73

One other point very clearly shown by these experi- CORRELATION BETWEEN DIAGNOSIS AND STERNAL

is that penicillamine is a very powerful agent for TENDERNESS IN 200 CASES

ments
the mobilisation of body-copper, and that the increased
copper which appears in the urine is released from body
stores and has not been carried through from the gut.
There is also support for the view that penicillamine is
more active than dimercaprol in this respect.

Summary
The excretion of an injected dose of 100 /C of 64CU was
studied in one healthy man and three patients with
Wilson’s disease together with the effect of oral penicilla-
mine and intramuscular dimercaprol.
The results show clearly that penicillamine is very
active in promoting the excretion of copper and appears
to be superior to dimercaprol in this respect. There is
good correspondence between the chemical and radioactive
determinations of urinary copper.
The bulk of the injected copper was concentrated in the 2 2 of these cases were found at necropsy, one and four weeks later, to have
marrow metastases. In 1 case the sternal-puncture needle had been
liver by ten hours in the healthy man, reaching a maximum inserted between two nodules of growth.
of more than 90% and then decreasing steadily to 70% by
fifty hours, whereas in Wilson’s disease the greatest Whitby and Britton (1953) and Lopes Cardozo (1954)
concentration in the liver never exceeded 50%. recommend puncture of tender bone in the diagnosis of
Study of the specific activity of the copper in the urine secondary carcinoma.
supports the theory that, in healthy people almost all the Amy and Jaimet (1953) and Jaimet and Amy (1956) empha-
sise the importance of selective puncture of tender bone in
injected copper becomes firmly bound to protein by patients presenting diagnostic problems, and report the
twenty-four hours, whereas in patients with Wilson’s finding of tumour cells in the marrow in unsuspected cases
disease it mixes with a large body pool of copper and of neoplasm.
remains readily available for excretion at the glomerulus. Varadi (1955) found Sternberg-Reed cells in the marrow of
We wish to thank Dr. Michael Ashby, Dr. H. Kryszek, and Dr. five patients with Hodgkin’s disease by " aimed " puncture of
S. Nevin for permission to study patients under their care; Mr. B. R. tender parts of the sternum. This degree of success is in
Payne and his associates at the Atomic Energy Research Establish- sharp contrast to that of other writers on the subject (Cooper
ment, Harwell, for their invaluable help in supplying copper of very and Watkins 1949, Baryd et al. 1954).
high specific activity; and Dr. W. P. Kennedy, of the Distillers
Company (Biochemicals) Ltd., for a most generous gift of Marrow puncture, however, is still generally done as a
penicillamine. blind biopsy of either the iliac crests or the upper part of
REFERENCES the sternum. Although this is satisfactory in the diagnosis
Anderson, J., Emery, E. W., McAlister, J. M., Osborn, S. B. (1956) Clin. of haemopoietic disorders it probably accounts for the
Sci. 15, 567.
Bearn, A. G. (1956) Amer. J. Med. 21, 134. comparative rarity with which neoplasms are diagnosed
(1957) ibid. 22, 747.
—

examination.
Kunkel, H. G. (1955) J. Lab. clin. Med. 45, 623.
—
by marrow
Bush, J. A., Mahoney, J. P., Markowitz, H., Gubler, C. J., Cartwright,
G. E., Wintrobe, M. M. (1955) J. clin. Invest. 34, 1766.
Denny-Brown, D., Porter, H. (1951) New Engl. J. Med. 245, 917. Method
Earl, C. J. (1954) Lancet, i, 234.
Moulton, M. J., Selverstone, B. (1954) Amer. J. Med. 17, 205.
—
To assess the frequency and significance of tenderness
Payne, B. R., Scargill, P., Cook, G. B. (1957) Proceedings of UNESCO
Radioisotope Conference, Paris. To be published. 200 consecutive patients about to undergo marrow punc-
Riddell, A. G., Griffiths, D. B., McAlister, J. M., Osborn, S. B. (1957) ture were examined for tenderness of the sternum. The
Clin. Sci. 16, 315.
Walshe, J. M. (1956) Amer. J. Med. 21, 487. bone was palpated from the manubrium downwards, firm
(1957) Brit. med. Bull. 13, 132.
—

pressure being made with the ball of the index finger.

THE CLINICAL SIGNIFICANCE OF STERNAL
TENDERNESS
THE VALUE OF SELECTIVE MARROW BIOPSY IN
MALIGNANT DISEASE
N. D. GOWER
M.B. Lond.
SENIOR REGISTRAR IN PATHOLOGY,
EDGWARE GENERAL HOSPITAL, LONDON
BONE tenderness in hxmopoietic disorders is well known
(Wintrobe 1946, Witts 1946, Whitby and Britton 1953),
and may affect any bone, most commonly the sternum,
in
particularly leukaemia, polycythasmia, and
tosis. Less attention has been paid to the occurrence of
bone tenderness in association with metastatic neoplasms
and reticuloses, although some workers have reported that
diagnostic material may be aspirated more regularly from
tender than from non-tender bone.
Many healthy people complain of discomfort over the
lower third of the sternum when examined by this method;
therefore tenderness was regarded as present only if it was
very definite. Most of the patients who experienced
tenderness on palpation also complained of pain on
light percussion of the sternum, but the tenderness was
elicited less constantly in this way.
Marrow was aspirated from these tender spots or,
if tenderness were absent, from the sternum at the
junction of its upper two-thirds and lower third.
Results
Of the 200 patients 61 were considered to have tenderness
of the sternum. In most cases the tenderness was quite
myeloma-
sharply localised to small areas, usually in the lower third of the
sternum. Diffuse sternal tenderness was seen in a few cases
of metastatic carcinoma, myelomatosis, acute leukaemia, and,
most noticably, in 4 of 6 patients with myeloid reticulosis
as defined by Israels (1951). In these patients generalised
bone tenderness and spontaneous bone pain were usual.
74
The diagnoses and presence or absence of sternal tenderness
in the 200 patients is summarised in the accompanying
table.
Although sternal tenderness was found, as expected, to be
common in patients with neoplastic blood disorders and in
those with bone-marrow metastases, it was not confined to
these groups of patients, nor was it found as often as expected
in patients with leukxmia or with myelomatosis. In the
megaloblastic ansemias sternal tenderness was found only in
severely anaemic patients; it disappeared with successful
treatment, as in the leukaemias, but very much more rapidly,
usually being absent after three or four days and indicating
improvement in advance of the rise in haemoglobin level,
sometimes even before the reticulocytosis began. The patients
with non-haemopoietic malignant disease studied did not
form a representative sample of all such cases in the hospital
being biased in favour of cases with known or suspected
metastases in the marrow. Even so, selective puncture of
tender areas of bone proved of diagnostic value in some
instances.
Illustrative Case-reports
Case 1.-A man, aged 60, with carcinoma of the prostate, deve-
loped refractory normochromic anaemia. No primitive cells were
found in his peripheral blood. Radiography of his skeleton showed
no evidence of metastases in bone. The acid and alkaline phos-
phatase levels in the serum were normal. The blood-urea level
was 80 mg. per 100 ml., and it was thought that the anaemia might
be secondary to renal impairment, but puncture of a tender sternum
revealed clumps of carcinoma cells. Simultaneous puncture of the
non-tender left iliac crest yielded normal marrow.
Case 2.-A man, aged 47, was admitted to hospital for the
investigation of sciatica. Radiography showed collapse of a lumbar
vertebra, and the peripheral blood showed leuco-erythroblastic
anaemia. A diagnosis of secondary carcinoma was considered, but
no primary growth was found. Marrow aspirated from a sharply
localised tender area of the sternum showed masses of abnormal
reticulum cells, yet simultaneous puncture 1 cm. above the tender
spot yielded normal marrow. The diagnosis of myeloid reticulosis
was confirmed at necropsy.
Case 3.-A woman, aged 76, was admitted to hospital for the
investigation of cervical lymphadenopathy. She had no anaemia,
but her peripheral blood showed neutrophil leucocytosis. Lymph-
node biopsy showed a necrotic tumour on which no firm opinion
could be given. The sternum and ribs were tender, and metastatic
carcinoma was diagnosed by sternal puncture. Necropsy disclosed
a small carcinoma of the stomach with metastases in lymph-nodes,
liver, and bones.
Conclusions and Summary
Bone tenderness, in particular sternal tenderness,
may develop in patients with various disorders but is
particularly common in those with bone-marrow meta-
stases and those with myeloid reticulosis.
Selective puncture of tender bone will improve the
chances of finding abnormal cells in such cases.
Selective puncture of the marrow is recommended in
the investigation of obscure cases, particularly if
unexplained anaemia, bone destruction, or lymphadeno-
pathy is present.
It is a pleasure to thank Dr. George Discombe for his advice and
for his criticism of this paper.
REFERENCES
Amy, H. E., Jaimet, C. H. (1953) Canad. med. Ass. J. 69, 424.
Bayrd, E. D., Paulson, G. S., Hargraves, M. M. (1954) Blood, 9, 46.
Cooper, T., Watkins, C. H. (1949) ibid. 4, 534.
Israëls, M. C. G. (1951) Lancet, i, 978.
Jaimet, C., Amy, H. E. (1956) Ann. intern. Med. 44, 617.
Lopes Cardozo, P. (1954) Clinical Cytology Using the May-Grünwald-
Giemsa Stained Smear. Leyden; chapter 6.
Varadi, S. (1955) Brit. J. Hœmat. 1, 184.
Whitby, L. E. H., Britton, C. J. C. (1953) Disorders of the Blood. 7th ed.,
London; pp. 509, 540, 552, 555.
Wintrobe, M. M. (1946) Clinical Hæmatology. 2nd ed., London; pp. 594,
695.
Witts, L. J. (1946) in Price, F. W. A Textbook of the Practice of Medicine.
7th ed., London; pp. 835, 838, 840.
SEX REVERSAL:
OVARIAN TISSUE ASSOCIATED WITH MALE
NUCLEAR SEX
D. J. B. ASHLEY C. H. JONES
M.D. Lpool M.D. Lpool
SENIOR REGISTRAR IN PATHOLOGY, ASSISTANT PATHOLOGIST,
DAVID LEWIS NORTHERN HOSPITAL, ALDER HEY CHILDREN’S
LIVERPOOL HOSPITAL, LIVERPOOL
THE syndrome of gonadal dysgenesis, Turner’s
syndrome, is now a well-recognised, although uncommon,
disorder of sexual development. In its classical form it is
characterised by female (or near female) bodily habitus,
atrophic gonads, absence of secondary sex characters,
amenorrhoea, and increased urinary excretion of pituitary
gonadotrophic hormones. Often there are associated
congenital defects-notably short stature, webbing
of the neck, and cubitus valgus. The principal anomaly
is in the gonads, which are represented only by a primitive
genital ridge consisting of connective tissue and a few
mesonephric remnants (Wilkins and Fleischmann 1944,
Grumbach et al. 1955).
"
Recently it has become possible to determine the
"
genetic sex of an individual by examining the cell
nuclei of the skin (Moore, Graham and Barr 1953)
and of the buccal mucosa (Moore and Barr 1955). Though
it has not been rigidly proved that the chromatin bodies
seen in a high proportion of the cells of normal females
are the XX-chromosome complex, the presence of these
bodies is generally held to indicate the female genotype
(Lennox 1956). These tests of genetic sex have been
applied to many people with Turner’s syndrome, and it
has been found, in most cases, that the epithelial cells
are chromatin-negative-i.e., that the genetic sex is
probably male (Polani, Hunter, and Lennox 1954,
Grumbach et al. 1955). This view is upheld by this
syndrome’s association with coarctation of the aorta,
a congenital anomaly normally largely confined to males,
and by the observation (Polani, Lessof, and Bishop 1956)
that 4 of 25 patients with Turner’s syndrome had
anomalies of red-green colour-vision, a defect inherited
as sex-linked recessive characteristic and ten times
a
commoner in males than in females.
The case we report here may be discussed within the
general framework of Turner’s syndrome but presents
certain anomalous features and shows a much closer
analogy with the syndrome of testicular agenesis
(Klinefelter et al. 1942).
Case-report
An child was referred to Alder Hey Children’s Hospital
only
at the age of 10 days because of doubts about the " true sex ".
The baby had labia majora and minora and a phallus suggestive
of an enlarged clitoris on which there was a hypospadiac
urethral opening through which urine passed. In front of the
anus was a vagina with a second urethral opening on its anterior
wall. It was found subsequently that a single urethra left the
bladder but divided into two after a short course. Otherwise
the baby, though small, was apparently normal, with no
evidence of cardiovascular or skeletal abnormalities. The bone
age at 18 months corresponded to the chronological age. The
urinary excretion of 17-ketosteroids, determined on three
occasions in the first 9 months, was 0-64, 0-22, and 0-25 mg.
daily. These results are within the normal range for this age
(Wilkins et al. 1955).
Laparotomy at 17 months of age revealed a uterus and
fallopian tubes of normal size. The two ovaries, in their normal
position, were slightly enlarged and cystic. There was no sign
of testicular tissue retroperitoneally or in the inguinal canals or