Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disorder (LPD) of the skin with a relatively good prognosis in the absence of high-stage disease.CD30+ LPDs comprise approximately 25%-30% of primary cutaneous lymphomas and as a group represent the second most common clonal T-cell neoplasm of the skin behind mycosis fungoides. Diagnosis of PC-ALCL relies strongly on clinicopathologic correlation given the potential morphologic, clinical and molecular overlap with the other cutaneous CD30+ LPD, lymphomatoid papulosis, and more aggressive hematolymphoid neoplasms. K E Y W O R D SCD30+ lymphoproliferative disorder, primary cutaneous anaplastic large cell lymphoma

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Malaria parasites are known to invade and develop in erythrocytes and reticulocytes, but little is known about their infection of nucleated erythroid precursors. We used an in vitro cell system that progressed through basophilic, polychromatic, orthochromatic, and reticulocyte stages to mature erythrocytes. We show that orthochromatic cells are the earliest stages that may be invaded by Plasmodium falciparum, the causative agent of fatal human malaria. Susceptibility to invasion is distinct from intracellular survival and occurs at a time of extensive erythroid remodeling. Together these data suggest that the potential for complexity of host interactions involved in infection may be vastly greater than hitherto realized. ( IntroductionApproximately 40% of the world's population is at risk of developing malaria, 1 which is caused by infections of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. During blood-stage infection, which causes all symptoms and pathologies of malaria, the parasite infects mature erythrocytes and reticulocytes. Isolated reports suggest that nucleated erythroid progenitors may also be infected, 2,3 but little is known of when in maturation they become susceptible and the complexity of associated cellular remodeling events. There is considerable interest in these parameters, because they underlie host interactions with a major human pathogen that is thought to have profoundly influenced erythroid development. 4 We have used an in vitro model system using primary cells to study commitment to the erythroid lineage and differentiation of committed progenitors to reticulocytes. 5,6 The advantages are that the kinetics of differentiation in vitro closely resembles that of erythroid cell maturation in the bone marrow, and differentiation occurs in a relatively synchronous manner. In this system we examine malarial infection during complex, cellular remodeling at terminal steps of erythroid differentiation. We show that despite prior reports, 3 only orthochromatic erythroblasts can be infected by falciparum malaria and that the process of infection is functionally segregated into 2 categories: early-mid orthochromatic erythroblasts can support parasite invasion, but only late orthochromatic/ nascent reticulocytes sustain intracellular parasite growth. Methods Primary human erythroid cultures and flow cytometryHuman primary erythroblasts were generated by culturing CD34 ϩ early hematopoietic progenitors initially isolated from growth factor-mobilized peripheral blood (purchased from ALL Cells Inc). Culture and subsequent flow cytometry sorting of cultured cells were carried out as previously described. 5 On day 7 of culture, erythroid cells positive for the transferrin receptor (CD71) were purified to 98% to 99% using a MoFlo high-speed flow cytometer (BD Biosciences). Sorted cells were subsequently cultured (in day 8 media formulation) and fed once more on day 10 with media containing only erythropoietin (2 units/mL). Parasite infectionP falciparum 3D7 was synchronized by s...

In this study, we evaluate the expression of p53 in core biopsies with acute myeloid leukemia and correlate the level of expression with acute myeloid leukemia subtype, TP53 mutation status, karyotype, and survival. Of the 143 cases evaluated, 71 fulfilled the WHO 2016 criteria for acute myeloid leukemia with myelodysplasia-related changes, 40 were acute myeloid leukemia-not otherwise specified, 25 were acute myeloid leukemia with recurrent genetic abnormalities, and 7 were therapy-related acute myeloid leukemia. By immunohistochemistry, 17% showed p53 expression in >5% of the cells. Of the 24 cases with >5% p53-positive cells, 17 were acute myeloid leukemia with myelodysplasia-related changes, 5 were acute myeloid leukemia-not otherwise specified, 1 was acute myeloid leukemia with recurrent genetic abormalities, and 1 was therapy-related acute myeloid leukemia. In cases for which data was available, expression of >5% p53-positive cells was significantly associated with genotype (n=67) and/or karyotype (n=130). Among the 115 cases for which clinical follow up was available, the overall survival of cases with p53 expression >15% (Median=102 days) was significantly shorter compared with cases with p53 expression ≤15% (Median=435 days). Within the acute myeloid leukemia with myelodysplasia-related changes group, this association remained significant, with cases with ≤15% p53-positive cells having a median overall survival of 405 days versus 102 days for cases with >15% p53-positive cells. Among acute myeloid leukemia with myelodysplasia-related changes cases with a complex karyotype, the finding of >15% p53-positive cells was significantly associated with worse overall survival. The poor prognosis associated with more than 15% p53-positive cells was independent of age and karyotype. In acute myeloid leukemia with myelodysplasia-related changes, p53 expression may be useful to infer TP53 mutation status, complex karyotype, and/or poor prognosis in situations where other modalities are not readily available.

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