Skin melanocytic tumor

Deep penetrating, BAP1 inactivated & pigmented epithelioid melanocytomas

WNT activated deep penetrating / plexiform melanocytoma (nevus)



Last author update: 21 September 2023
Last staff update: 21 September 2023

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PubMed Search: Deep penetrating nevus

Kaitlin Vanderbeck, M.D.
Carlos A. Torres-Cabala, M.D.
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Cite this page: Vanderbeck K, Torres-Cabala CA. WNT activated deep penetrating / plexiform melanocytoma (nevus). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticdeeppennevus.html. Accessed March 19th, 2024.
Definition / general
Essential features
Terminology
ICD coding
  • ICD-10: D22.9 - melanocytic nevi, unspecified
  • ICD-11: XH81Y1 - deep penetrating nevus
Epidemiology
Sites
Pathophysiology
  • Lesions demonstrate Wnt pathway activation via gain of function mutation in CTNNB1, which encodes beta catenin protein (Biology (Basel) 2022;11:460, Zhonghua Jie He He Hu Xi Za Zhi 1988;11:362)
  • Most arise from common acquired nevi and therefore may also exhibit mutations in the mitogen activated protein kinase (MAPK) pathway (BRAF [p.V600E], MEK1 / MAP2K1, HRAS) (Nat Commun 2017;8:644)
  • Mutations in beta catenin and BRAF result in activation of LEF1 (transcription factor), which leads to epithelial mesenchymal transition and tumor growth and development (Biology (Basel) 2022;11:460)
  • Rare cases may exhibit inactivation of APC (Biology (Basel) 2022;11:460)
  • Increased melanocyte size and pigmentation derived from Wnt pathway activation
Clinical features
Diagnosis
Case reports
Treatment
Clinical images

Images hosted on other servers:
Linear distribution of nevi behind ear

Linear distribution of nevi behind ear

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Kaitlin Vanderbeck, M.D. and Carlos A. Torres-Cabala, M.D.
Pigmented predominantly dermal melanocytic lesion

Pigmented
predominantly
dermal melanocytic
lesion

Pigmented epithelioid to spindled melanocytes

Pigmented epithelioid to spindled melanocytes

Combined nevus

Combined nevus

HMB45

HMB45

Ki67

Ki67


Beta catenin

Beta catenin

Beta catenin nuclear positivity

Beta catenin nuclear positivity

Cyclin D1

Cyclin D1

LEF1

LEF1

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Skin, right arm, excisional biopsy:
    • Deep penetrating nevus, margins appear free (see comment)
    • Comment: Sections show skin and subcutis with a cellular melanocytic proliferation within dermis with extension into subcutis. Cytologically, the melanocytes are epithelioid to spindled with abundant melanin pigment appreciated. The melanocytes are arranged in a wedge shaped orientation with focal encircling on adnexal structures and nerves within predominantly deep dermis. Nuclear pleomorphism, conspicuous cherry red nucleoli, lymphovascular invasion and mitotic activity are not identified. By immunohistochemistry, the lesional cells of interest are positive for HMB45, cyclin D1 (nuclear and cytoplasmic), beta catenin (nuclear, cytoplasmic and membranous), LEF1 (nuclear) and p16. Ki67 proliferation index is relatively low. Overall, the findings are supportive of the above interpretation. Further clinical correlation and follow up are recommended as appropriate.
Differential diagnosis
Board review style question #1

What immunohistochemical staining profile would you expect for the skin lesion pictured above?

  1. HMB45 negative; beta catenin negative; cyclin D1 shows cytoplasmic staining
  2. HMB45 negative; beta catenin shows nuclear, cytoplasmic and membranous staining; cyclin D1 negative
  3. HMB45 positive; beta catenin shows cytoplasmic staining; cyclin D1 negative
  4. HMB45 positive; beta catenin shows nuclear, cytoplasmic and membranous staining; cyclin D1 shows nuclear and cytoplasmic staining
Board review style answer #1
D. HMB45 positive; beta catenin shows nuclear, cytoplasmic and membranous staining; cyclin D1 shows nuclear and cytoplasmic staining. This is the expected staining profile for deep penetrating nevus / WNT activated deep penetrating / plexiform melanocytoma (DPN). DPN typically demonstrates positive staining for HMB45 and demonstrates nuclear, cytoplasmic and membranous staining for beta catenin and nuclear and cytoplasmic staining for cyclin D1. Of note, DPN typically demonstrates Wnt pathway activation via gain of function mutations of CTNNB1, which encodes beta catenin protein. Wnt activation results in the increased melanocyte size and pigmentation seen in DPN.

Answer B is incorrect because DPN is typically positive for HMB45 and demonstrates nuclear and cytoplasmic positivity for cyclin D1. DPN demonstrates nuclear, cytoplasmic and membranous staining for beta catenin. Answer C is incorrect because DPN typically demonstrates nuclear, cytoplasmic and membranous staining for beta catenin and nuclear and cytoplasmic staining for cyclin D1. DPN demonstrates positive staining for HMB45. Answer A is incorrect because DPN is typically positive for HMB45 and exhibits nuclear, cytoplasmic and membranous staining for beta catenin and nuclear and cytoplasmic staining for cyclin D1.

Comment Here

Reference: WNT activated deep penetrating / plexiform melanocytoma (nevus)
Board review style question #2


A 37 year old woman presented with a dark 5 mm papule on her forearm. An excisional biopsy is performed and is shown in the image above. What is the best diagnosis?

  1. Cellular blue nevus
  2. WNT activated deep penetrating / plexiform melanocytoma (deep penetrating nevus)
  3. Melanoma
  4. Spitz nevus
Board review style answer #2
B. WNT activated deep penetrating / plexiform melanocytoma (deep penetrating nevus). The image demonstrates a cellular wedge shaped melanocytic proliferation with abundant pigment and involvement of dermis and subcutis. A junctional component is not seen. These are hallmark features of deep penetrating nevus (DPN).

Answer D is incorrect. Typically compound, these nevi demonstrate a raining down appearance of melanocytes. Kamino bodies can be seen. These nevi are seen predominantly in younger / pediatric patients (see Spitz nevus). Answer A is incorrect because cellular blue nevus is usually more superficial and melanocytes are typically spindled in shape. Borders are typically pushing versus wedge shaped (see Blue nevus / cellular blue nevus). Answer C is incorrect because melanoma may have an atypical junctional component including pagetoid spread of melanocytes. Melanoma typically exhibits obvious mitotic figures (including atypical), marked atypia, lymphovascular invasion, ulceration, necrosis and other features of malignancy (see Melanoma).

Comment Here

Reference: WNT activated deep penetrating / plexiform melanocytoma (nevus)
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