Melanomas That Lack Classical Clinical Features

Home , Amelanotic melanoma, Desmoplastic melanoma, Nodular melanoma

Guideline summary Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features

Victoria J Mar1,2, Alex J Chamberlain1,2, John W Kelly1,2, William K Murray3, John F Thompson4,5

here is evidence that the rate of early detection of superficial Abstract spreading melanomas in Australia has improved, with a Introduction: A Cancer Council Australia multidisciplinary T corresponding reduction in both the median tumour working group is currently revising and updating the 2008 1 thickness and in melanoma mortality from this subtype. How- evidence-based clinical practice guidelines for the management ever, a number of studies in Australia and other countries have of cutaneous melanoma. While there have been many recent shown an increasing or stable incidence rate of thick melanomas.2-7 improvements in treatment options for metastatic melanoma, Nodular melanoma (NM), desmoplastic melanoma (DM) and acral early diagnosis remains critical to reducing mortality from the lentiginous melanoma (ALM) are often diagnosed when they are disease. Improved awareness of the atypical presentations of much thicker lesions compared with superficial spreading mela- this common malignancy is required to achieve this. A chapter noma (SSM).3,4,6,8-10 This is in part due to their atypical clinical of the new guidelines was therefore developed to aid recognition of atypical melanomas. features. Improved diagnostic accuracy of these subtypes can significantly reduce mortality from melanoma. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, The 2008 evidence-based clinical practice guidelines for the border irregularity, colour variegation, diameter > 6 mm) features management of cutaneous melanoma (http://www.cancer.org.au/ of melanoma, a thorough history of the lesion with regard to content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPract change in morphology and growth over time is essential. Any iceGuidelines-ManagementofMelanoma.pdf) are currently being lesion that is changing in morphology or growing over a period of revised and updated in a staged process by a multidisciplinary more than one month should be excised or referred for prompt expert opinion. working group under the auspices of Cancer Council Australia. This article summarises the atypical clinical features of melanoma. Changes in management as a result of the guidelines: These The new guidelines chapter containing more detailed descriptions guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, of the clinical presentations of distinct melanoma subtypes, as well as desmoplastic and acral lentiginous subtypes, with particular other completed chapters of the revised guidelines, can be accessed awareness of hypomelanotic and amelanotic lesions. online at http://wiki.cancer.org.au/australia/Guidelines:Melanoma.

Method (Box 1 and Box 2). A useful extension of the ABCD criteria involves adding EFG (elevated, firm and growing) criteria — any lesion that “ ” The study question How do atypical melanomas present? was is elevated, firm and growing over a period of more than one determined by the multidisciplinary Melanoma Guidelines Working month should raise suspicion for melanoma.11 Party. To collect all relevant evidence, a literature search was per- formed in 2015 by the Cancer Council Australia Clinical Guidelines Lack of pigment is significantly associated with poorer diagnostic 12 Network using PubMed and Embase, with the key words “atypical accuracy. Up to 20% of all melanomas are only partially pig- melanoma”, “typical melanoma”, “nodular melanoma”, “desmo- mented (hypomelanotic), with completely amelanotic melanomas 13,14 plastic melanoma”, “amelanotic melanoma”, “amelanosis”, “acral much less common. Nodular, desmoplastic and acral lentigi- lentiginous melanoma”, “subungal melanoma”, “scalp melanoma” nous subtypes are more commonly hypomelanotic (over 40% of and “clinical features”. Given the nature of the study question, a cases) compared with superficial spreading and lentigo maligna 13,15,16 broad range of study designs including caseecontrol, cohort and subtypes (about 10e25% of cases). Spitzoid melanomas are 17 comparative studies were included in the search criteria. Informa- also commonly non-pigmented. Hypomelanotic melanomas may tion from the search was collated and summarised, and key findings mimic basal cell carcinomas clinically, with a slightly shiny surface that directly addressed the study question formed the main evidence and atypical vessels on dermoscopy (Box 1). Other dermoscopic summary, with level of evidence determined using the National clues include scar-like depigmentation, an inverse network, irreg- 14,18 Health and Medical Research Council evidence hierarchy (https:// ular blue-grey dots, a blue-white veil, and milky pink areas or www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nh shiny white streaks (on polarised dermoscopy only; Box 2). While mrc_levels_grades_evidence_120423.pdf). Practice points were dermoscopic sensitivity is about 90% for pigmented lesions, it is included based on expert consensus. much lower for predominantly amelanotic lesions. Although many NMs are seemingly non-pigmented, closer in- 16 October 2017 j Recommendations spection reveals faint pigmentation in some and focal pigmentation in others. Dermoscopy shows melanin pigment in 90% of Melanomas may not conform to the usual ABCD (asymmetry, NMs, although 27% in one large series were lightly or focally border irregularity, colour variegation, diameter > 6 mm) criteria. pigmented and 9.6% were completely amelanotic.19 Compared

MJA 207 (8) They are sometimes symmetrical, dome shaped and skin coloured with non-nodular subtypes, dermoscopic features such as

1 Victorian Melanoma Service, Alfred Health, Melbourne, VIC. 2 Monash University, Melbourne, VIC. 3 Peter MacCallum Cancer Centre, Melbourne, VIC. 4 Melanoma Institute Australia, 5 348 Sydney, NSW. University of Sydney, Sydney, NSW. [email protected] j doi: 10.5694/mja17.00123 j See Editorial, p. 330 j Online ﬁrst 09/10/17 Podcast available at https://www.mja.com.au/podcasts Guideline summary

1 Amelanotic desmoplastic melanoma on the scalp 4 Ulcerated hypomelanotic acral lentiginous melanoma (5.8 mm thick) (4.8 mm thick)

A: Shiny, symmetrical, dome-shaped scalp nodule. B: Polarised dermoscopy (magnification, Â 10) demonstrates atypical polymorphic vessels (>), milky pink areas (x) and lacks the typical in-focus arborising vessels of a basal cell carcinoma. u A: Well circumscribed pink/red nodule, which could be mistaken for a verruca; however, it does not have the typical pinpoint vessels. B: Instead, polarised dermoscopy (magnification, Â 10) reveals atypical vessels (>), shiny white streaks (*) and focal pigmentation (arrow). u 2 Superficial spreading melanoma (0.5 mm thick) on the posterior leg non-melanoma skin cancer. Recurrence at the site of a previous biopsy diagnosed as benign on histopathology (eg, as dermatofi- broma, neurofibroma, scar) is not an uncommon presentation of DM, as the histopathology can be difficult in some cases, particularly with a partial biopsy. Review of previous pathology may be helpful when there is clinical suspicion. Over 30% of ALMs are hypomelanotic16 (Box 3 and Box 4). Occa- sionally, ALMs are verrucous and may mimic a plantar wart or macerated tinea infection. If an ALM were to be incorrectly diagnosed as a wart and inadvertently pared down, it would not show the typical pinpoint vessels of a wart (Box 4). Dermoscopy is helpful A: New and growing shiny pink plaque with focal hyperkeratosis, easily mistaken for an fi inflamed seborrhoeic keratosis. B: Polarised dermoscopy (magnification, Â 10) when the parallel ridge pattern of pigment can be identi ed. demonstrates an atypical vascular pattern with both dotted vessels and red globules Hypomelanotic subungual melanoma may present as nail dystro- (>) along with focal hyperkeratosis, shiny white streaks (crystalline structures) (<), phy and be readily mistaken for nail trauma or infection (Box 5). milky pink structureless areas (x) and trace light brown pigment (#). Pathology fi 2 u revealed a 0.5 mm thick super cial spreading melanoma with 2 mitoses/mm . Tumour thickness is not necessarily related to diagnostic delay.2,20-22 While some melanomas grow slowly over a number of years, blue-white veil, homogeneous blue areas, black areas, milky pink others will become thick and life- threatening over weeks or areas, atypical vessels and symmetrical (rather than asymmetrical) months. More rapid growth has been associated with nodular and pigment patterns are more commonly identified.19

Dermoscopy is less useful in diagnosing DM unless features of 5 Ulcerated subungal melanoma (6 mm thick) previously an associated radial growth phase melanoma are present. It mistaken for nail trauma may be misdiagnosed clinically as a dermatoﬁbroma, scar or

3 Acral lentiginous melanoma (3.1 mm thick) J 0 (8) 207 MJA j 6Otbr2017 October 16

A: Large linear hyperkeratotic and focally eroded plantar plaque with faint pigment at the rim and inferior pole (easily mistaken for verruca or chronic scar). B: Subtle Melanin pigment is evident at the proximal and lateral nail folds (Hutchinson sign pigmentation is more obvious under Wood lamp examination (white dotted line). u shown by arrows) and there is pigment in the nail bed with haemorrhage. u 349 Guideline summary

melanomas change in size, shape or colour, and vertical growth 6 Evidence summary for atypical presentations phase melanomas evolve with elevation and ulceration and may of melanoma bleed. A history of the duration of a lesion and any change in its Evidence NHMRC level* appearance is a minimum requirement for the assessment of any Nodular, acral lentiginous and desmoplastic III-2, III-3, IV potential skin cancer. subtypes more commonly present as thick lesions; improved diagnostic accuracy of A summary of the evidence relating to atypical clinical pre- these is therefore critical3,4,6-8,10 sentations of melanomas and the impact on diagnostic accuracy is Nodular melanomas are associated with III-3, IV shown in Box 6. more rapid vertical growth compared with fi 23-26 super cial spreading melanomas Practice points Up to 20% of all melanomas are amelanotic IV or only partially pigmented, with this being Melanomas are generally distinguished from benign lesions more common among nodular, acral lentiginous and desmoplastic subtypes10,13,16 by their history of change, and thick melanomas often do not conform to the ABCD rule but usually meet the EFG criteria. fi Amelanosis/hypomelanosis is signi cantly III-2, III-3 Therefore, careful history taking is important, and any lesion associated with poorer diagnostic accuracy12,14 that continues to grow or change in size, shape, colour or * For details of the National Health and Medical Research Council (NHMRC) elevation over a period of more than one month should have a evidence hierarchy, see https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/ developers/nhmrc_levels_grades_evidence_120423.pdf. u biopsy taken and be assessed histologically or referred for expert opinion. Suspicious raised lesions should be excised rather than desmoplastic subtypes as well as amelanosis.23-26 These subtypes monitored. are more common on chronically sun-damaged skin, typically on Acknowledgements: We thank Laura Wuellner, Jutta von Dincklage and Jackie Buck from the Cancer the head and neck and predominantly in older men.10 Council Australia Clinical Guidelines Network for their assistance in this work. Development of the new Clinical Practice Guidelines for the Diagnosis and Management of Melanoma was funded by Cancer Perhaps the most helpful clinical feature of biologically signifi- Council Australia and Melanoma Institute Australia, with additional support from the Skin Cancer College Australasia. cant melanomas is that they are changing, regardless of their other clinical features. If these changes have been accurately Competing interests: No relevant disclosures. recognised by the patient or if there is photographic evidence to Provenance: Not commissioned; externally peer reviewed. n demonstrate stability or change, this may be very helpful in determining the index of suspicion. Radial growth phase ª 2017 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved.

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