Hematology Interest Group 

 
Case Study 
 
June 11, 2017 
 

CASE HISTORY 
A 16-year-old female presented to the emergency room with complaints of ongoing fatigue, malaise, 
sore throat, fever, chills, aches, and nausea for a period of 10 days. Vitals were assessed and 
confirmed a fever of 99.5*F. On examination, tender posterior cervical lymphadenopathy was noted 
and abdominal inspection showed signs of mild hepatosplenomegaly. The physician ordered a STAT 
CBC with Differential, Erythrocyte Sedimentation Rate Test (ESR), Rapid Monospot Latex 
Agglutination, and a routine EBV IgM titer. 

 
LABORATORY RESULTS 
 
Patient’s Results Reference Range

ESR 65 mm/hour 0 – 20 mm/hour

 
 

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   Patient’s Results Reference Range

Red Blood Cell Count (RBC)  4.53 x 10 x10​6​/uL 4.2 – 5.4 x 10 x10​6​/uL

Hemoglobin (HgB)  13.1 g/dL 12-16 g/ dL

Hematocrit (Hct)  38.9 % 37-47%

Mean Corpuscular Volume (MCV)  85.9 fl 80-100 fl

Heam Corpuscular Hemoglobin (MCH)  29.0 pg 27-31 pg

Mean Corpuscular Hemoglobin Concentration (MCHC)  33.8 g/dL 32-36 g/dL

Red Cell Distribution Width (RDW)  12.6 % 11.5-14.5 %

Platelets  289 x 10​3​/uL 140-440 x 10​3​/uL

White Blood Cell Count (WBC)  11.0 x 10 x10​3​/uL 4.8-10.8 x 10​3​/uL

 
DxH 800 Interpretation/Flags  

According to the hospital laboratory protocol on slide criteria, a blood smear was prepared based on 
the following: 

​Definitive Flag:​ Lymphocytosis # >5.0​ x​10​3​/uL 

Suspect Flag: ​Variant LY 

The scatterplot shows marked populations in the variant lymphocyte region as indicated by the circled 
areas. There is also an increased predominance of the lymphocyte region.  

 
 

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Manual Differential 

Patient’s Results Reference Range

Neutrophils 34.7% 50 – 70%

3.8 x10​3​/uL 1.4-6.5 x10​3​/uL

Lymphocytes 23.5% 20 – 40%

6.1 x10​3​/uL 1.2 - 3.4x10​3​/uL

Monocytes 7.9% 2-9%

0.9 x10​3​/uL 0-0.7 x 10​3​/uL

Eosinophils 1.4% 0-4 %

0.2 x10​3​/uL 0-0.5 x 10​3​/uL

Basophils 0.5% 0-2 %

0.1 x10​3​/uL 0-0.2 x 10​3​/uL

Atypical Lymphocytes 32% 0-8%

RBC Morphology Normal Normal

PLT Count and Morphology Normal Normal

 
Patient’s Results Reference Range

Rapid Monospot Negative

Sample Agglutination

Positive Control 3+

Negative Control 0

Patient Sample 2+

Interpretation Positive

Patient’s Results Reference Range

EBV Antibody to Viral Capsid Antigen IgM 50.5 U/mL 0.0 - 43.9 U/mL
 

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Peripheral Blood Smear 

Manual differential showed pleomorphic population of many (32%) atypical lymphocytes favoring a reactive
process. Rare apoptotic lymphocytes (top right and bottom right panel shows apoptosis with nuclear
condensation and vacuoles) were also noted. Apoptosis, reactive lymphocytes, neutropenia, and monocytosis are
strong indicators of a viral infection, such as infectious mononucleosis.
 

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Diagnosis
The CBC showed that the patient had minor leukocytosis and >20% atypical lymphocytes. The ESR revealed a
high sedimentation rate. Finally, the EBV Antibody to Viral Capsid Antigen IgM test came back positive,
affirming the diagnosis of Mononucleosis.

Discussion
Infectious mononucleosis is a contagious clinical syndrome seen primarily in teenagers and young adults.
Infectious mononucleosis is most commonly caused by the Epstein-Barr virus (EBV) however other viruses can
also cause this disease. The virus is commonly spread through bodily fluids, especially saliva. Typical symptoms
of infectious mononucleosis include fatigue, headache, fever, sore throat and swollen lymph nodes with
symptoms lasting two to four weeks. Once infected the virus integrates itself into the cycle of healthy B
lymphocytes and remains as a lifelong latent infection. Reactivation of Epstein-Barr virus may occur in
immunocompromised patients and rarely, in immunocompetent patients and is occasionally associated with
malignancies such as Burkitt’s lymphoma.

Laboratory Test Explained

1. The CBC count is more useful in ruling out other diagnoses that may mimic IM. Leukocytosis is
considered the rule in infectious mononucleosis so the presence of a normal or decreased WBC count
should suggest an alternative diagnosis. Infectious mononucleosis is likely if the relative atypical
lymphocyte count is equal to or greater than 20%. Atypical lymphocytes should not be confused with
abnormal lymphocytes. Abnormal lymphocytes are associated with lymphoreticular malignancies,
whereas atypical lymphocytes are associated with various viral and noninfectious “benign” diseases.
2. ESR is most useful in differentiating group A streptococcal pharyngitis from EBV infectious
mononucleosis. The sedimentation rate is elevated in most patients with EBV infectious mononucleosis,
but it is not elevated in group A streptococcal pharyngitis. Because the liver is uniformly involved in
EBV infectious mononucleosis, mild elevation of the serum transaminases is a constant finding in early
EBV infectious mononucleosis. Mild increases in the serum transaminases are also a feature of the
infectious agents responsible for heterophile-negative infectious mononucleosis. High elevation of the
serum transaminases should suggest viral hepatitis. The serum alkaline phosphatase and
gamma-glutamyl transpeptidase levels are not usually elevated in individuals with EBV infx mono.
3. The monospot test is a latex agglutination assay that uses horse RBCs. Antibodies are sensitive and
specific for EBV heterophile ab. Sensitivity is ~85% and specificity is ~100%. The heterophile test is
less useful in children younger than 2 years, in whom the results are frequently negative.
 

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Method:​ ​The BBL-MonoSlide Mononucleosis Test is a rapid, differential test for the serological detection of IgM class
heterophile antibodies associated with infectious mononucleosis.

Principle: ​T​his test utilizes a disposable card, guinea pig kidney antigen for absorption, and specially treated horse
erythrocytes (color-enhanced) to increase specificity, sensitivity, and enhance readability.

4. EBV serological tests should be obtained in patients with a mononucleosis like illness and a negative
finding on the Monospot test. The antibody response to specific EBV serological testing consists of
measuring the antibody response to surface and core EBV viral proteins. For clinical purposes, the most
useful EBV-specific antibodies are the VCAs and the EBNA. Both VCA and EBNA antibodies are
usually reported as IgM or IgG antibodies. Acute infection is diagnosed in patients who have an
increased EBV IgM VCA titer. Later in the course of infection, the increase in IgM VCA antibodies may
be accompanied by an increase in IgG VCA antibodies and an increase in IgG EBNA antibodies.

References 
1. Lennon P, Crotty M, Fenton JE.​ Infectious mononucleosis.​ BMJ. 2015; 350: h1825. PubMed
2. Luzuriaga K, Sullivan JL.​ Infectious mononucleosis.​ N Engl J Med. 2010; 362(21): 1993-2000. PubMed
3. Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD.​ The immunology of Epstein-Barr
virus-induced disease.​ Annu Rev Immunol. 2015; 33: 787-821. PubMed
4. Vouloumanou EK, Rafailidis PI, Falagas ME.​ Current diagnosis and management of infectious
mononucleosis.​ Curr Opin Hematol 19:14-20, 2012.
5. https://www.cdc.gov/epstein-barr/laboratory-testing.html
 
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Samantha Dewey, MLS(ASCP)SH 

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