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Case Reports
. 2017:2017:3427343.
doi: 10.1155/2017/3427343. Epub 2017 Aug 3.

Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

Brett M Lowenthal  1 , Theresa W Chan  2 , John A Thorson  1 , Kaitlyn J Kelly  2 , Thomas J Savides  3 , Mark A Valasek  1
Affiliations
Case Reports

Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

Brett M Lowenthal et al. Case Rep Pathol. 2017.

Abstract

Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1) and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C) mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

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Figures

Figure 1
Figure 1
Esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS) of the gastric mass. (a)-(b) EGD shows the 3.5 × 2.5 × 1.5 cm subepithelial gastric mass with central umbilication (blue arrow). (c)-(d) EUS shows the gastric mass is hypoechoic (blue arrow).
Figure 2
Figure 2
Histologic H&E stained total gastrectomy. (a) Well-demarcated, poorly differentiated carcinoma with an organoid growth pattern and pushing borders ((a) 20x; (b) 100x). (c) High power view of organoid growth pattern and abundant peritumoral lymphocytic response (400x).
Figure 3
Figure 3
Mismatch repair protein expression immunohistochemical profile (100x). The gastric medullary carcinoma is located at the bottom half of each field, while the overlying unremarkable gastric mucosa is located at the top portion of each field. (a) Loss of MLH1 expression. (b) Loss of PMS2 expression. (c) Intact MSH2 expression. (d) Intact MSH6 expression.
See this image and copyright information in PMC

References

    1. Bosman F. T., Carneiro F., Hruban R. H., Theise N. D., editors. WHO Classification of Tumors of the Digestive System. 4th. Lyon, France: IARC Press; 2010.
    1. Minamoto T., Mai M., Watanabe K., et al. Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor. Cancer. 1990;66(5):945–952. doi: 10.1002/1097-0142(19900901)66:5<945::aid-cncr2820660523>3.0.co;2-x. - DOI - PubMed
    1. Dogan M., Savas B., Utkan G., Bayar S., Ensari A., Icli F. A rare gastric neoplasm: gastric medullary carcinoma. Medical Oncology. 2011;28(4):945–947. doi: 10.1007/s12032-010-9557-5. - DOI - PubMed
    1. Chetty R. Gastrointestinal cancers accompanied by a dense lymphoid component: an overview with special reference to gastric and colonic medullary and lymphoepithelioma-like carcinomas. Journal of Clinical Pathology. 2012;65(12):1062–1065. doi: 10.1136/jclinpath-2012-201067. - DOI - PubMed
    1. Aslan F., Yükrük F. A., Buğdaycı Başal F., Durnalı A. Gastric medullary carcinoma: a rare case report. Case Reports in Oncological Medicine. 2016;2016:3. doi: 10.1155/2016/2875471. - DOI - PMC - PubMed

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