| Pathology of
sarcoidosis.
Semin Respir Crit Care Med. 2007 Feb;28(1):36-52
The role of
pathology in the diagnosis of sarcoidosis is identification of
granulomas in tissue specimens and performance of studies to
exclude known causes of granulomatous inflammation. The granulomas
of sarcoidosis are nonspecific lesions that, by themselves and in
the absence of an identifiable etiologic agent, are not diagnostic
of sarcoidosis or any other specific disease. Among the diseases
to be excluded are mycobacterial, fungal, and parasitic
infections, chronic beryllium disease and other pneumoconiosis,
hypersensitivity pneumonitis, and Wegener's granulomatosis. Even
after extensive workup a substantial number of granulomas will
remain unclassified. Not every disease that features
nonnecrotizing granulomas of undetermined etiology is sarcoidosis.
The granulomas of sarcoidosis may exhibit focal necrosis of
minimal amount. In cases with granulomas that exhibit a greater
degree of necrosis an infectious or other nonsarcoid etiology
should be strongly suspected. Strict clinical, radiological, and
pathological criteria must be used for diagnosis. In cases that
exhibit necrotizing granulomas with more than minimal, focal
necrosis, extrathoracic involvement only, and/or incompatible
clinical and radiological findings, the diagnosis of sarcoidosis
should be approached with great caution. The diagnosis is most
secure when compatible clinical and radiological findings are
supported by the demonstration of microorganism-negative,
nonnecrotizing granulomas in a biopsy specimen accompanied by
biopsy evidence or strong clinical evidence of multisystem
involvement, and negative cultures for bacteria, mycobacteria, and
fungi. A positive Kveim-Siltzbach test provides strong support for
the diagnosis of sarcoidosis.
Histologic,
microbiologic, and clinical correlates of the diagnosis of
sarcoidosis by transbronchial biopsy.Arch
Pathol Lab Med. 1996 Apr;120(4):364-8
OBJECTIVE--To
determine the frequency of positive microbiologic cultures in
patients with epithelioid granulomas and negative histochemical
stains for microorganisms in transbronchial biopsy specimens.
Secondary objectives were to compare the histologic features of
sarcoidosis with those of infectious granulomas and to assess the
reliability of histology in establishing the diagnosis of
sarcoidosis. DESIGN--Retrospective study. Specific histologic
features of transbronchial biopsy specimens were correlated with
clinical and microbiologic data, final diagnosis, and an estimate
of the probability, on admission, that the patient had sarcoidosis.
SETTING--A large, urban, tertiary-care, university-affiliated
hospital. PATIENTS--Ninety-two adult patients in whom epithelioid
granulomas, negative for microorganisms on Ziehl-Neelsen and
Gomori methemaine silver stain, were found in transbronchial
biopsy specimens. Patients were identified through a search of
surgical pathology files from 1975 to 1987. RESULTS--Ten patients
(10.9%) had mycobacterial or fungal granulomas, while 82 had
sarcoidosis. In all patients with a high clinical probability of
sarcoidosis, the diagnosis was confirmed. Transbronchial biopsy
specimens from patients with infectious granulomas had fewer
granulomas (2.0 +/- 1.7 (SD) versus 7.1 +/- 6.6; P<.01), which
involved a smaller proportion of lung tissue per case (9.5 +/-
10.0% versus 26.6 +/- 24.0%; P<.01). Sarcoid granulomas often
exhibited Schaumann bodies (69.5% versus 10%; P<.01). Necrosis
tended to predominate in infectious granulomas (19.5 versus 40%;
not significant). CONCLUSIONS--Numerous granulomas, Schaumann
bodies, and a high clinical probability of sarcoidosis are
significantly associated with that diagnosis. Necrosis does not
exclude sarcoidosis. Clinicopathologic assessment of
transbronchial biopsy specimens is useful in predicting the final
diagnosis of sarcoidosis but does not obviate the need for
microbiologic cultures, which were positive in 10.9% of patients
in this study.
A study of epithelioid
cell granulomas in transbronchial lung biopsy specimens of
sarcoidosis patients--correlation between granulomas and clinical
activity or chest X-ray lesions.Nihon
Kyobu Shikkan Gakkai Zasshi. 1992 Apr;30(4):627-37.
The 565
pulmonary tissue specimens taken from 155 sarcoidosis patients by
transbronchial lung biopsy (TBLB) were studied by light
microscopy. Particular attention was paid to the mean number and
type of epithelioid cell granulomas, the mean number of giant
cells, and the degree of lymphocyte cuffing, perigranulomal
fibrosis, and granuloma confluence. The granulomas were divided
into three types, hypertrophic, atrophic, and hyalinofibrous. In
stage II and III patients, the mean number of granulomas and giant
cells, the positive rate of hyalinofibrous granuloma, the relative
proportion of the hyalinofibrous granuloma group, and the degree
of fibrosis and confluence were significantly higher than those in
stage O and I patients. The mean number of granulomas was related
to the serum level of angiotensin converting enzyme and 67Ga
uptake into lung parenchyma, but not to the cellular findings of
bronchoalveolar lavage fluid (BALF). The lymphocyte count of BALF
in the hypertrophic granuloma group was significantly higher than
that in the atrophic and hyalinofibrous granuloma groups. CD4/CD8
ratio of lymphocytes in BALF was significantly lower in the
hyalinofibrous granuloma group than in the other groups. In stage
I patients, the resolution of intrathoracic lesions on chest X-ray
was significantly more frequent in the atrophic granuloma group
than in the hypertrophic granuloma group, 2 and 5 years after TBLB
was performed. The pulmonary lesions had a tendency to persist for
a long time in stage II and III patients with hyalinofibrous
granuloma or granuloma confluence. Newly appearing pulmonary
lesions showed hypertrophic granulomas as well as marked
lymphocyte cuffing.
Pulmonary granulomatous inflammation: From
sarcoidosis to tuberculosis.
Semin Respir
Infect. 2003 Mar;18(1):23-32.
Granulomatous
inflammation of the lung is characterized by the recruitment and
organization of activated macrophages and lymphocytes in discrete
lesions laced in a network of matrix proteins. These lesions,
termed granulomas, represent an important defense mechanism
against infectious organisms such as fungi and mycobacteria, but
also can be elicited by noninfectious agents. Occasionally, this
inflammatory reaction can develop for unknown reasons, causing a
systemic illness termed sarcoidosis. The mechanisms involved in
granuloma formation in the lung have not been elucidated entirely.
However, studies performed in animal models of granuloma formation
and in humans suggest important roles for specific soluble
mediators (eg, cytokines, chemokines) produced by monocytic cells.
If uncontrolled, granulomatous inflammation leads to excessive
tissue remodeling, causing fibrosis and/or cavitation as seen in
tuberculosis. This review summarizes our current understanding of
the factors involved in granuloma formation in the lung with
particular attention to their role in sarcoidosis and
tuberculosis.
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