Breast Cancer and Non‐Hodgkin Lymphoma in a Young Male with Cowden Syndrome

Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene). We describe a patient with Cowden syndrome who was initially diagnosed with B‐cell lymphoblastic lymphoma at the age of 7 years, then MBC at the age of 31 years, and never received radiation therapy.     

Long-term follow-up of the modified Delorme procedure for rectal prolapse

HYPOTHESIS: The modified Delorme operation is a safe, effective, and durable treatment for complete rectal prolapse. DESIGN: Retrospective analysis of outcomes in adult patients undergoing the modified Delorme operation. SETTING: Community-based tertiary referral center with a 5-year general surgery residency program. PATIENTS: A total of 52 consecutive patients undergoing surgery for the treatment of complete rectal prolapse during the 26-year period ending December 2001. INTERVENTIONS: Modified Delorme operation.Main Outcomes Measured Method of anesthesia, morbidity, mortality, recurrence rates, length of follow-up, and incontinence. RESULTS: In the 52 patients, the mean length of prolapse was 8.2 cm. The mean operating time was 75 minutes. Forty-five patients were administered general anesthesia, 4 were administered spinal anesthesia, and 3 were administered local anesthesia. The mean postoperative stay was 4.9 days for 1975 through 2001 and 2.8 days for 1990 through 2001. No patients died as a result of the procedure. Patients were followed up for 61.4 months. Major medical comorbidities occurred in 40 patients. Preoperative incontinence was present in 12 patients, 10 of whom improved after the procedure, and postoperative incontinence in 8. The recurrent postoperative prolapse rate at 5 years was 6% (3/52) and the recurrent postoperative prolapse rate to the end of the study was 10% (5/52). Two patients (4%) had complications that required operative intervention in the postoperative period. CONCLUSIONS: The modified Delorme operation is a safe and effective surgical treatment for complete rectal prolapse. The risk of recurrent prolapse is low, and the procedure may be safely performed in patients with significant medical comorbidities.     

ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy

OBJECTIVES: The risks and benefits of hormone replacement therapy (HRT) are, at least in part, mediated by the metabolic individuality of women. Therefore, we investigated the association between polymorphisms at the estrogen receptor 1 gene (ESR1) and at the apolipoprotein E gene (APOE) with lipid and lipoprotein levels in order to verify whether these concentrations are modulated by these gene variants in women with different hormonal status. METHODS: One hundred and eighteen postmenopausal women using oral HRT with estrogen or estrogen plus progestagen (HRT+, mean age=56+/-6.7 years, 39-75 years) and 167 postmenopausal women that were not on HRT (HRT-, mean age=58+/-9.8 years, 38-85 years) participated in the study. The polymorphisms were genotyped by PCR-RFLP methods. RESULTS: No significant effect of ESR1 genotypes or haplotypes and ESR1*HRT interactions were detected on lipid levels in two-way analysis of variance. Postmenopausal women HRT nonusers carriers of the APOE*4 allele had higher T-chol and LDL-C levels than postmenopausal women HRT nonusers carriers of the APOE*3 and APOE*2 allele. T-chol and LDL-C concentrations in postmenopausal users of HRT that were APOE*4 carriers were similar to those in postmenopausal women nonusers of HRT homozygotes for APOE*3 and APOE*2 carriers. A significant APOE*4/HRT interaction was detected on T-chol and LDL-C levels by multiple regression analysis. CONCLUSION: The results from this study suggest that the HRT influence on T-chol and LDL-C levels is modulated by APOE isoforms but not by ESR1 polymorphisms.     

An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children’s Oncology Group study CCG‐5961

Burkitt lymphoma (BL), an aggressive B‐cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi‐centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high‐risk BL registered on Children’s Cancer Group study CCG‐5961 were investigated. Analysis with 13q14.3 and 13q34 loci specific probes demonstrated deletions of 13q in 38/90 (42%) cases. The loss of either 13q14.3 or 13q34 alone occurred in 14% and 8% respectively, while 20% exhibited loss of both regions. Gain of chromosome 7 was observed in 7/68 (10%) cases and MYC rearrangements were detected in 84/90 (93%). Prognostic analysis controlling for known risk factors demonstrated that patients exhibiting loss of 13q, particularly 13q14.3, had a significant decrease in 5‐year overall survival (77% vs. 95%, P = 0·012). These observations indicate that del(13q) occurs in childhood BL at frequencies higher than previously detected by classical cytogenetics and underscores the importance of molecular cytogenetics in risk stratification.     

Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma

Small cell osteosarcoma is a rare bone tumor of high-grade malignancy that most often arises in the metaphysis of long bones in the second decade of life. Cytogenetic and molecular genetic findings in small cell osteosarcoma are poorly defined. Conventional cytogenetic analysis of a small cell osteosarcoma arising in the proximal tibia of a 9-year-old male revealed a diploid chromosomal complement with complex structural rearrangements involving chromosomes 6, 16, and 17. Immunohistochemical assessment of p53 protein expression revealed nuclear p53 immunoreactivity in approximately 15% of the neoplastic cells. Subsequent fluorescence in situ hybridization (FISH) analyses confirmed loss of the p53 gene locus on the derivative chromosome 17 homolog and were negative for amplification of the MDM2, CDK4, c-MYC, HER-2/neu, CCND1, and COPS3 gene loci. To the best of our knowledge, this represents the first demonstration of monoallelic deletion of p53 in small cell osteosarcoma, suggesting that p53 alterations may play an important role in the development of small cell osteosarcoma as well as conventional osteosarcoma.     

A (9;11)(q34;q13) translocation in a hibernoma

The diagnosis of hibernoma has historically been made by histopathologic examination and finding of characteristic brown fat cells with granular multivacuolated cytoplasm. The diagnosis of hibernoma may be complicated, however, because seemingly diagnostic cells could be mistakenly identified as lipoblasts, leading to the erroneous diagnosis of well-differentiated liposarcoma. Cytogenetic alterations in lipomatous tumors are well established and could be used for diagnostic purposes. Previous cytogenetic abnormalities reported in hibernomas have included alteration of 11q13 region. Here, we present a case of a hibernoma with a novel cytogenetic alteration involving a reciprocal translocation between 9q and 11q that was useful in establishing the final diagnosis.