A Baffling Presentation of Metastatic Malignant Melanoma: Sporotrichoid Pattern Mimicking Vascular Tumor with Vitiligo-Like Depigmentation Following Immunotherapy

Dear Editor,

Melanoma is a malignant transformation of melanocytes. Lesions are dark blue-black or bluish-red, though 5% are amelanotic. The mortality rate due to metastatic melanoma is significantly higher than primary melanoma.[1] Immune checkpoint inhibitors (Nivolumab, Pembrolizumab, and Ipilimumab) and targeted therapy (B-raf murine sarcoma viral oncogene homolog B (BRAF) and Mitogen activated protein kinase (MEK) inhibitors) represent first-line treatments that may cause depigmentation as a side effect, which is associated with better prognosis.[2] We report a case of unusual presentation of malignant melanoma in a sporotrichoid pattern masquerading vascular tumor with vitiligo-like depigmentation during immunotherapy.

A 50-year-old woman presented with multiple asymptomatic nodules over her left leg in a linear distribution for 1 year showing discharge from few lesions after trivial trauma. General examination unveiled a solitary, hard, non-tender left inguinal lymph node of 3 × 4 cm and diffuse non-pitting edema on the ipsilateral leg. Upon cutaneous examination, multiple soft to firm skin colored to bluish hyperpigmented nodules with focal areas of ulceration were present extending from of left medial foot to midcalf [Figure 1a and b]. A single stellate scar was present on the left sole [Figure 1c]. On keen inquiry, the patient gave a history of a recurrent blackish corn-like lesion over the same site, which was excised 3 times in the last 2 years. However, the sample was never analyzed histopathologically. Based on these findings, the differentials of angiosarcoma, lymphoma, Kaposi sarcoma, and melanoma were considered. Further bedside evaluation by dermoscopy showed a bluish white veil, structureless white areas with peripheral brown-black pigment network, and crown vessels. Hematological analysis revealed increased erythrocyte sedimentation rate (ESR) (55 mm/hour) and lactate dehydrogenase (LDH) (346 U/L). Radiological evaluation by ultrasound Doppler and magnetic resonance imaging (MRI) depicted subcutaneous masses with increased vascularity and cellularity with increased uptake in inguinal lymph nodes on positron emission tomography (PET) scan.

Figure 1.

(a) Multiple, non-tender, soft to firm skin colored to bluish hyperpigmented nodules with smooth surface arranged over the medial aspect of the left foot. (b) Sporotrichoid arrangement of nodules with ulceration. (c) Post-surgical stellate scar (red circle)

Confirmatory histopathological examination revealed proliferative dermal growth consisting of cords and sheaths (upper dermis) and focal alveolar arrangement (lower dermis) [Figure 2a] of cells with high nucleo-cytoplasmic ratio and melanin pigment deposition [Figure 2b and c]. Immunohistochemical analysis showed positivity for S100, Melan A, and HMB 45 [Figure 2d-f]. Conclusively malignant melanoma was considered as the final diagnosis (Grade IV), and the patient was started on immunotherapy with fortnightly cycles of nivolumab (3 mg/kg). After 2 cycles of immunotherapy, the patient developed multiple areas of hypopigmentation over the left leg with depigmentation of a few nodules [Figure 3a] over the left foot. After 6 cycles, given a PET scan showing distant metastasis [Figure 3b], pseudoprogression, and positive BRAFV600 mutation on gene analysis, the patient was put on targeted therapy with dabrafenib (75 mg) and trametinib (1 mg) following which depigmentation increased. Unfortunately, the patient succumbed after 2 months of targeted therapy.

Figure 2.

Histopathology and immunohistochemistry: (a) Focal ulceration of epidermis with the extension of cells deep down and cord and sheath of cells with pigment deposit (upper dermis) and the island of cells arranged in an alveolar pattern (deep dermis) (H and E, 40×). (b) Atypical epithelioid melanocytes (H and E, 100×). (c) Plasmacytoid cells and epithelioid cells with conspicuous nucleoli and altered nucleo-cytoplasmic ratio (N/C) with pigment deposit (H and E, 400×). (d) S100 staining (diffusely positive) (40×). (e) Melan A staining (diffusely positive) (40×). (f) HMB 45 staining (focally positive) (40×)

Figure 3.

Images while the patient was on immunotherapy. (a) Clinical image showing vitiligo-like depigmentation of nodules after two fortnightly cycles of nivolumab (3 mg/kg). (b) PET scan showing metastatic spread― involvement of multiple lymph nodes, muscles, and lungs

Discussion

Malignant melanoma, although considered to be a signature tumor of Caucasian skin, has been recently showing a rising trend in the Indian population.[3] Etiological factors revolve around genetics, environment, and ultraviolet exposure. Nodular presentation is the earliest sign of melanoma metastasis, which mimics a plethora of innocuous and sinister dermatoses including vascular tumors like angiosarcoma (blue-red nodules), Kaposi sarcoma (violaceous papules, plaques, and nodules), a and cutaneous lymphoma (nodules with foci of ulceration).[3] Atypical morphologies and distribution as well as amelanotic variants pose a great diagnostic challenge. Ancillary bedside tests like dermoscopy showing blue-veil, white structureless areas, atypical pigment network, and crown of vessels are useful diagnostic aids. These findings prompted us to consider melanoma, which was confirmed by histopathological analysis showing asymmetric sheets of cells with atypia, nuclear pleomorphism, hyperchromatic nuclei, and the presence of mitoses. Clinical behaviour of melanoma initially shows invasion of draining lymph nodes and adjacent skin (as in our case), which eventually metastasizes to the lung and other organs. Ulceration, higher mitotic rate, raised LDH levels, lymph node involvement, and distant metastases (seen in our case) suggest a bad prognosis.

A possible cause of vitiligo in melanoma patients is melanoma-associated hypopigmentation (MAH), which has been observed in 2%−16% of melanoma patients either spontaneously or concurrently with treatment due to immune activation against melanoma-associated antigens expressed by normal melanocytes as a result of cross-reaction from melanoma cells that share the same antigens.[4]

Recently, experimental models exploring the role of vascular endothelial growth factor C (VEGF-C) in lymphangiogenesis and eventually melanoma metastasis have been developed. Although the exact mechanism of lymphatic invasion and metastasis is not known, the hypothesis suggesting its spread through lymphatic vasculature explains sporotrichoid distribution in our case.[5]

There are only two reports of malignant melanoma occurring in this pattern in Indian literature and few depict unilateral distribution. Our case is unique in its sporotrichoid distribution and mimicry with vascular tumours.

This case highlights the importance of thorough history taking and simple bedside tools such as dermoscopy which prompts a dermatologist toward diagnosis of grave malignancies such as melanoma.

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 that due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.