Features of invasive adenocarcinoma:
(1) haphazard growth pattern
(2) presence of glands adjacent to blood vessels
(3) presence of cells within vessels (intravascular invasion)
(4) perineural invasion
(5) presence of glands touching fat
(6) high variation in nuclear size within a gland
(7) incomplete glands
where:
• The area of nuclei within a reactive gland should not vary by more than 4 to 1 ("rule of four". For a circular nucleus, this means that the diameter of the largest nucleus is <= 2 times the diameter of the smallest nucleus.
• In a malignant gland ratio for the area of the largest nucleus to the area of the smallest nucleus exceeds 4 to 1.
Features that are seen more common in adenocarcinoma than in reactive glands:
(1) intraluminal necrosis
(2) CEA immunoreactivity
(3) mesothelin immunoreactivity
(4) B72.3 immunoreactivity
(5) loss of dpc4 (Smad4) immunoreactivity
