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Year : 2022  |  Volume : 18  |  Issue : 3  |  Page : 849-852

Metastatic malignant melanoma: A case of metastasis from foot to mandibular anterior region

1 Department of Oral Medicine and Radiology, Rural Dental College, Pravara Institute of Medical Sciences, Loni, Maharashtra, India
2 Department of Pathology, Rural Medical College, Pravara Institute of Medical Sciences, Loni, Maharashtra, India
3 Department of Oral Medicine and Radiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India

Date of Submission14-Aug-2020
Date of Decision28-Sep-2020
Date of Acceptance12-Jan-2021
Date of Web Publication25-Jul-2022

Correspondence Address:
Anita D Munde
Department of Oral Medicine and Radiology, Rural Dental College, Pravara Institute of Medical Sciences, Loni, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1123_20

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 > Abstract 

Metastatic malignant melanoma (MMM) of the oral cavity is extremely rare which generally presents in the setting of disseminated disease and have extremely poor prognosis. The most common site for MMM in the oral cavity is tongue followed by buccal mucosa for soft-tissue lesions and posterior mandible for bone involving lesions. Primary tumor sites of oral MMM are usually cutaneous lesions of the trunk, head and neck, limbs, and nasal septum mucosa. Patients bearing this diagnosis face median survival time of approximately 9 months with a probability of surviving 5 years after the initial presentation is <5%; hence, an early detection and treatment for the primary and metastatic lesion is crucial. Here, we present an unusual case of MMM of oral cavity involving gingiva and alveolar bone of the mandibular anterior region metastasizing from a primary lesion on the foot.

Keywords: Anterior mandible, foot, malignant melanoma, metastasis, oral cavity

How to cite this article:
Munde AD, Karle RR, Biradar S, Mishra S. Metastatic malignant melanoma: A case of metastasis from foot to mandibular anterior region. J Can Res Ther 2022;18:849-52

How to cite this URL:
Munde AD, Karle RR, Biradar S, Mishra S. Metastatic malignant melanoma: A case of metastasis from foot to mandibular anterior region. J Can Res Ther [serial online] 2022 [cited 2022 Oct 1];18:849-52. Available from: https://www.cancerjournal.net/text.asp?2022/18/3/849/348226

 > Introduction Top

Malignant melanoma (MM) arises from the uncontrolled growth of melanocytes, which are pigmented cells found in the basal layer of the epidermis and oral mucous membrane. Primary MM of the oral cavity is an uncommon tumor. Its actual incidence in the population at present is unknown but is estimated to vary widely between 0.2% and 8% of all melanomas and 1.3% of all cancers.[1],[2] It has a higher prevalence in Blacks, Japanese, and Indians of Asia due to more frequent finding of melanin pigmentation in oral mucosa of these races. These are mostly asymptomatic and detected only when there is ulceration or hemorrhage of the overlying epithelium. The delayed detection may be the cause for the poor prognosis with a 5-year survival being between 10% and 25%.[1],[2],[3]

MM may metastasize to any organ. The most common sites are lymph nodes, lungs, and liver with widespread involvement occurring in advanced disease.[4] Metastatic or secondary metastatic MM (MMM) of the oral cavity, which is an extremely rare tumor, occurs due to metastasis from distant sites. The most common site for MMM in the oral cavity is tongue followed by buccal mucosa, gingiva for soft-tissue lesions, and posterior mandible for bone invading lesions. Primary tumor sites of oral MMM are usually the skin of the trunk, skin of the head and neck, skin of the limbs, and nasal septum mucosa. Patients with MMM are known to have a very poor prognosis and hence an early detection and treatment for the primary and metastatic lesion are crucial.[3],[4] Here, we present an extremely rare case of MMM of gingiva and alveolar bone of the mandibular anterior region in a 50-year-male in whom the primary lesion was situated on the sole of the right foot.

 > Case Report Top

A 50-year-old male patient reported with a complaint of a gingival swelling in the lower anterior region for the past 6 months. Initially, the patient noticed a small grain-sized reddish-black growth in the mandibular anterior gingivae, which gradually progressed to attain the present size. He noticed bleeding from the lesion and experienced pain during biting. The patient was a chronic bidi smoker. He has given a history of growth on the sole of his right foot for 4 years, which was operated twice. The last surgery was done approximately 1 year back. In spite of the surgery, the growth continued to grow to attain the present size. Previous histopathological reports of these surgeries were not available.

On general examination, the patient was moderately built, showed a large exophytic growth on the sole of the right foot approximately 13 cm × 8 cm with color variegations blackish, bluish, and reddish [Figure 1]a. On palpation, it was firm, nontender and borders were indurated. Two right inguinal nodes were enlarged, fixed, and nontender. Intraoral examination revealed a well-defined proliferative growth of gingiva and alveolar mucosa in the lower anterior region on the labial aspect, of approximately size 3 cm × 3 cm with same color variations as seen on the foot lesion. The lesion was extending from mandibular left canine to the right lateral incisor region. The overlying mucosa was irregular and lobulated [Figure 1]b. The lesion was soft and nontender. There was Grade 3 mobility with lower central incisors, Grade 2 with the lateral incisors, and Grade 1 mobility with canines. Bilateral submandibular lymph nodes, one on each side and one submental lymph node, of 1 cm × 1 cm in size, were palpable. These nodes were firm, mobile, and tender. Considering the lesion on the right foot as a primary lesion, a provisional diagnosis of metastatic tumor such as melanoma was made. Lymphoma and squamous cell carcinoma were considered in the differential diagnosis.
Figure 1: (a) Lesion on the foot. (b) Lesion in the oral cavity

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Radiographic examination for oral lesion as well as foot lesion was done. Intraoral periapical radiographs with the lower anterior region, mandibular occlusal radiograph, and orthopantomagram showed alveolar bone destruction with both central incisors and periodontal space widening with lateral incisors and right central incisor suggesting an invasion by the tumor [Figure 2]a, [Figure 2]b, [Figure 2]c. Slight erosion of bone was evident in the foot lesion [Figure 3]a. Ultrasonography of the abdomen pelvis revealed a normal study. Chest X-ray revealed no definitive evidence of the secondaries and changes of bronchitis was seen with both the lung fields [Figure 3]b. Incisonal biopsy for both the lesions and fine-needle aspiration cytology (FNAC) for the inguinal node was performed. Histopathological report of the foot lesion showed tumor composed of cells arranged in nests, sheets and lobules separated by thin fibrocollagenous septa. The tumor cells were round to oval with round to oval nucleus with coarsely clumped chromatin and 1–2 prominent nucleoli and scanty cytoplasm. The cells contained coarsely granular black (melanin) pigment. The stroma was scanty and showed infiltration by these tumor cells. These histopathological features were consistent with MM [Figure 4]a. The incisional biopsy of the oral lesion also showed similar features [Figure 5]a and [Figure 5]b. Immunohistochemical studies (HMB 45 stain) for the oral lesion confirmed the diagnosis of MM [Figure 6]. FNAC report also revealed features suggestive of metastatic melanoma [Figure 4]b. Thus, our case satisfied the criteria for a metastatic malignant lesion as defined by Clausen and Poulsen in 1963: the location and histology of the primary tumor must be known, The metastatic diagnosis has to be confirmed by histological studies, no invasion by contiguity, and no oral primary location.[5] The patient was referred to an oncology center for the management, where he was advised six cycles of chemotherapy and immunotherapy (dacarbazine [DTIC] and interferon-α). The patient received only two cycles of the therapy and was lost for follow-up.
Figure 2: (a) Intaoral periapical radiograph, (b)occlusal radiograph, (c)panoramic radiograph

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Figure 3: (a and b) Radiograph of the foot lesion, chest X-ray

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Figure 4: (a)Histopathological features of the foot lesion (high power) and (b) FNAC features of inguinal node

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Figure 5: Histopathological features of the oral lesion, (a) low and (b) high power

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Figure 6: HMB 45 stain (×40)

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 > Discussion Top

Metastatic tumors to the oral region are uncommon comprising only 1%–3% of all malignant oral tumors. Most metastatic tumors to the oral region were seen in patients in their fifth to seventh decade. Metastatic lesions may occur in the oral soft tissues or jawbones or both. They have mostly been found in the jaws compared to the soft tissues. Metastasis to the jawbones mainly occurs in the posterior region of the mandible, ramus, and the condyle, which are rich in red bone marrow. The most common sites for primary tumors, metastatic to the oral cavity are breast, lungs, kidneys, and thyroid.[6],[7] These metastatic tumors are of great clinical significance as their appearance may be the first indication of an undiagnosed malignancy at a distant primary site or the first evidence of dissemination of a known primary tumor.

MM may metastasize to any organ, the most common sites are the lymph nodes, lungs, liver, and brain with a widespread involvement occurring in advanced disease.[3],[4] Metastatic melanomas to the oral cavity, however, are extremely rare. The primary tumor sites for oral MMM, in a retrospective study of 15 cases of MMM of the oral cavity, were cutaneous lesions of the trunk, head and neck, limbs, and nasal mucosa. The most common sites of metastasis for MMM in the oral cavity include the tongue, buccal mucosa, gingiva, followed by the lip, mandible, maxilla, and alveolar mucosa.[3] In our case, the primary tumor was present on the sole of the right foot and site for metastatic lesion was gingiva and alveolar bone in the mandibular anterior region, both are rare sites. The earliest manifestation of gingival metastases resembles a hyperplastic or reactive lesion such as pyogenic granuloma, peripheral giant cell granuloma, or fibrous epulis,[7] as in the present case. On the radiographic examination, metastatic lesions mostly appear as a radiolucent area with ill-defined borders.

MM metastasizes through lymphatic and vascular channels. In general, cutaneous melanomas spread to four main lymph nodes, i.e., intraparotid, cervical, axillary and ilioinguinal nodes. Primary cutaneous MM of the head, neck, and trunk often develop cervical lymph node metastasis.[4] Retrograde spread from cervical lymph node metastasis was thought to result in secondary upper aerodigestive tract involvement in a study of 54 cases of MM by Henderson et al. Oral MM lesions may also result from hematogenous dissemination through the systemic circulation or Batson's venous plexus.[8] In the present case, apart from the primary and secondary sites, lymph nodes were involved by the tumor and no internal organs were involved as proved by investigations. Thus, the pattern of metastasis in the present case is more in favor of lymphatic rather than hematogenous spread.

Patients with MMM are known to have a very poor prognosis. Median survival times after metastasis are reported at 4.7–8.6 months, with a 5-year survival rate of 3%–12.5%.[9],[10] The interval from primary tumor diagnosis to the clinical recognition of metastatic spread in the mandible ranged from 5 months to 40.8 years (median, 3.2 years). Survival from primary tumor diagnosis ranged from 7 months to 42 years (average, 7 years). Survival from oral metastasis diagnosis ranged from 2 days to 28 months (average 9 months) for 6-month and 1-year survival of 48% and 36%, respectively).[10]

Factors that are significant in predicting worse disease-specific survival includes high clinical stage at presentation, tumor thickness >5 mm, the presence of vascular invasion, absence of melanosis, and development of nodal and distant metastases. Conventionally, wide surgical excision with adequate negative margins with or without neck dissection is the treatment of choice for MM, with radiotherapy and chemotherapy as adjunctive treatment methods. Chemotherapy and immunotherapy may play a role in the treatment of disseminated melanomas. DTIC and interferon-alpha-2b are used, with the first line of drug being DTIC, alone or in combination with nimustine hydrochloride and vincristine, or in different combinations of BCG and recombinant interleukin-2.[1],[2]

The most effective treatments for metastatic melanoma to date are the immune checkpoint inhibitors (ICIs), which are novel therapeutic agents and have revolutionized the treatment of advanced melanoma and many other cancers. Tumor cells can evade destruction by the immune system by triggering ICIs, such as cytotoxic T-lymphocyte–associated protein 4, programmed cell death protein 1 or programmed death-ligand1, that are expressed on T-cells and whose engagement inhibit T-lymphocyte function. ICIs are monoclonal antibodies that prevent this immunosuppression by blocking the engagement of these checkpoint molecules, thereby reinvigorating the antitumor immune response leading to improved survival and durable responses in patients.[11] Combination ICI therapy with ipilimumab and nivolumab in metastatic melanoma has led to a 5-year survival rate of 52% and 56% respectively, by Larkin et al. and Corrie et al.[12],[13] compared with <25% before the availability of ICIs.

In a comprehensive literature review of melanoma metastasis to the mandible by Cervenka et al., 31 cases were included from 1941 to 2017. Out of these, only in four cases, primary melanoma was situated on foot and only in four cases lower anterior region of the mandible was the site of metastasis.[10] Thus, the foot was the rare site for primary melanoma and also lower anterior region was rare site for metastatic melanoma. Hence, the present case is an extremely rare presentation of MMM, where both the sites, for primary as well as metastatic lesions are rare. No such similar case, where MMM in the mandibular anterior region is metastasized from a primary MM on the foot, is reported in the literature.

Due to its rarity and deceiving clinical presentation, the diagnosis of a metastatic lesion in the oral cavity is challenging both to the clinician and to the pathologist, in recognizing that a lesion is metastatic and in determining the site of origin. MMM of the oral cavity is extremely rare which generally presents in the setting of disseminated disease and have extremely poor prognosis. Therefore, careful examination of the head and neck including the oral cavity should be part of the routine follow-up examination in all melanoma patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Bhullar RP, Bhullar A, Vanaki SS, Puranik RS, Sudhakara M, Kamat MS. Primary melanoma of oral mucosa: A case report and review of literature. Dent Res J (Isfahan) 2012;9:353-6.  Back to cited text no. 1
Munde A, Juvekar MV, Karle RR, Wankhede P. Malignant melanoma of the oral cavity: Report of two cases. Contemp Clin Dent 2014;5:227-30.  Back to cited text no. 2
[PUBMED]  [Full text]  
Patton LL, Brahim JS, Baker AR. Metastatic malignant melanoma of the oral cavity. A retrospective study. Oral Surg Oral Med Oral Pathol 1994;78:51-6.  Back to cited text no. 3
Patel JK, Didolkar MS, Pickren JW, Moore RH. Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 1978;135:807-10.  Back to cited text no. 4
Clausen F, Paulsen H. Metastatic carcinoma to the jaws. Acta Pathol Microbiol Scand 1963;57:361-74.  Back to cited text no. 5
Irani S. Metastasis to the jaw bones: A review of 453 cases. J Int Soc Prev Community Dent 2017;7:71-81  Back to cited text no. 6
Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R. Metastatic tumours to the oral cavity-Pathogenesis and analysis of 673 cases. Oral Oncol 2008;44:743-52.  Back to cited text no. 7
Henderson LT, Robbins KT, Weitzner S. Upper aerodigestive tract metastases in disseminated malignant melanoma. Arch Otolaryngol Head Neck Surg 1986;112:659-63.  Back to cited text no. 8
Kim S, Morinière S, Beutter P, Samimi M, Rousselot C, Bakhos D. Metastatic melanoma to the oropharynx. Rev Laryngol Otol Rhinol (Bord) 2011;132:237-9.  Back to cited text no. 9
Cervenka PD, Perez L Jr, Perez DE, Jones B. Melanoma metastasis to the mandible-case report and comprehensive literature review. J Oral Maxillofac Surg 2017;75:2025.  Back to cited text no. 10
Megan EH, Samuel DS, Alexandra PS. Immune checkpoint inhibitors in cancer immunotherapy. CMAJ 2020;192:E651.  Back to cited text no. 11
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2019;381:1535-46.  Back to cited text no. 12
Corrie PG, Chao D, Board R, Sarah L, Smittenaar R. Metastatic melanoma outcomes since introduction of clinical outcomes check point inhibitors in England between 2014 and 2018. Journal of Clinical Oncology 2020 38:5_suppl, 55-55.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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