Extension of Myeloid Tissue into the
Lower Extremities in Polycythemia
JOHN E. KURNICK, M.D., TARIQ MAHMOOD, M.D., NICHOLAS NAPOLI, M.D., AND MATTHEW H. BLOCK, PH.D., M.D.
Kurnick, John E., Mahmood, Tariq, Napoli, Nicholas, and
Block, Matthew H.: Extension of myeloid tissue into the lower
extremities in polycythemia. Am J Clin Pathol 74: 427-431,
1980. Biopsies of the posterior iliac crest, greater trochanter,
and proximal tibia were done for 27 polycythemic patients
before myelosuppressive therapy was begun. Five had relative
polycythemia, thirteen had secondary polycythemia, and nine
had polycythemia vera. None of five biopsy specimens of the
greater trochanter in cases of relative polycythemia contained
myeloid tissue (erythroblasts, granulocytic precursors, and
megakaryocytes). Four of six biopsy specimens of the greater
trochanter and one of eight of the tibia in cases of secondary
polycythemia contained myeloid tissue. All seven biopsy
specimens of the greater trochanter and two of five biopsy
specimens of the proximal tibia in cases of polycythemia vera
contained myeloid tissue. A trochanter biopsy specimen devoid
of myeloid tissue probably eliminates the diagnosis of polycythemia vera. Myeloid tissue extends from the axial skeleton to
the greater trochanter, thereafter to the tibia. Extension of
myeloid tissue does not imply that marrow failure is imminent
in polycythemia vera. (Key words: Myeloid tissue; Polycythemia; Bone marrow biopsy.)
EXAMINATION of sections of aspirated sternal
marrow for the diagnosis and differential diagnosis of
polycythemia vera was first reported in 1950.2 Such
examination to evaluate the effect of treatment with
F 2 was reported in 19524 and 1954.5 In 1972 we emphasized the sharp contrast between the grossly panhyperplastic sections of sternal and iliac crest marrow
of patients having polycythemia vera untreated by
myelosuppressive therapy and the usually normocellular or erythroid hyperplastic sections of the
marrow in patients having secondary polycythemia."
The latter report included one case with a solidly
cellular biopsy specimen of the greater trochanter of
the femur from a patient who had polycythemia vera.
We suggested that the differential diagnosis of polycythemia vera from secondary polycythemia might be
further simplified by an examination of this normally
acellular (fatty) site. In 1972 a preliminary report
Received October 24, 1979; accepted for publication November
19, 1979.
Supported in part by General Clinical Research Center RR 000-51.
Dr. Mahmood is a Research Associate of the United States
Veterans Administration.
Address reprint requests to Dr. Block: Hematology Division,
University of Colorado Medical Center, Denver, Colorado 80262.
Department of Medicine, University of Colorado School
of Medicine, and the Denver Veterans Administration
Hospital, Denver, Colorado
indicated that examination of trochanteric marrow
might be useful in diagnosis, differential diagnosis,
and evaluation of the effect of therapy on polycythemia
vera." 1 In 1976 the role of the histopathology of the
marrow in the axial and, to a minor extent, the appendicular skeleton was retrospectively evaluated in
polycythemic disorders. 3
In the present prospective investigation, we have
analyzed in detail sections of a total of 58 marrow
biopsy specimens from the posterior iliac crest, trochanter, and proximal tibia from polycythemic patients
before they were given myelosuppressive therapy,
to test the hypothesis that examination of marrow
from these two sites yields useful data by which polycythemia vera may be differentiated from secondary
polycythemia. The biopsies are easy to perform and are
well tolerated by the patients.
Materials and Methods
All patients examined at the Colorado General
Hospital or the Denver Veterans Administration
Hospital (DVAH) between 1974 and 1977 who had
packed cell volumes greater than 55% and who had not
been previously treated with F 12 or other myelosuppressive agents were eligible for this study. Informed
consent in accordance with the rules of the Human
Research Committee was obtained from each patient.
The following studies were done: (1) complete history
and physical examination; (2) complete blood count
with differential and platelet count; (3) erythrocyte
mass by 5l Cr and plasma volume by ''"I-labeled serum
albumin; (4) arterial blood gases on room air; (5) leukocyte alkaline phosphatase score; (6) serum vitamin B,2
concentration; (7) iliac crest bone marrow biopsy; (8)
biopsy of the greater trochanter of the femur and/or
proximal tibia. The first six studies were performed
by standard laboratory methods; Jamshidi needles
were used for the marrow biopsies."
Biopsy of the greater trochanter is done with the
0002-9173/80/1000/0427 $00.75 © American Society of Clinical Pathologists
427
FIG. 1. Core biopsy specimens obtained by an 8-gauge Jamshidi
needle from a 61-year-old woman with polycythemina vera untreated by myelosuppressive therapy. All biopsy specimens were
obtained within 24 hours of each other. Hematoxylin and eosinazure II. x400. (Upper, left) Iliac crest, 4+ cellularity, (77S-6253).
(Upper, right) Greater trochanter, 3+ cellularity (77S-6272).
(Lower) Proximal tibia, 2+ cellularity (77S-6274).
Vol. 74 . No. 4
429
EXTENSION OF MYELOID TISSUE IN POLYCYTHEMIA
patient in the lateral decubitus position. The usual skin
preparation, local anesthesia, and intravenous sedation with 5 to 15 mg of diazepam and analgesia with 50 to
100 mg of meperidine are recommended. The skin is
nicked with an abscess blade over the point where the
greater trochanter is closest to the skin. The biopsy
needle is inserted parallel to the long axis of the femur
and angled 30 degrees caudad from perpendicular because the trochanter forms an oblique angle of 120
degrees with the femoral shaft. Pressure is exerted
upon the biopsy site as soon as the biopsy needle
is withdrawn, and the patient is placed in the
lateral decubitus with the biopsy site resting on a sandbag for about four hours to prevent extravasation of
blood through the hole in the cortex. Although the
trochanteric cortex requires more force to enter than
the cortex of the posterior iliac crest, the biopsy causes
less discomfort than an iliac crest biopsy, probably
because the wide trochanter offers a better target than
the posterior or anterior iliac crest.
To do a biopsy of the proximal tibia the patient is
medicated as described for the greater trochanter.
With the patient supine, the needle is screwed through
the cortex at the level of the tibial tuberosity midway
between the anterolateral and posteromedial edges of
the tibia, at right angles to the flat surface of the tibia.
As with the trochanter, the tibial cortex is difficult to
penetrate. Pressure with a sandbag must be applied to
the biopsy site as soon as the biopsy needle is withdrawn to prevent extravasation of blood. Sandbag
pressure is continued for four hours, and the patient is
kept in bed overnight.
Biopsy specimens obtained at Colorado General
Hospital were fixed in neutral Zenker's formol solution, embedded in methacrylate, sectioned at 1.5 to
2.5jum, and stained with hematoxylin and eosin-azure
II.' 7 Biopsy specimens obtained at the DVAH were
fixed in Zenker's solution, cut in paraffin at 6 /AITI, and
stained with hematoxylin and eosin or Giemsa stain.
Posterior iliac crest biopsies were scored by a modification of the method of Ellis and associates 7 (Figs. 1 and
2). Since the greater trochanter and proximal tibia
in adults are normally devoid of myeloid tissue, any
myeloid tissue in these two areas is abnormal (Fig. 2).3-,i
The criteria of the Polycythemia Vera Study Group
were used forthe diagnosis of polycythemia vera (Table
1).' These criteria require an elevated erythrocyte
volume (males, s 3 6 ml/kg; females, ^32 ml/kg), an
arterial oxygen saturation > 92%, and either splenomegaly or two of the following four: (1) direct platelet
count > 400 x 10"/1: (2) leukocyte count > 12 x 10li/l
in the absence of fever or infection; (3) leukocyte alkaline phosphatase score > 100; (4) serum B, 2 binding
capacity > 2,200 pg/ml. The diagnosis of secondary
polycythemia was made on the basis of an elevated
13
»• •
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•
•
•
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8
> • •
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» • •
12
•
•
•
•
•
•
•
•
•
•
•
•
> • •
• •
> •• • •••
> •• • •••
PIC GT PT
PV
••• ••• •
PIC
• •
• •
• •
» • •
'3\
• •
» •• • •• •
•V,
2
GT PT
SP
5
1
1
5
5
5
PIC GT
RP
FIG. 2. Myeloid tissue in 58 marrow biopsy specimens obtained
from 27 polycythemic patients. The number of cases examined at
each biopsy site is listed at the top of each column. The number
of cases in each category of cellularity is listed in the vertical columns.
The greater trochanter and proximal tibia are normally devoid of
hematopoietic tissue. PIC, posterior iliac crest; GT, greater trochanter; PT, proximal tibia; PV, polycythemia vera; SP, secondary
polycythemia; RP, relative polycythemia. White areas, no myeloid
tissue; left-striped areas, 1+ (<35% myeloid tissue); dotted areas.
2+ (35%-54% myeloid tissue); right-striped areas, 3+ (55%-89%
myeloid tissue; solid areas, 4+ (90%-100% myeloid tissue).
erythrocyte volume and an arterial oxygen saturation
less than 90%, since all cases were secondary to pulmonary insufficiency. Patients whose erythrocyte cell
volumes were below the upper limit of normal for their
sex despite an elevated packed cell volume were considered to have relative polycythemia.
Results
Nine patients satisfied the criteria for polycythemia
vera, 13 for secondary polycythemia, and five for
relative polycythemia. Table 1 lists the pertinent clinical
and laboratory data, and Figure 2 the histopathologic
data, for the three patient populations.
Myeloid tissue was increased in amount in the iliac
crest of eight of nine patients who had polycythemia
vera (Fig. 2). The greater trochanter of all patients
who had polycythemia vera had myeloid tissue ranging
from 2+ to 4+ cellularity. The tibia of two of five patients who had polycythemia vera had 2+ cellularity. In
430
KURNICKE7ML.
A.J.C.P. . October 1980
Table 1. Clinical and Laboratory Data for the Patients Studied*
Polycythemia vera
(N = 9)
Secondary erythrocytosis
(N = 13)
Relative erythrocytosia
(N = 5)
Age
(Years)
Sex
(M:F)
67.7
(43-81)
54.2
(30-63)
6.04
(56-65)
4:5
10:3
4:1
Packed
Cell
Volume
(%)
Erythrocyte
Mass
(mVkg)
Sa0 2
(%)
Leukocyte
Count
(109/1)
Platelets
(109/1)
Leukocyte
Alkaline
Phosphatase
(Kaplow Units)
Serum
B12
(pg/ml)
60.4
(55-66)
60.0
(55-67)
57.6
(56-61)
50.1
(33-77)
43.6
(36-57)
30.7
(29-33)
93.4
(92-96)
82.9
(71-89)
92.6
(990-95)
19.6t
(6.7-35.3)
8.0t
(4.2-12.5)
8.3§
(6.3-14.0)
729t
(190-2600)
21 It
(75-488)
257
(133-381)
153t
(67-246)
78*
(10-178)
76
(50-93)
853t
(330-1230)
597
(330-812)
523
(330-700)
* Each figure represents the mean for the group. Figures in parentheses represent the
range.
t Leukocyte count < 12 in 1/9; platelets <400 in 2/9; leukocyte alkaline phosphatase < 100
in 2/9; serum B„ <900 in 3/9.
$ Leukocyte count >12 in 1/13; platelets >400 in 1/13; leukocyte alkaline phosphatase
>100 in 4/13.
§ Leukocyte count >12 in 1/5.
the three patients who had polycythemia vera who had
biopsies of all three sites—iliac crest, trochanter, and
tibia—myeloid tissue was 4+, 3 + , and 0; 4+, 3 + , and
2+ (Fig. I); and 4+, 2+, and 0, respectively. No marrow contained fibrous tissue demonstrable by hematoxylin and eosin or hematoxylin and eosin-azure
II stains.
Twelve of 13 patients who had untreated secondary polycythemia had normal myeloid tissue, and one
had a moderate increase in erythroid tissue in the
posterior iliac crest. Four of six patients who had secondary polycythemia had myeloid tissue in the greater
trochanter. Only one of eight patients who had secondary
polycythemia had myeloid tissue in the proximal tibia.
In the one patient who had secondary polycythemia
who had biopsies of all three sites, the iliac, trochanteric,
and tibial cellularities were 2+, 2+, and 0, respectively.
The five patients with relative polycythemia had
normal myeloid tissue in the iliac crest marrows and
none in the greater trochanter.
occupied less than 60% of the marrow in only 10% of
patients who had polycythemia vera untreated by
myelosuppressive therapy.7
Parkes-Weber commented in 1921 on the replacement of fatty marrow by red marrow in the shaft of the
long bones in autopsy specimens from patients who
had polycythemia vera.13 He cited a report of a biopsy
of the tibial shaft performed in 1908 under general
anesthesia in a patient who had polycythemia vera.8
This biopsy contained islands of erythropoiesis, and
its mention is the earliest we could find of a biopsy of
a long bone performed solely for the purpose of assessing
hematopoiesis in polycythemia vera.
The 52Fe positron camera studies of Van Dyke and
Anger and Van Dyke and associates demonstrated erythropoietic tissue in the proximal tibia of a patient
early in the natural history of polycythemia vera.1415
We found myeloid tissue in the proximal tibia in only
two of five patients. All our patients had myeloid tissue
in the greater trochanter (therefore, also in the proximal
femur), confirming the positron scans of Van Dyke and
associates15 and the autopsy data of Parkes-Weber.13
Van Dyke and associates also correlated the presence of erythroid tissue in the tibia (their type IV)
with impending marrow failure.15 We doubt this interpretation because two of our patients with myeloid
tissue in the tibia remained in the proliferative phase of
their diseases one to three years after biopsy. Van Dyke
and associates also implied that hematopoietic tissue in
the tibia will eventually develop in all patients who
have polycythemia vera.15 This can only be determined
by repeated observations of individual patients. However, our data and the data of Van Dyke and associates
show that all patients who have hematopoiesis in the
tibia also have hematopoiesis in the femur and posterior
iliac crest, and the reverse never occurs. Our data also
show that the amount of hematopoietic tissue decreases
from posterior iliac crest to greater trochanter to
proximal tibia.
Comment
Custer and Ahlfeldt showed that the proximal femur
and tibia of normal adults are devoid of myeloid tissue.6
Wallner and Block demonstrated a similar absence of
myeloid tissue in the greater trochanter.16 Since the
current investigation we have altered our biopsy technic
to include marrow from the proximal femur while doing
the greater trochanter biopsy. The femoral marrow is
identical to that in the greater trochanter. In contrast,
the 52Fe positron camera studies of Van Dyke and
AngerH demonstrated erythropoietic tissue in the
proximal femur of normal adults.
This study confirms prior reports on the hypercellularity of the iliac crest marrow in about 90% of
patients who had polycythemia vera untreated by
myelosuppressive therapy.2_510_12 In the detailed and
extensive study of Ellis and associates, myeloid tissue
Vol. 74 • No. 4
EXTENSION OF MYELOID TISSUE IN POLYCYTHEMIA
Myeloid tissue was present in four of six trochanters
and in one of eight tibias in patients who had secondary
polycythemia, in contrast to its uniform presence in
the greater trochanter in patients who had polycythemia
vera. The absence of myeloid tissue in the greater
trochanter therefore mitigates against the diagnosis of
polycythemia vera. It was surprising that extension
of myeloid tissue occurred in patients who had secondary polycythemia even when its concentration
in the posterior iliac crest was usually in the range of
normal variation. It was not surprising that the trochanters of all five patients who had relative polycythemia were devoid of myeloid tissue, since such patients do not have increased red cell volumes but rather
low plasma volumes. Hence, there is no stimulation to
form erythrocytes at an increased rate.
Although biopsy of the greater trochanter and proximal
tibia has less differential diagnostic value than we had
anticipated, our findings suggest that examination of
the appendicular skeleton may be of value in staging
polycythemia vera at onset and in following its natural
history and modification by therapy.
References
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Semin Hematol 12:339-351, 1975
2. Block M: Sections vs smears in the study of bone marrow, Illinois
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3. Block M: Myeloproliferative diseases, Text-atlas of hematology,
Philadelphia, Lea and Febiger, 1976, pp 33-36; 277-280
4. Block M, Berthard W: Bone marrow studies in polycythemia, J
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16. Wallner S, Block M: The clinical usefulness of biopsy of the
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