Amelanotic / hypomelanotic melanoma

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 Authored by: Teresa Russo     ·  Veronica Di Brizzi     ·  Giuseppe Argenziano

 Keywords:   amelanotic melanoma · hypomelanotic melanoma · ahm
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Author(s) Teresa Russo · Veronica Di Brizzi · Giuseppe Argenziano
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Amelanotic/hypomelanotic melanomaThis glossary term has not yet been described. (AHMThis glossary term has not yet been described.) represents 2-8% of all melanomas[1], but its real incidence is difficultneeding much effort or skill to accomplish to estimate because at the beginning it is often misdiagnosed and/or confused with inflammatory diseases, benignis any condition that is harmless in the long run tumors and other malignantThis glossary term has not yet been described. tumors (i.e. actinic keratosisActinic keratosis (also called solar keratosis and senile keratosis; abbreviated as AK) is a pre-cancerous patch of thick, scaly, or crusty skin., Bowenalso known as squamous cell carcinoma in situ[1] is a neoplastic skin disease. It can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after John T. Bowen’s disease, basal cell carcinomais the most common skin cancer, and one of the most common cancers in the United States.[1] While BCC has a very low metastatic risk, this tumor can cause significant disfigurement by invading surrounding tissues, keratoacanthomaThis glossary term has not yet been described., Merkel cell carcinoma, pyogenic granulomaThis glossary term has not yet been described., haemangioma, wart, etc). Definitely, if singly evaluated, the real prevalence of amelanotic melanomatype of skin cancer in which the cells do not make melanin is very low, since many of these tumors present a residual pigmentation that can be seen mostly at the periphery and should be considered hypomelanotic rather than amelanotic. The low or absent melanin production and the presence of regression are the two reasons why melanomaThis glossary term has not yet been described. could be amelanotic or hypomelanotic; both these phenomena may even occur within the same lesion.

AHM has been classified in several variants:

  1. True amelanotic melanoma (melanoma not producing any trace of pigment)
  2. Hypomelanotic melanomaThis glossary term has not yet been described. (with low production of melanin that may extend to the entire lesion)
  3. Partially pigmented melanoma(with a pigmentation occupying less than 25% of the lesion)
  4. Regressive melanoma (in advanced stages of regressionThis glossary term has not yet been described.)

AHM often occurs in sun-exposed skin of older people[1][2] and appears as a flat lesion, but more frequently as an elevated tumor, firm on palpation, and typified by rapid growth. This three characteristics (EFG: Elevation, Firmness, Growth) represent a precious clinical guide in melanomas without the classical ABCDThis glossary term has not yet been described. clinical criteriameasure of how well one variable or set of variables predicts an outcome[3][4].

By dermoscopyThe examination of [skin lesions] with a 'dermatoscope'. This traditionally consists of a magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of liquid medium and instead use polarised light to cancel out skin surface reflections., the diagnostic cluesEvidence, in an investigation for AHM are the vascular structuresThis glossary term has not yet been described., often also difficult to detect because require a minimal pressure of the dermatoscopeThis traditionally consists of a magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of liquid medium and instead use polarised light to cancel out skin surface reflections. on the lesion to avoid the compression of the blood vesselsare the part of the circulatory system, and microcirculation, that transports blood throughout the human body[5]. As general rule, six main categories of vascular morphologies can be seen in tumoral lesions[6]: comma vesselslinear curved short vessels dermal nevi (in intradermal neviThis glossary term has not yet been described.); dotted vesselstiny pinpoint vessels (in melanocyticThis glossary term has not yet been described. lesions, especially Spitz neviThis glossary term has not yet been described. and melanoma); linear–irregular vesselsThis glossary term has not yet been described. (in melanoma and other skin malignancies); arborizing vesselsanalytic term is branched vessels; Bright red sharply in focus large or thick diameter vessels dividing into smaller vessels; BCC (in basal cell carcinoma); hairpin vessels (in keratinizing tumors, especially if surrounded by a whitish halo, and melanoma); and glomerular vesselsThis glossary term has not yet been described. (in Bowen’s disease). Moreover, also the following three specific global morphologies can be identified: crown vesselsRadial serpentine or arborizing vessels at the periphery of the lesion that radiate towards the center but do not cross the midline od the lesion. sebaceous hyperplasia surrounding a white center, strawberry patternReddish pseudo-network (erythema and wavy fine vessels) around hair follicle openings which are accentuated with a white halo appearance and milky-red areas/globulesThis glossary term has not yet been described.[7][8][9][10]. (Fig.1)


Figure 1: The most common vessels in dermoscopy.
Figure 1: The most common vessels in dermoscopy.

The most common vascular structures in AHM are dotted vessels, linear-irregular vessels, hairpin-irregular vessels, serpentine vesselslinear irregular linear vessels with multiple bends flat BCC melanoma or a combinationThis glossary term has not yet been described. of them (polymorphic vessels)[5]; also milky-red areas can be frequently visualized[1].MorphologyThis glossary term has not yet been described. of vessels modifies during tumor growth. In fact, in early stages, the vessels often appear short and homogenous in shape, while in the advanced tumors, they appear longer and irregular. In thin melanoma (less than 0.5 mm Breslow thickness) the vessels are usually pointThis glossary term has not yet been described.-like with a rather regular arrangementThis glossary term has not yet been described.. Tumors of 0.5–2mm thickness show both point-like and hairpin vessels, again with a regular arrangement. When thickness is over 2 mm the hairpin loops are more twisted, splintered and irregularly distributed, while melanomas of more than 3 mm of thickness develop polymorphic vessels. A multicenter retrospective study from Menzies et al. evaluated several amelanotic and hypomelanotic melanomas to determine the diagnostic accuracyThis glossary term has not yet been described. of various dermoscopic features[5]. Positive predictors included blue-white veil, scar-like depigmentationArea of white that is whiter than surrounding normal skin (true scarring). It should not be confused with hypo- or depigmentation due to simple loss of melanin. Shiny white structures and blood vessels are not seen in areas of regression., multiple blue-gray dotsDots are small, round structures of less than 0.1 mm in diameter that have a red color when corresponding to blood vessels; however, when due to melanin, their color ranges from black, brown, to blue-gray depending on the depth and concentration of the melanin in the skin (Tyndall effect)., irregularly shaped depigmentation, irregular brown dots or globules, 5 to 6 colorsThis glossary term has not yet been described. within the same lesion and peripheral light brown structureless areas covering more than 10% of the lesion. Among vascular features, the positive predictors were predominant central vessels, milky red-areas, more than one shade of pink, and a combination of dotted and linear irregularlinear vessels with multiple bends vessels. The most significant negative predictors of melanoma were multiple (>3) milia-like cystsThis glossary term has not yet been described., the predominance of comma vessels with a regular arrangement, a symmetrical pigmentation, and regular and multiple blue-gray globules (Fig.2, 3,4,5,6,7).


Figure 2: Nodular hypomelanotic melanoma with hairpin, glomerular, linear irregular vessels (polymorphic vessels) and blue-white veil over a milky-red area.
Figure 2: Nodular hypomelanotic melanoma with hairpin, glomerular, linear irregular vessels (polymorphic vessels) and blue-white veil over a milky-red area.


Figure 3: Early invasive amelanotic melanoma with mainly dotted vessels irregularly distributed over a pinkish background.
Figure 3: Early invasive amelanotic melanoma with mainly dotted vessels irregularly distributed over a pinkish background.


Figure 4: Early invasive amelanotic melanoma with dotted vessels regularly distributed over a pinkish background (Spitzoid- looking melanoma).
Figure 4: Early invasive amelanotic melanoma with dotted vessels regularly distributed over a pinkish background (Spitzoid- looking melanoma).


Figure 5: More advanced hypomelanotic melanoma with polymorphous vessels. Blue-white veil, and remnants of pigment network and brown globules are also detectable.
Figure 5: More advanced hypomelanotic melanoma with polymorphous vesselsmultiple types of vessels are present may indicate malignancy in appropriate context for example in flat melanocytic lesions. Blue-white veil, and remnants of pigment networkThis glossary term has not yet been described. and brown globules are also detectable.


Figure 6: Early invasive hypomelanotic melanoma with dotted vessels in the upper part and pigment network in the lower part of the lesion.
Figure 6: Early invasive hypomelanotic melanoma with dotted vessels in the upper part and pigment network in the lower part of the lesion.


Figure 7: Regressive hypomelanotic melanoma with linear-irregular vessels and a peripheral residual pigmentation.
Figure 7: Regressive hypomelanotic melanoma with linear-irregular vessels and a peripheral residual pigmentation.




ReferencesThis is material contained in a footnote or bibliography holding further information.
  1. 1.01.11.2 Pizzichetta et al.: Amelanotic/hypomelanotic melanoma: clinical and dermoscopic features. Br. J. Dermatol. 2004;150:1117-24. PMID: 15214897. DOI.
  2. Adler & White: Amelanotic malignant melanoma. Semin Cutan Med Surg 1997;16:122-30. PMID: 9220551.
  3. Chamberlain et al.: Nodular melanomaThis glossary term has not yet been described.: patients' perceptions of presenting features and implications for earlier detection. J. Am. Acad. Dermatol. 2003;48:694-701. PMID: 12734497. DOI.
  4. Stojkovic-Filipovic & Kittler: DermatoscopyThe examination of [skin lesions] with a 'dermatoscope'. This traditionally consists of a magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of liquid medium and instead use polarised light to cancel out skin surface reflections. of amelanotic and hypomelanotic melanoma. J Dtsch Dermatol Ges 2014;12:467-72. PMID: 24825465. DOI.
  5. 5.05.15.2 Menzies et al.: Dermoscopic evaluation of amelanotic and hypomelanotic melanoma. Arch Dermatol 2008;144:1120-7. PMID: 18794455. DOI.
  6. Zalaudek et al.: How toGives basic instructions and directions to someone on the methods for doing or making something. diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. MelanocyticThis glossary term has not yet been described. skin tumors. J. Am. Acad. Dermatol. 2010;63:361-74; quiz 375-6. PMID: 20708469. DOI.
  7. Argenziano et al.: Vascular structuresThis glossary term has not yet been described. in skin tumors: a dermoscopy study. Arch Dermatol 2004;140:1485-9. PMID: 15611426. DOI.
  8. Kreusch & Koch: [Incident light microscopic characterization of vascular patternsThis glossary term has not yet been described. in skin tumors]. Hautarzt 1996;47:264-72. PMID: 8655309.
  9. Zalaudek I, Argenziano G, Oliviero M, Rabinovitz H. DermoscopyThe examination of [skin lesions] with a 'dermatoscope'. This traditionally consists of a magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of liquid medium and instead use polarised light to cancel out skin surface reflections. of non pigmented skin tumors. In: Thiers BH, Lang PG Jr, eds. Year bookA book is a set of sheets of paper, parchment, or similar materials that are fastened together to hinge at one side. of dermatology and dermatologic surgery. Philadelphia: Elsevier Mosby, 2007
  10. Zalaudek et al.: Dermoscopy in general dermatology. Dermatology (Basel) 2006;212:7-18. PMID: 16319467. DOI.