Disorders of Oral Pigmentation Workup

Updated: Jan 21, 2021
  • Author: Leticia Ferreira, DDS, MS; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Laboratory Studies

In Peutz-Jeghers syndrome (PJS), a complete blood cell count should be obtained because the polyps may be a source of blood loss.

For amalgam tattoos, a periapical radiograph reveals the presence of the amalgam.

The only study effective for diagnosing oral malignant melanoma (OMM) is tissue biopsy. A biopsy should be performed on any otherwise unexplained lesions.

To avoid iatrogenic pigmentations, eliminate the causes (eg, smoking, sun exposure).


Imaging Studies

Peutz-Jeghers syndrome

An enteroclysis study (preferred) and dedicated small bowel follow-through radiography are used to determine the presence and the location of small intestinal polyps.

Amalgam tattoos

These lesions can be seen on radiographs, which quickly verify the histologic findings.

Nevi and melanoma

Imaging studies are not required for oral nevi, with the exception of clinical photographs for documentation. However, contrast-enhanced CT scanning is required to determine the extent of the melanoma and whether local, regional, or lymph node metastasis is present.

Studies such as bone scanning with a gadolinium-based agent or chest radiography can be beneficial in assessing metastasis of melanoma.

MRI may be used to diagnose melanoma in soft tissue. Atypical intensity is correlated with the amount of intracytoplasmic melanin. On T1-weighted images, such melanomas are hypointense. On T2-weighted images, such melanomas are hyperintense and show increased melanin production. To the authors' knowledge, oral melanomas have not been assessed in this manner.

Positron-emission tomography has poor results in distinguishing melanoma from nevi. However, combined positron-emission tomography and CT scanning may have diagnostic value. Surgical lymph node harvesting depends on the identification of positive nodes after clinical or imaging examination.

Iatrogenic pigmented lesions

Iatrogenic pigmented lesions do not require any laboratory tests except photographs for documentation.


Other Tests

Periapical radiographs are helpful to verify the presence of an amalgam tattoo.



Peutz-Jeghers syndrome

An esophagogastroduodenoscopy and a colonoscopy may be performed.

Hemorrhagic or large polyps (>5 mm) should be removed by endoscopic polypectomy to confirm the diagnosis and to help control symptoms.

Laparotomy and resection should be performed for repeated or persistent small intestinal intussusception or obstruction or for persistent intestinal bleeding.


A pigmented lesion in the oral cavity always suggests OMM. Any pigmented lesion of the oral cavity for which no direct cause can be found requires biopsy.

Sentinel node biopsy or lymphoscintigraphy, which is beneficial in the staging of cutaneous melanoma, has little value in staging or treating oral melanoma. Complex drainage patterns may result in the bypass of some first-order nodes and in the occurrence of metastasis in contralateral nodes.


Histologic Findings

The characteristic pathologic finding of the pigmentation seen in the PJS is basilar hyperpigmentation.

Although any of the features of cutaneous malignancy can be found, most oral melanomas have characteristics of the acral lentiginous (mucosal lentiginous) and, occasionally, superficial spreading types. The malignant cells often nest or cluster in groups in an organoid fashion; however, single cells can predominate. The melanoma cells may have large nuclei, often with prominent nucleoli, and they have nuclear pseudoinclusions due to irregularity of the nuclear membrane. The abundant cytoplasm may be uniformly eosinophilic or optically clear. Occasionally, the cells become spindled or neurotize in areas.

Melanomas have a number of histopathologic mimics, including poorly differentiated carcinomas and anaplastic large cell lymphomas. Differentiation requires the use of immunohistochemical techniques to highlight intermediate filaments or antigens specific for a particular cell line. Leukocyte common antigen and Ki-1 are used to identify the lymphocytic lesions. Cytokeratin markers, often cocktails of high- and low-molecular–weight cytokeratins, can be used to help in the identification of epithelial malignancies.

S-100 protein and homatropine methylbromide (HMB-45) antigen positivity are characteristic of, although not specific for, melanoma. S-100 protein is frequently used to highlight the spindled, more neural-appearing melanocytes, whereas HMB-45 is used to identify the round cells. Melanomas, unlike epithelial lesions, are identified using vimentin, a marker of mesenchymal cells.

Microphthalmic transcription factor, tyrosinase, and melano-A immunostains have been used to highlight melanocytes. The inclusion of these stains in a panel of stains for melanoma may be beneficial.



The American Joint Committee on Cancer does not have published guidelines for the staging of OMMs. Most practitioners use general clinical stages in the assessment of oral mucosal melanoma, as follows:

  • Stage I - Localized disease

  • Stage II - Regional lymph node metastasis

  • Stage III - Distant metastasis

Tumor thickness and lymph node metastasis are reliable prognostic indicators. Lesions thinner than 0.75 mm rarely metastasize, but they do have metastatic potential. On occasion, a small primary lesion is discovered after an enlarged lymph node is found to harbor melanoma.