Clinico-pathological case 1 [Trinity College Dublin]

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Clinico-pathological case 1Trinity College
Dublin

• Prof T Rogers
• Prof O Sheils
• Dr C DAdhemar

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Clinical Summary

• A 66-year-old, emaciated man was admitted on the
  19/06 from a nursing home facility with a 2 day
  history of increasing confusion.
• He had been under continuous medical care in the
  nursing home for three months when he was
  admitted for a complaint of "feeling bad".
• There was a history of intravenous drug use
  (heroin), smoking crack cocaine, and hepatitis C,
  but he was HIV negative.
• He was afebrile.
• The white blood cell count was 8.3x109/L.

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• End-stage renal disease (membranoproliferative
  glomerulonephritis thought to be secondary to
  hepatitis C) requiring hemodialysis,
• R knee and L wrist septic arthritis (Staph aureus
  and Strep pneumoniae), and
• anaemia (Hct 28) were diagnosed.

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• Blood cultures were also positive for Staph
  aureus, and he was treated with flucloxacillin
  and gentamicin.
• The course was complicated by recurrent line
  infections and fasciitis.
• A trans-oesophageal echocardiogram showed no
  vegetations in the heart. In mid May, he was
  transferred to a nursing home for continued care.

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On admission from the nursing home, his
observations were as follows

• T 98.9, HR 80/min, RR 26/min, BP 144/83, and O2
  saturation of 96 on room air.
• Lungs were clear. No cardiac murmurs were heard.
  The R knee and L wrist were again swollen.
• Laboratory values were
• WBC 18x109/L, Hct 30, and platelets 187x109/L.
• A blood culture yielded gram positive cocci.
• Vancomycin was begun.

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• Q1. What is the differential diagnosis in this
  case?
• Q2. What clinical investigations would you
  perform?
• Q3. What organism was most likely identified in
  the blood culture?
• Q4. Discuss the antibiotic policy in this
  patient.

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• A trans-oesophageal echocardiogram was performed,
  and a chest radiograph was taken.

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• On the 22/06, a cross-sectional, two-dimensional
  echocardiographic view of the aortic and pulmonic
  (PV) valves showed thickening of the leaflets of
  the PV and one of two pedunculated vegetations
  that prolapsed 3 cm into the pulmonary artery
  during systole. There was no valvar
  insufficiency. The tic marks at the edge of the
  photograph are 1 cm apart. Landmarks are
  indicated on the same photo below.
• RV right ventricular chamber. PV thickened
  pulmonic valve. V and 2 arrows vegetation on
  stalk during systole. AO aorta. The small arrow
  below AO indicates a normal, thin aortic valve
  leaflet. The arrowheads indicate the wall of the
  pulmonary artery trunk.

The patient was not considered to be a candidate
for a surgical procedure.
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Questions

• Q5. What is the cause of the vegetations in the
  heart?
• Q6. Comment on the location of the vegetations.
• Q7. Can you list the causes of heart valve
  vegetations?

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Radiographic Findings

• On the 26/06, a frontal CXR film showing the
  right lung demonstrated multiple areas of
  mass-like consolidation, at least two of which
  showed central cavitation.
• There was a small right effusion.
• The left lung appeared normal.

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• The largest area of consolidation is at the right
  lung base (lower arrow).
• Superior to it is another mass-like consolidation
  containing a central cavity. A smaller mass-like
  consolidation is present in the right upper lobe
  (upper arrow). To its right is a well-formed
  cavity of approximately the same size.

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QUESTIONS

• Q8. What are the causes of the lung
  consolidation?
• Q9. What are the causes of the lung cavitations?
• Q10. How would you further investigate these
  lesions?

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• Bacteremia persisted, thrombocytopenia developed,
  and he remained confused.
• He was found dead on the 30/06.
• An autopsy was performed.

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• Autopsy Findings
• A serosanguineous pleural effusion (300 ml) was
  present on the right side. The heart was enlarged
  (380 g, normal 300 g). Look at each of the
  following photos and explain what has happened.

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• A. Valves were normal except for the pulmonic,
  which is shown here. Compare it with an example
  of a normal pulmonic valve below (B).
• One commissure is indicated at the arrow.
• B. Normal pulmonic valve. Note the thin,
  translucent cusps and normal commissures.

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• QUESTION
• Q11. What is the lesion on the pulmonic valve?

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Answer

• The pulmonic valve had large vegetations, about 2
  cm in diameter, on each of 2 cusps.
• They were very friable, and one (on the leaflet
  to the right of the arrow) was dislodged before
  the photo was taken, revealing a hole, 5 x 3 mm
  in diameter (not shown), in the cusp.
• The vegetation that is present (anterior leaflet)
  obscures the commissure and has spread to the
  wall of the pulmonary artery.
• No pedunculated portion was present at autopsy.
  The valve leaflets are thickened a congenital
  anomaly.

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• C. The right lung weighed 1000 g and the left,
  900 g (normal about 300-400g each).
• The right lung had a fibrinous pleuritis.
• After distension with formalin and fixation, one
  slice from the left lung showed two yellowish
  lesions.

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• QUESTION
• Q12. What is the lesion cut surface of the lung?

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Answer

• The slice of lung shows two segmental pulmonary
  arteries that are occluded by thrombus.
• Note the airway next to the vessel near the
  centre. No infarct or haemorrhage is present in
  the distal parenchyma.
• These two thrombi probably came from the
  pedunculated portions of the vegetations that
  were identified in the echocardiogram.

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• D. A slice of the right lower lobe showed two
  lesions.

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QUESTION

• Q13. What are the lung lesions in image D?

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Answer

• The slice of lung in D shows two cavities with
  thin walls.
• The larger abuts the pleura and may have been
  responsible for the para-pneumonic effusion.
• Both cavities show small amounts of residual
  necrotic lung, which is dark in the smaller
  cavity and pale in the larger one.
• The cavitation is the result of pneumonia and
  ischemia caused by septic thromboemboli as in C.
• Note the pleuritis at the base (lower left).

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QUESTION

• Q14. How did the patient get the lesions in the
  lung?

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• The photos show typical consequences of
  right-sided infective endocarditis cavitated,
  pneumonic infarcts and pulmonary emboli without
  infarction.
• The liver (2200 g, normal 1500-1800 g) and spleen
  (320 g, normal 100 g) were enlarged. The kidneys
  were shrunken (R 75 g, L 92 g, normal 150 g each)
  from the chronic membranoproliferative
  glomerulonephritis. The brain was normal.

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Histological changes at autopsy
The following sequence of photos shows the
histological features.

• The pulmonic vegetation is composed of a
  proteinaceous coagulum that contains neutrophils
  and bacteria (dark blue). There was no evidence
  of organization to indicate healing.

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• Section of the thrombus in one of the segmental
  arteries shown on the previous page shows the
  same pattern as the vegetation, with PMNs and
  bacteria.
• Note that the inflammation has spread into the
  vessel wall (blue staining at arrows).
• The lack of parenchymal hemorrhage or infarction
  related to this lesion, which is several days
  old, signifies that heart failure was absent.
• Heart failure is a major factor that predisposes
  to infarction after pulmonary embolism of a
  segmental artery.

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• Higher magnification of the same artery shown in
  B. The infected thrombus (T) has caused
  transmural inflammation of the arterial wall
  (between 2 arrows).
• A portion of normal arterial wall (N) is also
  shown. Rupture of the vessel can occur as a
  result of such an infective arteritis. When an
  infected vessel dilates, it is called a mycotic
  aneurysm

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• This vessel has an acute thrombus with some faint
  lines of Zahn (platelet-fibrin columns
  (arrow)), transmural arterial inflammation, and
  adjacent pneumonia with a necrotizing component
  (N) at the bottom left--the beginning of a septic
  infarct.

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• . A section from a cavitating lesion shows
  numerous, dark blue bacteria in vessels and
  surrounding pneumonic consolidation of parenchyma
  that shows coagulative necrosis with preservation
  of tissue outlines

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Other changes seen at autopsy 1 A slice of
lung from the left upper lobe (A) and a
histological section from the same area (B) are
shown.

• Q15. Look at the slices carefully and describe
  the lesions.

A. Hint The abnormality is related to colour.
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Answer

• Black pigment is present in a large area in
  addition to being present around respiratory
  bronchioles as small spots.
• While the latter are common in cigarette smokers,
  large areas of black pigment are not.
• Also, the air spaces in the blackened areas are
  slightly enlarged with thin walls emphysema.

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• B. Two abnormalities are present here.

Hint The colour of the macrophages is important.
What about alveolar size?
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• The histological section shows large numbers of
  alveolar macrophages with black pigment.
• A stain for hemosiderin pigment was negative.
• Air spaces are enlarged compared to normal.

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Diagnoses are

• excess black pigment caused by smoking crack
  cocaine
• focal emphysema.

The photo shows a tube of dusky lavage fluid from
another crack smoker.
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Pulmonary Complications of Smoking Crack Cocaine

• Black sputum or lavage fluid
• Barotrauma pneumomediastinum, pneumothorax
• Vascular injury noncardiogenic pulmonary edema,
  pulmonary hemorrhage, infarction
• Parenchymal injury acute eosinophilic pneumonia,
  organising pneumonia sometimes with granulomas

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Other changes seen at autopsy 2

• A. This photo taken with polarized light shows
  birefringent crystals (bright spots) in the lung
  of the patient.
• Numerous, scattered crystals up to 40 µm long
  were located mainly in the interstitium.
• A few foreign-body giant cells were present, but
  granulomas and scar were absent

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B.

• Similar crystals were found in macrophages in the
  portal triads of the liver shown here.
• Most were less than 10 µm long, as these crystals
  had traversed the pulmonary capillary bed.
• A granulomatous response was absent.
• Crystals were also found in the spleen.

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Crystals in intravenous drug users (IVDUs)

• Examination of the lung sections of this patient
  with polarized light showed deposits of foreign
  crystals.
• The crystals are deposited in arterioles and
  capillaries but may erode through the vessel wall
  into the interstitium.
• In some cases granulomas and fibrosis develop.

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Effects of injection of oral medications

• IVDUs sometimes inject intravenously drugs that
  are intended for oral use.
• The tablets are ground to a powder and dissolved
  in water before injection.
• Tablets, including methadone, methamphetamine
  (speed), and methylphenidate (Ritalin), contain
  fillers of talc, microcrystalline cellulose, or
  starch.

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• These particles are trapped primarily in the
  pulmonary vasculature, but some particles less
  than about 5 µm in diameter traverse the
  capillary bed.
• As a result of systemic spread, the crystals may
  be viewed in the microcirculation of the retina
  ophthalmoscopically.
• The crystals do not interfere with visual acuity
  or other organ function.
• Pulmonary effects may include fibrosis,
  emphysema, or hypertension.

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Diagnoses

• Infective endocarditis IE (methicillin
  resistant S. aureus), pulmonic valve
  congenitally malformed.
• Infected emboli, lung.
• Infective pulmonary arteritis.
• Infected, cavitated infarcts in the lung.
• Disseminated birefringent crystals in lungs,
  liver, spleen (intravenous drug use).
• Crack black lung.

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Clinical Comment

• Review of the trans-oesophageal echocardiogram
  from 05/05 (about 2 months before death) showed a
  small (0.7 cm) vegetation on an abnormally
  thickened pulmonic valve (PV).
• The diagnosis was probably dismissed because the
  PV is almost never involved in infective
  endocarditis (IE).
• The onset of IE probably coincided with the
  development of the septic arthritis.
• Death was ascribed to respiratory failure from
  septic emboli, infarcts, and pneumonia.