BRIEF SCIENTIFIC REPORTS
Vol. 79 • No. 2
centrated in the removed fragments was small, it was
necessary to allow the fragments to remain on the x-ray
cassette for two to eight hours for a "shadow" to form
on the x-ray film. In addition, x-ray cassettes with sensitive intensifying screens, such as rare earth screens,
were used.
Results
In all three cases, autoimaging on undeveloped x-ray
film was positive, and furthermore, the fragment with
most intense autoimaging corresponded to the microscopically proven nidus.
In case 1, only one specimen was received, a 3 X 2
X 1 centimeter fragment of cortical bone from the right
tibia of a 21-year-old man. Fine grain specimen x-rays
failed to show a nidus, but serial slices and subsequent
specimen x-rays revealed a 0.3-cm nidus (Fig. 1). Autoimaging was performed prior to slicing; it revealed
intense autoimaging.
In case 2, two bone specimens (0.5 and 0.8 cm, respectively) were excised from the right cuboid bone of
a 24-year-old man. Both were radiodense on specimen
x-rays (Fig. 1A) and both showed autoimaging (Fig. IE).
The osteoid osteoma was identified microscopically in
the more intense autoimaging sample.
In case 3, multiple bone samples were excised from
the right femur of a 34-year-old woman. The specimen
x-ray failed to identify the nidus (Fig. 3A). However, the
osteoid osteoma corresponded to the most intense autoimaging sample (Figs. 3B and 3C).
Discussion
Although the etiology of osteoid osteomas remains
obscure, it causes pain and requires surgical excision.
In some cases of clinically suspected osteoid osteoma,
the nidus is not found.4 Failure to surgically localize the
225
lesion or identify it pathologically in multiple submitted
specimens are probable explanations. Since bone scanning with 99mTc-labeled diphosphonate compounds has
been used to localize a broad range of osseous lesions,
including osteoid osteoma,1'3'6 we utilized a preoperative
technetium injection to localize the lesion intraoperatively and autoimaging of the excised fragments to identify the nidus pathologically. In all our cases, the nidus
showed the hottest autoimaging.
In summary, utilization of autoimaging has several
advantages over routine processing. Since it directs attention to the hottest fragment, which we have found
corresponds to the nidus, it should decrease the instances
of false-negative reports that presumably are due to sampling errors. Coupled with preoperative scanning and
intraoperative localization by scintillation probe, it assists in conservative surgical excision and, therefore, is
of considerable benefit to the patient.
Acknowledgments: The authors thank Ms. Jean Kilfoyle and Georgia Clingen for technical assistance, Ms. Dottie Page and Mr. Tony
Labissiere for photographic assistance, and Mrs. Pat Bennett for preparing the typed manuscript.
References
1. Bohne WHO, Levine DB, Lyden JP: 18F Scintimetric diagnosis
of osteoid osteoma of the carpal scaphoid bone. Clin Orthop
1975; 107:156-158
2. Ghelman B, Thompson FM, Arnold WD: Intraoperative radioactive localization of an osteoid osteoma: case report. J Bone
Joint Surg [Am] 1981; 63A:826-827
3. Gore DR, Mueller HA: Osteoid-osteoma of the spine with localization aided by "TC-Polyphosphate bone scan: case report.
Clin Orthop 1975; 113:132-134
4. Sim FH, Dahlin DC, Beabout JW: Osteoid osteoma. Diagnostic
problems. J Bone Joint Surg [Am] 1975; 57A:154-159
5. Swee RG, McLeod RA, Beabout JW: Osteoid osteoma. Detection,
diagnosis, and localization. Radiology 1979; 130:117-123
6. Winter PF, Johnson PM, Hilal SK, Feldman F: Scintigraphic detection of osteoid osteoma. Radiology 1977; 122:177-178
Intravascular Hematopoiesis in Chorionic Villi
ELIZABETH ALENGHAT, M.D. AND JOHN R. ESTERLY, M.D.
Mitotic figures can be found in the immature blood cells in the
fetal vessels of placental tissue in abortion specimens. Intravascular mitoses were noted only in the absence of degenerative
Department of Obstetrics and Gynecology and Pathology,
The University of Chicago, Chicago, Illinois
Received April 30, 1982; received revised manuscript and accepted
for publication June 21, 1982.
Address reprint requests to Dr. Esterly: Department of Obstetrics
and Gynecology, The University of Chicago, 5841 Maryland Avenue,
Chicago, Illinois 60637.
changes and during the first trimester of gestation. This finding
suggests that the vascular component is a normal site of hematopoiesis during this stage of development. (Key words:
Placenta; First trimester gestation; Hematopoiesis) Am J Clin
Pathol 1983; 79: 225-227
0002-9173/83/0200/0225 $00.95 © American Society of Clinical Pathologists
226
ALENGHAT AND ESTERLY
A.J.C.P. • February 1983
FIG. 1 (left). Intravascular mitosis in a fetal capillary of a chorionic villus. Mitotic figures in hematopoietic cells
were seen in only a minority of the chorionic tissue available for examination from each specimen. Hematoxylin and eosin (X 1,600).
FIG. 2 (right). Aggregates of nucleated blood cells. These were a more frequent finding than actual mitoses and
were considered presumptive evidence of intravascular hematopoiesis. Hematoxylin and eosin (X225).
HEMATOPOIESIS, as classically described in humans,
originates in the primitive yolk sac. During later development, it is prominent in the hepatic sinusoids and,
finally, is confined to the bone marrow. Under abnormal
conditions, it has been found in nearly every organ, including the placenta.
During routine examination of abortion specimens,
we have seen hematopoiesis in the chorionic villi during
the first trimester of gestation and have attempted to
document its timing and frequency.
Intravascular mitosis in immature blood cells was
defined as definite evidence of hematopoiesis (Fig. 1).
Aggregates of such cells (Fig. 2), with no mitotic figures,
was interpreted as probable evidence but was not included in this study. Conceptual age was estimated on
the basis of clinical information on menstruation (gestational age minus two weeks) and was confirmed in the
few instances in which embryonic tissues were also available for dating. The specimens were from elective procedures; nevertheless, the presence of hydropic changes
in the villi or other evidence of degenerative changes in
the histologic material was noted.
Intravascular mitoses were found in six randomly examined specimens over a period of several months, including two tubal pregnancies. The conceptual age was
six to eight weeks. Suspecting that it might be a normal
finding, the previous 50 consecutive cases were reviewed
and an additional eight examples (16%) were detected
in samples of both suction curettage and endometrial
curettings. The earliest example was atfiveweeks of age,
approximately one week after intravillous capillaries are
first noticed; the oldest specimen was 11 weeks old, but
the majority were in the same six- to eight-week range.
Degenerative changes were infrequent, and nearly all of
the specimens were well-preserved. In one of the several
cases with other embryonic tissues, intravascular hematopoiesis was also noted in the embryo. The proportion of villi in the histologic sections with intravascular
mitoses was estimated and averaged about 3% (ranging
from less than 1% to about 10%). Presumptive evidence
Vol. 79 • No. 2
BRIEF SCIENTIFIC REPORTS
of hematopoiesis with capillaries containing and often
distended by clusters of blast forms was a considerably
more frequent and more widespread finding. The cells
were predominantly erythropoietic. Cells in the myeloid
series were not easily recognized, and megakaryocytes
were not seen. In no instance was there any evidence
of hematopoiesis in specimens showing degenerative
changes, or in those from the second trimester of gestation.
Intravascular hematopoiesis in chorionic villi is not
cited in the standard references on the placenta or embryology. However, it was found by Gilmour in an examination of early embryos, 2 by Cibils, in a study of
early villous differentiation,1 and presumably, it has
been noted by other investigators as an incidental finding in other studies as well. Nevertheless, it seems likely
that an appreciation for this phase of embryonic he-
227
matopoiesis has been dependent upon the widespread
examination of elective abortion specimens, since the
finding is seen only in the absence of degenerative
changes. Furthermore, it may be easily overlooked because it is present in only a small fraction of the villi.
On the basis of these findings, we suggest that intravascular hematopoiesis in chorionic villi is a common
or normal finding. It is present during the second half
of the first trimester and can be detected in about one
out of six diagnostic specimens from elective abortions.
References
1. Cibils LA: Growth of the placental villi in the first trimester. J
Reprod Med 1968; 1:377-387
2. Gilmour JR: Normal haemopoiesis in intrauterine and neonatal
life: J Pathol Bacterid 1941; 52:25-55
Analysis of the Reliability of Serial Paraprotein Determinations
in Patients with Plasma Cell Dyscrasias
GARTH E. AUSTIN, PH.D., M.D., IRENE J. CHECK, PH.D., AND ROBERT L. HUNTER, PH.D., M.D.
Serum protein electrophoresis on cellulose acetate membranes
commonly is used to follow paraprotein levels, which helps
determine therapy in patients with multiple myeloma. To recognize true changes in paraprotein levels, it is necessary to be
able to distinguish true changes from random fluctuations due
to intrasample variation. We, therefore, determined the interassay variability of concentration determinations for 14 paraproteins ranging from 0.5 to 5.2 g/dL and calculated standard
deviations as a function of concentration. The minimum detectable difference for successive measurements was determined to be 2.8 times the appropriate standard deviation. Using
these data, we constructed a nomogram from which the minimum detectable difference at a given paraprotein concentration could be read. To interpret temporal changes in paraprotein for an individual patient, a plot was constructed of the
measured paraprotein concentration, plus or minus the minimum detectable difference obtained from the nomogram,
Received May 3, 1982; received revised manuscript and accepted
for publication July 22, 1982.
Presented in part at the meeting of the Academy of Clinical Laboratory Physicians and Scientists at Chapel Hill, North Carolina in
May 1981.
Address reprint requests to Dr. Austin: Department of Pathology
and Laboratory Medicine, Emory University School of Medicine,
Atlanta, Georgia 30322.
Department of Pathology and Laboratory Medicine, Emory
University School of Medicine, Atlanta, Georgia
against time. To evaluate the clinical usefulness of this procedure, we selected 11 patients with multiple myeloma whose
serial paraprotein levels had been measured a total of 241
times (median of 20 times/patient) over one to four years. The
changes in paraprotein levels were plotted and then correlated
with the patient's clinical status at each time point. The graphic
representation of serial paraprotein values provided a clear
picture of the course of a given patient's disease and gave
information that often was not apparent from clinical examination. This format should enable significant changes in paraprotein concentration to be detected at the earliest possible
time. (Key words: Paraprotein levels; Plasma cell dyscrasias;
Serum protein electrophoresis; Multiple myeloma; Interassay
variability) Am J Clin Pathol 1983; 79: 227-230
PATIENTS WITH MULTIPLE MYELOMA and other
plasma cell dyscrasias commonly have monoclonal immunoglobulins in the blood.1'3"5 These paraproteins are
secreted by malignant clones of plasma cells. Changes
in the serum concentration of a patient's paraprotein
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