Fine needle aspiration of extramedullary myeloid cell tumor in myelodysplastic syndrome. A report of three cases.

BACKGROUND: Soft tissue tumors are rare in myelodysplastic syndrome (MDS), and the role of fine needle aspiration (FNA) cytology in their diagnosis has not been explored. CASES: Two patients with refractory anemia with excess blasts in transformation (RAEB-t) developed soft tissue swellings during the course of the illness. In a third patient, soft tissue swelling was a presenting feature. The swellings in all three cases were diagnosed as extramedullary myeloid cell tumor (EMT) on FNA and showed increased blasts (10-14%), dyspoietic changes, Auer rods and monocytosis. CONCLUSION: Soft tissue tumors appearing in MDS are likely to be EMTs. FNA is therefore particularly valuable in their diagnosis as morphology, cytochemistry, immunophenotyping and flow cytometric analysis of hematopoietic cells are best studied on aspirated material. We suggest that FNA be preferred over excisional biopsy for the diagnosis of soft tissue swellings in MDS.     

Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice

Cholestasis-induced liver injury during bile duct obstruction causes an acute inflammatory response. To further characterize the mechanisms underlying the neutrophil-induced cell damage in the bile duct ligation (BDL) model, we performed experiments using wild-type (WT) and ICAM-1-deficient mice. After BDL for 3 days, increased ICAM-1 expression was observed along sinusoids, along portal veins, and on hepatocytes in livers of WT animals. Neutrophils accumulated in sinusoids [358 +/- 44 neutrophils/20 high-power fields (HPF)] and >50% extravasated into the parenchymal tissue. Plasma alanine transaminase (ALT) levels increased by 23-fold, and severe liver cell necrosis (47 +/- 11% of total cells) was observed. Chlorotyrosine-protein adducts (a marker for neutrophil-derived hypochlorous acid) and 4-hydroxynonenal adducts (a lipid peroxidation product) were detected in these livers. Neutrophils also accumulated in the portal venules and extravasated into the portal tracts. However, no evidence for chlorotyrosine or 4-hydroxynonenal protein adducts was detected in portal tracts. ICAM-1-deficient mice showed 67% reduction in plasma ALT levels and 83% reduction in necrosis after BDL compared with WT animals. The total number of neutrophils in the liver was reduced (126 +/- 25/20 HPF), and 85% of these leukocytes remained in sinusoids. Moreover, these livers showed minimal staining for chlorotyrosine and 4-hydroxynonenal adducts, indicating a substantially reduced oxidant stress and a diminished cytokine response. Thus neutrophils relevant for the aggravation of acute cholestatic liver injury in BDL mice accumulate in hepatic sinusoids, extravasate into the tissue dependent on ICAM-1, and cause cell damage involving reactive oxygen formation.     

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.     

Evolutionary and plastic changes in a native annual plant after a historic drought

Severe droughts are forecast to increase with global change. Approaches that enable the study of contemporary evolution, such as resurrection studies, are valuable for providing insights into the responses of populations to global change. In this study, we used a resurrection approach to study the evolution of the California native Leptosiphon bicolor (true babystars, Polemoniaceae) across populations differing in precipitation in response to the state's recent prolonged drought (2011–2017). In the Mediterranean climate region in which L. bicolor grows, this historic drought effectively shortened its growing season. We used seeds collected both before and after this drought from three populations found along a moisture availability gradient to assess contemporary evolution in a common garden greenhouse study. We coupled this with a drought experiment to examine plasticity. We found evolution toward earlier flowering after the historic drought in the wettest of the three populations, while plasticity to experimental drought was observed across all three. We also observed trade‐offs associated with earlier flowering. In the driest population, plants that flowered earlier had lower intrinsic water‐use efficiency than those flowering later, which was an expected pattern. Unexpectedly, earlier flowering plants had larger flowers. Two populations exhibited evolution and plasticity toward smaller flowers with drought. The third exhibited evolution toward larger flowers, but displayed no plasticity. Our results provide valuable insights into differences among native plant populations in response to drought.     

Characterization of cryptic rearrangements, deletion, complex variants of PML, RARA in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation t(15;17)(q22;q21) leading to the disruption of Promyelocytic leukemia (PML) and Retionic Acid Receptor Alpha (RARA) followed by reciprocal PML-RARA fusion in 90% of the cases. Fluorescence in situ hybridization (FISH) has overcome the hurdles of unavailability of abnormal and/or lack of metaphase cells, and detection of cryptic, submicroscopic rearrangements. In the present study, besides diagnostic approach we sought to analyze these cases for identification and characterization of cryptic rearrangements, deletion variants and unknown RARA translocation variants by application of D-FISH and RARA break-apart probe strategy on interphase and metaphase cells in a large series of 200 cases of APL. Forty cases (20%) had atypical PML-RARA and/or RARA variants. D-FISH with PML/RARA probe helped identification of RARA insertion to PML. By application of D-FISH on metaphase cells, we documented that translocation of 15 to 17 leads to 17q deletion which results in loss of reciprocal fusion and/or residual RARA on der(17). Among the complex variants of t(15;17), PML-RARA fusion followed by residual RARA insertion closed to PML-RARA on der(15) was unique and unusual. FISH with break-apart RARA probe on metaphase cells was found to be a very efficient strategy to detect unknown RARA variant translocations like t(11;17)(q23;q21), t(11;17)(q13;q21) and t(2;17)(p21;q21). These findings proved that D-FISH and break-apart probe strategy has potential to detect primary as well as secondary additional aberrations of PML, RARA and other additional loci. The long-term clinical follow-up is essential to evaluate the clinical importance of these findings.     

Childhood obesity and insulin resistance

Insulin resistance (IR) in childhood has importance to the understanding and prevention of the growing epidemic of insulin resistance syndrome (IRS) in adults with attendant obesity, type 2 diabetes (T2DM), atherosclerotic diseases, hypertension, gout, non-alcoholic, steato-hepatitis (NASH), gall bladder disease, nephropathy, polycystic ovarian disease (PCOS), infertility and premature senility. The severity of IR and its’ complications in children unfortunately and usually progresses in their pubertal transition to adulthood; affected young children are more likely than adults to have underlying causal monogenic disorders; the sequence of natural history and events give insights into disease pathogeneses, and optimal life style choices that last are best made during the early formative years. Some features of IR in children discussed herein are: a strong tendency to low birth weight for gestational age, adverse effects of adrenarche and therapeutic steroid therapy, predisposition to premature pubarche, acanthosis nigricans, tall stature despite pituitary GH suppression, allergic diathesis, hyperandrogenism and PCOS, dyslipidemia and fatty liver disease, and diagnosis by clinical and biochemical markers of IR including insulin regulated hepatic hormonal binding proteins such as IGFBP-1. The national preoccupation with the “metabolic syndrome” T2DM and obesity, should be appropriately directed to an improved understanding of IR in children and their management, if the looming health crisis in affected adults is to be seriously addressed. The nation is facing its’ first generation of children who will be less healthy and die younger than the previous generation (Marks (2005) Presentation to the American Association of Diabetes Educators 32nd Annual Meeting and Exhibition, August 10–13, Washington, DC).