[652] 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.

Table 1
AgeSexGermline mutationFamily history (tumor site)Personal history (tumor site)DiagnosisIHC
65FMSH6*1312insABreast, colon, larynx, brain, pancreasBreast, skinPancreatic acinar cell carcinomaMSH6 negative
56MMLH1*1456insTColonColon, skinPeritoneal mesotheliomaMLH1/PMS2 negative
50FNot doneColon, prostate, endometriumEndometrium, colonPancreatic endocrine neoplasmMSH2/MSH6 negative
29MMSH2*1906GCColon, breastAppendix, skinAdrenal cortical carcinomaMSH2/MSH6 negative
71MMSH2*1906GCColon, endometriumColon, pancreasPulmonary adenocarcinomaMSH2/MSH6 negative



Conclusions: Our report illustrates the occurrence of rare and previously not reported entities that occurred in LS patients. Given the IHC results being concordant with the genes mutated in these patients, the tumors are likely to be pathogenetically associated with MMR deficiency. Awareness of such occurrences would enhance our ability to identify patients at risk for LS, a genetic disorder that carries profound clinical and familial implications.
Category: Gastrointestinal

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 62, Wednesday Morning

 

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