Difference between revisions of "Dermatopathology"

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Dermatopathology (view source)

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'''Dermatopathology''' is the pathology of skin.
'''Dermatopathology''' is the pathology of skin.  


Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.
Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.


=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{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>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].
=Histology=
==Layers of the skin==
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.
*Subdermis - below the dermis, connective tissue.


===Layers of epidermis===
Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>
 
Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].
 
===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.  
*Stratum corneum.  
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Mnemonic: ''Corn Lovers Grow Several Bales''.
Mnemonic: ''Corn Lovers Grow Several Bales''.


==Adnexal structures==
====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dendritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.
 
====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal  | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).
 
===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.
 
Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>
 
===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
| '''Structure''' / '''Attribute
! Structure / Attribute
| '''Histomorphology'''
! Histomorphology
| '''Function'''
! Function
| '''[[IHC]]'''
! [[IHC]]
| '''Other'''
! Other
| '''Image'''
! Image
|-
|-
| '''Eccrine gland'''
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling)
| thermoregulation (cooling) - produce sweat
| CK7+, CEA+, CAM5.2+, EMA+
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
| ?
| ?
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| '''Nail'''
| '''Nail'''
| epidermal structure
| epidermal structure
| ? look pretty
| weapon (claw-like), look pretty?
| ?
| ?
| ?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|-
|}
|}
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*Eccrine ducts - cuboidal type subepithelial cells.
*Eccrine ducts - cuboidal type subepithelial cells.


==Common terms==
=Common terms=
*Acanthosis = thickening of the prickle layer (stratum spinosum) of epidermis.<ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
==Clinical descriptors==
*Parakeratosis = retention of nuclei in the stratum corneum, normal in mucous membranes
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
*Dyskeratosis = abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site).
{| class="wikitable sortable"
*Spongiosis = epidermal intercellular edema;<ref>{{Ref PBoD|1230}}</ref> cells appear to have a clear halo around 'em.
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.


Images:  
==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''.  The terms have to committed to memory.
 
===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum  corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal  | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal  | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal  | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi =  | PMID = 9537476 }}</ref>
 
Image:  
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].


==Skin diseases==
===Others terms===
===[[Cancer]]===
*Crust = epithelial elements, blood.
{{main|Dermatologic cancer}}
 
Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>
 
=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}
 
===Malignant===
Skin cancer is very common.  The basic DDx of a malignant skin lesion is:
Skin cancer is very common.  The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*[[Malignant melanoma]].
*Metstases.
*Metastases.


===Non-malignant disease===
==Non-malignant disease==
{{main|Non-malignant skin disease}}
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common.  It is the domain of dermatologists.  It can be scary for general anatomical pathologist because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.
Non-malignant skin disease is common.  It is the domain of dermatologists.  It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.


Bullous diseases, e.g. pemphigus vulgaris, is dealt with in the ''[[bullous disease]]'' article.
===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].


====Common entities====
=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Entity
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| stuck on appearance
| stuck on appearance
| none
| none
| [[Fibroepithelial polyp]]
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| Leser–Trélat sign = many SKs in malignancy
| [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_(1).jpg (WC)]
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
|-
| [[Dermatofibroma]]
| [[Dermatofibroma]]
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| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| +/-trauma Hx
| CD34-, Factor VIIIa+
| CD34-, Factor XIIIa+
| [[DFSP]]
| [[DFSP]]
| very common
| very common
| [http://www.pacificderm.org/newsflashcpcapril04.html (pacificderm.org)]
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
|-
| [[Fibroepithelial polyp]] (skin tag)
| [[Fibroepithelial polyp]] (skin tag)
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| raised lesion
| raised lesion
| none
| none
| [[Seborrheic keratosis]]
| [[seborrheic keratosis]]
| very common
| very common
| [http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1767547949 (dermatlas.med.jhmi.edu)]
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- <!--
| Entity
| Key histologic features
| Other features
| Clinical
| Stains/IHC
| DDx
| Other
| Image -->
|}
 
==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- <!--
|- <!--
| Entity
| Entity
Line 141: Line 479:
|}
|}


==Presentations==
==Non-malignant non-cystic - children==
===Leukoplakia===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}
 
==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}
 
==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}
 
==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]] 
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- <!--
| Entity
| Key histologic features
| Other features
| Clinical
| Stains/IHC
| DDx
| Other
| Image -->
|}
 
==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- <!--
| Entity
| Key histologic features
| Other features
| Clinical
| Stains/IHC
| DDx
| Other
| Image -->
|}
 
=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}
 
DDx:<ref>{{Ref PBoD|1065}}</ref>
DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Vitiligo (loss of pigment).
*Inflammation.  
*Inflammation.  
**Chronic dermatitis.
**Chronic dermatitis.
**Psoriasis.  
**[[Psoriasis]].  
*Neoplasia.  
*Neoplasia.  
**Vulvar intraepithelial neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
**Invasive carcinoma.
*Other.  
*Other.  
**[[Non-malignant_skin_disease#Lichen_sclerosus|Lichen sclerosus]].
**[[Lichen sclerosus]].
**[[Non-malignant_skin_disease#Lichen_simplex_chronicus|Lichen simplex chronicus]].
**[[Lichen simplex chronicus]].


==Skin disease and systemic conditions==
=Skin disease and systemic conditions=
===Acanthosis nigricans===
==Tabular list==
Associated with: [[diabetes mellitus]],<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref> malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- <!--
| Entity
| Disease/syndrome
| Key histologic feature
| Image -->
|}


====Microscopic====
==Acanthosis nigricans==
Features ''BPH'':<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>  
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
 
===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>  
*Basal cell hyperpigmentation.
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Prominent rete ridges.
*Hyperkeratosis.
*Hyperkeratosis.
DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.


Images:
Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].


===Others===
==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref>TN07 D23.</ref>
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref>TN07 D23.</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
 
===Lipoid proteinosis===
<gallery>
File:3767 dp sl 1.png |Lipoid proteinosis (A)
File:3767 dp sl 2.png |Lipoid proteinosis (B)
</gallery>
A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general.  B. The particularly glassy appearance of the material in areas is evident at high power.
 
===Xanthogranuloma in scrotal skin.===
<gallery>
File:DP16MR17 sl 1.png| Xanthogranuloma in scrotal skin. (A)
File:DP16MR17 sl 2.png| Xanthogranuloma in scrotal skin. (B)
File:DP16MR17 sl 3.png| Xanthogranuloma in scrotal skin. (C)
File:DP16MR17 sl 4.png| Xanthogranuloma in scrotal skin. (D)
</gallery>
A. Pseudoepitheliomatous hyperplasia seemingly forms a dermal mass. B. Parakeratosis tops epidermis. C. Neutrophils lie in the center of the apparent mass. D. Diagnostic xanthoma cells lie in dermal papillae.
 
===Silicone granuloma===
<gallery>
File:DP13AP17 sl1.png| Silicone granuloma (A)
File:DP13AP17 sl2.png| Silicone granuloma (B)
File:DP13AP17 sl3.png| Silicone granuloma (C)
File:DP13AP17 sl4.png| Silicone granuloma (D)
</gallery>
A. The dermis resembles Swiss cheese. B. Macrophages, some with more than one nucleus, accompany empty ovoid spaces. C. Some macrophages resemble Teuton body giant cells. D. An admixture of lymphocytes is not at all unusual.
 
====Histoplasmosis in skin====
<gallery>
File:DP20AP17 sl 1.png| Dermal histoplasmosis (A)
File:DP20AP17 sl 2.png| Dermal histoplasmosis (B)
File:DP20AP17 sl 3.png| Dermal histoplasmosis (C)
File:DP20AP17 sl 4.png| Dermal histoplasmosis (D)
</gallery>
A. Extending from papillary dermis into dermis is a chronic, blue inflammatory infiltrate. B. The infiltrate comprises lymphocytes, plasma cells, and macrophages. C. At the edge of the biopsy pink strews inflammatory cells; this pink invasion of inflammation, so to speak, is a good place to look for organisms.  D. High power reveals sometimes budding yeast forms in clear spaces.
 
===Herpes Zoster===
<gallery>
File:5.049889044 sl 1.png| Changes of herpes zoster (A)
File:5.049889044 sl 2.png| Changes of herpes zoster (B)
File:5.049889044 sl 3.png| Changes of herpes zoster (C)
File:5.049889044 sl 4.png| Changes of herpes zoster (D)
</gallery>
Changes of herpes zoster in lower right abdominal skin of a 48 yo Hispanic man. A. Note the edema at the dermoepidermal junction along with a focal separation at the left as well as the inflamed superficial and deep blood vessels. B,C. Careful examination along the junction uncovers smudged chromatin diagnostic of viral infection. D. Vasculitis associated changes include extravasated neutrophils with nuclear dust, as well as pervascular macrophages, lymphocytes and occasional eosinophils.


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Dermatopathology]]
[[Category:Dermatopathology]]
Alessandro
14

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