adenoma with invasive carcinoma

Definition: Adenoma containing carcinoma that invades through muscularis mucosae into submucosa.

 Malignant polyps’ incidence & their indolent behavior

• May have been falsely overestimated in past
• Misdiagnosis of misplaced epithelium as invasion

 False-positives (resection indicated, no residual cancer)

• Identify, examine/section entire polypectomy site
• Not uncommon even if polyp margin was obviously positive
• Cautery at time of polypectomy may destroy minimal residual disease

 Piecemeal removal hinders margin evaluation

• Diathermy (cautery artifact) may not represent true margin

 Stalk often retracts into polyp head after removal
 Cooperation needed between pathologist, endoscopist, and surgeon

Epidemiology

 Incidence: Invasion present in 0.2-9.4% (average 4.7%) of endoscopically removed (polypectomy) adenomas

Natural History

 Cumulative carcinoma risk in adenomas not removed

• 2.5% at 5 years,
• 8% at 10 years,
• 24% at 20 years

 Conversion rate to carcinoma: 0.25% per year
 90-95% of adenomas will not progress

Treatment

 Pedunculated polyp with invasive carcinoma

• Polypectomy considered curative when:
  • Polyp deemed completely excised at colonoscopy
  • Properly oriented section confirms that margin is negative
  • Absence of unfavorable histologic features

• Follow-up recommended in 2-6 months
  • Risk of synchronous, metachronous cancer
  • Evaluate polypectomy site (tattoo helps identify)

 Subtotal colectomy, lymph node dissection for

• • Pedunculated polyps with unfavorable histology
  • Sessile adenomas with invasive carcinoma / Risk of metastasis ( 20%)
  • Invasion into bowel wall submucosa (beyond stalk)
  • Polypoid adenocarcinomas = polyp head completely replaced by cancer; minimal or no residual adenoma

Prognosis

 Adverse outcome (recurrence &/or metastases) in pedunculated polyp with invasion

• Generally occurs with low incidence
• But in 20-30% polyps with unfavorable histology
• 1% false-negative (favorable histology, bad outcome)

 Unfavorable histologic features (poor prognosis)

• Poorly differentiated carcinoma, even focal
• Tumor budding
• Presence of lymphovascular invasion
• Tumor near cauterized margin (< 1-2 mm), depends on study

Microscopy

 Invasion into submucosa

• Invasion elicits desmoplastic stromal reaction
• Neoplastic cells within fat, blood vessels, nerve trunks, or lymphatics

 Architectural complexity & cytologic atypia

• Irregular angulated contours with jagged edges
• Infiltrative growth, single cells, or small clusters
• Greater degree of dysplasia than surface adenoma

 Mucinous (colloid) adenocarcinoma

• Irregular mucin pools dissecting submucosa
• Cytologically malignant cells floating in mucin

 Lymphatic/Vascular Invasion: CD34, CD31, FVIIIRAg, podoplanin can help differentiate from artifact
 Presence of desmoplasia key to diagnosis
 Step sections should be used liberally to better evaluate invasion, margin, lymphovascular invasion

Differential diagnosis

 "Localized" Colitis Cystica Profunda

• Epithelium in submucosa but nonneoplastic
• Usually ulcerated or hyperplastic, in rectum
• Often history of prolapse or radiation therapy

 Misplaced Epithelium ("Pseudoinvasion")

• Lobular architecture, smooth rounded crypts
• Same grade of dysplasia as adenoma surface
• Surrounded by rim of lamina propria (no desmoplasia)
• Hemorrhage or hemosiderin deposition

Etiology/Pathogenesis

 Invasion ↑ with size: 30% villous adenomas > 5 cm
 Most adenomas < 1 cm: Low malignant potential
 Villous component, dysplasia correlate with size
 Adenoma-Carcinoma Progression

• Invasion usually develops centrally, spreads outward
• Factors predisposing to carcinoma development
  • Incidence of invasion ↑ with adenoma size
  • 30% of villous adenomas > 5 cm contain carcinoma
  • But large sessile adenomas > 20 cm can be benign
  • Small adenomas: Lowest risk of malignancy
  • Not negligible: 4 mm adenoma can be malignant Villous component and high-grade dysplasia increases risk of carcinoma Both correlate with size; unclear if independent Most adenomas < 1 cm: Low-grade dysplasia only, low malignant potential (5% risk at 15 years) High-grade dysplasia ↑ malignancy rate to 27%

Clinical Issues

 Invasion: 0.2-9.4% (average 4.7%) of polypectomies
 Unfavorable histology: Poor differentiation, lymphovascular invasion, < 1-2 mm from margin
 20-43%: Recurrence &/or lymph node metastases
 Colectomy for unfavorable histology (pedunculated), invasion in sessile polyp, polypoid adenocarcinoma, invasion into bowel wall submucosa beyond stalk

Microscopic Pathology

 Irregular complex crypts, infiltrative, desmoplasia

Top Differential Diagnoses

 Misplaced epithelium ("pseudoinvasion")

• Lobular growth,
• rim of lamina propria,
• hemorrhage

References

 Cooper HS et al: Pathology of the malignant colorectal polyp. Hum Pathol. 29(1):15-26, 1998
 Volk EE et al: Management and outcome of patients with invasive carcinoma arising in colorectal polyps. Gastroenterology. 109(6):1801-7, 1995
 Coverlizza S et al: Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential. Cancer. 64(9):1937-47, 1989
 Morson BC et al: Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy. Gut. 25(5):437-44, 1984