1/51. Cytogenetic study of eight new cases of radiation-induced solid tumors.radiation-induced tumors were selected according to the criteria defined by Cahan (1948) for sarcomas. Cell cultures and/or xenografts in nude mice were performed with biopsies obtained from second primary tumors. Karyotypes of eight tumors were established after R-banding. After comparison with literature data on 15 other cases, two distinct cytogenetic patterns could be distinguished. One was characterized by polyclonal karyotypes, of which a large proportion were simple and carriers of balanced translocations. Another one was characterized by monoclonal chromosome alterations observed in highly aneuploid and complex karyotypes, in which many deletions were observed. These two different patterns could be related to the modality of metaphase harvesting. Polyclonal karyotypes were preferentially observed after long-term cultures, and monoclonal karyotypes after short-term cultures or xenografts. The following scheme of radiation oncogenesis is proposed: a) induction of recessive gene mutations including that of tumor suppressor genes; b) accumulation of genomic alterations in the irradiated tissue with aging, including deletions or mutations of normal alleles from mutated tumor suppressor genes; and c) loss of tumor suppressor gene function and initiation of a multistage tumor development and progression. Polyclonal abnormalities are assumed to exist in noncancerous cells which acquired radiation-induced chromosome aberrations.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/51. Metastatic testicular cancer presenting as spinal cord compression: report of two cases.BACKGROUND: Testicular cancers are heterogenous neoplasms often found in young adults. They tend to metastasize to the chest, retroperitoneum, or neck, but rarely to the long bones or skeleton. However, they can cause neurologic compromise and should be considered in young male patients who present with symptoms of a spine lesion and no known primary cancer. methods: Two patients presented with back pain and a rapid progression of lower extremity weakness. Both underwent radiographic workup and emergency surgery. Metastatic workup revealed testicular cancer and widespread metastases. RESULTS: Both patients improved neurologically after surgery, but neither regained the ability to ambulate independently. They both underwent chemotherapy. One patient is alive at 1 year follow-up; the other died 9 months after surgery of widespread metastases. CONCLUSIONS: Vertebral metastases from testicular tumors, although rare, should be considered in young men presenting with spinal cord compression. work-up should include magnetic resonance imaging (MRI) of the spine and computed tomography (CT) of the chest, abdomen, and pelvis. Urgent intervention may be required, as these two cases show that loss of neurologic function can be rapid and permanent.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
3/51. Postirradiation angiosarcoma of the chest wall and breast: issues of radiogenic origin, diagnosis and treatment in two cases.The authors report two cases of postradiation angiosarcoma (AS) among 5,100 breast cancer patients treated in the period 1980-1994 at the National Institute of Oncology, Budapest. Relevant data in the literature is also reviewed to analyze the questions of radiogenic origin, diagnosis and treatment. Secondary AS occurred in these cases in a previously irradiated field after a 6- and 8-year latency period, respectively. Detailed histopathological and immunohistochemical examinations from the biopsy specimens confirmed the diagnosis as AS. The first patient was treated successfully with radical surgery. The second patient, with unresectable AS, died of rapid local progression within 4 months. The incidence of chest wall and breast AS after radiotherapy was found to be 0.46 per 1,000 in our patient population, which means an estimated odds ratio of 2.9 for secondary AS. patients treated with radiotherapy for primary breast cancer are at higher risk for developing secondary AS compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of the chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long-term survival. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
4/51. Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases.BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment. CASE REPORT: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital. case reports IN THE literature: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose. CONCLUSIONS: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
5/51. Neurofibromatosis type 1-associated unusual pleomorphic astrocytoma displaying continual malignant progression.patients with neurofibromatosis type 1 (NF1) often have gliomas as a complication, most of which are benign pilocytic astrocytomas which have arisen in optic pathways. In the present case, a 17-year-old girl (at death) with stigmata of NF1, initially had a bulky tumor mass in the left thalamus, developing into the lateral ventricle, at 13 years of age. Partially resected tissue samples showed pleomorphic astrocytoma with abundant xanthoma cells and degenerative structures such as Rosenthal fibers (RF) and eosinophilic granular bodies. Fine eosinophilic granules identical to RF, both immunophenotypically and ultrastructurally, were also seen. The residual tumor was subtotally resected 6 months later, and the tumor histology was essentially similar as before, accompanying the regenerative structures; this was believed to be a good prognostic indicator. However, several anaplastic features such as mitosis, necrosis and vascular proliferation appeared even in areas rich in the regenerative structures. After a 2-year, disease-free interval, multiple tumor relapse occurred in June 1997. Partially resected tumor tissues were composed of monotonous small anaplastic cells with prominent proliferative activity. Surprisingly, the tumor cells had retained eosinophilic granules within the cell bodies. Postoperative chemotherapy with procarbazine, MCNU and vincristine (PCV) suppressed the residual tumor dramatically, but the regrowing tumor finally became uncontrollable, leading to the patient's death. TP53 mutation was not detected, while p27 immunopositivity was constantly high during malignant progression, suggesting acquisition of proliferative activity to overcome p53 and p27 inhibitory functions. A review of previously published reports failed to reveal any cases of this type.- - - - - - - - - - ranking = 5keywords = progression (Clic here for more details about this article) |
6/51. Cytogenetic and molecular characterization of a patient with simultaneous B-cell chronic lymphocytic leukemia and peripheral T-cell lymphoma.A patient is described who developed a peripheral T-cell lymphoma (PTCL) after a 6-year history of B-cell chronic lymphocytic leukemia (B-CLL). The progression of the T-cell disease spreading to pleura and skin terminated the course of the disease. A cytogenetic analysis performed six years after the first onset of the B-CLL showed the presence of two clones, one with trisomy 12 and another with inv(14)(q11q32.1) and trisomy 8. Combined immunophenotyping and fluorescence in situ hybridization demonstrated that only CD19 cells contained a trisomy 12, whereas CD3 cells contained a trisomy 8. Analyses of IgH and TCR rearrangements in single micromanipulated B- and T-cells lacked evidence for a clonal relation between B-CLL and PTCL cells. Based on our findings, we discuss the different hypotheses which might explain the development of simultaneous PTCL and B-CLL.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
7/51. Coexistence of independent myelodysplastic and philadelphia chromosome positive clones in a patient treated with hydroxyurea.We report a patient with philadelphia chromosome positive (Ph ve) chronic myelogenous leukemia (CML), treated with hydroxyurea alone, who upon disease progression developed an additional Ph - ve clone containing chromosomal abnormalities typical of myelodysplastic syndrome (MDS). Retrospective analysis of a cryopreserved stem cell specimen from diagnosis confirmed that this second clone developed during the course of treatment. The development of a clone with additional cytogenetic abnormalities in CML has only been reported after leukemogenic treatment, stem cell transplantation or interferon. We report a case of secondary Ph - ve MDS/AML during blast crisis in a patient treated with hydroxyurea for CML.- - - - - - - - - - ranking = 30.10207877972keywords = disease progression, progression (Clic here for more details about this article) |
8/51. Plasmablastic lymphoma in a patient with chronic lymphocytic leukemia heavily pretreated with cladribine (2-CdA): an unusual variant of Richter's syndrome.patients with chronic lymphocytic leukemia (CLL) may develop a large-cell transformation known as Richter's syndrome (RS). RS usually presents as diffuse large-cell lymphoma (DLCL) or its immunoblastic variant, and it can be recognized simultaneously with CLL or even 23 yr after its diagnosis. We describe an unusual case of CLL treated with cladribine (2-CdA) in whom DLCL of the plasmablastic type (PBL) developed 4 yr after CLL (Rai IV) diagnosis and 1.5 yr after the 10th course of 2-CdA treatment. Immmunologic, cytogenetic, and molecular studies performed at the time of CLL and PBL coappearance indicated that both tumors originated from different B-cell progenitors. Both malignancies were refractory to VAD (vincristine, doxorubicin, dexamethasone)-based chemotherapy, and only partial response was achieved with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) salvage treatment. However, the patient died 6 months after the occurrence of RS due to rapid progression of PBL. This is the first description of a CLL patient who developed an unusual plasmablastic variant of RS. Recently, the PBL entity has been identified among DLCL associated with the human immunodeficiency virus (hiv) infection. We suggest that in our CLL patient heavily pretreated with 2-CdA, PBL arose as a second clone due to the prolonged and severe state of the host's immunosuppression. overall survival with current strategies is poor, and further insight into the natural history, biology, and treatment of PBL are needed.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
9/51. Malignant mesenchymoma of the uterus, arising in a leiomyoma.AIMS: To document and find evidence for the rare occurrence of malignant progression of a benign uterine leiomyoma with divergent mesenchymal differentiation. In a 54-year-old female a large pedunculated tumour was encountered which had suddenly increased in size and had apparently arisen at the site of a subserosal uterine leiomyoma first described 19 years earlier. The tumour seemed histologically diverse in its composition. The possibility of malignant progression of the benign leiomyoma with divergent mesenchymal differentiation was entertained. methods AND RESULTS: In the resected tumour, smooth muscle, osseous and adipose components were identified and these were assessed using recognized histological criteria of malignancy. In addition to a benign smooth muscle component, malignant leiomyosarcomatous tissue was seen in addition to a malignant osseous component and a malignant adipose component. The tumour thus met the criteria of a malignant mesenchymoma. The relationship of the different components of the tumour was analysed by immunohistochemistry and with molecular loss of heterozygosity (LOH) analysis. In the osseous and leiomyosarcomatous components a similar LOH pattern was observed. The adipose component showed a distinct LOH pattern. Retention of smooth muscle differentiation in the osseous component was demonstrated by desmin immunostaining. CONCLUSION: Malignant transformation of benign uterine leiomyoma may rarely occur. Mesenchymal stem cells underlying these tumours may show divergent mesenchymal differentiation.- - - - - - - - - - ranking = 2keywords = progression (Clic here for more details about this article) |
10/51. High-grade vulval intraepithelial neoplasia (VIN 3): a retrospective analysis of patient characteristics, management, outcome and relationship to squamous cell carcinoma of the vulva 1989-1999.OBJECTIVES: To determine patient and disease characteristics, treatment patterns and long-term outcomes, in order to help direct management of patients with VIN 3, to examine the risk of development of cancer following a diagnosis of VIN 3 and the risk of recurrent disease requiring multiple treatment episodes, and to review patients with vulval cancer, in order to establish the relative prevalence of VIN 3 related vulval cancers. DESIGN: Retrospective chart review of 65 consecutive patients diagnosed with VIN 3 between 1989 and 1999. population OR SAMPLE: All patients diagnosed with VIN 3 at Christchurch Womens' Hospital (1 January 1989 to 31 December 1999) and Dunedin Public Hospital (1 January 1990 to 31 December 1999). MAIN OUTCOME MEASURES: Age at diagnosis, symptoms, medical history disease characteristics, treatment, outcome and follow-up. RESULTS: The median age at diagnosis was 38 years. Smokers were younger than non-smokers. Two-thirds had associated dysplasia of the lower genital tract, 43% had high-grade lesions. Seventy-nine per cent were symptomatic for a median of 9.5 months. All had macroscopically visible disease. colposcopy and histology diagnoses correlated in 72% of cases. Treatment by local excision was undertaken in 84% of cases of which 65% had involved margins. Fifty-one per cent required further treatment, risk factors were positive margins and multifocal disease. Three developed micro-invasive cancer. CONCLUSIONS: Treatment by local excision is both diagnostic and therapeutic. Excision may reveal micro-invasive cancer, patients are usually symptomatic and VIN 3 has some potential to become invasive. Treated patients may develop microinvasive disease but frank invasion was not seen. The true rate of malignant progression in untreated patients remains unclear and radical surgery is rarely indicated. All patients require long-term follow up.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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