Primary malignant biphasic tumors occurring in the lung parenchyma are rare, accounting for no more than 1% to 2% of all primary malignant tumors of the lung. The two most common neoplasms in this group are blastomas and carcinosarcomas. Not all pulmonary blastomas are biphasic, but because a majority are, the topic of pulmonary blastomas is covered in this chapter.
Pleuropulmonary blastomas also are included in this chapter. This tumor occurs predominantly in the pediatric population; however, the designation “blastoma” may cause it to be confused with blastoma in the adult.
|Characteristic||Monophasic Blastoma||Biphasic Blastoma||PPB||Carcinosarcoma|
|Age < 12 yr||Uncommon||Uncommon||Common||Uncommon|
|Histologic Feature||Monophasic Blastoma||Biphasic Blastoma||PPB||Carcinosarcoma|
|Squamous cell carcinoma||Never||Never or very unusual||Never||Common|
|Undifferentiated large cell carcinoma||Never||Never||Never||Common|
|Benign cystic component||Never||Never||Always||Never|
The group of tumors designated pulmonary blastoma probably represents less than 1% of all malignant primary lung neoplasms. Because of their rarity, these neoplasms often are addressed with similar tumors, such as pulmonary carcinosarcomas, in the category “biphasic tumors of the lung.” Pulmonary blastoma occasionally is confused with pleuropulmonary blastoma, a tumor that shares similar terminology but probably represents a different clinicopathologic entity. As noted previously, not all pulmonary blastomas are biphasic tumors, and currently the World Health Organization (WHO) classifies the monophasic variant of pulmonary blastoma as “well-differentiated fetal adenocarcinoma.” In this chapter, however, the term blastoma is used consistently.
In 1952, Barnard described a tumor in a 40-year-old woman who had survived 10 years after a pneumonectomy for an intrapulmonary tumor. Histologically, the tumor was characterized by a mixture of carcinoma and sarcoma, which Barnard found to be similar to the embryomata of the kidney, so he designating it “embryoma of the lung.” In 1961, Spencer described three similar tumors that he termed pulmonary blastoma , noting that they resembled nephroblastomas found in the kidney. In addition, he suggested that such terminology would lend support to the theory of dual development of the lung from the laryngotracheal bud and pulmonary mesenchyma. This theory had already been presented by Waddell, who suggested that the distal respiratory portion of the lung derives from the mesenchyma. However, other investigators disagreed with this view of lung histogenesis and supported the theory that the lung is formed from two germ cell layers. Many of these workers interpreted pulmonary blastoma as a form of carcinosarcoma that happened to resemble the fetal lung. By the early 1970s, pulmonary blastoma had been reported only sporadically in the literature, with fewer than 20 cases mentioned. All of the tumors occurred in adult patients and displayed the characteristic biphasic histologic features. Most of the cases had a fatal outcome, with variable range of survival. Nevertheless, there was still resistance to classifying pulmonary blastoma as a specific clinicopathologic condition, and on the basis of embryogenesis, some researchers still felt that it was a variant of carcinosarcoma. To address this view, some studies were published suggesting that all of the epithelium-lined structures, including alveoli, are of endodermal origin, whereas pulmonary blastomas are composed of two distinct components: epithelial and mesenchymal. Pulmonary blastomas have been described under a variety of names, including pulmonary endodermal tumor resembling fetal lung, adenocarcinoma simulating fetal tubules in pseudoglandular stage, and adenocarcinoma of the fetal lung type.
In the most recent WHO classification of tumors of the lung, the definition of pulmonary blastoma was limited to tumors with a biphasic morphology—that is, tumors that show areas of well-differentiated fetal adenocarcinoma and primitive mesenchymal stroma. Fetal adenocarcinoma (pulmonary blastoma, monophasic type) is defined as a distinctive form of adenocarcinoma with histopathologic features resembling those of fetal lung tubules. However, the WHO investigators also added that some of these fetal adenocarcinomas may rarely show other subtypes of adenocarcinoma. This statement is a bit ambiguous, because a wide range of histologic features may be seen in otherwise nonfetal adenocarcinomas of the lung, leading to problems with the evaluation and classification of these tumors. In our own experience with many tumors similar to those reported in the literature, the monophasic variant of pulmonary blastoma has been associated with another neoplasm but displays a different histologic pattern.
As stated previously, both fetal adenocarcinoma and biphasic pulmonary blastoma are designated in this chapter as monophasic and biphasic blastomas, respectively, because the main characteristic of these tumors is the presence of a glandular proliferation that mimics pulmonary development in embryonic life between weeks 11 and 18. Use of this nomenclature is recommended to promote uniformity in the evaluation and classification of these tumors.
Only a few series of pulmonary blastomas have been reported in the literature, and a majority of these reports discuss single, isolated cases, providing little meaningful clinical information. Koss and associates reported the largest series of pulmonary blastomas to date (including monophasic and biphasic tumors), analyzing data for 52 patients, and found that the great majority of these tumors occur in adults, with a mean and median age at diagnosis of 35 years. Two children younger than 10 years of age also were included in this group of patients, however. The occurrence of pulmonary blastomas in children is rare but has been recognized by other workers. In Koss and coworkers’ study, the tumors were more common among white patients than among African Americans, in a proportion of approximately 2:1, and no gender difference was noted. The most common clinical signs and symptoms were cough, hemoptysis, and chest pain; however, 21 of 52 patients (41%) were asymptomatic. Thirty-three of the 52 patients studied provided a history of tobacco use. In their series of six cases, which was limited to monophasic blastomas (fetal adenocarcinoma), Kodama and colleagues found that the tumor occurs predominantly in men between the ages of 23 to 67 years, with clinical signs and symptoms similar to those reported by Koss’s group. In the five cases reported by Nakatani and coworkers, all of the patients were women between the ages of 33 and 55 years with similar symptoms. Other investigators have observed similar clinical features in smaller series of cases. On the basis of those studies, a reasonable conclusion is that pulmonary blastoma has the same clinical presentation as for other non–small cell carcinomas of the lung.
Pulmonary blastomas are single pulmonary masses, well-circumscribed but not encapsulated. The cut surface may show a homogeneous or lobulated light tan surface. In some cases, the tumor also may appear as a dominant mass with adjacent nodules. The cut surface of the tumor also may show areas of hemorrhage or necrosis. Tumor size ranges from 1 cm to larger than 20 cm in greatest dimension. In Koss and coworkers’ analysis, only 36% of the tumors were less than 5 cm in size. A majority of tumors are found in the periphery of the lung ( Fig. 6-1 ); however, a small percentage will be in an endobronchial location, with polypoid growth.
As its name implies, the monophasic variant of pulmonary blastoma is composed exclusively of epithelial components and in many ways its appearance mimics the embryologic development of the lung during weeks 11 to 18 ( Fig. 6-2 ). The tumor may be central ( Fig. 6-3 ) or peripheral in location and usually appears to be well demarcated but not encapsulated ( Fig. 6-4 ). The low-power view shows a malignant glandular neoplasm destroying normal lung architecture. Three growth patterns may be observed:
Solid growth glandular pattern, with large lobules separated by thin fibrous septa ( Fig. 6-5 )
Solid glandular proliferation with pseudopapillary features and more prominent fibrous bands of fibroconnective tissue ( Fig. 6-6 )
Solid glandular proliferation with a cribriform-like pattern ( Fig. 6-7 )
These glands are of various sizes and shapes, and in many areas they are elongated, forming tubules with a minimal stromal component and resembling branching tubular structures ( Fig. 6-8 ). The glandular elements are typical of two distinct types:
Columnar cells with clear cytoplasm, nuclei displayed toward the periphery, and relatively little atypia ( Fig. 6-9 )
Glandular elements lined by a single layer of cells, displaying various degrees of cytologic atypia ( Fig. 6-10 )
Morules are identified in budding glandular structures; these can be rather inconspicuous ( Fig. 6-11 ) or very prominent ( Fig. 6-12 ), or they can fill the lumen of the glandular structures entirely ( Fig. 6-13 ). These morules are small “squamoid-like” cellular aggregates, without significant cytologic atypia. Their presence has been observed in up to 85% of cases. Necrosis may be present in differing proportions ranging from focal in the form of comedo-like necrosis ( Fig. 6-14 ) or extensive and admixed with glandular tumor structures ( Fig. 6-15 ). Marked nuclear pleomorphism may be present, but it is not common and is absent in a majority of cases ( Fig. 6-16 ). Monophasic pulmonary blastoma may show some unusual features, such as abundant foamy macrophages adjacent to tumor glands ( Fig. 6-17 ), presence of cholesterol cleft granulomas ( Fig. 6-18 ), metaplastic bone formation ( Fig. 6-19 ), inflammatory changes of the fibroconnective tissue stroma ( Fig. 6-20 ), or malignant glandular structures floating in alveolar spaces ( Fig. 6-21 ).
Nakatani and colleagues subdivided the monophasic blastomas (fetal adenocarcinoma) into two separate groups: low- and high-grade tumors. High-grade tumors were characterized by cells with prominent nucleoli, mitotic figures, and papillary infoldings. In at least two of the cases, however, a spindle cell component was recognized, which raises the possibility of a biphasic neoplasm from the outset. Of note, monophasic pulmonary blastomas may be associated with another type of malignancy. Cohen and associates described a single case in which the blastoma was associated with a melanoma, and in our own clinical experience, these tumors may be associated with hepatocellular differentiation ( Fig. 6-22 ).
At low magnification, biphasic blastomas will show a mixture of tubular epithelial structures separated by an immature spindle mesenchymal component. These components may be present in differing proportions ( Fig. 6-23 ). The glandular component is similar to that in monophasic blastoma: tubular structures lined by pseudostratified, nonciliated columnar cells with typically clear cytoplasm. In this growth pattern, it often is possible to identify increased mitotic activity, necrosis, hemorrhage, and nuclear pleomorphism ( Fig. 6-24 ). The stromal mesenchymal component is composed of an immature, monotonous proliferation of spindle cells that can be either fairly subtle or the predominant component of the tumor ( Fig. 6-25 ). In addition, the mesenchymal component may vary in the spectrum of differentiation ( Fig. 6-26 ). The presence of cartilage, bone, and skeletal muscle has been described in these cases ( Fig. 6-27 ). Some unusual cases show squamous cell carcinoma, and others display transition from blastic to more differentiated areas.