Necrotizing Sarcoid Granulomatosis With an Uncommon Manifestation: Clinicopathological Features and Review of Literature

Discussion

Since the first report by Liebow,² several authors have described the existence of NSG,^{1,3–10,12–21} mostly involving lung parenchyma (Table 1). The etiology and pathogenesis are unknown, and a biopsy specimen is required for final diagnosis.

The clinical presentation is quite variable and nonspecific. Cough is the most common clinical manifestation of NSG, followed by pleural chest pain, dyspnea, fever, and constitutional symptoms of weight loss.^6,18 However, ∼25% of patients are paucisymptomatic/asymptomatic.²⁰ Limited information is available in the literature regarding laboratory tests. The most important clinicoradiological differential diagnoses of NSG are Wegener's granulomatosis, rheumatoid arthritis, sarcoidosis, and metastasis. It is important to distinguish NSG from systemic vasculitis or metastasis because of differences in prognosis and response to treatment.

Unlike patients with Wegener's granulomatosis, patients with NSG have no upper airway disease, nephritis, or systemic vasculitis. Moreover, the round opacity typically demonstrates thick patchy wall cavitation areas,^22,23 which were completely absent in our case. Uveitis or cutaneous lesions, involvement of hilar lymph nodes, and increased angiotensin-converting enzyme levels, which are usually frequent in sarcoidosis, are rare in NSG, as in our case.

Although NSG and sarcoidosis seem to have different presentations, there is still debate about whether the 2 diseases are distinct entities.¹⁸ Indeed, there are some similarities between sarcoidosis and NSG. Both diseases have a favorable prognosis, a similar immune mechanism, and distribution of granulomas.²⁴ Furthermore, 5% of patients with sarcoidosis show the typical histology of NSG.^25,26

High-resolution computed tomography of rheumatoid lung nodules shows well defined nodules with lobulated margins. The size of isolated nodular lesions may increase during the acute phase of the disease proportional to the antibody titer. The hypothesis of rheumatoid lung disease was excluded in our case because all antibody titers were negative, and no arthralgias were reported in the clinical history.

In our case, the nodules were mainly peripheral and localized mostly in the lower lobes; thus, lung metastasis also had to be considered. Metastatic opacities usually have regular and well-defined margins but sometimes are hazy with a halo sign, as in choriocarcinomas and angiosarcomas. Cavitations or calcifications depend on the histological pattern of the primary tumor. We excluded metastatic disease because no primary tumor had been detected, and the patient was in a relatively stable condition.

Biohumoral analysis and high-resolution computed tomography can be used when NSG is suspected; however, lung biopsy is the cornerstone for establishing the diagnosis of NSG. This is particularly true in cases with subclinical or uncommon presentation, as in our patient. Indeed, back pain could be due to degenerative discopathy (spondyloarthrosis) or subpleural lower lobe localization of nodules (pleuritic chest pain).

From a pathological point of view, the most important differential diagnoses are Wegener's granulomatosis and infection. Well-formed non-necrotizing sarcoid granulomas are rarely seen in Wegener's granulomatosis. Moreover, the vasculitis of Wegener's granulomatosis is more necrotizing and often suppurative.^18,19,27 A differential diagnosis with infection is more difficult: conventional microbiological analysis and use of overall tissue ancillary techniques such as special stains, immunohistochemistry, and molecular analysis (the latter for mycobacterial detection) are important. Above all, the use of a highly specific and sensitive molecular technique such as nested polymerase chain reaction for mycobacterial detection is mandatory. This is particularly true in cases with subclinical or uncommon features, as in the case presented here.

The prognosis of patients with NSG has been described as favorable. Indeed, the clinical course is generally benign, with a good response to steroid treatment or without the need for therapy.^1,6,17 The known case reports/series on lung NSG are listed in Table 1. In many cases, no medical treatment was required, as in our case. Treatment seems to be associated with relapse and should be started only when symptoms are severe.

We have presented a case of NSG with an uncommon clinical manifestation. The final diagnosis was based on a multidisciplinary approach and overall on accurate morphological and molecular analysis. Our case supports the fact that the disease has a benign clinical course with complete spontaneous recovery especially when tissue lesions are not extensive and when there are no constitutional symptoms.