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Digital Case Challenge: Pleuropulmonary amyloidosis

Posted May 26 2010 12:52pm

A 68-year-old man presents with a history of recurrent bilateral pleural effusions over the past six months and recent CT scan of the chest showing persistent small bilateral effusions ground-glass opacities in the superior segment of the left lower lobe and surrounding atelectasis.  The patient underwent thoracoscopy and local pleurectomy and wedge biopsy of the left lower lobe.  Additional history obtained post hoc disclosed a 5-year history of Waldenstrom's macroglobulinemia.

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Typical area showing interstitial thickening and thickened vessel walls without significant interstitial inflammation

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A more solid nodular area with marked distortion of the alveolar architecture

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High power view showing thickened interstitium with amorphous eosinophilic material.  Note lack of interstitial inflammation.

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Congo red stain with and without polarization.  Note the apple-green birefringence characteristic of amyloid.

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Prominent perivascular accumulation with eosinophilic material (above) confirmed as amyloid with Congo red and polarization (below).

Pulmonary Amyloidosis

Pulmonary amyloidosis includes a spectrum of clinicopathologic entities that commonly have deposition of amorphous, eosinophilic, fibrillar amyloid proteins in extracellular spaces in the alveolar interstitum, around blood vessels, and/or in the tracheobronchial submucosa.Four clinical syndromes are associated with pulmonary amyloidosis:
  • Systemic or Generalized
  • Limited or Localized
  • Diffuse Alveolar Septal
  • Pleural
Systemic amyloidosis may be primary (idiopathic) and associated with AL amyloid protein, secondary (or "reactive") to a variety of conditions and associated with AA amyloid protein; senile associated with beta-2-microglobulin, or multiple myeloma-associated (AL).Secondary amyloidosis involving the lung can be associated with rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, tuberculosis, bronchiectasis, and familial Mediterranean fever but is most commonly found (as in this case) in monoclonal gammopathies accompanying lymphoproliferative disorders, e.g., Waldenstrom's macroglobulinemia, nodular lymphoid hyperplasia, LIP, and MALT lymphoma.
There are three main types of limited amyloidosis that involve the lung:
  • nodular
  • diffuse alveolar septal
  • tracheobronchial
In the nodular type the normal lung is replaced by a mass of amorphous, eosinophilic, extracellular material.  Focal areas like this were found in this specimen (see above).  This pattern may be found in an excised "coin lesion" found radiographically and may be referred to as an "amyloidoma."  The diffuse alveolar septal type is characterized by diffuse, uniform, fine interstitial and/or perivascular deposits; multiple small interstitial or perivascular nodules; or larger confluent nodules.  The appearance may be mistaken as interstitial fibrosis but a key feature is the lack of interstitial chronic inflammation which is seen in most interstitial pneumonitides.  The tracheobronchial pattern forms polypoid nodules in major bronchi and the protein is deposited in irregular nodular masses or diffuse sheets in the tracheobronchial walls.  Congo red stain with polarized microscopy should be performed to confirm the presence of amyloid protein deposition.  A trichrome stain is helpful to evaluate when the septal pattern is present; amyloid is blue-gray with Mallory's trichrome in contrast to the more distinct deep blue color of collagen.

Multinucleated foreign-body-type giant cells are frequently seen around the edges of nodular deposits but are an uncommon finding in the diffuse alveolar septal pattern.  This case showed an area with numerous giant cells and intracellular "ingested" amyloid could be demonstrated with a Congo red stain.  Stains for AFB and fungi were performed to rule out infection and were negative.

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The usual pulmonary pathology textbooks can be referenced.  Hope you enjoyed!



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