Table 1 Clinical, morphologic and immunohistochemical features of MCPyV-negative (n = 21) and -positive MCC (n = 80) cases. Characteristics of the two subsets were compared by non-parametric Mann Whitney and Fisher’s exact tests for quantitative and qualitative data, respectively. For survival analyses, log rank test was used. Positive likelihood ratios for MCPyV positivity were assessed for markers that differed between the two groups (p < 0.05), by MCPyV status, by real-time PCR as the gold standard and predetermined cutoffs (underlined criteria vs rest) [4, 6, 11]
Merkel cell carcinoma cases | ||||
|---|---|---|---|---|
MCPyV-negative (n = 21) | MCPyV-positive (n = 80) | P value* | Positive likelihood ratio (95% CI) | |
Clinical features | ||||
Age, years | 0.25 | – | ||
Median, quartiles | 81 (76–85) | 78 (69–84) | ||
Missing data | 3 | 4 | ||
Sex | 0.8 | – | ||
F/M | 12/8 | 45/35 | ||
Missing data | 1 | 0 | ||
Immunosuppressive status | 0.67 | – | ||
Yes | 1 (7%) | 9 (16%) | ||
No | 13 (93%) | 46 (84%) | ||
Missing data | 7 | 25 | ||
AJCC stage | 0.45 | – | ||
I | 7 (47%) | 18 (27%) | ||
II | 3 (20%) | 22 (32%) | ||
III | 5 (33%) | 24 (36%) | ||
IV | 0 | 2 (3%) | ||
Missing data | 6 | 14 | ||
Location | 0.09 | – | ||
Head | 9 (60%) | 21 (30%) | ||
Trunk | 0 | 4 (6%) | ||
Upper limb | 0 | 5 (7%) | ||
Lower limb | 5 (33%) | 28 (39%) | ||
Unknown primary | 1 (6.7%) | 13 (18%) | ||
Missing data | 6 | 9 | ||
Recurrence free, month | 0.005 | – | ||
Mean survival, 95% CI | 11 (9–13) | 66 (54–79) | ||
Missing data | 8 | 13 | ||
Specific death, month | 0.027 | – | ||
Mean survival, 95% CI | 30 (5–21) | 88 (76–99) | ||
Missing data | 8 | 13 | ||
Morphologic features | ||||
Nuclear shape | 0.005 | 1.39 | ||
Regular | 14 (67%) | 74 (93%) | (1.02–1.89) | |
Elongated | 7 (33%) | 6 (7%) | ||
Uninterpretable cases | 0 | 0 | ||
Nucleoli | 0.002 | 1.30 | ||
None/inconspicuous | 16 (76%) | 78 (99%) | (1.02–1.65) | |
Present | 5 (24%) | 1 (1%) | ||
Uninterpretable cases | 0 | 1 | ||
Cell size | 0.026 | 1.20 | ||
Small (<2 Lc) | 5 (24%) | 17 (22%) | (0.97–1.49) | |
Moderate (2–3 Lc) | 12 (57%) | 58 (75%) | ||
Large (>3 Lc) | 4 (19%) | 2 (3%) | ||
Uninterpretable cases | 0 | 3 | ||
Cytoplasm volume | 4×10 –7 | 2.70 | ||
None/inconspicious | 7 (33%) | 71 (90%) | (1.47–4.96) | |
Abundant | 14 (67%) | 8 (10%) | ||
Uninterpretable cases | 0 | 1 | ||
Clear cytoplasm | 2×10 -6 | 1.73 | ||
No | 12 (57%) | 78 (99%) | (1.19–2.50) | |
Yes | 9 (43%) | 1 (1%) | ||
Uninterpretable cases | 0 | 1 | ||
Rosette-like structure | 0.02 | 1.35 | ||
No | 14 (67%) | 71 (90%) | (0.99–1.84) | |
Yes | 7 (33%) | 8 (10%) | ||
Uninterpretable cases | 0 | 1 | ||
Intraepidermal component | 0.04 | 1.1 | ||
No | 19 (90%) | 80 (100%) | (0.96–1.27) | |
Yes | 2 (10%) | 0 | ||
Uninterpretable cases | 0 | 0 | ||
Divergent differentiation | 0.001 | 1.24 | ||
No | 17 (81%) | 80 (100%) | (1–1.52) | |
Yes | 4 (19%) | 0 | ||
Uninterpretable cases | 0 | 0 | ||
Associated intraepithelial neoplasia | 0.04 | 1.1 (0.96–1.27) | ||
No | 19 (90%) | 80 (100%) | ||
Yes | 2 (10%) | 0 | ||
Uninterpretable cases | 0 | 0 | ||
Immunohistochemical profile | ||||
Cytokeratin 20 | 0.02 | 4.5 | ||
Negative | 2 (10%) | 6 (8%) | (0.64–31.63) | |
Diffuse | 2 (10%) | 0 | ||
Mixed | 14 (75%) | 52 (68%) | ||
Dot-like pattern | 1 (5%) | 18 (23%) | ||
Uninterpretable cases | 2 | 4 | ||
Cytokeratin 8 | 0.02 | 1.73 | ||
Negative | 0 | 0 | (0.90–3.33) | |
Diffuse | 0 | 0 | ||
Mixed | 10 (63%) | 26 (35%) | ||
Dot-like pattern | 6 (37%) | 48 (65%) | ||
Uninterpretable cases | 5 | 6 | ||
Cytokeratin 18 | 0.006 | 2.18 | ||
Negative | 1 (5%) | 0 | (1.01–4.70) | |
Diffuse | 0 | 0 | ||
Mixed | 13 (69%) | 28 (39%) | ||
Dot-like pattern | 5 (26%) | 43 (61%) | ||
Uninterpretable cases | 2 | 9 | ||
TTF-1 | 4×10 –6 | 1.92 | ||
Negative | 10 (40%) | 72 (96%) | (1.24–2.98) | |
Positive | 10 (50%) | 3 (4%) | ||
Uninterpretable cases | 1 | 5 | ||
ATOH1 | 0.05 | – | ||
Negative | 0 | 1 (1%) | ||
Low/heterogenous | 3 (15%) | 29 (38%) | ||
High and diffuse | 17 (85%) | 46 (61%) | ||
Uninterpretable cases | 1 | 4 | ||
Neurofilament | 0.04 | 1.49 | ||
Negative | 9 (47%) | 17 (22%) | (0.95–2.31)) | |
Dot-like pattern | 10 (53%) | 61 (78%) | ||
Uninterpretable cases | 2 | 2 | ||
SATB2 | 0.07 | – | ||
Negative | 5 (25%) | 6 (8%) | ||
Low/heterogenous | 6 (30%) | 19 (24%) | ||
High and diffuse | 9 (45%) | 54 (68%) | ||
Uninterpretable cases | 1 | 1 | ||
CD99 | 0.02 | 8.08 | ||
Negative | 1 (5%) | 12 (15%) | (2.16–30.21) | |
Dot-like pattern | 2 (10%) | 63 (81%) | ||
Diffus | 17 (85%) | 3 (4%) | ||
Uninterpretable cases | 1 | 2 | ||
PAX5 | 0.90 | – | ||
Negative | 16 (80%) | 57 (74%) | ||
Low/heterogenous | 4 (20%) | 16 (21%) | ||
High and diffuse | 0 | 4 (5%) | ||
Uninterpretable cases | 1 | 3 | ||
TdT | 0.34 | – | ||
Negative | 16 (89%) | 60 (76%) | ||
Positive | 2 (11%) | 19 (23%) | ||
Uninterpretable cases | 3 | 1 | ||
EMA | 0.003 | 2.70 | ||
Negative | 5 (25%) | 22 (29%) | (1.10–6.64) | |
Low/heterogenous | 11 (55%) | 13 (17%) | ||
High and diffuse | 4 (20%) | 41 (54%) | ||
Uninterpretable cases | 1 | 4 | ||
Cytokeratin 7 | 0.006 | 1.36 | ||
Negative | 12 (71%) | 69 (96%) | (1–1.85) | |
Positive | 5 (29%) | 3 (4%) | ||
Uninterpretable cases | 4 | 8 | ||
p53 | 2×10 −9 | 3.63 | ||
No expression | 7 (37%) | 2 (3%) | (1.71–7.7118) | |
Heterogenous expression | 5 (26%) | 63 (95%) | ||
Overexpression | 7 (37%) | 1 (2%) | ||
Uninterpretable cases | 2 | 14 | ||
Large T antigen | 2×10 −9 | – | ||
Negative | 17 (100%) | 17 (23%) | ||
Positive | 0 | 58 (77%) | ||
Uninterpretable cases | 4 | 5 | ||