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SubungualSubungual MelanomaMelanoma
Paul K. Shitabata, M.D.Paul K. Shitabata, M.D.DermatopathologistDermatopathologist
Pathology Inc.Pathology Inc.
4 4 y.oy.o. boy. boyJapanese, Korean, ChineseJapanese, Korean, ChineseAsthma, mild CPAsthma, mild CP
8 mo8 mo--Thin black line on nail, 2Thin black line on nail, 2ndnd
fingerfinger13 mo13 mo--Widened to include half nailWidened to include half nail23 mo23 mo--Entire nail involvedEntire nail involved24 mo24 mo--Biopsy read as negativeBiopsy read as negative47 mo47 mo--Nail painful and bleedingNail painful and bleeding
Treatment Options?Treatment Options?
ObservationObservationBiopsyBiopsyAvulse nailAvulse nailThe DoctorThe Doctor’’s Doctors DoctorOtherOther
Clinical PresentationsClinical Presentations
Rapidly spreading darkly Rapidly spreading darkly pigmented patch with pigmented patch with irregular borderirregular borderInvasion associated with Invasion associated with papules, plaques and later papules, plaques and later lesionslesions--ulceration and nail ulceration and nail deformitydeformityInvasion in Invasion in perieccrineperieccrineadventitial dermis may adventitial dermis may remain flatremain flatRegressionRegression--gray whitegray whiteHutchinsonHutchinson’’s signs sign--extension extension of pigmentation around of pigmentation around cuticlecuticle
ABCDE of NABCDE of N
A=Age (5A=Age (5--77thth decades), Africans, Asians, Native decades), Africans, Asians, Native AmericansAmericansB=Brown to black discoloration B=Brown to black discoloration
Breadth of nail pigmentation >3mmBreadth of nail pigmentation >3mmC=Change in nail band or lack of change in nail C=Change in nail band or lack of change in nail morphologymorphologyD=Digit most commonly involvedD=Digit most commonly involvedE=Extension to proximal nail foldE=Extension to proximal nail fold
The ABC rule for clinical detection of subungual melanoma.Levit EK, etal. J Am Acad Dermatol. 2001 May;44(5):875.
MelanonychiaMelanonychia VariantsVariants
LinearLinearTransverseTransverseTotalTotal
EpidemiologyEpidemiology
JapaneseJapaneseAfrican AmericansAfrican AmericansNo clear connection to No clear connection to UV exposure UV exposure Usually increased moles Usually increased moles but less incidence of AK but less incidence of AK and other sunand other sun--related related lesionslesions
Epidemiology and prognosis of subungual melanoma in 34 Japanese patients.Kato T, etal. Br J Dermatol. 1996 Mar;134(3):383-7
Ethnic Ethnic GroupGroup
PercentagePercentage
AfricansAfricans 77%77%JapaneseJapanese 1010--20%20%CaucasiansCaucasians 1%1%
Japanese PatientsJapanese Patients
University Hospital University Hospital StudyStudy34/151 melanoma cases 34/151 melanoma cases over 25 years were over 25 years were subungualsubungualMajority Majority AcralAcrallentiginouslentiginous histologichistologictype followed by SS and type followed by SS and nodularnodular
Epidemiology and prognosis of subungual melanoma in 34 Japanese patients.Kato T, etal. Br J Dermatol. 1996 Mar;134(3):383-7.
SiteSite NumbersNumbersFingernailsFingernails 21 (62%)21 (62%)ToenailsToenails 13 (38%)13 (38%)Thumb or Thumb or great toegreat toe
25 (73%)25 (73%)
Activation Activation vsvs HyperplasiaHyperplasia
Functional Functional melanonychiamelanonychia73% of LM (longitudinal 73% of LM (longitudinal melanonychiamelanonychia) in adults) in adultsPhysiologicPhysiologic--EthnicEthnicTraumaTraumaDermatitidesDermatitidesSystemic diseaseSystemic disease
AddisonAddison’’ssPeutzPeutz--JegherJegher’’ss
Increased matrix Increased matrix melanocytesmelanocytes77.5% of LM in children77.5% of LM in children
PathogenesisPathogenesis
SiteSite BRAF BRAF mutationsmutations
ChromChrom 10 10 lossloss
CCND1 CCND1 gene copiesgene copies
Minimal UV Minimal UV exposureexposure
HighHigh FrequentFrequent LowLow
Increased Increased UV exposureUV exposure
LowLow LowLow IncreasedIncreased
Distinct sets of genetic alterations in melanoma. Curtin JA, etal. N Engl J Med. 2005 Nov 17;353(20):2104-7.
ImplicationsImplications
GroupGroup InterventionIntervention
BRAF mutations frequentBRAF mutations frequent Target RASTarget RAS--RAFRAF--ERKERKand PI3K pathwaysand PI3K pathways
BRAF mutations infrequent BRAF mutations infrequent Increased copies of CCND1 Increased copies of CCND1 or CDK4or CDK4
Less likely to respond to Less likely to respond to therapeutic interventions therapeutic interventions that target upstream that target upstream components of the components of the mitogenmitogen--activated protein activated protein kinasekinasepathway including BRAF pathway including BRAF ((sorafenibsorafenib))
HistopathologyHistopathology
ExpansileExpansile nests of nests of pleomorphicpleomorphicmelanocytesmelanocytesSuperficalSuperfical spreading to spreading to lentiginouslentiginous growth growth patternpatternIrregular pigment Irregular pigment incontinenceincontinence
HistopathologicHistopathologic VariantsVariants
Two cases of regressed Two cases of regressed subungualsubungual melanomamelanomaLymphoscintigraphyLymphoscintigraphy and and sentinel lymph node sentinel lymph node (SLN) biopsies(SLN) biopsies--1 1 positive and 1 negativepositive and 1 negative
Dermatol Surg. 2006 Apr;32(4):577-80
Clinical Differential DiagnosisClinical Differential Diagnosis
MelanonychiaMelanonychia StriataStriata
Frictional Frictional MelanonychiaMelanonychia
CoumadinCoumadin--Associated Associated MelanonychiaMelanonychia
Longitudinal Longitudinal ChromonychiaChromonychia((MelanonychiaMelanonychia) )
Secondary to TraumaSecondary to TraumaPseudoPseudo--Hutchinson's sign due to Hutchinson's sign due to
periungualperiungual tissue transparencytissue transparency
TineaTinea NigraNigra(T. (T. rubrumrubrum varvar nigricansnigricans))
Rule out Candida Rule out Candida paronychiaparonychia))
PsuedoPsuedo--Hutchinson SignsHutchinson Signs
RacialRacialLauzierLauzier--HunzikerHunziker and and PeutzPeutz--JeghersJeghers syndromessyndromesRadiation therapyRadiation therapyMalnutritionMalnutritionMinocyclineMinocyclineAIDSAIDSCongenital nevusCongenital nevusTraumaTraumaPseudomonas and Proteus Pseudomonas and Proteus infectionsinfectionsBowenBowen’’s diseases disease
PrognosisPrognosis
Worse than conventional Worse than conventional melanomas?melanomas?SubungualSubungual worse than other worse than other acralacral melanomas?melanomas?VariablesVariables
Delayed diagnosisDelayed diagnosisPoorer prognosis:Poorer prognosis:
BreslowBreslow thicknessthicknessMale Male AmelanosisAmelanosis
Mets to CNS, liver lungs, Mets to CNS, liver lungs, bone, and LNbone, and LN
Acral lentiginous melanoma: a clinicoprognostic study of 126 cases.Phan A, etal. Br J Dermatol. 2006 Sep;155(3):561-9
Delay in DiagnosisDelay in Diagnosis5YS 5YS
88% <2.5mm88% <2.5mm40% >2.5mm40% >2.5mm
Nail apparatus melanoma. Thai KE, etal Australas J Dermatol 2001;42:71-81The incidence and prognosis of nail apparatus melanoma. A retrospective study of 105 patients in four English regions. Banfield CC, etal. Br J Dermatol 1998;139:276-279.
SiteSite Mean Mean ThicknessThickness
NonNon--acralacral <1.0 mm<1.0 mm
AcralAcral 3.05 mm3.05 mm
SubungualSubungual vs. vs. AcralAcral
67 Japanese cases of 67 Japanese cases of acralacral malignant melanomasmalignant melanomas>40% >40% palmoplantarpalmoplantar and and subungualsubungual80% 80% acralacral lentiginouslentiginous typetype15% nodular malignant melanoma15% nodular malignant melanoma3% superficial spreading 3% superficial spreading No difference in prognosis of No difference in prognosis of acralacral malignant melanomas malignant melanomas vsvs otherotherbody sitesbody sitesPalmoplantarPalmoplantar and and subungualsubungual malignant melanoma malignant melanoma
Women younger, better survival ratesWomen younger, better survival ratesNo significant difference with thickness No significant difference with thickness
Biological behavior and natural course of acral malignant melanoma. Clinical and histologic features and prognosis of palmoplantar, subungual, and other acral malignant melanomas. Jimbow K, etal. Am J Dermatopathol 1984;6:43-53.
AcralAcral Melanomas vs. Other SitesMelanomas vs. Other Sites
84, 836 cases84, 836 casesNational Cancer Data Base (1985National Cancer Data Base (1985--1994)1994)Nodular MM and Nodular MM and AcralAcral MM decreased survivalMM decreased survivalIndependent prognostic variableIndependent prognostic variable
The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. Chang AE, etal. Cancer 1998;83:1664-1678.
Nail BiopsyNail Biopsy
TechniqueTechnique
Must biopsy proximal Must biopsy proximal nail fold, location where nail fold, location where tumor usually arisetumor usually ariseIncisionalIncisional bxbx of nail plate of nail plate or proximal foldor proximal foldPunch Punch bxbx of proximal of proximal foldfold
4 4 y.oy.o. boy. boyJapanese, Korean, ChineseJapanese, Korean, ChineseAsthma, mild CPAsthma, mild CP
8 mo8 mo--Thin black line on nail, 2Thin black line on nail, 2ndnd
fingerfinger13 mo13 mo--Widened to include half nailWidened to include half nail23 mo23 mo--Entire nail involvedEntire nail involved24 mo24 mo--Biopsy read as negativeBiopsy read as negative47 mo47 mo--Nail painful and bleedingNail painful and bleeding
Treatment OptionsTreatment Options
ObservationObservationBiopsyBiopsyAvulse nailAvulse nailThe DoctorThe Doctor’’s Doctors DoctorOtherOther
PatientPatient’’s Mothers Mother’’s Solutionss Solutions
1) Do Nothing & Monitor? = DISAGREE - Delay in treatment increases severity if Melanoma is found/treatment more invasive
2) Do Another Biopsy? = DOESN'T MAKE SENSE - b/canesthesia will still have to be used
3) REMOVE NAIL NOW? = LOGICAL - Eliminates Melanoma risk BUT Increases Anesthesia risk (If nail is benign - future risk remains)
4) Transplantation with Toenail? = Derm knew about recent success & wanted to investigate - DON'T LIKE -creates 2 trauma sites
Remove Now!Remove Now!
A = Age (Low - child); Race (High - Japanese/Asian)B = Band (High - visible bands); Pigment (High -
brown/black), Breadth (High - 9 mm size); Border (? - ?)C = Change (High - rapid/esp 1st yr); Dystrophy (High -
Mostly biopsy caused but is brittle, weak, & rough edgesD = Digit (High - single digit); Dominant Hand (Low - is not
dominant hand)E = Extension/Hutchinson's sign (High - visible pigment in
fold)
Family history is unknown.Parallels most cases in literature - starting with 1 line, widening
rapidly, completely covering nail
Literature SupportLiterature Support
Childhood subungual melanoma in situ in diffuse nail melanosis beginning as expanding longitudinal melanonychia. Antonovich DD, etal. Pediatr Dermatol 2005:22;210-212.
A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail. A possible sign of subungual melanoma in situ. Kato T, etal. Cancer. 1989 Nov 15;64(10):2191-7.
SolutionsSolutions
Dr. Beth Rubin, Dr. Beth Rubin, DermatopathologistDermatopathologist UCSFUCSFDr. Dr. ScherScher and Dr. and Dr. TostiTosti
Dr. Stefani TakahashiDr. Stefani Takahashi--UCLAUCLA