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DermPath Update
Curtis T. Thompson, M.D.
Associated Adjunct Professor
Department of Dermatology
Oregon Health Sciences University
Portland, Oregon
Thanks. Last lecture before adjourning to beautiful weather. Dont want to batter with slides but give you a fairly concise update of advances in dermpath. Mostly molecular but there are some that are relevant to clinical dermatologists, especially those reading the so-called bread and butter themselves.
Melanocytic Neoplasms
Nevus vs MelanomaStagingSentinel lymph nodeDesmoplastic MMNevus versus Melanoma
H&EProtein (Immunohistochemistry)DNA (Karyotypes)DNA probes (FISH)DNA probes fancy (CGH)Protein (Immunohistochemistry)H&ENevus versus Melanoma
DNA AlterationTagged DNA probesFluoresence in-situ hybridization (FISH)Comparative Genomic Hybridization (CGH)Fluorescence in-situ hybridization (FISH)
FISH
Comparative Genomic Hybridization (CGH)
Comparative Genomic Hybridization (CGH)
Array CGH
Array CGH
CGHNevus vs Melanoma
Spitzs nevus vs Melanoma
Spitzs nevus vs Melanoma
Spitz--Chromosome arm 11p gain or normalMelanomaMore alterationsSpitzs nevus vs Melanoma--CGH
Clinical Problem--CGH takes too longNevus versus Melanoma
FISH Nevus vs Melanoma
Four areas of interestChromosome 6p256 centromere6q2311q13Protein (Antigen/antibody IHC)
Overexpression of Protein in MM
Kashani-Sabet et al.5 Markers identified on gene expression dataSpitz, MM in nevus, dysplastic nevus, misdiagnosed nevi.Specificity 95%Sensitivity 91%JURY IS OUT BUT HAS POTENTIAL TO REPLACE FISH WHICH IS EXPENSIVE AND TECHNICALLY DIFFICULT.Nevus versus Melanoma
H&EProtein (Immunohistochemistry)DNA (Karyotypes)DNA probes (FISH)DNA probes fancy (CGH)Protein (Immunohistochemistry)H&EH&E?
Melanoma Staging
Good bye to Clarks levelsHello to mitotic figuresBalch et al. Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol 23:4799v1, 2009.Mitotic Figures
5X 40x fields is 1mm2Count the most active areasCount only dermal melanocytesBe careful of counting lymphocytes and other cells.Antiphosphohistone HC (Immunohistochemistry)Casper D et al. Use of Anti-phosphohistone H3 Immunohistochemistry to Determine Mitotic Rate in Thin Melanoma, Am J Dermatopathol, In press, 2010.Mitotic Figures
Antiphosphohistone HC (Immunohistochemistry)Casper D et al. Use of Anti-phosphohistone H3 Immunohistochemistry to Determine Mitotic Rate in Thin Melanoma, Am J Dermatopathol, In press, 2010.Antiphosphohistone--Mitotic Figures
Sentinel Lymph Node
Jury still out on utilityInterferon or not0.75? 1.00mm? Stage 1b?Kanzler MH, Sentinel node biopsy and standard of care for melanoma: A re-evaluation of the evidence. JAAD 62(5):880-882, 2010.Desmoplastic MM
Not as bad of an actorDiscovered later (>Breslow)Soares de Almeida L et al. Desmoplastic malignant melanoma: a clinicopathologic analysis of 113 cases. Am J Dermatopathol 30(3):207-215, 2008.Proliferative RateKi-67 IHC
Proliferative RateKi-67 IHC
Seborrheic keratosis versus SCCISNevus vs MelanomaTrichoepithelioma/trichoblastoma vs BCCTadashi T. Pigmented Bowen disease arising in pigmented reticulated seborrheic keratosis. Int J Clin Oncology, In press, 2010.Alopecia
Cytokeratin 15 (Stem cell in bulge)decreased in cicatricial processesPozdnyakova O. Involvement of the bulge region in primary scarring alopecia, J Cutaneous Pathology 35:922-925. 2008.Cytokeratin 15
Stem cellAlopecia
Will loss of Cytokeratin 15 in cicatricial (primary scarring) alopecia have prognostic significance?Nail
OnychomatricomaCentrifuging nail specimenOrienting specimenNail
Onychomatricoma
Nail matrix?tumor or reactiveEpithelial and stromal componentsDistinguish from fibroma/angiofibromaOnychomatricoma
Nail
Centrifuging nail specimen
Takiguchi R et al. Centrifuging nail specimen debris increased sensitivity of fungus detection. Abstract. American Society of Dermatopathology, Chicago, IL October 1, 2009.Nail Bed/Matrix Biopsy Processing
Nail Bed/Matrix Biopsy Processing
R
L
IdeaOrientation of Tissue
+
Tissue
Nail Bed/Matrix Biopsy Processing
Nail Bed/Matrix Biopsy Processing
Tissue on
Paper guide
Nail Bed/Matrix Biopsy Processing
Nail Bed/Matrix Biopsy Processing
Nail Bed/Matrix Biopsy Processing
Cassette
Tissue on
Paper Digit
Nail Bed/Matrix Biopsy Processing
Cover with sponge
to hold in place
Cassette
Tissue on
Paper Digit
Sponge
Medial
Lateral
Nail Bed/Matrix Biopsy Processing
Submit in an excess of
10% fresh formaldehyde
Medial
Lateral
Onychomycosis Diagnostics
Sampling is an issueSubungal debris is better than nail plate for sampling.Chang A et al. A modified approach to the histologic diagnosis of onychomycosis. JAAD 57:849-53, 2007.
Nail Fungus Diagnostics
Centrifuging Debris
Cytospin
Cytospin
Cytospin
Study204 Cases
132 cases positive on initial nail PAS52 cases centrifuged after negative nail PAS18 cases positive on centrifugeTotal 150 positive casesnail and centrifugeStudy204 Cases
Sensitivity increased 65% to 74% with nail centrifuge.20 cases (10%) centrifuge not performed, usually because nail was submitted dry.ConclusionCentrifuge of Nail Debris
Positive cases--increased 9% from 73% to 82% with centrifuge.Negative centrifuge cases often associated with bacteria (45%)Clinicians should consider submitting nail debris in a cytoprep solution rather than nail plate.AFX vs other
p63AFX--CD10, p63 and CD99Kanner W et al. CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma, spindle cell squamous cell carcinoma and desmoplastic melanoma. J Cutaneous Pathol 37:744-750, 2010.
Merkel
PolyomavirusNeurofilament dotMerkel
Merkel
Merkel
Merkel--Polyomavirus
Viral large T antigen gene (replication)Can send clinical samples for analysis (Memorial Sloan Kettering)Merkel Diagnostics
Neurofilament dotMcCalmont T. Paranuclear dots of neurofilament reliably identify Merkel cell carcinoma J Cutaneous Pathol 37:821, 2010.Merkel Diagnostics
Cytokeratin 20+ (CK7-)Synaptophysin+Chromogranin+Merkel Diagnostics
Neurofilament dotUseful in cases in which cytokeratin is nonspecific (no perinuclear dot)Infectious
HPV SubtypingUse probes from cervical studiesUsually patient requestsSubtypingHigh-riskLow-riskWide ScreenInfectious
SyphilisImmunohistochemistryReplaces Warthin-StarryAutoimmune
Autoimmune
C3d Antigen/Antibody--ImmunohistochemistryBullous pemphigoid Pemphigus vulgaris.C3d AntibodyBullous Pemphigoid
C3d AntibodyPemphigus Vulgaris
C3d Antibody
Formalin-fixed TissueNo Michels!Pfaltz K et al. C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin. J Cutaneous Pathol 37:654-8, 2009.
Lymphoma
Classification
Flow Cytometry
Can be a great diagnostic tool for cellular infiltratesCan test more antigens/antibodies.Wu et al. Contribution of flow cytometry in the diagnosis of cutaneous lymphoid lesions. Journal of Investigative Dermatology 121: 1522-30, 2003.Lymphoma
Kappa/lambda Light In-situ Hybridization
Thank you!
Brandon StokesRodd TakiguchiPhoebe RichJanet Roberts