1: Am J Surg Pathol. 2004 Feb;28(2):207-14.

Pulmonary meningothelial-like nodules: a genotypic comparison with meningiomas.

Ionescu DN, Sasatomi E, Aldeeb D, Omalu BI, Finkelstein SD, Swalsky PA, Yousem
SA.

Department of Pathology, Division of Anatomic Pathology, University of
Pittsburgh Medical Center, Presbyterian University Hospital, Room A610, 200
Lothrop St., Pittsburgh, PA 15213, USA. ionescudn@msx.upmc.edu

BACKGROUND: Minute pulmonary meningothelial-like nodules (MPMNs) are incidental
interstitial pulmonary nodules. They share histologic, ultrastructural, and
immunohistochemical features with meningiomas (MGs). DESIGN: Sixteen cases
yielding 33 separate MPMNs and 10 cases of benign MG were studied.
Immunohistochemical studies and mutational analyses were performed on
microdissected tissue using 20 polymorphic microsatellite markers targeting 11
genomic regions in an effort to identify genetic similarities of MPMN and MG.
RESULTS: A total of 96.6% of MPMNs stained positive for vimentin, 33.3% for
epithelial membrane antigen, 3% for S-100, and all were negative for cytokeratin
and synaptophysin. Loss of heterozygosity (LOH) was identified in 25% of single
MPMN affecting 3 genomic loci. No solitary MPMN had more than 1 LOH event.
Multiple LOHs were seen only in MPMN-omatosis syndrome, where 33.3% of MPMNs
showed LOH affecting 7 genomic loci. MG showed the highest frequency of LOH with
major events seen at 22q (60%), 14q (42.8%), and 1p (44.4%) that were not shared
by MPMN. CONCLUSION: Isolated MPMN lacks mutational damage, consistent with a
reactive origin. MPMN-omatosis syndrome might represent the transition between a
reactive and neoplastic proliferation. MPMNs are different from MG based on the
major molecular genetic events seen in their formation and progression.

2: Nihon Kokyuki Gakkai Zasshi. 2002 Jun;40(6):499-502.

[Minute pulmonary meningothelial-like nodules: a case report]

[Article in Japanese]

Park HY, Nishi Y, Tabe K, Yamamoto H, Shibasaki M, Sakata K, Nagata M, Kuramitu
K, Nakamura S, Morita R, Kaneko K, Shimizu Y, Sakamoto Y.

Pulmonary Division, Second Department of Internal Medicine, Saitama Medical
School, Saitama.

The presence of multiple small nodular shadows on a routine chest radiograph was
noticed in a 56-year-old woman who had undergone a left mastectomy on the
diagnosis of breast cancer 8 years before. Chest CT films revealed small nodules
scattered beneath the pleura mainly in both lower lobes. A biopsy was performed
during video-assisted thoracoscopy to rule out metastasis from breast cancer.
Biopsy specimens showed spindle--or oval-shaped cells arranged in nests
associated with a dedicated network of capillaries. These findings were
compatible with minute meningothelium-like nodules (MN). The pathogenesis of MN
is still unknown. It is common in elderly women, and the prognosis is excellent
without any treatment. MN is an important disease in the differential diagnosis
of multiple nodular shadows found on chest CT.

3: Virchows Arch. 2002 May;440(5):543-6. Epub 2002 Jan 22.

Progesterone receptor immunoreactivity in minute meningothelioid nodules of the
lung.

Pelosi G, Maffini F, Decarli N, Viale G.

Department of Pathology and Laboratory Medicine, European Institute of Oncology,
University of Milan School of Medicine, Via G. Ripamonti 435, 20141 Milan,
Italy. giuseppe.pelosi@ieo.it

Meningothelioid nodules (MNs) are not uncommon lesions of the pulmonary
interstitium composed of monomorphic round to spindle cells, likely reactive in
nature. Their origin is unsettled, though a derivation from arachnoid-like cells
in conditions of perturbed perfusion of the pulmonary tissue has been proposed.
Here we confirm the consistent occurrence of intense progesterone-receptor
immunoreactivity in MNs fortuitously detected in surgical specimens of lung
carcinomas. This finding corroborates the view that these proliferations exhibit
arachnoid cell-like differentiation and suggests a role for sex-steroid hormones
in the control of their growth.

4: Hum Pathol. 1999 Apr;30(4):425-9.

Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like
nodules.

Niho S, Yokose T, Nishiwaki Y, Mukai K.

Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa,
Chiba, Japan.

The histogenesis of meningothelial-like nodule or so-called minute pulmonary
chemodectoma remains unclear, with various immunohistochemical analyses giving
inconsistent results. We performed an immunohistochemical and clonal analysis of
minute pulmonary meningothelial-like nodules. Thirty-one histologically defined
meningothelial-like nodules in 14 cases were stained immunohistochemically. One
case had multiple lesions with brown pigment granules, which were positively
stained with Berlin blue method, indicating the presence of hemosiderin. All
meningothelial-like nodules were positive for vimentin and epithelial membrane
antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five
of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24
lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were
negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen.
Alveolar macrophages were intensely positive for CD68 and lysozyme in all
examined cases. We analyzed the clonality of 11 minute pulmonary
meningothelial-like nodule lesions in two female cases based on an
X-chromosome-linked polymorphic marker, the human androgen receptor gene
(HUMARA). The HUMARA was found to be amplified with or without prior digestion
by the methylation-sensitive restriction endonuclease HpaII. Six of 11 lesions
showed monoclonal expansion. Five lesions in a multiple case showed different
patterns of monoclonality. Our findings showed that minute pulmonary
meningothelial-like nodules have meningothelial-like and phagocytic
characteristics but no muscular phenotype. Furthermore, some minute pulmonary
meningothelial-like nodules may show monoclonal expansion, whereas others are
polyclonal. Our data indicate that minute pulmonary meningothelial-like nodules
are reactive rather than neoplastic.

5: Virchows Arch A Pathol Anat Histopathol. 1990;417(2):113-8.

So-called minute chemodectoma of the lung. An electron microscopic and
immunohistochemical study.

Torikata C, Mukai M.

Department of Pathology, Keio University School of Medicine, Tokyo, Japan.

So-called minute pulmonary chemodectoma is a curious, small lung tumour found
mainly in women. The nature and origin of the proliferating cells are still
obscure. In the first report on the tumour, the component cells were described
as resembling chemoreceptor cells and the tumour was named chemodectoma.
However, electron microscopic studies of the tumour have revealed no evidence of
neuronal characteristics and have shown a close resemblance to meningothelial
cells. In this study, the electron microscopic findings were similar to those
previously reported but in one of the two cases, tumour cells were filled with
abundant cytofilaments, giving them an occasional dense, patch-like appearance.
Immunostaining for myosin and vimentin was positive in all tumour cells, but
epithelial membrane antigen staining was not seen. These findings indicate that
the tumour might have its origin from muscle cells.

6: Am J Surg Pathol. 1988 Mar;12(3):167-75.

Minute pulmonary meningothelial-like nodules. A clinicopathologic study of
so-called minute pulmonary chemodectoma.

Gaffey MJ, Mills SE, Askin FB.

Department of Pathology, University of Virginia Medical Center, Charlottesville
22908.

The clinicopathologic features of 23 so-called minute pulmonary chemodectomas
from nine patients are presented. Eight patients were women and one was a man;
age range was 34-75 years (mean, 61). Two specimens were surgical resections and
seven were autopsies (incidence, one per 60 autopsies). There was no association
with a specific disease process or pathologic condition. Grossly, the lesions
were 1-3 mm, tan to yellow, pleural or parenchymal nodules. Six of nine cases
had multiple lesions; upper lobes were more often involved. Microscopically,
characteristic cell nests expanded alveolar septa. Larger lesions were connected
by intervening collagen, often imparting a stellate configuration. Smaller
lesions had closely apposed nests with mildly thickened alveolar septa. The
nodules were strongly reactive for epithelial membrane antigen (12 of 14) and
vimentin (10 of 14), and were uniformly negative for cytokeratin, S-100,
neuron-specific enolase, and actin. Ultrastructurally, complex interdigitating
cell processes were connected by desmosomes. Occasional cytoplasmic filaments
were seen. These nodules lack neuroendocrine features, differ from mesothelium,
and strongly resemble meningothelial cells. A more accurate term for these
lesions is minute meningothelial-like nodules. Their relationship to larger,
solitary pulmonary meningiomas is unclear.