Radiology/Pathology Correlation

Unknown 11

A 64-year-old woman with a 50-pack-year history of cigarette smoking presents with shortness of breath of 2-weeks' duration.



Figure 1. Coned Radiograph

A small right upper lobe nodule, noted on the frontal chest radiograph, is better appreciated on the coned radiograph of the right upper chest.

Find the nodule. Click on the structure in the image to get verification.



Figure 2. HRCT

CT scan performed with narrow (1 mm) collimation obtained at the same time as Figure 1 shows a lobulated right upper lobe pulmonary nodule. Many randomly-distributed, small (<3 mm in diameter) nodules are also present bilaterally and predominantly in the peripheral portions of lung.

Find 5 examples of the small nodules (3 in the left and 2 in the right lung).


Some of the more central nodules cannot be reliably distinguished from normal bronchiolovascular structures.

Figure 3. Routine CT

The small nodules seen in Figure 2 were not readily visible on the routine 7 mm collimation scan shown here.

The small right upper lobe nodule was suspicious for carcinoma. The patient underwent right upper hemilobectomy, and a diagnosis of moderately well-differentiated carcinoma was established. The patient recovered uneventfully.

In addition to the carcinoma, histologic examination of the resected lobe revealed numerous small nodules.

Figure 4. Follow-up HRCT: This scan was obtained approximately 3 years following surgery. In some areas, the small nodules appear to have grown slightly since the patient's surgical resection, although no clinical, laboratory, or imaging manifestations of metastatic disease have been noted to date.


Note again the nodules similar to those seen above in figure 2.

What is the differential diagnosis of the small nodules?




The following images are from similar lesions found in a resection of rheumatoid nodules from a 66-year-old man. The largest lesion was 3 mm in diameter.


Figure 5

Low-Power View of Lesion

This example of a minute nodule shows a focus of cellular interstitial thickening surrounded by normal lung. It arises around a vein and spreads through the adjacent alveolar wall interstitium. Note that it has fewer alveolar wall attachments than normal, indicating some rupture of walls as the lesion grows. Type II cell hyperplasia can be noted in several areas.

Find the vein within the lesion.

Find two veins just adjacent to the lesion.

Figure 6

High Magnification

At high magnification, the cells in the expanded interstitium have regular, ovoid nuclei and rounded to spindled cytoplasm with ill-defined boundaries. Mitoses are not seen. Alveolar capillaries surround the interstitial nest.

What is the diagnosis? What is the differential diagnosis?



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Minute Meningothelial-like Nodule (MMN)

Discussion: First described in 1960 on the basis of light microscopy, these lesions were initially thought to be chemoreceptors like the carotid body and were designated chemodectomas. Later, ultrastructural and immunohistochemical studies have repeatedly found that the nodules are composed of cells resembling arachnoid cells of the leptomeninges [1,2].

Clinical associations: When sought, these curious nodules, of interest primarily to pulmonary pathologists, have been found to occur in up to 1 in 25 autopsies. They have been found in persons from ages 12 to 91 (mean 58). Women predominate 5:1. Most cases have multiple nodules. Associated diseases--thromboembolism, heart disease, and malignancy, which are common findings at autopsy--have not yet been causally related [2]. Clinical significance, if any, remains unknown. MMNs used to be incidental lesions found only in resected lungs or at autopsy, but that changed with HRCT, which can detect nodules 2-3 mm in diameter.

Radiographic findings: In the present case, MMNs were incidentally discovered during the course of a preoperative evaluation for bronchogenic carcinoma. These nodules, rarely described in the radiologic literature, may be bilateral and predominantly peripheral. Some have ground-glass attenuation and are poorly defined, and others are relatively well-defined and solid-appearing.They are randomly distributed and <3mm in diameter [3,4].

In this case, the larger ill-defined nodule in the right upper lobe associated with numerous, randomly-distributed small nodules raised the possibility of carcinoma with metastatic disease. Conceivably, if the diagnosis of carcinoma in the right upper lobe were established by a method other than surgical excision, the patient may have been denied curative surgery based on the presence of these nodules. This pitfall may be avoided with awareness of the prevalence and imaging characteristics of MMNs. When this situation is encountered, a procedure that samples the dominant lesion as well as a small amount of surrounding lung parenchyma containing associated micronodules may be the preferred diagnostic strategy.

Gross appearance: MMNs are well-defined, greyish lesions up to 3 mm in diameter [2].

Histologic appearance: The nodules are composed of rounded to elongate cells with ovoid nuclei and ill-defined pink cytoplasm, and are arranged in whorled nests in the interstitium around small veins. From there, the nests radiate into alveolar walls where they produce a stellate appearance. The occasional presence of hemosiderin in the cells indicates phagocytic capability. Larger lesions show replacement of cells by collagen. Sometimes type II cells are hyperplastic. Mitoses are not seen [1,5]. Click here to see other features of the nodules.

Ultrastructure: The cells have characteristic interdigitating cell processes that fit snugly together and are connected by desmosomes, thus displaying ill-defined cytoplasmic borders by light microscopy. Cytoplasmic organelles are sparse, and intermediate filaments are present. Secretory granules are absent [1,2].

Immunohistochemistry: Most cells stain positively for epithelial membrane antigen, vimentin, and progesterone receptors and are negative for cytokeratin, S100, chromogranin, and actin. This phenotype also characterizes leptomeningeal arachnoid cells and cells of meningiomas [5,6].

Clonality: The authors of one study of 11 nodules in 2 patients found that some lesions were monoclonal and others polyclonal, and they concluded that all were probably reactive rather than neoplastic [5].

Possible function: The resemblance of cells of MMNs to leptomeningeal arachnoid cells suggests that they may have a similar function. The latter form minute nodules (pacchionian granulations), which make contact with cranial veins for fluid transfer from the CSF to the blood. The lung lesions with a similar relationship to veins may have a similar function for recycling fluid from the interstitial space to the veins [7].

Pulmonary meningiomas: A few primary meningiomas have been described in the lung as solitary tumors, mostly benign. They have been described in other locations outside the CNS as well, suggesting that arachnoid cells or their precursors exist as heterotopias in locations outside the brain and spinal cord. In a review of 29 cases of primary pulmonary meningioma, tumors occurred in 17 women and 12 men (a female/male ratio less than for MMNs), ages 24-74 (mean 56). Tumors were on the right in 12, left in 16 and multiple and bilateral in 1. Sizes ranged from 0.4 to 12 cm. Two tumors were considered to be malignant [8]. Two case reports have described the presence of both primary meningioma and MMNs in the lung, suggesting that MMNs may be precursors of meningiomas [9]. Nevertheless, meningiomas are rare and usually solitary, whereas MMNs are common and often multiple. However, similar behavior is found in neuroendocrine tumors where tumorlets are relatively common and multiple compared to carcinoid tumors and small cell carcinomas.

Nomenclature: The term minute pulmonary meningothelial-like nodule is cumbersome. The simpler term "arachnoid nodule" seems more apt because multiple lines of evidence (histologic, ultrastructural, and immunohistochemical similarity as well as a relationship to primary pulmonary meningioma) now support the resemblance of leptomeningeal arachnoid cells and cells of MMNs [7]. Further, the radiating shape of the nodules resembles a spider (the leptomeningeal arachnoid cells are so named because the leptomeninges resemble a spider's web).

Summary of Radiographic Features

Summary of Pathologic Features

Diagnosis: Minute pulmonary meningothelial-like nodules (arachnoid nodules)

References: To return to reference section after viewing abstract, click here before clicking on "abstract".

1. Churg A, Warnock M. So-called "minute pulmonary chemodectoma." A tumor not related to paragangliomas. Cancer 1976; 37:1759-1769. Abstract

2. Gaffey M, Mills S, Askin F. Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma. Am J Surg Pathol 1988; 12:167-175. Abstract

3. Sellami D, Gotway M, Hanks D, Webb W. Minute pulmonary meningothelial-like nodules: thin-section CT appearance. J Comput Assist Tomogr 2001; 25:311-313. Abstract

4. Kuroki M, Nakata H, Masuda T, Hashiguchi N, Tamura S, Nabeshima K, Matsuzaki Y, Onitsuka T. Minute pulmonary meningothelial-like nodules: high-resolution computed tomography and pathologic correlations. J Thorac Imaging 2002; 17:227-229. Abstract

5. Niho S, Yokose Y, Nishiwaki Y, Mukai K. Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules. Hum Pathol 1999; 30:425-429 Abstract

6. Pelosi G, Maffini F, Decarli N, Viale G. Progesterone receptor immunoreactivity in minute meningothelioid nodules of the lung. Virchows Arch 2002; 440:543-546. Abstract

7. Heath D, Williams D. Arachnoid nodules in the lungs of high altitude Indians. Thorax 1993; 48:743-745. Abstract

8. Cesario A, Galetta D, Margaritora S, Granone P. Unsuspected primary pulmonary meningioma. Eur J Cardiothorac Surg 2002; 21:553-555. Abstract

9. Gomez-Aracil V, Mayayo E, Alvira R, Arraiza A, Ramon y Cajal S. Fine needle aspiration cytology of primary pulmonary meningioma associated with minute meningotheliallike nodules. Report of a case with histologic, immunohistochemical and ultrastructural studies. Acta Cytol 2002; 46:899-903. Abstract

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Last modified 2/17/03






























Radiologic differential diagnosis: Minute meningothelial-like nodule, atypical adenomatous hyperplasia, respiratory bronchiolitis, bronchioloalveolar carcinoma, disseminated infection, metastatic tumor




























































Minute nodule(s)





























Vein within the lesion




























Vein outside the lesion