Synchronous Development of Acute Megakaryoblastic Leukaemia and Disseminated Melanoma following Treatment of a Germ Cell Tumour: A Case Report

Somatic malignant transformation of germ cell tumours is a well-described but poorly understood phenomenon. It is characterized by differentiation of pluripotent teratoma cells into somatic tumour cells. Following malignant transformation, the most common histologies are sarcomas and primitive neuroectodermal tumours; however, other subtypes have been recognized including melanoma, leukaemia, and renal cell carcinoma. We report a case of a 38-year-old male who had recently completed treatment for a mediastinal germ cell tumour with teratomatous components. He presented several months after completion of chemotherapy with metastatic lesions in his spine and liver accompanied with severe pancytopenia. He was subsequently diagnosed with acute megakaryoblastic leukaemia (AMKL), and a biopsy of a liver lesion was consistent with metastatic melanoma. This case illustrates the simultaneous development of 2 rare malignant entities: mediastinal germ cell tumour-associated AMKL and somatic malignant transformation to melanoma. It also highlights the importance of close surveillance to detect these metastatic sequelae and the emerging role of tumour sequencing to establish targetable pathways.

Pathological and immunohistochemical aspects of acute megakaryoblastic leukaemia in a cat – Short communication

An adult, mixed-breed, feline leukaemia virus (FeLV-) positive female cat was presented with mucosal jaundice and a history of anorexia and constipation for three days. Physical examination revealed splenomegaly, cachexia, and dehydration. Humane euthanasia was conducted, followed by postmortem examination. Grossly, the cat was icteric, and presented hepatomegaly with multifocal white spots and splenomegaly. Histologically, the bone marrow was nearly completely replaced by a proliferation of megakaryocytes and megakaryoblasts, and there was a proliferation of fibrous connective tissue. Similar neoplastic proliferation was observed infiltrating the liver, lymph nodes, spleen, kidney, skeletal muscle, and lungs. Immunohistochemistry was performed for von Willebrand Factor (VWF), CD79α, CD3, feline immunodeficiency virus, FeLV, and CD61. Marked cytoplasmic labelling was observed in the neoplastic cells for FeLV, VWF and CD61, corroborating the diagnosis of acute megakaryoblastic leukaemia.

PAK1 Inhibition Slows Growth and Partially Promotes Differentiation of AMKL Cells

Purpose Acute megakaryoblastic leukaemia is characterized by the expansion of megakaryoblasts, which are hyperproliferative and fail to undergo differentiation or polyploidization. Although recent studies have proposed that inducing immature AMKL cells to undergo differentiation is a good therapeutic strategy, there is still no satisfactory medicine for clinical application because of the unclear enrichment of megakaryoblasts. It has been reported that p21 (RAC1)-activated kinase 1 (PAK1) participates in megakaryoblastic proliferation and differentiation, and its upregulation is related to AML development, but its role in AMKL remains unclear. Method The mRNA level of PAK1 was analyzed according the GSE4119 dataset by calculating the copy numbers of PAK1 to GAPDH. The protein level of PAK1 was detected in primary mouse AMKL cells with overexpression of MPLW515L mutant gene. The biological function was examined in AMKL cells after PAK1 inhibition by EdU staining, western blot, Annexin V/FITC, and flow cytometry assay, respectively.Results Here, we found that the mRNA and protein level of PAK1 was enriched in AMKL patients or cells, and inhibition of PAK1 significantly induced the arrested growth of the AMKL cell line. Further analysis of the protein expression of downstream of PAK1 showed that blocking the activity of PAK1 downregulated the expression of cyclin D1. Two PAK1 inhibitors partially and modestly promoted polyploidy formation in both CHRF and CMK cells. Additionally, these PAK inhibitors consistently promoted cell apoptosis by upregulating cleaved caspase 3. In accordance with the inhibitor effects on AMKL cells, PAK1 knockdown also increased the polyploid DNA content of CHRF and CMK cells and significantly induced cell apoptosis. Conclusions These results suggest that PAK1 might be a critical gene that drives the proliferation and differentiation of AMKL cells, and inhibiting the activity of PAK1 might be an effective method of controlling AMKL.

Cases of transient abnormal myelopoiesis

Transient abnormal myelopoiesis (TAM) is a unique hematological syndrome specific for neonates with Down syndrome. Clinical and hematological manifestations of ТАМ are similar manifestations of acute leukemia, but they may resolve spontaneously by few weeks/months after birth. Summation trisomy 21 and GATA1 mutation in blast clone is a required element for development TAM. Presentation of this syndrome occurs in the first days of life; clinical manifestations may be absent (“silent” TAM) or even lead to death of fetus and neonate. The main interest in the study of this issue is the fact that after spontaneous regression there in 20% of cases at the age of 3–4 years developing acute megakaryoblastic leukaemia (AMKL). The basic transformation factors TAM to AMKL are unknown. In this article we represent 6 cases of TAM identified in Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology from 2012 to 2019. Parents of these patients gave their agreement to use personal data in research and publications.

Platelet morphology

BackgroundThe examination of a peripheral blood smear is mandatory in case of unexplained thrombocytopenia or thrombocytosis. First, the number of platelets should be estimated in order to confirm the platelet count determined by the haematology analyser, and to rule out causes of spuriously low or elevated platelet counts. Second, the size and morphological features of the platelets, which may provide information on the underlying cause of the low or enhanced platelet count, have to be assessed.ContentThis review summarizes the physiological and pathological features of platelet size and morphology, circulating megakaryocytes, micromegakaryocytes and megakaryoblasts, and provides an overview of current guidelines on the reporting of platelet morphology.SummaryIn the diagnostic work-up of a patient with thrombocytopenia, the size of the platelets is of diagnostic relevance. Thrombocytopenia with small platelets is suggestive of a defect in platelet production, whereas the presence of large platelets is more likely to be associated with enhanced platelet turnover or hereditary thrombocytopenias. Morphological platelet abnormalities may affect the granulation and the shape and are frequently associated with abnormalities of platelet size. Platelet anomalies can be found in various haematologic disorders, such as myelodysplastic syndromes, myeloproliferative neoplasms, acute megakaryoblastic leukaemia or hereditary thrombocytopenias.