Melanocytic lesions

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Melanocytic lesions are commonly encountered in dermatopathology and an area which causes some difficulty, i.e. it is hard to decide in some cases whether a lesion is benign (e.g. Spitz nevus) or malignant (malignant melanoma).

Overview

Identifying melanocytes

  • Clear or pigmented cytoplasm.
  • +/-Nuclear pseudoinclusions.
  • Epithelioid (superficial) or spindled (deep).

Benign lesions

Name Key feature Microscopic Clinical Gross Image Ref.
Lentigo simplex no nests, epidermis only slender rete with melanocytes; no nests of melanocytes; no dermal melanocytes < 40 years small flat pigmented lesion [1]
Junctional melanocytic nevus nests in epidermis nests of melanocytes at tips of rete, no dermal melanocytes usu. sun exposed skin, unusual in >50 years small flat (uniformly) pigmented lesion [1]
Compound melanocytic nevus benign nests in dermis & epidermis nests of melanocytes at tips of rete and in dermis; dermal melanocytes lack nucleoli, lack mitoses and "mature with depth" -- see Note 1. small slightly raised (uniformily) pigmented lesion [2]
Intradermal melanocytic nevus nested & individual melanocytes - only in dermis nested & individual melanocytes - only in dermis, +/- multinucleation, +/-pseudovascular spaces Clinical DDx: fibroepithelial polyp (skin tag), basal cell carcinoma raised, non-pigmented lesion [2]
Spitz nevus (epithelioid and spindle-cell nevus) long axis of nests perpendicular to surface, DE junction lesion spindled, epithelioid or mixed melanocytes, long axis of nests perpendicular to surface, superficial mitoses common, +/-hyperkeratosis, +/-acanthosis, +/-hypergranulosis Children & adolescents usu. non-pigmented Spitz nevus (drmihm.com) [2]
Pigmented spindle cell nevus of Reed (AKA Pigmented spindle cell nevus) nests of heavily pigmented spindle cells, DE junction lesion heavily pigmented spindle cells in epidermis & dermis, form "basket weave" pattern, well-circumscribed women in teens & 20s; location: shoulder, pelvic girdle region Pigmented +++, small size Reed nevus - low mag. (WC), Reed nevus - intermed. mag. (WC), Reed nevus - collection (histopathology-india.net) [3]
Blue nevus lentil-shaped (ovoid) nests btw collagen bundles, dermal lesion lentil-shaped nests, mix of spindle or dendritic or epithelioid cell morphology, nests btw collagen usu. head & neck or extremities; clinically confused with melanoma[4] blue flat or slightly raised lesion Blue nevus (WC), Blue nevus - very low mag. (WC), Blue nevus - intermed. mag. (WC) [5]
Cellular blue nevus dermal lesion with pigmented spindle cells & epithelioid cells deep dermis +/-subcutis extension; cells lack nucleoli; biphasic: (1) epithelioid cells with pale cytoplasm, (2) pigmented spindle cells +/- melanophages congenital or acquired; usu. scalp or butt blue flat or raised lesion [5]
Congenital-pattern nevus growth along dermal structures extend along dermal structures (e.g. nerves, hair shafts, ducts); lacks atypia; +/-mitoses congenital or acquired; large ones increased melanoma risk[6] small, intermediate (2-20 cm) or large [5]
Dysplastic nevus (Clark's nevus) melanocyte bridges, lamellar fibrosis melanocytes "bridges" between sides of rete ridges, "lamellar fibrosis" (collagen deep to epidermis), mod. atypia may be familial - precursor to melanoma may have asymmetry in shape or pigmentation Dysplastic nevus - low mag., Dysplastic nevus - high mag. [7]
Halo nevus lymphocytes +++ lymphocytes at perimeter of melanocytic; epidermal melanocytes not nested; may be dermal, epidermal or both central zone of pigment [7]

Note 1:

  • "Maturation" in the context of melanocytic lesions means (1) the cells get smaller with depth, (2) cells are less mitotic with depth.

Melanocytic nevus

General

  • Benign.
  • Think melanoma.
  • In common language: mole.

Clinical:

  • ABCD = asymmetric, borders (irregular), colour (black), diameter (large).

Microscopic

Features:

  • Symmetrical lesion.
  • "Matures" with depth
    • Less cellular with depth
    • Less nuclear atypia with depth.
    • Smaller cells with depth.
    • Smaller nests with depth.
  • Rare mitoses (superficial).
    • No deep mitoses.
  • No destruction of surrounding structures.
  • No nucleoli.

Subtypes

Compound melanocytic nevus
  • In the dermis and epidermis - key feature.
Junctional melanocytic nevus
  • In the epidermis - key feature.
Intradermal melanocytic nevus
  • AKA dermal nevus, AKA intradermal melanocytic nevus.
  • Only in the dermis - key feature.
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SKIN, PUNCH BIOPSY: 
	- INTRADERMAL MELANOCYTIC NEVUS.

Congenital-pattern nevus

  • AKA congenital nevus.

General

  • Congenital or acquired - thus "congenital-pattern".
  • Large ones increase melanoma risk.[6]
    • Small (<2 cm), intermediate (2-20 cm), large (>20 cm).

Microscopic

Features:[5]

  • Growth along dermal structures - key feature.
    • Nerves, hair shafts, ducts.
  • Lacks nuclear atypia.
  • +/-Mitoses.

Recurrent nevus

General

  • Partially excised nevi. (???)

Microscopic

Features - three layers (often described as a "sandwich"):

  1. Features of a compound nevus or junctional nevus.
  2. Scar.
    • Thick collagen bundles arranged parallel to the skin surface.
  3. Features of an intradermal nevus.

Pigmented spindle cell nevus

  • AKA pigmented spindle cell nevus of Reed.

General

  • Uncommon.
  • Women in teens & 20s.
  • Location: shoulder, pelvic girdle region.

Microscopic

Features:[3]

  • Nests of heavily pigmented spindle cells at dermal-epidermal junction - key feature.
    • Nevoid cells in epidermis & dermis - form "basket weave" pattern
  • Well-circumscribed lesion.

Notes:

  • No epithelioid nevus cells.

DDx:

Images:

Spitz nevus

  • AKA epithelioid and spindle-cell nevus.

General

  • May be very difficult to differentiate from melanoma.

Epidemiology:

  • Children & adolescents.

Treatment:

  • Complete excision.[8]

Gross

  • Usually face or extremity.[9]

Microscopic

Features:[2]

  • Architecture:
    • Nests of cells (spindle, epithelioid or spindle/epithelioid) - in both dermis and epidermis.
      • Nests are vertically arranged, i.e. the long axis of the nests are perpendicular to the skin surface.
        • Nest arrangement/orientation described as "cluster of bananas".
  • +/-Hyperkeratosis (more keratin, i.e. thick stratum corneum).
  • +/-Hypergranulosis (thick stratum granulosum).
  • +/-Acanthosis (thick stratum spinosum).
  • Kamino bodies (also written Camino bodies) - dense eosinophilic bodies.[10]
    • Apoptotic cells.
    • Kamino bodies are rare in melanoma.

Notes:

  • Never in the setting of solar elastosis.[11]
    • If there is solar elastosis -- it's melanoma.

DDx:

Images:

Blue nevus

  • Abbreviated BN.

General

  • Usually head & neck, extremities (e.g. dorsum of wrist or foot) or buttock.[12]
  • Clinically confused with malignant melanoma.[4]

Clinical:

  • Blue flat or slightly raised lesion.

Microscopic

Features:[5]

  • Lentil-shaped (ovoid) nests between collagen bundles.
  • Mix of spindle or dendritic or epithelioid cell morphology.

Notes:[13]

  • No epidermal component.
  • May be assoc. with a hair follicle.

DDx:

Images:

Variants of blue nevus

Several histologic variants:[13]

  • Common blue nevus - the BN not otherwise specified.
  • Sclerosing blue nevus - has stromal fibrosis.
  • Amelanotic blue nevus - may be confused with a dermatofibroma.
  • Epithelioid blue nevus.
  • Cellular blue nevus.

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SKIN LESION, RIGHT WRIST DORSUM, PUNCH BIOPSY: 
	- COMMON BLUE NEVUS.

Cellular blue nevus

General

  • Congenital or acquired.
  • Usu. scalp or butt.

Microscopic

Features:[5]

  • Dermal lesion with pigmented spindle cells & epithelioid cells - key feature.
  • Cells lack nucleoli.
  • Biphasic:
    1. Epithelioid cells with pale cytoplasm.
    2. Pigmented spindle cells +/- melanophages.

Images:

Acral nevus

  • AKA melanocytic nevus with intraepidermal ascent of cells (MANIAC).

General

  • Palms or soles.

Microscopic

Features:

  • Nevus with intraepidermal ascent of cells.

Notes:

  • Intraepidermal ascent of cells is usually suggestive of melanoma.
    • In acral sites the criteria are relaxed, i.e. this is considered benign for this site.

Clark nevus

  • AKA dysplastic nevus.
  • AKA dysplastic melanocytic nevus.

General

  • Benign.
  • Clark nevi are considered a risk factor for melanoma and may be a precursor of melanoma, as the name dysplastic nevus suggests.[14]
    • Most melanoma cases do not have evidence of a pre-existing (dysplastic) nevus.[15]
  • Large numbers of these nevi (10-100) are seen in dysplastic nevus syndrome.[16]
    • Individuals with this syndrome have an increased risk of melanoma and approximately one third of their melanomas arise from a Clark nevus. The other two thirds arise de novo.

Clinical:[17]

  • Associated with sun exposure.

Treatment:

  • Clark nevi with severe nuclear atypia are treated like melanoma.

Gross

Features:[17]

  • "Ugly duckling sign" - lesion looks different than the rest.
  • ABCDE criteria of in melanoma.

Microscopic

Features:[7]

  • Melanocytes "bridges" between sides of rete ridges.
  • Drapping fibrous tissue - "lamellar fibrosis" - collagen deep to epidermis.
  • Usually moderate nuclear atypia (small nucleoli present) - see grading section.
  • Junctional component (cells in the epidermis at the DE junction) larger than the intradermal component - shoulder phenomenon.

DDx:

Images:

Grading

These lesions are usually graded:[18]

Grade Size of nucleus Other features
Mild 1x keratinocyte nucleus no nucleoli/very small nucleoli †,[19] slight hyperchromasia
Moderate 1-2x keratinocyte nucleus small nucleoli †, irregular nuclear contours
Severe >2x keratinocyte nucleus prominent nucleoli †‡

† The sizes "very small", "small" and "prominent" are not defined; it is suggested that "very small" is visible with the 40x objective, "small" with the 20x objective and "prominent" with the 10x objective. Focal, rare small nucleoli are not significant; they can be seen in benign melanocytic nevi.
‡ Prominent nucleoli (alone) is considered enough to call "severe".[18]

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SKIN, EXCISION:
- DYSPLASTIC NEVUS WITH MILD NUCLEAR ATYPIA.
- MARGINS NEGATIVE FOR NEVUS CELLS.

Neurocristic hamartoma

Main article: Neurocristic hamartoma

See also

References

  1. ↑ 1.0 1.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 498. ISBN 978-0781765275.
  2. ↑ 2.0 2.1 2.2 2.3 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 499. ISBN 978-0781765275.
  3. ↑ 3.0 3.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 500. ISBN 978-0781765275.
  4. ↑ 4.0 4.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 592. ISBN 978-1416054542.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 501. ISBN 978-0781765275.
  6. ↑ 6.0 6.1 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1170. ISBN 978-1416031215.
  7. ↑ 7.0 7.1 7.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 502. ISBN 978-0781765275.
  8. ↑ Gelbard, SN.; Tripp, JM.; Marghoob, AA.; Kopf, AW.; Koenig, KL.; Kim, JY.; Bart, RS. (Aug 2002). "Management of Spitz nevi: a survey of dermatologists in the United States.". J Am Acad Dermatol 47 (2): 224-30. PMID 12140468.
  9. ↑ Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 449. ISBN 978-0443066542.
  10. ↑ Kirkwood, John M.; Jukic, Drazen; Averbook, Bruce J.; Sender, Leonard S. (October 2009). "Melanoma in Pediatric, Adolescent, and Young Adult Patients". Semin Oncol. 36 (5): 419-31. PMC 2797485. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797485/.
  11. ↑ Jakubovic, H. 16 July 2010.
  12. ↑ Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 456. ISBN 978-0443066542.
  13. ↑ 13.0 13.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 457. ISBN 978-0443066542.
  14. ↑ Rezze, GG.; Leon, A.; Duprat, J. (Dec 2010). "Dysplastic nevus (atypical nevus).". An Bras Dermatol 85 (6): 863-71. PMID 21308311.
  15. ↑ Longo, C.; Rito, C.; Beretti, F.; Cesinaro, AM.; Piñeiro-Maceira, J.; Seidenari, S.; Pellacani, G. (Sep 2011). "De novo melanoma and melanoma arising from pre-existing nevus: in vivo morphologic differences as evaluated by confocal microscopy.". J Am Acad Dermatol 65 (3): 604-14. doi:10.1016/j.jaad.2010.10.035. PMID 21715047.
  16. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 155600
  17. ↑ 17.0 17.1 Dediol, I.; Bulat, V.; Zivković, MV.; Marković, BM.; Situm, M. (Sep 2011). "Dysplastic nevus--risk factor or disguise for melanoma.". Coll Antropol 35 Suppl 2: 311-3. PMID 22220461.
  18. ↑ 18.0 18.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 447-8. ISBN 978-0443066542.
  19. ↑ Arumi-Uria, M.; McNutt, NS.; Finnerty, B. (Aug 2003). "Grading of atypia in nevi: correlation with melanoma risk.". Mod Pathol 16 (8): 764-71. doi:10.1097/01.MP.0000082394.91761.E5. PMID 12920220.
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