Indian Journal of Dermatology
: 2022  |  Volume : 67  |  Issue : 5  |  Page : 627-

Metastatic melanoma with an unknown primary

Anuradha Kakkanatt Babu1, Z Mizaj1, Vaishnavi Gowda1, Ameena Jaleel1, Nita Mary John2, Shagos Gopalan Nair Santhamma3, Soumya John4,  
1 Department of Dermatology, Aster Medcity, Cheranalloor, Kochi, Kerala, India
2 Department of Pathology, Aster Medcity, Cheranalloor, Kochi, Kerala, India
3 Department of Nuclear Medicine, Aster Medcity, Cheranalloor, Kochi, Kerala, India
4 Department of General Surgery, Aster Medcity, Cheranalloor, Kochi, Kerala, India

Correspondence Address:
Anuradha Kakkanatt Babu
Department of Dermatology, Aster Medcity, Cheranalloor, Kochi, Kerala

How to cite this article:
Babu AK, Mizaj Z, Gowda V, Jaleel A, John NM, Nair Santhamma SG, John S. Metastatic melanoma with an unknown primary.Indian J Dermatol 2022;67:627-627

How to cite this URL:
Babu AK, Mizaj Z, Gowda V, Jaleel A, John NM, Nair Santhamma SG, John S. Metastatic melanoma with an unknown primary. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 28 ];67:627-627
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Full Text


Melanoma with an unknown primary (MUP) is a metastatic melanoma with an occult primary site.

A 73-year-old lady presented with multiple asymptomatic skin-coloured and hyper-pigmented swellings on the right lower limb. These appeared 9 months back and gradually increased in size. Her general and systemic examinations were within normal limits except for multiple enlarged firm lymph nodes in the right inguinal region. On local examination, there were multiple hyper-pigmented nodules, a few with central erosion and crusting on the right leg [Figure 1]a, [Figure 1]b, [Figure 1]c and a firm skin-coloured swelling of 5 cm × 5 cm size on the medial aspect of the right popliteal fossa [Figure 2]. We considered the differential diagnoses of sporotrichosis, chromoblastomycosis, atypical mycobacterial infection, and cutaneous metastasis from an unknown primary. Routine blood investigations were within normal limits. A biopsy was performed from a nodule on the right leg. Histopathological examination revealed a neoplasm in the dermis, with no continuity with the epidermis, composed of lobules of cells with neoplastic cells arranged in sheets. The cells had a moderate amount of eosinophilic cytoplasm and a pleomorphic vesicular/hyper-chromatic nucleus, many with a prominent nucleolus. Frequent mitotic figures were seen. These histopathological features were consistent with malignant melanoma (metastatic/primary) [Figure 3]a, [Figure 3]b, [Figure 3]c. Immunohistochemistry was positive for S100, Melan-A, and HMB-45 and negative for CK (AE1/AE3) and GATA-3 [Figure 4]a, [Figure 4]b, [Figure 4]c, [Figure 4]d, [Figure 4]e. The PDL1 positive tumour cell percentage was 3. A fluorodeoxy glucose (FDG) positron emission tomography (PET) scan showed metabolically active metastatic deposits in soft tissues and lymph nodes metastatic predominantly along the medial aspect of the right lower limb along the lymphatic chain from the inguinal region to the ankle as well as the medial aspect of the left upper arm. Multiple FDG avid lymph nodes were also seen in the right upper paratracheal, right inguinofemoral, and intermuscular plane in the right thigh. In addition, metabolically active metastatic deposits were also noted in the lungs, pancreatic tail, and right lower anterior abdominal wall and both lobes of the bulky thyroid gland [Figure 5]. On clinical examination, there was neither any hyper-pigmented macule, papule, or nodule in the skin or mucosae (ocular, oral, and anogenital) suspicious of a primary melanoma nor any history of regression or removal of such a lesion. Hence, a final diagnosis of metastatic MUP was made, and she was referred to the oncology department for expert management.{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}

MUP is defined as the histologically established presence of melanoma in a lymph node, a visceral organ, or remote skin/subcutaneous tissues in the absence of a clinical history or associated evidence of a cutaneous, mucosal, or ocular primary lesion.[1] It has been postulated that primary lesions may completely regress secondary to a robust host immune response.[2]

MUP accounts for 3.2% of all melanoma cases with a male preponderance. It is found to peak in the fourth and fifth decades of life, similar to cutaneous melanoma.[3]

The accepted hypothesis for MUP involves the spontaneous immune-mediated regression of melanoma from a known primary site.[3] It has also been suggested that the improved survival rate observed in patients of MUP in comparison to metastatic melanoma with a known primary may be attributed to these same immune mechanisms.[4]

Primary lesions are often missed, wrongly diagnosed, or missed out on physical examination. Das Gupta et al. excluded patients satisfying any of the following described criteria: (1) previous history of orbital exenteration or enucleation; (2) prior history of excision, electro-desiccation or cauterisation of a mole, birthmark, freckle, chronic paronychia, or skin blemish; (3) presence of scars in the region of the affected draining nodal basin; and (4) patients not having a thorough physical examination including ophthalmoscopy and adequate local examination of the anus and the genitalia.[5] None of the above were present in our patient.

Lymph nodes are observed to be the most commonly affected site in MUP accounting for nearly 40–60%, with axillary and cervical nodal involvement predominating among males and an increased incidence of inguinal nodal involvement among females.[6] Among the extra nodal sites of involvement in MUP, the subcutaneous tissues were found to be the most affected (30%), whereas visceral organ involvement was found in 20%.[6]

The histopathological diagnosis of the excised tissue needs to be further confirmed by immunohistochemistry using immunostains (S-100 Protein, HMB-45, and Melan-A).[6]

A comprehensive evaluation of patients suspected to have MUP includes cross-sectional imaging such as computed tomography or positron emission tomography (PET) scanning to map out the extent of metastatic disease involvement. The range of treatment modalities that can be offered to these patients includes surgery, immunotherapy, chemotherapy, and radiation.[4]

Visceral metastases tend to be associated with a poorer prognosis and a higher risk of relapse with most recurrences (45–65%) occurring within 2 years of treatment.[4]

Metastatic melanoma should always be among the differentials considered in patients who present with a malignancy of unknown origin, particularly when lymph nodes or cutaneous metastases comprise the presenting site of involvement.

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 initials 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.


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