The pathology of pulmonary sarcoidosis: update
Section snippets
Gross appearance
The lung shows no gross abnormalities in the very early stages of sarcoidosis. Still, as the disease advances, small nodules become visible in the pleura and within the lung parenchyma (Figure 1).2 On section of the lung, the nodules are white, usually 1 to 2 mm in diameter, granular, and distributed in a lymphangitic pattern, namely along subpleural and pleural areas, interlobular septa and around bronchovascular regions—regions with a rich lymphatic supply. In more advanced cases, the lungs
Histopathology
Microscopically, the different stages of the disease in lung show different appearances. The earliest stage of the disease has a mild nonspecific interstitial mononuclear inflammatory infiltrate or alveolitis that precedes granuloma formation.3, 5, 6, 7 However, the pathologic diagnosis of sarcoidosis requires the presence of multifocal, nonnecrotizing epithelioid granulomas, which occur somewhat later in the development of the disease. The granulomas are of uniform histologic stage, and they
Inclusions in sarcoidosis
A number of nonspecific cytoplasmic structures/inclusions can be identified within the granulomas of sarcoidosis (Figure 7). These inclusions may falsely lead pathologists to the conclusion that the granulomas are of foreign-body origin.
Asteroid bodies are star-shaped spiculated structures that typically occur within multinucleated giant cells (Figure 7). They are seen in only 2% to 9% of sarcoidal granulomas.7 By electron microscopy, these structures consist of an amorphous matrix embedded
Diagnosis of sarcoidosis
Sarcoidosis is a clinicopathologic diagnosis, and it remains a diagnosis of exclusion of other conditions that can produce similar granulomas. Currently, the diagnosis of sarcoidosis depends on a combination of three different features: a typical clinico-radiological presentation; the histologic presence of nonnecrotizing epithelioid granulomas in a tissue biopsy; and exclusion of other possible diseases, especially those of infectious etiology, which may produce nonnecrotizing or minimally
Extra-pulmonary sarcoidosis
Sarcoidosis is a systemic disease that can affect many organs. The diagnosis can be delayed in patients who have isolated extra-pulmonary findings, in those in whom extra-pulmonary manifestations precede or overshadow the pulmonary disease, or in those who have unusual sites or patterns of extra-pulmonary disease.
There are several examples of unusual patterns of organ involvement in sarcoidosis. Subcutaneous sarcoidosis31 or scleritis32 can be the first manifestation of systemic disease at
Necrotizing sarcoidoid granulomatosis and nodular sarcoidosis
Necrotizing sarcoid granulomatosis (NSG) is both controversial and rare. Liebow described this disease in 1973.39 The current consensus is that most cases are examples of sarcoidosis with necrosis and vasculitis, but we are of the opinion that the definition, which is based on descriptive histopathology, is such as to allow for more than one entity.
Radiologically, NSG can present as bilateral nodules, solitary nodules, or a military pattern preceding the formation of nodules.40 Microscopically,
Lung transplantation for sarcoidosis
Lung transplantation is an ultimate option in selected patients with fibrotic late-stage sarcoidosis. Of interest, there is a high reported frequency of recurrence of disease in the pulmonary allograft, ranging from 47% to 67%.66, 67, 68, 69 However, recurrent granulomas usually have no significant impact on lung function or on short-term outcome.69
Of 4721 patients who had lung transplantation in the United States, 2.8% of them had a pretransplantation diagnosis of sarcoidosis.70 Patients who
Differential diagnosis of sarcoidosis
Because of the lack of a specific and currently available pathognomonic test for sarcoidosis and its diversity of clinical expression, diagnosis of this disease remains one of exclusion of other disorders that may show similar clinical features and pathologic changes on biopsy.
In a recent review article of the pathology of interstitial lung disease, sarcoidosis is placed in the category of “interstitial lung diseases dominated by a nodular pattern,”72 in which the differential diagnosis
Studies on the etiology and pathogenesis of sarcoidosis
Although there have been many advances in the understanding of sarcoidosis, its etiology and pathogenesis remain unknown. Current thinking is that sarcoidosis has more than one etiology, which may in turn lead to different patterns of the disease. Put in another way, the disease is viewed as a chronic immunological response produced by a genetic susceptibility and exposure to specific environmental factors.
Racial and ethnic factors affect disease frequency and prognosis.88 In the United States,
References (113)
Murray Kornfeld, American College of Chest Physician, and sarcoidosis: a historical footnote
Chest
(2005)Pathology of sarcoidosis
Clin Chest Med
(1997)- et al.
Sarcoidosis and aspergilloma
Am J Med
(1969) - et al.
Aspergillomas complicating sarcoidosisA prospective study in 100 patients
Chest
(1984) - et al.
Pulmonary sarcoidosis
Clin Chest Med
(1997) - et al.
Endobronchial biopsy for sarcoidosis: a prospective study
Chest
(2001) - et al.
Diagnosing sarcoidosis using endosonography-guided fine-needle aspiration
Chest
(2000) Sarcoidosis
Mayo Clin Proc
(1995)- et al.
[Subcutaneous sarcoidosis as the first manifestation of systemic disease]
Actas Dermosifiliogr
(2005) Sarcoidosis of the liver and bile ducts
Mayo Clin Proc
(1998)
A new tool to assess sarcoidosis severity
Chest
Necrotizing sarcoid granulomatosis
Chest
Necrotizing sarcoid granulomatosis with and without extrapulmonary involvement
Path Res Pract
Necrotizing sarcoid granulomatosis with pleural involvementClinical and radiographic features
Chest
[Necrotizing sarcoid granulomatosis with ocular, pulmonary and cerebral involvement]
Rev Med Interne
Necrotizing sarcoid granulomatosis with neurologic lesions in a child
J Pediatr
Necrotizing sarcoid granulomatosis mimicking an intracranial neoplasm: clinicopathologic features and review of the literature
Mod Pathol
Nodular sarcoidosis: an unusual radiographic appearance
Chest
Nodular pulmonary sarcoidosisClinical, roentgenographic, and physiologic course in five patients
Chest
Sarcoidosis, race, and short-term outcomes following lung transplantation
Chest
Pathology of interstitial lung disease
Clin Chest Med
The clinical application and cost analysis of fine-needle aspiration biopsy in the diagnosis of mass lesions in sarcoidosis
Chest
Granulomatous Pneumocystis carinii pneumonia complicating hematopoetic cell transplantation
Pathol Res Pract
Beryllium disease
Am J Med Sci
Sarcoid reactions in malignant tumors
Cancer Treat Rev
Relationship of environmental exposures to the clinical phenotype of sarcoidosis
Chest
Tumor necrosis factor polymorphism in sarcoidosis
Chest
Non-neoplastic disorders of the lower respiratory tract
Pulmonary sarcoidosis: a disease characterized and perpetuated by activated T-lymphocytes
Ann Intern Med
Solitary necrotizing granulomas of the lung: differentiating features and etiology
Am J Surg Pathol
Sarcoidosis: from the pathologist’s vantage point
Pathol Annu
Current concepts of the pathogenesis of sarcoidosis
Am Rev Respir Dis
The pathology of sarcoidosis
Curr Opin Pulm Med
Pulmonary sarcoidosis
Allergy
Sarcoidosis-associated bronchiolitis obliterans organizing pneumonia
Arch Intern Med
Pulmonary sarcoidosis: a mimic of respiratory infection
Semin Respir Infect
Spectrum of pleural involvement in sarcoidosis
Arch Intern Med
Pleural involvement in sarcoidosis
Curr Opin Pulm Med
Heterogeneity of pulmonary fibrosis: interstitial pneumonias and sarcoidosis
Curr Opin Pulm Med
Sarcoidosis
N Engl J Med
Sarcoidosis
Significance of crystalline inclusions in lung granulomas
Mod Pathol
Calcium oxalate in sarcoid granulomasWith particular reference to the small ovoid body and a note on the finding of dolomite
Am J Clin Pathol
Calcium oxalate crystal deposition in epithelioid histiocyties of granulomatous lymphadenitis: analysis by light and electron microscopy
Histopathology
Cockade-like structures in alveolar macrophages in extrinsic allergic alveolitis
Respiration
The nature of yellow-brown bodies in peritoneal lymph nodes
Arch Pathol
Yellow-brown (Hamazaki-Wesenberg) bodies mimicking fungal yeasts
Arch Pathol Lab Med
Histologic, microbiologic, and clinical correlates of the diagnosis of sarcoidosis by transbronchial biopsy
Arch Pathol Lab Med
Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis
Eur Respir J
Scleritis associated with sarcoidosis
Ocul Immunol Inflamm
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