Smudge cells (SCs) also known as “basket cells”, are remnants of B lymphocytes ruptured during slide preparation (photo below). Although at low numbers (~0-5% of lymphocytes) SCs may be observed in healthy individuals, when found at higher numbers (>10%) they are associated with chronic lymphocytic leukemia (CLL) and other lymphoproliferative diseases1; the percentage of SCs may not discriminate between these malignancies, however2.
For nearly a century, SCs were thought to be just an artifact of slide preparation resulting from the fragility of CLL cells3. Although the mechanism accounting for the appearance of SCs is still unclear, their formation is inversely correlated with B cell content of vimentin, a cytoskeletal protein essential for rigidity and integrity of lymphocytes 3-5.
High vimentin expression is associated with an aggressive variant of CLL and shorter survival times3-5. Therefore, higher number of SCs at the time of CLL diagnosis (>20% or >30%) may actually indicate a better prognosis4-6!
Photo courtesy of U.S. National Library of Medicine
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- Petrakis NL, Lieberman E, Fullerton J. The dead leukocyte content of the blood in normal and leukemic patients. Blood. 1957 Apr;12:367-72. https://www.ncbi.nlm.nih.gov/pubmed/13412765
- Matos DM, Perini G, Kruzich C, Rego EM, Falcao RP. Smudge cells in peripheral blood smears did not differentiate chronic lymphocytic leukemia from other B-cell chronic lymphoprolipherative diseases. Rev Bras Hematol Hemoter. 2009;31:333–6. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842009000500010
- Nowakowski GS1, Hoyer JD, Shanafelt TD, et al. Percentage of smudge cells on routine blood smear predicts survival in chronic lymphocytic leukemia. J Clin Oncol. 2009;27:1844-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668708/
- Nowakowski GS, Hoyer JD, Shanafelt TD, et al. Using smudge cells on routine blood smears to predict clinical outcome in chronic lymphocytic leukemia: a universally available prognostic test. Mayo Clin Proc. 2007;82:449-53. https://www.mayoclinicproceedings.org/article/S0025-6196(11)61073-2/fulltext
- Johansson P, Eisele L, Klein-Hitpass L, et al. Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in chronic lymphocytic leukemia. Leuk Res. 2010;34:892-8. https://reference.medscape.com/medline/abstract/20353875
- Gogia A, Raina V, Gupta R, et al. Prognostic and predictive significance of smudge cell percentage on routine blood smear in chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk. 2014;14(6):514-7. https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00049-4/abstract
Contributed by Khin-Kyemon Aung, medical student, Harvard Medical School, Boston.
The most significant risk factor for PCP prophylaxis is defect in cell-mediated immunity including high-dose glucocorticoid (HDGC, ≥20 mg of prednisone daily) treatment1. A systematic review concluded that at a PCP rate of 6.2% in control groups, PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) is highly effective (85% risk reduction) in non-HIV patients with acute leukemia or solid organ/autologous bone marrow transplantation (number needed to treat 19)2.
Other Indications for PCP prophylaxis include1:
- HDGC treatment for ≥1month plus another cause of immunocompromise.
- Combination of immunosuppressive drugs, such as tumor-necrosing factor- α inhibitors plus HDGC or other immunosuppression.
- Polymyositis/dermatomyositis with interstitial pulmonary fibrosis on glucocorticoids.
- Certain primary immunodeficiencies (eg idiopathic CD4-lymphopenia, hyper-IgM syndrome).
- Granulomatosis with polyangiitis (Wegener’s) on methotrexate and HDGC
- Rheumatologic diseases on HDGC and a second immunosuppressive drug
- T-cell depleting agents (eg, fludarabine)
- Severe malnutrition
TMP/STX may be given either as double-strength 3x/week or single-strength daily1,2.
- Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.
- Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3.
POWV is a neuroinvasive arbovirus transmitted by Ixodes ticks (similar to Lyme disease). It has been reported in Canada, Russia and, increasingly, in northeastern states and Great lakes region of United States1. Although many cases occur during warmer months, nearly 30% of cases reported from New York occurred during November, December and January 2. Rather remarkably, POWV may be transmitted within 15 minutes of a tick bite in contrast to the agent of Lyme disease which typically takes at least 48 hours2!
The most common clinical presentation is a febrile illness associated with encephalitis, meningoencephalitis or aseptic meningitis. Seizures, focal deficits, aphasia, and dysarthria have been reported2. Typically, cerebrospinal fluid shows lymphocytic pleocytosis, normal glucose, and normal or mildly elevated protein. Electroencephalography (EEG) reveals generalized slow wave activity and MRI of the brain may suggest microvascular ischemia or demyelinating disease in the parietal or temporal lobes. Collectively, the clinical presentation may resemble those seen in herpes simplex virus encephalitis.
POWV disease carries 10% mortality with severe neurological sequelae in 50% of survivors4. Despite lack of effective treatment, POWV should be considered in the differential diagnosis of acute encephalitis in endemic areas.
- CDC. https://www.cdc.gov/powassan/statistics.html
- El Khoury MC, Camargo JF, White JL. Potential role of deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas of New York, USA. Emerg Infect Dis 2013;19:1928-33.
- CDC. www.cdc.gov/powassan/clincallabeval.html
- Hermance ME, Thanagamai S. Tick saliva enhances Powassan virus transmission to the host, influencing its dissemination and the course of disease. J Virol 2015; 89:7852-60.
The risk of infection in patients on glucocorticoids (GCs) is likely determined not only by the dose and duration of treatment but also by the nature of the underlying disease requiring GC therapy (eg, asthma, autoimmune disease, malignancy), use of additional immunosuppressants, as well as individual host sensitivity to the effects of GCs1,2. For these reasons, it is often difficult to determine how much GCs will be too much for a specific patient when discussing opportunistic infections such as PCP in patients without HIV infection.
In patients with an autoimmune disease such as ours, as little as 12 mg/day of prednisone on presentation or as few as 5 days of GC therapy has been associated with PCP3. Because the critical amount of immunosuppression necessary for PCP to cause disease is unclear4, and autoimmunity is often associated with T-cell dysregulation5, it is prudent to consider PCP in the differential of diagnosis of dyspnea (along with fever or pulmonary infiltrates if present) in this patient despite not receiving “high” doses of prednisone daily. It is also important to remember that many cases of PCP occur during GC taper4.
- Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet 2003;362:1828-38.
- Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroids. Rheum Dis Clin N Am 2016; 42; 157-176.
- Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996;71:5-13.
- Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. Arch Intern Med 1995;1125-28.
- Arkwright PD, Abinun M, Cant AJ. Autoimmunity in human immunodeficiency diseases. Blood 2002;99:2694-2707.