Dermatopathology

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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.

Histology

Layers of the skin

  • 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.
  • Subdermis - below the dermis, connective tissue.

Epidermis

Epidermis layers - from the surface to epidermal-dermal junction:

  • Stratum corneum.
  • Stratum lucidum.
    • Present only in "thick" skin.[1]
  • Stratum granulosum.
  • Stratum spinosum (aka prickle layer).
  • Stratum basale (germinativum).

Mnemonic: Corn Lovers Grow Several Bales.

Cells of the epidermis

  • Keratinocytes.
    • Usu. eosinophilic cytoplasm - important feature.
    • May have clear perinuclear halo (glycogenated keratinocytes).
    • Intercellular bridges (high power) - key feature.
  • Melanocytes.
    • Usu. basal location.
    • Epithelioid or dentritic 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.

Adnexal structures

The top five structures of the skin:[2]

Structure / Attribute Histomorphology Function IHC Other Image
Eccrine gland clusters of tubular structures, pale cytoplasm thermoregulation (cooling) - produce sweat CK7+, CEA+, CAM5.2+, EMA+ ? ?
Apocrine gland apical snouts, tubular structures ear wax, body odor ? ? ?
Sebaceous gland clusters of cells side-by-side, pale fluffy cytoplasm grease hair, sexual lubrication ? assoc. with hair follicle ?
Hair follicle linear structure keep individual warm ? assoc. with sebaceous glands ?
Nail epidermal structure ? look pretty ? ? ?

Ducts vs. glands:[3]

  • Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
  • Eccrine ducts - cuboidal type subepithelial cells.

Common terms

  • Acanthosis = thickening of the prickle layer (stratum spinosum) of epidermis.[4]
  • Parakeratosis = retention of nuclei in the stratum corneum, normal in mucous membranes
  • Dyskeratosis = abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site).
  • Spongiosis = epidermal intercellular edema;[5] cells appear to have a clear halo around 'em.

Images:

Skin diseases

Neoplasms

Main article: Dermatologic neoplasms

Malignant

Skin cancer is very common. The basic DDx of a malignant skin lesion is:

Non-malignant disease

Main article: Non-malignant skin disease

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.

Subarticles

Common entities in tables

Non-malignant non-cystic - very common

Entity Key histologic feature Other features Clinical Stains/IHC DDx Other Image
Seborrheic keratosis (SK) horn cysts (intraepidermal collections of keratin) hyperkeratosis, brown granular material at the DE junction, sharply demarcated stuck on appearance none fibroepithelial polyp Leser–Trélat sign = many SKs in malignancy (WC)
Dermatofibroma fibrous bundles esp. at edge of lesion "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation +/-trauma Hx CD34-, Factor XIIIa+ DFSP very common (pacificderm.org)
Fibroepithelial polyp (skin tag) on a stalk (epithelium on 3+ sides) no horn nests, no hyperkeratosis raised lesion none seborrheic keratosis very common (dermatlas.med.jhmi.edu)
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) (ahajournals.org)
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 residual disease, hypertrophic scar (WC).

Non-malignant non-cystic - common

Entity Key histologic feature Other features Clinical Stains/IHC DDx Other Image
Neurofibroma bland spindle cells mixed with collagen (???) may be associated with neurofibromatosis S100+ (???) dermal nevus (???) Other ? (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 (WC)
Molluscum contagiosum suprabasilar cells with abundant granular eosinophilic cytoplasm small peripheral nucleus polypoid lesion (?) none (?) DDx (?) favourite exam case (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+?) DDx ? caused by HPV (WC)
Condyloma acuminatum koilocytes parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look genital lesion none (p16+) DDx Other (WC)
Granuloma annulare dermal palisading granuloma around necrotic collagen mucin in centre of lesion, (peripheral) chronic inflammatory cells benign, self-limited none (CD68?) necrobiosis lipoidica, rheumatoid nodule Other ? (dermaamin.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 Angiofibroma (drdittmar.lu)
Keloid thick collagen bundles - surrounded by paler staining fibroblasts replaces adnexal structures site of previous trauma, esp. in blacks none dermatofibroma (???) hypertrophic scar (ucsf.edu).
Eccrine poroma abundant basaloid cells with (small) ductal structures incloses islands of sclerotic stroma with edema erythematous lesions Stains/IHC ? DDx ? Other ? (flickr.com), (flickr.com)
Syringoma bilayered ducts, occasionally tadpole like shape usu. close to eyelid Stains/IHC ? DDx ? Other ? (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 ?

Non-malignant non-cystic - children

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 DDx mutations of CTNNB1 gene (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 (WC)

Non-malignant cystic

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 cyst none pilar cyst Other? (ucsf.edu)
Pilar cyst cyst lined by squamous epithelium without a granular layer keratinous debris cyst none epidermal cyst Other? Image?
Steatocystoma cyst lined by squamous epithelium with a corrugated eosinophilic lining epidermis has no granular layer cyst none dermoid cyst, follicular cyst Other? Image?
Dermoid cyst cyst lined by keratinizing squamous epithelium with adnexal structures adnexal structure = hair, sebaceous gland, sweat glands cyst none epidermal cyst, follicular cyst may be seen in the ovary (uiowa.edu)

Pre-malignant

Entity Key histologic feature Other features Clinical Stains/IHC DDx Other Image
Actinic keratosis epidermal atypia, esp. (basal) nuclear enlargement var. of size, shape and staining yellow-brown scaly none squamous carcinoma, Bowen disease seen with solar elastosis (WC)
Bowen disease (squamous cell carcinoma in situ) epidermal atypia, esp. suprabasal nuclear enlargement var. of size, shape and staining none squamous carcinoma, actinic keratosis typically seen with solar elastosis (WC)

Common malignant

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 assoc. nevoid basal cell carcinoma syndrome, Bazex syndrome (ucsf.edu)
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, Melanoma, Toker cell hyperplasia Other (WC)
Malignant melanoma nuclear atypia (nucleoli), spindle and/or epithelioid morphology mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+ melanocytic lesions may be familial, dysplastic nevus (WC)

Less common malignant

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 Other (WC)
Cutaneous T-cell lymphoma (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 (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 (cdlib.org)[6]
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 rare, aggressive (bccancer.bc.ca)
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 (WC)

Presentations

Leukoplakia

DDx:[7]

Skin disease and systemic conditions

Tabular list

Entity Disease/syndrome Key histologic feature Image
Acanthosis nigricans diabetes mellitus, malignancy basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges (cdlib.org)
Trichilemmoma Cowden disease
Angiokeratoma Fabry disease
Dermatitis herpetiformis Celiac disease subepidermal bullous disease
Angiofibroma tuberous sclerosis

Acanthosis nigricans

Associated with: diabetes mellitus,[8] malignancy.[9]

Microscopic

Features BPH:[9]

  • Basal cell hyperpigmentation.
  • Prominent rete ridges.
  • Hyperkeratosis.

Images:

Others

References

  1. ↑ Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 1. ISBN 978-0443066542.
  2. ↑ Busam, Klaus J. (2009). Dermatopathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Saunders. pp. 4-8. ISBN 978-0443066542.
  3. ↑ HJ. 27 Feb 2009.
  4. ↑ http://dictionary.reference.com/browse/acanthosis
  5. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1230. ISBN 0-7216-0187-1.
  6. ↑ Vandergriff, TW.; Reed, JA.; Orengo, IF. (2008). "An unusual presentation of atypical fibroxanthoma.". Dermatol Online J 14 (1): 6. PMID 18319023.
  7. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1065. ISBN 0-7216-0187-1.
  8. ↑ URL: http://www.emedicine.com/derm/topic1.htm, URL: [1].
  9. ↑ 9.0 9.1 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. 596. ISBN 978-1416054542.
  10. ↑ TN07 D23.
  11. ↑ TN07 D23.
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