A 65 year old man has not seen a physician for 5 years. He has been feeling tired and has had to buy a larger shirt size because of an increase in the size of his neck. On physical examination, he was found to have enlarged cervical and axillary lymph nodes, and moderate splenomegaly. His CBC was abnormal. His physician ordered a lymph node biopsy.
CBC:
Patient
Normal Male
WBC
150x103
3.5 – 10.6 x103/μL
Bands
0
0 – 720 /μL
Neutrophils
7,500
1,730 – 7,100 /μL
Monocytes
1,500
70 – 870 /μL
Lymphocytes
141,000
900 – 3,120 /μL
Eosinophils
0
0 – 490 /μL
Basophils
0
0 – 140 /μL
RBC
3.5
4.27 – 5.69 x106/μL
HGB
9.8
13.3 – 17.1 g/dL
HCT
33
38.9 – 48.0 %
MCV
84
81.0 – 98.0 fL
MCH
30
27.1 – 34.0 pg
Platelets
160x103
150 - 450 x103/μL
Question #1: What would you like to do next?
Correct answer! since it is simple, quick, informative about the diagnosis and can guide further work up and management decisions.
VM System: Click here to view this patient's blood smear.
Wrong answer! You should never make treatment decisions before establishing a diagnosis
Wrong answer! Although the BM is most likely involved by the same process when the WBC is this high, doing BM procedure is not necessary before examining the blood smear and may not be needed. You can get the same diagnostic information by examination of the blood, thus avoiding patient discomfort, expense and save time
Wrong answer! This is not appropriate decision before examining the blood smear. Admitting the patient is appropriate if you suspect acute leukemia after blood smear review; however, most patients with chronic leukemia can have such a high WBC without need for immediate treatment or admission to the hospital
Question #2: Based on your review of the patient’s blood smear, what is the predominant WBC type?
Wrong answer! Blast cells are large in size- about 2-4times the size of red blood cells- have open chromatin network and one or more nucleoli. Presence of blasts suggest acute leukemia
Wrong answer! These cells have abundant cytoplasm with ground-glass appearance and vacuoles; the nucleus is irregular shape
Correct answer! Round cells with scant amount of cytoplasm, high nuclear to cytoplasm (N:C ratio) and clumped chromatin of the nucleus
Wrong answer! These cells have multilobed nuclei, irregular shape and granules in the cytoplasm
Question #3: The lymphoid cells in this patient’s blood are best described as which of the followings?
Correct answer! Cells are small with round nucleus about the size of red blood cell, chromatin is clumped, scant amount of blue cytoplasm without granules
Wrong answer! These cells are larger than mature lymphocytes with more abundant cytoplasm, nuclear chromatin is clumped (which is a sign of cell maturation) and a nucleolus (a sign of cell immaturity)
Wrong answer! Lymphoblasts are larger cells, 2-3 times the size of red blood cells with open chromatin network of the nucleus and one or 2 nucleoli; cytoplasm is usually deep blue
Wrong answer! These cells-which form about 10% of normal lymphocytes- are larger in size with more abundant cytoplasm that has azurophilic granules
Question 4: This patient’s blood smear picture is most consistent with which of the following types of leukemia?
Wrong answer! AL is characterized by the presence of BLAST cells in blood and/or bone marrow
Wrong answer! In this case you will see increased WBC of the myeloid (granulocytic) series at different stages of maturation; cells will have granulated cytoplasm
Correct answer! This disease is characterized by increased number of mature-looking lymphocytes indistinguishable from normal lymphocytes, just increased number
Wrong answer! Hairy cells are usually larger than normal lymphocytes, characteristically distinguished by their irregular cytoplasmic membrane due to hair-like projections
Question 5: At low power projection, is the LN architecture preserved or effaced (replaced)?
Wrong answer! Normal architecture of LN consists of the cortex (which contains the lymphoid follicles) and medulla with its loose medullary cords. In this case, one cannot distinguish between the cortex and medulla
Correct answer! The normal architecture of LN is diffusely replaced by sheets of cells throughout the LN. This pattern suggests a malignant process
Question 6: What is the predominant cell (use high power projection)?
Correct answer! Most of the cells in this LN section are mature, normal-looking lymphocytes similar to the ones seen in the blood smear. In tissue sections, small cells appear as darkly-stained nuclei with only tiny clear spaces in between.
Wrong answer! Large cells in tissue sections have ‘vesicular’ (less darkly stained) nuclei surrounded by clear cytoplasm. Such cells are seen in aggressive non-Hodgkin’s lymphoma.
Wrong answer! This description is typical of Hodgkin lymphoma where the ‘heterogeneous’ cell population represent normal reactive host cells like lymphocytes, plasma cells, histiocytes and eosinophils. The large binucleated cells refer to the Reed-Sternberg cells.
Question 7: Based on the information you have so far, what is the most likely diagnosis?
Wrong answer! As a time-honored principle in clinical medicine, you should always try to explain all findings in a given patient by one underlying Pathology. Your clue in this case is the presence of increased number of mature lymphocytes in the blood and replacement of the lymph node by the same cells.
Wrong answer! Histologically, HL is characterized by presence of heterogenous population of cells and typical or variant Reed-Sternberg cells which are not seen in this case. Moreover, it is very unusual for HL patients to have such a high WBC count.
Correct answer! This case is typical example of a ‘leukemia/lymphoma syndrome’ where features of both entities are present in the same patient, ie. Leukemia as indicated by high WBC count due to presence of malignant cells and Lymphoma due to presence of enlarged lymph nodes (lymphadenopathy). The common underlying Pathology in this case is malignant transformation of mature-looking B-lymphocytes which have, with time, populated the lymph nodes, blood and other organs.
Wrong answer! This is an acute disease of the young characterized by fever, sore throat and malaise. Leukocytosis and lymphocytosis are common in this disease but rarely, if ever this high. The lymphocytes are larger than normal with more abundant cytoplasm.
Question 8: Which of the following tests would you order next to confirm the diagnosis?
Wrong answer! Practically all tests needed to establish and confirm the diagnosis in this case can be done on the peripheral blood lymphocytes which are abundant and readily obtainable. The bone marrow in such cases will show involvement by the same abnormal lymphocytes just as shown in the lymph node biopsy. Doing a bone marrow, therefore is not necessary and can cause pain/discomfort, add to patient cost and may delay work up.
Correct answer! This test is diagnostic when CLL/SLL is suspected. A typical phenotype will show expression of B-cell markers by the lymphocytes (CD 19 and CD20) with light chain restriction (kappa or lambda) and co-expression of CD5. The only other disease which co-expresses this combination is mantle cell lymphoma (MCL). Two additional markers are used to distinguish between the 2 entities: CLL/SLL is CD23+, FMC7- whereas MCL is CD23-, FMC+.
Wrong answer! The patient has no sore throat or acute symptoms. Moreover, it is not usual to have this degree of leukocytosis with benign infectious conditions.
Wrong answer! These titers are useful when you suspect infectious mononucleosis.
Question 9: Was the lymph node biopsy necessary?
Wrong answer! The LN is involved by the same cells in the blood; the diagnosis can be established through blood tests without a need for LN biopsy. Always check CBC in patients with lymphadenopathy before deciding on LN biopsy. Like this case, CBC may reveal strong clues to the diagnosis and indicate where blood can be used to establish a diagnosis without LN biopsy.
Correct answer! The CBC in this patient provided key information about the diagnosis which readily explains the lymphadenopathy as part of the CLL/SLL clinical picture.
Question 10: Using the Rai system, what is the stage of disease in this patient?
Wrong answer! In this stage there is only lymphocytosis.
Wrong answer! In this stage, the lymph nodes are enlarged but there is no anemia or thrombocytopenia.
Wrong answer! In this stage, the liver and/or spleen are enlarged regardless whether there is lymphadenopathy or not; no anemia or thrombocytopenia.
Correct answer! In this stage, there is anemia (Hb<11gm/dl) regardless of status of LN, liver or spleen.
Fast Facts about this disease
- CLL/SLL is a chronic incurable disease with median survival ranging from 2years in advanced stages (Rai III-IV) to more than 12 years for early stages. It is disease of the elderly.
- Complications of CLL are 10-15% - autoimmune hemolytic anemia, thrombocytopenia.
- Serum hypogammaglobulinemia and increased susceptibility to bacterial infections.
- Transformation to diffuse large B-cell lymphoma (Richter’s Syndrome)
Wrong answer! In this stage, the platelets are <100K regardless of requirements in stages I-III.