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adenoma with invasive carcinoma

Sunday 10 February 2013

Malignant (epithelial) polyp; malignant colorectal polyp

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