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), Spitz nevus - high mag. (WC), Spitz nevus - intermed. mag. (WC) [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.

Lentiginous melanocytic lesions

Lentigo simplex

General

  • Benign.
  • Usually <40 years old.

Fits into the larger category of lentiginous melanocytic proliferations - these include:[9]

Associated syndromes:[10]

Gross

  • Small flat pigmented lesion.[1]

DDx - clinical:

Microscopic

Features:[1]

  • Melanocytes in epidermis only.
    • Melanocytes basally located (normal location) with hyperpigmentation.
  • No melanocytic nests.
  • +/-Mild/moderate elongation of the rete ridges.[11]

DDx:[12]

Images

  • Simple lentigo. (WC)

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SKIN LESION, LEFT ABDOMEN, BIOPSY:
- SIMPLE LENTIGO, COMPLETELY EXCISED IN THE PLANE OF SECTION.

SKIN LESION, LEFT ABDOMEN, BIOPSY:
- BENIGN SIMPLE LENTIGO.

Micro

The sections show skin with increased numbers of small pigmented melanocytes at the dermal-epidermal junction. The rete ridges are mildly elongated. No solar damage is apparent. No dermal melanocytes are identified. No melanocytic nests are identified. No nuclear atypia is apparent.

Solar lentigo

  • Plural solar lentigines.

General

  • Benign.

Fits into the larger category of lentiginous melanocytic proliferations - these include:[9]

Gross

Features:[9]

  • Small (< 4 mm), irregular brown macule.
  • Usu. sun-exposed area.

DDx (clinical):

Microscopic

Features:[14]

  • Hyperpigmented melanocytes - may be present in increased quantities - key feature.
    • Classically at the tips of the rete ridges.
  • No (melanocyte) nuclear atypia.
  • Solar damage (solar elastosis).[11]

Notes:

  • Should not be present:[9]
    • Nests of melanocytes.
    • Pagetoid spread of melanocytes.

DDx:[14]

Images=

  • Solar lentigo. (WC)

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FOREARM LESION, RIGHT, PUNCH BIOPSY:
- SOLAR LENTIGO.

Micro

The sections show hair-bearing skin with basilar pigmentation at the tips of the rete ridges and solar elastosis. No melanocytic nests are identified. The epidermal cells mature to the surface. No significant inflammation is present.

Lentiginous melanocytic nevus

  • AKA lentiginous nevus.

General

  • Benign.

Fits into the larger category of lentiginous melanocytic proliferations - these include:[9]

Gross

  • Small flat pigmented lesion.

Microscopic

Features:[9]

  • Melanocytes without atypia in the epidermis only - key feature.
  • Melanocytic nests.
  • +/-Rete ridge elongation.

DDx:

Images

www:

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SKIN LESION, BACK, SHAVE EXCISION:
- JUNCTIONAL LENTIGINOUS NEVUS.
-- COMPLETELY EXCISED (LATERAL CLEARANCE 1 MM).

Micro

The sections show skin with non-nested melanocytes in the epidermis. The melanocytes have no significant cytologic atypia. There is no upward scatter of melanocytes. The lesion is completely excised the in plane of section.

Nested melanocytic lesions

Common melanocytic nevus

  • AKA common nevus.
  • In common language: mole.

General

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
  • Abbreviated CMN and CN.
  • In the dermis and epidermis - key feature.
Junctional melanocytic nevus
  • Abbreviated JN.
  • In the epidermis - key feature.
Intradermal melanocytic nevus
  • AKA dermal nevus.
  • AKA intradermal melanocytic nevus.
  • AKA intradermal nevus, abbreviated IDN.[15]
  • Only in the dermis - key feature.
  • +/-Adipocytes - uncommon.[16]

Note:

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Junctional melanocytic nevus

SKIN LESION, RIGHT LATERAL UPPER ARM, BIOPSY:
- BENIGN JUNCTIONAL NEVUS.
Micro

The sections show melanocytes in nest confined to the epidermis. The lesion is symmetrical in its architecture and pigment distribution. There is no pagetoid spread of melanocytes in the epidermis. No significant nuclear atypia is identified. No mitotic activity is appreciated.

The lesion is completely excised in the plane of section.

Compound melanocytic nevus

SKIN LESION, RIGHT NECK, SHAVE BIOPSY:
- BENIGN COMPOUND NEVUS.
Micro

The sections show melanocytes in the dermis and epidermis. The lesion is symmetrical in its architecture and pigment distribution. There is no pagetoid spread of melanocytes in the epidermis. Superficially, melanocytes are in nests. Melanocytes show no apparent cytologic atypia and mature with depth. No mitotic activity is appreciated.

The lesion is completely excised in the plane of section.

Barely compound

The sections show melanocytes predominantly in the dermis. Rare melanocytic nests are seen at the dermal-epidermal junction. There is no pagetoid spread of melanocytes in the epidermis. The lesion is symmetrical in its architecture. Superficially, melanocytes are in nests and pigment is present. The melanocytes mature with depth. No mitotic activity is appreciated.

The lesion is present at the margin.

CN with congenital features

The sections show melanocytes in the dermis and epidermis. There is no pagetoid spread of melanocytes in the epidermis. Superficially, melanocytes are in nests. Melanocytes show mild nuclear enlargement but mature with depth. Nucleoli are not prominent. Melanocytes are found adjacent to adnexal structures and blood vessels. No mitotic activity is appreciated. The lesion is incompletely excised.

Intradermal melanocytic nevus

SKIN LESION, BACK, PUNCH BIOPSY: 
- BENIGN INTRADERMAL NEVUS.
Adipocytes present
SKIN LESION, BACK, PUNCH BIOPSY: 
- BENIGN INTRADERMAL NEVUS WITH MATURE ADIPOCYTES.
Clinically suspicious
SKIN LESION, LEFT UPPER ARM, PUNCH BIOPSY:
- BENIGN INTRADERMAL NEVUS, INCOMPLETELY EXCISED.

COMMENT:
HMB-45 marks very rare superficial cells. Ki-67 staining does not show apparent melanocyte
staining. MITF marks the melanocytes and demonstrates maturation of the melanocytes with depth.
Micro

The sections show melanocytes in the dermis separated from the epidermis by a Grenz zone. The lesion is symmetrical in its architecture and pigment distribution. Superficially, melanocytes are in nests. Melanocytes mature with depth. No mitotic activity is appreciated.

The lesion is completely excised in the plane of section.

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.
    • "Deep" melanocytes.
  • Lacks nuclear atypia.
  • +/-Mitoses.
  • +/-Less nesting.[17]

DDx:

Images:

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SKIN LESION, LEFT UPPER BACK, BIOPSY:
- COMPOUND MELANOCYTIC NEVUS WITH CONGENITAL FEATURES.

Recurrent melanocytic nevus

  • AKA persistent melanocytic nevus.
  • AKA pseudomelanoma.

General

  • Classically, arises at the site of a partially excised nevus.[18]

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.

May have:[18]

  • Pagetoid spread of melanocytes.
  • Confluent nests at the DE junction.
  • Nuclear atypia - uncommon.

DDx:[18]

IHC

  • HMB-45 deep component -ve.
  • Ki-67 - non-proliferative.

Sclerosing melanocytic nevus

  • AKA sclerosing nevus.

General

Microscopic

Features:[19]

  • Trizonal - may be described as a sandwich:
    1. Junctional or compound nevus.
      • May have pagetoid spread of melanocytes, i.e. non-basal melanocytes in the epidermis.
      • Cannot have cytologic atypia - presence of cytologic atypia in this layer makes it melanoma.
    2. Fibrotic tissue with irregular melanocytic nests.
    3. Nevus below scar - may be common, congenital-type, dysplastic, Spitz.

DDx:

Pigmented spindle cell nevus

  • AKA pigmented spindle cell nevus of Reed.
Main article: Pigmented spindle cell nevus

Spitz nevus

  • AKA epithelioid and spindle cell nevus.
Main article: Spitz nevus

Acral nevus

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

General

  • Palms or soles.

Note:

  • Volar refers to the palmar aspect or plantar aspect.[20]

Gross

  • Pigmented lesion.

Note:

  • Should be bisected perpendicular to the dermatoglyphs (ridges).[21]
    • Lesions sectioned parallel to the ridges (on microscopy) may appear to have confluent junctional nests (leading to the diagnosis of melanoma).

Microscopic

Features:

  • Acral skin:
    • Thick stratum corneum (hyperkeratotic).
    • Thick stratum spinosum (acanthotic).
  • Nevus with intraepidermal ascent of cells.
    • May be referred to as Pagetoid scatter.
    • Should not be present at the edge of the lesion - key feature.[21]

Notes:

  • Intraepidermal ascent of cells is usually suggestive of melanoma.
    • In acral sites (esp. at the centre of a lesion) the criteria are relaxed, i.e. this is considered benign for this site.
  • Nests in the ridges raise the suspicion of melanoma.
    • Memory device "ridges are risky, furrows are fine".[21]

DDx:

Dysplastic melanocytic nevus

  • AKA dysplastic nevus.
  • AKA Clark nevus.
  • AKA nevus with architectural disorder.
    • This term is recommended by the American NIH; however, it is not widely adopted.[21]
Main article: Dysplastic nevus

Desmoplastic melanocytic nevus

  • AKA sclerosing melanocytic nevus.

General

  • Benign.

Gross

  • Usu. "small" and symmetric.

Clinical DDx:

Microscopic

Features:[22]

DDx:

IHC

Features:[22]

  • Melan A (MART-1) +ve.
    • Usually -ve in desmoplastic melanoma.[22]
  • S-100 +ve.
    • Should stain approximally the same number of cells as Melan A.
  • Ki-67 -- only rare cells.

Miscellaneous

Blue nevus

Common blue nevus redirects here.
  • Abbreviated BN.

General

Gross

  • 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:[25]

  • Classically no epidermal component.
    • The entity compound blue nevus has been described; it is rare.[26]
  • May be assoc. with a hair follicle.

DDx:

Images

  • Blue nevus (WC)

  • Blue nevus - very low mag. (WC)

  • Blue nevus - intermed. mag. (WC)

www:

Variants of blue nevus

Several histologic variants:[25]

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

Memory device:

  • C CASE = Common, Cellular, Amelanotic, Sclerosing, Epithelioid.

IHC

  • HMB-45 diffusely +ve.[citation needed]
    • Melanoma patchy +ve.
  • MART-1 diffusely +ve.
  • Ki-67 low.

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

SKIN LESION, LEFT SHIN, PUNCH BIOPSY: 
- SCLEROSING BLUE NEVUS.

Micro

The sections show pigmented spindle cells in the dermis between collagen bundles. The spindle cells show no nuclear atypia and no mitotic activity is appreciated.

The lesion does not extend into the epidermis. There are no melanocyte nests. There is no significant inflammation. The lesion is completely excised.

The pigmented cells are negative on the Prussian blue stain.

Sclerosing blue nevus

The sections show pigmented spindle cells in the dermis between densely packed collagen fibres. The spindle cells show no significant nuclear atypia, and no mitotic activity is appreciated. The lesion extends up to the epidermis; however, it does not appear to involve the epidermis. The overlying epidermis has hyperkeratosis; otherwise, it is unremarkable. There are no nests of melanocytes. There is no significant inflammation. The lesion is completely excised in the plane of section.

Cellular blue nevus

General

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:

Combined melanocytic nevus

  • AKA combined nevus.

General

  • Uncommon.
  • Morphologic features of two types of melanocytic nevi.

Microscopic

Features:[28]

  • Morphologic features of two types of melanocytic nevi.

DDx:

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A. SKIN LESION, LEFT UPPER ARM, PUNCH BIOPSY:
- BENIGN COMBINED MELANOCYTIC NEVUS (INTRADERMAL MELANOCYTIC NEVUS AND BLUE NEVUS).

Neurocristic hamartoma

Main article: Neurocristic hamartoma

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 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 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. ↑ 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 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. ↑ URL: http://www.dermnetnz.org/lesions/lentigo-simplex.html. Accessed on: 27 March 2013.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 438. ISBN 978-0443066542.
  10. ↑ 10.0 10.1 URL: http://dermaamin.com/site/histopathology-of-the-skin/64-l/1852-lentigo-simplex-.html. Accessed on: 17 December 2012.
  11. ↑ 11.0 11.1 11.2 Hafner, C.; Stoehr, R.; van Oers, JM.; Zwarthoff, EC.; Hofstaedter, F.; Klein, C.; Landthaler, M.; Hartmann, A. et al. (Nov 2009). "The absence of BRAF, FGFR3, and PIK3CA mutations differentiates lentigo simplex from melanocytic nevus and solar lentigo.". J Invest Dermatol 129 (11): 2730-5. doi:10.1038/jid.2009.146. PMID 19536147.
  12. ↑ 12.0 12.1 URL: http://www.humpath.com/?lentigo-simplex. Accessed on: 17 December 2012.
  13. ↑ 13.0 13.1 URL: http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html. Accessed on: 6 May 2013.
  14. ↑ 14.0 14.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 437. ISBN 978-0443066542.
  15. ↑ Fullen, DR.; Reed, JA.; Finnerty, B.; McNutt, NS. (Sep 2001). "S100A6 preferentially labels type C nevus cells and nevic corpuscles: additional support for Schwannian differentiation of intradermal nevi.". J Cutan Pathol 28 (8): 393-9. PMID 11493376.
  16. ↑ Eng, W.; Cohen, PR. (Nov 1998). "Nevus with fat: clinical characteristics of 100 nevi containing mature adipose cells.". J Am Acad Dermatol 39 (5 Pt 1): 704-11. PMID 9810886.
  17. ↑ 17.0 17.1 URL: http://www.dermpedia.org/dermpedia-textbook/congenital-nevus. Accessed on: 27 December 2012.
  18. ↑ 18.0 18.1 18.2 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 465. ISBN 978-0443066542.
  19. ↑ 19.0 19.1 Fabrizi, G.; Pennacchia, I.; Pagliarello, C.; Massi, G. (Nov 2008). "Sclerosing nevus with pseudomelanomatous features.". J Cutan Pathol 35 (11): 995-1002. doi:10.1111/j.1600-0560.2007.00941.x. PMID 18537860.
  20. ↑ URL: http://www.medterms.com/script/main/art.asp?articlekey=9907. Accessed on: 14 January 2013.
  21. ↑ 21.0 21.1 21.2 21.3 Elston, D. (Jul 2012). "Practical advice regarding problematic pigmented lesions.". J Am Acad Dermatol 67 (1): 148-55. doi:10.1016/j.jaad.2012.04.006. PMID 22703907.
  22. ↑ 22.0 22.1 22.2 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 464. ISBN 978-0443066542.
  23. ↑ Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 456. ISBN 978-0443066542.
  24. ↑ URL: http://emedicine.medscape.com/article/1079272-overview. Accessed on: 10 December 2012.
  25. ↑ 25.0 25.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 457. ISBN 978-0443066542.
  26. ↑ Kamino, H.; Tam, ST. (Oct 1990). "Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases.". Arch Dermatol 126 (10): 1330-3. PMID 2221938.
  27. ↑ 27.0 27.1 Magro, CM.; Crowson, AN.; Mihm, MC. (Feb 2006). "Unusual variants of malignant melanoma.". Mod Pathol 19 Suppl 2: S41-70. doi:10.1038/modpathol.3800516. PMID 16446716.
  28. ↑ 28.0 28.1 Baran, JL.; Duncan, LM. (Oct 2011). "Combined melanocytic nevi: histologic variants and melanoma mimics.". Am J Surg Pathol 35 (10): 1540-8. doi:10.1097/PAS.0b013e31822e9f5e. PMID 21881487.

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