Table 1.
Clinical, histologic, viral, and genetic features of the seven patients and 45 lesions analyzed.
Pt | Sex/age (years) | Lesion code | Weeks on BRAFi1 (weeks) | Body site | SE/NSE2 | Diagnosis3 | Viral features4 | Mutations5 | Beta-PV6 | Alpha-PV | Gamma-PV | IHC7 | HPyV68 | HPyV78 | HPyV98 | TSPyV8 | MCPyV8 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | M/67 | V1 | 9 | Scalp | SE | VW | Y | NOTCH1, CREBBP | 8, 9, 36, 38, 111 | 28 | ND | 7.5 × 10−6 | 3.6 × 10−2 | Neg | Neg | 1.7 × 10−2 | |
V2 | 9 | Suprapubic | NSE | V K | Y | NOTCH1, HRAS, CARD11 | 8, 24, 36, 92, 111 | ND | ND | ND | ND | ND | ND | ||||
V3 | 9 | Post-auricular | SE | VW | Y | TGFBR2, CDKN2a, CARD11, NOTCH2, CREBBP | 8, 36 | ND | ND | ND | ND | ND | ND | ||||
V4 | 9 | Arm | SE | SCC | Y | TGFBR1, NOTCH1, HRAS | 8, 12, 24, 36, 111, FA51 | ND | Neg | 1.7 × 10−4 | Neg | Neg | 4.6 × 10−2 | ||||
V5 | 9 | Inner Thigh | NSE | VW | Y | NOTCH1, NOTCH2, HRAS, CREBBP | 8, 12, 36, 111 | ND | 2.9 × 10−4 | Neg | Neg | Neg | 2.8 × 10−2 | ||||
V6 | 9 | Lower Back | NSE | SCC | Y | TP53, HRAS | 12, 36, 92 | ND | 5.12 × 10−5 | 1.3 × 10−1 | Neg | Neg | 3.9 × 10−3 | ||||
V7 | 9 | Shoulder | NSE | SCC | Y | NOTCH1, TP53, TGFBR1, CREBBP | 15, 24, 36, 76, 92, 107, FA84 | Neg | Neg | 3.9 × 10−5 | Neg | Neg | 1.8 × 10−2 | ||||
V8 | 9 | Posterior neck | SE | VK | Y | NOTCH1, CARD11, TGFBR1 | 8, 24, 36, 93 | Neg | 4.6 × 10−5 | 4.8 × 10−4 | Neg | Neg | 2.3 × 10−1 | ||||
V9 | 9 | Cheek | SE | VW | Y | HRAS, TP53∗, NOTCH1,∗ NOTCH2∗ | 8, 12, 24, 36, 76, 92 93 | 28 | ND | ND | ND | ND | ND | ND | |||
V11 | 13 | Scalp | SE | VW | Y | NOTCH1, TGFBR2, CARD11, CREBBP | 8,23, 36, 92, 93 | Neg | Neg | 2.2 × 10−4 | Neg | Neg | 1 × 10−1 | ||||
V12 | 13 | Abdomen | NSE | N-NSE | N | NOTCH1 | 5, 92 | ND | ND | ND | ND | ND | ND | ||||
V13 | 13 | Lower back | NSE | SCC | Y | Nil | 8, 24, 92, 107, 111, FA14 | Neg | 3.9 × 10−5 | 2.4 × 10−4 | Neg | Neg | 5.9 × 10−3 | ||||
V14 | 13 | Popliteal Fossa | NSE | VW | Y | NOTCH1, CREBBP | 12, 24, 36 | ND | Neg | 1.3 × 10−2 | Neg | Neg | 1.7 × 10−3 | ||||
V15 | 13 | Post-auricular | SE | VW | Y | CARD11 | 93 | ND | Neg | 1.6 × 10−3 | Neg | Neg | 5.6 × 10−2 | ||||
V16 | 13 | Abdomen | NSE | VW | Y | TP53, HRAS | 8, 36, 92, 93 | ND | Neg | 6, × 10−4 | Neg | Neg | 9.9 × 10−3 | ||||
V17 | 13 | Abdomen | NSE | VW | Y | NOTCH1, CDKN2a | 8, 36, 92, 113 | ND | Neg | 1.4 × 10−1 | Neg | Neg | 6.2 × 10−4 | ||||
V18 | 14 | Chest | NSE | VW | Y | NOTCH1, HRAS, KRAS | 8∗∗, 12, 24, 76, 92∗∗, 111 | Neg | 1.12 × 10−5 | 5, × 10−5 | Neg | Neg | 5.8 × 10−3 | ||||
V19 | 14 | Groin | NSE | SCC | Y | HRAS, NOTCH1 | 8, 12, 24, 36, 92 | Neg | 3.93 × 10−6 | 1.4 × 10−4 | Neg | Neg | 3.6 × 10−3 | ||||
V20 | 14 | Chest | SE | SCC | Y | Nil | 8, 12, 24, 92∗∗, 93 | Neg | 1.29 × 10−5 | 2.4 × 10−4 | Neg | Neg | 1.2 × 10−2 | ||||
V25 | 18 | Arm | SE | N-P V27 | N | NOTCH1 | Neg | ND | ND | ND | ND | ND | ND | ||||
V26 | 18 | Abdomen | NSE | VW | Y | CARD11, NOTCH1, HRAS, CREBBP | 8, 92 | Neg | Neg | 5.9 × 10−5 | Neg | Neg | 5.3 × 10−3 | ||||
V27 | 18 | Upper arm | SE | SCC | Y | HRAS, CARD11, CREBBP, NOTCH1 NOTCH2∗ KRAS∗ TP53∗ | Novel | Neg | Neg | Neg | Neg | Neg | Neg | ||||
V28 | 18 | Lower abdomen | NSE | SCC | Y | NOTCH2, NOTCH1∗ | Neg | Neg | ND | ND | ND | ND | ND | ||||
V31 | 34 | Cheek | SE | VK | N | Nil | Novel | ND | 3.66 × 10−6 | 2.4 × 10−4 | Neg | Neg | 7.6 × 10−3 | ||||
V32 | 34 | Upper Arm | SE | VW | Y | NOTCH1, NOTCH2, HRAS, CREBBP, TP53∗ | 24∗∗, 36, 92, 93 | ND | ND | ND | ND | ND | ND | ||||
2 | M/35 | V10 | 13 | Chin | SE | VW | Y | Nil | 8, 12, 80∗∗, 76 | 57∗∗ | 57, beta | ND | ND | ND | ND | ND | |
V29 | 28 | Scapula | NSE | VW | Y | NOTCH2, CREBBP | 12∗∗, 8, 20, 23, 36,76, 80, 92, 96 | 57 | ND | ND | D | ND | ND | ND | |||
3 | M/56 | V21 | 8 | Neck | SE | VK | N | HRAS, CARD11, NOTCH1 ∗ NOTCH2∗ | 22, 115, 150 | ND | 3.73 × 10−5 | 6.4 × 10−5 | Neg | Neg | Neg | ||
V22 | 14 | Post-auricular | SE | VW | Y | TGFBR1, HRAS NOTCH2∗ | 22, 107 | ND | ND | ND | ND | ND | ND | ||||
V23 | 14 | Upper arm | SE | SCC | Y | CREBBP, CARD11, TGFBR1, NOTCH2∗ | 2, 14D, 22, 38, 107, 115 | Neg | Neg | Neg | Neg | Neg | 1.3 × 10−4 | ||||
V24 | 14 | Upper Arm | SE | N-P to V23 | N | NOTCH1 | Novel | ND | ND | ND | ND | ND | ND | ||||
4 | F/33 | V30 | 16 | Abdomen | NSE | SCC | N | TP53, HRAS, NOTCH1∗ NOTCH2∗ | Neg | FA49 | ND | Neg | Neg | Neg | Neg | Neg | |
5 | M/87 | V33 | 6 | Ear | SE | VW | Y | NOTCH1, TP53 | 9 | ND | Neg | Neg | Neg | Neg | Neg | ||
V34 | 6 | Chin | SE | AK | Y | Nil | 9, 38 | ND | Neg | 1.5 × 10−5 | Neg | Neg | Neg | ||||
6 | F/82 | V35 | 12 | Neck | SE | SCC | Y | TGFBR1, TGFBR2, NOTCH1, TP53, KRAS, NOTCH2, CARD11, CREBBP | Neg | ND | Neg | Neg | Neg | Neg | Neg | ||
V36 | 12 | Neck | SE | N-P V35 | N | Nil | Neg | ND | ND | ND | ND | ND | ND | ||||
V37 | 12 | Neck | SE | N -SE | N | NOTCH1, CARD11 | Neg | ND | ND | ND | ND | ND | ND | ||||
V38 | 12 | Shoulder | NSE | VW | Y | TGFBR1, TGFBR2, TP53, KRAS, NRAS, CARD11, CREBBP | Neg | ND | ND | ND | ND | ND | ND | ||||
V39 | 12 | Lower Leg | SE | SP | Y | TGFBR1, NOTCH1, NOTCH2,, TP53, CREBBP | Neg | ND | Neg | Neg | Neg | Neg | 1.5 × 10−3 | ||||
V40 | 12 | Arm | SE | SCC | Y | TGFBR2, CREBBP | Neg | ND | Neg | Neg | 4 × 10−4 | Neg | 2.9 × 10−3 | ||||
7 | F/54 | V41 | 11.5 | Neck | SE | N-SE | N | NOTCH2, CREBBP | Novel | ND | ND | ND | ND | ND | ND | ||
V42 | 11.5 | Back | NSE | VW | Y | TP53 | 80 | ND | Neg | Neg | Neg | Neg | Neg | ||||
V43 | 11.5 | Back | NSE | M | NOTCH1, NOTCH2, NRAS, CARD11, CREBBP | 80 | ND | Neg | Neg | Neg | Neg | 9 × 10−4 | |||||
V44 | 11.5 | Back | NSE | VW | Y | CARD11 | 80∗∗ | ND | Neg | Neg | Neg | Neg | Neg | ||||
V45 | 11.5 | Back | NSE | AK | Y | NOTCH1, TP53 | 80 | ND | Neg | Neg | Neg | Neg | 1.4 × 10−4 |
1Weeks on BRAFi: number of weeks on vemurafenib at the time lesion was removed. 2SE/NSE: Sun exposed or non-sun exposed body site. 3Diagnosis: SCC – well differentiated SCC; V, viral wart; VK, verrucous keratosis; AK, actinic keratosis; N-P, normal skin perilesional to; N-SE, normal skin sun exposed; N-NSE – normal skin non sun exposed; M, benign melanocytic; SP, squamoproliferative lesion with viral features and dysplasia but no clear evidence of invasion. 4Viral features: Y, yes; N, no: yes if koilocytosis was observed in conjunction with at least 3 of the following 5 features: acanthosis, hypergranulosis, parakeratosis, hyperkeratosis and typical papillomatous architecture. 5Mutations: these have previously been published (South, 2014; Cammareri, 2016). ∗ indicates lesion bisected and results represent total mutations found across both portions. 6Beta-PV: beta HPV types. Beta-PV types associated with strong bands on the RH assay are recorded as ∗∗; neg, negative. 7 IHC; immunohistochemistry – performed on 12 selected lesions. 8HPyV6, -7, -9, TSPyV and MCPyV: neg, negative; N/D, not done; values recorded are viral copies per cell.