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Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e318216980c
Review Articles

Malignant Biphasic Tumors of the Lungs

Weissferdt, Annikka MD; Moran, Cesar A. MD

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Department of Pathology, MD Anderson Cancer Center, Houston, TX

Reprints: Annikka Weissferdt, MD, Department of Pathology, MD Anderson Cancer Center, Houston, TX 77030 (e-mail: aweissferdt@doctors.org.uk).

All figures can be viewed online in color at http://www.anatomicpathology.com.

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Abstract

Malignant biphasic tumors of the lungs are rare primary tumors of the bronchopulmonary system. These tumors are composed of malignant epithelial and mesenchymal elements and together comprise <2% of all primary pulmonary neoplasms. The tumors belonging to this group include pulmonary blastoma, pleuropulmonary blastoma, and carcinosarcoma. In this study, the clinicopathologic features, immunohistochemical phenotype, molecular biological characteristics, and the differential diagnosis of these uncommon neoplasms are discussed.

Malignant biphasic neoplasms arising as primary tumors of the lungs are vanishingly rare. Biphasic tumors may not only be composed of epithelial and mesenchymal elements but may also show epithelial-epithelial or mesenchymal-mesenchymal differentiation. Examples of the latter 2 groups of tumors include pleomorphic carcinoma or malignant Triton tumor to name but a few. The focus of this study, however, lies in the discussion of malignant tumors of epithelial-mesenchymal lineage.

In the adult population, the 2 most common tumors among this group are pulmonary blastoma and carcinosarcoma. Pulmonary blastomas are tumors with an epithelial element resembling the developing fetal lung during the 11th to 18th week of gestation. In the past, this tumor had been subdivided into 2 variants: a monophasic type composed predominantly of an epithelial component and a biphasic variant showing an additional embryonal stromal component. The monophasic variant is also known in the literature under a variety of other terms including pulmonary embryoma, adenocarcinoma of fetal lung type, well-differentiated fetal adenocarcinoma, and pulmonary endodermal tumor resembling fetal lung. More recently, the World Health Organization classification of lung tumors1 classified this so-called “fetal adenocarcinoma” as a distinctive variant of adenocarcinoma due to its glandular differentiation and association with other subtypes of adenocarcinoma. This classification limits the use of the term pulmonary blastoma to the biphasic variant. The striking fetal-like glandular component of both the so-called “fetal adenocarcinoma” and the biphasic variant lead us to include these tumors as monophasic and biphasic pulmonary blastomas in this study, respectively.

Carcinosarcomas are tumors that are composed of morphologically malignant epithelial and mesenchymal elements. Importantly, the mesenchymal elements in these tumors should be easily recognizable histologically as unequivocal forms of a malignant mesenchymal tumor resembling osteosarcoma, chondrosarcoma, rhabdomyosarcoma, angiosarcoma, or liposarcoma to distinguish them from spindle cell carcinomas.2–4 The World Health Organization actually classifies carcinosarcomas as a subtype of sarcomatoid carcinoma, whereby their definition of sarcomatoid carcinomas includes tumors composed of poorly differentiated non-small cell carcinoma that contain a component of sarcoma or sarcoma-like differentiation.4 Other investigators have proposed to regard carcinosarcomas as “sarcomatoid” or “metaplastic” carcinomas based on the belief that the presence of malignant osseous, chondromatous, or myogenous elements represents divergent differentiation rather than a true sarcoma component.5 We consider carcinosarcoma as an independent clinicopathologic entity and true malignant biphasic neoplasm warranting inclusion of this tumor in this study.

Pleuropulmonary blastomas are primary thoracic neoplasms predominantly affecting children. This tumor is discussed here among the adult tumors because its designation as “pleuropulmonary blastoma” very often causes confusion with the adult-type “pulmonary blastoma.” It is important to note that these tumors have very different clinical, histologic, and prognostic features making distinction of these entities critical. Pleuropulmonary blastomas are composed of an embryonal-like blastemal element, an uncommitted stroma with focal sarcomatous differentiation, and variable cyst formation. Although histologic similarities to the adult-type pulmonary blastoma exist, the defining feature of pleuropulmonary blastoma is a striking absence of any malignant epithelial component thereby separating this lesion from the other biphasic lung neoplasms.

The most pertinent clinical, histologic, immunohistochemical, and molecular features of the tumors discussed are summarized in Tables 1 to 4.

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PULMONARY BLASTOMA

Clinical Features

Pulmonary blastomas are highly uncommon tumors of the lungs and to date only approximately 200 cases have been described in the literature.6 Although most commonly seen in the adult population (mean age, 35 y),7 pulmonary blastomas have also rarely been identified in children and even neonates.8,9 Female individuals are slightly more commonly affected than male individuals.6,10 Although often the presenting symptoms include chest pain, hemoptysis, and cough, a large proportion of patients (up to 40%) may be entirely asymptomatic.3,7 Radiologically, pulmonary blastomas have nonspecific features and usually present as solitary lesions in the lung parenchyma or less commonly as a multifocal process.6,11 Often, the changes seen on computed tomography resemble other, less ominous processes like infections or benign cysts.6,11 Rarely, endobronchial lesions may mimic carcinoid tumors radiologically.6,11 An analysis of a series of pure monophasic pulmonary blastomas showed no significant difference in the clinical findings when compared with the biphasic variant.12

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Gross Features

Grossly, pulmonary blastomas are circumscribed tumors with a mean diameter of 6 cm. The tumors are typically solitary and located in the lung periphery. Occasionally, smaller satellite lesions may be identified and in up to 25% of cases an endobronchial component may be present. On cut surface, the tumors are white-to-tan brown with a fish flesh appearance. Central necrosis and cystic breakdown can be observed in about half of the cases.3,7

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Histologic Features
Monophasic Pulmonary Blastoma

The most striking feature of pulmonary blastomas is its epithelial component resembling the developing lung during gestational weeks 11 to 18.3,7 In monophasic pulmonary blastoma, the tumor is composed only of a glandular component, lacking the blastematous element of the biphasic variant.13 The glands vary in size and shape and often form complex branching tubules lined by a columnar epithelium (Figs. 1–3). This epithelium has clear cytoplasm, uniform nuclei, and characteristic subnuclear or supranuclear cytoplasmic vacuoles (Fig. 4). A variety of growth patterns can be seen in these glands, including solid or cribriform areas, cords, ribbons, or rosette-like structures (Fig. 5). Another peculiarity often found in this tumor is the presence of so-called “morules.” These are nests of squamoid cells with eosinophilic cytoplasm and optically clear nuclei which often show neuroendocrine differentiation (Fig. 6).3,7 As many as 86% to 100% of monophasic pulmonary blastomas contain morules and these are a characteristic finding in these tumors. The mitotic activity is usually low and necrosis if present is only focally seen. Another important feature is the fact that mucin may be present in the glandular lumina but intracytoplasmic mucin is generally not identified thereby distinguishing this tumor from conventional adenocarcinoma. The stromal component separating the glands is scant and composed of a benign myofibroblastic stroma without significant atypia or mitotic activity (Fig. 7).

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Biphasic Pulmonary Blastoma

The biphasic variant will show a glandular component similar to the one seen in monophasic pulmonary blastoma and in addition contains a malignant stroma with an embryonic or blastematous appearance (Fig. 8). This undifferentiated stroma can show striking condensation around the glandular structures and exhibit significant mitotic activity and nuclear pleomorphism (Figs. 9, 10). More importantly, the stroma may show various types of differentiation, including immature striated muscle, cartilage, bone, smooth muscle, yolk sac-like areas or melanocytic differentiation (Fig. 11).3,7,14–17 Increased mitotic activity, nuclear pleomorphism, and necrosis can also be identified in the glandular component of this tumor (Fig. 12).3 Morules are not as often seen in the biphasic variant compared with the monophasic type.3,7

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Immunohistochemical and Molecular Features

The epithelial elements of pulmonary blastomas show an immunohistochemical staining pattern similar to pulmonary adenocarcinomas. Positive staining can be seen for pancytokeratin (CK), carcinoembryonic antigen, epithelial membrane antigen (EMA), thyroid transcription factor 1, CK7, and surfactant protein α.3,7,18–20 The morules are often immunoreactive for neuroendocrine markers like synaptophysin and chromogranin but can also show positive staining for CD10 and biotin.3,7,21 The stromal component can show various staining patterns depending on the degree and type of differentiation; vimentin, desmin, muscle specific actin, myoglobin, or S100 protein may thus be positive in the stromal cells.3,7,18–20

Only few studies have investigated the molecular characteristics of pulmonary blastomas. Two of these described the presence of p53 protein overexpression and p53 gene mutations in the epithelial and mesenchymal elements of biphasic blastomas but not in the monophasic variant.22,23 β-catenin mutations, however, have been described in both blastoma variants implying a common genetic link.24,25

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Differential Diagnosis

The monophasic variant of pulmonary blastoma is often confused with conventional adenocarcinoma, especially the secretory endometrioid-like adenocarcinoma of the lung. The embryonal nature of the glandular component and the presence of morules in blastomas should facilitate correct diagnosis. In addition, intracellular mucin which is often found in adenocarcinoma should be absent in pulmonary blastoma. Carcinosarcoma enters the differential diagnosis in cases of biphasic blastoma. Carcinosarcoma most often shows squamous cell carcinoma as the epithelial component and should lack a blastematous stroma. The embryonal appearance of the glandular component and presence of morules in blastomas will further differentiate these tumors from carcinosarcoma. Rarely, malignant salivary gland-like tumors may be confused for blastomas. These tumors may show a biphasic pattern due to their dual epithelial and myoepithelial components. Again, the embryonal appearing glands and blastemal elements in blastoma along with an absence of immunohistochemical staining for myoepithelial elements should help to differentiate both lesions.3

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Treatment and Prognosis

The treatment of choice for pulmonary blastomas is primarily complete surgical resection. Whether chemotherapy or radiation play a role in the adjuvant setting is still not clear and thus definitive regimens have not been established.

The prognosis of pulmonary blastomas largely depends on their subtype. Monophasic pulmonary blastomas appear to be less aggressive than their biphasic counterparts. Although the former is associated with recurrence rates as high as 30%, the tumor associated mortality is only 10% to 14% leading some investigators to believe that they represent low-grade malignancies.26 Factors influencing survival include the presence of thoracic lymphadenopathy, metastatic disease at presentation, tumor recurrence, and tumor stage.13 It has been suggested that this improved survival compared with biphasic blastoma is due to lower biological aggressiveness and a higher tendency of monophasic blastomas to recur within the lungs thereby facilitating surgical resection.7

On the contrary, biphasic pulmonary blastoma is considered an aggressive neoplasm with a high recurrence rate in up to 50% of cases and frequent metastases to brain, thoracic cavity, liver, or soft tissues.3,7,27,28 The survival rate is similarly ominous with average survival rates of 66%, 16%, and 8% at 2, 5, and 10 years, respectively.7 Early tumor stage, small tumor size (<5 cm), and an absence of tumor recurrence and metastasis were factors influencing the survival in one of the largest series on pulmonary blastomas by Koss et al13 in 1991.

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PLEUROPULMONARY BLASTOMA

Clinical Features

Pleuropulmonary blastomas are rare tumors that are virtually restricted to the pediatric age group with an average age at presentation of 3 years.29,30 Few case reports have documented the presence of this tumor also in adults but generally speaking the tumor is rare in children older than 12 years.29,31–33 More recently it has been shown that the age at presentation varies depending on the histologic subtype of pleuropulmonary blastoma with median ages of 10 months for type 1, 36 months for type 2, and 44 months for type 3 tumors.34 Girls and boys are equally affected and symptoms include cough, fever, chest pain, respiratory distress, lethargy, or weight loss.29,30 Pleuropulmonary blastomas may arise anywhere in the thorax but most often arise in the periphery of the lungs and less commonly in the pleura or mediastinum.29,30,35 The right hemithorax appears to be more often involved than the left side.29,36 On imaging, pleuropulmonary blastomas are often mistaken for more indolent lesions like benign cystic lung disease as they often present as cystic lesions arising in the lung or as pleural/mediastinal based masses.35,37 In comparison to other neoplastic processes, chest wall invasion is strikingly absent.36,38

Pleuropulmonary blastoma is often seen in association with other childhood diseases including benign and malignant conditions. Bronchogenic cysts or cystic adenomatoid pulmonary malformation (CPAM)29,30,39 belong to the benign spectrum of disease often seen with pleuropulmonary blastoma, whereas in up to 25% of cases other malignant neoplasms may affect the same individual or a close family member.29,40–42 These neoplasms include cystic nephroma, thyroid carcinoma, germ cell tumors, or other sarcomas prompting close surveillance of the patients and their family members when a diagnosis of pleuropulmonary blastoma is rendered.29,41,42

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Gross Features

The gross features of pleuropulmonary blastoma largely depend on the histologic subtype. They are generally large tumors which may reach a size larger than 20 cm and often affect the lower lobes of the lungs.29,39 Depending on the subtype, the gross appearance may range from predominantly cystic tumors (type 1) to solid rubbery masses (type 3) or solid-cystic lesions (type 2). Areas of necrosis, hemorrhage, gelatinous or mucoid change may be seen in all subtypes. Rarely, the tumors may extend into the bronchial system.43

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Histologic Features

Pleuropulmonary blastomas can be subtyped depending on the degree of cystic change.35,39 Type 1 pleuropulmonary blastoma is a predominantly cystic tumor (Fig. 13). The cystic structures in this lesion are separated by thin fibrous septa lined by benign cuboidal or respiratory type epithelium (Fig. 14). The stroma separating the cysts is composed of oval-to-spindle shaped undifferentiated blastemal cells that may in some cases form a continuous layer beneath the epithelium reminiscent of the cambium layer in embryonal rhabdomyosarcoma (Fig. 15). In addition, cells showing rhabdomyoblastic differentiation may be focally present (Fig. 16). Types 2 and 3 pleuropulmonary blastomas only differ in the degree of cystic differentiation with mixed solid-cystic changes in type 2 and predominantly solid tumor representing type 3 (Fig. 17). In addition to rhabdomyoblastic cells, cartilaginous differentiation, anaplastic cells, and tumor giant cells may be seen in type 2 and 3 lesions. These higher grade tumors can also contain necrotic areas and pseudocyst formation.35,39

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Immunohistochemical and Molecular Features

Immunohistochemical studies are predominantly used to characterize the sarcomatous component of pleuropulmonary blastomas. Markers like desmin, myoglobin, muscle specific actin, myogenin, and myoD1 will confirm rhabdomyosarcomatous differentiation, S100 protein can aid in the diagnosis of cartilaginous components, and histiocytic markers including α-1-antitrypsin, α-1-antichymotrypsin, and CD68 have been reported to be positive in the blastematous component.29,31,39,44,45 The benign epithelium lining the cystic spaces has been shown to be positive for CK and EMA.29,31,44

Molecular studies have repeatedly identified trisomies 2 and 8 in pleuropulmonary blastoma and p53 mutations have also been described.45–50 All these genetic abnormalities are similar to the ones that have been observed in other pediatric neoplasms like embryonal rhabdomyosarcoma and hepatoblastoma raising the possibility of a common genetic pathway in the development of these tumors. More recently, familial cases of pleuropulmonary blastoma have been shown to harbor DICER1 mutations.51

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Differential Diagnosis

The most important differential diagnosis of pleuropulmonary blastoma is CPAM, which may be difficult to distinguish from type 1 tumors. A spectrum of benign cystic lung disorders has been combined under the name CPAM, which in turn has been divided into 5 histologic subtypes. Both, CPAM and pleuropulmonary blastoma can be multicystic lesions lined by a benign epithelium. The latter, however, will contain small primitive cells within the septa and careful search for this blastematous component is indicated not to mistake pleuropulmonary blastoma for a benign cystic process.52,53 Among the malignant tumors mimicking pleuropulmonary blastoma are pulmonary blastoma and rhabdomyosarcoma. Pulmonary blastoma is a predominantly solid tumor affecting mainly the adult population and which is composed of malignant blastemal, stromal, and epithelial elements, whereas rhabdomyosarcoma may be more difficult to differentiate from pleuropulmonary blastoma. However, primary rhabdomyosarcomas of the thoracic cavity are exceedingly rare tumors showing monodirectional differentiation towards skeletal muscle. The blastematous and epithelial elements seen in pleuropulmonary blastomas should be absent.29,31

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Treatment and Prognosis

Regardless of subtype, the treatment of pleuropulmonary blastoma generally consists of complete surgical resection followed by chemotherapy and/or radiotherapy.29,30,39,54 In advanced cases, neoadjuvant chemotherapy followed by resection and adjuvant chemoradiation may produce long-term survival.55 Pleuropulmonary blastomas are generally aggressive tumors with an overall 5-year survival rate of only 45%.39 Contrary to the treatment, the prognosis largely depends on tumor subtype; whereas the overall 2-year survival for patients with type 1 tumors is 80%, this rate drops to 73% for patients with type 2 tumors and 48% for patients with type 3 tumors.39 Unresectable tumor at diagnosis, tumor recurrence, mediastinal or pleural involvement, and type 2 or 3 histology are factors adversely affecting the prognosis.30,35,39,56 Pleuropulmonary blastomas metastasize to the brain more than any other childhood sarcoma but metastases to the bone, liver, and soft tissue have also been described.34 Important to note is that type 1 pleuropulmonary blastomas may recur as grade 2 or 3 tumors and elective surgery is therefore recommended in all children with cystic appearing lung lesions to avoid potential transformation.37,39,57,58

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CARCINOSARCOMA

Clinical Features

One of the rarest primary tumors of the lungs is carcinosarcoma. This tumor has an estimated incidence of only 0.2% to 0.4% of all pulmonary neoplasms.59–61 Carcinosarcomas predominantly occur in men with a male to female ratio of 7:1.59,62,63 The tumor seems to be more common in the older age group with a mean age at diagnosis in the seventh decade. Presenting symptoms depend on the location of the tumors; those with an endobronchial component produce cough, dyspnea, hemoptysis, and shortness of breath. Patients with peripheral lesions on the other hand often present with chest pain, recurrent pneumonic episodes, weight loss, and fever.5,59,62,64,65 In up to 1 of 3 cases, carcinosarcomas are diagnosed incidentally.62 Smoking has been implicated as an etiologic factor by several investigators.5,59,62 Radiologically, endobronchial carcinosarcomas show features of obstruction, whereas peripheral lesions are characterized by large round parenchymal-based masses; they may present with local invasion into the chest wall, pericardium, or pulmonary vein.66

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Gross Features

Primary pulmonary carcinosarcomas can be relatively small polypoid lesions in an endobronchial location or larger peripheral tumors, the size ranging from 1.5 to 16 cm with a mean size of 7 cm.59,62 The tumors are usually solitary lesions that are well circumscribed but not encapsulated.65 On cut surface, the tumors can show homogenous or heterologenous patterns, the epithelial component often showing a soft and friable consistency whereas the mesenchymal component is commonly firm and rubbery or even cartilaginous or osseous depending on the type of differentiation.59,62

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Histologic Features

Histologically, pulmonary carcinosarcomas, like their counterparts in other organ systems, are composed of an intimate admixture of carcinoma and sarcoma. The most common carcinomatous component is squamous cell carcinoma followed by adenocarcinoma, adenosquamous carcinoma, and large cell carcinoma (Figs. 18–22).62 Occasional case reports also comment on the presence of neuroendocrine or salivary gland-type carcinoma but this is exceedingly rare.3,67–70 Rhabdomyosarcoma is the most common mesenchymal component and is followed in frequency by osteosarcoma and chondrosarcoma (Figs. 23–25). More rarely, leiomyosarcoma, liposarcoma, or undifferentiated sarcoma may be identified (Fig. 26).62,65,71 All tumor components usually resemble their counterparts in other organ systems and variable proportions of epithelial and mesenchymal elements may be encountered. Hemorrhage, necrosis, and pseudocyst formation are frequently seen (Fig. 27).5 Metastatic carcinosarcoma can show features of only one of the components or a mixture of both.62

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Immunohistochemical and Molecular Features

Carcinosarcoma will most often be diagnosable histologically, but if less well differentiated tumor components are present immunohistochemical stains may facilitate correct diagnosis. Generally, the epithelial component may be identified by CK, EMA, or CAM5.2. If squamous cell carcinoma is suspected, CK5/6 and p63 may be helpful; for adenocarcinomas the markers of choice will be CK7, thyroid transcription factor 1, and napsin. Muscle markers like desmin, myogenin, or myoD1 may confirm rhabdomyoblastic differentiation and when chondrosarcoma or liposarcoma is suspected S100 protein can be used to confirm the diagnosis. In those rare cases, in which the epithelial component has neuroendocrine features the markers of choice would be synaptophysin, chromogranin, and CD56.

Owing to the rarity of pulmonary carcinosarcomas only few studies have investigated the molecular features of these tumors. In one of these studies, the investigators found allelic losses involving chromosomes 3q, 5q, and 17p in the epithelial and mesenchymal components strongly suggesting a monoclonal origin of this tumor.72 These findings were supported by Pardo et al73 in 2008, who found many common alterations between carcinomatous and sarcomatous areas characterized by gains in chromosomes 1q, 3q, 5p, 8q, and 12p. In contrast, K-ras and β-catenin mutations were not identified in carcinosarcoma and p53 mutations were variable.23,25 As β-catenin mutations are frequently found in pulmonary blastoma, it has been proposed that carcinosarcoma and pulmonary blastoma are unrelated.24,25

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Differential Diagnosis

Pulmonary carcinosarcomas are often mistaken for either entirely epithelial or mesenchymal neoplasms, especially when the initial diagnosis is rendered on a small endobronchial or needle-core biopsy. Formal resection of the tumor will often unveil the true nature of the neoplasm; however, even the fully resected tumor may mimick other neoplasms. Among these, spindle cell carcinoma may be difficult to distinguish from carcinosarcoma. Spindle cell carcinoma normally lacks a specialized mesenchymal component such as rhabdomyosarcoma, chondrosarcoma, or osteosarcoma and is composed only of malignant epithelial elements that have the form of spindle cells.4 In cases in which the epithelial component is composed of adenocarcinoma, pulmonary blastoma enters the differential diagnosis. Both tumors share similar clinical features and show biphasic histologic features, pulmonary blastomas, however, are composed of characteristic fetal appearing glands and an undifferentiated blastemal stroma, features which are not typically seen in carcinosarcoma.74 Lastly, primary mesenchymal tumors may arise in the lungs; these lesions, however, are exceedingly rare and will lack epithelial differentiation.

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Treatment and Prognosis

Complete surgical resection is the treatment of choice in patients with resectable tumors.62,75 Chemotherapy and radiation can be used in an adjuvant setting. Specific chemotherapy regimens, however, have not yet been established. The prognosis for patients with carcinosarcoma is poor with a median survival of only 1 year and reported 5-year survival rates that range from 20% to 50%.59,62,75,76 Interestingly, neither endobronchial location nor tumor stage seem to affect the prognosis significantly, the only relevant parameter affecting survival being tumor size with a cut off at 6 cm.62 Carcinosarcomas most commonly metastasize to the lymph nodes, kidney, bone, thorax, liver, spleen, adrenal gland, and brain.5,62 The metastatic deposits can be composed of either the epithelial or mesenchymal elements or both. Metastatic disease, tumor recurrence, and distant metastasis are often the eventual cause of death in patients with pulmonary carcinosarcoma.70

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REFERENCES

1. Travis WD, Brambilla E, Müller-Hermelink HK, et al. Tumours of the Lung, Pleura, Thymus and Heart. 2004 Lyon, France IARC Press:35–44

2. Humphrey PA, Scroggs MW, Roggli VL, et al. Pulmonary carcinomas with a sarcomatoid element: an immunocytochemical and ultrastructural analysis Hum Pathol.. 1988;19:155–165

3. Berho M, Moran CA, Suster S. Malignant mixed epithelial/mesenchymal neoplasms of the lung Semin Diagn Pathol.. 1995;12:123–139

4. Travis WD, Brambilla E, Müller-Hermelink HK, et al. Tumours of the Lung, Pleura, Thymus and Heart. 2004 Lyon, France IARC Press:53–58

5. Nappi O, Wick MR. Sarcomatoid neoplasms of the respiratory tract Semin Diagn Pathol.. 1993;10:137–147

6. Adluri RK, Boddu SR, Martin-Ucar A, et al. Pulmonary blastoma: a rare tumor with variable presentation Eur J Cardiothorac Surg.. 2006;29:236–239

7. Koss MN. Pulmonary blastomas Lung Cancer.. 1994:349–362

8. Majid OA, Rajendran U, Baker LT. Pulmonary blastoma Ann Thorac Cardiovasc Surg.. 1998;4:47–52

9. Reichman M, Kovanlikaya A, Mathew S, et al. Pulmonary blastoma in a neonate: a lesion distinct from pleuropulmonary blastoma with unique cytogenetic features Pediatr Radiol.. 2010;40:366–370

10. Robert J, Pache JC, Seium Y, et al. Pulmonary blastoma: report of five cases and identification of clinical features suggestive of the disease Eur J Cardiothorac Surg.. 2002;22:708–711

11. Lee HJ, Goo JM, Kim KW, et al. Pulmonary blastoma: radiologic findings in five patients Clin Imaging.. 2004;28:113–118

12. Sato S, Koike T, Yamato Y, et al. Resected well-differentiated fetal pulmonary adenocarcinoma and summary of 25 cases reported in Japan Jpn J Thorac Cardiovasc Surg.. 2006;54:539–542

13. Koss MN, Hochholzer L, O'Leary T. Pulmonary blastomas Cancer.. 1991;67:2368–2381

14. Cohen RE, Weaver MG, Montenegro HD, et al. Pulmonary blastoma with malignant melanoma component Arch Pathol Lab Med.. 1990;114:1076–1078

15. Siegel RJ, Bueso-Ramos C, Cohen C, et al. Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases Mod Pathol.. 1991;4:566–570

16. Oshika Y, Matsukuma S, Hashimoto H, et al. Biphasic pulmonary blastoma with a lesion of yolk sac tumor Gen Thorac Cardiovasc Surg.. 2007;55:243–247

17. Archie PH, Beasley MB, Ross HJ. Biphasic pulmonary blastoma with germ cell differentiation in a 36-year-old man J Thorac Oncol.. 2008;3:1185–1187

18. Rossi G, Cavazza A, Sturm N, et al. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases Am J Surg Pathol.. 2003;27:311–324

19. Hansen T, Bittinger F, Kortsik C, et al. Expression of KIT (CD117) in biphasic pulmonary blastoma. Novel data on histogenesis Lung.. 2003;181:193–200

20. García-Escudero A, González-Cámpora R, Villar-Rodríguez JL, et al. Thyroid transcription factor-1 expression in pulmonary blastoma Histopathology.. 2004;44:507–508

21. Cameselle-Teijeiro J, Alberte-Lista L, Chiarelli S, et al. CD10 is a characteristic marker of tumours forming morules with biotin-rich, optically clear nuclei that occur in different organs Histopathology.. 2008;52:389–392

22. Bodner SM, Koss MN. Mutations in the p53 gene in pulmonary blastomas: immunohistochemical and molecular studies Hum Pathol.. 1996;27:1117–1123

23. Holst VA, Finkelstein S, Colby TV, et al. p53 and K-ras mutational genotyping in pulmonary carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma: implications for histogenesis Am J Surg Pathol.. 1997;21:801–811

24. Sekine S, Shibata T, Matsuno Y, et al. Beta-catenin mutations in pulmonary blastomas: association with morule formation J Pathol.. 2003;200:214–221

25. Nakatani Y, Miyagi Y, Takemura T, et al. Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma Am J Surg Pathol.. 2004;28:921–927

26. Nakatani Y, Dickersin GR, Mark EJ. Pulmonary endodermal tumor resembling fetal lung: a clinicopathologic study of five cases with immunohistochemical and ultrastructural characterization Hum Pathol.. 1990;21:1097–1107

27. Novotny JE, Huiras CM. Resection and adjuvant chemotherapy of pulmonary blastoma: a case report Cancer.. 1995;76:1537–1539

28. Kouvaris JR, Gogou PV, Papacharalampous XN, et al. Solitary brain metastasis from classic biphasic pulmonary blastoma: a case report and review of the literature Onkologie.. 2006;29:568–570

29. Manivel JC, Priest JR, Watterson J, et al. Pleuropulmonary blastoma: the so-called pulmonary blastoma of childhood Cancer.. 1988 15;62:1516–1526

30. Indolfi P, Casale F, Carli M, et al. Pleuropulmonary blastoma: management and prognosis of 11 cases Cancer.. 2000;89:1396–1401

31. Hachitanda Y, Aoyama C, Sato JK, et al. Pleuropulmonary blastoma in childhood: a tumor of divergent differentiation Am J Surg Pathol.. 1993;17:382–391

32. Hill DA, Sadeghi S, Schultz MZ, et al. Pleuropulmonary blastoma in an adult: an initial case report Cancer.. 1999;85:2368–2374

33. Zuker NB, Dietl CA, Kenna S, et al. Unusual survival of an adult with pleuropulmonary blastoma and neurofibromatosis J Thorac Cardiovasc Surg.. 2007;134:541–542

34. Priest JR, Magnuson J, Williams GM, et al. Cerebral metastasis and other central nervous system complications of pleuropulmonary blastoma Pediatr Blood Cancer.. 2007;49:266–273

35. Dehner LP. Pleuropulmonary blastoma is THE pulmonary blastoma of childhood Semin Diagn Pathol.. 1994;11:144–151

36. Naffaa LN, Donnelly LF. Imaging findings in pleuropulmonary blastoma Pediatr Radiol.. 2005;35:387–391

37. Miniati DN, Chintagumpala M, Langston C, et al. Prenatal presentation and outcome of children with pleuropulmonary blastoma J Pediatr Surg.. 2006;41:66–71

38. Papaioannou G, Sebire NJ, McHugh K. Imaging of the unusual pediatric “blastomas” Cancer Imaging.. 2009;9:1–11

39. Priest JR, McDermott MB, Bhatia S, et al. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases Cancer.. 1997;80:147–161

40. Priest JR, Watterson J, Strong L, et al. Pleuropulmonary blastoma: a marker for familial disease J Pediatr.. 1996;128:220–224

41. Boman F, Hill DA, Williams GM, et al. Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the international pleuropulmonary blastoma registry J Pediatr.. 2006;149:850–854

42. Priest JR, Williams GM, Hill DA, et al. Pulmonary cysts in early childhood and the risk of malignancy Pediatr Pulmonol.. 2009;44:14–30

43. Goel P, Panda S, Srinivas M, et al. Pleuropulmonary blastoma with intrabronchial extension Pediatr Blood Cancer.. 2010;54:1026–1028

44. Cohen M, Emms M, Kaschula RO. Childhood pulmonary blastoma: a pleuropulmonary variant of the adult-type pulmonary blastoma Pediatr Pathol.. 1991;11:737–749

45. de Krijger RR, Claessen SM, van der Ham F, et al. Gain of chromosome 8q is a frequent finding in pleuropulmonary blastoma Mod Pathol.. 2007;20:1191–1199

46. Sciot R, Dal Cin P, Brock P, et al. Pleuropulmonary blastoma (pulmonary blastoma of childhood): genetic link with other embryonal malignancies? Histopathology.. 1994;24:559–563

47. Novak R, Dasu S, Agamanolis D, et al. Trisomy 8 is a characteristic finding in pleuropulmonary blastoma Pediatr Pathol Lab Med.. 1997;17:99–103

48. Sebire NJ, Rampling D, Malone M, et al. Gains of chromosome 8 in pleuropulmonary blastomas of childhood Pediatr Dev Pathol.. 2002;5:221–222

49. Roque L, Rodrigues R, Martins C, et al. Comparative genomic hybridization analysis of a pleuropulmonary blastoma Cancer Genet Cytogenet.. 2004;149:58–62

50. Kusafuka T, Kuroda S, Inoue M, et al. P53 gene mutations in pleuropulmonary blastomas Pediatr Hematol Oncol.. 2002;19:117–128

51. Hill DA, Ivanovich J, Priest JR, et al. DICER1 mutations in familial pleuropulmonary blastoma Science.. 2009;325:965

52. Hill DA, Jarzembowski JA, Priest JR, et al. Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry Am J Surg Pathol.. 2008;32:282–295

53. MacSweeney F, Papagiannopoulos K, Goldstraw P, et al. An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation Am J Surg Pathol.. 2003;27:1139–1146

54. Kukkady A, Upadhyay V, Pease PW, et al. Pleuropulmonary blastoma: four cases Pediatr Surg Int.. 2000;16:595–598

55. Parsons SK, Fishman SJ, Hoorntje LE, et al. Aggressive multimodal treatment of pleuropulmonary blastoma Ann Thorac Surg.. 2001;72:939–942

56. Indolfi P, Bisogno G, Casale F, et al. Prognostic factors in pleuro-pulmonary blastoma Pediatr Blood Cancer.. 2007;48:318–323

57. Papagiannopoulos K, Hughes S, Nicholson AG, et al. Cystic lung lesions in the pediatric and adult population: surgical experience at the Brompton Hospital Ann Thorac Surg.. 2002;73:1594–1598

58. Dosios T, Stinios J, Nicolaides P, et al. Pleuropulmonary blastoma in childhood: a malignant degeneration of pulmonary cysts Pediatr Surg Int.. 2004;20:863–865

59. Davis MP, Eagan RT, Weiland LH, et al. Carcinosarcoma of the lung: Mayo Clinic experience and response to chemotherapy Mayo Clin Proc.. 1984;59:598–603

60. Cabarcos A, Gomez Dorronsoro M, Lobo Beristain JL. Pulmonary carcinosarcoma: a case study and review of the literature Br J Dis Chest.. 1985;79:83–94

61. Heremans A, Verbeken E, Deneffe G, et al. Carcinosarcoma of the lung. Report of two cases and review of the literature Acta Clin Belg.. 1989;44:110–115

62. Koss MN, Hochholzer L, Frommelt RA. Carcinosarcomas of the lung: a clinicopathologic study of 66 patients Am J Surg Pathol.. 1999;23:1514–1526

63. Sato S, Koike T, Yamato Y, et al. A case of rapidly growing pulmonary carcinosarcoma Int J Clin Oncol.. 2010;15:319–324

64. Moore TC. Carcinosarcoma of the lung Surgery.. 1961;50:886–893

65. Stackhouse EM, Harrison EG Jr, Ellis FH Jr. Primary mixed malignancies of lung: carcinosarcoma and blastoma J Thorac Cardiovasc Surg.. 1969;57:385–399

66. Kim KI, Flint JD, Müller NL. Pulmonary carcinosarcoma: radiologic and pathologic findings in three patients AJR Am J Roentgenol.. 1997;169:691–694

67. Tsubota YT, Kawaguchi T, Hoso T, et al. A combined small cell and spindle cell carcinoma of the lung: report of a unique case with immunohistochemical and ultrastructural studies Am J Surg Pathol.. 1992;16:1108–1115

68. Rainosek DE, Ro JY, Ordonez NG, et al. Sarcomatoid carcinoma of the lung: a case with atypical carcinoid and rhabdomyosarcomatous components Am J Clin Pathol.. 1994;102:360–364

69. Koss MN, Moran CA, Stocker JTSaldana MJ. Mixed epithelial-mesenchymal tumors Pathology of Pulmonary Disease. 1994 Philadelphia, PA Lippincott:618–619

70. Huwer H, Kalweit G, Straub U, et al. Pulmonary carcinosarcoma: diagnostic problems and determinants of the prognosis Eur J Cardiothorac Surg.. 1996;10:403–407

71. Kitazawa R, Kitazawa S, Nishimura Y, et al. Lung carcinosarcoma with liposarcoma element: autopsy case Pathol Int.. 2006;56:449–452

72. Dacic S, Finkelstein SD, Sasatomi E, et al. Molecular pathogenesis of pulmonary carcinosarcoma as determined by microdissection-based allelotyping Am J Surg Pathol.. 2002;26:510–516

73. Pardo J, Aisa G, Alava E, et al. Primary mixed squamous carcinoma and osteosarcoma (carcinosarcomas) of the lung have a CGH mapping similar to primitive squamous carcinomas and osteosarcomas Diagn Mol Pathol.. 2008;17:151–158

74. Davis PW, Briggs JC, Seal RM, et al. Benign and malignant mixed tumours of the lung Thorax.. 1972;27:657–673

75. Petrov DB, Vlassov VI, Kalaydjiev GT, et al. Primary pulmonary sarcomas and carcinosarcomas: postoperative results and comparative survival analysis Eur J Cardiothorac Surg.. 2003;23:461–466

76. Wick MR, Ritter JH, Humphrey PA. Sarcomatoid carcinomas of the lung: a clinicopathologic review Am J Clin Pathol.. 1997;108:40–53

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Keywords:

biphasic tumors; lung; pulmonary blastoma; carcinosarcoma; pleuropulmonary blastoma

© 2011 Lippincott Williams & Wilkins, Inc.

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