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Skin melanocytic tumor

Congenital nevi and associated neoplasms

Melanoma arising in giant congenital nevus


Resident / Fellow Advisory Board: Caroline I.M. Underwood, M.D.
Anila Chughtai, M.B.B.S.
Saba Anjum, M.B.B.S.

Last author update: 7 June 2023
Last staff update: 7 June 2023

Copyright: 2022-2024, PathologyOutlines.com, Inc.

PubMed Search: Melanoma arising in giant congenital nevus

Anila Chughtai, M.B.B.S.
Saba Anjum, M.B.B.S.
Page views in 2023: 801
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Chughtai A, Anjum S. Melanoma arising in giant congenital nevus. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticmelanomagiantcongenitalnevus.html. Accessed April 25th, 2024.
Definition / general
  • Malignant tumors arising from melanocytes in pre-existing, benign melanocytic nevi of skin (e.g., giant congenital melanocytic nevi) (Br J Dermatol 2017;176:1131)
Essential features
Terminology
ICD coding
  • ICD-O: 8761/3 - malignant melanoma in giant pigmented nevus
  • ICD-10: C43.9 - malignant melanoma of skin, unspecified
Epidemiology
  • Higher risk of malignant change is reported in women; F:M = 14.1:6.4
  • Incidence of malignant change in large congenital nevi is reported to range from 3.8 to 18%
  • Malignant change mostly occurs before puberty and has also been reported at birth
  • Giant congenital nevi are associated with neurocutaneous melanosis in 3 - 15% of cases; this is associated with significantly higher risk of primary CNS melanoma
  • Primary CNS melanoma accounts for ~33% of melanoma occurring in patients with giant congenital nevi (Br J Dermatol 2017;176:1131)
  • Risk of melanoma development is exceedingly low in small to medium sized congenital nevi
  • References: Elder: Lever's Histopathology of the Skin, 11th Edition, 2014, Calonje: McKee's Pathology of the Skin, 5th Edition, 2019
Sites
Pathophysiology
Etiology
  • Melanoma can occur de novo or develop on a pre-existing nevus, known as melanoma arising in nevus
  • Melanomas arise through either cumulative sun damage pathway or noncumulative sun damage pathway; melanomas arising in congenital nevi belong to the latter category (Annu Rev Pathol 2014;9:239, Arch Pathol Lab Med 2020;144:500)
Clinical features
Diagnosis
Radiology description
  • MRI is the modality of choice for CNS screening in settings of congenital nevus syndrome / neurocutaneous melanosis and is currently the best predictor of all adverse outcomes in children
  • Those with a normal scan are in a low risk group for all complications independent of the rest of their clinical phenotype (Br J Dermatol 2017;176:1131)
  • Abnormal MRI is an indicator of a higher burden of mutated cells in the body (Br J Dermatol 2017;176:1131)
Prognostic factors
Case reports
Treatment
Clinical images

Contributed by Anila Chughtai, M.B.B.S.
Nodular ulcerated mass in CMN

Nodular ulcerated mass in CMN

Multiple congenital melanocytic nevi

Multiple congenital melanocytic nevi

After excision of malignant growth   After excision of malignant growth   After excision of malignant growth

After excision of malignant growth

Gross description
Microscopic (histologic) description
  • Benign melanocytic nevus can be identified in background of malignant proliferation
  • Malignant proliferation / melanoma exhibits the following morphological features
    • Epidermal ulceration is commonly present
    • Architectural asymmetry is evident with either radial growth phase or vertical growth phase
      • Radial growth phase comprises growth predominantly along the dermoepidermal junction with lateral spread and only small nests or individual cells in superficial dermis
      • Vertical growth phase comprises growth predominantly occupying dermis in form of large dermal nest and expansile sheet-like areas
    • Atypical melanocytes show irregular distribution at dermoepidermal junction (confluent growth alternating with skip area)
    • Junctional melanocytic nests show significant variation in size
    • Singly scattered melanocytes in the superficial part of the epidermis (pagetoid spread)
    • Atypical melanocytes can be round, epithelioid or spindle shaped with prominent nuclear pleomorphism, nuclear hyperchromasia, prominent nucleoli and irregular distribution of melanin pigment
    • Absence of maturation
    • Increased dermal mitotic activity (> 1/mm2) with atypical mitotic figures
    • Tumor necrosis might be present
    • Tumor infiltrating lymphocytes can be seen (brisk / nonbrisk / absent)
  • Evidence of lymph node metastasis is usually present at the time of first clinical presentation
  • Primary CNS melanoma in settings of congenital melanocytic nevi (CMN) can present either as solid tumors within the brain parenchyma or as leptomeningeal lesions (Br J Dermatol 2017;176:1131)
  • Leptomeningeal melanosis shows diffuse proliferation of melanin producing cells in leptomeninges which exhibits minimal cellular atypia and usually no brain parenchymal invasion
    • Transformation to leptomeningeal melanoma is documented on the basis of unequivocal brain parenchymal invasion or cytological atypia (Br J Dermatol 2017;176:1131)
  • References: Elder: Lever's Histopathology of the Skin, 11th Edition, 2014, Calonje: McKee's Pathology of the Skin, 5th Edition, 2019
Microscopic (histologic) images

Contributed by Anila Chughtai, M.B.B.S.
Dermal based proliferation of atypical melanocytes

Dermal based proliferation of atypical melanocytes

Architectural arrangement of melanoma

Architectural arrangement of melanoma

Architectural arrangement of background nevus

Architectural arrangement of background nevus

Background nevus cell around sebaceous units

Background nevus cell around sebaceous units

Cellular features of melanoma cells

Cellular features of melanoma cells


Cellular features of melanoma cells   Cellular features of melanoma cells

Cellular features of melanoma cells

Brisk mitotic activity

Brisk mitotic activity

Tumor necrosis   Tumor necrosis

Tumor necrosis


Variable pigmentation

Variable pigmentation

Epidermal consumption

Epidermal consumption

Tumor infiltrating lymphocytes

Tumor infiltrating lymphocytes

Nonbrisk tumor infiltrating lymphocytes

Nonbrisk tumor infiltrating lymphocytes

Brisk tumor infiltrating lymphocytes

Brisk tumor infiltrating lymphocytes


Melanoma metastasis to lymph node   Melanoma metastasis to lymph node

Melanoma metastasis to lymph node

S100 stain

S100 stain

HMB45 stain

HMB45 stain

MelanA stain

MelanA stain

Cytology description
Cytology images

Contributed by Anila Chughtai, M.B.B.S.
Diff-Quik stained smear   Diff-Quik stained smear

Diff-Quik stained smear

Papanicolaou stained smear   Papanicolaou stained smear

Papanicolaou stained smear

Cytoplasmic melanin pigment

Cytoplasmic melanin pigment


Cytoplasmic melanin pigment

Cytoplasmic melanin pigment

Cell block preparation   Cell block preparation

Cell block preparation

HMB45 stain on cell block

HMB45 stain on cell block

MelanA stain on cell block

MelanA stain on cell block

Electron microscopy description
Molecular / cytogenetics description
  • Melanoma harbors KIT, PTEN, TERT-p, CDKN2A, TP53 and NRAS mutations (Cell 2015;161:1681)
  • BRAF mutations have not been described in melanoma arising in congenital nevi (Br J Dermatol 2017;176:1131)
  • Copy number abnormalities (loss or gain of part of or whole chromosome) are commonly documented in melanoma arising in settings of congenital nevi (Br J Cancer 2017;116:990)
Videos

Melanocytic dermpath basics: melanoma

Sample pathology report
  • Lesion, right arm, excisional biopsy:
    • Malignant melanoma arising in background of congenital nevus
    • Macroscopic:
      • Received elliptical skin excision specimen (4.3 x 3.7 x 2.4 cm) with ulcerated pigmented nodular lesion (3.1 x 2.5 cm). Representative sections of the lesion are taken along with margins.
    • Microscopy:
      • Sheet and confluent nests of atypical melanocytes with enlarged pleomorphic nuclei having prominent eosinophilic nucleoli, eosinophilic cytoplasm, brisk and abnormal mitotic activity. Cytoplasmic melanin pigment is identified. Necrosis and epidermal ulceration are seen. Pagetoid spread to epidermis is noted. Benign melanocytic nevus is seen at the periphery of malignant proliferation. Tumor infiltrating lymphocytes are noted and are brisk. Resection margins are free.
    • Details of morphological prognostic parameters are as follows
      • Ulceration: present
      • Growth phase: vertical
      • Breslow depth: 3.8 mm
      • Dermal mitotic rate (mitoses/mm2): 3
      • Microsatellites: absent
      • Regression: absent
      • Neurotropism: absent
      • Lymphatic invasion: absent
      • Tumor infiltrating lymphocytes (TILs): present (brisk)
      • Margin: all margins are free with closest being free by 2.0 cm
      • TNM staging: pT3; pNx; pMx
Differential diagnosis
  • Proliferating nodule (Elder: Lever's Histopathology of the Skin, 11th Edition, 2014, Calonje: McKee's Pathology of the Skin, 5th Edition, 2019):
    • Proliferating nodules can mimic melanoma arising in congenital melanocytic nevus
    • Proliferating nodules exhibit large melanocytes with conspicuous nucleoli (however, nucleoli are not prominent), rare mitotic activity (< 1/mm2), no abnormal mitosis, no necrosis, no pagetoid spread, rare epidermal involvement
    • Proliferating nodules merge with adjacent nevus cells while malignant melanoma usually exhibits sharp delineation
    • Melanocytes in proliferation nodules retain nuclear expression of H3K27me3 stain while melanoma cells show nuclear loss
    • PRAME stain is positive in melanoma
    • Proliferating nodules exhibit HMB45 expression in only the superficial part of the lesion while melanoma shows its expression in the superficial as well as in the deeper part of the lesion
    • Melanoma harbors BRAF, KIT, PTEN, TERT-p, CDKN2A, TP53 mutations in addition to the NRAS mutation, which is commonly seen in proliferating nodules (Cell 2015;161:1681)
Board review style question #1


A 21 year old man presented with a new lump that appeared in previously known congenital nevus. The histopathology features of the nodule are shown in the photograph. Which of the following immunohistochemical stains would help differentiate proliferating nodule from melanoma?

  1. H3K27me3
  2. HMB45
  3. MelanA / MART1
  4. S100
  5. SOX10
Board review style answer #1
A. H3K27me3. The majority of melanoma cells show nuclear loss of H3Kme3 IHC stain while it is retained in proliferating nodule as well as in background nevus cells. Answers B, C, D and E are incorrect because HMB45, MelanA, S100 and SOX10 IHC stains will be positive in both benign proliferating nodules and melanoma; therefore, these will not help in differentiation.

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Reference: Melanoma arising in giant congenital nevus
Board review style question #2
Which of the following morphological features is the most important in determining prognosis of malignant melanoma arising in congenital nevi?

  1. Breslow thickness
  2. Necrosis
  3. Pagetoid spread to epidermis
  4. Surface ulceration
  5. Tumor regression
Board review style answer #2
A. Breslow thickness. Breslow thickness is the most important morphological parameter that helps determine pathological stage of the tumor and ultimately prognosis. Answers B, C, D and E are incorrect because while tumor necrosis, pagetoid spread, surface ulceration and tumor regression are all important parameters and add significant prognostic value, Breslow thickness is the most important parameter out of all others.

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Reference: Melanoma arising in giant congenital nevus
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