Davoli, Fabio

Pulmonary minute meningothelial-like nodules (MMNs) are common incidental findings in surgical specimens, consisting of tiny proliferation (usually no larger than 5–6 mm) of bland-looking meningothelial cells showing a perivenular and interstitial distribution, sharing morphologic, ultrastructural, and immunohistochemical profiles with meningiomas. The identification of multiple bilateral MMNs leading to an interstitial lung disease characterized by diffuse and micronodular/miliariform patterns radiologically allows the diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Nevertheless, the lung is the most common site of metastatic primary intracranial meningioma, and differential diagnosis with DPM may be impossible without clinic–radiologic integration. Herein, we report four cases (three females; mean age, 57.5 years) fitting the criteria of DPM, all incidentally discovered and histologically evidenced on transbronchial biopsy (2) and surgical resection (2). All cases showed immunohistochemical expression of epithelial membrane antigen (EMA), progesterone receptor, and CD56. Notably, three of these patients had a proven or radiologically suspected intracranial meningioma; in two cases, it was discovered before, and in one case, after the diagnosis of DPM. An extensive literature review (44 patients with DPM) revealed similar cases with imaging studies excluding intracranial meningioma in only 9% (4 of 44 cases studied). The diagnosis of DPM requires close correlation with the clinic–radiologic data since a subset of cases coexist with or follow a previously diagnosed intracranial meningioma and, thus, may represent incidental and indolent metastatic deposits of meningioma.

Pulmonary hamartoma (PH) may show various combinations of mesenchymal tissues with entrapment of respiratory epithelium. An uncommon variant of PH prevalently consisting of smooth muscle with mucinous proliferation has been reported in literature under several definitions as sporadic reports. We collected a series of 6 leiomyomatous PH associated with mucinous growth from consultation files (3 cases) and multicentric revision of archival files among 128 consecutive surgically resected PH. The lesions have a prevalence for male gender (5:1) and lower lobes (5:1), with a mean age at diagnosis of 61 years. All cases were incidentally disclosed in asymptomatic patients and had an indolent behavior. At histology, 2 cases consisted uniquely of smooth muscle and 4 also showed mature adipose tissue. The mucinous proliferation consisted of a monotonous growth of columnar cells lacking p63-positive basal cells and expressing pan-CKs, MUC5A, and CK7, but negative with TTF-1, napsin, MUC1, MUC2, MUC6, CK20, and CDX2. Smooth muscle was negative with hormonal receptors. Molecular analysis using a multiplex gene panel did not reveal gene mutations, while ALK, BRAF, and ROS1 were negative. In conclusion, we describe a small series of uncommon PH with prevalent leiomyomatous mesenchymal component associated with a mucinous growth (mucinous adenomyomatous hamartoma). Despite the lack of basal cells coating mucinous proliferation and irregular architecture, the favorable outcome and lack of molecular alterations most likely lay for a benign/low-grade tumor. Pathologists should be aware of this unusual occurrence to prevent a diagnosis of overt malignancy, particularly in frozen section, small biopsy, and cytology.