The emergence of non-secretory multiple myeloma during the non-cytotoxic treatment of essential thrombocythemia: A case report

Introduction. The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing out the impact of a cytotoxic effect during treatment of essential thrombocythemia on the development of multiple myeloma. Case presentation. We report the case of a 52-year-old Caucasian man who presented to our hospital because of leukocytosis, a slightly decreased hemoglobin level and thrombocytosis. After a complete hematological work-up, essential thrombocythemia was diagnosed. The patient was included in a multicenter clinical study, treated with anagrelide and his platelet counts were maintained in the normal range for more than 3 years. A sudden drop in his hemoglobin level with normal leukocyte and platelet count occurred at the same time as a back pain. Magnetic resonance imaging of his spine revealed the existence of a pathological fracture of Th4, the collapse of the upper edge of Th7 and osteolytic lesions of multiple thoracic vertebrae. Repeated hematological examinations, including bone biopsy with immunohistochemistry, disclosed diagnosis of multiple myeloma of the non-secretory type. Conclusions: To the best of our knowledge this is the first published case in which multiple myeloma developed during the treatment of essential thrombocythemia with the non-cytotoxic drug anagrelide. Our attempts to find a common origin for the coexistence of multiple myeloma and essential thrombocythemia have not confirmed the genetic basis of their appearance. Further studies are needed to determine the biological impact of this coexistence

Late-appearing pseudocentric fission event during chronic myeloid leukemia progression

Pseudocentric fission is a rare event consisting of the splitting of one functional centromere into two new products, of which only one can give rise to a functionally competent kinetochore. We report here a pseudocentric fission event within the D5Z2 alphoid subset disrupting the centromeric region of chromosome 5 in a case of chronic myeloid leukemia (CML) after treatment with imatinib and interferon. The breakage generated unequal partitioning of alpha-satellite sequences between the two fission products. One product was inserted within the long arm of chromosome 12 at band 14.3, becoming the only functional centromere of chromosome der(5). The other fission product was rearranged to form a sandwich-like dicentric-but functionally monocentric-chromosome der(6), made up of material from chromosomes 5, 12, and 6. The intercentric distance on der(6) was shown to be largely >20 Mb. To our knowledge, this is the first pseudocentric fission event described in CML. Moreover, our results confirm the susceptibility to breakage of the centromeric region of chromosome 5

t(5;6;12 ) associated with resistance to imatinib mesylate in chronic myeloid leukemia

A patient with t(9;22)-positive chronic myelogenous leukemia (CML) developed a resistance to therapy with imatinib mesylate (Glivec) which coincided with the appearance of t(5;6;12) in the same cells with t(9;22) [46,XX,t(5;6;12)(q14?;q21?;q23?),t(9;22)(q34;q11)]. She remains in a continuous chronic phase of CML. This is the first reported instance of karyotype evolution temporally associated, and possibly involved, with the induction of resistance to imatinib mesylate but without any signs of evolution of leukemia toward a more anaplastic and aggressive form

Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe

Abstract: Background: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). Materials and methods: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. Results: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for singletest sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. Conclusions: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe