Clear cell / pylorocardiac adenocarcinoma may have bland cytologic features leading to confusion with an adenoma on a biopsy
Grading / Staging
Grading
WHO recommends well, moderately, poorly and undifferentiated
No precise criteria given
WHO gastric adenocarcinoma grading criteria
Low grade
Well differentiated – well formed glands
In areas may be difficult to distinguish from benign atypia
Moderately differentiated - may be combined with well as low grade
High grade
Poorly differentiated
Highly irregular glands, difficult to discern, or
Single cells and clusters
Undifferentiated
Staging
EGJ TNM is the same as that used for esophagus
Intramucosal carcinoma is variably defined
and has poor interobserver agreement
A strict definition requires at least focal identification of detached single infiltrating cell(s)
A looser definition requires a cribriform pattern or growth in a pattern incompatible with pre-existing glands
Dense crowding, extensive branching and budding
In either case, there is no invasion beyond the muscularis mucosae
Duplication of muscularis mucosae can make staging difficult
Common in Barrett esophagus (92% of cases)
Not caused by the carcinoma
Outer layer of duplication (or triplication) is generally continuous with the original layer
Invasion between the duplicated layers is still considered T1 (intramucosal)
Lewis 2008 reports 17% lymphatic invasion rate and 10% nodal metastases
Higher than expected for T1
Lower than expected for T2
Estrella 2011 found no increase in nodal metastases
Level of invasion should be described and thickness measured and given in report
Recognition of this phenomenon can avoid over staging
Duplicated muscularis mucosae is generally fragmented and not tightly bundled
Normal muscularis propria is composed of well defined bundles of muscle
Endoscopic biopsies and EMRs rarely contain muscularis propria
Attention to edge of larger specimens can also be helpful
True submucosa contains thick walled vessels and thick ropey collagen
Stroma between muscularis mucosae layers contains thin walled vessels and fine collagen (in areas not involved by carcinoma)
Collagen may become thicker in areas of desmoplasia
Bibliography
Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
Sarbia M, Becker KF, Höfler H. Pathology of upper gastrointestinal malignancies. Semin Oncol. 2004 Aug;31(4):465-75.
Ghotli ZA, Serra S, Chetty R. Clear cell (glycogen rich) gastric adenocarcinoma: a distinct tubulo-papillary variant with a predilection for the cardia/gastro-oesophageal region. Pathology. 2007 Oct;39(5):466-9.
Carr N. Tubulopapillary clear cell carcinoma of the stomach may be a type of pylorocardiac carcinoma. Pathology. 2008 Apr;40(3):333.
Mandal RV, Forcione DG, Brugge WR, Nishioka NS, Mino-Kenudson M, Lauwers GY. Effect of Tumor Characteristics and Duplication of the Muscularis Mucosae on the Endoscopic Staging of Superficial Barrett Esophagus-related Neoplasia. Am J Surg Pathol. 2008 Nov 26.
Abraham SC, Krasinskas AM, Correa AM, Hofstetter WL, Ajani JA, Swisher SG, Wu TT. Duplication of the muscularis mucosae in Barrett esophagus: an under recognized feature and its implication for staging of adenocarcinoma. Am J Surg Pathol. 2007 Nov;31(11):1719-25.
Lewis JT, Wang KK, Abraham SC. Muscularis mucosae duplication and the musculo-fibrous anomaly in endoscopic mucosal resections for barrett esophagus: implications for staging of adenocarcinoma. Am J Surg Pathol. 2008 Apr;32(4):566-71.
Siewert JR, Feith M, Stein HJ. Biologic and clinical variations of adenocarcinoma at the esophago-gastric junction: relevance of a topographic-anatomic subclassification. J Surg Oncol. 2005 Jun 1;90(3):139-46
Estrella JS, Hofstetter WL, Correa AM, Swisher SG, Ajani JA, Lee JH, Bhutani MS, Abraham SC, Rashid A, Maru DM. Duplicated Muscularis Mucosae Invasion has Similar Risk of Lymph Node Metastasis and Recurrence-free Survival as Intramucosal Esophageal Adenocarcinoma. Am J Surg Pathol. 2011 Jul;35(7):1045-53.
