Treatment of lentigo maligna of the head and neck with staged excision in South Africa : assessing surgical excision margins with Melan A, SOX10 and PRAME immunohistochemistry

Simple item page
dc.contributor.advisorSchneider, Johann Wilhelmen_ZA
dc.contributor.advisordu Plessis, Pieteren_ZA
dc.contributor.authorde Wet, Johannen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Anatomical Pathology.en-ZA
dc.date.accessioned2023-02-21T16:44:24Z
dc.date.accessioned2023-05-18T07:02:22Z
dc.date.available2023-02-21T16:44:24Z
dc.date.available2023-05-18T07:02:22Z
dc.date.issued2022-11
dc.descriptionThesis (MMed)--Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH SUMMARY: Lentigo Maligna (LM) is a subtype of melanoma in situ that occurs on sun-damaged skin, typically on the head and neck area of older individuals. LM is associated with significant subclinical extension beyond the visible clinical margins and therefore recommended surgical excision margins may be inadequate for complete surgical clearance of the tumour. Staged Excision (SE) has emerged as the treatment of choice for LM of the head and neck. It allows for complete margin control, superior clearance, and lower recurrence rates compared to conventional wide local excision (WLE). Differentiating between actinic melanocyte hyperplasia (AMH) and LM at the peripheral margin complicates the assessment of completeness of excision when using this technique. Objectives: The study aimed to describe the patient demographics, tumour characteristics, and histological findings of LM cases on the head and neck treated with SE. Secondary objectives included: (1) To determine if standard recommended surgical excision margins for LM of the head and neck are adequate to achieve a 97% clearance rate and if any patient or tumour characteristics warranted wider margins, (2) To determine whether immunohistochemical (IHC) staining with SOX10 and PRAME aids in diagnosing LM on excision margins compared to conventional Hematoxylin and Eosin (H&E) and Melan A IHC staining. Methodology: The study involved a retrospective chart review of all patients diagnosed with LM of the head and neck and treated with SE at the Skinmatters Mohs Micrographic Surgery and Reconstructive Unit. Tissue sections of LM cases with LM reported to be present at margins were immunohistochemically stained with SOX10 and PRAME and reviewed by a Mohs surgeon and a pathologist with expertise in melanoma pathology. Results: The first component of the study showed that 6mm, 9mm, and 12mm surgical excision margins obtained complete excision in 60.94%, 71.88%, and 90.64% of the LM cases, respectively. A surgical excision margin of 18mm correlated with complete excision in 96.7% of tumors, while complete excision in 100% of LM cases required a 21mm margin. Recurrent tumors (p-value = 0.01) and tumour size larger than 20mm were associated with wider surgical excision margins (pvalue= 0.154). The second study component evaluated IHC stains and consisted of 35 sections. Based on H&E and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 cases consistent with a diagnosis of LM and 9 revealing actinic melanocyte hyperplasia (AMH). PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of AMH (p=0.009). The presence of melanocyte nests (p=0.29) and pagetoid spread (p = 0.003) were the most reliable histological findings for distinguishing LM from its mimics. Conclusion: This study of LM in a South African population corroborates that the standard surgical excision margins recommended by international melanoma guidelines for LM are inadequate to achieve a 97% clearance rate. Recurrent LM cases and tumours larger than 20mm may require wider margins. The study further concluded that SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared to Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Agtergrond: Lentigo Maligna (LM) is 'n subtipe melanoom in situ wat voorkom op sonbeskadigde vel, tipies op die kop- en nek area van ouer individue. LM word geassosieer met beduidende subkliniese uitbreiding buite die sigbare kliniese marges en daarom kan chirurgies aanbevole eksisie marges onvoldoende wees vir die volledige eksisie van die tumor. Stapsgewyse Eksisie (SE) is die behandeling van keuse vir LM van die kop en nek. Dit maak voorsiening vir volledige marge beheer, beter verwydering van die tumor en minder herhaling in vergelyking met konvensionele wye lokale eksisie (WLE). Onderskeid tussen aktiniese melanosiet hiperplasie (AMH) en LM by die perifere marge bemoeilik die beoordeling van volledigheid van eksisie wanneer hierdie tegniek gebruik word. Doelwitte: Die studie het eerstens die pasient demografie, tumor eienskappe, en histologiese bevindings van LM-gevalle op die kop en nek wat met SE behandel is beskryf. Sekondere doelwitte het ingesluit: (1) Om vas te stel of standaard aanbevole chirurgiese eksisie marges vir LM van die kop en nek voldoende is om volledige eksisie 'n 97% van gevalle te bereik en of enige pasient of tumor eienskappe wyer marges regverdig; (2) Om vas te stel of immunohistochemiese (IHC) kleuring met SOX10 en PRAME die diagnose van LM op eksisie marges verbeter in vergelyking met konvensionele Hematoksilien en Eosien (H&E) en Melan-A IHC kleuring. Metodologie: Die studie was 'n retrospektiewe oorsig van alle pasiente gediagnoseer met LM van die kop en nek en wat SE behandeling by die Skinmatters Mohs Mikrografiese Chirurgie en Rekonstruktiewe Eenheid ontvang het. Weefsel snitte van LM-gevalle met LM aanwesig op die eksisie marge, was met SOX10 en PRAME IHC gekleur en hersien deur 'n Mohs-chirurg en 'n patoloog met kundigheid in melanoom patologie. Resultate: Die eerste deel van die studie het getoon dat 6 mm, 9 mm en 12 mm chirurgiese eksisie marges volledige eksisie verkry het in onderskeidelik 60.94%, 71.88% en 90.64% van die LMgevalle. 'n Chirurgiese eksisie marge van 18 mm het gekorreleer met volledige eksisie in 96,7% van gewasse, terwyl volledige eksisie in 100% van LM gevalle 'n 21mm marge vereis het. Herhalende LM (p-waarde = 0.01) en ‘n tumor deursnit groter as 20 mm is geassosieer met wyer chirurgiese eksisie marges (p-waarde = 0,154). Die tweede studie deel het IHC-kleurings geevalueer op 35 snitte. Gebaseer op H&E en Melan-A IHC-kleuring, het die aanvanklike patoloog 23 van hierdie snitte gediagnoseer as LM. SOX10 IHC kleuring het 8 gevalle getoon met 'n diagnose van LM en 9 gevalle met aktiniese melanosiet hiperplasie (AMH). PRAME was positief in 5 van die 8 gevalle van LM en negatief in die 9 gevalle van AMH (p=0.009). Die teenwoordigheid van melanosietneste (p=0.29) en pagetoide verspreiding (p = 0,003) was die mees betroubare histologiese bevindinge om LM te onderskei van sy nabootsers. Gevolgtrekking: Hierdie studie van LM in 'n Suid-Afrikaanse bevolking bevestig dat die standard chirurgiese eksisie marges vir LM soos aanbeveel deur internasionale riglyne onvoldoende is om 97% van LM volledig te eksideer. Herhalende LM-gevalle en tumore groter as 20 mm mag wyer marges vereis. Die studie het aangetoon dat SOX10 'n meer spesifieke en sensitiewe merker is as Melan-A vir die beoordeling van melanosiete en LM op eksisie marges. PRAME kan nuttig wees om die diagnose in uitdagende gevalle te bevestig of uit te sluit.af_ZA
dc.description.versionMasters
dc.format.extent27 pages : illustrations
dc.identifier.urihttp://hdl.handle.net/10019.1/127061
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.rights.holderStellenbosch University
dc.subject.lcshMelanoma -- Treatment -- South Africaen_ZA
dc.subject.lcshSkin -- Diseases -- South Africaen_ZA
dc.subject.lcshHead -- Cancer -- Surgery -- South Africaen_ZA
dc.subject.lcshNeck -- Cancer -- Surgery -- South Africaen_ZA
dc.subject.nameUCTD
dc.titleTreatment of lentigo maligna of the head and neck with staged excision in South Africa : assessing surgical excision margins with Melan A, SOX10 and PRAME immunohistochemistryen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
dewet_treatment_2023.pdf
Size:
2.07 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Masters Degrees (Anatomical Pathology)