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CLINICO
PATHOLOGICAL
CONFERENCE
17 10 2008
.
CASE HISTORY:
A 67 year-old gentleman of no fixed abode
who suffers from chronic alcoholism is found
collapsed by Heuston Railway station. He is
taken as an emergency to St James’s
Hospital.
On examination he is found to be semiconscious but rousable and there is a smell
of alcohol from his breath. He is also
dehydrated.
Initial investigations reveal the following:
White blood count: 13 X 109/l
Proportion neutrophils 70%
Haemoglobin: 10g.dl
Chest X-ray reveals the abnormalities
shown below
Radiographic Changes
A mass-like, 3 cm density overlies the left hilum (arrow) on
the frontal chest radiograph. On the lateral projection it is
shown to be in the superior segment of the LLL (arrow),
posterior to the tortuous aorta.
Q: At this stage what is you differential diagnosis (name 3
options)?:
1
2
3
Q: What investigations would you order/carry out next?:
1
2
3
A mass-like, 3 cm density overlies the left hilum (arrow) on
the frontal chest radiograph. On the lateral projection it is
shown to be in the superior segment of the LLL (arrow),
posterior to the tortuous aorta.
Q: At this stage what is you differential diagnosis (name 3
options)?:
1 Malignancy
2 Tuberculosis
3 Other infection
Q: What investigations would you order/carry out next?:
1 CT scan
2 Bronchoscopy (? Biopsy)
3 Sputum microscopy & culture, histology
Progress: in the meantime in view of the patient’s poor
physical state, he is admitted to the Care of the Elderly
ward and placed on intravenous antibiotics.
Q: Do you consider this to be appropriate management so
far?
Further investigations:
Blood cultures are negative at 48 hours incubation, sputum
microscopy (gram stain) and culture yield no predominant
organism, just “normal flora”.
The patient is now conscious but somewhat disorientated.
He has an intermittent fever up to 38°C.
A chest CT-scan is performed (shown below):
CT shows a 3-cm mass in the superior segment of
the LLL. The mass has central low attenuation
consistent with necrosis. Note the positive
bronchus sign--a subsegmental bronchus leading
directly to the lesion (arrow). This sign is often
associated with increased diagnostic yield at
bronchoscopy.
It is decided to perform a bronchoscopy and
transbronchial biopsy.
The sample is sent to Histopathology and part of it
is sent to Microbiology.
Comment on the histology picture series shown below:
1
Comment on the histology picture series shown below:
2
At low power, nodular collections of confluent granulomas are
surrounded by dark blue lymphoid cells. Note the small,
rounded granulomas at the edge of the central nodule. At the
centre of the confluent granulomas is a pink zone of necrosis.
At the edge of the necrotic zone are lymphocytes, epithelioid
cells, and multinucleated giant cells but no well-formed
granulomas. Note the two types of multinucleated giant cells: the
Langhans' cell with nuclei at the edge and the foreign body type
giant cell with nuclei scattered throughout the cytoplasm.
The individual, rounded granulomas are composed of
activated, epithelioid histiocytes with abundant cytoplasm,
multinucleated giant cells, which represent fused epithelioid
cells, and lymphocytes.
Differential diagnosis:
The differential diagnosis includes mycobacterial or fungal
granulomas, and special stains for organisms were
performed.
No fungi were found. Most fungi, with the exception of
Pneumocystis jiroveci, can be seen with ordinary H&E
stains. The Gomori methenamine silver stain is performed,
nevertheless, to find rare organisms and to help identify
them.
In this particular biopsy, two acid-fast organisms were
found on the Ziehl-Neelsen stain. The organisms were
found in the necrotic areas and not in the cellular rim.
Three weeks later, the culture of the tissue was positive for
M. tuberculosis.
Non-infectious diseases in the differential diagnosis include
Wegener's granulomatosis and nodular sarcoidosis
This Ziehl-Neelsen-stained section from another case shows
many acid-fast tubercle bacilli that are associated with cells
undergoing lysis.
Diagnosis: Active tuberculosis, superior
segment of left lower lobe
Q: what is the incidence of tuberculosis in
Ireland per 100,000 population?
Tuberculosis notification rates (1)
World, 2005
Notified TB cases (new and
relapse) per 100 000 population
No report
0–24
25–49
50–99
100 or more
Source: WHO, 2007
Further progress: 3 early morning sputum samples reveal
the presence of acid and alcohol fast bacilli consistent with
M tuberculosis
Q: What Microbiology tests will be performed on the
sputum samples to confirm the diagnosis and guide
treatment?
The patient is started on anti-tuberculous antibiotics
Q: what are these likely to be?
Q: What infection control and public health measures need
to be taken in this case?
The patient self-discharges and is lost to follow-up.
Further progress: 3 early morning sputum samples reveal
the presence of acid and alcohol fast bacilli consistent with
M tuberculosis
Q: What Microbiology tests will be performed on the
sputum samples to confirm the diagnosis and guide
treatment? Culture for Mtb, I.D., sensitivities
The patient is started on anti-tuberculous antibiotics
Q: what are these likely to be?
Isoniazid, rifampicin, pyrazinamide, ethambutol,
Q: What infection control and public health measures need
to be taken in this case?
Single room isolation, notification to Public Health
The patient self-discharges and is lost to follow-up.
16 weeks later the patient is re-admitted in poor general
condition, with significant weight loss and productive cough
from last admission with extensive bi-lateralr infiltrates.
He claims he continued to take his medication but only
intermittently as he didn’t have enough tablets.
A test is performed on his urine
Q: what test is this?
Sputum smear is strongly positive for acid fast bacilli.
16 weeks later the patient is re-admitted in poor general
condition, with significant weight loss and productive cough
from last admission with extensive bi-lateral infiltrates.
He claims he continued to take his medication but only
intermittently as he didn’t have enough tablets.
A test is performed on his urine
Q: what test is this? Colour (orange)
Sputum smear is strongly positive for acid fast bacilli.
A test is performed in the Tuberculosis laboratory
which reveals that the organism is resistant to one
of the antituberculous antibiotics:
Q: which antibiotic is this?
Q: What infection control measure should be
implemented?
Further results from the TB laboratory show that
the strain of Mtb is resistant to two of the
antibiotics the patient was originally treated with.
A test is performed in the Tuberculosis laboratory
which reveals that the organism is resistant to one
of the antituberculous antibiotics:
Q: which antibiotic is this? rifampicin
Q: What infection control measure should be
implemented? Negative pressure room
Further results from the TB laboratory show that
the strain of Mtb is resistant to two of the
antibiotics the patient was originally treated with.
The patient is now treated by DOT
Q: What is DOT?
Q: What antituberculous antibiotics are available to
treat him?
Q: what type of tuberculosis does he have?
Q: What is the incidence of this type of TB in
Ireland?
Q: what is its incidence in other parts of Europe
eg,former USSR states?
The patient is now treated by DOT
Q: What is DOT? Directly observed therapy
Q: What antituberculous antibiotics are available to treat
him? Ethionamide, cycloserine, fluoroquinolone
Q: what type of tuberculosis does he have? MDR
Q: What is the incidence of this type of TB in Ireland? 1%
Q: what is its incidence in other parts of Europe eg,former
USSR states?
0
* Including only countries with nationwide, representative data and with more than 60 new TB cases reported
Montenegro
Slovenia
Bosnia & Herzegovina
Netherlands
Sweden
Switzerland
United Kingdom
Croatia
Finland
France
Belgium
Norway
Denmark
Germany
Austria
Romania (2003-4)
Israel
Cyprus
Georgia
Lithuania
Latvia
14
Estonia
Multi-drug resistance, new TB cases, 2005*
% resistance
12
10
8
6
4
2
SUMMARY
A case of pulmonary tuberculosis with failed
treatment due to poor compliance.
This resulted in the development of MDRTB
infection
Creates particular problems for therapy and
infection control
Patient required DOT and special isolation
facility in hospital