Adenocarcinoma of the Colon and Rectum

Differential Diagnosis

Metastatic adenocarcinoma of unknown type

Tall columnar cells with prominent dirty necrosis should suggest colorectal primary
Immunohistochemistry can be quite useful:

CK7 and CK20 expression in carcinomas
CK7+20+	CK7-20+
Ovary mucinous 90%	Colorectal adeno 80%
Transitional cell 65%	Merkel cell 70%
Pancreas adeno 65%	Gastric adeno 35%
Cholangio 65%
Gastric adeno 40%
Excluded tumors 5% or less Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno	Excluded tumors 5% or less Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
CK7+20-	CK7-20-
Ovary non-mucinous 100%	Adrenal 100%
Thyroid (all 3 types) 100%	Seminoma & Yolk Sac 95%
Breast 90%	Prostate 85%
Lung adeno 90%	Hepatocellular 80%
Uterus endometrioid 85%	Renal adeno 80%
Embryonal 80%	Carcinoid intestinal & lung 80%
Mesothelioma 65%	Lung small cell & squam 75%
Transitional cell 35%	Esoph squam 70%
Pancreas adeno 30%	Head/neck squam 70%
Cholangio 30%	Mesothelioma 35%
Excluded tumors 5% or less Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma	Excluded tumors 5% or less Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno

Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources

Colorectal Adenoma Containing Invasive Adenocarcinoma	Colorectal Adenoma with Benign Misplacement of Glands / Pseudoinvasion
Usually significant architectural and/or cytologic atypia	Usually lacks significant architectural and/or cytologic atypia (high grade dysplasia may be misplaced occasionally but is typically accompanied by bland adenoma tissue)
Desmoplastic stroma	Inflammatory or fibrotic stroma
Infiltrates through muscularis mucosae	Frequently demonstrable continuity with surface through a gap in the muscularis mucosae
Hemosiderin restricted to head of polyp	Hemosiderin common in stalk stroma
Glands not accompanied by lamina propria	Glands may be accompanied by lamina propria
Usually infiltrative, non-circumscribed	Frequently circumscribed
May occur throughout the colorectum	Virtually restricted to left colon
Collagen type IV weak, discontinuous	Collagen type IV strong, continuous around epithelial nests
E cadherin markedly decreased staining compared to overlying adenoma	E cadherin same intensity as overlying adenoma (high grade dysplasia may show decrease)

Mucosal Prolapse / Cloacogenic Polyp (Localized Colitis Cystica Profunda)	Invasive Colorectal Adenocarcinoma
No surface carcinoma component	Surface component usually present
No high grade nuclear atypia	High grade nuclear atypia usually present
No cribriform glands or complex architecture	Complex architecture with cribriform glands frequent
No desmoplastic stromal response	Desmoplastic stromal response
Lamina propria may accompany displaced glands	No lamina propria accompanying invasive glands
Mean age 35 years	Occurs in older patients

Colorectal Medullary Carcinoma	Colorectal Poorly Differentiated Carcinoma NOS
Lacks any gland formation	At least 5% gland formation
Uniform small to medium sized nuclei	Pleomorphic large nuclei
Uniformly prominent nucleoli	Variable nucleoli
Pushing border	Infiltrative border
Prominent lymphoid infiltrate in virtually all cases	Lymphoid infiltrate variable

Colorectal Medullary Carcinoma	Colorectal Undifferentiated Carcinoma NOS
Lacks any gland formation	May have <5% gland formation
Uniform small to medium sized nuclei	Pleomorphic large nuclei
Uniformly prominent nucleoli	Variable nucleoli
Pushing border	Infiltrative border
Prominent lymphoid infiltrate in virtually all cases	Lymphoid infiltrate variable