대한흉부영상의학회 Korean Society of Thoracic Radiology

Discussion

Diagnosis With Brief Discussion

Diagnosis

Diffuse pulmonary meningotheliomatosis

Radiologic Findings

Fig 1. Chest PA shows no definite abnormality.
Fig 2-5. CT scans reveals multiple 2~6mm ground-glass nodules with or without cystic airway dilatation in both lungs.

Brief Review

Diffuse pulmonary meningotheliomatosis (DPM) is an extremely rare condition characterized by the presence of multiple minute meningothelial nodules throughout the lungs. The characteristic pathologic lesions were first described by Korn et al in 1960. They described rounded polyhedral or spindle-shaped cells that were arranged in nests (zellballen) and initially were considered to be pulmonary tumors resembling chemodectomas. A characteristic feature was their interstitial location and their relationship to blood vessels because they were always centered on pulmonary venules, especially where the interlobular septa inserted on the pleura. However, later studies showed that meningothelial nodules are located randomly along alveolar septa. Subsequent immunohistochemical studies were positive for epithelial membrane antigen and vimentin, which strongly suggests their meningothelial origin. This led Gaffey et al to coin the term “minute pulmonary meningothelial nodules” in 1988. Despite the advancement in their characterization from a pathologic point of view, their exact cause and clinical significance remain unclear.
Pulmonary meningothelial-like nodules have been found in patients who range in age from 22 to 84 years, with a peak during the sixth decade (median, 62 years). They are rarely observed under the age of 40 years. Their absence in infants and children argues against a congenital origin. There is a female predominance with a female-to-male ratio of 2.2:1. Most patients with DPM are asymptomatic and are discovered incidentally. Some patients report shortness of breath and cough. However, it is unclear whether these symptoms are causally related to DPM.
Imaging is characterized by the presence of multiple, diffuse bilateral nodules that are depicted better on HRCT. These nodules are typically small (approximately 5 mm; smaller than 10 mm), usually centrilobular, and tend to be peripheral involving the outer third of the lung parenchyma. In some cases, there is a diffuse distribution in line with a military pattern. A characteristic finding is that some of the nodules depict the “cheerio sign” (pulmonary nodules with a central lucent area). It is frequently reported as “central cavitation,” but this is a misnomer because it does not always correspond to histologic necrosis, depending on the underlying disease.
Because most patients are asymptomatic or present with no specific symptoms and clinical examination is unremarkable, differential diagnosis is based on imaging findings. The “cheerio sign” is characteristic of DPM but is by no means pathognomonic because it has been described in several infectious diseases (mainly mycobacterial and fungal), neoplastic diseases (mainly adenocarcinoma both primary and metastatic), granulomatosis with polyangiitis, rheumatoid arthritis (corresponding to necrobiotic nodules) and pulmonary Langerhans cell histiocytosis. In the latter Case, nodules with the “cheerio sign” is also characteristic, but the upper/mid lung distribution of findings with sparing of the costophrenic angles points to the correct diagnosis. When a miliary pattern is present, the differential diagnosis includes hematogenous spread of an infectious or neoplastic process to the lungs. Typically, in all the aforementioned cases, there are clinical symptoms and associated imaging findings pointing to the correct diagnosis. Particular attention is needed when there is a history or concomitant malignancy. In such cases, it is of utmost importance not to miss a diagnosis of underlying malignancy but, at the same time, not to consider DPM erroneously as metastatic disease. For a definitive diagnosis, tissue confirmation is required, usually by surgical lung biopsy, although there are cases in which diagnosis was made by transbronchial biopsy.
The clinical course of DPM is benign, and no therapeutic intervention is required. It is worth noting that pulmonary minute meningothelial-like nodules are found significantly more often in patients with malignant pulmonary tumors than in those with benign diseases. Furthermore, they might represent the transition between a reactive and neoplastic proliferation, although this has been challenged because they have been described in the context of various diseases that include infections, neoplasms, and pulmonary embolism. Nevertheless, in cases of DPM, a workup for unidentified malignancy can be a reasonable choice on an individualized basis.

References

1. Tzilas V, Bouros D. A 58-Year-Old Woman With Lung Nodules and Chronic Cough. Chest. 2021 Sep;160(3):e285-e288.

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