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Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases
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...
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| Published in: | Annals of surgical oncology 2015-09, Vol.22 (9), p.2988-2996 |
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| container_title | Annals of surgical oncology |
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| creator | Knox, Robert D. Luey, Nathan Sioson, Loretta Kedziora, Andrew Clarkson, Adele Watson, Nicole Toon, Christopher W. Cussigh, Carmen Pincott, Stuart Pillinger, Stephen Salama, Yasser Evans, Justin Percy, John Schnitzler, Margaret Engel, Alexander Gill, Anthony J. |
| description | 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
|
| doi_str_mv | 10.1245/s10434-014-4355-5 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1855073191</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1703697503</sourcerecordid><originalsourceid>FETCH-LOGICAL-p245t-51d37cee1f695a4d8cffb7c245a75194f275217820aff688d33fcdd1dc5c509c3</originalsourceid><addsrcrecordid>eNqFkctLw0AQxhdRbK3-AV4k4MVLdF-T3XgrwRdUFB_gbdnuo6akSc0mQv97t7aCePE0w3y_GfjmQ-iY4HNCOVwEgjnjKSY85QwghR00JBAnPJNkN_Y4k2lOMxiggxDmGBPBMOyjAQUQNJMwRG_3zvZVpdtVUjRV0zrT6SopdGvKulno5Ml9lqHsnL1MxklRlXVpoq5rmzzq7j1uzL4Hz11vV0njE4Jp3A4uHKI9r6vgjrZ1hF6vr16K23TycHNXjCfpMjroUiCWCeMc8VkOmltpvJ8KEzUtgOTcUwGUCEmx9j6T0jLmjbXEGjCAc8NG6Gxzd9k2H70LnVqUwbhoqXZNHxSRAFgwkpP_UYFZlgvALKKnf9B507d1NLKmqMRCSBypky3VTxfOqmVbLuIn1c97I0A3QIhSPXPtrzNYrTNUmwxVzFCtM1TAvgDpV4oG</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1702807780</pqid></control><display><type>article</type><title>Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases</title><source>Springer Nature</source><creator>Knox, Robert D. ; Luey, Nathan ; Sioson, Loretta ; Kedziora, Andrew ; Clarkson, Adele ; Watson, Nicole ; Toon, Christopher W. ; Cussigh, Carmen ; Pincott, Stuart ; Pillinger, Stephen ; Salama, Yasser ; Evans, Justin ; Percy, John ; Schnitzler, Margaret ; Engel, Alexander ; Gill, Anthony J.</creator><creatorcontrib>Knox, Robert D. ; Luey, Nathan ; Sioson, Loretta ; Kedziora, Andrew ; Clarkson, Adele ; Watson, Nicole ; Toon, Christopher W. ; Cussigh, Carmen ; Pincott, Stuart ; Pillinger, Stephen ; Salama, Yasser ; Evans, Justin ; Percy, John ; Schnitzler, Margaret ; Engel, Alexander ; Gill, Anthony J.</creatorcontrib><description>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.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-014-4355-5</identifier><identifier>PMID: 25572685</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Aged ; Aged, 80 and over ; Carcinoma, Medullary - mortality ; Carcinoma, Medullary - pathology ; Colorectal Cancer ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Female ; Follow-Up Studies ; Humans ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Staging ; Oncology ; Prognosis ; Prospective Studies ; Retrospective Studies ; Surgery ; Surgical Oncology ; Survival Rate</subject><ispartof>Annals of surgical oncology, 2015-09, Vol.22 (9), p.2988-2996</ispartof><rights>Society of Surgical Oncology 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p245t-51d37cee1f695a4d8cffb7c245a75194f275217820aff688d33fcdd1dc5c509c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25572685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knox, Robert D.</creatorcontrib><creatorcontrib>Luey, Nathan</creatorcontrib><creatorcontrib>Sioson, Loretta</creatorcontrib><creatorcontrib>Kedziora, Andrew</creatorcontrib><creatorcontrib>Clarkson, Adele</creatorcontrib><creatorcontrib>Watson, Nicole</creatorcontrib><creatorcontrib>Toon, Christopher W.</creatorcontrib><creatorcontrib>Cussigh, Carmen</creatorcontrib><creatorcontrib>Pincott, Stuart</creatorcontrib><creatorcontrib>Pillinger, Stephen</creatorcontrib><creatorcontrib>Salama, Yasser</creatorcontrib><creatorcontrib>Evans, Justin</creatorcontrib><creatorcontrib>Percy, John</creatorcontrib><creatorcontrib>Schnitzler, Margaret</creatorcontrib><creatorcontrib>Engel, Alexander</creatorcontrib><creatorcontrib>Gill, Anthony J.</creatorcontrib><title>Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>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.</description><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinoma, Medullary - mortality</subject><subject>Carcinoma, Medullary - pathology</subject><subject>Colorectal Cancer</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFkctLw0AQxhdRbK3-AV4k4MVLdF-T3XgrwRdUFB_gbdnuo6akSc0mQv97t7aCePE0w3y_GfjmQ-iY4HNCOVwEgjnjKSY85QwghR00JBAnPJNkN_Y4k2lOMxiggxDmGBPBMOyjAQUQNJMwRG_3zvZVpdtVUjRV0zrT6SopdGvKulno5Ml9lqHsnL1MxklRlXVpoq5rmzzq7j1uzL4Hz11vV0njE4Jp3A4uHKI9r6vgjrZ1hF6vr16K23TycHNXjCfpMjroUiCWCeMc8VkOmltpvJ8KEzUtgOTcUwGUCEmx9j6T0jLmjbXEGjCAc8NG6Gxzd9k2H70LnVqUwbhoqXZNHxSRAFgwkpP_UYFZlgvALKKnf9B507d1NLKmqMRCSBypky3VTxfOqmVbLuIn1c97I0A3QIhSPXPtrzNYrTNUmwxVzFCtM1TAvgDpV4oG</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Knox, Robert D.</creator><creator>Luey, Nathan</creator><creator>Sioson, Loretta</creator><creator>Kedziora, Andrew</creator><creator>Clarkson, Adele</creator><creator>Watson, Nicole</creator><creator>Toon, Christopher W.</creator><creator>Cussigh, Carmen</creator><creator>Pincott, Stuart</creator><creator>Pillinger, Stephen</creator><creator>Salama, Yasser</creator><creator>Evans, Justin</creator><creator>Percy, John</creator><creator>Schnitzler, Margaret</creator><creator>Engel, Alexander</creator><creator>Gill, Anthony J.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20150901</creationdate><title>Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases</title><author>Knox, Robert D. ; Luey, Nathan ; Sioson, Loretta ; Kedziora, Andrew ; Clarkson, Adele ; Watson, Nicole ; Toon, Christopher W. ; Cussigh, Carmen ; Pincott, Stuart ; Pillinger, Stephen ; Salama, Yasser ; Evans, Justin ; Percy, John ; Schnitzler, Margaret ; Engel, Alexander ; Gill, Anthony J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p245t-51d37cee1f695a4d8cffb7c245a75194f275217820aff688d33fcdd1dc5c509c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Carcinoma, Medullary - mortality</topic><topic>Carcinoma, Medullary - pathology</topic><topic>Colorectal Cancer</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knox, Robert D.</creatorcontrib><creatorcontrib>Luey, Nathan</creatorcontrib><creatorcontrib>Sioson, Loretta</creatorcontrib><creatorcontrib>Kedziora, Andrew</creatorcontrib><creatorcontrib>Clarkson, Adele</creatorcontrib><creatorcontrib>Watson, Nicole</creatorcontrib><creatorcontrib>Toon, Christopher W.</creatorcontrib><creatorcontrib>Cussigh, Carmen</creatorcontrib><creatorcontrib>Pincott, Stuart</creatorcontrib><creatorcontrib>Pillinger, Stephen</creatorcontrib><creatorcontrib>Salama, Yasser</creatorcontrib><creatorcontrib>Evans, Justin</creatorcontrib><creatorcontrib>Percy, John</creatorcontrib><creatorcontrib>Schnitzler, Margaret</creatorcontrib><creatorcontrib>Engel, Alexander</creatorcontrib><creatorcontrib>Gill, Anthony J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knox, Robert D.</au><au>Luey, Nathan</au><au>Sioson, Loretta</au><au>Kedziora, Andrew</au><au>Clarkson, Adele</au><au>Watson, Nicole</au><au>Toon, Christopher W.</au><au>Cussigh, Carmen</au><au>Pincott, Stuart</au><au>Pillinger, Stephen</au><au>Salama, Yasser</au><au>Evans, Justin</au><au>Percy, John</au><au>Schnitzler, Margaret</au><au>Engel, Alexander</au><au>Gill, Anthony J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>22</volume><issue>9</issue><spage>2988</spage><epage>2996</epage><pages>2988-2996</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>25572685</pmid><doi>10.1245/s10434-014-4355-5</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 1068-9265 |
| ispartof | Annals of surgical oncology, 2015-09, Vol.22 (9), p.2988-2996 |
| issn | 1068-9265 1534-4681 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1855073191 |
| source | Springer Nature |
| subjects | Adenocarcinoma - mortality Adenocarcinoma - pathology Aged Aged, 80 and over Carcinoma, Medullary - mortality Carcinoma, Medullary - pathology Colorectal Cancer Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Female Follow-Up Studies Humans Male Medicine Medicine & Public Health Middle Aged Neoplasm Staging Oncology Prognosis Prospective Studies Retrospective Studies Surgery Surgical Oncology Survival Rate |
| title | Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases |
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