Integration of conventional cytogenetics, comparative genomic hybridisation and interphase fluorescence in situ hybridisation for the detection of genomic rearrangements in acute leukaemia.

AIMS: To screen for genomic imbalances in patients with acute leukaemia using conventional (G-banding) and molecular (comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH)) methods to determine whether an integrative screening approach increases abnormality detection rate. METHODS: G-banded analysis was performed on unstimulated bone marrow (BM) or peripheral blood (PB) cells after short-term (24-hour) culture. CGH was performed on reference (control) and neoplastic (test patient) genomic DNA extracted from BM or PB samples. Interphase FISH (i-FISH) was selectively carried out at disease diagnosis on patients with acute lymphoblastic leukaemia and acute myeloid leukaemia using conventional methods. RESULTS: Genomic rearrangements were detected in 4, 7 and 6 patients using G-banding, CGH and i-FISH respectively. Discordance in results between G-banding, CGH and/or i-FISH was found in 7 of the 12 patients screened. G-banding and CGH, when used individually, detected a genomic imbalance/rearrangement in 33.3% and 58.3%, respectively, of the patients screened. However, when both screening methods were integrated, the abnormality detection rate increased to 66.7%. This detection rate increased further to 75.0% with the use of i-FISH screening. CONCLUSIONS: The advantages and disadvantages of using G-banding, CGH and i-FISH as either stand-alone or integrated screening methods for the detection and characterisation of genomic imbalances in acute leukaemia are clearly demonstrated. Abnormality detection rate significantly increased when an integrated screening approach was employed which could potentially provide valuable information for risk stratification in patients with acute leukaemia.

Thrombotic thrombocytopenic purpura secondary to Streptococcus.

We describe a 16 year old female who developed thrombotic thrombocytopenic purpura (TTP) following infection due to Streptococcus. Initially presenting a fever and systemic upset she progressed to develop dialysis dependent acute renal failure, seizures, thrombocytopenia and a haemolytic anaemia--the pentad of features seen in TTP. Prior to the diagnosis she was found to have unexplained and previously undescribed MRI findings of diffuse increased signal intensity in the white matter of the left cerebellar hemisphere posteriorly and also increased signal intensity in the overlying cortex. She was commenced on plasmapheresis, and her anaemia, thrombocytopenia, creatinine and LDH all fully responded. In addition, she had no further seizures following plasmapheresis and has not relapsed to date. We review both the rare association of TTP and streptococcal infection, and the neuroradiological findings described in the literature. This is only the third case report describing TTP following streptococcal infection, and only the second in the era of plasmapheresis.

Novel and Mediterranean beta thalassemia mutations in the indigenous Northern Ireland population.

beta thalassemia is one of the most common genetic diseases worldwide resulting from aberrant beta-globin chain production. It is highly prevalent in regions with endemic malaria, but it is also present at low frequency in the indigenous populations of non-tropical areas such as Britain. Screening beta thalassemia trait individuals from Northern Ireland has detected 2 Mediterranean mutations, 39 (C --> T) and IVS-I-110 (G --> A); the previously reported IVS-II-850 (G --> A) mutation originally described in individuals of Scottish/English ancestry; and 2 novel mutations, initiation codon A --> C and 109 delG. Haplotype analysis indicates that the Mediterranean mutations are present on previously described haplotypes, suggesting that they have arisen due to migration. It remains to be established whether the novel mutations have arisen de novo in Northern Ireland.

Acute myeloid leukemia with concurrent myeloid sarcoma treated with autologous bone marrow transplantation: two illustrative cases and a literature review.

Myeloid sarcoma (MS) is an invasive extramedullary solid tumor composed of immature cells of the myeloid series. It complicates the clinical course of a minority of patients with acute myeloid leukemia (AML). Traditionally its presence has been regarded as an indicator of aggressive disease. Currently, the optimal treatment of AML with concurrent MS remains to be determined. We report two cases of autologous bone marrow transplantation (auto-BMT) for AML with concurrent MS followed by a review of the literature.

Glucose-6-phosphate dehydrogenase Guadalajara--a case of chronic non-spherocytic haemolytic anaemia responding to splenectomy and the role of splenectomy in this disorder.

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme of the pentose phosphate shunt pathway a major function of which is to prevent cellular oxidative damage. Deficiency in red blood cells is associated with a number of varied clinical manifestations. Chronic non-spherocytic haemolytic anaemia is uncommon but is usually characterized by chronic haemolysis, often with severe anaemia. In the past splenectomy in this condition has been thought to be of questionable benefit. We report a case of G6PD Guadalajara where splenectomy produced transfusion independence and have reviewed the literature. Those cases with exon 10 mutations often have a severe clinical phenotype, which responds to splenectomy. This procedure should be considered in this condition.

Plasmacytoma: an unusual cause of a pituitary mass lesion. A case report and a review of the literature.

A sixty six year old female presented with headache and decreased hearing. Clinical examination confirmed the presence of impaired hearing on the left side. Visual fields were full to confrontation and corrected visual acuity was normal. CT scan of brain revealed a pituitary mass. Preoperative anterior pituitary function was normal. Transsphenoidal decompression was performed, and histology was that of a plasmacytoma. Post operative pituitary function was normal. The patient had no symptoms or signs of multiple myeloma and subsequent investigations revealed no evidence of the disease. One year after diagnosis a course of radiotherapy was administered for local tumour recurrence. During seven years of follow-up, no evidence of multiple myeloma has emerged. Only thirteen similar cases have been described. Four of these had evidence of multiple myeloma at presentation and six progressed to it during follow-up. In twelve patients cranial nerve deficits were recorded. In any cases where it was documented, preoperative anterior pituitary function was normal. In a number of cases histology was reported initially as being that of a non-functioning adenoma, the true diagnosis being discovered, either by electron microscopy findings or after the development of multiple myeloma. Plasma cell tumours of the pituitary area are rare and can present with symptoms and signs indistinguishable from non-functioning adenoma. Atypical symptoms such as cranial nerve involvement or unexpected preservation of anterior pituitary function should arouse suspicion.