Medullary carcinoma in the colorectum: a systematic review and meta-analysis

Pyo, Jung‐Soo; Sohn, Jin Hee; Kang, Gyu-Hong

doi:10.1016/j.humpath.2016.02.018

Cited by 47 publications

(50 citation statements)

References 22 publications

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“…What appears to have been under-recognized, however, is that the morphological diagnosis of MC can be problematic and the clinical outcome of these tumors can be variable [7]. For the issue of diagnosis, our study shows that a wide spectrum of “medullary” morphology exists in CRCs, and there are frequent intermediate forms between classic MC and conventional poorly differentiated carcinoma.…”

Section: Discussionmentioning

confidence: 73%

“…Of the various emerging pathological and molecular characteristics of CRC that may bear clinical significance [2], medullary histology has received particular attention [3–7]. In both clinical and research settings, medullary carcinoma (MC) is commonly perceived as a distinct clinico-pathological entity with specific prognostic relevance and molecular pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

et al. 2017

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Colorectal medullary carcinoma, recognized by the World-Health-Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as-yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from “classic medullary histology” to non-medullary poorly-differentiated histologies and demonstrated significant overlapping between categories. By assessing a selected subset (n=30) that represented the spectrum of histologies, we showed that the inter-observer agreement for diagnosing medullary carcinoma by using 2010 World-Health-Organization criteria was poor; the Kappa value among 5 gastrointestinal pathologists was only 0.157 (95% confidence-interval, 0.127–0.263; p=0.001). When we arbitrarily classified the entire cohort into "classic" and “indeterminate” medullary tumors (group 1, n=19; group 2, n=26, respectively) and non-medullary poorly-differentiated tumors (group 3, n=35), groups 1 and 2 were more likely to exhibit mismatch-repair-protein-deficiency than group 3 (p<0.001); however, improved survival could not be detected in neither group compared to group 3. Our findings suggest that the diagnosis of medullary carcinoma, as currently applied, may only serve as a morphological descriptor indicating an increased likelihood of mismatch-repair-deficiency. Additional evidence including more objective classification system is needed before medullary carcinoma can be regarded as a distinct entity with prognostic relevance. Until such evidence becomes available, caution should be exercised when making this diagnosis, and when comparing results across different studies.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

et al. 2017

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“…In the present study, all 21 of the MMR-deficient solid-type PDAs (100%) and 30 of the 33 MMR-proficient solid-type PDAs (91%) showed a complete or partial loss of at least 1 of the SWI/SNF complex subunits. Several studies indicated that the loss of ARID1A or INI1 was associated with medullary morphology in colorectal cancer, 13,14,25,26 and that the loss of BRG1 or BRM was associated with solid morphology in lung cancer. 27 Our present findings suggest that the loss of the SWI/SNF complex plays a role in a morphological shift from glandular to solid component as a second hit rather than carcinogenesis.…”

Section: Ini1mentioning

confidence: 99%

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

et al. 2020

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ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.

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“…MC presents like conventional colonic carcinoma and can be confused with poorly differentiated colorectal carcinoma (PDC) due to undifferentiated complexion and high mitotic activity (2,3). MC of the colon is accepted as a subtype of colonic adenocarcinoma with a better clinical course and prognosis than other subtypes (1,4).There are few reports in the literature, but it has been shown that MC is frequently located at the proximal parts of the colon with low incidence of lymphnode metastases. It also has a female tendency according to the literature (2,4,5).…”

Section: Introductionmentioning

confidence: 99%

“…MC of the colon is accepted as a subtype of colonic adenocarcinoma with a better clinical course and prognosis than other subtypes (1,4).There are few reports in the literature, but it has been shown that MC is frequently located at the proximal parts of the colon with low incidence of lymphnode metastases. It also has a female tendency according to the literature (2,4,5). It has also been reported that it might have an expansive growth pattern and an association with Lynch syndrome and high microsatellite instability (MSI) (3,6).…”

Section: Introductionmentioning

confidence: 99%

Colonic Medullary Carcinoma: A Rare Case

Bağ¹,

Kar²,

Cin³

et al. 2017

Istanbul Med J

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Medullary carcinoma (MC) is a rare subtype of colorectal cancer making up less than 0.1% of all colorectal malignancies (1). MC presents like conventional colonic carcinoma and can be confused with poorly differentiated colorectal carcinoma (PDC) due to undifferentiated complexion and high mitotic activity (2, 3). MC of the colon is accepted as a subtype of colonic adenocarcinoma with a better clinical course and prognosis than other subtypes (1, 4).There are few reports in the literature, but it has been shown that MC is frequently located at the proximal parts of the colon with low incidence of lymphnode metastases. It also has a female tendency according to the literature (2, 4, 5). It has also been reported that it might have an expansive growth pattern and an association with Lynch syndrome and high microsatellite instability (MSI) (3, 6). Inrecent years, the incidence of MC has increased due to increased incidence of colon cancer and improved histopathological investigation methods. In this report, we present an MC of the colon in a 72-year-old male patient along with a literature review. Case ReportA 72-year-old male patient was admitted to our unit with a one-month history of abdominal pain and rectal bleeding. The patient had no family history of colon cancer. The colonoscopy revealed a huge lobulated polypoid tumor protruding into the lumen located in the middle part of the transverse colon. The pathological diagnosis obtained by colonoscopic biopsy was fibrinopurulent exudate. Blood carcinoembryonic antigen (CEA) level was measured as 1.9 ng/ mL. Computed tomography showed that there was a well-defined 5 cm round lesion compressing the periintestinal fat tissue homogenously, and there was no invasion into the surrounding tissues (figure 1). The patient was scheduled for elective laparotomy after the diagnosis of the colonic mass.Midline laparotomy was performed, and a mobile polypoid tumor 5.5 cm in diameter with no serozal invasion in the middle part of the transverse colon was detected (Figure 2). The lesion was totally intraluminal and felt like a lipoma during the palpation. Multiple reactive lymphadenopathies were also observed within the transverse mesocolon. There was no additional pathologic finding during the exploration. The patient underwent segmental colon resection with proper mesocolon excision consisting of palpable lymph nodes. The frozen section revealed that lymph nodes were not metastatic. Thus, the operation was ended as a segmental colon resection with end-to-end anastomosis (Figure 3). The postoperative period was uneventful, and the patient was discharged on postoperative day 8. Colonic Medullary Carcinoma: A Rare CaseMedullary carcinoma is a rare subtype of colorectal cancer making up less than 0.1% of all colorectal malignancies. This subtype can be confused with poorly differentiated colorectal carcinoma due to undifferentiated complexion morphology and high mitotic activity. Medullary carcinoma is a subtype of colonic adenocarcinoma with a better prognosis than other subtype...

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Medullary carcinoma in the colorectum: a systematic review and meta-analysis

Cited by 47 publications

References 22 publications

Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

Colonic Medullary Carcinoma: A Rare Case

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