Lung Biopsy Interpretation
Case 5 -
Anna-Luise A. Katzenstein & Jeffrey L. Myers
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.
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.
Case 5 - Figure 3 - Granulomatous vasculitis involving a medium sized artery.
This biopsy shows extensive non-necrotizing granulomatous inflammation in the lung
interstitium. The granulomas are well-demarcated, mature, and "sarcoid-like", and they are present
around bronchioles and arteries as well as in alveolar septa and in the pleura. Extensive hyalinization
is present in the center of some confluent areas of granuloma formation, and there are small foci of
necrosis. The interstitium adjacent to the granulomatous areas is normal with no significant
inflammation. A prominent granulomatous vasculitis is present in most arteries and is characterized by
the infiltration of the media and intima by non-necrotizing granulomas. The vascular elastic layer is
often distorted by the process, and there is intimal thickening by fibrosis and chronic inflammation with
Non-necrotizing granulomas are the histologic hallmark of sarcoidosis, and although granulomas can
have numerous etiologies, sarcoid granulomas have several features that should suggest the diagnosis.
First, the granulomas are located exclusively in the interstitium where they follow a lymphangitic
distribution along bronchovascular bundles, interlobular septa and the pleura. Second, they appear
sharply demarcated, composed of central tightly organized epithelioid histiocytes surrounded by a
peripheral rim of fibroblasts and variable numbers of lymphocytes. Third, areas of hyalinized fibrosis
frequently replace portions of the cellular components of the granulomas, and they may be prominent as in
this case. Common but entirely non-specific associated findings include multinucleated giant cells and
various intracytoplasmic structures such as asteroid bodies, Schaumann or conchoid bodies and crystalloid
A variety of atypical histological features may be encountered in well documented examples of
Atypical Histologic Features in Sarcoidosis
|Prominent granulomatous vasculitis|
|Necrosis in granulomas|
|Loosely formed granulomas|
|Large, polarizable crystals|
Sometimes, as in this particular case, granulomatous vasculitis is
prominent, and the possibility of necrotizing sarcoid granulomatosis or
other primary vasculitis enters the differential diagnosis. Granulomatous vasculitis is common in
ordinary sarcoidosis, however, occurring in about 60% of cases where it is found in and around the
parenchymal granulomatous inflammation. In some reported cases the granulomatous vasculitis was so
severe and extensive that pulmonary hypertension developed due to occlusion of arteries and veins by the
vascular granulomas. Necrotizing sarcoid granulomatosis differs from ordinary sarcoidosis in that the
granulomatous vasculitis is found in areas of lung not containing parenchymal granulomas, and there is
prominent parenchymal necrosis. Wegener's granulomatosis is not a serious consideration in the
differential diagnosis since it does not have non-necrotizing granulomas. Another unusual feature is the
presence of small foci of necrosis within the granulomas. Although necrosis
should stimulate careful search of special stains for organisms, it does not preclude the diagnosis of
sarcoidosis, and unless it is extensive, necrotizing sarcoid granulomatosis should not be considered in
the differential diagnosis. Sometimes the granulomas in sarcoid are loose
rather than well-formed. In such cases other causes of granulomatous inflammation need to be carefully
excluded, especially infection, and the diagnosis will ultimately rest on the clinical assessment.
Occasionally the granulomas contain large, polarizable crystals that are so
numerous as to suggest the possibility of inhaled or injected exogenous substances in the etiology.
These crystals have been shown to be calcium oxalate and calcium carbonate and are thought to represent
metabolic breakdown products of cellular metabolism. They can be found in any chronic granulomatous
process and are not unique to sarcoidosis.
The diagnosis of sarcoidosis requires careful correlation of the clinical with the pathologic findings
as well as exclusion of other known causes of granulomatous inflammation, especially infections.
Interestingly, sarcoidosis has been described in patients with HIV infection, usually in association with
highly active anti-retroviral treatment (HAART), and rare cases have also been described in patients
receiving interferon therapy for hepatitis C. Because of the need for clinical correlation, the
pathologist usually can only make a descriptive diagnosis of "non-necrotizing granulomas", although in
histologically typical cases the phrase, "consistent with sarcoidosis", can be added and is often helpful
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