Difference between revisions of "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]]).
[[Image:Blue nevus - intermed mag.jpg|thumb|right|A melanocytic lesion ([[blue nevus]]). [[H&E stain]]. (WC/Nephron)]]
'''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==
=Overview=
===Identifying melanocytes===
===Identifying melanocytes===
*Clear ''or'' pigmented cytoplasm.
*Clear ''or'' pigmented cytoplasm.
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| Children & adolescents
| Children & adolescents
| usu. non-pigmented
| usu. non-pigmented
| [http://www.drmihm.com/cases/casefigure.cfm?figID=931&CaseID=51 Spitz nevus (drmihm.com)]
| [http://www.drmihm.com/cases/casefigure.cfm?figID=931&CaseID=51 Spitz nevus (drmihm.com)], [http://commons.wikimedia.org/wiki/File:Spitz_nevus_-_high_mag.jpg Spitz nevus - high mag. (WC)], [http://commons.wikimedia.org/wiki/File:Spitz_nevus_-_intermed_mag.jpg Spitz nevus - intermed. mag. (WC)]
| <ref name=Ref_WMSP499>{{Ref WMSP|499}}</ref>
| <ref name=Ref_WMSP499>{{Ref WMSP|499}}</ref>
|-
|-
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| may be familial - precursor to melanoma
| may be familial - precursor to melanoma
| may have asymmetry in shape or pigmentation
| may have asymmetry in shape or pigmentation
| [http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_low_mag.jpg Dysplastic nevus - low mag.], [http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_add_-_high_mag.jpg Dysplastic nevus - high mag.]
| [http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_low_mag.jpg Dysplastic nevus - low mag.], [http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_add_-_high_mag.jpg Dysplastic nevus - high mag.]  
| <ref name=Ref_WMSP502>{{Ref WMSP|502}}</ref>
| <ref name=Ref_WMSP502>{{Ref WMSP|502}}</ref>
|-
|-
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*"Maturation" in the context of melanocytic lesions ''means'' (1) the cells get smaller with depth, (2) cells are less mitotic with depth.
*"Maturation" in the context of melanocytic lesions ''means'' (1) the cells get smaller with depth, (2) cells are less mitotic with depth.


==Melanocytic nevus==
=Lentiginous melanocytic lesions=
==Lentigo simplex==
{{Main|Lentigo simplex}}
 
==Solar lentigo==
*Plural ''solar lentigines''.
===General===
===General===
*Benign.
*Benign.
*Think ''melanoma''.
 
Fits into the larger category of ''lentiginous melanocytic proliferations'' - these include:<ref name=Ref_Derm438>{{Ref Derm|438}}</ref>
*Solar lentigo.
*[[Lentigo simplex]].
*Lentiginous nevus.
*Lentiginous [[melanoma in situ]].
 
===Gross===
Features:<ref name=Ref_Derm438>{{Ref Derm|438}}</ref>
*Small (< 4 mm), irregular brown [[macule]].
*Usu. sun-exposed area.
 
DDx (clinical):
*[[Lentigo maligna]] - melanoma in situ on sun damaged skin.
*[[Seborrheic keratosis]], flat.<ref name=dermammin_sl>URL: [http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html]. Accessed on: 6 May 2013.</ref>
 
===Microscopic===
Features:<ref name=Ref_Derm437>{{Ref Derm|437}}</ref>
*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]]).<ref name=pmid19536147>{{Cite journal  | last1 = Hafner | first1 = C. | last2 = Stoehr | first2 = R. | last3 = van Oers | first3 = JM. | last4 = Zwarthoff | first4 = EC. | last5 = Hofstaedter | first5 = F. | last6 = Klein | first6 = C. | last7 = Landthaler | first7 = M. | last8 = Hartmann | first8 = A. | last9 = Vogt | first9 = T. | title = The absence of BRAF, FGFR3, and PIK3CA mutations differentiates lentigo simplex from melanocytic nevus and solar lentigo. | journal = J Invest Dermatol | volume = 129 | issue = 11 | pages = 2730-5 | month = Nov | year = 2009 | doi = 10.1038/jid.2009.146 | PMID = 19536147 }}</ref>
 
Notes:
*Should ''not'' be present:<ref name=Ref_Derm438>{{Ref Derm|438}}</ref>
**Nests of melanocytes.
**Pagetoid spread of melanocytes.
 
DDx:<ref name=Ref_Derm437>{{Ref Derm|437}}</ref>
*Pigmented [[actinic keratosis]].
*[[Lichen planus-like keratosis]].
*Pigmented [[seborrheic keratosis]].
*[[Ephelis]] (freckle).
 
====Images====
<gallery>
Image:Skin_tumors_181.jpg | Solar lentigo. (WC)
</gallery>
*[http://www.dermaamin.com/site/images/histo-pic/a/actinic-lentigo/actinic-lentigo1.jpg Solar lentigo (dermammin.com)].<ref name=dermammin_sl>URL: [http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html]. Accessed on: 6 May 2013.</ref>
 
===Sign out===
<pre>
FOREARM LESION, RIGHT, PUNCH BIOPSY:
- SOLAR LENTIGO.
</pre>
 
====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:<ref name=Ref_Derm438>{{Ref Derm|438}}</ref>
*[[Solar lentigo]].
*[[Lentigo simplex]].
*Lentiginous nevus.
*Lentiginous [[melanoma in situ]].
 
===Gross===
*Small flat pigmented lesion.
 
===Microscopic===
Features:<ref name=Ref_Derm438>{{Ref Derm|438}}</ref>
*Melanocytes without atypia in the epidermis only - '''key feature'''.
*Melanocytic nests.
*+/-Rete ridge elongation.
 
DDx:
*[[Atypical lentiginous nevus]].
*[[Dysplastic nevus]].
*[[Melanoma in situ]] - especially if [[solar elastosis]] is present.
 
====Images====
www:
*[http://www.derm101.com/Popups/FigurePopup.aspx?id=dp0101a06f005&aid=740564&filename=dp0101a06g005b Lentiginous nevus (derm101.com)].
 
===Sign out===
<pre>
SKIN LESION, BACK, SHAVE EXCISION:
- JUNCTIONAL LENTIGINOUS NEVUS.
-- COMPLETELY EXCISED (LATERAL CLEARANCE 1 MM).
</pre>
 
====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''.
*In common language: ''mole''.
 
===General===
*Benign.
*Common.
*Think ''[[melanoma]]''.
Clinical:  
Clinical:  
*''ABCD'' = asymmetric, borders (irregular), colour (black), diameter (large).
*''ABCD'' = asymmetric, borders (irregular), colour (black), diameter (large).
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====Subtypes====
====Subtypes====
=====Compound melanocytic nevus=====
=====Compound melanocytic nevus=====
*Abbreviated ''CMN'' and ''CN''.
*In the dermis '''and''' epidermis - '''key feature'''.
*In the dermis '''and''' epidermis - '''key feature'''.


=====Junctional melanocytic nevus=====
=====Junctional melanocytic nevus=====
*Abbreviated ''JN''.
*In the epidermis - '''key feature'''.
*In the epidermis - '''key feature'''.


=====Intradermal melanocytic nevus=====
=====Intradermal melanocytic nevus=====
*[[AKA]] ''dermal nevus'', [[AKA]] ''intradermal melanocytic nevus''.
*[[AKA]] ''dermal nevus''.
*Only in the dermis - '''key feature'''.
*[[AKA]] ''intradermal melanocytic nevus''.
*[[AKA]] ''intradermal nevus'', abbreviated ''IDN''.<ref name=pmid11493376>{{Cite journal  | last1 = Fullen | first1 = DR. | last2 = Reed | first2 = JA. | last3 = Finnerty | first3 = B. | last4 = McNutt | first4 = NS. | title = S100A6 preferentially labels type C nevus cells and nevic corpuscles: additional support for Schwannian differentiation of intradermal nevi. | journal = J Cutan Pathol | volume = 28 | issue = 8 | pages = 393-9 | month = Sep | year = 2001 | doi =  | PMID = 11493376 }}</ref>
{{Main|Intradermal nevus}}


======Sign out======
===Sign out===
 
====Junctional melanocytic nevus====
<pre>
<pre>
SKIN, PUNCH BIOPSY:  
SKIN LESION, RIGHT LATERAL UPPER ARM, BIOPSY:
- INTRADERMAL MELANOCYTIC NEVUS.
- BENIGN JUNCTIONAL NEVUS.
</pre>
</pre>
=====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====
{{Main|Compound nevus}}
====Intradermal melanocytic nevus====
{{Main|Intradermal nevus}}


==Congenital-pattern nevus==
==Congenital-pattern nevus==
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*Growth along dermal structures - '''key feature'''.
*Growth along dermal structures - '''key feature'''.
**Nerves, hair shafts, ducts.
**Nerves, hair shafts, ducts.
**"Deep" melanocytes.
*Lacks nuclear atypia.
*Lacks nuclear atypia.
*+/-Mitoses.
*+/-Mitoses.
*+/-Less nesting.<ref name=cong_nevus_dermpedia/>
DDx:
*[[Intradermal melanocytic nevus]].
*[[Malignant melanoma]].
Images:
*[http://www.dermpedia.org/image/congenital-nevus-4 Congenital nevus - 4 (dermpedia.org)].<ref name=cong_nevus_dermpedia>URL: [http://www.dermpedia.org/dermpedia-textbook/congenital-nevus http://www.dermpedia.org/dermpedia-textbook/congenital-nevus]. Accessed on: 27 December 2012.</ref>
*[http://www.dermpedia.org/image/congenital-nevus-5 Congenital nevus - 5 (dermpedia.org)].
===Sign out===
<pre>
SKIN LESION, LEFT UPPER BACK, BIOPSY:
- COMPOUND MELANOCYTIC NEVUS WITH CONGENITAL FEATURES.
</pre>


==Recurrent nevus==
==Recurrent melanocytic nevus==
*[[AKA]] ''persistent melanocytic nevus''.
*[[AKA]] ''pseudomelanoma''.
===General===
===General===
*Partially excised nevi. (???)
*Classically, arises at the site of a partially excised nevus.<ref name=Ref_Derm465>{{Ref Derm|465}}</ref>


===Microscopic===
===Microscopic===
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#Features of an [[intradermal nevus]].
#Features of an [[intradermal nevus]].


==Pigmented spindle cell nevus==
May have:<ref name=Ref_Derm465>{{Ref Derm|465}}</ref>
*[[AKA]] ''pigmented spindle cell nevus of Reed''.
*Pagetoid spread of melanocytes.
*Confluent nests at the DE junction.
*Nuclear atypia - uncommon.
 
DDx:<ref name=Ref_Derm465>{{Ref Derm|465}}</ref>
*[[Melanoma in situ]] - classically spread beyond the scar, unlike pseudomelanoma - growth confined to epidermis.
*[[Sclerosing nevus]].
 
===IHC===
*HMB-45 deep component -ve.
*Ki-67 - non-proliferative.
 
==Sclerosing melanocytic nevus==
*[[AKA]] ''sclerosing nevus''.


===General===
===General===
*Uncommon.
*Similar to ''[[recurrent nevus]]''.
*Women in teens & 20s.
*Clinically may be confused with [[melanoma]].
*Location: shoulder, pelvic girdle region.
*No history of trauma or prior excision.


===Microscopic===
===Microscopic===
Features:<ref name=Ref_WMSP500>{{Ref WMSP|500}}</ref>
Features:<ref name=pmid18537860 >{{Cite journal  | last1 = Fabrizi | first1 = G. | last2 = Pennacchia | first2 = I. | last3 = Pagliarello | first3 = C. | last4 = Massi | first4 = G. | title = Sclerosing nevus with pseudomelanomatous features. | journal = J Cutan Pathol | volume = 35 | issue = 11 | pages = 995-1002 | month = Nov | year = 2008 | doi = 10.1111/j.1600-0560.2007.00941.x | PMID = 18537860 }}</ref>
*Nests of heavily pigmented spindle cells at dermal-epidermal junction - '''key feature'''.
*Trizonal - may be described as a ''sandwich'':
**Nevoid cells in epidermis & dermis - form "basket weave" pattern
*# [[Junctional melanocytic nevus|Junctional]] ''or'' [[compound nevus]].
*Well-circumscribed lesion.
*#* 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]].
Notes:
*# Fibrotic tissue with irregular melanocytic nests.
*No epithelioid nevus cells.
*# Nevus below scar - may be [[common melanocytic nevus|common]], congenital-type, [[dysplastic nevus|dysplastic]], [[spitz nevus|Spitz]].


DDx:
DDx:
*[[Spitz nevus]].
*[[Malignant melanoma]].
*[[Melanoma]].
*[[Recurrent melanocytic nevus]] - also trizonal; however, has a fibrotic layer that does ''not'' have melanocytes in it.<ref name=pmid18537860 />


Images:
==Pigmented spindle cell nevus==
*[http://commons.wikimedia.org/wiki/File:Pigmented_spindle_cell_nevus_-_low_mag.jpg PSCN - low mag. (WC)]. *[http://commons.wikimedia.org/wiki/File:Pigmented_spindle_cell_nevus_-_2_-_intermed_mag.jpg PSCN - intermed. mag. (WC)]. *[http://www.histopathology-india.net/Reed.htm Reed nevus - collection (histopathology-india.net)].
*[[AKA]] ''pigmented spindle cell nevus of Reed''.
{{Main|Pigmented spindle cell nevus}}


==Spitz nevus==
==Spitz nevus==
*AKA ''epithelioid and spindle-cell nevus''.
*[[AKA]] ''epithelioid and spindle cell nevus''.
{{Main|Spitz nevus}}


===General===
==Acral nevus==
*May be very difficult to differentiate from [[melanoma]].
*[[AKA]] ''melanocytic nevus with intraepidermal ascent of cells'' ([[MANIAC]]).
*[[AKA]] ''volar nevus''.
{{Main|Acral nevus}}


Epidemiology:
==Dysplastic melanocytic nevus==
*Children & adolescents.
*[[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.<ref name=pmid22703907>{{Cite journal  | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}</ref>
{{Main|Dysplastic nevus}}


Treatment:
==Desmoplastic melanocytic nevus==
*Complete excision.<ref name=pmid12140468>{{Cite journal  | last1 = Gelbard | first1 = SN. | last2 = Tripp | first2 = JM. | last3 = Marghoob | first3 = AA. | last4 = Kopf | first4 = AW. | last5 = Koenig | first5 = KL. | last6 = Kim | first6 = JY. | last7 = Bart | first7 = RS. | title = Management of Spitz nevi: a survey of dermatologists in the United States. | journal = J Am Acad Dermatol | volume = 47 | issue = 2 | pages = 224-30 | month = Aug | year = 2002 | doi =  | PMID = 12140468 }}</ref>
*[[AKA]] ''sclerosing melanocytic nevus''.
 
===General===
*Benign.


===Gross===
===Gross===
*Usually face ''or'' extremity.<ref name=Ref_Derm449>{{Ref Derm|449}}</ref>
*Usu. "small" and symmetric.
 
Clinical DDx:
*[[Dermatofibroma]].
*[[Dermal scar]].


===Microscopic===
===Microscopic===
Features:<ref name=Ref_WMSP499>{{Ref WMSP|499}}</ref>
Features:<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*Architecture:
*[[Compound nevus]] ''or'' [[intradermal nevus]] with prominent dermal fibrosis.
**Nests of cells (spindle, epithelioid or spindle/epithelioid) - in both dermis and epidermis.
**Fibrosis: extra pink - versus surrounding.
***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.<ref name=PMC2797485>{{Cite journal  | last1 = Kirkwood | first1 = John M. | last2 = Jukic | first2 = Drazen | last3 = Averbook | first3 = Bruce J. | last4 = Sender | first4 = Leonard S. | title = Melanoma in Pediatric, Adolescent, and Young Adult Patients | journal = Semin Oncol. | volume = 36 | issue = 5 | pages = 419-31 | month = October | year = 2009 | doi =  | PMID =  | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797485/?tool=pmcentrez |PMC = 2797485 }}</ref>
**Apoptotic cells.
**Kamino bodies are rare in melanoma.


Notes:
DDx:
*'''Never''' in the setting of solar elastosis.<ref>Jakubovic, H. 16 July 2010.</ref>
*[[Desmoplastic neurotropic malignant melanoma]] - usually mitotic figures, nuclear atypia (enlarged, hyperchromatic).
**If there is solar elastosis -- it's melanoma.
*[[Dermatofibroma]].
*[[Dermal scar]] - no adnexal structures.


DDx:
===IHC===
*[[Malignant melanoma]].
Features:<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*[[Pigmented spindle cell nevus of Reed]].
*Melan A (MART-1) +ve.
**Usually -ve in desmoplastic melanoma.<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*S-100 +ve.
**Should stain approximally the same number of cells as Melan A.
*Ki-67 -- only rare cells.


Images:
==Nodal nevus==
*www:
*AKA ''nevus in lymph node'' and ''benign nevus cells in lymph node''.
**[http://www.drmihm.com/cases/case.cfm?CaseID=51 Spitz nevus - collection of images (drmihm.com)].
{{Main|Nodal nevus}}
**[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=006734 Spitz nevus with arrow to camino body (unibas.ch)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Spitz_nevus_-_intermed_mag.jpg Spitz nevus - intermed. mag. (WC)].


=Miscellaneous=
==Blue nevus==
==Blue nevus==
:'''''Common blue nevus''' redirects here''.
*Abbreviated ''BN''.
*Abbreviated ''BN''.
===General===
===General===
*Usually head & neck, extremities (e.g. dorsum of wrist or foot) or buttock.<ref name=Ref_Derm456>{{Ref Derm|456}}</ref>
*Usually head & neck, extremities (e.g. dorsum of wrist or foot) or buttock.<ref name=Ref_Derm456>{{Ref Derm|456}}</ref>
*Clinically confused with [[malignant melanoma]].<ref name=Ref_PCPBoD8_592>{{Ref PCPBoD8|592}}</ref>
*Clinically confused with [[malignant melanoma]].<ref name=Ref_PCPBoD8_592>{{Ref PCPBoD8|592}}</ref>
*Second most common melanocytic lesion of the oral cavity.<ref>URL: [http://emedicine.medscape.com/article/1079272-overview http://emedicine.medscape.com/article/1079272-overview]. Accessed on: 10 December 2012.</ref>
**Most common melanocytic lesion ''[[intramucosal melanocytic nevus]]''.


Clinical:
===Gross===
*Blue flat or slightly raised lesion.
*Blue flat or slightly raised lesion.


Line 254: Line 416:


Notes:<ref name=Ref_Derm457>{{Ref Derm|457}}</ref>
Notes:<ref name=Ref_Derm457>{{Ref Derm|457}}</ref>
*No epidermal component.
*Classically no epidermal component.
** The entity ''compound blue nevus'' has been described; it is rare.<ref name=pmid2221938>{{Cite journal  | last1 = Kamino | first1 = H. | last2 = Tam | first2 = ST. | title = Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases. | journal = Arch Dermatol | volume = 126 | issue = 10 | pages = 1330-3 | month = Oct | year = 1990 | doi =  | PMID = 2221938 }}
</ref>
*May be assoc. with a hair follicle.
*May be assoc. with a hair follicle.


DDx:
DDx:
*[[Malignant melanoma]] - often lacks a Grenz zone (lesion in papillary dermis),<ref name=pmid16446716/> mitotic figures, [[necrosis]], cytologic atypia, asymmetry (architecture, pigment).
*Atypical blue nevus - have some of the features of melanoma.
*[[Clear cell sarcoma]].
*[[Dermatofibroma]] - esp. amelanotic BN.
*[[Dermatofibroma]] - esp. amelanotic BN.
*[[Malignant melanoma]].
*[[Combined melanocytic nevus]] - blue nevus found together with another nevus (classically [[common melanocytic nevus]]), superficial.
*[[Clear cell sarcoma]].
*[[Pigmented epithelioid melanocytoma]] - superificial dermis, has nuclear atypia.
*[[Vascular lesions]] ([[venous lake]], [[hemangioma]]).


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Blue_nevus_%281_of_4%29.jpg Blue nevus (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Blue_nevus_-_very_low_mag.jpg Blue nevus - very low mag. (WC)].  
Image:Blue_nevus_%281_of_4%29.jpg | Blue nevus (WC)
*[http://commons.wikimedia.org/wiki/File:Blue_nevus_-_intermed_mag.jpg Blue nevus - intermed. mag. (WC)].
Image:Blue_nevus_-_very_low_mag.jpg | Blue nevus - very low mag. (WC)
Image:Blue_nevus_-_intermed_mag.jpg | Blue nevus - intermed. mag. (WC)
</gallery>
www:
*[http://www.dermatopathonline.com/blue%20nevus2.html Several types of blue nevi (dermatopathonline.com)].
*[http://www.nature.com/modpathol/journal/v19/n2s/fig_tab/3800516f25.html#figure-title Melanoma that looks a bit like a blue nevus (nature.com)].<ref name=pmid16446716>{{Cite journal  | last1 = Magro | first1 = CM. | last2 = Crowson | first2 = AN. | last3 = Mihm | first3 = MC. | title = Unusual variants of malignant melanoma. | journal = Mod Pathol | volume = 19 Suppl 2 | issue =  | pages = S41-70 | month = Feb | year = 2006 | doi = 10.1038/modpathol.3800516 | PMID = 16446716 }}</ref>


====Variant of blue nevus====
====Variants of blue nevus====
Several histologic variants:<ref name=Ref_Derm457>{{Ref Derm|457}}</ref>
Several histologic variants:<ref name=Ref_Derm457>{{Ref Derm|457}}</ref>
*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.
*Sclerosing blue nevus - has stromal fibrosis.
*Amelanotic blue nevus - may be confused with a [[dermatofibroma]].
*Epithelioid blue nevus.
*Epithelioid blue nevus.
*Cellular blue nevus.
 
Memory device:
*''C CASE'' = '''C'''ommon, '''C'''ellular, '''A'''melanotic, '''S'''clerosing, '''E'''pithelioid.
 
===IHC===
*HMB-45 diffusely +ve.{{fact}}
**Melanoma patchy +ve.
*MART-1 diffusely +ve.
*Ki-67 low.
 
===Sign out===
<pre>
SKIN LESION, RIGHT WRIST DORSUM, PUNCH BIOPSY:
- COMMON BLUE NEVUS.
</pre>
 
<pre>
SKIN LESION, LEFT SHIN, PUNCH BIOPSY:
- SCLEROSING BLUE NEVUS.
</pre>
 
====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 and is separated from it by a Grenz zone. 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==
==Cellular blue nevus==
===General===
===General===
*Congenital or acquired.
*Congenital or acquired.
*Usu. scalp or butt.
*Usually scalp or butt.
*Variant of the ''[[common blue nevus]]''.


===Microscopic===
===Microscopic===
Line 290: Line 495:
*[http://www.dermpedia.org/case/cellular-blue-nevus-0 Cellular blue nevus (dermpedia.org)].
*[http://www.dermpedia.org/case/cellular-blue-nevus-0 Cellular blue nevus (dermpedia.org)].


==Acral nevus==
==Combined melanocytic nevus==
*[[AKA]] melanocytic nevus with intraepidermal ascent of cells (MANIAC).
*[[AKA]] ''combined nevus''.
===General===
===General===
*Palms or soles.
*Uncommon.
 
*Morphologic features of two types of melanocytic nevi.
===Microscopic===
**Most common: [[blue nevus]] and common nevus.<ref name=pmid21881487>{{Cite journal  | last1 = Baran | first1 = JL. | last2 = Duncan | first2 = LM. | title = Combined melanocytic nevi: histologic variants and melanoma mimics. | journal = Am J Surg Pathol | volume = 35 | issue = 10 | pages = 1540-8 | month = Oct | year = 2011 | doi = 10.1097/PAS.0b013e31822e9f5e | PMID = 21881487 }}</ref>
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 [[malignant melanoma|melanoma]] and may be a precursor of melanoma, as the name ''dysplastic nevus'' suggests.<ref name=pmid21308311>{{Cite journal  | last1 = Rezze | first1 = GG. | last2 = Leon | first2 = A. | last3 = Duprat | first3 = J. | title = Dysplastic nevus (atypical nevus). | journal = An Bras Dermatol | volume = 85 | issue = 6 | pages = 863-71 | month = Dec | year = 2010 | doi =  | PMID = 21308311 }}</ref>
**Most melanoma cases do not have evidence of a pre-existing (dysplastic) nevus.<ref name=pmid21715047>{{Cite journal  | last1 = Longo | first1 = C. | last2 = Rito | first2 = C. | last3 = Beretti | first3 = F. | last4 = Cesinaro | first4 = AM. | last5 = Piñeiro-Maceira | first5 = J. | last6 = Seidenari | first6 = S. | last7 = Pellacani | first7 = G. | title = De novo melanoma and melanoma arising from pre-existing nevus: in vivo morphologic differences as evaluated by confocal microscopy. | journal = J Am Acad Dermatol | volume = 65 | issue = 3 | pages = 604-14 | month = Sep | year = 2011 | doi = 10.1016/j.jaad.2010.10.035 | PMID = 21715047 }}</ref>
*Large numbers of these nevi (10-100) are seen in ''dysplastic nevus syndrome''.<ref name=omim155600>{{OMIM|155600}}</ref>
**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:<ref name=pmid22220461>{{Cite journal  | last1 = Dediol | first1 = I. | last2 = Bulat | first2 = V. | last3 = Zivković | first3 = MV. | last4 = Marković | first4 = BM. | last5 = Situm | first5 = M. | title = Dysplastic nevus--risk factor or disguise for melanoma. | journal = Coll Antropol | volume = 35 Suppl 2 | issue =  | pages = 311-3 | month = Sep | year = 2011 | doi =  | PMID = 22220461 }}</ref>
*Associated with sun exposure.
 
Treatment:
*Clark nevi with severe nuclear atypia are treated like melanoma.
 
===Gross===
Features:<ref name=pmid22220461/>
*"Ugly duckling sign" - lesion looks different than the rest.
*ABCDE criteria of in melanoma.


===Microscopic===
===Microscopic===
Features:<ref name=Ref_WMSP502>{{Ref WMSP|502}}</ref>
Features:<ref name=pmid21881487/>
*Melanocytes "bridges" between sides of rete ridges.
*Morphologic features of two types of melanocytic nevi.
*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:
DDx:
*[[Malignant melanoma]].
*[[Malignant melanoma]].
*[[Compound melanocytic nevus]].
*[[Pigmented epithelioid melanocytoma]] - superificial dermis, has nuclear atypia.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_low_mag.jpg Dysplastic nevus - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_intermed_mag.jpg Dysplastic nevus - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_add_-_high_mag.jpg Dysplastic nevus - high mag. (WC)] - shows bridging and lamellar fibrosis.
*[http://commons.wikimedia.org/wiki/File:Dysplastic_nevus_-_add_-_very_high_mag.jpg Dysplastic nevus - very high mag. (WC)] - shows bridging and lamellar fibrosis.
 
====Grading====
These lesions are usually graded:<ref name=Ref_Derm447-8>{{Ref Derm|447-8}}</ref>
{| class="wikitable sortable"
! Grade
! Size of nucleus
! Other features
|-
| Mild
| 1x keratinocyte nucleus
| no [[nucleoli]]/very small nucleoli †,<ref name=pmid12920220>{{Cite journal  | last1 = Arumi-Uria | first1 = M. | last2 = McNutt | first2 = NS. | last3 = Finnerty | first3 = B. | title = Grading of atypia in nevi: correlation with melanoma risk. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 764-71 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000082394.91761.E5 | PMID = 12920220 | URL = http://www.nature.com/modpathol/journal/v16/n8/full/3880837a.html }}</ref> 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.<br>
‡ Prominent nucleoli (alone) is considered enough to call "severe".<ref name=Ref_Derm447-8>{{Ref Derm|447-8}}</ref>


===Sign out===
===Sign out===
<pre>
<pre>
SKIN, EXCISION:
A. SKIN LESION, LEFT UPPER ARM, PUNCH BIOPSY:
- DYSPLASTIC NEVUS WITH MILD NUCLEAR ATYPIA.
- BENIGN COMBINED MELANOCYTIC NEVUS (INTRADERMAL MELANOCYTIC NEVUS AND BLUE NEVUS).
- MARGINS NEGATIVE FOR NEVUS CELLS.
</pre>
</pre>


Line 374: Line 519:
{{Main|Neurocristic hamartoma}}
{{Main|Neurocristic hamartoma}}


==See also==
=See also=
*[[Dermatopathology]].
*[[Dermatopathology]].
*[[Cytopathology]].
*[[Cytopathology]].
*[[Non-malignant skin disease]].
*[[Non-malignant skin disease]].
*[[Pigmented lesions of the oral cavity]].
*[[Melanosis coli]].
*[[Small bowel pseudomelanosis]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}
=External links=
*[http://www.youtube.com/watch?v=_4jgUcxMezM Dear 16 year-old me (youtube.com)] - with Dr. G.


[[Category:Dermatopathology]]
[[Category:Dermatopathology]]
[[Category:Melanocytic lesions]]

Latest revision as of 18:47, 11 February 2021

A melanocytic lesion (blue nevus). H&E stain. (WC/Nephron)

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

Solar lentigo

  • Plural solar lentigines.

General

  • Benign.

Fits into the larger category of lentiginous melanocytic proliferations - these include:[8]

Gross

Features:[8]

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

DDx (clinical):

Microscopic

Features:[10]

  • 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:[8]
    • Nests of melanocytes.
    • Pagetoid spread of melanocytes.

DDx:[10]

Images

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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:[8]

Gross

  • Small flat pigmented lesion.

Microscopic

Features:[8]

  • 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.[12]

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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

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.
    • "Deep" melanocytes.
  • Lacks nuclear atypia.
  • +/-Mitoses.
  • +/-Less nesting.[13]

DDx:

Images:

Sign out

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.[14]

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:[14]

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

DDx:[14]

IHC

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

Sclerosing melanocytic nevus

  • AKA sclerosing nevus.

General

Microscopic

Features:[15]

  • 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.

Spitz nevus

  • AKA epithelioid and spindle cell nevus.

Acral nevus

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

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.[16]

Desmoplastic melanocytic nevus

  • AKA sclerosing melanocytic nevus.

General

  • Benign.

Gross

  • Usu. "small" and symmetric.

Clinical DDx:

Microscopic

Features:[17]

DDx:

IHC

Features:[17]

  • Melan A (MART-1) +ve.
    • Usually -ve in desmoplastic melanoma.[17]
  • S-100 +ve.
    • Should stain approximally the same number of cells as Melan A.
  • Ki-67 -- only rare cells.

Nodal nevus

  • AKA nevus in lymph node and benign nevus cells in lymph node.

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:[20]

  • Classically no epidermal component.
    • The entity compound blue nevus has been described; it is rare.[21]
  • May be assoc. with a hair follicle.

DDx:

Images

www:

Variants of blue nevus

Several histologic variants:[20]

  • 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 and is separated from it by a Grenz zone. 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:[23]

  • Morphologic features of two types of melanocytic nevi.

DDx:

Sign out

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

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 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. 8.0 8.1 8.2 8.3 8.4 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 438. ISBN 978-0443066542.
  9. 9.0 9.1 URL: http://www.dermaamin.com/site/histopathology-of-the-skin/53-a/1555-actinic-lentigo-.html. Accessed on: 6 May 2013.
  10. 10.0 10.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 437. ISBN 978-0443066542.
  11. 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. 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.
  13. 13.0 13.1 URL: http://www.dermpedia.org/dermpedia-textbook/congenital-nevus. Accessed on: 27 December 2012.
  14. 14.0 14.1 14.2 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 465. ISBN 978-0443066542.
  15. 15.0 15.1 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.
  16. 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.
  17. 17.0 17.1 17.2 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 464. ISBN 978-0443066542.
  18. Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 456. ISBN 978-0443066542.
  19. URL: http://emedicine.medscape.com/article/1079272-overview. Accessed on: 10 December 2012.
  20. 20.0 20.1 Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 457. ISBN 978-0443066542.
  21. 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.
  22. 22.0 22.1 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.
  23. 23.0 23.1 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.

External links