LYMPH NODE ASPIRATION
CLINICAL AND HEMATOLOGIC OBSERVATIONS IN 101
PATIENTS*
MAURICE MORRISON, M.D., A. A. SAMWICK, M.D., JOSHUA RUBINSTEIN, M.D.,
MELVIN STICH, M.D., AND LEO LOEYVE, M.D.
From the Jewish Hospital of Brooklyn, the Jeioish Sanitarium and Hospital for Chronic
Diseases, the Beth El Hospital and the Brooklyn Cancer Institute, Brooklyn, ATeio York
Lymph node aspiration has become an important adjunct to the study of
lymphadenopathies. 1 ' 3 " Si 8> 10 The procedure is of great value for the diagnosis
of Hodgkin's disease, lymphosarcoma, leukemia and infectious mononucleosis.
An aspiration may be repeated at intervals thus furnishing a guide to the effect
of treatment. This procedure may also obviate the necessity of surgical excision
of a node for biopsy. The most detailed recent study of the subject is the treatise
by Tage Strange of Copenhagen.9 The present report is based on our experiences
in 101 patients with biopsy of tissue aspirated from lymph nodes.
MATERIAL AND METHODS
The diagnoses are indicated in Table 1. In addition to lymph node aspiration,
other studies included those of peripheral blood and bone marrow, biopsy of
splenic tissue obtained by puncture 6 or surgical removal of the spleen, and of
surgically removed lymph nodes, and necropsy.
The apparatus required includes a 20-gauge needle, a dry syringe and an alcohol
sponge. No anesthetic is necessary. The operator grasps the node securely between the thumb and index finger of the left hand. He pierces the node, aspirates
the tissue rapidly and then promptly withdraws the needle. He then makes a
smear of the aspirate on a clean slide for staining with Wright's stain.
ILLUSTRATIVE CASES
1. Myelogenous leukemia. (Fig. 5). A. B., a woman, age 50, was admitted to the hospital
with pallor, fever, extreme adenopathy and ascites. The spleen extended four fingerbreadths
below the left costal margin and the liver, three fingerbreadths below the right costal
margin. The clinical picture favored a diagnosis of chronic lymphatic leukemia or Hodgkin's
disease because of the collar of enlarged lymph nodes about the neck and the extreme
enlargement of the nodes in the cervical, axillary and inguinal regions. The peripheral
blood study determined the true nature of the process and tissue aspirated from the lymph
node and spleen was confirmatory. The unusual feature was the striking lymph node involvement in a patient with myelogenous leukemia in a pre-agonal state.
2. Chronic lymphatic leukemia. (Figs. 3 and 4). A. G., a woman, age 62, represented a
typical instance of chronic lymphatic leukemia in an older person. The lymphoblasts were
prominent with a predominance of Grumel6e cells. This feature usually indicates either
that the patient is entering an acute phase, or that x-ray therapy has induced in the patient a tendency to lymphoblastic "left shift". The presence of the Grumel6e cell serves to
eliminate the diagnosis of lymphosarcoma. At times, this distinction is difficult. It may be
stated that, as pointed out by Strunge, the characteristic Grumel<5e cell is present in pre* Aided by a grant from the Jacques Loewe Research Foundation, New York, New York.
Received for publication, July 19, 1951.
255
256
MORRISON ET AL.
ponderant numbers only in lymphatic leukemia. In acute lymphatic leukemia or after
radiation therapy, lymphoblasts with characteristic nucleoli overshadow the presence of
Grumel^e cells.
3. Lymphosarcoma. (Fig. 2). M. Y., a woman, age 39, was admitted with pallor and ecehymoses. On examination, lymphadenopathy and an enlarged spleen were found. T h e
peripheral blood showed no evidence of the disease. The bone marrow showed an eosinophilia of 10 per cent. The latter finding suggested the possibility of Hodgkin's disease b u t
the lymph node aspirate revealed the presence of lymphosarcoma cells. A biopsy had resulted in a diagnosis of lymphadenitis. In view of this discrepancy, the pathologist reviewed
the original section and found evidence in it of lymphosarcoma.
4. Giant follicular lymphoblastoma. M. A., a woman, age 53, was admitted to the hospital
because of enlarged axillary and inguinal nodes. Lymph node aspiration revealed cells suggesting lymphosarcoma. Biopsy of a lymph node showed giant lymphfollicular lymphoblastoma.
TABLE 1
D I A G N O S E S IX 101 P A T I E N T S FROM W H O M L Y M P H N O D E T I S S U E WAS
ASPIRATED
LEUKEMIA
Acute myeloblastic
Chronic myelocytic
Monocytic
Chronic lymphatic
Chronic lymphatic, terminal (acute phase)
Stem cell
3
1
2
19
1
1
' -LYMPHOSARCOMA
Lymphosarcoma (small cell type)
Follicular lymphoblastoma
H O D G K I N ' S DISEASE
M E T A S T A T I C CANCER
INFECTIONS
Tuberculosis
Boeck's sarcoidosis
H e p a t i t i s , infectious
Infectious mononucleosis
Lymphadenitis
12
2
15
7
3
1
1
5
11
ANEMIAS
Congenital hemolytic icterus
Cooley's anemia
1
1
M I S C E L L A N E O U S CONDITIONS
Lipoid dystrophy
Chondroma
Cirrhosis of liver
A S P I R A T E D TISSUE INADEQUATE FOR DIAGNOSIS
1
1
1
12
5. Hodgkin's disease. (Fig. 1). S. D . , a man, age 35, was admitted to the hospital with
pain in the chest, fever, and generalized adenopathy. A lymph node aspiration revealed
evidence of Hodgkin's disease, i.e., Reed-Sternberg cells, monocytoid cells, pleomorphism
and eosinophilia. Some time later a biopsy confirmed the diagnosis.
6. Metastatic cancer. (Figs. 7 and S). A: B., a woman, age 64, was admitted to the hospital
because of carcinoma of the breast with axillary nodes. Lymph node aspiration confirmed
the diagnosis.
All figures were made from material aspirated from lymph nodes.
F I G . 1 (upper left). Dorothy-Reed cell in Hodgkin's disease. X 980.
F I G . 2 (upper right). " L y m p h o s a r c o m a " cell (Patient M. Y . ) . Notice large cells with
scant cytoplasm. These do not have appearance of Grumel<5e cells. X 1300.
F I G . 3 (lower left). Grumel(5e cell from P a t i e n t A. G. with chronic lymphatic leukemia.
N o t e checkerboard appearance of nucleoplasm and occasional lymphoblast. X 1300.
F I G . 4 (lower right). P a t i e n t A. G. with chronic lymphatic leukemia. Grumel6e cell,
enlarged. X 3000.
&t
if/
«/
ti%
m®.
%
/^.A*""
F I G S . 1-4
257
'HI *
258
MORRISON ET AL.
7. Infectious mononucleosis. (Fig. 6). E. L., a male college student, age 19, was admitted
to the hospital with two months' history of enlarged firm, nontender, discrete nodes in the
cervical, axillary, inguinal and occipital regions. There was no evidence of enlargement
of the nodes in the mediastinum. The liver and spleen were not enlarged. Cells suggestive
of infectious mononucleosis were seen in the peripheral blood and in tissue aspirated from
a node.
8. Lymphadenitis. B. S., a man, age 59, was admitted to the hospital with an enlarged
cervical lymph node. The liver and spleen were foundto be enlarged. Clinically a diagnosis
of Hodgkin's disease was suggested. The peripheral blood and bone aspiration'were noncontributory. Biopsy of a lymph node showed lymphadenitis, an occasional polymorphonuclear neutrophil, but no lymphoblasts, Crumel<?e or Reed-Sternberg cells.
DISCUSSION
.
Progress has been made within recent years in developing methods for the
diagnosis of a number of blood dyscrasias. In Hodgkin's disease, lymphosarcoma,
giant follicular lymphoblastoma, and metastatic cancer in the nodes, often no
definite diagnosis can be made on hematolqgjc.yfindings. At times the answer is
found only on biopsy or necropsy. Lymph-node aspiration is therefore a helpful
diagnostic method. In addition, certain instances of infectious mononucleosis
difficult of diagnosis and leukemia are recognized after study of tissue aspirated
from a lymph node. Some conditions, such as tuberculosis, Boeck's sarcoidosis
and metastatic cancer require further experience with the method of biopsy of
tissue aspirated from lymph nodes.
'
As will be noted in Table 1, approximately SO per cent of the patients studied
had leukemia, lymphosarcoma, Hodgkin's disease;'•lymphadenitis or metastatic
cancer. There were also 5 patients with infectious mononucleosis and 3 with
tuberculosis. Five of the patients were children, the youngest being four months
old and the oldest eight years old.
Table 2 offers a brief description of the cell type; the frequency of occurrence
and the specific condition where these cells are found.
Based upon the morphologic character of these elements, we set down tentative hematologic criteria for lymph node aspiration in different conditions
(Table 3).
In Table 4, one notes that lymph node aspiration provided the means for making the correct diagnosis most often in Hodgkin's disease, lymphosarcoma, lymphadenitis and metastatic cancer. In contrast, study of the peripheral blood alone
was diagnostic in' lymphatic leukemia and infectious mononucleosis. In our
study, information was obtained by concomitant aspirations of the spleen in
15 of 19 patients with lymphatic leukemia, in each of our 12 patients with lymphosarcoma, in three of our 15 subjects with Hodgkin's disease and in one of our
patients with giant follicular lymphoblastoma.
The question arises: will the diagnosis sometimes be overlooked in biopsy of
FIG. 5 (upper left). Patient A. B. with myelosis of lymph node in late chronic myelogenous leukemia. Note myelocytes and myeloblasts. X 1000.
FIG. 6 (upper right). Patient A. W. Large cells of infectious mononucleosis. X 2500.
FIG. 7 (lower left). Clusters of malignant cells within a lymph node. X 550.
FIG.-8 (lower right). Same as Figure 7. X 1100.
FIGS. 5-S
259
260
MORRISON ET AL.
aspirated tissue when the conventional biopsy would be more revealing? We have
never found this to be true. The same objection was raised in 1938 concerning the
feasibility of biopsy of aspirated bone marrow as compared to that of biopsy of
trephined bone marrow.2 In time, it was found that each method has its place.
Furthermore, bone marrow aspiration has become almost indispensable in hematology. We predict that similarly lymph node aspiration will prove of great value
in replacing or supplementing surgical biopsy in the hematologic study of the
TABLE 2
D E S C R I P T I O N OF C E L L T Y P E S N O T E D IN T I S S U E A S P I R A T E D FROM
LYMPH NODES
CELL TYPE
FREQUENCY
1. Small lymphocvte
2. Large lvmphocvte
3. Reticulum cell
S5%
15%
Occasional
4. Syncytial cell
Occasional
5. l l c m o e y t o b l a s t
Occasional
6. Grumelee cell*
Many
7. Lymphoblast
Occasional
8. Infectious mononucleosis cell
Many
0. Myeloblast
10. Monocytoid cell
Many
Occasional
11. E r v t h r o i d elements M a n y
OCCURRENCE
DESCRIPTION
Same as peripheral blood
Same as peripheral blood
Large nucleus (2-3 times size
of small lymphocyte) surrounded by irregular cytoplasmic processes
Groups of reticulum cells in
masses with a common
bluish cytoplasmic background
Inflammations,
Large cell (4-5 times size of
small
lymphocyte)
with
lymphosarcoma
large nucleus of fine texture
with one or more nucleoli,
surrounded by a deep basophilic cytoplasm (forerunner of lymphoid series)
elements
with
L y m p h a t i c leukemia Lymphoid
" c h e c k e r b o a r d " nucleus
Normal and inflam- Lymphoid
elements
with
. mations
nucleoli
Infectious monoLarge lymphoid elements with
indented nucleus and bluish
nucleosis
cytoplasm
Myeloses
Same as peripheral blood
Like monocytes in peripheral
Hodgkin's disease
blood, occasionally
with
more t h a n one nucleus—
Reed-Sternberg cells
Extramedullar}'
Same as peripheral blood and
hematopoiesis;
bone marrow
spent polycythemia; osteosclerotic anemia
Normal
Normal
* T h e t e r m " G r u m e l e e " is freely used b y Tage Strunge in his monograph. 9 I t is t a k e n
from the French language and literally means " c l o t t e d " . I t applies to a cell with
a lymphocytic nucleus of mosaic appearance and a " c h e c k e r b o a r d " configuration.
lymphadenopathies. At any rate, cytologic study of material aspirated from the
lymph node is meant to be an adjunct and not a substitute for histologic study.
It is easier to convince a patient to have an aspiration for cytologic study or
biopsy than to have him submit to the conventional surgical removal of a lymph
node for biopsy.
SUMMARY
Lymph node aspiration is a relatively simple procedure and can often be repeated either for subsequent study or in determining the effect of treatment.
261
LYMPH NODE ASPIRATION
TABLE 3
CHARACTERISTIC F I N D I N G S IN T I S S U E A S P I R A T E D FROM L Y M P H
NODES
I. H O D G K I N ' S DISEASE
A.
B.
C.
D.
E.
D o r o t h y Reed-Sternberg cells
Increase in monocytoid cells
Eosinophils
Polymorphonuclear neutrophils (10 to 50 per cent)
Increase in large lymphoid cells. R a t i o of small to large (S:L) lymphoid
cells is 30:70 (normal S:L, 90:10)
¥. Reticulum cells
II.
LYMPHOSARCOMA
A. Large lymphoid cells increased (S:L, 10:90). These cells have large nuclei,
rare nucleoli and scant cytoplasm (no " c h e c k e r b o a r d " appearance).
B. Mitotic figures prominent
C. Occasional hemocytoblast
111.
LYMPHATIC LEUKEMIA
A. Chronic
1. Small lymphoid cells (Grumel6e cells) increased (S:L, 90:10). These cells
are medium-sized and have a " c h e c k e r b o a r d " appearance.
2. Large lymphoid elements (rare)
3. No polymorphonuclear neutrophils
B. Acute
1. Few Omnicide cells
2. Preponderance of lymphoblasts with nucleoli
3. Rare mitotic figure
C. Subacute
1. Grumelde cells and lymphoblasts equal in number
lV. r M Y E L O G E N O U S LEUKEMIA
A. Chronic, myelocytes (90 per cent of the cells)
B.' Acute, myelocytes (90 per cent of the cells)
V.
L Y M P H A D E N I T I S , IRRITATIVE
A.
B.
C.
D.
VI.
R a t i o of small to large lymphoid elements (S:L, S0:20)
Moderate number of polymorphonuclear neutrophils
Occasional hemocytoblast
R a r e eosinophil
L Y M P H A D E N I T I S , INFECTIOUS
(PURULENT)
A. Many polymorphonuclear neutrophils, degenerated, " t o x i c "
B. M a n y smudged cells
VII.
I N F E C T I O U S MONONUCLEOSIS
A. Large cells with indented nucleus and a b u n d a n t basophilic cytoplasm
B. Lymphoblasts (rare)
C. No polymorphonuclear neutrophils
V I I I . N O D E WITH METASTATIC CANCER
A. Clusters of atypical cells
B . Mitotic figures
IX.
G I A N T FOLLICULAR
LYMPHOBLASTOMA
(Same as lymphosarcoma with addition of occasional monocytoid and small
lymphoid cells)
TABLE 4
COMPARATIVE D I A G N O S T I C V A L U E OF S T U D I E S OF P E R I P H E R A L BLOOD, B O N E
M A R R O W AND LYMPH N O D E A S P I R A T I O N IN P A T I E N T S WITH
LYMPHADENOPATHY
Hodgkin's disease
Lymphosarcoma
Infectious mononucleosis
Lymphadenitis
M e t a s t a t i c cancer
L y m p h a t i c leukemia
NO. OF
BLOOD
STUDIES
PER CENT
OK CORRECT
DIAGNOSES
NO. OF BONE
MARROW
STUDIES
15
12
5
11
7
19
0
0
100
0
0
100
15
12
5
11
7
19
PER CENT
OF CORRECT
DIAGNOSES
0
0
0
0
0
100
NO. OF
LYMPH NODE
STUDIES
PER CENT
OF CORRECT
DIAGNOSES
15
12
5
11
7
19
S3
SO
100
90
. 100
100
262
MORRISON ET Ah.
Aspiration of material from enlarged lymph nodes will often provide diagnostic
hematologic data in Hodgkin's disease, lymphosarcoma, lymphadenitis and
metastatic cancer.
A description is given of type cells encountered in material aspirated from enlarged nodes. Criteria are given for the diagnosis of enlargement of lymph nodes,
based on cells found in the aspirate.
1.
BOVER,
1947.
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Company, 1949, p. 301.
3. F O R K N E R , C. E . : Material from lymph nodes of man. Studies on living and fixed cells
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578-589, 1934.
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SAMWICK, A.
A.,
R U B I N S T E I N , J.,
MORRISON, H.,
AND L O E W E ,
L.:
Splenic aspiration. J. A. M. A., 146: 1575-1581, 1951.
8. PAVLOVSKY, A.: La Ponction Ganglionar: Su Conticucion al Diagnostico Clinicoquirurgico de las Affeciones Ganglionares. Buenos Aires: Thesis, 1934, 82 p p .
9. STRUNGE, T . : La Ponction des Ganglions Lymphatiques. Copenhagen: Ejnar M u n k s gaard, 1944, 137 p p .
10. T E M P K A , T., AND KUBICZEK, M . : Normal and pathological lymphadenograin in t h e
light of own research. Acta med. Scandinav., 131: 434-450, 1948.