Clear cell colorectal carcinoma: Time to clarify diagnosis

Our plain-English summary of Clear cell colorectal carcinoma: Time to clarify diagnosis, by A. Remo, F. Grillo, L. Mastracci, et al (Pathology, Research and Practice, 2017).

The study

• Authors: A. Remo, F. Grillo, L. Mastracci, M. Fassan, S. Sina, C. Zanella, P. Parcesepe, E. Damiano Urso, M. Pancione, G. Bortuzzo, A. Scarpa, E. Manfrin
• Journal: Pathology, Research and Practice
• Published: 2017;213(5):447-452
• Type of article: Case report, Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Primary clear cell colorectal carcinoma (CCC) is a very rare entity accounting for only 35 cases reported in the Literature. CCC is neither classified as a distinct entity nor is it defined as a CRC variant because its ontogeny remains unclear. Most of the reported CCC were found in the distal colon in patients with a mean age of 56 years. Histologically, clear cell change is the main morphologic feature and may present in a "pure" form, composed exclusively of clear cells, or in a "composite" form, admixed with other morphologically different components. It is possible to distinguish two biologically different types of CCC, with different clinical-pathologic features, therapeutic management and diagnostic criteria: a) Intestinal CCC consisting of an aggressive neoplasm, affecting mainly adult men, characterized by an intestinal-type immunoprofile (CK20+, CK7-, CEA+, CDX-2+) and b) Müllerian CCC consisting of an indolent carcinoma of the sigmoid-rectum, affecting young women, characterized by a different (CK7+, CK20-, CEA-, CA125 +) immunoprofile. Considerable diagnostic difficulties can arise in distinguishing CCC and primary or secondary clear cell neoplasms, such as metastases from renal carcinoma, lower urinary tract, female genital tract, adrenal gland, mesothelioma, melanoma and primary intestinal PEComa. In this paper we review the Literature with two additional cases in order to define the diagnostic criteria of CCC.

Copyright © 2017 Elsevier GmbH. All rights reserved.

In plain English

This article combined two new patient reports with a review of published cases of clear cell carcinoma of the colon and rectum, a rare bowel cancer. It is not a study of asbestos. Mesothelioma appears only as one of several tumors that can look similar under the microscope: the authors listed it among them and included its tissue-staining profile in a comparison table. Both new patients were men, aged 58 and 79, treated at Legnago's Hospital in Verona, Italy, for right colon tumors. After surgery and chemotherapy, the first died 9 months later from recurrence. The second, who also had clear cell prostate cancer, died of disease after 18 months. The authors counted 35 published cases from 1964 to 2016, with a mean patient age of 56.5 years. They sorted the cases into an 'intestinal' type (24 cases) and a 'Müllerian' type linked to endometriosis or pregnancy (9 cases). In the intestinal type, 8 of 24 had already spread at first diagnosis, and 8 of 16 patients with follow-up died of the disease. The authors concluded that the intestinal type was aggressive and mainly affected adult men, while the Müllerian type was indolent and affected younger women.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Report of two new cases combined with a review of published case reports and case series
• Who was studied: Two men (aged 58 and 79) treated at Legnago's Hospital, Verona, Italy, plus published case reports and series of histologically proven clear cell carcinoma of the colon-rectum found in PubMed and Google Scholar before 1 December 2016 (35 cases from 1964 to 2016)
• Main results:
  • New case 1: a 58-year-old man with a 7 cm right colon tumor perforating the visceral serosa (pT4a) and lymph node metastases. The tumor was KRAS wild type with a BRAF mutation and MSI-H. He died 9 months after surgery and chemotherapy, from recurrence and metastatic disease.
  • New case 2: a 79-year-old man with a clear cell adenocarcinoma of the right colon (pT4a) without lymph node involvement and with a KRAS mutation. He had also been diagnosed with clear cell adenocarcinoma of the prostate, and died of disease after 18 months.
  • Across the reviewed cases, the authors counted 15 composite and 13 pure clear cell carcinomas; morphological details were not available in 7 cases.
  • Mean age of patients with clear cell carcinoma was 56.5 years (range 27 to 89), versus 67 for ordinary colorectal carcinoma. Women had a mean age of 51.9 years and men 61.5 years.
  • Intestinal type (24 cases): 8 of 24 (33%) were already metastatic at first diagnosis, and 11 of 24 (46%) had nodal metastases.
  • Intestinal type: follow-up was available for 16 patients, of whom 8 died from the disease, with a mean overall survival of 13.8 months.
  • Müllerian type (9 cases): tumors occurred only in women (mean age 51.7), in the rectum (77%) or sigmoid colon (23%).
  • The authors listed mesothelioma among the clear cell tumors that can be hard to distinguish from clear cell colorectal carcinoma.
  • Table 3 compared the immunohistochemical marker profile of mesothelioma with those of the intestinal and Müllerian types and of other clear cell tumors considered in differential diagnosis. No mesothelioma patients were studied.
• The authors' conclusion: The authors concluded that there are two biologically different types of clear cell colorectal carcinoma. The intestinal type is an aggressive tumor mainly affecting adult men, with an intestinal-type marker profile. The Müllerian type is an indolent tumor of the sigmoid colon and rectum affecting younger women, with a different marker profile (CK7 positive, CK20 negative, CEA negative, CA125 positive).
• Limitations the authors state:
  • The proportion of clear cells needed to diagnose the composite form is not evidence-based.
  • How often this cancer occurs is unknown and may be underestimated, especially for the composite type.
  • Molecular features were largely unexplored, with only six cases studied, including the authors' two.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Carcinoma, Neoplasm, Mesothelioma.

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