A 63-year-old woman presents with vague abdominal pain. Imaging studies reveal right-sided colon wall thickening with a large obstructing mass. Gross examination of the colon resection specimen shows a 7.2 cm fungating mass with ulceration. Sectioning through the mass demonstrates that a majority (70%) of the tumor has a gelatinous cut surface.

Master List of Diagnoses

  • Colitis cystica profunda
  • Medullary carcinoma
  • Mucinous adenocarcinoma
  • Neuroendocrine neoplasm of the colon
  • Signet ring cell adenocarcinoma
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This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2017, Case 18, and is mucinous adenocarcinoma of the colon.

Criteria for Diagnosis and Comments

The histological sections demonstrate an invasive adenocarcinoma arising in the background of extensive high-grade dysplasia in a tubulovillous adenoma. Most of the invasive tumor is comprised of pools of extracellular mucin with associated malignant epithelium. Malignant epithelium is present as strips, glands, and, in some areas, as individual cells within the mucin pools. The mucin can be seen dissecting through the stroma to involve the muscularis propria and into the peri-colonic adipose tissue. Cytologically, the neoplastic cells have increased nuclear to cytoplasmic ratio, nuclear pleomorphism, elevated mitotic rate, prominent nucleoli, and scattered foci of cells with signet ring cell morphology. Overall, these features are most consistent with mucinous colorectal adenocarcinoma.

Mucinous colorectal adenocarcinomas, also known as “colloid type,” comprise approximately 15% of colorectal carcinomas. In contrast, mucinous adenocarcinomas and cystadenocarcinomas account for approximately 50% of appendiceal adenocarcinomas. Mucinous colorectal adenocarcinomas arise in younger patients and females and are often seen in the proximal colon. They are less common in patients in Asian countries; higher rates are noted in Europe, North America, and Australia. Patients with inflammatory bowel disease or those with a history of pelvic and abdominal radiation are more likely to develop mucinous adenocarcinomas.

Grossly mucinous colorectal adenocarcinomas are exophytic/fungating intraluminal masses. The cut surface has tan-white firm foci admixed with softer gray gelatinous areas.

The designation of mucinous adenocarcinoma is utilized when more than or equal to 50% of the tumor is comprised of pools of extracellular mucin containing malignant cells. The cells can be present as strips of epithelium, neoplastic glands, clusters of neoplastic cells, or individual malignant cells with or without signet ring cell features. Tumors where the mucinous areas make up less than 50% of the lesion should be classified as adenocarcinomas with a mucinous component.

There is increased microsatellite instability (MSI) in mucinous carcinomas as compared to adenocarcinoma NOS. MSI status does not have independent prognostic value. Tumor grading is based on glandular formation and epithelial maturation.

These tumors are diagnosed at an advanced stage. There is an association between right sided mucinous colorectal adenocarcinomas and hereditary disorders such as those noted in Lynch syndrome and MUTYH-associated polyposis. Current data do not show that a mucinous histology imparts a negative impact on overall survival and cancer-specific survival. Mucinous colorectal carcinomas frequently spread along the peritoneal surface and to the ovaries. The current American Joint Committee on Cancer (AJCC, 8th edition) stages mucinous colorectal cancers as conventional colorectal adenocarcinomas. It should be noted that in resection specimens that are post neo-adjuvant therapy, pools of mucin without epithelial cells are considered negative for residual tumor at both the primary site and in lymph nodes.

Although neuroendocrine tumors can produce mucin, it is not as extensive in amount as noted in mucinous adenocarcinomas. The neoplastic cells retain neuroendocrine morphological features (eg, round to oval nuclei with coarse granular chromatin and indistinct nucleoli). Moreover, as is the case with neuroendocrine tumors arising elsewhere, colorectal neuroendocrine neoplasms can be highlighted by neuroendocrine immunohistochemical markers (synaptophysin, chromogranin and neuron specific enolase).

Colitis cystica profunda is a benign lesion often seen in patients with a history of prior surgical intervention. It is associated with glandular herniation into the deeper layers of the colon wall. Deep displacement of the glandular elements into the colon wall or the formation of an exophytic component dictates whether the terms profunda or polyposa are used. The glands often splay the muscle fibers mimicking invasive carcinoma. However, these glands lack an associated desmoplastic reaction that is typically noted in a neoplastic process.

Signet ring cell adenocarcinoma is defined by greater than 50% of the neoplastic cells having prominent intracytoplasmic mucin that displaces the nucleus. Signet ring cells can infiltrate the colorectal wall in a linitis plastica pattern or are associated with pools of extracellular mucin.

Medullary adenocarcinoma arises frequently in the right colon. It is characterized by having sheets of malignant cells with little to no gland formation. The cells have vesicular nuclei with prominent nucleoli, and frequent mitotic figures are present. The tumor has a prominent infiltrate by tumor infiltrating lymphocytes. Mucin production is not a prominent feature of this tumor and may be patchy or absent. The tumor has a pushing border.

  1. Which of the following is true regarding mucinous colorectal adenocarcinomas?
    1. Based on WHO 2019 criteria, 20% of the tumor should be comprised of extracellular mucin containing malignant cells.
    2. Mucinous colorectal adenocarcinomas are most common in Asian countries.
    3. Patients with inflammatory bowel disease show a lower incidence of mucinous colorectal adenocarcinoma.
    4. They are frequently right sided.
    5. They are more common in men.
  2. Which of the following hereditary disorders has been associated with mucinous colorectal adenocarcinoma?
    1. Familial adenomatous polyposis
    2. Juvenile polyposis
    3. Lynch syndrome
    4. Neurofibromatosis type 1
    5. Peutz-Jeghers syndrome
  3. Moderately-differentiated colorectal adenocarcinomas, in which 30% of the tumor is comprised of extracellular mucin and neoplastic cells, are best categorized as which of the following?
    1. Cystadenocarcinoma with mucinous features
    2. High-grade adenocarcinoma with extracellular mucin
    3. Moderately-differentiated adenocarcinoma with mucinous features
    4. Mucinous adenocarcinoma
    5. Poorly-differentiated adenocarcinoma with signet ring cell features

References

  1. Andrici J, Farzin M, Sioson L, et al. Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer. Mod Pathol. 2016;29(3):266-274.
  2. Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID. Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol. 2016;13(6):361-369.
  3. Hugen N, van Beek JJ, de Wilt JH, Nagtegaal ID. Insight into mucinous colorectal carcinoma: clues from etiology. Ann Surg Oncol. 2014;21(9):2963-2970.
  4. Warschkow R, Tarantino I, Huttner FJ, et al. Predictive value of mucinous histology in colon cancer: a population-based, propensity score matched analysis. Br J Cancer. 2016;114(9):1027-1032.

Author

Safia N. Salaria, MD
Surgical Pathology Committee
Vanderbilt University Medical Center
Nashville, TN


Answer Key

  1. They are frequently right sided. (d)
  2. Lynch syndrome (c)
  3. Moderately-differentiated adenocarcinoma with mucinous features (c)