Nuclear features in malignant cells:
(1) nuclear enlargement with hyperchromasia (compared to cells in adjacent normal glands)
(2) prominent nucleoli
(3) mitotic figures
(4) clustered nuclei
(5) marginated nucleoli
(6) multiple nucleoli
Cytoplasmic features in malignant cells:
(1) amphophilic staining
(2) luminal borders that are sharp/straight/even, without budding
(3) positive immunostaining for AMACR (alpha-methyl-acyl-CoA racemase)
Luminal features in malignant glands:
(1) blue-tinged (basophilic) mucinous secretions
(2) pink, dense, amorphous secretions
(3) intra-luminal crystalloids
Glandular features:
(1) absence of a basal cellular layer (basal cells can be demonstrated with a high molecular cytokeratin
stain such as 34beta-E12)
The diagnosis of a malignancy should not be made based on any single feature.
Reasons for being cautious in making the diagnosis of adenocarcinoma:
(1) atrophic cytoplasm
(2) severe inflammation
(3) poor histologic preparation (processing or sectioning)
(4) presence of cytoplasmic lipofuscin (usually seen in the epithelium of the seminal vesicles)
(5) adjacent area of high grade PIN (just make sure not a tangential cut of a PIN gland)
(6) merging of suspicious glands with typical benign glands (seen with adenosis)