Histopathologic review of granulomatous inflammation

Abstract

Granulomatous inflammation is a histologic pattern of tissue reaction which appears following cell injury. Granulomatous inflammation is caused by a variety of conditions including infection, autoimmune, toxic, allergic, drug, and neoplastic conditions. The tissue reaction pattern narrows the pathologic and clinical differential diagnosis and subsequent clinical management. Common reaction patterns include necrotizing granulomas, non necrotizing granulomas, suppurative granulomas, diffuse granulomatous inflammation, and foreign body giant cell reaction. Prototypical examples of necrotizing granulomas are seen with mycobacterial infections and non-necrotizing granulomas with sarcoidosis. However, broad differential diagnoses exist within each category. Using a pattern based algorithmic approach, identification of the etiology becomes apparent when taken with clinical context. The pulmonary system is one of the most commonly affected sites to encounter granulomatous inflammation. Infectious causes of granuloma are most prevalent with mycobacteria and dimorphic fungi leading the differential diagnoses. Unlike the lung, skin can be affected by several routes, including direct inoculation, endogenous sources, and hematogenous spread. This broad basis of involvement introduces a variety of infectious agents, which can present as necrotizing or non-necrotizing granulomatous inflammation. Non-infectious etiologies require a thorough clinicopathologic review to narrow the scope of the pathogenesis which include: foreign body reaction, autoimmune, neoplastic, and drug related etiologies. Granulomatous inflammation of the kidney, often referred to as granulomatous interstitial nephritis (GIN) is unlike organ systems such as the skin or lungs. The differential diagnosis of GIN is more frequently due to drugs and sarcoidosis as compared to infections (fungal and mycobacterial). Herein we discuss the pathogenesis and histologic patterns seen in a variety of organ systems and clinical conditions.

Keywords: Foreign-body; Granuloma; Granulomatous inflammation; Mycobacterial; Sarcoidal; Tuberculous.

Fig. 1

Edge of a necrotizing granuloma seen in mycobacterial tuberculosis showing a peripheral rim of epithelioid histiocytes (arrows) surrounding the central necrotic region (asterisk; H&E, 200x). Some histiocytes are also forming multinucleated giant cells (arrow heads). External to the rim of histiocytes is an outer rim of lymphocytes and plasma cells.

Fig. 2

Foreign body giant cell reaction within the lung alveoli, with macrophages engulfing inhaled talc (H&E, 200x). The inset highlights refractile foreign material with plane polarizable light (H&E with polarized light, 200x).

Fig. 3

Laminated Coccidioides spp. granuloma (coccidioidoma) of the lung, showing a central necrotic focus.

Fig. 4

Edge of a necrotizing granuloma formed by Coccidioides immitis showing a large caseating necrotic center (asterisk) and outer rim of epithelioid histiocytes and lymphoplasmacytic inflammation (Left panel, H&E, 20x). On higher magnification (400x), a spherule containing endospores can be seen on H&E (upper right panel) and GMS (lower right panel). Note that the GMS also highlight maturing spherules to the left of the mature spherule.

Fig. 5

The renal parenchyma is replaced by numerous non-necrotizing granulomas in a patient with sarcoidosis (Periodic-acid Schiff, 200X).

Fig. 6

Skin biopsy in a patient with lepromatous leprosy showing a dermal infiltrate of histiocytes containing numerous bacilli of Mycobacterium leprae (H&E, 200x). The organisms are visible using a Fite stain which highlights partially acid fast organisms (inset, 1000x).

Fig. 7

The skin punch biopsy of Langerhans cell histiocytosis (inset, H&E) shows a dermal infiltrate of non-necrotizing granulomatous inflammation with epithelioid histiocytes which have reniform nuclei and occasional nuclear grooves in a background of sparse chronic inflammation (larger image, H&E 400x).

Fig. 8

Skin punch biopsy (left) showing a palisaded granulomatous inflammation dispersed throughout the dermis diagnostic of granuloma annulare (H&E, 10x). The inset (top) shows the corresponding clinical image with an erythematous annular plaque. The bottom inset (400x) highlights the palisading histiocytes cuffing degenerative collagen.