Mutations in the KIT gene occur in 8% of all testicular germ cell tumors (TGCT) and KIT is the most frequently mutated known cancer gene. One report has shown that 93% of patients with bilateral disease have a mutation at codon 816 of the KIT gene. Importantly, this suggests that the identification of a mutation in KIT is predictive of the development of a contralateral TGCT. We investigated the frequency and type of mutations in KIT in a series of 220 tumors from 211 patients with TGCTs and extragonadal germ cell tumors. In 170 patients with unilateral TGCT and no additional germ cell tumour, we identified one exon 11 mutation in a patient with unilateral TGCT and eight activating KIT mutations in exon 17 (9/175, 5.1%). In 32 patients with bilateral TGCT, one patient had an activating KIT mutation in exon 17 (3.1%). The incidence of activating KIT mutations in sporadic TGCT vs. familial TGCT was not significantly different. All mutations were identified in seminomas. Three extragonadal primary germ cell tumors were examined and in one tumor an activating KIT mutation was demonstrated in the pineal germinoma. Interestingly, this mutation was also seen in the patient's testicular seminoma. We find no evidence for an increased frequency of KIT mutations in bilateral TGCT. V V C 2007 Wiley-Liss, Inc.

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Testicular microlithiasis (TM) is characterised by small intratesticular calcifications, which can be visualised by ultrasound. Men with testicular germ cell tumour (TGCT) have a higher frequency of TM than men without TGCT. To clarify the association between TGCT and TM and to investigate the relationship between TGCT susceptibility and TM, we recruited TGCT patients with and without family history of TGCT, unaffected male relatives and healthy male controls from the UK. Testicular ultrasound data were analysed from 328 men. Testicular microlithiasis was more frequent in TGCT cases than controls (36.7 vs 17.8%, age adjusted Po0.0001) and in unaffected male relatives than controls (34.5 vs 17.8%, age adjusted P ¼ 0.02). Testicular germ cell tumour case and matched relative pairs showed greater concordance for TM than would be expected by chance (P ¼ 0.05). We show that TM is present at a higher frequency in relatives of TGCT cases than expected by chance indicating that TM is a familial risk factor for TGCT. Although the familiality of TM could be due to shared exposures, it is likely that there exists a genetic susceptibility to TM that also predisposes to TGCT. We suggest that TM is an alternative manifestation of a TGCT susceptibility allele. (Forman et al, 1992;Westergaard et al, 1996;Heimdal et al, 1996a;Sonneveld et al, 1999;Hemminki and Li, 2004), a previously diagnosed germ cell tumour (Osterlind et al, 1991;Wanderas et al, 1997), a history of undescended testis (Brown et al, 1987;Swerdlow et al, 1997), infertility (Petersen et al, 1998;Moller and Skakkebaek, 1999;Jacobsen et al, 2001;Richiardi et al, 2004), atrophy (Harland et al, 1998), and gonadal dysgenesis (Verp and Simpson, 1987). In a proportion of cases (B2%), a first-degree family member is also affected with the disease (Forman et al, 1992). The relative risk to a brother of a TGCT case is 8 -10 (Forman et al, 1992;Heimdal et al, 1996b;Hemminki and Li, 2004), which is higher than for most other cancer types that rarely exceed four (Dong and Hemminki, 2001) and suggests that predisposition genes are important in this disease. However, despite intensive efforts, susceptibility genes are yet to be identified (Crockford et al, 2006). Testicular microlithiasis (TM), the presence of multiple small deposits of calcium within the testis, shows characteristic sonographic findings of multiple, intratesticular, nonshadowing echogenic foci. Since the original description of ultrasounddetected TM (Doherty et al, 1987), a number of studies have reported an association between TGCT and TM (Backus et al, 1994;Miller et al, 1996Miller et al, , 2006Cast et al, 2000;Bach et al, 2001;Bennett et al, 2001;Derogee et al, 2001;Middleton et al, 2002;Sakamoto et al, 2006). All the studies report ultrasound findings for men investigated for a suspect testicular pathology (infertility, hydrocele, varicocele or suspected tumour) and compare the rate of TM in men found to have TGCT with those that have other diagnoses, including normal testes. The studies have shown a hig...

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Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas, especially gastric MALT lymphoma, deserves special attention because of the high response rate to Helicobacter pylori eradication therapy.

We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach.

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Background: Primary lymphoma of the breast accounts for 0.04–0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. Case Report: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin‘s lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no ‘B’ symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. Conclusion: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.