|Year : 2015 | Volume
| Issue : 1 | Page : 51-53
In-transit metastases of acral lentiginous melanoma
Shilpa Y Krishnegowda, N Sudhir Kumar
Department of Dermatology, Adichunchanagiri Institute of Medical Sciences, Rajiv Gandhi University of Medical Sciences, Mandya, Karnataka, India
|Date of Web Publication||26-Jun-2015|
N Sudhir Kumar
Department of Dermatology, Adichunchanagiri Institute of Medical Sciences, B. G. Nagar, Mandya - 571 448, Karnataka
Source of Support: None, Conflict of Interest: None
Cutaneous melanomas, tumors of epidermal melanocytes are infrequent but highly lethal skin cancers. Initial stages of acral lentiginous melanoma (ALM) may be difficult to differentiate from the plantar wart, black heel and other benign nevus conditions. Even with available modern treatment options, the mortality is still on the rise, which in part is related to the delay in diagnosis. Here, we present a case of ALM, previously treated with excision and lymphadenectomy who presented with in-transit metastases (ITM).
Keywords: Acral lentiginous melanoma, cutaneous melanoma, in-transit metastases
|How to cite this article:|
Krishnegowda SY, Kumar N S. In-transit metastases of acral lentiginous melanoma. Pigment Int 2015;2:51-3
| Introduction|| |
Melanoma, a tumor of epidermal melanocytes, includes superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma and acral lentiginous melanoma (ALM). Though the incidence is on the rise throughout the world, Asians have reported low incidence, but a high mortality rate.  The incidence rate of cutaneous melanoma in India is noted to be <0.5/1,000,000.  ALM, attributed to its aggressiveness, misdiagnosis, and late presentation accounts for nearly 50% of all melanoma cases among Asians.  We report a case of ALM presenting with in-transit metastases (ITM) after excision of the primary tumor and left inguinal nodes.
| Case Report|| |
A 55-year-old male presented to our department with multiple, asymptomatic, rapidly enlarging swellings over the left lower limb associated with loss of appetite and weight. A similar swelling was present over the left big toe 2 years back, which was diagnosed as ALM with T 4 N 1 M x stage and clark level 4 invasion, which was excised along with left inguinal nodes. After a period of 6 months, multiple, nontender, firm, fixed and indurated swellings ranging from 0.5 to 5 cm developed over the left leg and medial aspect of left thigh [Figure 1]. There was no lymphadenopathy or any other systemic symptoms.
|Figure 1: Multiple, pigmented, firm nodules of varying sizes present over left leg|
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Routine hematological, renal and liver function tests, urine tests, chest radiograph, ultrasonography of abdomen and pelvis were in normal limits. Excision biopsy revealed a proliferation of atypical melanocytes along dermo-epidermal junction, pagetoid melanocytes with pleomorphism and mitotic figures [Figure 2] and [Figure 3]. The patient was diagnosed with ITM and was put on interferon-alpha therapy. After a 2 months period of treatment, metastases increased both in number and size with large painful growths [Figure 4] and involvement of contralateral inguinal lymph nodes. He failed to respond to current treatment and succumbed to the disease.
|Figure 2: Proliferation of atypical melanocytes along dermo-epidermal junction (H and E, ×10)|
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|Figure 3: In-transit metastasis in acral lentiginous melanoma showing atypical and pagetoid melanocytes (H and E, ×10)|
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|Figure 4: Large ulcerative metastases over the medial aspect of left thigh|
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| Discussion|| |
Cutaneous melanoma contributes for nearly 75% of all skin cancer-related deaths.  Melanomas has a radial and a vertical growth phase, the latter phase is usually associated with metastasis. Tumor progression involves proliferation of atypical melanocytes, neovascularization, lymphangionesis and extravasation of atypical melanocytes. ALM, introduced by Reed in 1976, occurs over the volar surface of hands and feet, subungual areas, fingers and toes.  The hidden location of lesions in ALM contributes to its poor prognosis as the initial lesions could be easily missed.
To the best of our knowledge, there are 16 cases of ALM since 1995 reported from India but none of the cases showed ITM. ITM is defined as, any skin or subcutaneous metastasis that is >2 cm from the primary lesion but not beyond the regional nodal basin.  ITM, seen in 10% of melanoma cases, is located in dermal and subdermal lymphatics before reaching lymph nodes.  ITM has an aggressive pattern of recurrence and poor prognosis. The median time to develop ITM is nearly 16 months after definitive treatment.  However, there are very few cases of ITM from ALM. Deshmane reported in-transit melanoma in 10.29% of cases with a mean duration for occurrence being 8.3 months, but he did not specify the type of melanoma which resulted in ITM, though ALM was the commonest type. 
The risk factors for the development of ITM include increasing age, breslow thickness (>4 mm), ulceration, high mitotic rate, angiolymphatic invasion, positive sentinel lymph nodes and extremist location. In our case, patient was an elderly male, with an ulcerated primary tumor in an acral location, positive lymph node metastases all of which suggested a poorer prognosis.
The differentiating points of ALM from that of plantar warts, black heel or other benign nevus conditions mainly rely on dermoscopic features and histopathology; hence most of the cases are misdiagnosed resulting in delay in initiation of therapy. The characteristic dermoscopic features of pigmented plantar warts is parallel ridge pattern, whereas black heel shows pebbling over the ridge pattern and nevi show parallel furrow, lattice-like or fibrillar pattern. However, histopathology is always confirmatory.
Treatment of melanoma involves multimodality approach involving surgery, radiotherapy, chemotherapy and immunotherapy. The various immunostimulants being tried are, mitogen-activated protein kinases/MEK/extracellular signal-regulated kinase inhibitors such as sorafenib, vemurafenib, dabrafenib, selumetinib, trametinib and interleukin-2, ipilimumab, nivolumab and interferon-alpha [Table 1].
There is the difference of opinion among authors about the role of regional lymphadenectomy in the causation of ITM. Mechanical interruption of lymphatic flow to the regional lymph nodes could predispose to ITM.  However, the current data provide evidence that lymph node dissection does not increase the incidence of ITM.  Cutaneous melanoma with ITM being aggressive needs early diagnosis, treatment and regular follow-up for improving the quality of life of the patient. Combining immunophenotyping along with routine histopathology will prevent under reporting of this aggressive malignancy.
| References|| |
Verma KK, D'Souza P, Sirka CS, Raman RS, Rathi SK. Disseminated malignant melanoma. Indian J Dermatol Venereol Leprol 1999;65:230-1.
Nair MK, Varghese C, Mahadevan S, Cherian T, Joseph F. Cutaneous malignant melanoma - Clinical epidemiology and survival. J Indian Med Assoc 1998;96:19-20, 28.
Bishop JA. Lentigos, melanocytic naevi and melanoma. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8 th
ed. Ch. 54. Oxford: Wiley-Blackwell Publishing; 2010. p. 44.
Sharma K, Mohanti BK, Rath GK. Malignant melanoma: A retrospective series from a regional cancer center in India. J Cancer Res Ther 2009;5:173-80.
Khandpur S, Reddy BSN. Acral lentiginous melanoma. Indian J Dermatol Venereol Leprol 2000;66:37-8.
Grotz TE, Mansfield AS, Kottschade LA, Erickson LA, Otley CC, Markovic SN, et al.
In-transit melanoma: An individualized approach. Oncology (Williston Park) 2011;25:1340-8.
Oashi K, Furukawa H, Nishihara H, Ozaki M, Oyama A, Funayama E, et al.
Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model. J Invest Dermatol 2013;133:537-44.
Deshmane V, Kalloli M, Chikaraddi S, Keerthi B, Krishnappa R. Predictive factors for loco regional recurrence and distant metastasis following primary surgical treatment of cutaneous melanoma. Indian J Dermatol 2014;59:241-6.
Roses DF, Harris MN, Rigel D, Carrey Z, Friedman R, Kopf AW. Local and in-transit metastases following definitive excision for primary cutaneous malignant melanoma. Ann Surg 1983;198:65-9.
Pawlik TM, Ross MI, Thompson JF, Eggermont AM, Gershenwald JE. The risk of in-transit melanoma metastasis depends on tumor biology and not the surgical approach to regional lymph nodes. J Clin Oncol 2005;23:4588-90.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]