Unusual Tumors in Lynch Syndrome Patients: Potential Entities within Tumor Spectrum.
Yevgeniy Karamurzin, David Klimstra, Hikmat Al-Ahmadie, Christine Sempoux, Zsofia Stadler, Robert Soslow, Jinru Shia. Memorial Sloan Kettering Cancer Center, New York, NY; Cliniques Universitaires Saint-Luc, UCL, Brussels, Belgium
Background: The well-established group of malignancies commonly associated with Lynch syndrome (LS) includes carcinomas of colorectum, endometrium, renal pelvis, upper gastrointestinal tract, ovaries, as well as tumors of skin and brain. Recently discovered histologic, immunohistochemical (IHC), and molecular signatures of the tumors have significantly facilitated the recognition of the syndrome. These include specific histologic features of the tumors, DNA mismatch repair (MMR) proteins detection by IHC, microsatellite instability (MSI) analysis, and, as the final and the most definitive step, MMR genes germline mutation analysis. Due to progressively increasing availability and precision of the diagnostic tools, more tumor entities are being identified in LS. In this report, we describe 2 rare and 3 not previously reported tumors that occurred in LS patients.
Design: Unusual tumor entities were collected from the pathology and clinical genetics service databases. Clinical information was retrieved from the electronic medical records. Tumor material was evaluated histologically and immunohistochemically.
Results: 5 unusual tumors were identified in LS patients (Table 1). 2 tumors (adrenal cortical carcinoma and lung adenocarcinoma) have been reported in LS patients previously; 3 ( pancreatic acinar cell carcinoma, pancreatic endocrine tumor, and mesothelioma), to the best of our knowledge, have not been previously reported.
|Age||Sex||Germline mutation||Family history (tumor site)||Personal history (tumor site)||Diagnosis||IHC|
|65||F||MSH6*1312insA||Breast, colon, larynx, brain, pancreas||Breast, skin||Pancreatic acinar cell carcinoma||MSH6 negative|
|56||M||MLH1*1456insT||Colon||Colon, skin||Peritoneal mesothelioma||MLH1/PMS2 negative|
|50||F||Not done||Colon, prostate, endometrium||Endometrium, colon||Pancreatic endocrine neoplasm||MSH2/MSH6 negative|
|29||M||MSH2*1906GC||Colon, breast||Appendix, skin||Adrenal cortical carcinoma||MSH2/MSH6 negative|
|71||M||MSH2*1906GC||Colon, endometrium||Colon, pancreas||Pulmonary adenocarcinoma||MSH2/MSH6 negative|