Skin melanocytic tumor

Melanocytic tumors on acral skin and nail apparatus

Acral melanoma



Last author update: 13 March 2024
Last staff update: 13 March 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Acral melanoma

Kaitlin Vanderbeck, M.D.
Carlos A. Torres-Cabala, M.D.
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Cite this page: Vanderbeck K, Torres-Cabala CA. Acral melanoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticacrallentiginous.html. Accessed March 18th, 2024.
Definition / general
  • Acral melanoma (AM): melanoma relating to or affecting the non-hair bearing / glabrous or volar skin of the soles, palms and digits as well as the nail apparatus
Essential features
  • Occurs in nail apparatus as well as on volar surfaces of feet and hands (Cancer 1980;46:2492)
  • Multiple histologic subtypes, including acral lentiginous melanoma (ALM) as well as other conventional histologic subtypes such as superficial spreading melanoma (SSM, also known as low cumulative sun damage [CSD] melanoma), nodular melanoma (NM) and desmoplastic melanoma
Terminology
  • Acral lentiginous melanoma
  • Nail apparatus melanoma
ICD coding
  • ICD-10: C43.9 - malignant melanoma of skin, unspecified
  • ICD-11: 2C30.3 - acral lentiginous melanoma, primary
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
Diagnosis
  • Clinical presentation
  • Definitive diagnosis is made on biopsy or excisional specimen through histologic examination
Prognostic factors
Case reports
Clinical images

Images hosted on other servers:
Plantar surface

Plantar surface

Erosive and macerated lesion

Erosive and macerated lesion

In situ

In situ

Invasive ALM

Invasive ALM

Microscopic (histologic) description
  • Prominent acanthosis of epidermis with elongated rete ridges can be seen
  • Pagetoid spread
  • Atypical nuclei
  • Increased N:C ratio
  • Proliferation of melanocytes downward along eccrine ducts
  • Consumption of epidermis present (attenuation of basal / suprabasal layers with rete ridge loss) (J Cutan Pathol 2012;39:577)
  • Early lesions may show proliferation of solitary melanocytes in the epidermal rete ridge (crista profunda intermedia) underlying the ridge of the skin marking (Am J Dermatopathol 2006;28:21)
  • Nail lesions show confluent stretches of solitary melanocytes, multinucleation, lichenoid inflammatory reaction and florid pagetoid spread (Am J Surg Pathol 2008;32:835)
  • Heterologous osseocartilaginous differentiation seen more commonly in acral melanoma
  • ALM is the most common histopathologic subtype, followed by NM and SSM (JAMA Dermatol 2013;149:1281, Sci Rep 2016;6:31432, Melanoma Res 2017;27:315)
  • ALM
    • ALM in situ demonstrates an increased number of irregularly distributed melanocytes at basal epidermis
    • Variable cytologic atypia of melanocytes with hyperchromatic nuclei
    • Prominent dendrites and confluent distribution of melanocytes
    • Later vertical growth phase develops with invasion into dermis
    • Melanocytes comprising the vertical growth phase are spindled (NF1 mutations) to epithelioid (BRAF mutations) (J Invest Dermatol 2018;138:933)
  • Subungual melanoma: first demonstrates a mild proliferation of atypical melanocytes with hyperchromatic nuclei, increased N:C ratio and elongated dendrites (Am J Surg Pathol 2007;31:1902, J Dermatol 2008;35:695, J Cutan Pathol 2016;43:41)
    • Important histologic features in subungual melanoma in situ include irregular and hyperchromatic nuclei and increased melanocyte count (Histopathology 2021;78:717)
Microscopic (histologic) images

Contributed by Carlos A. Torres-Cabala, M.D.
Atypical compound melanocytic proliferation

Atypical compound melanocytic proliferation

Atypical junctional component

Atypical junctional component

Vertical growth phase

Vertical growth phase

Atypical melanocytes

Atypical melanocytes

Pagetoid spread

Pagetoid spread


Atypical epithelioid melanocytes

Atypical epithelioid melanocytes

Confluence of atypical junctional melanocytes

Confluence of atypical junctional melanocytes

Epithelioid to spindled cytology

Epithelioid to spindled cytology

SOX10

SOX10

D2-40 / MITF double stain

D2-40 / MITF double stain


HMB45

HMB45

MelanA

MelanA

SOX10 in invasive component

SOX10 in invasive component

PRAME

PRAME

Positive stains
Negative stains
  • HMB45, MelanA are negative in desmoplastic melanoma subtype
Molecular / cytogenetics description
Sample pathology report
  • Skin, right toe, punch biopsy:
    • Invasive melanoma, acral lentiginous type (see comment)
    • Tumor thickness (Breslow): at least 0.9 mm
    • Clark level: at least IV
    • Ulceration: present (0.2 mm width)
    • Regression: not identified
    • Mitotic count: 1/mm2
    • Tumor infiltrating lymphocytes: present, nonbrisk
    • Lymphovascular invasion: not identified
    • Perineural invasion: not identified
    • Tissue edges: melanoma present at deep and peripheral tissue edges
    • Comment: Sections show skin and subcutis with a cellular and atypical compound melanocytic proliferation that extends to deep and peripheral tissue edges. Confluence of atypical melanocytes is appreciated at the dermoepidermal junction. Pagetoid spread is also readily seen. Cytologically, the melanocytes are epithelioid to spindled with abundant intracytoplasmic melanin pigment. These melanocytes have atypical and enlarged nuclei with readily identifiable mitotic figures within the dermal component. By immunohistochemistry, the tumor cells are positive for MelanA, HMB45, S100, SOX10 and PRAME. Overall, the findings are supportive of the above interpretation. Correlation with the subsequent excisional specimen is recommended for further definite staging information and classification.
Differential diagnosis
  • Acral lentiginous melanocytic nevi:
    • ALM and nevi with pagetoid scatter are difficult to differentiate
    • Acral nevi:
      • Melanocytes have less hyperchromatic and irregular nuclei
      • Melanocytes appear smaller in acral nevi with mitotic activity rare or absent
      • Inflammation and confluence of melanocytes at dermoepidermal junction are less common with acral nevi
      • Patient demographics, including age, size, clinical appearance, dermoscopic impressions, are required for diagnosis
      • In compound nevi, maturation of melanocytes is seen with descent
      • Acral nevi tend to be negative for PRAME and, if compound, to show decreased expression of HMB45 and LEF1 with descent (Mod Pathol 2020;33:2067)
      • Acral melanoma is more likely to be positive for cyclin D1 than acral nevi (Diagn Pathol 2021;16:60)
    • Acral lentiginous nevus:
      • Predominantly junctional growth pattern with melanocytes arranged in nests of single cells along basal layer of the epidermis, giving a lentiginous appearance
      • Mild to moderate cytologic atypia; this cytologic atypia is less than that seen with ALM
      • Some cases may demonstrate pagetoid spread (see MANIAC below); typically lack significant dermal involvement
    • Compound acral nevus:
      • Junctional component demonstrates melanocytes in nests and single cells along the basal layer of the epidermis with mild to moderate cytologic atypia; this cytologic atypia is less that that seen in acral melanoma
      • Some cases may demonstrate pagetoid spread
      • Dermal component demonstrates melanocytes in nests that are surrounded by fibroblasts and collagen fibers, typically without sclerosis, desmoplasia or significant inflammatory reaction (as in melanoma)
      • Melanocytes demonstrate maturation with depth within the dermis
    • Melanocytic acral nevus with intraepithelial ascent of cells, variant of acral nevus (MANIAC), also known as lentiginous nevus with upward migration of melanocytes:
      • Defining feature of the variant is the presence of upward migration of melanocytes from the basal layer into the overlying epithelium
      • Pagetoid spread is most often seen toward the center of the lesion
      • This nevus otherwise demonstrates a predominantly junctional growth pattern with mild to moderate cytologic atypia; the cytologic atypia is typically less than that expected with ALM
      • Dermal component can be seen in these nevi; if dermal component is present, maturation of melanocytes with depth is observed and mitotic activity is usually rare or absent (see compound acral nevus above)
  • Other clinically relevant diagnostic considerations include the following
    • Fibroma:
      • Well circumscribed proliferation of spindled fibroblasts in collagenous stroma
      • There is an absence of a melanocytic proliferation
      • Fibroblasts are cytologically bland
    • Subungual hematoma:
      • Often demonstrate pigmentation clinically; examination demonstrates hemorrhage, hemosiderin, hemosiderin laden macrophages
      • There is an absence of a melanocytic proliferation
    • Verruca:
      • Hyperkeratosis, epidermal hyperplasia, papillomatosis and hypergranulosis
      • Koilocytic / viral cytopathic change appreciated within keratinocytes
      • Dilated capillaries may also be seen within superficial dermis
    • Squamous cell carcinoma:
      • Atypical and invasive squamous proliferation with increased mitotic activity and cytologic atypia
    • Pyogenic granuloma:
      • Relatively bland vascular proliferation with superficial vessels
      • Predominantly lobular configuration of vessels
      • Overlying epidermal hyperplasia
    • Lentigo:
      • Increased (melanin) pigmentation within predominantly basal layer of epidermis without an increase in melanocytes
      • Melanocytic proliferation appears absent
Board review style question #1

A 60 year old man presented with a dark 7 mm nodule on his heel (see images above). What is the best diagnosis?

  1. Acral melanoma
  2. Acral nevus
  3. Deep penetrating nevus / WNT activated deep penetrating / plexiform melanocytoma
  4. Hemangioma

Board review style answer #1
A. Acral melanoma. The images demonstrate an atypical compound melanocytic proliferation with a confluence of atypical melanocytes apparent at the dermoepidermal junction. Answer B is incorrect as the images lack benign features. The confluence of melanocytes, atypia of melanocytes with hyperchromatic, irregular and enlarged nuclei, increased N:C ratio and apparent mitotic figures are more in keeping with melanoma. Answer C is incorrect as the images do not show a wedge shaped melanocytic proliferation that is predominantly dermal. The images demonstrate marked cytologic and nuclear atypia as described that are more in keeping with melanoma versus deep penetrating nevus. Answer D is incorrect as the images demonstrate a melanocytic lesion and not a vascular lesion.

Comment Here

Reference: Acral melanoma
Board review style question #2
What immunohistochemical profile would be expected in an acral lentiginous melanoma?

  1. MelanA-, SOX10+, S100+, PRAME+, HMB45+, cyclin D1-
  2. MelanA+, SOX10-, S100-, PRAME+, HMB45+, cyclin D1+
  3. MelanA+, SOX10+, S100+, PRAME-, HMB45+, cyclin D1+
  4. MelanA+, SOX10+, S100+, PRAME+, HMB45+, cyclin D1+

Board review style answer #2
D. MelanA+, SOX10+, S100+, PRAME+, HMB45+, cyclin D1+. Via immunohistochemistry, acral lentiginous melanomas are positive for conventional melanoma markers including MelanA, SOX10, S100, PRAME and HMB45 as well as cyclin D1. Answers A, B and C are incorrect because acral lentiginous melanoma (ALM) is typically positive for all markers listed.

Comment Here

Reference: Acral melanoma
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