WebPath Respiratory Case Studies

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WebPath Respiratory Case Studies

• Dr. Spencer Gilbert

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Laboratory Part I
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CASE 1

• Clinical History
• A 49 year old male with a 25 pack year smoking
  history presented to you at the homeless clinic
  with complaints of increasing cough that had
  gradually been getting worse over the previous
  six months. He noted that the sputum was
  blood-tinged on one occasion. He also felt
  extremely tired. His x-ray showed upper lobe
  cavitations with nodular infiltrates.

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Slide 1.1Cavitary lung lesions are seen here
grossly.
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Slide 1.2The lung lesions are seen here
microscopically at low power.
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Slide 1.3The lung lesions are seen here
microscopically at medium power.
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Slide 1.4The lung lesions are seen here
microscopically at higher power.
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Slide 1.5Note the subpleural lesion along with
the lesion in the hilar lymph node.
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Slide 1.6Note the small millet seed sized
lesions scattered in the lung parenchyma.
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Case 1

• Questions
• Describe the gross appearance of this lung
  representative of the disease process in your
  patient's lungs (Slide 1.1).
• Describe the microscopic appearance of the lungs
  (Slides 1.2 - 1.4). What is the probable
  diagnosis?
• What tests can be performed to diagnose this
  condition? What additional clinical findings
  might be present?
• Describe the additional gross pathologic patterns
  for this disease process (Slides 1.5 and 1.6).
  What is the differential diagnosis?

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CASE 1 Tuberculosis

• Answers
• Describe the gross appearance of this lung
  representative of the disease process in your
  patient's lungs. There is extensive granulomatous
  disease involving the lung parenchyma. Mainly
  upper lobe is involved. The larger tan-white
  granulomas have caseation with central necrosis
  and in some areas become almost confluent.
• Describe the microscopic appearance of the lungs.
  What is the probable diagnosis? Granulomatous
  inflammation is present. The granulomas
  demonstrate central caseation and surrounding
  epithelioid macrophages. Some Langhans giant
  cells are seen. Also contributing to the
  inflammatory reaction are lymphocytes. The acid
  fast stain demonstrates many slender red rods
  consistent in morphology with Mycobacteria.
• What tests can be performed to diagnose this
  condition? What additional clinical findings
  might be present? A tuberculin skin test is used
  mainly for screening patients for possible
  tuberculosis. Sputum samples can be obtained for
  acid fast smear and culture. This patient's acid
  fast smear was 3 positive, and the culture grew
  Mycobacterium tuberculosis that was sensitive to
  rifampin, isoniazid, and ethambutol. A chest
  radiograph will show the extent of pulmonary
  disease (in this case it was extensive, because
  of the cavitation).
• Describe the additional gross pathologic patterns
  for this disease process. What is the
  differential diagnosis? Primary tuberculosis is
  often seen in children, and is often subclinical.
  There is a subpleural granuloma and extensive
  hilar lymph node granulomatous disease (the
  so-called Ghon complex, as seen in Slide 1.5). In
  adults, when health status declines, the
  quiescent infection may reactivate, or the
  patient may be reinfected, and then secondary
  tuberculosis is seen. Secondary tuberculosis is
  what the patient in this case had, because of the
  extensive upper lobe cavitary disease. When
  resistance to infection is very poor, a miliary
  pattern of infection may be seen, with numerous
  millet seed (1 to 3 mm) sized granulomas
  scattered extensively throughout the lungs (Slide
  1.6). The infection may also disseminate to other
  organs.

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CASE 2

• Clinical History
• A 50 year old man worked in a foundry (casting
  metal materials using earthen molds) for thirty
  years. He was asymptomatic until a few months
  ago, but now has increasing dyspnea. A routine
  chest x-ray shows a "snow-storm" appearance.

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Slide 2.1One of multiple lung nodules is seen
here at low power.
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Slide 2.2One of multiple lung nodules is seen
here with polarized light microscopy.
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Case 2

• Questions
• Describe what you see in slides 2.1 and 2.2. What
  is the probable diagnosis?
• How does this lesion form? What are the offending
  particles seen in Slide 2.2?
• How do you explain the lengthy hiatus between
  exposure and symptomatology?
• These patients are at high risk for developing
  what disease?

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CASE 2 Silicosis

• Answers
• Describe what you see in slides 2.1 and 2.2. What
  is the probable diagnosis? The lesion consists of
  concentric whirled bundles of hyalinized collagen
  fibers with scattered black pigment. The pattern
  is usually random, with some nodules located in
  perivascular or peribronchiolar location, and
  others scattered within the lung parenchyma. The
  lesion in Slide 2.2 is viewed under polarized
  light, and demonstrates numerous polarizable
  crystals. This is a characteristic picture of
  silicosis.
• How does this lesion form? What are the offending
  particles seen in Slide 2.2? The lesion forms in
  reaction to cellular damage thought to be caused
  by interaction between SiOH groups on the
  hydrated surface of the silica crystals, the
  offending particles, with cellular macromolecules
  in macrophages, including phospholipids and
  proteins. There is damage to lipid membranes,
  with cell injury and death leading to release of
  a soluble protein factor that stimulates
  fibroblast proliferation and collagen synthesis.
• How do you explain the lengthy hiatus between
  exposure and symptomatology? Silicosis is a
  chronic disease that does not manifest itself
  clinically until 20-40 years after the initial
  exposure. The reason can be seen by examining the
  pattern of injury, and realizing that initially
  the hyalinized nodules will be tiny and
  insignificant, but that cellular injury continues
  with ongoing increasing fibrosis and collagen
  deposition until eventually enough normal lung is
  damaged to cause symptoms. This ongoing damage
  does not require continued exposure, rather the
  residual crystals in the lung cause the continued
  damage.
• These patients are at high risk for developing
  what disease? Tuberculosis. Patients with
  silicosis have impaired resistance to tubercle
  bacilli, possibly on the basis of silica-induced
  injury to macrophages. 0.5 to 5.0 of all cases
  of silicosis contract TB, and up to 60 of
  patients with conglomerate silicosis become
  infected.

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CASE 3

• Clinical History
• The patient is a 67 year old veteran with a 50
  pack year history of smoking who is currently
  hospitalized for pancreatitis. He developed a
  productive cough with thick yellow sputum, fever,
  and hypotension after a week in hospital. He had
  an elevated WBC count with left shift. A chest
  radiograph shows increased AP diameter and areas
  of patchy consolidation.

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Slide 3.1The lung is seen here grossly with
lesions more numerous in upper lung fields.
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Slide 3.2The microscopic appearance of the upper
lung field lesions is seen here.
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Slide 3.3The gross appearance of a lung with
patchy infiltrates on chest radiograph is seen
here.
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Slide 3.4The microscopic appearance of an area
of consolidation is seen here at medium power.
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Slide 3.5The microscopic appearance of an area
of consolidation is seen here at higher power.
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Slide 3.6The microscopic appearance of an area
of consolidation is seen here at higher power.
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Case 3

• Questions
• The patient has both a chronic and an acute
  process. Slides 3.1 and 3.2 demonstrates the
  gross and microscopic appearance of the chronic
  process. Slides 3.3 to 3.6 show gross and
  microscopic findings with the acute process.
  Describe both processes.
• What is the chronic process? How does it develop,
  and to what in the clinical history is it
  related?
• This represents one form of this type of lung
  damage. Name the other types, and what their
  respective etiologies are.
• What is the acute process? How might this have
  developed and/or be related to his hospital
  course?

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CASE 3 Centrilobular Emphysema w/Bronchopneumonia

• Answers
• The patient has both a chronic and an acute
  process. Slides 3.1 and 3.2 demonstrates the
  gross and microscopic appearance of the chronic
  process. Slides 3.3 to 3.6 show gross and
  microscopic findings with the acute process.
  Describe both processes. Chronic process The
  airspaces are dilated grossly, and respiratory
  bronchioles are dilated microscopically, with
  preservation of alveolar sacs. The result is the
  appearance of clubbed septa.
• Acute process There are gross areas of
  tan-yellow consolidation, and microscopically
  there are large collections of polymorphonuclear
  leukocytes in the alveoli along with some
  hemorrhage.
• What is the chronic process? How does it develop,
  and to what in the clinical history is it
  related? Centrilobular emphysema. The destructive
  mechanism is thought to be increased protease
  activity in the face of decreased protease
  inhibitors. It is related to smoking.
• This represents one form of this type of lung
  damage. Name the other types, and what their
  respective etiologies are. The other forms of
  emphysema are
• Panacinar emphysema, related to the genetic
  absence or decrease of alpha-1-antitrypsin. The
  acini are uniformly damaged and dilated, from the
  respiratory bronchiole to the terminal acinus.
• Paraseptal emphysema, in which the proximal
  airway is normal and only the distal acinus is
  affected. Greatest in the apices subpleurally,
  and along connective tissue septa. Etiology is
  idiopathic.
• Irregular emphysema, in which acinus is
  irregularly involved, and process is associated
  with scarring.
• What is the acute process? How might this have
  developed and/or be related to his hospital
  course? The acute process is acute
  bronchopneumonia. With pancreatitis the patient
  is already ill, is probably not inspiring deeply,
  and is a set up for hospital acquired pneumonia.
  Common bacterial organisms for hospital acquired
  pneumonias include Staphylococcus aureus,
  Pseudomonas aeruginosa, Streptococcus pneumoniae,
  E. Coli, Klebsiella, and Hemophilus. The most
  common organism for community acquired pneumonias
  is Streptococcus pneumoniae.

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CASE 4

• Clinical History
• A 40 year old female has had a cough that is
  productive of purulent sputum. On occasion, she
  notes spots of blood in the sputum. She has been
  hospitalized for pneumonia twice in the past
  year. She does not have dyspnea, but she has
  recently developed wheezing episodes. Laboratory
  findings include an elevated WBC count with
  neutrophilia and left shift. Sputum culture grew
  3 Serratia marcescens and 2 Pseudomonas
  aeruginosa. A chest radiograph reveals thickened
  bronchi as seen on end, along with linear streaks
  in the right middle lobe.

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Slide 4.1The lung lesion is seen here grossly.
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Slide 4.2The lung lesion is seen here at low
power microscopically.
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Slide 4.3The lung lesion has adjacent parenchyma
seen here microscopically.
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• Questions
• What is the most striking architectural change in
  the lung? Describe it and the related changes?
• What are the possible etiologies of this
  condition?
• Further Clinical History
• A 24 year old male had the findings at autopsy
  shown below. At autopsy his heart weighed 450
  grams and had a dilated right heart with right
  ventricular wall measuring 0.7 cm thick (normal lt
  0.5 cm).

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Slide 4.4The lung of a patient with cystic
fibrosis is seen here grossly.
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Slide 4.5The lung of a patient with cystic
fibrosis is seen here microscopically at medium
power.
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Slide 4.6The lung of a patient with cystic
fibrosis is seen here microscopically at higher
power.
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Slide 4.7The peripheral pulmonary arteries have
the appearance shown here.
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Case 4

• Questions
• What do you think is the etiology for his
  pulmonary findings? What changes do you see in
  the pulmonary vessels, slide 4.7? How does this
  relate to autopsy findings?
• Do you think he was currently suffering from
  acute respiratory symptoms when he died? Why or
  why not?

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CASE 4 Bronchiectasis

• Answers
• What is the most striking architectural change in
  the lung? Describe it and the related changes?
  There is bronchiectasis, with the bronchi
  markedly dilated. There has been destruction of
  the bronchial walls, and there is an intense
  chronic inflammatory infiltrate around them. Note
  that although these are "large" bronchi, there is
  no cartilage present. The epithelial lining is
  focally eroded, with underlying granulation
  tissue. There is peribronchial scarring and
  parenchymal collapse.
• What are the possible etiologies of this
  condition? Multiple possible etiologies,
  including congenital bronchiectasis, post
  obstructive, secondary to necrotizing pneumonia
  (Staphylococcal or TB), immunodeficiency
  disorders, or the immotile cilia and Kartagener's
  syndromes.

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CASE 4 Bronchiectasis

• Answers
• What do you think is the etiology for his
  pulmonary findings? What changes do you see in
  the pulmonary vessels, slide 4.7? How does this
  relate to autopsy findings? The extensive nature
  of the bronchiectasis here, along with the young
  age of the patient, is consistent with cystic
  fibrosis. This is probably the most common
  etiology overall for bronchiectasis, but in such
  cases both lungs are extensively involved. The
  pulmonary arteries show changes of pulmonary
  hypertension, as shown by slide 4.7 which
  highlights a plexiform arteriopathy typical for
  pulmonary hypertension. There is thickening of
  arterial and arteriolar walls, and narrowing of
  lumina. This is related to the relative cardiac
  hypertrophy, and thickening of the right
  ventricular wall (normal is up to 0.5 cm thick),
  indicating a degree of cor pulmonale.
• Do you think he was currently suffering from
  acute respiratory symptoms when he died? Why or
  why not? Probably, as there are areas of
  consolidation and acute pneumonia. Depending on
  the severity of the generalized process
  throughout the lungs he may or may not have been
  in severe distress. Many cystic fibrosis patients
  have chronic infections with Pseudomonas.

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CASE 5

• Clinical History
• The patient is an 84 year old woman who was
  hospitalized for a broken hip. She spiked a fever
  on the second hospital day, with cough producing
  a watery sputum, shaking chills, and marked
  malaise, but antibiotics were not started and she
  died within 36 hours of becoming systemically
  ill. Chest x-ray shows a diffuse consolidation
  in the left lower lobe. CBC showed an elevated
  WBC count with increased bands. Blood cultures
  were reported positive after she died.

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Slide 5.1The lung is seen here grossly.
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Slide 5.2The lung is seen here microscopically.
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Slide 5.3A complicating lesion of the lung
--abscess formation-- is seen here
microscopically.
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Case 5

• Questions
• What is the process demonstrated in these
  sections? How does this differ in pattern from
  what you saw in Case 3?
• What organism(s) might have been cultured from
  her blood, had blood cultures been ordered?
• Does the disease process in these sections look
  severe enough to result in a respiratory death?

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CASE 5 Lobar Pneumonia

• Answers
• What is the process demonstrated in these
  sections? How does this differ in pattern from
  what you saw in Case 3? These slides show a lobar
  pneumonia. There is a diffuse infiltrate of acute
  polymorphonuclear cells in the consolidated lobe.
  In case 3, the infiltrate showed a patchy
  pattern. However, the distinction between
  bronchopneumonia and lobar pneumonia is often not
  clear, as some organisms cause one pattern in
  some patients, and another pattern in other
  patients. Also, treatment with antibiotics can
  alter the pattern as well.
• What organism(s) might have been cultured from
  her blood, had blood cultures been ordered?
  Streptococcus pneumoniae causes 95 of the lobar
  pneumonias, although Klebsiella, Staphylococci,
  Hemophilus influenze, and some gram negative
  enteric bacteria (E. Coli, Klebsiella) may also
  cause it. S. pneumoniae characteristically
  produces a septic phase within the first 24 to 48
  hours during which the organism can readily be
  cultured from the blood.
• Does the disease process in these sections look
  severe enough to result in a respiratory death?
  What else might have contributed to her death?
  Although this looks like a relatively early
  pneumonia, the patient also was septic, which
  causes vascular collapse and hypotension. She
  likely died due to a combination of
  susceptibility due to old age, shock of trauma,
  septic shock and pneumonia.

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CASE 6

• Clinical History
• The patient is a 47 year old migrant farm worker
  who had recently moved from Florida to Southern
  California. Three weeks after beginning work in
  the orchards he presented to a local clinic with
  fever, cough, night sweats and pleuritic chest
  pain. Chest radiograph revealed segmental
  infiltrates, some hilar adenopathy and a small
  pleural effusion.

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Slide 6.1The lung lesion is seen here
microscopically at medium power.
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Slide 6.2The lung lesion is seen here
microscopically at higher power.
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Slide 6.3The lung lesion is seen here
microscopically with Gomori methenamine silver
(GMS) stain.
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Case 6

• Questions
• What type of inflammatory process is present?
  Describe the features of this process.
• What is the differential diagnosis? Which of
  these is most likely given the history? What
  organism do you see?
• How would the histopathology differ if the
  patient had underlying AIDS?
• What proportion of normal hosts exposed to this
  organism develop clinical symptomatology? What
  are the possible outcomes/sequelae of this
  infection?

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CASE 6 Coccidioidomycosis

• Answers
• What type of inflammatory process is present?
  Describe the features of this process. The
  process is granulomatous. The well-formed
  granulomas are formed by palisading epithelioid
  macrophages and chronic inflammatory cells with
  surrounding fibroblasts and collagen. The
  macrophages are large pink cells, oval to
  spindled, which line up around the center, and
  Langhans giant cells are also seen.
• What is the differential diagnosis? Which of
  these is most likely given the history? What
  organism do you see? The differential diagnosis
  includes Mycobacterium tuberculosis, which causes
  caseating granulomas, and the various invasive
  fungal organisms that can cause pulmonary
  disease. In the absence of immune compromise, the
  possibilities include Histoplasmosis,
  Cryptococcosis, Blastomycosis, Coccidioidomycosis,
  and Paracoccidioidomycosis. These each have
  fairly distinctive morphology on GMS (a silver
  stain that highlights the walls of fungal
  organisms in black, on a green background
  counterstain.) The history and morphology in this
  case are classic for Coccidioidomycosis.
• How would the histopathology differ if the
  patient had underlying AIDS? If the patient were
  immunocompromised, particularly with AIDS, the
  histopathology of Cocci is far less granulomatous
  and more suppurative (acute inflammatory cells.)
• What proportion of normal hosts exposed to this
  organism develop clinical symptomatology? What
  are the possible outcomes/sequelae of this
  infection? Only about 10 of the people exposed
  develop clinically evident disease. Of those, the
  vast majority resolve completely either
  spontaneously or with antifungal treatment. gt2 to
  4 may go on to develop systemic dissemination,
  with worsening pulmonary involvement, and spread
  to skin, bones, CNS and other organs.

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CASE 7

• Clinical History
• A 37 year old patient known to be infected with
  the human immunodeficiency virus (HIV) and whose
  last CD4 lymphocyte count was 75/microliter died
  in respiratory failure.

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Slide 7.1The high power microscopic appearance
of one etiologic agent for pulmonary infection is
seen here.
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Slide 7.2The high power microscopic appearance
of the same etiologic agent for pulmonary
infection is seen here.
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Slide 7.3Multiple pulmonary lesions appear in
this immunocompromised patient.
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Slide 7.4The microscopic appearance of one of
the multiple pulmonary lesions is seen here.
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Case 7

• Questions
• There are two etiologic agents. Identify and
  describe the manifestations of each, and name the
  probable organisms.
• Why might this patient have had significant
  bleeding into his lung?
• What other organs might be involved by these
  organisms?

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CASE 7 Cytomegalovirus and Aspergillus Infection

• Answers
• There are two etiologic agents. Identify and
  describe the manifestations of each, and name the
  probable organisms. The more diffuse of the two
  organisms is cytomegalovirus (Slides 7.1 and
  7.2), with numerous affected alveolar cells. The
  affected cells are markedly enlarged, have large
  nuclei with huge pink intranuclear inclusions
  surrounded by a halo. These inclusions occupy
  half the size of the nucleus. In some cells
  multiple smaller basophilic inclusions can be
  seen in they cytoplasm. These represent viral
  coat, or complete virions.
• The second organism (Slides 7.3 and 7.4) is found
  focally in two or three areas showing necrosis
  surrounded by acute inflammatory cells and
  nuclear debris (Slides 7.3 and 7.4). Within these
  areas are starbursts of branching hyphae. These
  are evident even on HE stain, but are
  highlighted by a GMS stain, where again the walls
  of the hyphae are stained black by the silver.
  The probably organism is Aspergillus, which can
  be seen in immunocompromised hosts. Other
  possibilities include Candida, which has
  pseudohyphae and budding yeasts.
• Why might this patient have had significant
  bleeding into his lung? Aspergillus is an
  angioinvasive organism, and causes vasculitis and
  necrosis of vessel walls. Necrosis results in
  holes, holes in vessel walls results in bleeding.
• What other organs might be involved by these
  organisms? Although any organ may be affected,
  CMV infection is especially prominent in the
  lung, adrenal, brain, eye, and gastrointestinal
  tract.
• The pulmonary route is the most common site of
  invasion of Aspergillus in immunocompromised
  hosts, though invasion through the GI tract can
  also occur. In disseminated aspergillosis
  virtually any site can be involved, but brain and
  kidney are the most common.

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CASE 8

• Clinical History
• A 56 year old financial officer with a large
  health maintenance organization with no prior
  major medical illnesses presented to the
  emergency room with acute onset of fever, cough,
  and dyspnea. His chest x-ray showed diffuse
  bilateral fluffy perihilar infiltrates.

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Slide 8.1The gross appearance of the lung is
seen here.
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Slide 8.2The microscopic appearance of the lung
at high power is seen here with HE stain.
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Slide 8.3The microscopic appearance of the lung
at high power is seen here with a GMS stain.
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Case 8

• Questions
• What is the material in the alveoli?
• What do you see on GMS (silver) stain in Slide
  8.3?
• What is his likely underlying condition?
• If this patient had some other reason for being
  immunosuppressed, such as being on
  corticosteroids, receiving chemotherapy for
  malignancy, or having an undiagnosed lymphoma,
  how would the biopsy differ most likely?

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CASE 8 Pneumocystis carinii Pneumonia

• Answers
• What is the material in the alveoli? A foamy
  proteinaceous exudate fills each alveolus. There
  is minimal accompanying inflammation.
• What do you see on GMS (silver) stain in Slide
  8.3? Numerous cup shaped rather delicate
  organisms that look a little like RBC's, however
  notice that the staining is different from RBC's
  in that in the Pneumocystis carinii (PCP) the
  delicate cell wall stains and the center is
  clear, where the RBC's stain more darkly in the
  center.
• What is his likely underlying condition? Probably
  AIDS with HIV infection, but additional history
  and an HIV test are needed.
• If this patient had some other reason for being
  immunosuppressed, such as being on
  corticosteroids, receiving chemotherapy for
  malignancy, or having an undiagnosed lymphoma,
  how would the biopsy differ most likely? In PCP
  infection in AIDS the organism burden is
  overwhelming, with the alveoli packed with
  organisms. In immunosuppression due to other
  causes such as lymphoma, chemotherapy, or steroid
  use, often there are many fewer organisms present
  and one has to hunt to find them.

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CASE 9

• Clinical History
• A 9 year old girl has the sudden onset of severe
  dyspnea with wheezing. She has had similar
  episodes in the past.

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Slide 9.1A sputum cytology specimen is shown
here with a curled thread of inspissated mucus
known as a Curschmann spiral.
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Slide 9.2A sputum cytology specimen is shown
here with several Charcot-Leyden crystals.
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Slide 9.3The appearance of a bronchial wall is
seen here at high magnification. Note the many
eosinophils and the dilated submucosal venules.
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Case 9

• Questions
• How do you explain the sputum cytologic findings?
  
• Why do you seen the inflammatory cell type that
  predominates in Slide 9.3?
• How is this disease likely to differ in adults?
• What are the consequences of this disease?

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CASE 9 Asthma

• Answers
• How do you explain the sputum cytologic findings?
  There is an outpouring of mucus into the airways,
  some of which becomes inspissated and can further
  block expiration, exacerbating the air-trapping
  from the bronchoconstriction. The mucus forms the
  Curschman spirals. The Charcot-Leyden crystals
  are the conglomerates of the reddish granules
  released from eosinophils.
• Why do you seen the inflammatory cell type that
  predominates in Slide 9.3? Asthma in children is
  most often an allergic phenomenon, and many
  asthmatics will demonstrate other forms of atopy.
  This is a form of type I hypersensitivity
  response. The offending allergen reacts with IgE
  coating mast cells lining the airways, resulting
  in release of mast cell granules containing
  cytokines such as histamine that lead to
  bronchoconstriction and edema. Eosinophil
  chemotactic factor is also released.
• How is this disease likely to differ in adults?
  In adults, asthma is typically the "intrinsic"
  variety in which the reaction occurs to stimuli
  such as exercise or cold, not an external
  allergen. However, the end result is the same.
• What are the consequences of this disease? The
  acute episodes can be severe--status
  asthmaticus--which is life-threatening and
  requires immediate treatment with
  bronchodilators. There is a chronic component to
  this disease, since over time there is bronchial
  smooth muscle hypertrophy and submucosal
  glandular hyperplasia. Since this disease is
  typically episodic, chronic obstructive pulmonary
  disease is unlikely to be a result.

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The END!!
Wait, what? More? Are you kidding me right now?
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Laboratory Part II
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CASE 1

• Clinical History
• Slides 1 and 2 are from a neonate was born
  prematurely at 28 weeks gestation, weighing 700
  grams (normal for 28 weeks is 950 grams). The
  mother was a two pack per day smoker who refused
  to cut down or stop smoking during her pregnancy.
  The baby survived for 6 days on a respirator
  requiring very high oxygen levels. Diffuse
  infiltrates were seen on chest x-ray, with a
  "ground glass" appearance, and the PO2 was low on
  blood gas analysis.
• Clinical History
• Slide 1.3 is from an infant with
  hyperbilirubinemia.

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Slide 1.1The lung is shown here at low power
microscopically.
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Slide 1.2The lung is shown here at higher power
microscopically.
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Slide 1.3The lung is shown here at low power
microscopically in a baby with hyperbilirubinemia.

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Case 1

• Questions
• Describe the microscopic appearance of the lung
  sections.
• What is the material in the alveoli? What other
  findings are present that are significant in
  understanding this infant's demise?
• What is the diagnosis? What are the clinical
  manifestations of this disease?
• How might the mother's smoking history have
  contributed to the outcome? What factors are felt
  to contribute to the development of this disease?
  
• What is the chronic form of this disease called?

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CASE 1 Hyaline Membrane Disease

• Answers
• Describe the microscopic appearance of the lung
  sections (Slides 1.1 - 1.3). Sections show
  immature lung with alternating areas of
  atelectasis and alveolar dilatation. Alveolar
  walls are thick, there is marked vascular
  congestion, air spaces contain fluid and
  scattered macrophages, and alveoli are lined by
  thick pink hyaline membranes. In Slide 1.3, the
  jaundice has stained the hyaline membranes
  yellow.
• What is the material in the alveoli? What other
  findings are present that are significant in
  understanding this infant's demise? Hyaline
  membranes are made of coagulated protein and
  fibrin. The low ratio of air space to
  interstitium is evidence of the lung's
  immaturity, a significant risk factor for
  recovery. Another finding indicating immaturity
  that is not demonstrated in the kodachromes is
  the presence of immature cartilage around
  bronchi.
• What is the diagnosis? What are the clinical
  manifestations of this disease? Hyaline membrane
  disease of the newborn. Rapid respirations,
  inspiratory rib retraction, expiratory grunting,
  hypoxemia, and cyanosis.
• How might the mother's smoking history have
  contributed to the outcome? What factors are felt
  to contribute to the development of this disease?
  Smoking during pregnancy is associated with low
  birth weight infants. Possible contributors to
  HMD are prematurity, low birth weight, maternal
  diabetes, intrapartum fetal aspiration, cord
  asphyxia, birth by Caesarean section, maternal
  sedation, and neonatal brain injury, with
  prematurity being by far the most important
  factor.
• What is the chronic form of this disease called?
  Bronchopulmonary dysplasia. It is characterized
  by interstitial and peribronchial fibrosis, and
  epithelial hyperplasia and squamous metaplasia of
  the large airways.

77
CASE 2

• Clinical History
• A 50 year old male with a history of myotonic
  muscular dystrophy was admitted for pneumonia. He
  was doing well and improving after several days
  of IV antibiotics when he suffered a sudden
  cardiac arrest which did not respond to
  resuscitative efforts.

78
Slide 2.1The lesion is seen here grossly.
79
Slide 2.2The microscopic apperance is shown
here.
80
Slide 2.3The microscopic apperance is shown here
at high magnification.
81
Case 2

• Questions
• The gross and microscopic appearance of a
  thromboembolus in a pulmonary artery is shown.
  What acute changes might you see in the heart?
• What do you see in the clot (Slide 2.3) that
  helps you to know this is a pre-mortem and not a
  post-mortem clot? Where do these clots come from?
  
• Name as many predisposing conditions as you can
  think of that could lead to pulmonary emboli.
• What might we see in other sections of the lung
  that would be related to the PE? What are these
  called? What are the signs and symptoms that
  should lead you to suspect PE?

82
CASE 2 Pulmonary Thromboembolism

• Answers
• The gross and microscopic appearance of a
  thromboembolus in a pulmonary artery is shown.
  What acute changes might you see in the heart?
  Acute dilatation of the right ventricle, and
  possible right atrium, with thinning of the
  ventricular wall.
• What do you see in the clot (Slide 2.3) that
  helps you to know this is a pre-mortem and not a
  post-mortem clot? Where do these clots come from?
  Layering of RBC's, fibrin, and WBC's is typical
  of pre-mortem clot, the so called lines of Zahn.
  Thromboemboli in the lungs usually come from deep
  veins in the legs, but may also come from the
  pelvic veins.
• What factors are involved in thrombogenesis? Name
  as many predisposing conditions as you can think
  of that could lead to pulmonary emboli. The three
  factors involved in thrombogenesis are stasis,
  abnormalities in the vessel wall, and alterations
  in the coagulation system. Conditions associated
  with high risk of thromboembolism include the
  postoperative state, pregnancy, use of birth
  control pills, congestive heart failure, chronic
  pulmonary disease, fractures or other injuries of
  the lower extremities, chronic deep venous
  insufficiency of the legs, prolonged bed rest,
  and carcinoma.
• What might we see in other sections of the lung
  that would be related to the PE? What are these
  called? What are the signs and symptoms that
  should lead you to suspect PE? You may see
  evidence of earlier PE's, which consist of
  thromboemboli in various states of organization,
  from unorganized clot to thin fibrous bands or
  endothelialized scars on the vessel walls. The
  bands are called "fiddle-strings." The sudden
  onset of severe unexplained dyspnea, syncope, or
  breathlessness should suggest PE. The most
  consistent sign is tachycardia.

83
CASE 3

• Clinical History
• This is a 50 year old woman with a previous
  diagnosis of infiltrating ductal carcinoma of the
  breast. She underwent mastectomy. She now
  presents with bilateral serosanguineous pleural
  effusions.

84
Slide 3.1Note what is distending the lymphatic
spaces.
85
Slide 3.2The microscopic appearance of the lung
is seen at low power.
86
Slide 3.3The microscopic appearance of the
adjacent lung parenchyma is seen at high power.
87
Case 3

• Questions
• The clusters of malignant cells in this section
  are metastatic breast carcinoma. Where are they
  located?
• Look carefully at the smaller arterioles? What
  changes do you see in the vessels? What is the
  mechanism?
• What is/has gone on in the alveolar spaces? What
  is the brown pigment?
• What do you think this woman's respiratory
  symptomatology was during her terminal phase?
• What is the most common tumor in the lung?

88
CASE 3 Metastatic Carcinoma

• Answer
• The clusters of malignant cells in this section
  are metastatic breast cancer. Where are they
  located? Primarily in lymphatics which run around
  the bronchovascular bundles and in the
  interlobular septa, but you can also see tumor in
  vessels and a few nodules in the parenchyma.
• Look carefully at the smaller arterioles in Slide
  3.2 What changes do you see in the vessels? What
  is the mechanism? This section demonstrates
  changes of pulmonary hypertension as well as the
  lymphatic and vascular spread of cancer. The
  change you see is marked thickening of vessel
  walls, with luminal compromise, due to intimal
  proliferation and medial hypertrophy. The likely
  mechanism in this case is obstruction downstream
  in the vessels by cancer.
• What is/has gone on in the alveolar spaces in
  Slide 3.3? What is the brown pigment? Hemorrhage
  is present in the alveoli. The brown pigment is
  hemosiderin.
• What do you think this woman's respiratory
  symptomatology was during her terminal phase? She
  was likely quite dyspneic and hypoxemic.
• What is the most common tumor in the lung?
  Metastatic cancer.

89
CASE 4

• Clinical History
• A 63 year old male presented with hemoptysis of
  three weeks duration. He had a 50 pack year
  history of smoking. His chest x-ray showed a
  large central peri-hilar mass. A fine needle
  aspiration (FNA) of the mass was performed.

90
Slide 4.1There is a large mass adjacent to the
hilum of the right lung.
91
Slide 4.2There are dark, angular cells with
orange-staining cytoplasm seen in this fine
needle aspiration cytologic smear of cells from
the mass.
92
Slide 4.3The microscopic appearance of the
lesion is seen here at medium power.
93
Slide 4.3The microscopic appearance of the
lesion is seen here at medium power.
94
Slide 4.4The microscopic appearance of the
lesion is seen here at high power.
95
Slide 4.6The microscopic appearance of the
pulmonary parenchyma distal to the lesion is seen
here at high power.
96
Case 4

• Questions
• Describe the histopathology of the mass lesion
  (Slides 4.2 - 4.5). What is the diagnosis? What
  features do you use to make this diagnosis?
• Where does this lesion usually arise? What is the
  hypothesized mechanism of carcinogenesis?
• What might you see in the parenchyma of the lung
  behind the lesion (Slide 4.6)?

97
CASE 4 Squamous Cell Carcinoma

• Answers
• Describe the histopathology of the mass lesion.
  What is the diagnosis? What features do you use
  to make this diagnosis? There are cords and
  sheets of large cells intertwining with whorls of
  desmoplastic fibrous tissue. The large cells are
  arranged in a mosaic pattern, and have abundant
  eosinophilic cytoplasm and large nuclei. The
  nuclei show the malignant features of
  hyperchromasia, irregular nuclear border,
  chromatin clumping, and numerous mitoses. This is
  a moderately differentiated squamous carcinoma.
  To make this diagnosis you need to see
  keratinization and/or keratin pearls, and/or
  intercellular bridges. In this case, bridges are
  fairly easy to find, and there are occasional
  individually keratinized cells, though
  keratinization is not a prominent feature in this
  case.
• Where does this lesion usually arise? What is the
  hypothesized mechanism of carcinogenesis?
  Squamous carcinomas are most often central,
  arising in the mainstem, 1st, 2nd, or 3rd order
  bronchi. The mechanism of carcinogenesis is
  thought to be a response to a carcinogen, most
  often smoking, in the bronchial epithelium
  resulting first in metaplasia from columnar to
  squamous, going on to cytologic atypia and then
  carcinoma.
• What might you see (Slide 4.6) in the parenchyma
  of the lung behind the lesion? Since bronchogenic
  carcinoma often arises in bronchi, there is often
  bronchial plugging. This may lead to
  bronchopneumonia in the lung behind the cancer,
  or to endogenous lipid pneumonia. In the first
  case you would see acute inflammation, in the
  second numerous large lipid laden macrophages in
  the alveolar space.

98
CASE 5

• Clinical History
• A 32 year old housewife presented to her family
  doctor with cough of six weeks duration and
  recent onset of fever and malaise. A chest x-ray
  showed a right upper lobe infiltrate with
  suggestion of a proximal mass on lateral film.
  She underwent bronchoscopy, biopsy, and
  subsequent right upper lobectomy.

99
Slide 5.1The microscopic appearance of the
lesion is seen here at low power.
100
Slide 5.2The microscopic appearance of the
lesion is seen here at high power.
101
Case 5

• Questions
• Describe the main lesion. Where is it located?
  What is the diagnosis?
• The patient bled profusely when the lesion was
  biopsied. Why? Why had she recently developed
  fever and malaise and how does this relate to her
  chest x-ray findings?
• What is the characteristic feature of these
  tumors by electron microscopy?
• In what other organs do these commonly arise?
  What is the prognosis of these tumors?
• What is the related neoplasm with a more ominous
  prognosis? How does it differ histologically?

102
CASE 5 Pulmonary Carcinoid Tumor

• Answer
• Describe the main lesion. Where is it located?
  What is the diagnosis? The mass is composed of
  nests, cords, and sheets of cells lined by
  delicate fibrous septa. The cells are round,
  regular with small uniform nuclei and infrequent
  mitoses. It is located in the bronchus. It is a
  carcinoid tumor.
• The patient bled profusely when the lesion was
  biopsied. Why? Why had she recently developed
  fever and malaise and how does this relate to her
  chest x-ray findings? Carcinoid tumors are
  extremely vascular and thus often bleed when
  biopsied. The parenchyma behind the tumor shows
  abundant neutrophils and thus she has a
  superimposed pneumonia explaining the symptoms
  and chest x-ray.
• What is the characteristic feature of these
  tumors by electron microscopy? By electron
  microscopy these tumors show electron dense
  neurosecretory granules.
• In what other organs do these commonly arise?
  What is the prognosis of these tumors? They often
  arise also in the GI tract, with the appendix
  being a fairly frequent site. The prognosis is
  usually excellent, though they may metastasize to
  regional nodes.
• What is the related neoplasm with a more ominous
  prognosis? How does it differ histologically? The
  most malignant end of the neuroendocrine spectrum
  is oat cell, or small cell carcinoma of the lung,
  which has an almost uniformly fatal outcome. The
  cells are more hyperchromatic with almost no
  cytoplasm. They show little overall architecture.
  Nuclear molding (nucleus of one cell wrapping
  around that of another) is a distinctive feature.
  Usually the chromatin has a kind of "salt and
  pepper" look to it.

103
CASE 6

• Clinical History
• A 47 year old school teacher, a non-smoker, was
  admitted for inguinal herniorrhaphy. A
  pre-operative routine chest x-ray revealed a 3 cm
  nodule in the right upper lobe which was not
  present on an x-ray taken two years prior. No
  evidence of mediastinal adenopathy was found on
  CT scan. A right upper lobectomy was performed.

104
Slide 6.1The chest radiograph is shown here,
with the right upper lobe mass lesion. This
patient has had a previous coronary bypass graft
placed, and there are vascular clips and sternal
wire sutures.
105
Slide 6.2The chest CT scan shown here
demonstrates the right upper lobe mass lesion
which causes a focal scar of the overlying pleura.
106
Slide 6.3This nuclear medicine PET tumor image
scan which looks like a series of paper doll
cutouts demonstrates the right upper lobe mass
lesion but no other areas suggesting metastases.
The brain and bladder have marked uptake.
107
Slide 6.4The gross appearance of a similar
lesion in the left lower lobe is seen here.
108
Slide 6.5The microscopic appearance of the
lesion is seen here at medium power.
109
Case 6

• Questions
• Describe the location, gross appearance, and
  histopathology of this lesion.
• What is the diagnosis? Where are these lesions
  usually located?
• This lesion was enclosed within the lung and all
  of the hilar and mediastinal nodes sampled were
  free of tumor. What stage is this tumor? What is
  the prognosis for this patient?

110
CASE 6 Adenocarcinoma

• Answers
• Describe the histopathology of this lesion. This
  lesion shows sheets and cords of large cells with
  glandular formation, and mucin production. The
  cells have abundant pink to grey, somewhat bubbly
  cytoplasm. The nuclei are oval to angulated and
  have prominent nucleoli. Mitoses are easy to
  find, but not numerous. Areas of necrosis can be
  seen.
• What is the diagnosis? Where are these lesions
  usually located? This is an adenocarcinoma. They
  are more often peripheral than central.
• This lesion was enclosed within the lung and all
  of the hilar and mediastinal nodes sampled were
  free of tumor. What stage is this tumor? What is
  the prognosis for this woman? This is a stage T2
  N0 M0 tumor (a T1 tumor of the lung is lt3 cm).
  Five year survival is still only about 30,
  despite the small size and absence of positive
  lymph node involvement.

111
CASE 7

• Clinical History
• A 54 year old man suffered chest injuries in a
  car accident. X-rays showed no evidence of broken
  ribs, but an incidental finding of a solitary
  lung nodule was seen peripherally in the right
  lower lobe. No prior x-rays were available for
  comparison. CT scan showed the lesion to be
  sharply circumscribed, with no associated
  detectable adenopathy. Percutaneous CT guided
  fine needle aspiration (FNA) was attempted, but
  no cellular elements were obtained. He went to
  surgery, and after a frozen section diagnosis, a
  segmental wedge resection was performed and the
  patient spared a lobectomy.

112
Slide 7.1The radiographic appearance of this
"coin lesion" is seen here.
113
Slide 7.2The gross appearance of the lesion is
seen here on the right. A similar but smaller
lesion is seen at the left.
114
Slide 7.3The microscopic appearance of the
lesion is seen here.
115
Case 7

• Questions
• Describe the gross appearance of the lesion and
  then identify histopathologic features, including
  as many elements as you can identify. Why do you
  think they were unable to obtain cellular
  material by FNA. Had they been able to make the
  diagnosis by FNA, what do you think they would
  have done differently?
• What is the diagnosis? What is the significance?
• Where does this lesion arise from?
• Why was the surgeon able to shell it out, rather
  than remove a lobe?

116
CASE 7 Pulmonary Hamartoma

• Answers
• What is the diagnosis? What is the significance?
  This is a pulmonary hamartoma. They are benign,
  harmless lesions, but can be confused on chest
  x-ray with malignancies.
• Where does this lesion arise from? They are
  thought to arise as abnormal proliferations of
  normal elements in the lung.
• Why was the surgeon able to shell it out, rather
  than remove a lobe? They are benign, never
  metastasize, and are well- circumscribed and easy
  to separate from the surrounding lung parenchyma.

117
One More

• Finally

118
CASE 8

• Clinical History
• A fire inside a house results in minimal
  superficial burn injuries involving 22 total
  body surface area, mainly the head and neck area,
  to a 28 year old female. However, inhalation of
  hot gases from the fire in an enclosed space
  leads to inhalation injury. In hospital, she
  requires increasing FIO2 to 100 to maintain
  arterial oxygen saturations.

119
Slide 8.1The gross appearance of the lung is
seen here. The lung is diffusely firm and
rubbery.
120
Slide 8.2The microscopic appearance of the lung
is seen here at high magnification. Note the pink
hyaline membranes and the type II cell
hyperplasia.
121
Slide 8.3The gross appearance of the lung is
seen here after a month of mechanical
ventilation.
122
Case 8

• Questions
• Describe the gross and microscopic appearances of
  the lungs
• What is the diagnosis? How does this process
  occur?
• What is the natural history of this process?

123
CASE 8Diffuse Alveolar Damage (DAD)

• Answers
• Describe the gross and microscopic appearances of
  the lungs There is diffuse consolidation along
  with the hyaline membrane formation and type II
  cell hyperplasia.
• What is the diagnosis? How does this process
  occur? This is pulmonary diffuse alveolar damage
  (DAD) which clinically is often called adult
  respiratory distress syndrome (ARDS). There are
  many causes, including shock from trauma,
  infections, inhalation of chemical irritants or
  hot gases in a fire, drug therapy, and others.
  DAD is essentially the final common pathway for
  any severe lung injury. Oxygen toxicity also
  potentiates the lung injury leading to DAD.
  Unfortunately, oxygen therapy is needed to treat
  the lung injury. DAD starts with injury to the
  alveoli and capillaries, resulting in exudation
  of fluids and proteins that form the hyaline
  membranes.
• What is the natural history of this process? The
  early acute, or exudative, phase of DAD, most
  prominent in the first week of injury, is
  characterized by interstitial and intra-alveolar
  edema, passive congestion, inflammation, and
  hyaline membranes. The hyaline membranes are
  composed of fibrin-rich edema fluid mixed with
  the cytoplasmic remnants of necrotic epithelial
  cells. The type II epithelial cells undergo
  proliferation in an attempt to regenerate to
  alveolar lining.
• As the process continues, the hyaline membranes
  diminish and the type II cells increase, while
  there is interstitial thickening and increasing
  numbers of mononuclear inflammatory cells. The
  next stage, the proliferative or organizing stage
  of DAD, occurs after 1 to 2 weeks. The exudates
  organize, and interstitial thickening becomes
  more prominent. Fibroblasts begin laying down
  more collagen. Near the end of a month, there is
  extensive fibrosis, with gross changes (seen in
  slide 8.3) of "honeycomb" lung.

124
That all,The End,Fini!

• This is the last WebPath PowerPoint of 2004. I
  hope you enjoyed!
• Now go take a nap!

125
(No Transcript)