**2. Sarcoidosis**

Lung lesions in sarcoidosis are described in 90% of cases. The morphological feature of sarcoidosis is epithelioid cell granuloma, which is a compact formation of mononuclear phagocytes (macrophages and epithelioid cells). Each sarcoid granuloma has certain stages of development. These stages are as follows:


**49**

**Figure 2.**

*Typical "stamped" sarcoid granuloma. H&E.*

**Figure 1.**

*Macrophage granuloma.*

*Pathology of Sarcoidosis and Differential Diagnostics of other Granulomatous Diseases*

in the same samples; granulomas often form conglomerates (**Figure 3**) [4].

The process of granuloma organization begins at the periphery; that is why they

Moreover, in sarcoidosis, granulomas of different "age" may be frequently found

A significant number of lymphocytes in lung tissue in patients with sarcoidosis are predominantly represented by T-cells. It is useful to evaluate the bronchioloalveolar lavage (BAL) while carrying out the differential diagnosis: In sarcoidosis

*DOI: http://dx.doi.org/10.5772/intechopen.90693*

have well-defined, "stamped" appearance (**Figure 2**).

8.Hyalinized granuloma.

### *Pathology of Sarcoidosis and Differential Diagnostics of other Granulomatous Diseases DOI: http://dx.doi.org/10.5772/intechopen.90693*

The process of granuloma organization begins at the periphery; that is why they have well-defined, "stamped" appearance (**Figure 2**).

Moreover, in sarcoidosis, granulomas of different "age" may be frequently found in the same samples; granulomas often form conglomerates (**Figure 3**) [4].

A significant number of lymphocytes in lung tissue in patients with sarcoidosis are predominantly represented by T-cells. It is useful to evaluate the bronchioloalveolar lavage (BAL) while carrying out the differential diagnosis: In sarcoidosis

**Figure 1.** *Macrophage granuloma.*

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

T-suppressors.

mentioned.

**2. Sarcoidosis**

the periphery;

The term granuloma comes from the Latin word "*granulum*" which means "grain," and the Greek suffix ""-*oma*" used to refer to its nodular formation.

Granuloma is a nodular defined formation. This term designates compact cell aggregates on microscopy; granulomas may consist of histiocytes and/or epithelioid cells, giant multinucleated cells, and other inflammatory cells (lymphocytes, neutrophils, and eosinophils). Epithelioid and giant multinucleated cells are monocytes/macrophages derivatives; the former represents good differentiated secretory cells, while the latter specializes in phagocytosis [1]. Giant multinucleated cells are formed by fusion or incomplete cell division, proven in experimental studies [2]; moreover, foreign-body giant cells are formed earlier, than Langhans cells. Lymphocytes are located mainly at the periphery of a granuloma and are represented by T-cells while B-lymphocytes are scattered outside the granuloma. Depending on the disease, T-lymphocytes are predominantly represented by T-helpers 1 and 2 or cytotoxic

Granulomatous diseases are the heterogeneous group of the diseases of different etiology with a variety of clinic syndromes and morphological features, nonuniform sensitivity to therapy [3]. This chapter aims to highlight the variety of granulomatous lung diseases, to characterize the key morphological features of various diseases of infectious and noninfectious nature, as well as to delineate the diagnostic approach. First, the granulomatous diseases, with arising granulomas which do not lead to necrosis development, with some exceptions are

Lung lesions in sarcoidosis are described in 90% of cases. The morphological feature of sarcoidosis is epithelioid cell granuloma, which is a compact formation of mononuclear phagocytes (macrophages and epithelioid cells). Each sarcoid granu-

1.Early or macrophage granuloma, sometimes with a few histiocytes, lympho-

2.Granuloma with an epithelioid cell cluster in the center and macrophages at

4.The appearance of giant multinucleated cells (at first foreign-body giant cells,

5.Early cell necrosis in the center of the granuloma due to nuclear pycnosis, the

6.Central fibrinoid, granular, coagulative ischemic necrosis, as a rule, in small

7.Granuloma with fibrosis (or hyalinosis); silver stain is used to detect reticulin

loma has certain stages of development. These stages are as follows:

formation of apoptotic bodies, and epithelial cell necrosis;

cytes, or neutrophils (**Figure 1**);

3.Lymphocytic epithelioid granuloma;

followed by Langhans cells);

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foci;

fibers;

8.Hyalinized granuloma.

**Figure 2.** *Typical "stamped" sarcoid granuloma. H&E.*

T-helpers predominate. Giant cells in granulomas may contain cytoplasmic inclusions, such as asteroid bodies, Schaumann bodies, or crystalloid structures. These inclusions are characteristic of sarcoidosis, but they are not pathognomonic, as they may be found in other granulomatous diseases [5]. The end stage of sarcoidosis is characterized with prominent fibrosis, sometimes with honeycombing, in which only the remnants of granulomas could be found (**Figure 4**).

Typical locations of granulomas in sarcoidosis are perilymphatic or subpleural zones. Granulomas in bronchi and bronchioles may be found in 15–55% cases of sarcoidosis. Furthermore, granulomas are often located in the vessel wall; the frequency of granulomatous vasculitis may reach 69% (**Figure 5**). In these cases,

#### **Figure 3.** *Multiple well-defined epithelioid cell sarcoid granulomas, forming the conglomerates. H&E.*

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*Pathology of Sarcoidosis and Differential Diagnostics of other Granulomatous Diseases*

sarcoidosis should be differentiated from necrotizing sarcoid granulomatosis. The latter is attributed by some authors to the nodular form of sarcoidosis; necrosis is

Summing up, sarcoidosis is characterized by sharply defined, "stamped" granulomas located along the lymphatic vessels with concentric fibrosis around the granulomas and hyalinosis inside and between the granulomas, also by granulomatous vasculitis, the absence of chronic interstitial inflammation outside the granulomatous lesions, and the absence of organized pneumonia foci. Apart from sarcoidosis, a so-called nonspecific sarcoid reaction occurs in the form of epithelioid cell granulomatosis. It is usually observed in regional lymph nodes, but may also be found in lung tissue in pseudotumors, malignant neoplasms, parasitic diseases, and tuberculosis. Histologically, the sarcoid reaction is characterized by its locality

The pathogenesis of hypersensitivity pneumonitis is based on type III (immunocomplex) and type IV immunological reactions in the lung during allergen inhalation. The etiological factor of this medical condition is usually thermophilic bacteria, fungi, and animal proteins. Other bacteria and their products, amoeba, and some chemicals are much less likely to cause the disease. In case of hypersensitivity pneumonitis, granulomas are poorly formed, and loose, composed of histiocytes, lymphocytes and, multinucleated cells; some eosinophils may also be

Unlike sarcoidosis, peribronchiolar localization of granulomas is typical for hypersensitivity pneumonitis. The triad of pathomorphological features characterizes hypersensitivity pneumonitis: Nonspecific interstitial pneumonia in the peribronchiolar zones, non-necrotizing histiocytic (giant cell) granulomas, and foci of bronchiolitis obliterans. "Needle-like" inclusions are often observed inside giant cells in the granuloma areas and the alveoli in hypersensitivity pneumonitis. In the late, fibrous stage of the disease, the histological features are similar to those in

and a topical relationship with these pathological processes.

*DOI: http://dx.doi.org/10.5772/intechopen.90693*

typical for this disease [6].

*Granulomatous vasculitis in sarcoidosis. H&E.*

**Figure 5.**

**2.1 Hypersensitivity pneumonitis**

identified (**Figure 6**) [7].

*Pathology of Sarcoidosis and Differential Diagnostics of other Granulomatous Diseases DOI: http://dx.doi.org/10.5772/intechopen.90693*

**Figure 5.** *Granulomatous vasculitis in sarcoidosis. H&E.*

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

only the remnants of granulomas could be found (**Figure 4**).

*Multiple well-defined epithelioid cell sarcoid granulomas, forming the conglomerates. H&E.*

*Late-stage sarcoidosis with prominent fibrosis and remnants of granulomas. H&E.*

T-helpers predominate. Giant cells in granulomas may contain cytoplasmic inclusions, such as asteroid bodies, Schaumann bodies, or crystalloid structures. These inclusions are characteristic of sarcoidosis, but they are not pathognomonic, as they may be found in other granulomatous diseases [5]. The end stage of sarcoidosis is characterized with prominent fibrosis, sometimes with honeycombing, in which

Typical locations of granulomas in sarcoidosis are perilymphatic or subpleural zones. Granulomas in bronchi and bronchioles may be found in 15–55% cases of sarcoidosis. Furthermore, granulomas are often located in the vessel wall; the frequency of granulomatous vasculitis may reach 69% (**Figure 5**). In these cases,

**50**

**Figure 4.**

**Figure 3.**

sarcoidosis should be differentiated from necrotizing sarcoid granulomatosis. The latter is attributed by some authors to the nodular form of sarcoidosis; necrosis is typical for this disease [6].

Summing up, sarcoidosis is characterized by sharply defined, "stamped" granulomas located along the lymphatic vessels with concentric fibrosis around the granulomas and hyalinosis inside and between the granulomas, also by granulomatous vasculitis, the absence of chronic interstitial inflammation outside the granulomatous lesions, and the absence of organized pneumonia foci. Apart from sarcoidosis, a so-called nonspecific sarcoid reaction occurs in the form of epithelioid cell granulomatosis. It is usually observed in regional lymph nodes, but may also be found in lung tissue in pseudotumors, malignant neoplasms, parasitic diseases, and tuberculosis. Histologically, the sarcoid reaction is characterized by its locality and a topical relationship with these pathological processes.

#### **2.1 Hypersensitivity pneumonitis**

The pathogenesis of hypersensitivity pneumonitis is based on type III (immunocomplex) and type IV immunological reactions in the lung during allergen inhalation. The etiological factor of this medical condition is usually thermophilic bacteria, fungi, and animal proteins. Other bacteria and their products, amoeba, and some chemicals are much less likely to cause the disease. In case of hypersensitivity pneumonitis, granulomas are poorly formed, and loose, composed of histiocytes, lymphocytes and, multinucleated cells; some eosinophils may also be identified (**Figure 6**) [7].

Unlike sarcoidosis, peribronchiolar localization of granulomas is typical for hypersensitivity pneumonitis. The triad of pathomorphological features characterizes hypersensitivity pneumonitis: Nonspecific interstitial pneumonia in the peribronchiolar zones, non-necrotizing histiocytic (giant cell) granulomas, and foci of bronchiolitis obliterans. "Needle-like" inclusions are often observed inside giant cells in the granuloma areas and the alveoli in hypersensitivity pneumonitis. In the late, fibrous stage of the disease, the histological features are similar to those in

#### **Figure 6.**

*Hypersensitivity pneumonitis: Ill-defined granuloma consisting of giant multinucleated cells with needle-like structures surrounded by lymphocytes, lymphocytic infiltration of interalveolar septa. H&E.*

usual interstitial pneumonia, only scattered giant cells or remnants of granulomas may be found in the fibrotic areas or in the honeycomb zones in hypersensitivity pneumonitis [8].
