Difference between revisions of "Melanocytic lesions"

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[[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]]).
'''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]]).


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=Lentiginous melanocytic lesions=
=Lentiginous melanocytic lesions=
==Lentigo simplex==
==Lentigo simplex==
*[[AKA]] ''simple lentigo''.<ref>URL: [http://www.dermnetnz.org/lesions/lentigo-simplex.html http://www.dermnetnz.org/lesions/lentigo-simplex.html]. Accessed on: 27 March 2013.</ref>
{{Main|Lentigo simplex}}
===General===
*Benign.
*Usually <40 years old.
 
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]].
 
Associated syndromes:<ref name=dermamin_ls>URL: [http://dermaamin.com/site/histopathology-of-the-skin/64-l/1852-lentigo-simplex-.html http://dermaamin.com/site/histopathology-of-the-skin/64-l/1852-lentigo-simplex-.html]. Accessed on: 17 December 2012.</ref>
*[[Peutz-Jeghers syndrome]].
*[[LEOPARD syndrome]].
*[[LAMB syndrome]].
 
===Gross===
*Small flat pigmented lesion.<ref name=Ref_WMSP498>{{Ref WMSP|498}}</ref>
 
DDx - clinical:
*[[Melanocytic nevus]].<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>
 
===Microscopic===
Features:<ref name=Ref_WMSP498>{{Ref WMSP|498}}</ref>
*Melanocytes in epidermis only.
**Melanocytes basally located (normal location) with hyperpigmentation.
*No melanocytic nests.
*+/-Mild/moderate elongation of the rete ridges.<ref name=pmid19536147/>
 
DDx:<ref name=humpath_ls/>
*[[Solar lentigo]] - in sun exposed areas.
*[[Ephelis]] (freckle) - change with UV light exposure.
*Melanotic macule.
*Lentiginous nevus.
 
Images:
*[http://dermaamin.com/site/histopathology-of-the-skin/64-l/1852-lentigo-simplex-.html Lentigo simplex - several images (dermamin.com)].<ref name=dermamin_ls/>
*[http://www.humpath.com/IMG/jpg/lentigo_simplex_20x.jpg Lentigo simplex (humpath.com)].<ref name=humpath_ls>URL: [http://www.humpath.com/?lentigo-simplex http://www.humpath.com/?lentigo-simplex]. Accessed on: 17 December 2012.</ref>
 
===Sign out===
<pre>
SKIN LESION, LEFT ABDOMEN, BIOPSY:
- SIMPLE LENTIGO, COMPLETELY EXCISED IN THE PLANE OF SECTION.
</pre>
 
<pre>
SKIN LESION, LEFT ABDOMEN, BIOPSY:
- BENIGN SIMPLE LENTIGO.
</pre>


==Solar lentigo==
==Solar lentigo==
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**Classically at the tips of the rete ridges.
**Classically at the tips of the rete ridges.
*No (melanocyte) nuclear atypia.
*No (melanocyte) nuclear atypia.
*Solar damage ([[solar elastosis]]).<ref name=pmid19536147/>
*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:
Notes:
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*[[Lichen planus-like keratosis]].
*[[Lichen planus-like keratosis]].
*Pigmented [[seborrheic keratosis]].
*Pigmented [[seborrheic keratosis]].
*[[Ephelis]] (freckle).


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Skin_tumors_181.jpg Solar lentigo (WC)].
<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>
*[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>


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www:
www:
*[http://www.derm101.com/Popups/FigurePopup.aspx?id=dp0101a06f005&aid=740564&filename=dp0101a06g005b Lentiginous nevus (derm101.com)].
*[http://www.derm101.com/Popups/FigurePopup.aspx?id=dp0101a06f005&aid=740564&filename=dp0101a06g005b Lentiginous nevus (derm101.com)].
<gallery>
Image:Skin_Tumors-171.jpg | Lentiginous nevus. (WC)
</gallery>


===Sign out===
===Sign out===
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*[[AKA]] ''intradermal melanocytic nevus''.
*[[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>
*[[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}}
*Only in the dermis - '''key feature'''.
*+/-Adipocytes - uncommon.<ref name=pmid9810886>{{Cite journal  | last1 = Eng | first1 = W. | last2 = Cohen | first2 = PR. | title = Nevus with fat: clinical characteristics of 100 nevi containing mature adipose cells. | journal = J Am Acad Dermatol | volume = 39 | issue = 5 Pt 1 | pages = 704-11 | month = Nov | year = 1998 | doi =  | PMID = 9810886 }}</ref>
 
Note:
*In the oral cavity these are known as ''[[intramucosal melanocytic nevus|intramucosal nevi]]''.


===Sign out===
===Sign out===
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====Compound melanocytic nevus====
====Compound melanocytic nevus====
<pre>
{{Main|Compound nevus}}
SKIN LESION, RIGHT NECK, SHAVE BIOPSY:
- BENIGN COMPOUND NEVUS.
</pre>
 
=====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.


====Intradermal melanocytic nevus====
====Intradermal melanocytic nevus====
<pre>
{{Main|Intradermal nevus}}
SKIN LESION, BACK, PUNCH BIOPSY:
- BENIGN INTRADERMAL NEVUS.
</pre>
 
=====Adipocytes present=====
<pre>
SKIN LESION, BACK, PUNCH BIOPSY:
- BENIGN INTRADERMAL NEVUS WITH MATURE ADIPOCYTES.
</pre>
 
=====Clinically suspicious=====
<pre>
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.
</pre>
 
=====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==
==Congenital-pattern nevus==
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==Pigmented spindle cell nevus==
==Pigmented spindle cell nevus==
*[[AKA]] ''pigmented spindle cell nevus of Reed''.
*[[AKA]] ''pigmented spindle cell nevus of Reed''.
 
{{Main|Pigmented spindle cell nevus}}
===General===
*Uncommon.
*Women in teens & 20s.
*Location: shoulder, pelvic girdle region.
 
===Microscopic===
Features:<ref name=Ref_WMSP500>{{Ref WMSP|500}}</ref>
*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:
*[[Spitz nevus]].
*[[Malignant melanoma]].
 
====Images====
<gallery>
Image:Pigmented_spindle_cell_nevus_-_low_mag.jpg | PSCN - low mag. (WC)
Image:Pigmented_spindle_cell_nevus_-_2_-_intermed_mag.jpg | PSCN - intermed. mag. (WC)
Image:Pigmented_spindle_cell_nevus_-_2_-_high_mag.jpg | PSCN - high mag. (WC)
</gallery>
www:
*[http://www.histopathology-india.net/Reed.htm Reed nevus - collection (histopathology-india.net)].
 
===Sign out===
<pre>
SKIN LESION, RIGHT POSTERIOR NECK, EXCISION:
- PIGMENTED SPINDLE CELL NEVUS OF REED.
-- COMPLETELY EXCISED (CLEARANCE ~ 1 MM).
</pre>
 
====Micro====
The sections show spindled pigmented melanocytes in nests 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. Melanophages are present in the superficial
dermis. The lesion is completely excised in the plane of section.


==Spitz nevus==
==Spitz nevus==
*AKA ''epithelioid and spindle-cell nevus''.
*[[AKA]] ''epithelioid and spindle cell nevus''.
 
{{Main|Spitz nevus}}
===General===
*May be very difficult to differentiate from [[melanoma]].
 
Epidemiology:
*Children & adolescents.
 
Treatment:
*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>
 
===Gross===
*Usually face ''or'' extremity.<ref name=Ref_Derm449>{{Ref Derm|449}}</ref>
 
===Microscopic===
Features:<ref name=Ref_WMSP499>{{Ref WMSP|499}}</ref>
*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.<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:
*'''Never''' in the setting of [[solar elastosis]].<ref>Jakubovic, H. 16 July 2010.</ref>
**If there is solar elastosis -- it's melanoma.
 
DDx:
*[[Malignant melanoma]].
*[[Pigmented spindle cell nevus of Reed]].
 
Images:
*www:
**[http://www.drmihm.com/cases/case.cfm?CaseID=51 Spitz nevus - collection of images (drmihm.com)].
**[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)].


==Acral nevus==
==Acral nevus==
*[[AKA]] ''melanocytic nevus with intraepidermal ascent of cells'' (MANIAC).
*[[AKA]] ''melanocytic nevus with intraepidermal ascent of cells'' ([[MANIAC]]).
*[[AKA]] ''volar nevus''.
*[[AKA]] ''volar nevus''.
===General===
{{Main|Acral nevus}}
*Palms ''or'' soles.
 
Note:
*''Volar'' refers to the palmar aspect ''or'' plantar aspect.<ref>URL: [http://www.medterms.com/script/main/art.asp?articlekey=9907 http://www.medterms.com/script/main/art.asp?articlekey=9907]. Accessed on: 14 January 2013.</ref>
 
===Gross===
*Pigmented lesion.
 
Note:
*Should be bisected perpendicular to the dermatoglyphs (ridges).<ref name=pmid22703907/>
**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'''.<ref name=pmid22703907/>
 
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".<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>
 
DDx:
*Acral lentiginous [[melanoma]].


==Dysplastic melanocytic nevus==
==Dysplastic melanocytic nevus==
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*[[AKA]] ''nevus with architectural disorder''.
*[[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>
**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}}
===General===
*Benign.
*Dysplastic 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:
*Dysplastic nevi with severe nuclear atypia are treated like melanoma - excision with a 5 mm margin.
*Dysplastic nevi with moderate nuclear atypia with margin involvement are re-excised.<ref name=pmid15509670>{{Cite journal  | last1 = Culpepper | first1 = KS. | last2 = Granter | first2 = SR. | last3 = McKee | first3 = PH. | title = My approach to atypical melanocytic lesions. | journal = J Clin Pathol | volume = 57 | issue = 11 | pages = 1121-31 | month = Nov | year = 2004 | doi = 10.1136/jcp.2003.008516 | PMID = 15509670 }}</ref>
 
===Gross===
Features:<ref name=pmid22220461/>
*"Ugly duckling sign" - lesion looks different than the rest.
*[[Malignant_melanoma#Gross|ABCDE criteria of in melanoma]].
*Tend to be greater than 5 mm - '''important'''.† <ref name=pmid3275948>{{Cite journal  | last1 = Barnhill | first1 = RL. | last2 = Hurwitz | first2 = S. | last3 = Duray | first3 = PH. | last4 = Arons | first4 = MS. | title = The dysplastic nevus: recognition and management. | journal = Plast Reconstr Surg | volume = 81 | issue = 2 | pages = 280-9 | month = Feb | year = 1988 | doi =  | PMID = 3275948 }}</ref>
 
Note:
* † Size matters - things smaller than 4 mm are usually ''not'' a dysplastic nevus.
 
===Microscopic===
Features:<ref name=Ref_WMSP502>{{Ref WMSP|502}}</ref>
*Melanocytes "bridges" between sides of rete ridges.
**Joining of three or more adjacent rete ridges = suspicious for melanoma.<ref name=pmid15509670/>
*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:
*[[Melanoma in situ]] - especially on [[solar elastosis|sun damaged skin]] ([[lentigo maligna]]).<ref name=pmid15953373>{{Cite journal  | last1 = Farrahi | first1 = F. | last2 = Egbert | first2 = BM. | last3 = Swetter | first3 = SM. | title = Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction. | journal = J Cutan Pathol | volume = 32 | issue = 6 | pages = 405-12 | month = Jul | year = 2005 | doi = 10.1111/j.0303-6987.2005.00355.x | PMID = 15953373 }}</ref><ref name=pmid10911797>{{Cite journal  | last1 = Edwards | first1 = SL. | last2 = Blessing | first2 = K. | title = Problematic pigmented lesions: approach to diagnosis. | journal = J Clin Pathol | volume = 53 | issue = 6 | pages = 409-18 | month = Jun | year = 2000 | doi =  | PMID = 10911797 }}</ref>
*[[Malignant melanoma]] - especially on sun damaged skin ([[lentigo maligna melanoma]]).
*[[Compound melanocytic nevus]].
*[[Atypical lentiginous nevus]].
 
====Images====
<gallery>
Image:Dysplastic_nevus_-_low_mag.jpg | Dysplastic nevus - low mag. (WC/Nephron)
Image:Dysplastic_nevus_-_intermed_mag.jpg | Dysplastic nevus - intermed. mag. (WC/Nephron)
Image:Dysplastic_nevus_-_add_-_high_mag.jpg | Dysplastic nevus - high mag. - shows bridging and lamellar fibrosis. (WC/Nephron)
Image:Dysplastic_nevus_-_add_-_very_high_mag.jpg | Dysplastic nevus - very high mag. - shows bridging and lamellar fibrosis. (WC/Nephron)
</gallery>
 
====Grading====
These lesions are often 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>
 
Notes:
*§ There is no consensus on this and practise (embarrassingly) is all over the map.<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>
**A two-tier grading system also exists (''low-grade'' (leave it alone) / ''high-grade'' (cut it out)).
**Some pathologists do not grade dysplastic nevi.
 
===Sign out===
====Compound====
<pre>
SKIN LESION, BACK, EXCISION:
- DYSPLASTIC COMPOUND NEVUS WITH MILD CYTOLOGIC ATYPIA AND MILD ARCHITECTURAL ATYPIA,
  COMPLETELY EXCISED IN THE PLANE OF SECTION (2 MM CLEARANCE).
</pre>
 
<pre>
SKIN LESION, CENTRAL BACK, EXCISION:
- DYSPLASTIC COMPOUND NEVUS WITH MILD CYTOLOGIC ATYPIA.
- NEAREST MARGIN (LATERAL MARGIN) 6 MM.
</pre>
=====Micro=====
The sections show hair-bearing skin with a compound melanocytic lesion.  The epidermal component extends at least three rete ridges further than the dermal component (shoulder phenomenon). There is bridging between the sides of the rete ridges and lamellar fibrosis.  The melanocyte nuclei are approximately the size of the keratinocyte nuclei, and do not have a prominent nucleolus (mild cytologic atypia).
 
There is no upward scatter of melanocytes and melanocytes in the dermis are mature.  No mitotic activity is appreciated.
 
====Junctional====
<pre>
SKIN LESION, LOWER BACK, EXCISION:
- DYSPLASTIC JUNCTIONAL MELANOCYTIC NEVUS WITH MILD NUCLEAR ATYPIA.
- NEAREST MARGIN (LATERAL MARGIN) 1 MM.
</pre>
 
=====Micro=====
The sections show hair-bearing skin with a junctional melanocytic lesion.  There is bridging between the sides of the rete ridges and lamellar fibrosis.  The melanocyte nuclei are approximately the size of the keratinocyte nuclei, and do not have a prominent
nucleolus (mild nuclear atypia).
 
There is no upward scatter of melanocytes.  No mitotic activity is appreciated.


==Desmoplastic melanocytic nevus==
==Desmoplastic melanocytic nevus==
Line 679: Line 381:


DDx:
DDx:
*[[Desmoplastic neurotropic malignant melanoma]].
*[[Desmoplastic neurotropic malignant melanoma]] - usually mitotic figures, nuclear atypia (enlarged, hyperchromatic).
*[[Dermatofibroma]].
*[[Dermatofibroma]].
*[[Dermal scar]] - no adnexal structures.


===IHC===
===IHC===
Features:<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
Features:<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*Melan A (MART-1) +ve (not usu. +ve in desmoplastic melanoma).<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*Melan A (MART-1) +ve.
**Usually -ve in desmoplastic melanoma.<ref name=Ref_Derm_464>{{Ref Derm|464}}</ref>
*S-100 +ve.
*S-100 +ve.
**Should stain approximally the same number of cells as Melan A.
*Ki-67 -- only rare cells.
*Ki-67 -- only rare cells.
==Nodal nevus==
*AKA ''nevus in lymph node'' and ''benign nevus cells in lymph node''.
{{Main|Nodal nevus}}


=Miscellaneous=
=Miscellaneous=
Line 713: Line 422:


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]].
*[[Clear cell sarcoma]].
*[[Combined melanocytic nevus]] - blue nevus found together with another nevus (classically [[common melanocytic nevus]]), superficial.
*[[Combined melanocytic nevus]] - blue nevus found together with another nevus (classically [[common melanocytic nevus]]), superficial.
*[[Pigmented epithelioid melanocytoma]] - superificial dermis, has nuclear atypia.  
*[[Pigmented epithelioid melanocytoma]] - superificial dermis, has nuclear atypia.  
Line 728: Line 438:
www:
www:
*[http://www.dermatopathonline.com/blue%20nevus2.html Several types of blue nevi (dermatopathonline.com)].
*[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>


====Variants of blue nevus====
====Variants of blue nevus====
Line 739: Line 450:
Memory device:  
Memory device:  
*''C CASE'' = '''C'''ommon, '''C'''ellular, '''A'''melanotic, '''S'''clerosing, '''E'''pithelioid.
*''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===
===Sign out===
Line 754: Line 471:
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 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 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.
The pigmented cells are negative on the Prussian blue stain.
Line 806: Line 523:
*[[Cytopathology]].
*[[Cytopathology]].
*[[Non-malignant skin disease]].
*[[Non-malignant skin disease]].
*[[Pigmented lesions of the oral cavity]].
*[[Melanosis coli]].
*[[Small bowel pseudomelanosis]].


=References=
=References=
Line 814: Line 534:


[[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

Main article: 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

  • Solar lentigo. (WC)

Sign out

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:

Sign out

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]
Main article: Intradermal nevus

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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

Main article: Compound nevus

Intradermal melanocytic nevus

Main article: Intradermal 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.
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.
Main article: Acral 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]
Main article: Dysplastic nevus

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.
Main article: Nodal nevus

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

  • Blue nevus (WC)

  • Blue nevus - very low mag. (WC)

  • Blue nevus - intermed. mag. (WC)

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.

Sign out

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

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 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

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