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Hamartomas of the lung
Hamartomas of the Lung Richard I. Whyte and Jessica S. Donington © 2003 Elsevier Inc. All rights reserved. Key words:
P
ulmonary hamartomas are the most common benign tumors of the lung. They are also referred to as chondroid hamartoma and chondromyxoid hamartomas and, incorrectly, chondromas. These tumors account for approximately 75% of all benign lung tumors, 4% of all solitary pulmonary nodules, and 8% of pulmonary neoplasms.1-3 Although relatively rare overall, being found in only 0.25% of autopsies, they often present thoracic surgeons due to the need to distinguish them from carcinomas.4
Clinical Characteristics and Presentation Pulmonary hamartomas occur in all patient age ranges, although most are common in the 30- to 60-year-old bracket. They occur 2 to 3 times more frequently in men than women and usually present as unsuspected findings on chest radiographs or computerized tomography that are performed for unrelated reasons. The majority of pulmonary hamartomas are asymptomatic.5 Although Hansen reported that 39% of patients had symptoms at presentation (e.g., cough, dyspnea, pneumonia, hemoptysis, chest pain), it is likely that these symptoms are what prompted the radiographic evaluation and were not related to the hamartoma.4 The majority of hamartomas are 1 to 3 cm in size, although larger ones have been reported. They do not grow quickly, and many show no enlargement at all. In the series of Hansen et al, 50% of lesions that were followed reFrom the Division of Thoracic Surgery, Stanford University, Stanford, CA. Address reprint requests to Richard I. Whyte, MD, Department of Cardiothoracic Surgery, CVRB 205, 300 Pasteur Drive, Stanford, CA 94305. E-mail: [email protected] © 2003 Elsevier Inc. All rights reserved. 1043-0679/03/1503-0000$30.00/0 doi:10.1016/S1043-0679(03)00085-6
mained stable in size, while the other 50% grew at a rate of approximately 3 mm per year. These lesions, while generally peripheral or subpleural in location, are distributed evenly throughout all lobes of the lung. A subset of hamartomas, endobronchial hamartomas, account for 1% to 20% of lesions and are more likely to cause signs or symptoms such as dyspnea, wheezing, or recurrent infections due to airway obstruction.5,6 Endobronchial hamartomas are particularly interesting because cytogenetics studies have shown specific chromosomal abnormalities that suggest a clonal origin of these lesions.7
Radiology The majority of hamartomas present as solitary pulmonary nodules. They are typically smooth, well-circumscribed peripheral pulmonary nodules measuring, which are generally round or lobulated in appearance (Fig 1). Although the description of “popcorn calcifications” is entrenched in the literature as referring to pulmonary hamartomas, calcifications are detected on routine chest radiography only 10% to 30% of the time. Computerized tomography is more likely than plain film to show calcifications, although a more common finding (occurring in up to 50% of cases) is areas of fat density. These findings in a peripheral solitary nodule are highly suggestive of the lesion being a hamartoma. When present, calcifications may be diffuse or eccentric (Fig 2).
Pathology The definition of hamartoma is “a focal malformation of tissue that resembles a neoplasm, grossly and even microscopically, but results from faulty development in an organ.”8 Hamartomas are composed of an abnormal mixture of tissue elements or an abnormal proportion of a single element. They typically grow at a rate similar to
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Figure 1. Posteroanterior (PA)chest radiograph of a patient with a left lung hamartoma. The lesion is adjacent to the left heart border and is typically sized, measuring approximately 2 cm in diameter. The lesion is smooth, round, and slightly lobulated.
normal tissue components and, unlike true neoplasms, rarely result in compression of normal adjacent tissue.
Figure 3. Gross pathology of a small, left lower lobe hamartoma. The lesion is round and subpleural in location. Resection would be easily accomplished either by wedge resection or simple enucleation.
In the lung, hamartomas are usually solitary foci of normal lung tissue elements arranged in abnormal proportions, thereby creating a nodule or “tumor.” Grossly, they appear as firm, round, or lobulated masses that are loosely attached to adjacent tissue (Fig 3). Histologically, they are composed of cartilage, fat, mesenchymal tissue, and occasional bronchial glands (Fig 4). Cytology using a fine needle biopsy may show myxofibromatoustissue that stains metachromatically with Giemsa and Wright stains. Fragments of columnar epithelium may be seen and show cartilage that is highly suggestive of the lesion being a hamartoma.
Diagnosis and Treatment Figure 2. Computerized tomography of a left, lower lobe hamartoma. The lesion is approximately 1.5 cm in diameter and is more central in location than is normal. The lesion shows focal areas of calcification, with other areas of fat density.
The diagnosis of pulmonary hamartoma may be suggested by the radiographic appearance, as described previously. If there is doubt about the diagnosis, resection is generally indicated. Of the patients in whom surgery is contraindicated, a
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Figure 4. Histology of a pulmonary hamartoma. The section shows the myxofibromatous and fatty components (left), and the cartilaginous component (right) of the lesion.
percutaneous fine needle aspiration (FNA) biopsy may be helpful. The role of FNA in this condition is debatable because the diagnostic yield has been reported to range from “minimal” to 85%.9 Clearly, if a patient is at high risk for complications following thoracotomy or thoracoscopy, a FNA with findings highly suggestive of a hamartoma may allow the patient to avoid surgery safely. However, in most cases, resection is diagnostic and therapeutic. Because most hamartomas are small and peripheral, simple enucleation is adequate. At surgery, after incising the overlying pleura, the nodule frequently “pops” out, leaving a small pneumonotomy to be closed. When the tumor is deeper in the lung or if the resection is being performed with a thoracoscope, a wedge resection may be preferable to enucleation. When performing a wedge resection, a minimal amount of surrounding lung tissue should be resected and, because the differential diagnosis includes malignancy, the specimen should be extracted using an endoscopic retrieval bag. For endobronchial hamartomas, a more extensive resection, such as lobectomy or sleeve resection, may be necessary to remove the tumor and any chronically infected lung tissue distal to the obstruction.
Carney Syndrome In 1979, Carney, from the Mayo Clinic, described a syndrome consisting of functioning extra-adrenal paraganglioma, gastric epithelioid leiomyosarcoma, and pulmonary hamartoma.10 This syndrome is now known as Carney Triad and was originally reported as a series of 15 patients, all young women between the ages ?and 24 years, who presented with 2 of the aforementioned 3 conditions. Symptoms were generally from either the gastric tumor or the paraganglioma, and the lung lesions were nearly always discovered later.
Association With Malignancy Occasional reports in the literature have suggested an association between hamartomas and malignant lung tumors– either in the hamartoma, in the site of a resected hamartoma, malignant degeneration of a hamartoma, or elsewhere in the lung of a patient with a hamartoma.1,11 None of the reports shows a clear, causal relationship, although the incidence of unrelated carcinomas in patients with hamartomas is the strongest association. Shields and Robinson collated a number of published series totaling approximately 600 patients and found a rate of
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occurrence of lung cancer of 5.9%.1 Whether this rate is simply due to increased scrutiny, selection bias, or an actual etiologic relationship is not clear.
Summary Pulmonary hamartomas are the most common of benign lung tumors and are important because they (1) compose a common etiology of solitary pulmonary nodules and (2) must be differentiated from malignant tumors of the lung. Although the lesions have characteristic radiographic findings, they frequently must be resected to confirm the diagnosis. Resection of these lesions can often be accomplished using minimally invasive techniques because they are generally small and subpleural in location. In contrast to malignant tumors of the lung, a minimal amount of surrounding parenchyma needs to be resected, and there is no need to assess the regional lymph nodes. Resection should have minimal morbidity and, in patients who have a higher than normal operative risk, a preoperative needle biopsy may be appropriate.
References 1. Shields TW, Robison PG: Benign tumors of the lung, in Shields TW, LoCicero J III, Ponn RB (eds): General Thoracic Surgery (ed 5). Philadelphia, PA, Lippincott, Williams & Wilkins, 2000, 1515-1519 2. Bateson EM: So-called hamartoma of the lung: A true neoplasm of fibrous connective tissue of the bronchi. Cancer 31:1458, 1973 3. Khouri NF, Meziane MA, Zerhouni EA, et al: The solitary pulmonary nodule. Assessment, diagnosis, and management. Chest 91:128-133, 1987 4. Hansen CP, Holtveg H, Francis D, et al: Pulmonary hamartoma. J Thorac Cardiovasc Surg 104:674-678, 1992 5. Gjevre JA, Myers JL, Prakash UB: Pulmonary hamartomas. Mayo Clin Proc 71:14-20, 1996 6. Cosio BG, Villena V, Echave-Sustaeta J, et al: Endobronchial hamartoma. Chest 122:202-205, 2002 7. Fletcher JA, Pinkus GS, Donovan K, et al: Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma. Cancer Res 52:6224-6228, 1992 8. Steadman’s Medical Dictionary (ed 27). 9. Hamper UM, Khouri NF, Stitik FP, et al: Pulmonary hamartoma: Diagnosis by transthoracic needle aspiration biopsy. Radiology 155:15-18, 1985 10. Carney JA: The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer 43:374, 1979 11. Higashita R, Ichikawa S, Ban T, et al: Coexistence of lung cancer and hamartoma. Jpn J Thorac Cardiovasc Surg 49:258260, 2001
P
ulmonary hamartomas are the most common benign tumors of the lung. They are also referred to as chondroid hamartoma and chondromyxoid hamartomas and, incorrectly, chondromas. These tumors account for approximately 75% of all benign lung tumors, 4% of all solitary pulmonary nodules, and 8% of pulmonary neoplasms.1-3 Although relatively rare overall, being found in only 0.25% of autopsies, they often present thoracic surgeons due to the need to distinguish them from carcinomas.4
Clinical Characteristics and Presentation Pulmonary hamartomas occur in all patient age ranges, although most are common in the 30- to 60-year-old bracket. They occur 2 to 3 times more frequently in men than women and usually present as unsuspected findings on chest radiographs or computerized tomography that are performed for unrelated reasons. The majority of pulmonary hamartomas are asymptomatic.5 Although Hansen reported that 39% of patients had symptoms at presentation (e.g., cough, dyspnea, pneumonia, hemoptysis, chest pain), it is likely that these symptoms are what prompted the radiographic evaluation and were not related to the hamartoma.4 The majority of hamartomas are 1 to 3 cm in size, although larger ones have been reported. They do not grow quickly, and many show no enlargement at all. In the series of Hansen et al, 50% of lesions that were followed reFrom the Division of Thoracic Surgery, Stanford University, Stanford, CA. Address reprint requests to Richard I. Whyte, MD, Department of Cardiothoracic Surgery, CVRB 205, 300 Pasteur Drive, Stanford, CA 94305. E-mail: [email protected] © 2003 Elsevier Inc. All rights reserved. 1043-0679/03/1503-0000$30.00/0 doi:10.1016/S1043-0679(03)00085-6
mained stable in size, while the other 50% grew at a rate of approximately 3 mm per year. These lesions, while generally peripheral or subpleural in location, are distributed evenly throughout all lobes of the lung. A subset of hamartomas, endobronchial hamartomas, account for 1% to 20% of lesions and are more likely to cause signs or symptoms such as dyspnea, wheezing, or recurrent infections due to airway obstruction.5,6 Endobronchial hamartomas are particularly interesting because cytogenetics studies have shown specific chromosomal abnormalities that suggest a clonal origin of these lesions.7
Radiology The majority of hamartomas present as solitary pulmonary nodules. They are typically smooth, well-circumscribed peripheral pulmonary nodules measuring, which are generally round or lobulated in appearance (Fig 1). Although the description of “popcorn calcifications” is entrenched in the literature as referring to pulmonary hamartomas, calcifications are detected on routine chest radiography only 10% to 30% of the time. Computerized tomography is more likely than plain film to show calcifications, although a more common finding (occurring in up to 50% of cases) is areas of fat density. These findings in a peripheral solitary nodule are highly suggestive of the lesion being a hamartoma. When present, calcifications may be diffuse or eccentric (Fig 2).
Pathology The definition of hamartoma is “a focal malformation of tissue that resembles a neoplasm, grossly and even microscopically, but results from faulty development in an organ.”8 Hamartomas are composed of an abnormal mixture of tissue elements or an abnormal proportion of a single element. They typically grow at a rate similar to
Seminars in Thoracic and Cardiovascular Surgery, Vol 15, No 3 ( July), 2003: pp 301-304
301
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Figure 1. Posteroanterior (PA)chest radiograph of a patient with a left lung hamartoma. The lesion is adjacent to the left heart border and is typically sized, measuring approximately 2 cm in diameter. The lesion is smooth, round, and slightly lobulated.
normal tissue components and, unlike true neoplasms, rarely result in compression of normal adjacent tissue.
Figure 3. Gross pathology of a small, left lower lobe hamartoma. The lesion is round and subpleural in location. Resection would be easily accomplished either by wedge resection or simple enucleation.
In the lung, hamartomas are usually solitary foci of normal lung tissue elements arranged in abnormal proportions, thereby creating a nodule or “tumor.” Grossly, they appear as firm, round, or lobulated masses that are loosely attached to adjacent tissue (Fig 3). Histologically, they are composed of cartilage, fat, mesenchymal tissue, and occasional bronchial glands (Fig 4). Cytology using a fine needle biopsy may show myxofibromatoustissue that stains metachromatically with Giemsa and Wright stains. Fragments of columnar epithelium may be seen and show cartilage that is highly suggestive of the lesion being a hamartoma.
Diagnosis and Treatment Figure 2. Computerized tomography of a left, lower lobe hamartoma. The lesion is approximately 1.5 cm in diameter and is more central in location than is normal. The lesion shows focal areas of calcification, with other areas of fat density.
The diagnosis of pulmonary hamartoma may be suggested by the radiographic appearance, as described previously. If there is doubt about the diagnosis, resection is generally indicated. Of the patients in whom surgery is contraindicated, a
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303
Figure 4. Histology of a pulmonary hamartoma. The section shows the myxofibromatous and fatty components (left), and the cartilaginous component (right) of the lesion.
percutaneous fine needle aspiration (FNA) biopsy may be helpful. The role of FNA in this condition is debatable because the diagnostic yield has been reported to range from “minimal” to 85%.9 Clearly, if a patient is at high risk for complications following thoracotomy or thoracoscopy, a FNA with findings highly suggestive of a hamartoma may allow the patient to avoid surgery safely. However, in most cases, resection is diagnostic and therapeutic. Because most hamartomas are small and peripheral, simple enucleation is adequate. At surgery, after incising the overlying pleura, the nodule frequently “pops” out, leaving a small pneumonotomy to be closed. When the tumor is deeper in the lung or if the resection is being performed with a thoracoscope, a wedge resection may be preferable to enucleation. When performing a wedge resection, a minimal amount of surrounding lung tissue should be resected and, because the differential diagnosis includes malignancy, the specimen should be extracted using an endoscopic retrieval bag. For endobronchial hamartomas, a more extensive resection, such as lobectomy or sleeve resection, may be necessary to remove the tumor and any chronically infected lung tissue distal to the obstruction.
Carney Syndrome In 1979, Carney, from the Mayo Clinic, described a syndrome consisting of functioning extra-adrenal paraganglioma, gastric epithelioid leiomyosarcoma, and pulmonary hamartoma.10 This syndrome is now known as Carney Triad and was originally reported as a series of 15 patients, all young women between the ages ?and 24 years, who presented with 2 of the aforementioned 3 conditions. Symptoms were generally from either the gastric tumor or the paraganglioma, and the lung lesions were nearly always discovered later.
Association With Malignancy Occasional reports in the literature have suggested an association between hamartomas and malignant lung tumors– either in the hamartoma, in the site of a resected hamartoma, malignant degeneration of a hamartoma, or elsewhere in the lung of a patient with a hamartoma.1,11 None of the reports shows a clear, causal relationship, although the incidence of unrelated carcinomas in patients with hamartomas is the strongest association. Shields and Robinson collated a number of published series totaling approximately 600 patients and found a rate of
304
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occurrence of lung cancer of 5.9%.1 Whether this rate is simply due to increased scrutiny, selection bias, or an actual etiologic relationship is not clear.
Summary Pulmonary hamartomas are the most common of benign lung tumors and are important because they (1) compose a common etiology of solitary pulmonary nodules and (2) must be differentiated from malignant tumors of the lung. Although the lesions have characteristic radiographic findings, they frequently must be resected to confirm the diagnosis. Resection of these lesions can often be accomplished using minimally invasive techniques because they are generally small and subpleural in location. In contrast to malignant tumors of the lung, a minimal amount of surrounding parenchyma needs to be resected, and there is no need to assess the regional lymph nodes. Resection should have minimal morbidity and, in patients who have a higher than normal operative risk, a preoperative needle biopsy may be appropriate.
References 1. Shields TW, Robison PG: Benign tumors of the lung, in Shields TW, LoCicero J III, Ponn RB (eds): General Thoracic Surgery (ed 5). Philadelphia, PA, Lippincott, Williams & Wilkins, 2000, 1515-1519 2. Bateson EM: So-called hamartoma of the lung: A true neoplasm of fibrous connective tissue of the bronchi. Cancer 31:1458, 1973 3. Khouri NF, Meziane MA, Zerhouni EA, et al: The solitary pulmonary nodule. Assessment, diagnosis, and management. Chest 91:128-133, 1987 4. Hansen CP, Holtveg H, Francis D, et al: Pulmonary hamartoma. J Thorac Cardiovasc Surg 104:674-678, 1992 5. Gjevre JA, Myers JL, Prakash UB: Pulmonary hamartomas. Mayo Clin Proc 71:14-20, 1996 6. Cosio BG, Villena V, Echave-Sustaeta J, et al: Endobronchial hamartoma. Chest 122:202-205, 2002 7. Fletcher JA, Pinkus GS, Donovan K, et al: Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma. Cancer Res 52:6224-6228, 1992 8. Steadman’s Medical Dictionary (ed 27). 9. Hamper UM, Khouri NF, Stitik FP, et al: Pulmonary hamartoma: Diagnosis by transthoracic needle aspiration biopsy. Radiology 155:15-18, 1985 10. Carney JA: The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer 43:374, 1979 11. Higashita R, Ichikawa S, Ban T, et al: Coexistence of lung cancer and hamartoma. Jpn J Thorac Cardiovasc Surg 49:258260, 2001