OTHER NEOPLASTIC LESIONS
Introduction
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Histologically most cases of lung cancer are adenocarcinoma, squamous cell carcinoma, large cell undifferentiated carcinoma, and small cell carcinoma.
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If carcinoid and atypical carcinoid tumors are added to the above-mentioned histopathologic types, 99% of all primary lung neoplasms are accounted for.
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In addition to carcinoid tumors, this chapter will focus on benign lung tumors, as well as a variety of nonbronchogenic primary pulmonary malignancies.
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Classification of these neoplasms is problematic because of disagreement regarding the histogenesis of these varied tumors.
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It is easiest to just discuss these neoplasms individually.
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BENIGN NEOPLASMS OF THE LUNG
Hamartoma
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Most common benign lung neoplasm
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Arrigoni and colleagues reported on 130 benign lung tumors from Mayo Clinic and found that 100 (76.9%) were hamartomas ( Table 33-1 ).
TABLE 33-1 ▪
BENIGN LUNG TUMORS AND THEIR INCIDENCE *
Tumor
Number (%)
Hamartoma
100 (76.9)
Benign mesothelioma
16 (12.3)
Xanthomatous and inflammatory pseudotumors
7 (5.4)
Lipoma
2 (1.5)
Leiomyoma
2 (1.5)
Hemangioma
1 (0.8)
Mucous gland adenoma
1 (0.8)
Mixed tumor
1 (0.8)
* Adapted from Arrigoni MG, Woolner LB, Bernatz PE, Miller WE, Fontana WS. Benign tumors of the lung. A ten-year experience. J Thorac Cardiovasc Surg 1970;60:589-599.
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Pathology: These tumors are derived from peribronchial mesenchyme and are composed mostly of cartilage, connective tissue, fat, smooth muscle, and respiratory epithelium ( Fig. 33-1 ).
Figure 33-1
Hamartoma. It is well demarcated from the surrounding lung. Note the variegated white and yellow appearance which corresponds to the cartilage and fat.
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Clinical presentation: Most are asymptomatic and account for 7% to 14% of pulmonary coin lesions.
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In a review of 215 patients with hamartomas, Gjevre and associates found only 3% were symptomatic.
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Commonly occur between the ages of 40 and 70 years, with a 2:1 to 4:1 male-to-female ratio.
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Radiology: often solitary and can occur in any part of the lung but are more common in the periphery
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The tumors measure from 1 to 7 cm (average 2 cm) in diameter.
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A characteristic popcorn pattern of calcification may be present on computed tomography (CT) scan in up to 30% of cases, but some authors report a much lower incidence of calcification.
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CT may also demonstrate fat within the lesion. Siegelman and colleagues reported fat in 50% of hamartomas ( Fig. 33-2 ).
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The presence of fat density by high-resolution CT in a peripheral solitary lesion is strong presumptive evidence for a benign hamartoma.
Figure 33-2
Computed tomography scan showing a 1-cm pulmonary nodule with a central fat density ( arrow ). This lesion has an appearance consistent with a hamartoma.
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Pathology: Malignant transformation is rare.
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Growth is slow.
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Needle biopsy may be diagnostic.
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This may be useful after CT studies when the diagnosis of hamartoma is still in doubt and the patient is poor risk for surgical intervention.
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Treatment
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Excision should be considered if the diagnosis is in doubt.
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Small (<2 cm) hamartomas can be observed.
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Hamartomas larger than 2.5 cm should be considered for excision.
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Video-assisted thoracoscopic wedge resection is the preferred treatment.
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Segmentectomy or lobectomy may be required, and pneumonectomy should be avoided.
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Recurrence is highly unlikely.
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Inflammatory Pseudotumor
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Numerous synonyms: histiocytoma, plasma cell granuloma, plasmacytoma, xanthoma, xanthogranuloma, xanthofibroma, and inflammatory myofibroblastic tumor.
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Pathology: Classically considered a non-neoplastic process characterized by unregulated growth of inflammatory cells.
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Historically, cause was unknown but thought to represent an exaggerated tissue response to injury.
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Now thought to be of neoplastic origin with evidence of rearrangement of the anaplastic lymphoma kinase gene on chromosome 2p23.
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Presentation: The true incidence is unknown; however, in 56,400 general thoracic surgical procedures performed at Mayo Clinic between 1946 and 1993, 23 patients (0.04%) had resection of inflammatory pseudotumors.
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Median age 47 years (range, 5 to 77 years).
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They are the most common benign lung tumor in children.
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Presentation is usually with symptoms: cough, weight loss, fever, fatigue.
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Radiology: usually appear as well-defined solitary parenchymal masses 0.5 to 36 cm in diameter; the most common size is 1 cm to 6 cm.
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Pathology: Grossly they consist of multilobular or bosselated tumor with a rubbery surface. They commonly have a white shiny appearance due to the large amount of fibrous tissue present; however, as the number of histiocytes or xanthomatous cells increase, their color becomes more yellow due to lipid accumulation ( Fig. 33-3 ).
Figure 33-3
Inflammatory pseudotumor. Note the sharp demarcation from the surrounding lung. The presence of xanthoma cells imparts a yellow color, plasma cells and lymphocytes a tan color, and fibrous connective tissue a white color.
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Treatment is complete resection to avoid local recurrence.
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In the Mayo Clinic series, complete resection was accomplished in 18 (78%) patients. Resection required pneumonectomy in six patients, bilobectomy in one, lobectomy in six, segmentectomy in one, wedge resection in seven, and chest wall resection in two.
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Two patients with positive margins underwent re-resection, and two have been observed without evidence of tumor growth.
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The 5-, 8-, and 10-year survival rates were 91.3%, 91.3%, and 77.7% respectively.
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Lipoma
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Presentation: Rare, with only two found out of 130 benign lung tumors in the Mayo Clinic series.
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Most are endobronchial and cause obstruction.
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Radiology: Because of their fatty composition, CT may strongly suggest the diagnosis of endobronchial lipoma.
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Treatment: Use bronchoscopic removal whenever possible.
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Muraoka and associates reported on 64 cases with surgical procedures including pneumonectomy in four patients, lobectomy in 24, bilobectomy in eight, bronchotomy in four, bronchoscopic removal with Nd:YAG laser in 17, cautery in five, and a combination of laser and cautery in five.
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Reasons for surgical resection include
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Difficulty in obtaining a definitive diagnosis and the existence of a possible complicated malignant tumor
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Peripheral destruction of the lung secondary to long-standing atelectasis or pneumonia
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Extrabronchial growth or the existence of subpleural lipomatous disease
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Technical difficulties encountered during the bronchoscopic procedure
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Leiomyoma
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Presentation:
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Account for 1.5% to 2% of benign lung neoplasms
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Most common in young and middle-aged women
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Location split almost evenly between lung parenchyma and tracheobronchial
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Peripheral lung parenchymal leiomyoma are often asymptomatic while tracheobronchial leiomyoma may cause pulmonary obstruction.
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Radiology: On CT, there are no distinguishing features from other pulmonary nodules.
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Pathology: Grossly, they resemble smooth muscle tumors ( Fig. 33-4 ).
Figure 33-4
Benign pulmonary leiomyoma. The nodule is lobulated with a typical pale white smooth muscle appearance.
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Treatment
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Endobronchial leiomyoma without destroyed distal lung parenchyma may be treated with endobronchial resection with or without the use of Nd:YAG laser.
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Surgical resection is the treatment of choice for peripheral leiomyoma and those endobronchial leiomyoma with destroyed distal lung tissue.
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Benign metastasizing leiomyoma
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Term used for multiple (occasionally single) well-differentiated pulmonary smooth muscle nodules found almost exclusively in women, many of whom have a history of uterine leiomyoma.
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Pathology: very bland cytologic appearance, with minimal mitosis or necrosis very similar to uterine leiomyomas.
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Controversial term because they have hematogenously spread from benign uterine leiomyoma; this contradicts their “benign” designation.
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Kayser and colleagues compared benign metastasizing leiomyomas with uterine leiomyomas using a variety of markers such as estrogen receptor (ER) and progesterone receptor (PR) receptors and Ki-67. They concluded that benign metastasizing leiomyomas are in reality slow-growing uterine leiomyosarcomas.
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Takemura and colleagues believe that benign metastasizing leiomyomas could be due to multicentric benign leiomyomatous growths instead of actual metastases.
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Treatment
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Pulmonary resection can be considered when feasible and for establishment of diagnosis.
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These tumors can regress following oophorectomy.
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Because these tumors are ER- and PR-receptor positive, they may respond favorably to hormonal therapy.
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Hemangioma
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Sclerosing hemangioma
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Presentation: Sugio and colleagues reported sclerosing hemangioma as the 2nd most common benign lung neoplasm following hamartoma.
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Eighty percent occur in women.
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Most are asymptomatic.
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Radiology: they appear as a solitary, circumscribed, homogeneous mass that occasionally is calcified.
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They range in size from 0.4 cm to 8.0 cm, with an average of 2.8 cm.
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Pathology: Four major histologic patterns exist: solid, papillary, sclerotic, and hemorrhagic. Most of these neoplasms exhibit combinations of these patterns.
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Treatment: Surgical resection is the procedure of choice.
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Miyagawa-Hayashino and colleagues have reported on 4 patients with sclerosing hemangioma and lymph node metastases.
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Lymph node metastases were described as peribronchial, regional, and hilar.
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Despite the presence of lymph node metastases, these authors still consider sclerosing hemangiomas to be benign.
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Because of the possibility of lymph node metastases, a regional and hilar lymph node dissection should be done in addition to surgical resection of the sclerosing hemangioma.
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Prognosis is excellent, and prognosis did not appear to be affected by the presence of lymph node metastases.
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Cavernous hemangioma
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Presentation: Extremely rare, occurring in all age groups
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Shields and Robinson consider these to be pulmonary arteriovenous malformations (AVMs).
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May occur in the tracheobronchial tree or in the peripheral lung parenchyma
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Presentation may be asymptomatic or include hemoptysis, respiratory distress, or congestive heart failure.
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Treatment
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Endobronchial lesions are managed by Nd:YAG laser.
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Parenchymal AVMs can be embolized with metal coils and occasionally require surgical excision.
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Mucous Gland Adenoma
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Synonyms: mucous gland cystadenoma, adenomatous polyp, and adenomas of mucous gland type
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Presentation: Rare neoplasm that occurs in both children and adults, and is more common in women.
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Arises in the bronchus and derived from bronchial mucus glands
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Because of their bronchial location, patients often have symptoms secondary to obstruction or hemorrhage: cough, fever, hemoptysis, recurrent pneumonia.
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Pathology: Grossly the tumors are soft, spherical, polypoid endobronchial nodules that are usually smaller than 2 cm in diameter but may range up to 7 cm.
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They are more common lower or middle lobe lobar or segmental bronchi.
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The differential diagnosis includes low-grade mucoepidermoid carcinoma.
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Distinguishing between the two types may be difficult with small biopsies. The lack of cytologic atypia, mitoses, and necrosis aids in differentiation.
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Treatment
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Endobronchial resection with or without the use of Nd:YAG laser or cryotherapy if there is no distal lung destruction
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Surgical resection is the treatment of choice for these neoplasms if there is destroyed distal lung parenchyma or there are contraindications to endoscopic resection
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Prognosis: excellent.
Chondroma
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Benign tumors composed of hyaline cartilage, which may be parenchymal or involve the cartilaginous airways.
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Presentation:
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Endobronchial chondromas are often associated with obstructive symptoms, are more common in men, and may be treated by endobronchial removal or surgical resection.
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Although parenchymal chondromas are frequently asymptomatic, they are more common in women and may be associated with Carney’s triad. In fact, the presence of a pulmonary chondroma in a young woman should lead to consideration of this triad, which includes
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Chondroma of the lung single or multiple
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Gastrointestinal stromal tumor
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Extra-adrenal paraganglioma
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Treatment: repeated surgical resections of the respective tumors
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Lung parenchymal–sparing resections are adequate for pulmonary chondromas.
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Prognosis
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For a single pulmonary chondroma, overall survival is excellent.
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For patients with Carney’s triad, despite repeated resections, the development of recurrent neoplasms is common. Neoplasms that grow or cause symptoms should be resected. Carney’s triad is a chronic, persistent, indolent disease extending over a long period of follow-up. Sixteen percent of patients eventually die of the disease.
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Atypical Adenomatous Hyperplasia
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Atypical adenomatous hyperplasia (AAH) is of increasing interest because of its association with bronchoalveolar carcinoma (BAC).
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Pathology: AAH is a focal lesion smaller than 5 mm in diameter due to proliferation of atypical bronchoalveolar cells lining centriacinar alveoli.
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Autopsy studies have demonstrated AAH in 2% to 4% of cases.
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Presentation: Demographic data are conflicting.
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May be more common in women
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May be more frequent in Japanese individuals
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Radiology:
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Most AAH is completely invisible; however, when visible, it may present on thin-section high-resolution CT as tiny foci of ground-glass opacification within the lung parenchyma.
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These ground-glass features, however, are not specific to AAH.
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Differential diagnosis is primarily with BAC.
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Grossly, AAH is typically smaller than 5 mm in diameter and BAC is larger than 10 mm; however, size alone cannot reliably make the distinction between the two.
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Pathology: cell population of AAH may be more heterogenous and BAC more monomorphic. Of the following histologic features, AAH rarely demonstrates more than one, whereas BAC exhibits three or more.
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Marked cell stratification
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High cell density, with marked overlapping of nuclei
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Coarse nuclear chromatin and prominent nucleoli
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True papillae or an obvious picket-fence growth pattern
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Increase in columnar cell height in excess of those lining terminal bronchioles
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BAC
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There are little data on the appropriate treatment of AAH.
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In most cases, treatment is determined by the associated lesions that may be present.
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If a ground-glass opacity is resected and AAH is identified, then only a wedge resection with free margins is required.
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Even for BAC, there is a growing consensus that sublobar resection may be adequate therapy.
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MALIGNANT NEOPLASMS OF THE LUNG
Bronchial Adenomas
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Describe a group of slow-growing neoplasms, most of which arise from the bronchial glands
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Three histologic types of tumors
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Bronchial carcinoids
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Adenoid cystic carcinoma
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Mucoepidermoid carcinoma
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The term bronchial adenoma is a misnomer because these tumors are usually low-grade malignancies and not benign neoplasms as the term adenoma implies.
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The term bronchial adenoma should be avoided whenever possible.
Carcinoid Tumors
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History: First described by Otto Lubarsch in 1888 who identified multiple tumors in the distal ileum of two patients at autopsy.
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Sigfried Oberndorfer in 1907 coined the term karzinoide to describe tumors with carcinoma-like features but a much more indolent behavior.
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Pathology
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Pulmonary carcinoids are malignant neuroendocrine tumors comprising 1% to 2% of all primary lung tumors and 85% of bronchial gland tumors.
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Carcinoid tumors are part of the spectrum of malignant neuroendocrine tumors, which range from low-grade typical carcinoid tumors to intermediate-grade atypical carcinoid tumors to high-grade tumors, including large cell neuroendocrine carcinoma and small cell lung carcinoma.
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Most pulmonary carcinoid tumors arise in major bronchi.
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Ten percent in mainstem bronchi
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Seventy-five percent in lobar bronchi
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Fifteen percent in the lung periphery that is segmental bronchi and distal
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Frequently have a large endobronchial component with a fleshy smooth polypoid mass protruding into the bronchial lumen ( Fig. 33-5 ). The cut surface may appear tan-yellow or red depending on the extent of vascularity.
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