Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia.

AIMS: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia. METHODS AND RESULTS: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

A comparative analysis of the karyotypes of three dolphins - Tursiops truncatus Montagu, 1821, Tursiops australis Charlton-Robb et al., 2011, and Grampus griseus Cuvier, 1812.

The aim of this study is to produce G-banded karyotypes of three dolphin species, Tursiops truncatus Montagu, 1821, Tursiops australisCharlton-Robb et al., 2011, and Grampus griseus Cuvier, 1812, and to determine if any differences between the species can be observed. Monolayer skin cultures were established and processed for chromosome study by trypsin banding. The results indicate that the three species here investigated have the same diploid number (2n = 44) and very similar gross chromosome morphology, however G-banding allows distinction between each species. Chromosome 1 in G. griseus is significantly different from the other 2 species, and chromosome 2 in T. australis is subtly different from the other 2 species. This result is of potential significance in taxonomic studies, and can provide an unequivocal answer in the assessment of suspected hybrids between these species.

Monotypic Plasma Cell Proliferation of Uncertain Clinical Significance Mimicking Interstitial Cystitis: An Early Lesion of MALT Lymphoma?

We prospectively studied our institutional experience of bladder extranodal marginal zone (mucosa-associated lymphoid tissue [MALT]) lymphoma including bladder biopsies in which the possibility of MALT lymphoma was considered. We identified a subset of cases primary to the urinary bladder, presenting with prominent plasma cell infiltrates and symptoms mimicking bladder pain syndrome/interstitial cystitis. These proliferations were designated for this study as "monotypic plasma cell proliferation of uncertain clinical significance" (MPCP-US), as the features were insufficient for diagnosis of MALT lymphoma. We identified 33 patients, consisting of 22 cases of MPCP-US (6 of which were associated with amyloid deposition) and 11 cases of MALT lymphoma. MPCP-US was more prevalent in men (73%), a mass lesion was not identified at cystoscopy, and only 1 case had an accompanying urinary tract infection (4.5%). Histologically, MPCP-US presented as monotypic plasma cells arranged in a superficial band-like distribution in the lamina propria, predominantly kappa restricted (68%) and IgA+ or IgM+ (64% and 23%, respectively) and without a histologic mass of atypical B cells or plasma cells, not diagnostic for established MALT lymphoma or plasmacytoma. Secondary involvement of the bladder by other lymphoproliferative disorders was excluded and there was no evidence of progressive disease. MALT lymphomas are presented for comparison and our analysis demonstrated that MPCP-US represent a different clinicopathologic entity compared with classic MALT lymphoma. We present the first series of cases of MPCP-US. The recognition of this entity is fundamental to the development of management protocols to relieve intractable symptoms mimicking bladder pain syndrome/interstitial cystitis in these patients.

The Karyotype of Blainville's Beaked Whale, Mesoplodon densirostris.

The karyotype of the Odontocete whale, Mesoplodon densirostris, has not been previously reported. The chromosome number is determined to be 2n = 42, and the karyotype is presented using G-, C-, and nucleolar organizer region (NOR) banding. The findings include NOR regions on 2 chromosomes, regions of heterochromatic variation, a large block of heterochromatin on the X chromosome, and a relatively large Y chromosome. The karyotype is compared to published karyograms of 2 other species of Mesoplodon.

The architecture and evolution of cancer neochromosomes.

We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation.

FISH detection of PML-RARA fusion in ins(15;17) acute promyelocytic leukaemia depends on probe size.

The diagnosis of acute promyelocytic leukaemia (APL) is usually confirmed by cytogenetics showing the characteristic t(15;17), but a minority of patients have a masked PML/RARA fusion. We report ten patients with APL and no evidence of the t(15;17), in whom the insertion of RARA into PML could not be demonstrated by initial FISH studies using a standard dual fusion probe but was readily identified using smaller probes. Given the need for rapid diagnosis of APL, it is important to be aware of the false negative rate for large PML/RARA FISH probes in the setting of masked rearrangements.