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
Case 26: M 37. Right jawline 5mm nodule?keloid
Case 26: M 37. Right jawline 5mm nodule?keloid
S100 useful for architecture
Ill-defined deep border, some lack of maturation
mitoses and nuclear pleomorphism
Case 26: M 37 Diagnosis? p16 variable expression Ki67 low (5%)
Atypical Spitz tumour:? slightly favouring benign
Case 26: atypical Spitz tumour Differential diagnosis: desmoplastic Spitz naevus Similar but more sclerotic stroma, less atypia
Case 26: atypical Spitz tumour Differential diagnosis: Spitzoid melanoma Similar but more atypia, asymmetry, mitoses etc.
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
Differential diagnosis: deep penetrating naevus wedge-shaped, less atypia
Case 26: atypical Spitz tumour Differential diagnosis: deep penetrating naevus wedge-shaped, less atypia,
Differential diagnosis: Spitz naevus more symmetry, clefts surrounding nests, Kamino bodies, less atypia
Case 26: atypical Spitz tumour Differential diagnosis: Spitz naevus more symmetry, less atypia,
FISH results Vysis Melanoma FISH Probe Kit Total Value Parameters +/- (Gerami et al.am J Surg Pathol 2008;33:1146-1156) % of nuclei with > 2 CCND1 signals 1 3.33% Cut-off >/- 38.00% - % of nuclei with > 2 RREB1 signals 0 0.00% Cut-off >/- 29.00% - % of nuclei with gain of RREB1 relative to CEP6 5 16.67% Cut-off >/- 55.00% - % of nuclei with loss of MYB (6q23) relative to CEP6 17 56.67% Cut-off >/- 40.00% + Abbott Average CCND1 signals per nucleus 50 1.67 Cut-off >/- 2.50 - % of atypical nuclei (signals/nucleus >or<2) for RREB1 10 33.33% Cut-off >/- 63.00% - Average MYB signals per nucleus 37 2.23 Cut-off >/- 2.50 - % of nuclei with loss of MYB (6q23) 8 relative to CEP6 17 56.67% Cut-off >/- 31.00% + FISH positive for 6q23 loss with both probe kits FISH courtesy of JE Calonje
Case 26: M 37. Final diagnosis? Atypical Spitz tumour with 6q23 deletion
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. 2013 Dec;35(8):804-12 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)
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. 2013 Dec;35(8):804-12 Can we predict the deletion histologically? NO! minimal pagetoid spread (P = 0.004) expansile nodular growth (P = 0.08) focal ulceration (P = 0.19)
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
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. 2013 May;37(5):676-84. 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.
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
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