Research report: Melanin pigmented dentigerous cyst report of a case and review of relevant literature

Dentists and oral surgeons rarely encounter a jaw cyst that looks like tar, but a case reported in Discover Medicine describes exactly that. A 27-year-old Black man was referred to an oral surgeon for the evaluation of a radiolucent lesion in the posterior left maxilla, associated with an impacted left third molar, tooth #16, and a supernumerary tooth, #16A, in the universal numbering system. Computed tomography revealed a well-circumscribed, unilocular radiolucent lesion measuring 2.4 by 2.2 by 1.6 centimeters that projected into the alveolar recess of the left maxillary antrum. Based on the clinical and radiographic findings, the team suspected a dentigerous cyst, a cyst defined by its association with the crown of an unerupted, impacted or embedded tooth. The patient was admitted shortly thereafter and underwent surgical excision of the lesion, and his postoperative course was uneventful.

What happened during surgery set this case apart from the routine. The lesion, observed directly in the operative field, was black in color and appeared tar-like, an appearance that is decidedly abnormal for an odontogenic cyst. The surgical specimen measured 3.5 by 2.0 by 1.5 centimeters and consisted of the black-colored cystic lesion together with surrounding tissue, teeth and bone. Macroscopic photographs show the cyst attached to the cementoenamel junction of the supernumerary molar tooth, with black-brown pigmentation within the cyst lining and additional pigmented fragments of soft tissue and tooth #16 submitted for examination. Under the microscope, the cyst was lined by stratified squamous epithelium, and the fibromyxomatous cyst wall contained an infiltrate of lymphocytes and macrophages. The cyst lumen contained numerous slit-like cholesterol clefts, a feature that would prove central to the case’s most distinctive finding.

To characterize the mysterious pigment, the authors, Naomi Ramer, Chris Davlantes and Suchie Chawla, deployed a panel of histochemical and immunohistochemical stains on paraffin-embedded tissue. Masson-Fontana staining confirmed that the pigment within the lesion was melanin, revealing that the cystic lumen was filled with slit-like clefts containing melanin particles. Immunohistochemistry for S-100 revealed melanocytes within the cyst lining and dendritic cells within the cyst wall, while Melan-A staining independently demonstrated melanocytes within the epithelial cyst lining. A stain for HMB-45, a marker commonly used to identify immature or neoplastic melanocytes, was negative. CD68 immunostaining showed scant scattered macrophage positivity within the cyst lining and wall. The final diagnosis of a melanin-pigmented dentigerous cyst was rendered upon microscopic identification of melanin pigment that was also visible macroscopically.

The negative HMB-45 result carries its own interpretive weight. According to the authors, HMB-45 typically shows limited or absent reactivity in normal melanocytes and nevus cells, so the lack of reactivity in the spindle and dendritic cells observed in this case does not exclude a melanocytic origin. Instead, they argue, the pattern favors a benign population of melanocytes responsible for melanin production. The presence of melanocytes within the epithelial lining, confirmed by two independent immunostains, combined with the Masson-Fontana confirmation of melanin, provided converging lines of evidence for the diagnosis.

The localization of melanin within the cholesterol clefts of the cyst lumen was, according to the report, a unique and distinctive finding not shared by any of the other 68 reported pigmented odontogenic cysts and tumors. The authors propose that inflammation may have played a role in this localized pigmentation. Inflammation has been implicated as a potential stimulus for melanin deposition, as seen in postinflammatory pigmentary alterations, and inflammatory changes were evident in the fibrous cyst wall in the form of an infiltrate of macrophages and lymphocytes. The authors suggest that melanocytes within odontogenic lesions may remain inactive, similar to those present in clinically non-pigmented oral mucosa, but may become activated under certain conditions, leading to the synthesis of melanin. The pigment may then be transferred to adjacent epithelial cells, phagocytosed by macrophages within the connective tissue, or released into the cystic lumen.

To place the case in context, the team conducted a PubMed/Medline search using terms such as “pigmented odontogenic cysts,” “pigmented odontogenic neoplasms,” “pigmented odontogenic tumors” and “melanin pigmented odontogenic.” The search identified sixty-six manuscripts, whose abstracts and titles were read, and fifty-six were accepted for inclusion, with the references of each paper examined for additional publications. Combining this review with existing reviews of pigmented odontogenic lesions, the authors tallied 69 cases of melanin-pigmented odontogenic cysts and tumors reported to date, including the present case. Of these, 44 were pigmented odontogenic cysts: 23 calcifying odontogenic cysts, 10 odontogenic keratocysts, 5 dentigerous cysts, 2 botryoid odontogenic cysts, 2 lateral periodontal cysts, 1 gingival cyst and 1 other. A further 22 cases involved benign odontogenic tumors, and three melanin-pigmented odontogenic malignancies have also been described.

Within that landscape, the calcifying odontogenic cyst emerges as the most common pigmented odontogenic lesion, with 23 reported cases, two of which were the result of reclassification. Eight of those 23 cases were reported in association with odontoma. Thirteen of the calcifying odontogenic cysts involved the mandible and 10 the maxilla; fourteen patients were female and nine were male. Second in frequency was the uncommon presence of melanin in the odontogenic keratocyst, with 10 cases reported in the literature. Other pigmented odontogenic cysts include a gingival cyst, two botryoid odontogenic cysts and two lateral periodontal cysts, and in the majority of reported pigmented cysts the pigment was found in the cyst epithelial lining. Among the tumors, nine melanin-pigmented odontomas have been reported, along with four adenomatoid odontogenic tumors, two calcifying epithelial odontogenic tumors, two odontoameloblastomas, two dentinogenic ghost cell tumors, and one case each of ameloblastoma, ameloblastic fibroma and odontogenic fibroma, with several cases reclassified according to the 2022 WHO classification.

Dentigerous cysts themselves are the second most common odontogenic cysts after radicular cysts, yet melanin-pigmented examples are extraordinarily scarce. With the inclusion of the present case, only five melanin-pigmented dentigerous cysts have been reported to date, and three of the five involved the mandible. The current report therefore represents only the second documented case involving the maxilla. Two of the five dentigerous cysts, including the present case, presented with macroscopic pigmentation that led to the microscopic diagnosis; the other three presented with microscopic pigmentation and no macroscopic pigment. An additional case of a dentigerous cyst in association with an adenomatoid odontogenic tumor was reported in 1990, but the authors of the present study note that they were unable to exclude the possibility that this case may have represented an adenomatoid odontogenic tumor with a prominent cystic component. Overall, only 5.8 percent of the 69 pigmented odontogenic cysts and neoplasms reported to date presented as macroscopic pigmentation, meaning that grossly visible pigmentation prompting further histochemical and immunohistochemical evaluation remains exceptional.

The demographic pattern of reported cases has fueled debate about why melanin appears in these lesions at all. Sixty-six of the 69 cases disclosed data on the patient’s race, and most lesions, about 90 percent, were identified predominantly in Asian and Black patients. Six cases have been reported in Caucasian individuals, and an additional case involved a patient of mixed Caucasian and Asian descent, meaning that 9 percent of cases with available racial data occurred in Caucasian patients. The authors argue that this challenges the racial pigmentation theory and suggests that the pigmentation is not racially determined. Supporting a developmental explanation, Lawson and colleagues investigated the distribution of melanocytes in the dental primordium of human fetuses and identified melanocytes within the dental lamina and the outer enamel epithelium of the developing tooth bud in three of eleven White fetuses and in all six Black fetuses examined. These findings support the possibility that melanocytes may become incorporated into odontogenic tissues during development.

Several mechanisms have been proposed for how melanocytes arrive in odontogenic lesions. Melanocytes are dendritic cells of neural crest origin, and because pigmentation of the oral mucosa is relatively common and the dental lamina is derived from primitive oral epithelium, the occasional presence of melanin within odontogenic lesions is not unexpected. Some studies indicate that odontogenic tissues may possess the capacity for neuroectodermal differentiation under specific conditions, potentially giving rise to melanocytes, while others point to odontogenesis as a multifactorial process involving reciprocal interactions between oral epithelium and cranial neural crest-derived ectomesenchyme, from which melanocytes also originate. The rarity of the phenomenon is underscored by one study of 108 ameloblastoma cases in Black Africans in which only a single pigmented ameloblastoma was identified, a frequency of less than 1 percent even within that population. The origin of melanocytes in odontogenic cysts and tumors remains uncertain and continues to be debated, although melanocytes are recognized as a normal constituent of the oral epithelium. With this report, the fifth well-documented melanin-pigmented dentigerous cyst enters the English-language literature, distinguished by grossly visible pigmentation and melanin deposited within cholesterol clefts, a combination no other reported case has shown.

Subject of Research: A rare melanin-pigmented dentigerous cyst of the maxilla and a review of pigmented odontogenic cysts and tumors

Article Title: Melanin pigmented dentigerous cyst report of a case and review of relevant literature

Article References: Ramer, N., Davlantes, C., & Chawla, S. (2026). Melanin pigmented dentigerous cyst report of a case and review of relevant literature. Discover Medicine, 3(1), Article 158. https://doi.org/10.1007/s44337-026-00717-2

Image Credits: AI Generated

DOI: 10.1007/s44337-026-00717-2

Keywords: dentigerous cyst, melanin, odontogenic cysts, oral pathology, maxilla, case report, melanocytes, Masson-Fontana stain, immunohistochemistry, cholesterol clefts, neural crest, jaw lesion