Case 26 Male 37. Right jawline 5mm nodule?keloid. The best diagnosis is:

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1 Case 26 Male 37. Right jawline 5mm nodule?keloid. The best diagnosis is: A. Desmoplastic Spitz naevus B. Atypical Spitz Tumour C. Spitzoid melanoma D. Deep penetrating naevus E. Spitz naevus

2 Case 26: M 37. Right jawline 5mm nodule?keloid

3 Case 26: M 37. Right jawline 5mm nodule?keloid

4 S100 useful for architecture

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10 Ill-defined deep border, some lack of maturation

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13 mitoses and nuclear pleomorphism

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15 Case 26: M 37 Diagnosis? p16 variable expression Ki67 low (5%)

16 Atypical Spitz tumour:? slightly favouring benign

17 Case 26: atypical Spitz tumour Differential diagnosis: desmoplastic Spitz naevus Similar but more sclerotic stroma, less atypia

18 Case 26: atypical Spitz tumour Differential diagnosis: Spitzoid melanoma Similar but more atypia, asymmetry, mitoses etc.

19 Differential diagnosis: Spitzoid melanoma Similar but more atypia, asymmetry, mitoses etc. Slides courtesy of melanocytepathology.com Free access site by Prof Wolter Mooi, 2013 BSD guest speaker

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21 Differential diagnosis: deep penetrating naevus wedge-shaped, less atypia

22 Case 26: atypical Spitz tumour Differential diagnosis: deep penetrating naevus wedge-shaped, less atypia,

23 Differential diagnosis: Spitz naevus more symmetry, clefts surrounding nests, Kamino bodies, less atypia

24 Case 26: atypical Spitz tumour Differential diagnosis: Spitz naevus more symmetry, less atypia,

25 FISH results Vysis Melanoma FISH Probe Kit Total Value Parameters +/- (Gerami et al.am J Surg Pathol 2008;33: ) % of nuclei with > 2 CCND1 signals % Cut-off >/ % - % of nuclei with > 2 RREB1 signals % Cut-off >/ % - % of nuclei with gain of RREB1 relative to CEP % Cut-off >/ % - % of nuclei with loss of MYB (6q23) relative to CEP % Cut-off >/ % + Abbott Average CCND1 signals per nucleus Cut-off >/ % of atypical nuclei (signals/nucleus >or<2) for RREB % Cut-off >/ % - Average MYB signals per nucleus Cut-off >/ % of nuclei with loss of MYB (6q23) 8 relative to CEP % Cut-off >/ % + FISH positive for 6q23 loss with both probe kits FISH courtesy of JE Calonje

26 Case 26: M 37. Final diagnosis? Atypical Spitz tumour with 6q23 deletion

27 Atypical spitz tumors with 6q23 deletions: a clinical, histological, and molecular study. Shen L, Cooper C, Bajaj S, Liu P, Pestova E, Guitart J, Gerami P. Am J Dermatopathol Dec;35(8): retrospective case-controlled study probes targeting 6p25, 6q23, Cep6, 11q13, 9p21, and Cep9. 24 cases of atypical Spitz tumours (ASTs) with isolated copy number deletions in 6q23 6 of 11 patients had a positive sentinel node biopsy, BUT none of the patients developed tumor in a non-sentinel node, palpable adenopathy, in transit metastasis, or distant metastasis BUT mean follow up only 22 months (2 of 3 cases with at least 5 yrs had positive sentinel node)

28 Atypical spitz tumors with 6q23 deletions: a clinical, histological, and molecular study. Shen L, Cooper C, Bajaj S, Liu P, Pestova E, Guitart J, Gerami P. Am J Dermatopathol Dec;35(8): Can we predict the deletion histologically? NO! minimal pagetoid spread (P = 0.004) expansile nodular growth (P = 0.08) focal ulceration (P = 0.19)

29 Atypical Spitz tumours with possible good prognosis: 3p21 and 6q23 loss 3p21 (BAPoma / BAP1 associated Spitz tumour) 6q23 but is it really a good prognosis? as 6 of 11 patients had a positive sentinel node biopsy! Both can show much cytological atypia

30 Atypical Spitz tumours with possible poor prognosis: HOMOZYGOUS 9p21 loss, 6p25gain, 11q13 gain Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Gerami P, Scolyer RA, Xu X, Elder DE, Abraham RM, Fullen D, Prieto VG, Leboit PE, Barnhill RL, Cooper C, Yazdan P, Guitart J, Liu P, Pestova E, Busam K. Am J Surg Pathol May;37(5): FISH detecting a limited number of chromosomal copy number aberrations can provide clinically useful and statistically significant risk assessment for atypical Spitz tumors. In multivariate analysis, homozygous 9p21 deletion was highly associated with clinically aggressive behavior (P<0.0001) and death due to disease (P=0.003). Cases with 6p25 or 11q13 gains also have higher risk for aggressive clinical behavior than FISH-negative atypical Spitz tumors or cases with 6q23 deletions.

31 Atypical Spitz tumours with possible poor prognosis: HOMOZYGOUS 9p21 loss, 6p25gain, 11q13 gain HOMOZYGOUS 9p21 loss Severe cytologic atypia predominance of epithelioid cytomorphology increased dermal mitotic activity p16-100% of cases had areas with complete loss of staining

32 Case 26 Male 37. Right jawline 5mm nodule?keloid. The best diagnosis is: A. Desmoplastic Spitz naevus B. Atypical Spitz Tumour C. Spitzoid melanoma D. Deep penetrating naevus E. Spitz naevus

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