Epidermotropic Metastatic Melanoma

Authors: I. Coutinho1, A.Agarwal2, P. Nathan3, V. Bataille4

1) Consultant dermatologist, Coimbra University Hospital, Portugal

2) Consultant histopathologist, West Herts NHS Trust, UK

3) Consultant oncologist, Mount Vernon Cancer Centre, UK

4) Consultant dermatologist, Mount Vernon Cancer Centre, UK

 

An 86 year old man presented to the dermatology department in 2015 with a pigmented lesion on the right arm which had appeared recently. The melanocytic lesion was macular, dark-brown, with regular, sharp borders. It was excised and the histology report described a melanoma in situ. Wide local excision was completed with a 5 mm margin, pathology showing no residual tumour.

During follow up visits in early 2016, the patient presented with further multiple pigmented lesions on both thighs (Fig.1) and right arm which had appeared quickly over weeks. These were darkly pigmented macules varying in diameter between 3 mm and 7 mm. Dermoscopy revealed atypical features such as a dark brown asymmetrical structureless pattern with peripheral thick blotches (Fig.2a) and a structureless brown-black blotch with peripheral thick reticular lines ending abruptly (Fig.2b).

Fig 1 – Irregular darkly pigmented lesions arising rapidly on both thighs 

Fig.2 – Dermoscopy of the lesions 

Fig 3 – Histopathology of the lesion of the left thigh a)H&E x5 magnification - extensive junctional and intraepidermal melanocytic proliferation with elongation of rete ridges. b) H&E x10 magnification - atypical epitehlioid and spindle-shaped cells with a nested pattern in the dermal-epidermal junction and pagetoid spread within the epidermis (compatible with melanoma in situ)

   

The case was discussed at the local multi-disciplinary meeting and, in view of the rapid onset of multiple apparent superficial spreading melanomas, a diagnosis of epidermotropic metastatic  melanoma was made. The patient had an MRI of the head and CT scan of neck, chest, abdomen and pelvis which were normal. He is currently being followed up and remaining lesions, that were not excised, have stayed stable with no recent growth and no new lesions appearing. He will remain under follow up in the melanoma clinic with imaging every 6 months.

It is important to be aware of epidermotropic metastatic melanoma. Lesions tend to occur in “crops” and cluster around certain anatomic regions, characteristically in the vicinity of the known primary lesion. More rarely they can be diffuse and hazardously distributed.1-3 In our case report it is unlikely that the first lesion noticed was the primary melanoma – since it was found to be in situ (thus, a low-risk lesion) and since it was closely followed by the sudden appearance of many similar lesions in clusters over different anatomical locations (arm but also both thighs).

It seems reasonable to make the diagnosis of epidermotropic metastatic melanoma of unknown primary over multiple synchronous primaries. Not only is it well recognized that melanoma metastases favour the skin, but also, according to a review by Savoia et al.4, multiples synchronous primary melanomas are very rare. In 270 patients from a single institution, over a 34-year period, only 3.7% of patients had 4 synchronous primary melanomas and only 2 patients had more than 7 synchronous primary melanomas. Moreover, the evolution of the lesions – appearing in crops during a short period of time, and clustering in some anatomical areas is coherent with metastatic behavior.

Nonetheless, clinically and dermatoscopically, individual lesions can resemble primary melanomas. Even histopathology can prove challenging in view of the overlapping features between purely epidermotropic metastatic melanoma and primary melanoma2,5. In these cases, if clinicopathological correlation is insufficient to make a diagnosis, molecular analysis can be helpful in establishing a link between primary and metastatic lesions. An article by Bahrami et al.5 has described loss of heterozigosity (LOH) on chromosome 9 (the region of the tumor suppressor gene p16INK4), and at 10q (close to the tumor suppressor genes PTEN/MMAC and MXI1), both in primary melanomas and their epidermotropic metastases. Other microsatellite regions that showed LOH were on chromosomes 1p, 6q, 11q and 18q. Non-random X-chromosome inactivation was also seen in the majority of cases occurring in women. The same paper, however, also mentioned that some metastastic lesions were clonally independent from their primary – either representing divergent clones or the novo primary lesions. 

                When considering a final diagnosis, history, clinical features, histopathology and even molecular findings should be discussed in a multidisciplinary meeting, as this may alter further management.

Multiple excisions of individual lesions may be stopped since aggressive surgical interventions can likely cause morbidity without overall impact on prognosis. Although being metastatic disease – thus rendering poor prognosis – cases reported in the literature seem to hint at that epidermotropic metastatic melanoma may have a slower progression to visceral involvement6. Close follow-up is nonetheless advisable in order to introduce timely treatment.

 

This paper was done with the support of the Cabral de Ascenção grant from the Portuguese Society of Dermatology and under the auspices of the EADO Exchange Fellowship Program

References

1) Komberg R, Harris M, Ackerman AB. Epidermotropically metastatic malignant melanoma. Arch Dermatol 1978; 114:67-9.

2) Lestre S, João A, Ponte P, Peixoto A, Vieira J, Teixeira MR, Fidalgo A. Intraepidermal epidermotropic metastatic melanoma: a clinical and histopathological mimicker of melanoma in situ occurring in multiplicity. J Cutan Pathol. 2011 Jun;38(6):514-20.

3) Skala SL, Arps DP, Zhao L, Cha KB, Wang M, Harms PW, Andea AA, Fullen DR, Chan MP. Comprehensive Histopathologic Comparison of Epidermotropic/Dermal Metastatic Melanoma and Primary Nodular Melanoma. Histopathology. 2017 Sep 7. [Epub ahead of print] 

4) Savoia P, Osella-Abate S, Deboli T, Marenco F, Stroppiana E, Novelli M, Fierro MT, Bernengo MG. Clinical and prognostic reports from 270 patients with multiple primary melanomas: a 34-year single-institution study. J Eur Acad Dermatol Venereol. 2012 Jul;26(7):882-8

5) Bahrami S, Cheng L, Wang M, Jones TD, Malone JC, Billings SD. Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis. Mod Pathol. 2007 Aug;20(8):821-7

6) Ishii A, Nishiguchi T, Kitagawa T, Yoji M, Hakamada A, Isoda K, Kurokawa I, Hara K, Mizutani H. A Case of Epidermotropic Metastatic Malignant Melanoma with Multiple Nodular Lesions of the Scalp. J Dermatol. 2005 Oct;32(10):821-6