalgam tattoo.
No treatment is required. Elimination of all local irritating factors should lead to lesion resolution.
MELANOMA
Melanoma refers to a highly aggressive tumor that develops from cutaneous melanocytes derived from the neural crest cells in the basal layer of the epithelium. Oral malignant melanoma is an extremely rare malignancy. It has a higher tendency to metastasize to underlying tissues and a relatively low (<20%) 5 year survival rate. Risk factors for mucosal malignant melanoma include alcohol consumption, tobacco use, and denture irritation. The common clinical presentation includes:
- Early lesion – pigmented macular patch with irregular borders.
- Mature lesion – deeply pigmented nodular lesion with possible ulceration.
- Usually seen on the maxillary gingiva and hard palate.
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Atypical melanocytes (hyperchromatism and nuclear pleomorphism)
- Advanced lesions may include infiltration into lamina propria and muscle.
- Positive immunohistochemical markers (S-100, HMB-45, fatty acid synthase).
Your differential diagnosis should include:
- Mucosal nevus.
- Normal physiological pigmentation.
- Melanoacanthoma.
- Kaposi’s sarcoma.
- Vascular malformation.
- Amalgam tattoo.
- Mucosal melanotic macule.
Treatment options include:
- Surgical excision (wide margin).
- Neck dissection in cases of deep invasion.
MELANOTIC MACULES
Mucosal Melanotic Macules (ephelides, freckles) may be seen in a broad range of conditions ranging from physiologic pigmentation to a sign of an underlying life-threatening disease. Most are idiopathic. Isolated lesions may be drug-induced or linked to inflammation. Multiple/widespread lesions suggest a systemic condition like Peutz-Jeghers syndrome, Laugier-Hunziker syndrome, Carney’s syndrome, or LEOPARD syndrome. The common clinical presentation includes:
- Small (<5mm), well circumscribed solitary macules with slight border irregularity.
- Brown, uniformly pigmented, round to ovoid shape.
- Most commonly seen on the lower lip vermilion border.
- May be seen on the buccal mucosa, palate, and attached gingiva.
Diagnosis is based on the lesion history and clinical presentation only. If biopsied, microscopic findings may include:
- Normal melanocyte density and morphology.
- Increased melanin in basal cells and subjacent macrophages.
- Elongated rete pegs.
Your differential diagnosis should include:
- Melanoacanthoma.
- Congenital syndromes (Carney’s, Peutz-Jeghers, LEOPARD, Laugier-Hunziker).
- Melanoma.
- Addison’s disease.
No treatment is required though these may be removed to rule out malignant melanoma or to improve aesthetics.
NEVUS
A nevus (mole, beauty mark) is a nonspecific medical term that describes melanocytic hyperplasia. Oral nevi are uncommon benign melanocytic neoplasms involving oral mucosa that share histological similarities to their cutaneous counterparts. The common clinical presentation includes:
- Elevated, symmetric, pigmented papule.
- Pigmentation is usually uniformly distributed.
- Though they are commonly found on skin they are rare intraorally.
- Most commonly seen on the palate and gingiva.
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Blue nevi are deeply situated and are composed of spindled nevus cells.
- Nevus cells found in unencapsulated nests (theques).
- Variable melanin production.
Your differential diagnosis should include:
- Melanoma.
- Varices.
- Amalgam tattoo
- Mucosal melanotic macule.
- Kaposi’s sarcoma.
- Traumatic lesion (Ecchymosis).
- Melanoacanthoma.
Treatment usually involves surgical excision to rule out malignant melanoma.
