Acral lentiginous melanoma and Bob Marley - Mavericks in their own right

ALM-non-conformist and outlier

ALM is a distinctive subtype of melanoma with very stark features:^7-11

• Rare subtype of melanoma but comprises a much higher proportion of melanomas in darker-skinned individuals (i.e, African ancestry, Asians, and Hispanics)

• Occurring more commonly in older age group

• Less commonly associated with naevi

• Less commonly associated with chronic intermittent sun-exposure due to its occurrence on acral sites (more on lower limbs) and nail unit

• Distinct genetic markers, although the tumour genetic profile is poorly understood

• Distinct histopathological features

• More association with ulceration and higher Breslow thickness

• More likely to be misdiagnosed, leading to a delay in management

• Aggressive disease with a poor outcome, even when diagnosed early. It has 5- and 10-year survival rates; lower than all other cutaneous melanomas

• Poor understanding of ALM genetic and immune microenvironment characteristics makes therapeutic options challenging, and combining it with the rarity of this disease makes studies and data reporting limited and inconsistent

Let’s talk numbers

Malignant melanoma (MM) is the most lethal form of skin cancer and accounts for ∼78% of all skin cancer deaths. Out of the four histological subtypes of MM, superficial spreading melanoma is the most common (∼70% of cases), and ALM is the least common (∼2-3% of all melanomas).¹⁰ ALM was first introduced as a distinct clinico-histopathological entity by Reed^7,8 in 1976. Reed was the first to notice this subtype of melanoma in people of colour. In his study, ALM patients had an average 3-year survival rate of 11%, partly due to a delay in diagnosis.¹⁰

Although most dermatological disorders do not discriminate based on race, ALM seems to be one such exception. The proportion of ALM amongst all subtypes of melanoma was greatest in African-Americans, and 5- and 10-year melanoma-specific survival rates for ALM were lower in them when compared to Caucasians.^10,11

The Population-based registry study (1986-2005)¹⁰, the National Cancer Database (NCDB) data from the United States on ALM (2004-2016)¹¹, and other studies^7,8,12 give us the following data regarding ALM:

• The proportion of ALM was greatest in African Americans (13.3%), superseding other histopathological subtypes of melanoma, like superficial spreading melanoma at 12.9%, nodular melanoma at 8.2%, lentigo maligna melanoma at 2.4%, spindle cell melanoma and desmoplastic melanoma at 1.7% and 1.1%, respectively

• The mean (median) age of diagnosis was 62.9 years

• Time between noticing signs to seeking treatment varies with a statistical mode of 1 to 3 years, contributing to a delayed diagnosis and referral

• Women were affected fractionally more (55.4%) than their male counterparts

• Lower extremities represented the majority (82%) of cases

• ALM had 5- and 10-year melanoma-specific survival rates of 80.3% and 67.5%, respectively, which were less than those for all overall MM, 91.3% and 87.5%

• The 5- and 10-year melanoma-specific survival rates for ALM were highest in Non-Hispanic Whites (82.6% and 69.4%) and intermediate in African Americans (77.2% and 71.5%)

• Breslow thickness >4mm, ulcerated lesions, increased age, and stage IV disease showed an increased hazard of death

• Age, tumor thickness, ulceration, and a greater number of comorbidities were independently associated with decreased overall survival

• Prognostic value of sentinel lymph node (SLN) biopsy in patients with thick (1 mm) or ulcerated ALM is high

• Patients with positive SLN had significantly shorter melanoma-specific survival (5-year survival of around 20% in thick and ulcerated ALM) when compared to the negative SLN group (5-year survival of 60-80%)

• Breslow thickness and ulceration of the primary lesion were strongly correlated with metastasis in SLN, with the National Comprehensive Cancer Network encouraging SLN biopsy for patients with melanoma greater than 1 mm in thickness or an ulcerated melanoma

• Surgery alone was performed in 91.7% of patients, with wide local excision being the most common method

• Median overall survival was 10.7 years, although treatment-specific outcomes are not mentioned

Revision with fresh insights

Although ALM is common on lower limbs and predominantly in people of colour, Bob Marley was a child of mixed race, and data on ALM in mixed races is grossly deficient. Bob was diagnosed with melanoma at the age of 32 years; drastically different from the ‘older age’ ALM is known to affect. His delayed diagnosis was due to an assumption that soccer-related trauma led to the lesion. Timeline of events of Bob’s life and medical fraternity’s developments with regard to ALM have been mentioned in Figure 2.^4,7,8,13-15

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Figure 2:

Bob Marley’s life and ALM: Timeline of events.

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Breslow, in 1970, published regarding the thickness and depth of invasion in melanomas,¹³ considering the study by Clark et al. published just a year prior. It was revisited in 1978.¹⁴ However, no information is provided regarding the Breslow thickness or stage of Bob Marley’s melanoma, so retrospective prognostication is not possible. The ulcer was present for years before medical help was sought, delaying the diagnosis and contributing to the advancement of his disease by the time his diagnosis of ALM was made in 1977. Although the lymphatic spread of melanoma was known, SLN biopsy in melanoma was a concept widely introduced by Morton et al., almost a decade after Bob passed away.¹⁵

Although amputation was advised, there is no way to confirm if his ALM was already at an advanced stage and if amputation could have prevented this disease from metastasising in the long run. For what it’s worth, wide local excision of the primary tumour is the most common treatment modality opted for ALM, albeit the margin of resection in his case is not known. His choice to reject amputation was a personal one, possibly influenced by his Rastafarian beliefs and a hindrance he believed it would place in his performing career.⁴

Most data regarding adjuvant and neoadjuvant therapy, as summarised by Dugan et al.,⁹ were not available in the 70’s. Although he briefly received radiation treatments after metastatic disease was detected, he predominantly opted for alternative medicine.