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Lung Biopsy Interpretation
Wednesday, March 10, 2004
Anna-Luise A. Katzenstein & Jeffrey L. Myers
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Guidelines for Handling and Interpreting Lung Biopsy Specimens
From the Operating Room
 | The tissue should be cultured. It is easiest if the surgeon places a piece of tissue in sterile media in the operating room. |
| Frozen section may be helpful, both to assess adequacy of the biopsy specimen and to determine what additional studies may need to be performed on the tissue. |
| Snap-freezing for immunofluorescence is rarely necessary. The only situation in which it is indicated is in cases of alveolar hemorrhage. |
| Probably the most important part of the procedure is to keep most of the specimen for light microscopy. |
| Electron microscopy has no role in diagnosing non-neoplastic lung disease, and inflation of lung biopsy specimens is not necessary. |
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In the Histology Laboratory
| Routine H & E stains are the mainstay for evaluating non-neoplastic lung diseases. |
| The most important special stains are those for detecting microorganisms, and, in our experience, the Ziehl-Neelsen for acid fast bacilli and the Gomori methenamine silver (GMS) for fungi are the most reliable. |
| The Prussian blue stain for iron can be useful in distinguishing hemosiderin from smokers' pigment, and it is also helpful in identifying asbestos bodies. |
| The trichrome stain has no role in evaluating non-neoplastic lung disease, and elastic tissue stains are of limited use. The latter can help in evaluating the vasculature in pulmonary hypertension, but they should be interpreted cautiously in cases of suspected vasculitis. |
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Interaction with Clinicians
Although some non-neoplastic diseases can be diagnosed without clinical history, knowledge of at least a few minimal clinical features is necessary in most cases. This information does not need to be detailed, but includes the following:
| Immune status (is the patient immunocompromised?) |
| Nature of the onset (acute, subacute, or chronic?) |
| Radiographic findings (is the disease localized or diffuse, interstitial or airspace?) |
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Sometimes the clinical information can be inferred from the clinical impression (ie., "suspected IPF" would imply a diffuse interstitial process with chronic course).
Making the Diagnosis
An organized approach to the slides is imperative:
- Start with low magnification to determine the main site of involvement (interstitial, airspace, mixed), the extent (patchy or diffuse), and the distribution (perivascular, peribronchiolar, lymphangitic, random).
- Go to high magnification to determine the nature of cellular infiltrate or other abnormality.
This 73 year old man complained of increasing dyspnea and dry cough for two years. He currently is unable to walk more than a few feet without becoming dyspneic. Rales were noted bilaterally on physical examination and there was evidence of early clubbing. Pulmonary function tests showed severe restrictive defects. Chest x-ray and CT showed bilateral interstitial reticular opacities worse at the bases with foci of subpleural honey-comb change. An open lung biopsy was performed.
Case 1 - Figure 1 - Low magnification view showing an interstitial process with distinctly non-uniform appearance. There are alternating zones of alveolar septal fibrosis, inflammation and normal lung.
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Case 1 - Figure 2 - Another area from the same slide composed of end-stage, honey-comb lung.
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Case 1 - Figure 3 - The area in this photo contains prominent interstitial inflammation and fibrosis within which a small, well-delineated, lightly staining fibroblast focus is visible.
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Case 1 - Figure 4 - Higher magnification of fibroblast focus shown in Figure 3. This lesion is an aggregate of oval to spindle-shaped fibroblasts and myofibroblasts arranged with their long axes parallel to the long axis of the alveolar septum. They are embedded in lightly staining, myxoid appearing stroma.
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This 38-year-old man presented for evaluation of persistent non-productive cough and increasing shortness of breath with exertion. He was first seen approximately 9 months prior to admission for evaluation of an abnormal chest radiograph. At that time his PA chest film and CT scan were described as showing numerous small nodular opacities throughout both lungs with bilateral hilar adenopathy. Repeat CT scan showed diffuse bilateral faintly nodular infiltrates with predominantly upper lung cystic changes and mild mediastinal and hilar adenopathy. He continued to smoke one pack of cigarettes per day as he had for approximately 20 years. He underwent video assisted thoracoscopic lung biopsy.
Case 2 - Figure 1 - Low magnification photomicrograph showing a stellate nodule with associated enlargement of surrounding air spaces ("paracicatricial airspace enlargement").
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Case 2 - Figure 2 - Higher magnification photomicrograph showing expansion of interstitium by a mixed population of mainly mononuclear cells. Extension of the polymorphic infiltrate from peribronchiolar interstitium into contiguous alveolar septa results in the stellate configuration illustrated in Figure 1.
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Case 2 - Figure 3 - High magnification photomicrograph demonstrating Langerhans cells. Langerhans cells closely resemble histiocytes and are distinguished by their irregular, highly convoluted nuclear contours.
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This 43 year old man was hospitalized for shortness of breath, fever, pleuritic chest pain, and headache that began several days before admission. He was found to be severely hypoxemic with a pO2 of 53 and oxygen saturation of 86% on 4 liters of oxygen. Chest x-ray showed bilateral lung opacification. The patient had a history of a similar illness one year previously requiring mechanical ventilation and treated with antibiotics and corticosteroids. He had a history of crack cocaine use in the past, but vigorously denied recent use. He was taking methadone for chronic back pain and had a history of gastroesophageal reflux disease. He was intubated and a thorascopic lung biopsy performed.
Case 3 - Figure 1 - Low magnification view showing interstitial thickening and hyaline membranes lining alveolar septa.
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Case 3 - Figure 2 - Higher magnification showing the homogeneous eosinophilic hyaline membranes lining thickened alveolar septa.
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This 52 year old woman was admitted for orthotopic right lung allotransplantation. Her respiratory problems began at the age of 36 years when she developed recurrent spontaneous pneumothoraces. About three years after experiencing her first pneumothorax she underwent sequential left and right parietal pleurectomies. She suffered no pneumothoraces after surgery, but experienced progressive shortness of breath and a steady decline in exercise tolerance. She underwent transplantation for presumed idiopathic bullous emphysema.
Case 4 - Figure 1 - Low magnification photomicrograph demonstrating cystic space associated with nodular aggregates of spindle cells.
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Case 4 - Figure 2 - Higher magnification view highlighting the nodular aggregate of spindle cells. The cells are haphazardly arranged in the wall of the cystic space and surround vascular spaces.
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Case 4 - Figure 3 - High magnification view showing plump spindle cells with cytologic attributes resembling smooth muscle cells.
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This 28 year old man presented with a several month history of dry cough and was found to have a collapsed left upper lobe and enlarged hilar and mediastinal lymph nodes. The patient underwent thoracotomy. At surgery firm tumor-like tissue was found in the hilar area and also in nodules studding the pleural surface. A left upper lobectomy was performed.
Case 5 - Figure 1 - Non-necrotizing granuloma located along an interlobular septum. The granuloma is well-demarcated from the surrounding tissue, and the adjacent alveolar septa are normal without evidence of interstitial inflammation.
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Case 5 - Figure 2 - Higher magnification view of the non-necrotizing granuloma in Figure 1 showing focal hyalinization and a surrounding thin rim of lymphocytes.
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Case 5 - Figure 3 - Granulomatous vasculitis involving a medium sized artery.
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This 67 year old South American physician presented with a 9 month history of episodic cough and malaise associated with shortness of breath. Chest x-ray showed nonspecific patchy bilateral air-space opacities. Pulmonary function studies showed moderate restriction (FVC 51% of the predicted value) with reduction in diffusing capacity (DLCO 48% of the predicted value) and desaturation at rest and during exercise (O2 saturation 79% at rest and 72% after exercise). He underwent thoracotomy and open lung biopsy.
Case 6 - Figure 1 - Low magnification photomicrograph showing an area of intraluminal fibrosis ("organizing pneumonia").
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Case 6 - Figure 2 - Higher magnification view showing the polypoid configuration of the intraluminal fibroblastic plugs characteristic of BOOP.
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Case 6 - Figure 3 - Photomicrograph showing another area of organizing pneumonia, here associated with prominent foamy histiocytes in surrounding air spaces. Although not specific, the presence of foamy histiocytes is characteristic of BOOP and is sometimes a helpful clue to the diagnosis.
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This 64 year old woman presented with a 5 month history of nonproductive cough and weight loss. Chest x-ray and CT showed two right upper lobe nodules, one of which was cavitating. A right upper lobectomy was performed because of the clinical suspicion of malignancy. Grossly, the lesions were well circumscribed, rubbery, pink to tan, and focally necrotic. They measured 8 and 4 cm in diameter each. The patient had no history of sinus or renal disease. An ANCA test was negative.
Case 7 - Figure 1 - Low magnification showing haphazardly arranged, basophilic appearing necrotic zone within background fibrosis and chronic inflammation.
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Case 7 - Figure 2 - Higher magnification of necrotic zone showing karyorrhectic nuclear debris and surrounding rim of palisading epithelioid histiocytes and multinucleated giant cells.
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Case 7 - Figure 3 - Necrotizing vasculitis involving a portion of the wall of a medium sized pulmonary artery.
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Case 7 - Figure 4 - Necrotizing acute capillaritis in lung tissue adjacent to an area of necrotizing granulomatous inflammation. Note the acute inflammation and histiocytes that infiltrate, expand and destroy the alveolar septum.
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This 24 year old man presented with fever and nonhealing erosive skin lesions on his lower extremities. Chest x-ray revealed bilateral circumscribed opacities. Skin biopsy was nondiagnostic and he underwent open lung biopsy.
Case 8 - Figure 1 - Low magnification photomicrograph illustrating a zone of necrosis bounded by a densely cellular infiltrate.
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Case 8 - Figure 2 - High magnification view illustrating a polymorphic lymphocytic infiltrate that includes isolated large atypical cells with coarsely clumped chromatin and prominent nucleoli. Large atypical cells represent the population of neoplastic EBV-infected B cells.
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Case 8 - Figure 3 - Photomicrograph demonstrating a transmural infiltrate of lymphoid cells involving a pulmonary artery.
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This 51 year old woman complained of fever and malaise for several weeks. Chest x-ray showed a large infiltrate involving the right upper, middle and lower lobes. She was hospitalized for three weeks during which time she was treated with antibiotics and gradually improved. Eosinophilia ranging from 3 to 11% was noted and a total eosinophil count measured 1320 at one point. One week following discharge she noted recurrence of fever and chills and a chest x-ray showed a new left mid-lung field infiltrate with clearing of the right lung. White blood count was 10.9 with 5% eosinophils.
Case 9 - Figure 1 - Low magnification photomicrograph showing combined interstitial and airspace inflammatory infiltrate.
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Case 9 - Figure 2 - Higher magnification showing numerous eosinophils and some macrophages within alveolar spaces. There is mild chronic inflammation in alveolar septa and prominent edema in alveolar spaces.
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Case 9 - Figure 3 - High magnification view showing cluster of eosinophils in the center of an alveolus with surrounding proteinaceous exudate.
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This 54 year old man presented with a year long history of persistent shortness of breath on exertion. He was hospitalized elsewhere 5 months prior to admission for a right lower lobe "pneumonitis" without an identified etiology. His dyspnea worsened and he developed a daily cough productive of scant yellow to clear sputum. He smoked a pack of cigarettes a day for 35 to 40 years. Occupational history included significant exposure to asbestos and calcium silicate powder in a steel mill. Admission CT scans showed extensive areas of ground glass attenuation.
Case 10 - Figure 1 - Photomicrograph illustrating extensive filling of alveolar spaces by a granular eosinophilic exudate.
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Case 10 - Figure 2 - High magnification photomicrograph showing the granular, paucicellular, eosinophilic exudate typical of PAP. The exudate includes occasional histiocytes and "ghosts" of necrotic mononuclear cells.
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