ABSTRACT
A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Germ-Line Mutation , High-Throughput Nucleotide Sequencing , Adult , Aged , Colorectal Neoplasms/genetics , DNA Polymerase II/genetics , DNA Polymerase III/genetics , Family Health , Female , Gene Deletion , Heterozygote , Humans , Male , Middle Aged , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/genetics , Pedigree , Poly-ADP-Ribose Binding Proteins/genetics , Tunisia , Young AdultABSTRACT
CONTEXT: Pancreatitis is a very rare adverse effect of tamoxifen with only six cases of tamoxifen-associated pancreatitis reported in the English literature until now. In these cases, rechallenge with tamoxifen was not carried out. CASE REPORT: We report a case of recurrent severe acute pancreatitis in a 44-year-old female induced by tamoxifen therapy and review the literature with regards to tamoxifen-associated pancreatitis. CONCLUSION: Clinicians should be aware of the risks of developing severe acute pancreatitis when using tamoxifen therapy. If tamoxifen is suspected as the probable causative agent, rechallenge with this drug should be prohibited.
Subject(s)
Hypertriglyceridemia/chemically induced , Hypertriglyceridemia/complications , Pancreatitis/etiology , Tamoxifen/adverse effects , Acute Disease , Adult , Antineoplastic Agents, Hormonal/adverse effects , Diagnostic Techniques, Endocrine , Female , Humans , Pancreatitis/metabolism , Recurrence , Severity of Illness IndexABSTRACT
Endometriosis is a frequent benign disorder. Malignancy arising in extraovarian endometriosis is a rare event. A 49-year-old woman is presented with a large painful abdominal wall mass. She underwent a myomectomy, 20 years before, for uterus leiomyoma. Computed tomography suggested that this was a desmoid tumor and she underwent surgery. Histological examination showed a clear cell adenocarcinoma associated with endometriosis foci. Pelvic ultrasound, computed tomography, and endometrial curettage did not show any malignancy or endometriosis in the uterus and ovaries. Adjuvant chemotherapy was recommended, but the patient was lost to follow up. Six months later, she returned with a recurrence of the abdominal wall mass. She was given chemotherapy and then she was reoperated.
