This subclassification is based upon the degree of gland formation, regularity of gland architecture, cytologic features, presence of amount of solid areas, level of mitotic activity and the presence and amount of necrosis. Accurate grading also requires an adequate sample, small biopsies tend to be of little value, and initial grades are often changed with more thorough sampling. Histologic grading is not reliable in cases with metastatic disease or following chemotherapy or radiation treatment. Histologic grade tends to correlate poorly with survival data, however, poorly differentiated adenocarcinoma does have a poor prognosis and is rapidly fatal. The better differentiated tumors form orderly glands lined by tall columnar cells with a regular array of nuclei.
Papillary architecture begins with the protrusion of cells into the gland lumen.
Generally the more well differentiated papillary variants show a core of fibrous connective tissue which is covered by a single layer of uniform cuboidal to columnar cells. Stratification and loss of uniformity are associated with a loss of differentiation. Since the solid variant is poorly differentiated by definition, it may be difficult to perceive gland formation. Mucin stains are necessary to demonstrate mucin and differentiate the tumor from a large cell carcinoma. Mackay B, JM Lukeman and NG Ordonez.