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More on granulomatous lung disease: Pneumocystis jiroveci

Speaking of granulomatous lung disease (previous post), Hartel et al. have written a clinicopathologic review of the largest published series (20) of cases of pulmonary granulomatous inflammation associated with Pneumocystits jiroveci (formerly known as Prince).

I recall first seeing a case of Pneumocystis pulmonary granulomatous inflammation in an Illinois Registry of Anatomic Pathology case probably about 17-18 years ago--apparently, it made quite an impression!  Of course, I've only seen one similar case since them "in real life."

Several important findings from the paper:

1. The granulomas were well-formed in 80% of cases, necrotizing in 80% of cases, and multiple in 90% of cases.
2. Radiographic appearance is atypical for Pneumocystis pneumonia: Nodular infiltrates were present in 50% (8/16) of cases with studies and a solitary nodule was present in 19% of cases (3/16).
3. Open biopsy was required to make the diagnosis in 65% of cases and the diagnosis was made at autopsy in 25%.  Bronchoalveolar lavage--the main diagnostic tool in conventional Pneumocystis pneumonia--is of low yield in the diagnosis of granulomatous Pneumocystis pneumonia--as are bronchial washings, FNA, and transbronchial biopsy.  The fact that these tests are usually negative in this setting may explain why the diagnosis was made post-mortem a quarter of the time.
4. The authors discuss the role of host factors as most likely contributing to the atypical pathological manifestations of Pneumocystis since studies have repeatedly concluded that identical organisms are present in the various histologic reactions identified.
5. Good discussion of distinguishing between P. jiroveci and H. capsulatum on GMS stain: the lack of budding forms, shape and size (Pneumocystis--spherical, Histoplasma--ovoid)of yeast, and size of capsular dots (larger in Pneumocystis versus Histoplasma).

Review of Granulomatous Lung Disease: a few highlights

Drs. Mukhopadhyay and Gal have written an excellent review of granulomatous lung disease in the May 2010 issue of Archives of Pathology and Laboratory Medicine, which has a "Special Section" featuring non-neoplastic lung disease.

One of their points, that cannot be emphasized enough IMHO, is the crucial importance of trying to identify an organism since infection is the most common cause of pulmonary granulomas.  This is tedious work and requires a certain grim determination.  It often feels like trying to "find a needle in a haystack."  But I can also say that it is very rewarding to identify an organism so that proper therapy can be administered to the patient.  Re-emphasizing a point made by Ulbright and Katzenstein (1980), examination of additional blocks or sections showing necrosis with special stains is indicated when the histologic appearance suggests infection.  The authors also provide some helpful guidance in reporting situations when the stains are still negative.

Another very helpful item is in Table 2. which lists key diagnostic features of major non-infectious causes of granulomatous inflammation in the lung.  Keep this in your vade mecum.

Keep in mind the distribution of the granulomas.  I find this to be very helpful in generating a differential diagnosis, especially when special stains for organisms are negative.  The authors nicely reiterate this point.

Another important point is to be aware of PCR and other immunohistochemical and molecular methods for identifying organisms in FFPE tissue, especially for suspected mycobacterial infection.  It is worth considering ordering these additional tests when tissue was not obtained for culture or when mycobacterial infection is suspected clinically but routine ZN stains are negative.

The descriptions of the various major non-infectious entities associated with pulmonary granulomatous disease are as good as found in the major specialty textbooks and are a great reference.  I mean, 196 references, are you serious?!