MJA 00olume 187 Number 700 October 2007
413
NOTABLE CASES
The Medical Journal of Australia ISSN: 0025-
729X 1 October 2007 187 7 413-415
漏The Medical Journal of Australia 2007
www.mja.com.au
Notable Cases
Clinical record
In early September 2002, a 61-year-old woman was referred to our
centre from the emergency room of a local private hospital. She had
presented with a 2-day history of intermittent, sudden onset, severe
right-sided lateral pleuritic chest pain lasting a few minutes. In the
private hospital emergency room, chest radiography and computed
tomography (CT) had shown pleural masses, which were subsequently
found to be poorly differentiated epithelial mesothelioma.
The patient reported that, over the previous week, she had felt
weak and lethargic, but was otherwise well. She had no previous
serious illnesses, but had recently started taking iron supplements
for anaemia and occasionally took non-steroidal anti-inflammatory
agents for osteoarthritis. She was a non-drinker, and had ceased
smoking 5 months previously. (She started smoking at the age of
16 years and had been smoking 40 cigarettes a day.) She was a
widow with three adult children, and had emigrated from the
United Kingdom in 1969. Her husband died at the age of 39 years
of a myocardial infarction. Her father died of carcinoma of the
oesophagus, and her mother of "old age". Her four siblings and
three adult children were all well.
Although she had no history of asbestos exposure from any of
her husband's occupations, she could have been exposed to
asbestos during two periods of her life. From the age of 15-22
years in the UK, she worked as a machinist in a factory where
asbestos lagging was used for the steam pipes of steam presses and
central heating. Then, in 1984, her son worked for a year for a
company making asbestos gaskets, and throughout this period she
washed his work overalls.
On examination, she looked well and was not in pain. She
weighed 74kg and was of normal build, but had slight conjunctival
pallor. An electrocardiogram showed sinus rhythm; her blood
pressure was 140/60mmHg, and her jugular venous pressure was
not elevated. There was no cyanosis or clubbing. Examination of
the chest, cardiovascular system, breast, abdomen and peripheries
showed no abnormalities.
Investigations
A chest radiograph taken before referral showed a pleural density
measuring 10 cm * 2cm overlying the posterior aspect of the right
lower lobe, with no pleural plaques or other stigmata of asbestos
exposure. A CT pulmonary angiogram performed the same day to
exclude pulmonary embolism showed three pleural masses in the
right side of the chest 00the first corresponding to the opacity
visible on the chest radiograph in the right costovertebral gutter at
the level of the tracheal bifurcation, the second having a diameter
of 6cm and located in the right cardiophrenic angle (not of fatty
attenuation), and the third in the right posteromedial costophrenic
recess, just above the diaphragm (Box 1A and Box 1B). The lungs,
mediastinum and upper abdomen (including the pancreas and
para-aortic nodes) were normal.
Laboratory tests showed her haemoglobin level was 104g/L
(reference range [RR], 115-160g/L), with a normochromic nor-
mocytic anaemia; she had thrombocytosis (555 * 109/L [RR, 150-
450 * 109/L]) and leukocytosis (11.2 * 109/L [RR, 4.0-11.0 * 109/L]),
with mild neutrophilia (8.2 * 109/L [RR, 2.0-7.5 * 109/L]). Her
erythrocyte sedimentation rate was markedly elevated at 110mm/
h (RR, 1-30mm/h), as was her serum C-reactive protein level
(294mg/L [RR, 0-6mg/L]). She had mildly elevated concentrations
of liver enzymes (alanine aminotransferase, 98U/L [RR, 0-
45U/L]; aspartate aminotransferase, 70U/L [RR, 0-41U/L]; and
lactate dehydrogenase, 268U/L [RR, 80-250U/L]), with normal
serum bilirubin and alkaline phosphatase levels. Her serum iron
level was low (2 渭 mol/L [RR, 10-33 渭 mol/L]).
A core biopsy (20 mm * 1mm) of one of the right pleural masses
showed morphological and immunohistochemical features of a
poorly differentiated epithelial mesothelioma. A pathology report
by an experienced pathologist with a special interest in pulmonary
and pleural pathology read:
There is a proliferation of poorly cohesive large cells many of
which had vesicular nuclei, prominent nucleoli and abundant
eosinophilic cytoplasm. Occasional binucleate and multinucleate
forms are present and there is a small amount of associated
collagenous stroma with a mild chronic inflammatory cell
infiltrate [Box 2A]. There is no evidence of mucin production,
and immunoperoxidase stains for a variety of keratins are
strongly positive, along with positive staining for calretinin
[Box 2B] and cytokeratin 5/6, both markers of mesothelial differentiation
[Box 2C]. Stains for LCA and S100 protein are negative.
The pathology results were later reviewed by another pathologist
with considerable experience of mesothelioma, who drew
the same conclusion.
Management
The patient was told the diagnosis and referred to an oncologist
with a special interest in mesothelioma in another tertiary hospital
where clinical trials of drugs for the treatment of mesothelioma
were in progress. She was offered chemotherapy and entry in a
thalidomide trial, but, by the time she was entered, the tumour
was already showing signs of spontaneous regression.
The patient opted for no treatment, as she felt well. By 30
December 2002, a repeat CT scan of the chest showed a decrease in
the size of the large, right-sided pleural mass in the costovertebral
Apparent spontaneous complete regression of a
multifocal malignant mesothelioma of the pleura
Roger KA Allen
A 61-year-old woman diagnosed with multifocal, poorly differentiated epithelial mesothelioma in
September 2002 went into sustained spontaneous remission within months. She was completely disease-free
within 6 months, and remained so 5 years later. This case demonstrates that this tumour may, very rarely,
regress spontaneously, with no recurrence for many years. A greater knowledge of the underlying immune
mechanisms would aid future management of this and other tumours. (MJA 2007; 187: 413-415)
414
MJA 00olume 187 Number 700 October 2007
NOTABLE CASES
gutter from 17 mm * 9mm (CT chest scan, 29 November 2002) to
12 mm * 6mm. The second pleural mass was now so small it was
difficult to see. The third mass was not visible, and there were two
small intrapulmonary nodules 00one in the right middle lobe and
the other in the left lower lobe. By March 2003, the first and second
pleural masses were even smaller (Box 1C) and, by June 2003, they
had disappeared (Box 1D). A CT chest scan in June 2004 was
normal except for the two tiny intrapulmonary nodules that had not
changed in size and were probably granulomas. The patient was last
reviewed in June 2007 and was in good health, with no evidence of
tumour, and was scheduled for next review in 6 months.
Discussion
There have been a few reports of spontaneous regression of
malignant mesothelioma, but prolonged, disease-free periods are
rare. Our report appears to be the first to describe a patient in
Australia with a poorly differentiated, multifocal epithelial mesothelioma
that regressed spontaneously, with the disease remaining
in remission for 5 years.
There has been one case report of a patient with malignant
mesothelioma of the pleura that regressed spontaneously, but after
6 years there was a single recurrence, which was resected surgically,
and the patient was followed up for a total of 12 years.1 This
raises the question in such cases of the duration of follow-up. In
the latter case, a prominent host response to tumour was seen in
both the primary tumour and the recurrence. In another case, a
patient had a spontaneous remission of a malignant peritoneal
mesothelioma, and had high spiking fevers when the tumour
recurred.2
A report from Western Australia described a woman whose
tumour regressed spontaneously but who eventually died 20
months later.3 It was noted that the tumour tissue was infiltrated
with mononuclear cells, and as the tumour recurred some malignant
mesothelioma antigens disappeared.
Several aspects of our case should be noted.
00Histopathology
忙
The histopathological findings for our patient's tumour were
re-examined by another pathologist.
忙
Not all three lesions were biopsied, as it was felt highly
probable that the pathological findings for all three would be
identical.
00Author's experience
忙
I have considerable experience in the management of mesothelioma
and benign asbestos-related conditions and currently
see about 600 patients with this condition a year. I
also act as an expert witness for the courts.
2Histological examination of a core biopsy specimen from one of the pleural masses (Box 1)
A: Histological section of the core biopsy of the pleural mass in Box 1A showing sheet-like proliferation of pleomorphic epithelioid cells with
abundant eosinophilic cytoplasm, representing a poorly differentiated epithelioid malignant mesothelioma. B: Core biopsy showing a positive
result on immunoperoxidase staining for calretinin. C: Core biopsy showing a positive result on immunoperoxidase staining for cytokeratin 5/6. 00/span>
1Computed tomography (CT) scans of the chest at referral (September 2002) and 6 and 9 months later
A, B: CT pulmonary angiogram at referral (September 2002) showing (A) the pleural-based mass in the right costovertebral gutter at the level of
the tracheal bifurcation (arrow) and (B) the two lower pleural-based masses 00one in the right cardiophrenic angle and the other in the right
posteromedial costophrenic recess (arrows). C: CT scan (March 2003) showing that the pleural-based mass in the right costovertebral gutter had all
but disappeared (arrow). D: CT scan (June 2003) which appeared normal apart from a small stable nodule in the left lower lobe which was probably
a granuloma (arrow).
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MJA 00olume 187 Number 700 October 2007
415
NOTABLE CASES
忙
Mesothelioma is a relatively common condition in Australia at
present and, as a result, our thoracic physicians, oncologists
and pathologists have considerable experience in this area.
00Course of the disease
忙
The patient had markedly elevated inflammatory markers
and is likely to have had the tumour for several months
before diagnosis. It is suspected that her natural killer cells
and cell-mediated immunity accounted for the regression of
the tumour.
忙
Evidence of the beginning of spontaneous regression was
unusually rapid, occurring within months of diagnosis.
00Exposure
忙
Our patient's exposure to asbestos seems to have been
relatively mild and incidental, as often occurs with women
who develop mesothelioma.
00Self-treatment
忙
The patient did not use any unusual therapies, such as alternative
medicines, diets and faith healing, after the diagnosis.
This case highlights the possibility that spontaneous regression
of mesothelioma may occur occasionally. Spontaneous tumour
regression therefore should be seen as part of the spectrum of the
natural history of mesothelioma and other tumours. A detailed
study of the immunity of such individuals "after the event" is
unlikely to reveal any particular abnormality but, in hindsight, it
would have been interesting to have performed detailed immunological
studies during the initial regression period. The role of
mesothelin-related serum proteins needs further evaluation. The
understanding of this process is likely to be pivotal in the
improved treatment of this usually lethal condition.
Acknowledgements
I would like to thank Dr Rick Abraham, Medical Oncologist and Senior
Lecturer in Medicine, University of Queensland, for his assistance in the
management of this patient; Dr Ian LeFevre, Histopathologist, QML Pathology,
Brisbane, and Dr Lyndie Clark, Histopathologist, Prince Charles Hospital,
Brisbane, for reviewing the histological sections; and Dr Ian LeFevre
and QML Pathology for supplying the photomicrographs.
Competing interests
None identified.
Author details
Roger KA Allen, FRACP, FCCP, PhD, Thoracic and Sleep Physician
Wesley Medical Centre, Brisbane, QLD.
Correspondence: rogerallen@internode.on.net
References
1Pilling JE, Nicholson AG, Harmer C, Goldstraw P. Prolonged survival due
to spontaneous regression and surgical excision of malignant mesothelioma.
Ann Thorac Surg 2007; 83: 314-315.
2Schwartz E, Maayan C, Mouallem M, et al. Malignant peritoneal mesothelioma:
long-term spontaneous clinical remission. Med Pediatr Oncol
1991; 19: 325-328.
3Robinson BW, Robinson C, Lake RA. Localised spontaneous remission in
mesothelioma 00possible immunological mechanism. Lung Cancer
2001; 32: 197-201.
(Received 5 Jan 2007, accepted 6 Jun 2007)
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