Amelanotic melanoma of the palate: report of a case
- 1 Oral and Maxillofacial Pathology & Microbiology, Institute of Dental Sciences, Siksha 'O' Anusandhan deemed to be University, Bhubaneswar, Odisha, India
- 2 Oral Medicine & Radiology, Institute of Dental Sciences, Siksha 'O' Ansuandhan deemed to be University, Bhubaneswar, India
- Correspondence to Professor Neeta Mohanty; neetamohanty@soa.ac.in
Abstract
Primary amelanotic melanoma is an infrequent occurrence in the oral cavity. Owing to the high rate of local invasion and distant metastasis, oral amelanotic melanoma (OAM) carries a very poor prognosis. The absence of pathognomonic clinical and routine histological features in OAM is the reason for diagnosticdelay, which further worsens the prognosis. This case report discusses the masquerading nature of OAM that was clinically and histologically mimicking several malignant neoplasms. This case also demonstrates the poor prognosis of OAM. The objective of presenting this case is that the diagnostic delay of OAM can be avoided through enhanced clinical awareness and subsequent appropriate immunohistochemical investigations, in addition to the routine H&E-stained histopathological evaluation.
Background
Primary malignant mucosal melanoma is a rare malignant neoplasm of melanocytes or melanocytic precursors of basal layers.1 Head and neck represent the most common site (41%)2 in which oral malignant melanoma is the least frequent (0.2 per million per year).3 Amelanotic melanoma is the group of malignant melanoma that shows very few to the absence of melanin pigments on clinical and histopathological examination. Although the reported incidence of cutaneous amelanotic melanoma ranges from 2% to 8% of all melanomas, the actual incidence may exceed this figure owing to the frequent misdiagnosis.4 This may also hold good for oral amelanotic melanoma (OAM). To date, only fewer than 43 cases are described in the literature including the most recent analysis of clinicopathologic features of eight cases by Soares et al.5 The aggressiveness of OAM is associated with a propensity for rapid growth, a high incidence of local recurrence and distant metastasis. This case report discusses the clinicopathologic features and prognosis, which would not only reinforce the poor prognosis, but also provides epidemiological insight into OAM.
Case presentation
A 60-year-old well-built female patient presented with an ulceroproliferative growth in the palate having irregular undermined border, the size being approximately 1.5×2 cm in diameter (figure 1). The growth has been increasing in size for 4 months and there was a history of several visits to multiple dental surgeons. The lesion was soft to firm in consistency and non-tender on palpation. On careful examination, there was minimal macular pigmentation noticed on the periphery of the growth. Similar pigmentation was also noticed in the gingiva and buccal mucosa of the patient. Level 2 lymph node was tender on palpation but not fixed to the underlying connective tissue. The provisional diagnosis of minor salivary gland neoplasm was made. Malignant ulcer of the palatal mucosa and metastatic tumour were the differential diagnoses. The patient was sent for orthopantomograph and CT. The tumour was excised and sent for microscopic examination.
Ulceroproliferative lesion in the palate.
Investigations
Orthopantomograph did not show any contributory finding and the patient could not afford to get the CT done. Microscopic evaluation of the tissue section stained with H&E-evidenced pleomorphic hyperchromatic spindle and epithelioid cells infiltrated in the connective tissue stroma in organoid manner (figure 2). Multiple sections were evaluated to rule out melanoma. Several histopathological provisional diagnoses such as poorly differentiated squamous cell carcinoma, sarcoma, lymphoma and amelanotic melanoma were committed because of lack of melanin. Immunohistochemistry was done with a panel of markers. Pan cytokeratin, epithelial membrane antigen, CD45 and desmin were negative, which ruled out carcinoma, lymphoma and sarcoma, respectively. The tumour cells were strongly positive for Human Melanoma Black 45 (HMB-45) in the cytoplasm (figure 3) and S-100 in the nucleus. These immunohistochemical findings confirmed the diagnosis of amelanotic melanoma of the palate.
Photomicrograph of H&E-stained section (×10) showing pleomorphic spindle cells.
Photomicrograph (×10) of section-stained positive with cytoplasmic Immunohistochemistry marker Human Melanoma Black 45.
Outcome and follow-up
The patient denied undergoing any treatment. After 9 months of the diagnosis, the patient developed brain metastasis followed by death due to a cerebrovascular accident.
Discussion
By virtue of minimal or absence of pigmentation, OAM possesses diagnostic challenges. This report presents a case of OAM encountering such diagnostic challenges and discusses the clinicopathologic features and fatal outcomes in light of similar reported cases.
Owing to the difference in risk factors, the pathogenesis of OAM may not be related to that of cutaneous melanoma. Differences in the molecular mechanisms such as infrequent BRAFV600E 6 and frequent c-KIT mutations7 in mucosal melanoma as opposed to cutaneous melanoma have been suggested. In the process of the development from stage 1 to stage 4, melanosomes of the melanocytes acquire melanin pigments in stage 3. Therefore, amelanotic melanoma may contain melanosomes at stages 1 and 2.
Although there are many analyses on cutaneous amelanotic melanoma, clinicopathologic features of OAM has been discussed in only two articles.5 8 While Soares et al 5 reported male predilection, Adisa et al in 20128 mentioned minimal gender variation. Gingiva was found to be the most common location.5 The female patient and palatal location in this case was contradicting Soares’s findings. Because of the diverse microscopical structures in H&E-stained sections, OAM has been correctly referred to as the ‘great pretender’. According to the review by Soares et al,5 epithelioid and spindle cells are predominant findings, which are also the predominant microscopic features in this case. An array of lesions such as malignant fibrous histiocytoma,9 poorly differentiated squamous cell carcinoma,10 schwannoma11 and spindle cell carcinoma are the differential diagnoses in routine H&E staining. Despite the presence of mild pigmentation during the clinical examination the present case did not demonstrate any pigments in the H&E-stained multiple tissue sections. Immunohistochemistry with a panel of markers was found to be a valuable, advanced, diagnostic tool in diagnosing this case. HMB-45, S-100 and Melan A are the most frequently used to differentiate amelanotic melanoma from other atypical neoplasms.12 Lack of sensitivity of HMB-45 and lack of specificity of S-10012 made us use both antibodies for confirmation of diagnosis. Both HMB-45 and S-100 were found to be positive in the cases reviewed and reported by Soares et al.5 Localisation of HMB-45 in stage 2 melanosomes and detection of melanosomal glycoprotein gp100 by anti HMB-45 antibody may suggest the stage-wise transformation of the amelanotic phenotype of melanocytes where melanosomes of the melanocytes would acquire melanin pigments only in stage 3.
The survival of 9 months in this case is consistent with Soares et al who reported death in five of eight patients a few months after the initial consultation.5 On analysing 27 cases of OAM, distant metastasis was found in 55% of cases mostly to the liver, brain and lungs.13 Unlike prognostic features in cutaneous melanoma such as depth and level of invasion, lymphatic metastasis at the time of clinical presentation may be a good adverse prognostic factor for OAM.14 Presentation of such case reports is essential, which helps dental surgeons consider amelanotic melanoma while committing a differential diagnosis of proliferative oral lesions. Early diagnosis followed by routine and advanced histological staining is the key to improve the prognosis in such patients.
Learning points
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Mortality in oral amelanotic melanoma is poorer compared with the melanotic melanoma mostly attributed to the diagnostic delay.
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It is important to include the amelanotic melanoma in the differential diagnosis of oral ulceroproliferative growth and careful observation for pigmentation surrounding the lesion is required.
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Combined immunohistochemistry of Human Melanoma Black 45 and S-100 is advised to rule out amelanotic melanoma.
Ethics statements
Patient consent for publication
Footnotes
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Contributors SRM examined the patient. NM and SC performed the investigations. SP prepared the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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