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Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Aim

Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection.

Methods

All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs.

Results

From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30–0.96; p = 0.037).

Conclusions

Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.

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Disclosure

Robert D. Knox, Nathan Luey, Loretta Sioson, Andrew Kedziora, Adele Clarkson, Nicole Watson, Christopher W. Toon, Carmen Cussigh, Stuart Pincott, Stephen Pillinger, Yasser Salama, Justin Evans, John Percy, Margaret Schnitzler, Alexander Engel, and Anthony J. Gill report no conflict of interest.

Funding support

This study was supported by funding from the Cancer Institute NSW as part of a translational research center grant.

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Authors and Affiliations

  1. Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Robert D. Knox MBBS, Nathan Luey BSc, Christopher W. Toon FRCPA, Stuart Pincott FRACS, Stephen Pillinger FRACS, Yasser Salama FRACS, Justin Evans FRACS, John Percy FRACS, Margaret Schnitzler PhD, FRACS, Alexander Engel PhD, FRACS & Anthony J. Gill MD, FRCPA

  2. Department of Colorectal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia

    Robert D. Knox MBBS, Christopher W. Toon FRCPA, Stuart Pincott FRACS, Stephen Pillinger FRACS, Yasser Salama FRACS, Justin Evans FRACS, John Percy FRACS, Margaret Schnitzler PhD, FRACS & Alexander Engel PhD, FRACS

  3. Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia

    Loretta Sioson BSc, Andrew Kedziora FRCPA, Adele Clarkson BSc, Nicole Watson, Christopher W. Toon FRCPA, Carmen Cussigh & Anthony J. Gill MD, FRCPA

  4. Histopath Pathology, North Ryde, NSW, Australia

    Christopher W. Toon FRCPA

  5. Sydney Vital Translational Research Centre, Royal North Shore Hospital, St Leonards, NSW, Australia

    Loretta Sioson BSc, Adele Clarkson BSc, Alexander Engel PhD, FRACS & Anthony J. Gill MD, FRCPA

  6. Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW, Australia

    Loretta Sioson BSc & Anthony J. Gill MD, FRCPA

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  1. Robert D. Knox MBBS
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  2. Nathan Luey BSc
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  6. Nicole Watson
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  7. Christopher W. Toon FRCPA
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  8. Carmen Cussigh
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  9. Stuart Pincott FRACS
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  11. Yasser Salama FRACS
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  12. Justin Evans FRACS
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  14. Margaret Schnitzler PhD, FRACS
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  15. Alexander Engel PhD, FRACS
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  16. Anthony J. Gill MD, FRCPA
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Corresponding author

Correspondence to Anthony J. Gill MD, FRCPA.

Additional information

Alexander Engel and Anthony J. Gill have contributed equally to this manuscript.

Electronic supplementary material

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10434_2014_4355_MOESM1_ESM.tiff

Typical morphology and immunohistochemical profile of medullary carcinoma. A,B,C – The tumour demonstrates a solid architecture with a lobulated, pushing growth pattern. D,E – The tumour grows as solid sheet of malignant cells with conspicuous nucleoli, prominent cytoplasm and frequent intra-epithelial lymphocytes. F – The tumour shows mismatch repair deficiency (MMRd) in this case characterised by loss of staining for PMS2 in all malignant cells, with preserved positive staining in non-neoplastic cells which act as an internal positive control. (A H&E 100x, B H&E 1000x, C H&E 200x, D H&E 200x, E H&E400x, F MLH1 IHC 400x) (TIFF 18371 kb)

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Knox, R.D., Luey, N., Sioson, L. et al. Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases. Ann Surg Oncol 22, 2988–2996 (2015). https://doi.org/10.1245/s10434-014-4355-5

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  • DOI: https://doi.org/10.1245/s10434-014-4355-5

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