Pulmonary Hamartoma (synonyms: mesenchymoma, chondroid mesenchymoma)

Introduction: Hamartomas of the lung are benign lesions composed of an abnormal mixture of epithelial and mesenchymal elements. Traditionally, they were considered to be developmental abnormalities, but now they are considered to be benign mesenchymal neoplasms: the epithelial component is reactive [1].

Epidemiology: Hamartomas are more frequent in men than women, 1.6 to 3:1 [1-6]. Most are found in the 6th to 7th decades [1-5,7], and most persons with hamartomas are smokers; in one series, only 30/215 (14%) never smoked [1]. Over 90% of the tumors are peripheral, and 10% or less are endobronchial [1,4,6]. The peripheral tumors constitute 7-14% of radiographic, solitary pulmonary nodules [4]. Prevalence of peripheral hamartomas at autopsy in African miners was found to increase gradually from 1/1000 in the third decade to 12/1000 in the eighth decade [8]. The tumors first appear in adulthood and continue to increase in size at a slow rate [1,4]. Two tumors occurred in 4 of 154 patients, and 2 recurred 10 and 12 years after enucleation [4]. Two synchronous tumors were also reported in a 52-year-old man [9].

Clinical features: Peripheral nodules are asymptomatic; endobronchial lesions are frequently associated with symptoms or signs of obstruction like endobronchial lipomas. As such, they must be distinguished from malignant neoplasms or recognized as the cause of a pneumonia or atelectasis [6].

Radiographic changes: Peripheral lesions have no predilection for any lobe [1]. They appear as solitary, round nodules. Characteristic punctate or popcorn calcification occurs on plain films in about 10% of cases [6]. On HRCT, lesions are considered to be diagnostic of hamartoma if they are less than 2.5 cm in diameter, have a sharp, smooth wall, and contain fat, or calcification and fat. With these criteria, 62% of 45 lesions could be diagnosed by HRCT. None of 355 cases of lung cancer had these features [10]. Conservative operative management or non-operative follow-up for slowly-growing asymptomatic lesions <2.5 cm in diameter has been advocated [10]. Parenchymal opacities or atelectasis occur with endobronchial tumors, and the lesion is found by bronchoscopy [6].

Gross appearance: The photo shows cross sections of a peripheral hamartoma removed surgically. Note the lobulated appearance. The pearly-white tissue is cartilage. The more translucent areas are loose, myxoid tissue. The surface has been inked to indicate surgical margins.

Histopathologic changes: Tumors vary in size from 1 to 9 cm, mean about 1.5 cm [1,4]. They develop as nodular endobronchial or bronchiolar growths covered by non-neoplastic epithelium. The tumor consists of lobules of cartilage, fat, fibromyxoid tissue, and sometimes smooth muscle and bone (the benign neoplasm) that are separated by clefts lined by non-neoplastic respiratory epithelium. Parenchymal tumors tend to have more epithelial clefts than do endobronchial tumors. Endobronchial lesions tend to have more fat, and 3 of 17 in one series were composed predominantly of fat [2].

This non-encapsulated, rounded hamartoma is surrounded by lung (bottom and left). Lobules of cartilage (upper right) and loose connective tissue (arrow) are separated by low, cuboid epithelium.

Another field shows the epithelial-lined lobules, which contain a mixture of cartilage (bottom), fat, and connective tissue.

Here, the connective tissue has a myxoid appearance defined by the abundant bluish matrix. Fatty tissue and a strand of compressed epithelial cells (arrow) are also present.

Diagnostic procedures: Fine needle aspirates (FNA) of peripheral lesions are diagnostic if cartilage or fibromyxoid fragments are recognized. Epithelial cells and fat are non-specific [11]. In one series, diagnosis was made by transthoracic FNA in 34 of 40 (85%) patients [5]. Endobronchial biopsy of lesions may be non-diagnostic if the significance of the fibromyxoid tissue is not recognized. Immunoperoxidase staining for S-100 has been reported to be positive in the fibromyxoid tissue as well as in the cartilage and may be a helpful adjunct in diagnosis [12]. In any case, the results of FNA or biopsies should be correlated with clinical and radiographic findings.

FNA of a solitary pulmonary nodule showed this fragment of cartilage as well as fibromyxoid tissue as shown below. Note the rounded capsules around the cells of the cartilage (arrows).

This loose, connective tissue and the cartilage above both stain with antibody to S-100 protein, which can be helpful in diagnosis. The finding of cartilage and fibromyxoid tissue was considered to confirm a diagnosis of hamartoma in this case: no surgical procedure was performed.

Other associations: The high rate of synchronous pulmonary carcinomas (about 15%) has been attributed to finding asymptomatic lesions in patients being studied for symptoms of lung cancer [1,4,6].

Natural history and therapy: Most tumors grow slowly (average of 3 mm/y) during follow-up [5]. Treatment consists of wedge resection or enucleation of peripheral tumors and bronchoscopic removal of endobronchial lesions [1]. Although almost always benign, one patient with a tumor of 37 years' duration had apparent malignant sarcomatous change after resection of a 12 cm tumor. She died 3 months later [13].

Differential diagnosis:

Endobronchial hamartomas

Peripheral hamartomas

Bronchogenic carcinoma

Any benign or malignant lung tumor

Papilloma

Metastatic tumor

Granular cell tumor

Infectious granulomas

Adenoid cystic carcinoma

Amyloidoma

Mucoepidermoid carcinoma

Carney's triad (gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma): usually in young women [14]

Carcinoid tumor

Leiomyoma

Lipoma

Tracheobronchopathia osteochondroplastica

Metastatic tumor

References

1. Gjevre J, Myers J, Prakash U. Pulmonary hamartomas. Mayo Clin Proc 1996; 71:14-20.

2. Tomashefski Jr J. Benign endobronchial mesenchymal tumors. Their relationship to parenchymal pulmonary hamartomas. Am J Surg Pathol 1982; 6:531-540.

3. Borro J, Moya J, Botella J, Padilla J, Canto A, Paris F. Endobronchial hamartoma. Report of 7 cases. Scand J Thor Cardiovasc Surg 1989; 23:285-287.

4. Van den Bosch J, Wagenaar S, Corrin B, Elbers J. Mesenchymoma of the lung (so-called hamartoma): a review of 154 parenchymal and endobronchial cases. Thorax 1987; 42:790-793.

5. Hansen C, Holtveg H, Francis D, Rasch L, Bertelsen S. Pulmonary hamartoma. J Thorac Cardiovasc Surg 1992; 104:674-678.

6. Fudge T, Ochsner J, Mills N. Clinical spectrum of pulmonary hamartomas. Ann Thorac Surg 1980; 30:36-39.

7. Bateson E. So-called hamartoma of the lung--a true neoplasm of fibrous connective tissue of the bronchi. Cancer 1973; 31:1458-1467.

8. Murray J, Kielkowski D, Leiman G. The prevalence and age distribution of peripheral pulmonary hamartomas in adult males. An autopsy-based study. S Afr Med J 1991; 79:247-249.

9. King Jr T, Christopher K, Schwarz M. Multiple pulmonary chondromatous hamartomas. Hum Pathol 1982; 13:496-497.

10. Siegelman S, Khouri N, Scott Jr W, Leo F, Hamper U, Fishman E, Zerhouni E. Pulmonary hamartoma: CT findings. Radiology 1986; 160:313-317.

11. Dunbar F, Leiman G. The aspiration cytology of pulmonary hamartomas. Diagn Cytopathol 1989; 5:174-180.

12. Wiatrowska B, Yazdi H, Matzinger F, MacDonald L. Fine needle aspiration biopsy of pulmonary hamartomas. Radiologic, cytologic and immunocytochemical study of 15 cases. Acta Cytol 1995; 39:1167-1174.

13. Basile A, Gregoris A, Antoci B, Romanelli M. Malignant change in a benign pulmonary hamartoma. Thorax 1989; 44:232-233.

14. Carney J. The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. Cancer 1979; 43:374-382.

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