Sarcoidosis is a disease in which the immune system forms many small clusters of inflammatory cells, called granulomas, in one or more organs. It most often affects the lungs and the lymph nodes in the chest, but it can also involve the skin, eyes, heart, liver, and other organs. Sarcoidosis is not cancer and is not contagious. A pathologist plays a key role in diagnosis by identifying the typical granulomas and ensuring another disease, especially an infection, is not the cause.
This article explains what sarcoidosis is, who gets it, how a pathologist identifies it, and what your pathology report may say.
The exact cause of sarcoidosis is not known. Doctors believe it starts when the immune system overreacts to something in the environment, in people whose genes make them more likely to react this way. The immune cells gather together and form granulomas, which can build up and affect how an organ works. Sarcoidosis can run in families, but it is not passed directly from parent to child, and it does not spread from person to person.
Sarcoidosis can affect people of any age, but most people receive the diagnosis between their forties and sixties. Sarcoidosis affects women about twice as often as men. In North America, the disease is most common in people of African descent. Many people have no symptoms, and doctors find the disease by chance on a chest X-ray or scan done for another reason. Others develop a cough, shortness of breath, tiredness, a skin rash, red or painful eyes, or swollen lymph nodes.
Under the microscope, sarcoidosis shows tight, well-formed granulomas. Each granuloma is a round cluster of immune cells called histiocytes, often with large multinucleated giant cells that form when several histiocytes join together. The center of the granulomas usually shows no dead tissue. Pathologists describe this pattern as non-necrotizing granulomatous inflammation.
The giant cells sometimes contain small star-shaped or layered structures called asteroid bodies and Schaumann bodies. These features are common in sarcoidosis, but they can also appear in other conditions. In long-standing disease, scar tissue or fibrosis may form around the granulomas.
According to the 2020 American Thoracic Society guideline, diagnosing sarcoidosis depends on three things. The person must have symptoms or imaging findings consistent with the disease. A tissue sample must show non-necrotizing granulomas. Finally, doctors must rule out other causes of granulomas. Because of this last step, doctors often describe sarcoidosis as a diagnosis of exclusion.
Tissue for diagnosis usually comes from a biopsy of an enlarged lymph node in the chest, the lung, or the skin. Doctors often sample chest lymph nodes with a thin needle guided by an ultrasound probe on a bronchoscope, a procedure called EBUS. In a few typical situations, such as a specific combination of fever, painful red skin bumps, and swollen chest lymph nodes, doctors may diagnose it without a biopsy.
The pathologist tests for infection because tuberculosis and some fungal infections also cause granulomas that can look very similar to sarcoidosis. To look for these germs, the pathologist usually orders special stains on the biopsy:
Negative stains support sarcoidosis, but they cannot completely rule out an infection, because germs can be very sparse. For this reason, doctors may also send part of the sample for fungal or tuberculosis testing, such as a culture. Your doctors combine all of these results before confirming the diagnosis.
A pathology report rarely states the diagnosis of sarcoidosis on its own, because the final diagnosis depends on your symptoms, scans, and other tests. Instead, the report usually describes the granulomas and the results of the infection stains. Common wording includes:
After diagnosing sarcoidosis, doctors assess which organs the disease involves and how much it affects them. The 2020 American Thoracic Society guideline suggests baseline blood tests for calcium, kidney function, and liver function, and an eye examination, even in people without symptoms in those areas. Heart involvement is less common but still important, so doctors may order heart tests if they have concerns.
Many people with sarcoidosis need no treatment, and the disease often improves on its own over months to years. When the disease affects organ function or quality of life, the 2021 European Respiratory Society guideline recommends glucocorticoids, such as prednisone, as the first treatment. Doctors may add other medicines, such as methotrexate or infliximab, if steroids do not work well or cause side effects. Most people have regular follow-up with chest X-rays, breathing tests, and eye examinations.