Green neutrophilic inclusions could be a sign of impending death!

Abstract

A n 88-year-old African American man was evaluated for altered mental status and was found to have a urinary tract infection. He developed septic shock with a positive blood culture for Escherichia coli, confirmed as extended spectrum beta-lactamase. During the course of infection, the aspartate aminotransferase and alanine aminotransferase increased rapidly from 50 U/L and 22 U/L to 348 U/L and 116 U/L, respectively. The bilirubin increased from 3.4 mg/dL to 4.4 mg/dL (direct: 3.2 mg/dL) with increased international normalized ratio, prolonged prothrombin time and activated partial thromboplastin time, and elevated creatinine. The peripheral blood smear showed normocytic normochromic anemia with acanthocytes and neutrophilic leukocytosis (white blood cells: 21.8 3 10 9 /L). Variable-sized, ill-defined, bright-green cytoplasmic inclusions (panels A and B) were seen in a subset of the patient's neutrophils (15% of total neutrophils). Associated reactive changes, including toxic granulation, cytoplasmic vacuoles, and Döhle bodies, were noted in some of these neutrophils, as well as others. The green inclusions were negative for iron, myeloperoxidase, and bilirubin special stains. The platelets were 117 3 10 9 /L with normal morphology. The patient's condition deteriorated rapidly, and he expired 2 days after admission. Similar neutrophilic inclusions have been reported (Harris VN, Malysz J, Smith MD. Green neutrophilic inclusions in liver disease. J Clin Pathol. 2009;62[9]:853-854) in 2 patients with fatal acute hepatic failure just prior to death; we support the suggestion in this report that the presence of such inclusions may serve as a prognostic indicator of impending death.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

Green neutrophil and monocyte inclusions – time to acknowledge and report

“…They can be seen in both neutrophils and monocytes. These inclusions are associated with a high mortality rate, but we show that their appearance is not always fatal, as suggested in previous reports (Harris et al , ; Jazaerly & Gabali, ). Because of their strong association with death and critical illness, we suggest they be described as ‘critical green inclusions’.…”

“…In the three reported cases, death occurred within 2 d of recognition of the inclusions (Harris et al , ; Jazaerly & Gabali, ). Disease associations with green neutrophil inclusions included acute liver failure secondary to acetaminophin overdose, lactic acidosis with multisystem organ failure subsequent to trauma (Harris et al , ) and Escherichia coli ‐associated septic shock (Jazaerly & Gabali, ). Harris et al () suggested that the inclusions were related to blood‐borne bile products.…”

Green inclusions in neutrophils: A critical finding that must be reported

“…In the past decade, nine publications encompassing 70 cases have reported green cytoplasmic inclusions in neutrophils and occasionally in monocytes in patients suffering from acute liver damage. [1][2][3][4][5][6][7][8][9] The presence of these cytoplasmic deposits within the neutrophils is most probably due to a lipofuscin-like substance released from necrotic liver parenchymal cells and taken up by phagocytosis. 3,7 Biological findings described in these patients are as follows: (a) elevated liver transaminases associated with acute liver tissue damage, (b) elevated lactate dehydrogenase (LDH) levels probably secondary to hepatic necrosis, and (c) elevated lactate values, seen as a predictor of survival.…”

“…3,4 The second case showed a much higher percentage of inclusion-filled neutrophils (peak at 18%) in accordance with the first described cases. 1,2 Other studies refer to multiple or incidental neutrophils with green inclusions. [5][6][7][8] It is reasonable to think that the higher the number of neutrophils with inclusions, the more extensive the tissue damage, as more lipofuscin-like substance is released from the necrotic tissue and taken up by neutrophils.…”

Green Inclusions in Neutrophils and Monocytes Are an Indicator of Acute Liver Injury and High Mortality

“…The earliest published cases include anecdotal reports from patients with a wide variety of comorbid conditions and associated liver dysfunction [1,2,3,4,5]. Subsequent reports emphasized that such inclusions are associated with impending death and a high rate of mortality [6,7,8]. In the most comprehensive study to date, Hodgson et al [7 ]described 20 such patients including the first nonfatal cases, and also reported biochemical findings suggesting that the inclusions are comprised of a lipid-rich, lipofuscin-like material or lysosomal degradation product(s) that may be released from necrotic hepatocytes.…”