Pulmonary blastoma and related primary malignant pulmonary neoplasms

During the last decade more diagnoses of pulmonary blastoma were made worldwide than in previous decades. Whether this increased frequency is caused by better diagnostic procedures (immunochemistry, electron microscopy) or by the growing number of patients having this neoplasm is difficult to distinguish. We present controversies concerning pulmonary blastoma and related biphasic primary pulmonary neoplasms. We agree with Wick et al. that cases in children (called pleuropulmonary blastoma) should be differentiated from cases in adults, which show many similarities to bronchogenic lung cancer. However, our opinion is that the new classification system proposed by Wick et al. does not take into account cases of PB in young adults with intropulmonary growth of the tumor.     

Pulmonary blastomas of childhood: histologic, immunohistochemical, ultrastructural aspects and therapeutic considerations

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothize new possible therapeutic implications for these tumors.     

Pulmonary Blastomas of Childhood: Histologic,Immunohistochemical, Ultrastructural Aspects and Therapeutic Considerations

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothize new possible therapeutic implications for these tumors.     

Pulmonary blastoma with malignant melanoma component

Pulmonary blastomas are rare primary tumors that consist of tubular or glandular structures embedded in an undifferentiated mesenchymal stroma. Focal cartilage, bone, and skeletal muscle as well as squamous differentiation have been described in these tumors. We report a unique case of a pulmonary blastoma showing a malignant melanoma component. Immunohistochemical stains for S100 protein and HMB-45 were positive in the areas of melanocytic differentiation.     

Primary soft tissue tumours of the lung

Although primary mesenchymal tumours of the lung are rare, a working knowledge of the morphology, clinical features, genetic abnormalities, and appropriate ancillary studies applicable to these lesions will be very helpful to practising pathologists who review pulmonary material. This is especially important since mesenchymal neoplasms frequently enter the differential diagnosis of other more common pulmonary tumours with sarcomatoid appearance, including sarcomatoid carcinoma and mesothelioma. This review will cover the key morphologic and clinicopathologic features of primary soft tissue tumours of the lung, including solitary fibrous tumour, synovial sarcoma, inflammatory myofibroblastic tumour, pleuropulmonary blastoma, vascular lesions, and others. A practical approach to the differential diagnosis and appropriate use of relevant immunohistochemical markers and ancillary genetic studies will be discussed.     

Classic biphasic pulmonary blastoma with brain and axillary metastases: a case report with molecular analysis and review of literature

Pulmonary blastoma is a rare series of malignant lung tumor, which contains three categories: classic biphasic pulmonary blastoma, pluropulmonary blastoma, and well-differentiated fetal adenocarcinoma. In this study, a 19-year old female suffering with classic biphasic pulmonary blastoma and metastases in brain and axilla was presented with special interest in clinicopathological presentations, immunohistochemical features, and molecular characterizations. However, this case was misdiagnosed initially with small biopsy specimen. Comprehensive management should be used for the treatment of this malignancy.     

Colloid carcinoma of the lung: Current views

Colloid carcinomas of the lung are rare and unusual neoplasms. These tumors need special attention in order to be properly coded as primary pulmonary tumors as they closely resemble their extrathoracic counterparts in their morphologic and immunohistochemical characteristics. Even though, the latest version of the World Health Organization (WHO) has trivialized this entity into garden variety of adenocarcinomas, recently proposed guidelines on pulmonary adenocarcinomas have created some potential to bring back the controversy that appeared to have been settled a decade ago regarding these tumors. Thus, the current review will highlight not only the current concepts but also will bring the historical perspective in an effort to clarify some misconceptions regarding this rare entity.     

Pulmonary blastoma

Summary A primary pulmonary tumour in a four year old boy arising from the subpleural zone of the lung is described. It contains both stromal and epithelial elements at the primary site and in the bony metastases. The combination of the age of the patient, the site of the tumour, the stromal and epithelial elements present in the tumour suggest that this is a true pulmonary blastoma. Electronmicroscopy showed the presence of intranuclear viral particles.     

Molecular profiling of primary and metastatic neoplasms in the lung using cytologic material obtained by fine-needle aspiration: report of two cases

Two cases are presented in which molecular analyses of cytologic material obtained by fine-needle aspiration were helpful in establishing relationships between morphologically similar neoplasms in the same patient. For appropriate clinical management, it is important to ascertain whether the tumors represent independent primaries or metastases. Alcohol-fixed cytologic material prepared as cell blocks and formalin-fixed paraffin-embedded tissue were microdissected and analyzed for allelic loss of heterozygosity at multiple preselected genetic loci. The first case illustrates a 69-yr-old man with multiple intrapulmonary nodules involving the upper and lower lobes of the left lung. Genomic analysis showed that the neoplasms in the left upper and lower lung lobes were independent primaries, because the loss of heterozygosity (LOH) patterns were substantially different. By contrast, the second case is that of a 58-yr-old man with a right thyroid nodule and multiple pulmonary tumors. LOH analysis confirmed that a sampled pulmonary tumor represented a metastasis from the thyroid primary, as similar LOH patterns involving locus D9S252 were observed on comparison of the thyroid and pulmonary neoplasms. These cases illustrate the practical diagnostic utility of genomic analysis using cytologic material in the assessment of primary and metastatic malignancies.     

Pulmonary blastoma, a true congenital neoplasm

An infant, after a difficult delivery, had X-ray shadowing in the right lung. After 32 days sudden death occurred, a pulmonary blastoma being found at autopsy. The controversy over whether this tumour is a blastoma or a carcinosarcoma is discussed and arguments are advanced for acceptance of the designation pulmonary blastoma when the tumour occurs in infancy and childhood. When the equivalent tumour occurs in adults with or without the addition of areas of carcinoma and/or sarcoma, the title 'mixed tumour of lung' should replace the term carcinosarcoma.     

Sarcomatoid neoplasms of the lung and pleura

Sarcomatoid neoplasms of the lung and pleura are rare tumors that present a complex differential diagnosis, making them challenging for surgical pathologists. In the lung, the main tumors are the sarcomatoid carcinomas, including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. They are characterized by histologic heterogeneity; molecular data support their origin from a pluripotent stem cell that undergoes neoplastic transformation with divergent epithelial and sarcomatous differentiation. Diagnosis is difficult in small biopsy specimens and typically requires a resection specimen. Despite the presence of sarcomatoid features, these tumors are classified as lung carcinomas. Pulmonary blastomas must be distinguished from pleuropulmonary blastomas, which are a unique type of thoracic sarcoma typically occurring in young children. In the pleura, the main tumors to consider are the sarcomatoid and desmoplastic types of malignant mesothelioma, solitary fibrous tumor, and desmoid tumor. While light microscopy is sufficient to diagnose most of these tumors, immunohistochemistry can be useful in selected settings. In particular, it can aid to confirm epithelial differentiation in spindle cell carcinomas and the presence of rhabdomyosarcoma in sarcomatoid carcinomas, mesotheliomas, or pleuropulmonary blastomas. For sarcomatoid and desmoplastic mesothelioma, keratin is the most useful stain because it can highlight invasive growth and mesothelial markers are positive in only the minority of cases. Clinical and radiologic correlation is needed to separate some pleomorphic carcinomas with pleural involvement from sarcomatoid malignant mesothelioma, since these poorly differentiated tumors may not express the usual immunohistochemical markers for carcinoma or mesothelioma.     

Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases.

Pulmonary blastoma is a rare lung neoplasm of disputed histogenesis and variable biologic behavior. Typical cases contain both epithelial and mesenchymal tissues, and a variety of patterns of differentiation have been described. While expression of oncofetal antigens in these tumors has been noted rarely, a coexisting component of germ cell tumor has not been reported previously. We describe the clinical and pathologic features of two cases of pulmonary blastoma having alpha-fetoprotein production and histologic areas of yolk sac tumor. We also report the finding of immunohistochemical staining of fetal lung tissue for alpha-fetoprotein.     

Neuroendocrine Tumors of the Urinary Bladder According to the 2016 World Health Organization Classification: Molecular and Clinical Characteristics

Neuroendocrine neoplasms of the urinary bladder are a rare type of tumor that account for a small percentage of urinary bladder neoplasms. These tumors of the urinary bladder range from well-differentiated neuroendocrine neoplasms (carcinoids) to the more aggressive subtypes such as small cell carcinoma. Despite the rarity of the neuroendocrine tumors of the bladder, there has been substantial investigation into the underlying genomic, molecular, and the cellular alterations within this group of neoplasms. Accordingly, these findings are increasingly incorporated into the understanding of clinical aspects of these neoplasms. In this review, we provide an overview of recent literature related to the 2016 World Health Organization Classification of Neuroendocrine Tumors of the Urinary Bladder. Particular emphasis is placed on molecular alterations and recently described gene expression. The neuroendocrine tumors of the urinary bladder are subdivided into four subtypes. Similar to their pulmonary and other extrapulmonary site counterparts, these have different degrees of neuroendocrine differentiation and morphological features. The clinical aspects of four subtypes of neuroendocrine tumor are discussed with emphasis of the most recent developments in diagnosis, treatment, and prognosis. An understanding of molecular basis of neuroendocrine tumors will provide a base of knowledge for future investigations into this group of unusual bladder neoplasms.     

Gain of chromosome 8q is a frequent finding in pleuropulmonary blastoma.

Pleuropulmonary blastomas are rare malignant intrathoracic tumors of early childhood. They appear as a pulmonary- and/or pleural-based mass and their pathogenesis and relationship to other pediatric solid tumors is not well understood. In this study, paraffin-embedded material of five cases of pleuropulmonary blastoma was analyzed for genetic alterations by comparative genomic hybridization and five genetic loci by fluorescence in situ hybridization. Comparative genomic hybridization identified aberrations in all pleuropulmonary blastomas, including four amplifications in three tumors at chromosomes 5q33-34, 11q22.2-ter, 15q25-ter, and 19q11-13.2. The most frequent DNA gains involved 8q11-22.2 (four cases) and 20q (two cases), whereas the most common losses included 9p21-24 (two cases) and 11p14 (three cases). Chromosome 8 gains were confirmed by fluorescent in situ hybridization, resulting in the detection of up to five copies of chromosome 8 centromeres per nucleus. In the two surviving patients, chromosome 8 gains were the only genetic abnormality, suggesting that this might be an early event in pleuropulmonary blastoma carcinogenesis. The identification of new genetic alterations as well as the confirmation of previously reported ones (especially 8q gains) in pleuropulmonary blastoma should help to improve our understanding of both the molecular mechanisms underlying the tumorigenesis of pleuropulmonary blastoma and the relationship of pleuropulmonary blastoma with other pediatric tumors.     

Molecular discrimination of multiple primary versus metastatic squamous cell cancers of the head/neck and lung

Patients with squamous cell carcinoma (SqCa) arising in the head and neck (H/N) commonly develop solitary pulmonary metastases that mimic the clinical, radiographic, and pathologic presentation of new primary lung SqCa. Primary pulmonary and metastatic SqCas cannot be differentiated from each other histologically. However, distinguishing multiple independent primary neoplasms from a primary H/N SqCa with pulmonary metastasis has prognostic significance due to its impact on tumor stage, the most important determinant of prognosis. Since genomic instability is a common feature of cancer, we hypothesized that independently-arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. In this study, we describe a molecular approach for analysis of genetic variation among multiple tumors from a single patient that does not rely on collection of normal tissue, and which can be performed with minimal tumor samples. Genomic DNA from H/N and lung SqCas from individual patients were analyzed by microsatellite PCR to identify discordant allelic variation. This method is rapid, sensitive, does not require constitutional DNA for comparison, and can be applied to the analysis of archival tumor DNA. Our results demonstrate that microsatellite PCR can identify discordant genetic variation among multiple tumors from a single patient, facilitating the molecular discrimination of metachronous primary SqCa versus solitary pulmonary metastasis from a H/N primary SqCa.     

Pulmonary endodermal tumor resembling fetal lung: a clinicopathologic study of five cases with immunohistochemical and ultrastructural characterization

Pulmonary endodermal tumor resembling fetal lung describes an uncommon neoplasm of the lung which also has been referred to as pulmonary blastoma and adenocarcinoma of fetal lung type. We describe five cases which fall within a narrow band on the spectrum of pulmonary neoplasms with both epithelial and mesenchymal features. These five cases all occurred as well-defined masses visible on chest radiograph in middle-aged females, and were treated by surgical excision. Histopathologically, low and high grades of malignancy are found. Well-formed racimose glands with cytoplasmic vacuolization resemble endometrioid carcinoma. Neoplastic columnar cells have abundant glycogen in the cytoplasm. Morules of cells within the glands have optically clear nuclei. Ultrastructurally, the optically clear nuclei are occupied by a filamentous substructure of chromatin. Multiple neuroendocrine hormones are present in low-grade malignancy. Nuclear pleomorphism, lymphatic invasion, multifocal necrosis, lack of mesenchyme at the pulmonary interface, and restricted neuroendocrine expression suggest high-grade malignancy. A mesenchymal stroma surrounding the glands is an intrinsic part of the neoplasm, but the stroma does not appear malignant, and did not form part of the metastasis in the single case where a metastasis occurred. Stromal cells show fibroblastic and myofibroblastic differentiation. Pulmonary endodermal tumor resembling fetal lung typically is a low-grade malignancy, with a better prognosis than the majority of lesions sometimes described as pulmonary blastoma or adenocarcinoma of fetal lung type.     

Primary intrathoracic meningioma: histopathological, immunohistochemical and ultrastructural study of two cases

Meningiomas are common, usually benign slow-growing neoplasms of the central nervous system thought to arise from meningocytes capping arachnoid villi. Primary ectopic meningiomas are exceedingly rare extracranial and extraspinal tumors of controversial origin; they are usually limited to the head and neck region or to the paravertebral soft tissues. Only one mediastinal ectopic meningioma and few pulmonary ectopic meningiomas have been described in the literature until now. Because of their rarity and their intriguing pathogenesis, we report here a second case of primary mediastinal meningioma and an additional case of primary pulmonary meningioma. Their possible origin and differential diagnosis are discussed.     

Unusual Primary Lung Neoplasms: Spindle Cell and Undifferentiated Lung Carcinomas Expressing only Vimentin

Two unusual primary carcinomas of the lung are described. One occurred in a 31-year-old man and was composed of large, undifferentiated, ovoid to polygonal cells. The other occurred in a 72-year-old man, was composed of spindle-shaped cells, and was initially diagnosed as a localized fibrous mesothelioma. The neoplastic cells of these tumors expressed only vimentin intermediate filaments and showed no other immunohistochemical features of epithelial neoplasms, although they exhibited a metastatic pattern characteristic of lung carcinomas. These two malignant neoplasms further expand the spectrum of unusual lung neoplasms, and suggest that there are pulmonary carcinomas that contain only vimentin intermediate filaments.     

Primary tumors of the heart and pericardium

Primary tumors of heart and pericardium are rare. In consequence of modern noninvasive diagnostic procedures, some of these tumors today can be detected intra vitam and become accessible to operative therapy, too. The authors describe 10 primary cardiac tumors (7 atrial myxomas, 1 endocardial endothelioma of the right ventricle, 1 papilloma of the pulmonary valve, 1 sarcoma of the right atrium) and 3 diffuse malignant mesotheliomas of the pericardium. On the basis of the own material the histomorphologic variability and the dangerous complications of these neoplasms are discussed.