Indian Journal of Dermatology
: 2013  |  Volume : 58  |  Issue : 5  |  Page : 396--399

Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

Bhavana Doshi, Sunanda Mahajan, Uday S Khopkar, Vidya Kharkar, Prachi Agarwal 
 Department of Dermatology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India

Correspondence Address:
Bhavana Doshi
C/O Uday Khopkar, Department of Dermatology, Seth G.S. Medical College and K.E.M. Hospital, Parel, Mumbai - 400012


Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male.

How to cite this article:
Doshi B, Mahajan S, Khopkar US, Kharkar V, Agarwal P. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male.Indian J Dermatol 2013;58:396-399

How to cite this URL:
Doshi B, Mahajan S, Khopkar US, Kharkar V, Agarwal P. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male. Indian J Dermatol [serial online] 2013 [cited 2019 Dec 11 ];58:396-399
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Full Text


Most skin metastases of melanoma are located in the reticular dermis and are not difficult to differentiate from a primary melanoma, however epidermotropic metastasis poses a significant difficulty on histopathology to distinguish it from a new primary lesion. The concept of epidermotropic metastatic malignant melanoma (EMMM) was developed in the 1970's [1] thereby which distinguishing the primary from epidermotropic metastasis became important, since recognition of this histopathologic variant catapults the disease from stage 1 to stage IV which has a bad prognosis. [1],[2] Lesions of melanoma are known to show the occurrence of vitiligo like lesions at the site of regressing primary or at distant sites but rarely around epidermotropic secondaries.We present a clinical case of epidermotropic secondaries with vitiligo like depigmentation around it.

 Case Report

A 78 year old male presented to us with complaints of multiple, small, dark colored raised lesions over the left leg which were gradually increasing in size and number over a period of two months. A few of them occasionally ulcerated, bled, discharged pus and were associated with pain. The patient also complained of multiple asymptomatic swellings in left groin region since one month. A darkly pigmented scar was seen over the heel of left foot.

On enquiry, he gave history of single, small, dark colored pea sized raised lesion on the sole of left foot which over a period of two years gradually increased in size to ulcerate and form a non healing ulcer which would bleed occasionally. Complete excision with skin grafting of the lesion was done at his hometown six months prior and was reported as acral lentiginous malignant melanoma on histopathological examination. He gave no history of abdominal pain, bony pain, vomiting, chest pain, convulsions or breathlessness. He had been operated for varicosities of left leg three years back and was a known hypertensive on treatment since two years.

Clinical examination of the patient revealed multiple, soft, friable, well defined, jet black colored, firm papulonodular lesions ranging in size from 3 mm to 6 cm in dimension. These lesions extended from dorsa of left foot up to the knee. Many of these papulonodular lesions showed a surrounding rim of depigmentation. A few of these had undergone ulceration with overlying crusting [Figure 1]. A single well defined dark colored plaque of 5 × 6 cm was also seen on the heel of the left sole [Figure 2]. The left sided inguinal region showed three enlarged lymph nodes which were mobile, 2-3 cm sized, hard and non tender.{Figure 1}{Figure 2}

Complete blood count showed mild anemia (Hb-12.3 gms/dl). Platelet count, total leukocyte count and differential leukocyte count was normal except for mild eosinophilia. ESR was raised significantly (92 mm) at the end of one hour. Findings of liver and renal function tests were within normal limits. The serum lactate dehydrogenase levels were found to be raised (506 IU/L).

Biopsy done from a jet back papule revealed an asymmetric melanocytic neoplasm with irregular distribution of melanocytes and nests of variable size. There was epidermal flattening overlying the dermal nests of atypical melanocytes extending up to mid reticular dermis [Figure 3]. Several melanocytes were present in solitary units above basal layer of the epidermis. Neoplastic melanocytes showed mild to moderate atypia with occasional mitotic figures with haphazard pigment distribution in both normal and atypical melanocytes. Several neoplastic melanocytes were present within some of the dilated capillaries in the deep dermis suggestive of angioinvasion.{Figure 3}

Biopsy from a papule showing peripheral rim of depigmentation revealed melanocytic neoplasm made up of irregular shaped and sized nests within the mid and upper dermis with numerous solitary melanocytes scattered throughout the surrounding epidermis including the stratum corneum with epidermal flattening. Atypical melanocytes were noted in the deep dermal capillaries. Moderately dense superficial perivascular lymphocytic and plasma cellular infiltrate underlying the dermal nests were seen in addition which were responsible for the depigmented halo clinically [Figure 4].{Figure 4}

Ultrasonography of abdomen and pelvis showed normal sized liver with multiple hypo echoic lesions involving both lobes, measuring 2.3 by 2.2 cm in size suggestive of secondary metastatic deposits. Chest X ray was reported to be within normal limits. Fine needle aspiration cytology of the left inguinal lymph nodes confirmed metastasis. Reports of Positron emission tomography (PET) revealed presence of metastatic deposits in the lungs, liver, spleen, left para-aortic group of lymph nodes, left inguinal group of lymph nodes and in the subcutaneous tissue over left thigh region [Figure 5]. Computed tomography of the brain was normal.{Figure 5}

On co-relating the above findings we reached a diagnosis of epidermotropic metastatic melanoma stage IV (T2N3M1c) with peri-metastatic depigmentation. The patient, however refused further treatment and succumbed to death over a span of two months.


One of the rare forms of melanoma metastasis is the epidermotropic metastasis which poses a significant difficulty on histopathology in its distinction not only from a new primary melanoma but also from residual incompletely excised primary melanoma. It may be seen on histopathology to include the dermo-epidermal junction, extend into the epidermis with intra-epidermal component not beyond the dermal component and as an epidermal-only pattern. This distinction has a great bearing on the staging and prognosis since staging of multiple primary melanomas is based on the primary lesion with the worst prognostic features, whereas a patient with a distant cutaneous metastasis catapults to stage IV disease with an approximate 10% five year survival rate. [2],[3],[4]

In 1978, Kornberg for the first time proposed histopathologic characteristics for differentiating epidermotropic metastatic melanoma from a primary melanoma. [1] These features were: (1) Thinning of the epidermis by the underlying aggregates of atypical melanocytes in the dermis, often in association with widened dermal papillae and an epidermal collarette at the periphery of the tumor (2) atypical melanocytes present within endothelial lined spaces, and (3) a zone of atypical melanocytes in the dermis equal to or broader than the epidermal component. However, over a period of time, multiple reports have described the varied histopathologic presentations of epidermotropic metastatic melanomas and proposed additional criteria. [5],[6],[7],[8],[9],[10],[11] such as angiotropic nature of metastasis, maturation and spread in a pagetoid pattern. [5],[7] Other histologic features considered by some workers to be present in a metastatic lesion are localization of the metastatic atypical melanocyte nests in the superficial dermis, the presence of evident inflammatory infiltrate, presence of monomorphic, monoclonal malignant cells [12] and occurrence of small sized lesions. However, all these features can also be seen in primary melanomas.

Studies on melanoma and its metastasis have shown that loss of heterozygosity (LOH) on short arm of chromosome 9 and long arm of chromosome 10 i.e., (9p and 10q) is associated with early-stage primary disease, whereas LOH on 6q, 1p, 8q, and 11q has been associated with its progression and metastasis. LOH at 10q was found most frequently and in higher proportion in the epidermotropic metastatic melanomas. However, variable patterns within the same case indicate that, while some epidermotropic metastatic melanomas are clonally related to the primary, others are of independent origin. [13]

Vitiligo like leukoderma has been estimated to involve 20% cases of melanoma. Four patterns of hypomelanosis around melanomas have been observed such as i) areas of depigmentation confined to primary lesion suggestive of a regressed lesion ii) halos of depigmentation around the primary tumour iii) a primary tumour with co-existent halo nevi i.e., leukoderma around benign nevocytic nevi and iv) wide spread hypomelanosis at sites distant from primary site. [14] The postulated mechanism is the occurrence of immune response leading to circulating anti-melanocyte antibodies formation. These are capable of attracting natural killer cells which cause vitiligo by attacking and destroying normal melanocytes. [15],[16]

Becker et al.[14] demonstrated that the cells infiltrating the depigmented skin were identical to the T lymphocytes infiltrating the adjacent tumor, indicating that the same cells responsible for tumor reduction were also responsible for depigmentation. In case of vitiligo and melanoma-related depigmentation, studies suggest CD8+ T cell reactivity to be directed against the Melan-A/Melanoma associated antigen recognized by T-cells (MART-1) epitope 27-35 in HLA-A2 patients. [17]

In MMM associated with widespread vitiligo the 5-year survival rate is 60%, [16],[18] and survival up to 29 years has been documented. [18],[19] Death eventually occurs as a consequence of metastatic disease. [20] Thus, the presence of vitiligo may delay the inevitable outcome but does not eradicate the malignancy. The favourable influence of vitiligo on the prognosis of MMM does not seem to be related to whether the depigmentation develops before or after diagnosis of the malignant disease. [2]

The process of hemo-lymphatic spread of the atypical melanocytes of the primary lead to cryptic exposure of the tumor antigens eventuating in a T-cell mediated immune response of the body which manifested as peri-lesional depigmentary changes around the secondary metastatic deposits in our case. However, the occurrence of T-cell mediated immune response did not seem to confer any protection against metastatic spread of the disease.


Hence in cases with multiple lesions of melanoma, the clinician needs to be on a constant look out to distinguish multiple primary from the rare epidermotropic metastasis. The occurrence of vitilgo like changes around primary lesions have been reported to confer better survival chances in patients, however its occurrence around secondaries did not seem to confer any prognostic advantage in our case.


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