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intramucosal colorectal adenocarcinoma

Sunday 10 February 2013

WHO Stage Tis; small flat carcinoma; polyps with severe atypia; intramucosal colorectal carcinoma; high grade intramucosal neoplasia; Carcinoma in situ; High grade dysplasia; High grade intraepithelial neoplasia; High grade intramucosal neoplasia; Intramucosal carcinoma

Definition: The malignant change are confined to mucosa.

The diagnosis of invasive malignancy on biopsies from colorectal neoplasms can be challenging. The concept of intramucosal carcinoma as an indicator of invasive malignancy is somewhat controversial within histopathology circles despite current World Health Organization (WHO) definitions.

For adenomas:
- no invasion into submucosal stalk,
- no undifferentiated carcinoma
no vascular invasion
- no desmoplastic stroma

This controversial terminology may reflect differing thresholds for malignancy between West (higher threshold) and Japan (lower threshold), as Japanese pathologists diagnose as malignant what West calls high grade dysplastic lesions.

Little metastatic potential as there are minimal lymphatic channels in colonic mucosa, so resection is not indicated.

If tumor invades stalk of polyp, then bowel resection may be justified.


High grade intramucosal neoplasia (high grade dysplasia) requires any one of three criteria below:
- Cribriform architecture

  • Back to back gland lumens without intervening stroma
    • Should clearly be a manifestation of total loss of polarity by atypical cells

- Severe cytologic atypia

  • This is unusual in the absence of cribriform architecture, but can occur

- Invasion with a desmoplastic response confined to the lamina propria including muscularis mucosae


In a 2009 study of 89 patients, 97% were shown to have frankly invasive adenocarcinoma by the current WHO definition. The positive predictive value of intramucosal carcinoma at biopsy for invasive cancer was 96.6%. This study indicated that there should be a greater willingness among colorectal pathologists to accept the biopsy finding of intramucosal carcinoma as the earlier form of invasive malignancy. Clinicians should alter their treatment algorithms accordingly. (#19820998#)

Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and therefore have no potential for metastases and local intervention (usually polypectomy) should be adequate treatment. For this reason, they are classified as "Tis" in the TNM system.

It is believed that carcinomas invading the submucosa with unfavorable histology (tumors at/near the margin, and/or vascular invasion, and/or poor differentiation) require additional intervention after polypectomy, whereas those with favorable histology can be safely treated endoscopically.

There are few data on poorly differentiated (PD) carcinomas showing invasion confined to the LP. Polypectomy is theoretically curative but in practice this has not been well demonstrated. Preliminary findings suggest that patients with isolated intramucosal PD CRCs may be managed endoscopically.

Differential diagnosis

- Frequently, well differentiated mucin producing cells will pile up in adenomas, forming lumens, technically appearing cribriform

  • Nuclei show regular basal orientation
  • Nuclei typically not markedly enlarged
  • This should not be considered evidence of high grade dysplasia


- Adenoma and Adenocarcinoma Arising in Adenoma. UNDERSTANDING YOUR PATHOLOGY REPORT: A FAQ SHEET


- Intramucosal carcinoma on biopsy reliably predicts invasive colorectal cancer. MacDonald AW, Tayyab M, Arsalani-Zadeh R, Hartley JE, Monson JR. Ann Surg Oncol. 2009 Dec;16(12):3267-70. doi: 10.1245/s10434-009-0727-7. PMID: #19820998#

- Intramucosal poorly differentiated colorectal carcinoma: can it be managed conservatively? Shia J, Klimstra DS. Am J Surg Pathol. 2008 Oct;32(10):1586-8; author reply 1588-9. doi: 10.1097/PAS.0b013e31817ec2cd. PMID: #18724239#

- Poorly differentiated colorectal carcinoma with invasion restricted to lamina propria (intramucosal carcinoma): a follow-up study of 15 cases.Lewin MR, Fenton H, Burkart AL, Sheridan T, Abu-Alfa AK, Montgomery EA. Am J Surg Pathol. 2007 Dec;31(12):1882-6. PMID: #18043043#

- Intramucosal carcinoma on biopsy reliably predicts invasive colorectal cancer.
MacDonald AW, Tayyab M, Arsalani-Zadeh R, Hartley JE, Monson JR. Ann Surg Oncol. 2009 Dec;16(12):3267-70. doi: 10.1245/s10434-009-0727-7 . PMID: #19820998#