Search

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy., Methods: A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis., Results: PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (≤4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05)., Conclusions: PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this entity which has no systematic data associated with its incidence in order to discuss clinical, histopathological, immunohistochemical features and the differential diagnosis. A three-year-old boy presented with fever showed signs of upper respiratory tract infection. Radiological examination revealed a solid mass filling the right hemithorax. The patient underwent core needle biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined histopathologically. The tumor was composed of predominantly solid areas consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid stroma. Immunohistochemical staining of the tumor cells were positive with vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma was also infiltrated with the tumor. The patient was treated with chemotherapy and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary blastoma is a very rare childhood cancer that needs to be kept in mind in the pathological differential diagnosis of thoracic tumors in the children.

Objective: To study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children., Methods: PPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods., Results: Among 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died., Conclusions: PPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about 1 % of non-small cell lung carcinoma (NSCLC). In 2004, World Health Organization classification united under this name all the carcinomas with sarcomatous or sarcomatous-like component with spindle cell or giant cell appearance. There are five subtypes: spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma, carcino-sarcoma and pulmonary blastoma. Clinical characteristics are not specific from the others subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastasis are frequent with atypical locations such as peritoneal or retroperitoneal sites. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here, we present a review of litterature in order to better describe these tumors.

Embryonal rhabdomyosarcoma of the uterine cervix is an uncommon presentation of the most common soft-tissue sarcoma in the first decades of life. Unlike embryonal rhabdomyosarcoma in other anatomic sites, in which 70-80% of cases present before 9 years of age, the average age in our series of 14 cervical cases was 12.4 years (median, 13 years), with an age range of 9 months to 32 years at diagnosis. Of the 14 cases, 12 presented as a polyp at the cervical os; two patients had an infiltrative mass in the cervix without a botryoid polyp. The polyps measured 1.5-5 cm and all had the histopathological pattern of the sarcoma botryoides variant of embryonal rhabdomyosarcoma, with condensations of primitive and differentiated rhabdomyoblasts beneath the surface epithelium and around endocervical glands. Nodules of benign-appearing cartilage were present in the stroma of six cases (43%). One of the embyronal rhabdomyosarcomas from the youngest patient, 9 months old, also had a distinctive microscopic focus of immature tubular profiles in a primitive stroma; these tubules expressed epithelial and neuroendocrine markers. Two patients had a pleuropulmonary blastoma, one diagnosed 9 years before the embryonal rhabdomyosarcoma of the cervix and the other recognized synchronously. This latter 9-year old had a DICER1 germline mutation. One patient presented with hirsutism and had a Sertoli-Leydig cell tumor, an incidentally detected cervical embryonal rhabdomyosarcoma, and nodular hyperplasia of the thyroid. Although a pleuropulmonary blastoma was not documented in the latter patient, ovarian sex-cord stromal tumors and nodular hyperplasia of the thyroid are manifestations of the pleuropulmonary blastoma family tumor and dysplasia syndrome (OMIM 601200). Embryonal rhabdomyosarcoma of the cervix must be distinguished from other rare entities, including adenosarcoma, malignant mixed Mullerian tumor and low-grade stromal sarcoma, as the former has a better prognosis; 12 of our 14 patients remain disease-free following conservative surgery and chemotherapy. Our study suggests that cervical embryonal rhabdomyosarcoma may be another pathological manifestation in the spectrum of extrapulmonary pathology in the setting of pleuropulmonary blastoma., Competing Interests: Disclosure/conflict of interest The authors declare no conflict of interest.

We report a rare case of classic pulmonary blastema (CPB) without recurrence for 3 years after the operation. A 70-year-old man presented with cough and sputum for a month. Chest computed tomography (CT) showed a 5cm-sized mass in the right middle lobe. Bronchoscopic examination was performed, and the mass was suspected as adenocarcinoma of the lung. Right middle lobectomy and lymph node dissection were performed. The pathologic histology diagnosis was classic pulmonary blastoma, a subtype of biphasic pulmonary blastoma.

TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin sections from 38 rhabdomyosarcomas, five leiomyomas, five leiomyosarcomas, five rhabdomyomas, five rhabdomyomatous Wilms tumors, three normal cardiac muscles, one medullomyoblastoma, one pleuropulmonary blastoma with rhabdomyomatous differentiation, and one teratoma with prominent rhabdomyoblasts. Each case was also stained with desmin. Unlike the nuclear staining scored in myoepithelial cells, only cytoplasmic staining for p63 was considered positive. Of 38 cases of rhabdomyosarcoma, 36 showed cytoplasmic p63 staining; 24 of these showed highlighting of cross-striations superior to that of desmin. In addition, 5/5 rhabdomyomas, 5/5 rhabdomyomatous Wilms tumors, 1/1 pleuropulmonary blastoma with rhabdomyomatous differentiation, 1/1 teratoma with atypical rhabdoblasts, and 1/1 medullomyoblastoma exhibited cytoplasmic p63 staining. Normal cardiac muscle samples (3/3) also demonstrated positive cytoplasmic staining and distinct cross-striations. Smooth muscle tumors exhibited only very focal and faint cytoplasmic staining in 5/5 leiomyomas and 4/5 leiomyosarcomas. Immunoelectron microscopic study of skeletal muscle showed p63 localization to the Z bands of sarcomeres. We conclude that p63 immunostain is a sensitive marker for skeletal muscle differentiation and highlights the cross-striations of strap cells with exceptional definition.

Pulmonary sarcomatoid carcinomas (PSCs) are currently defined as poorly differentiated non-small-cell carcinomas containing a component with sarcoma or sarcoma-like (spindle and/or giant cell) features. They consist of 5 major histological variants, namely pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. The segregation of PSCs into a distinct clinicopathologic entity seems justified on the basis of morphologic, behavioral, and genotypic/phenotypic attributes. As a group, PSCs generally run an aggressive clinical course and may cause major difficulties in the differential diagnosis with other primary and secondary malignancies of the lung. At present, PSCs are believed to represent a family of carcinomas "in transition," in which diverse pathways of clonal evolution account for histological differences of a common ancestor lesion. The sarcomatous or sarcomatoid component of these tumors is thought to derive from carcinoma cells during the progression of carcinogenesis through the activation of an epithelial-mesenchymal transition program leading to sarcomatous transformation or metaplasia (conversion paradigm). Conceivably, targeting the epithelial-mesenchymal transition program could become a valid therapeutic strategy for these life-threatening tumors, whose sensitivity to current medical manipulation is disappointing.

Well-differentiated fetal adenocarcinoma (WDFA), also known as low grade adenocarcinoma of the fetal lung type, is a rare pulmonary neoplasm now considered to be a variant of lung adenocarcinoma rather than a type of pulmonary blastoma. Upregulation of the Wnt signaling pathway with subsequent aberrant nuclear/cytoplasmic beta-catenin expression has been recently described in these tumors providing a possible pathogenetic role for this gene in WDFA. We describe the cytomorphologic findings of a case of WDFA in a 36-yr-old female patient and emphasize the diagnostic utility of aberrant nuclear/cytoplasmic expression of beta-catenin as an adjunct to the correct preoperative recognition of this tumor on aspiration cytology.

We describe a rare tumor occurring in the left pulmonary lobe of a 71-year-old Japanese man. The tumor, which was resected by left lower lobectomy, measured 65 x 50 x 50 mm. Histologic examination revealed papillary adenocarcinoma in small cell carcinoma, and chondrosarcoma. Also, the blastemal cells were located between the small cell carcinoma and the chondrosarcoma, and intermingled with both components. In blastemal cells, some glands resembled a well-differentiated fetal adenocarcinoma. The tumor was diagnosed as combined small cell carcinoma with pulmonary blastoma and papillary adenocarcinoma according to the 2004 WHO classification. Immunohistochemically, the small cell carcinoma expressed TTF-1, pancytokeratin, CD56, synaptophysin, and S100 protein, while blastemal cells expressed vimentin, desmin, smooth muscle actin, CD56, and S100 protein. To investigate whether the tumor was clonal or not, p53 gene mutation of each tumor component was analyzed by laser-captured microdissection, polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. Despite the histologic complexity, all components showed the same mutation at exon5 of the p53 gene. These results indicate that the tumor was clonal and arose from a relatively primitive cell, and that p53 mutation occurred before histologic metamorphosis or differentiation.

Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm of childhood, typically presenting as a pulmonary and/or pleural-based mass with cystic, solid, or combined features. Histologically, the tumor is well characterized with a mixture of primitive mesenchymal and variably differentiated sarcomatous components, and the cytologic features described in the three previous reports are also compatible to the histologic ones. Now, we present another case of PPB showing unusual features. A 3-yr-old boy presented with a pleural- or chest wall-based tumor. The fine-needle aspiration cytologic smears were highly cellular with poorly differentiated cells showing variable size and shape rather than those of typical blastemal cells. The histologic findings were also distinctive, exhibiting diffuse sheets of poorly differentiated cells without typical blastemal cell component. Diagnosis was confirmed by the support of immunohistochemical and ultrastructural features. The patient underwent a typical aggressive clinical course to death within 8 mo after diagnosis., (Copyright 2001 Wiley-Liss, Inc.)

Pleuropulmonary blastoma, an aggressive tumor that is emerging as a distinct entity of childhood, is characterized by mesenchymal elements (including undifferentiated blastema and often cartilaginous, rhabdomyoblastic, or fibroblastic differentiation) and epithelium-lined spaces. We investigated two patients with pleuropulmonary blastoma, a 3-year-old boy and an 11-year-old girl, both with large cystic masses replacing one lung. In both children, the post-chemotherapy resection specimens showed more maturation of rhabdomyoblasts and more nuclear pleomorphism in all mesenchymal cell lines, compared with biopsies sampled before treatment. Karyotypic analysis demonstrated gains in chromosome 8 in both cases and 17p deletion in one case. Fluorescent in situ hybridization analysis demonstrated that the chromosome 8 gains were present in all mesenchymal elements, including undifferentiated blastematous, rhabdomyoblastic, fibroblastic, and chondroblastic areas. Epithelial cells showed no chromosome 8 gains. The chromosome 8 aberrations were not appreciably different in pre- versus post-chemotherapy tissue. Our findings substantiate previous reports that polysomy of chromosome 8 is a consistent feature of pleuropulmonary blastoma. Further, they indicate that clonal proliferation in pleuropulmonary blastoma is restricted to the malignant mesenchymal elements, supporting the notion that the epithelial components of this tumor are non-neoplastic.

Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer pathogenesis is a multistep process. Proliferative activity, p53 accumulation and angiogenesis are of well-known relevance and ought to be evaluated in the epithelial and mesenchymal components of these tumors. Using antibodies against Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10 carcinosarcomas, tumors revealed a significantly higher proliferative activity in the epithelial component compared with the mesenchymal component in the MIB1 reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype, proliferative activity was similar in both parts. In five of 10 carcinosarcomas and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab 1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel density was found compared with the central parts (p < or = 0.015) using a monoclonal antibody against human endothelium (CD 31). No differences were found between carcinosarcomas and pulmoblastomas. Higher proliferative activity in carcinosarcomas revealed a better prognosis regarding metastasis behavior (p = 0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53 accumulation and microvessel density were of no prognostic value. This is in contrast to results in non-small cell lung cancer, pointing to a different biologic behavior.

Seven cases of high-grade adenocarcinoma of fetal lung type (H-FLAC) are compared with nine cases of pulmonary endodermal tumor resembling fetal lung or low-grade adenocarcinoma of fetal lung type (L-FLAC). Of the seven patients with of H-FLAC, four were men and three were women. All of the patients but one were in their 60s or 70s. Five patients were smokers. After resection of the tumor, three patients died of metastases, two patients are alive with no evidence of disease, and two patients died of a postoperative complication. Histologically, H-FLAC and L-FLAC have both complex glandular structures resembling fetal lung and neuroendocrine differentiation. Two cases of H-FLAC had stromal proliferation typical of biphasic pulmonary blastoma. The H-FLAC was distinguished from L-FLAC by the presence of disorganized glands, large vesicular nuclei, prominent nucleoli, pronounced anisonucleosis, absence of morules, transition to conventional adenocarcinoma, broad areas of necrosis, desmoplastic stroma, overexpression of p53 protein, and production of alpha-fetoprotein. High and low grades of FLAC explain discrepancies in previously reported clinicopathologic features of FLAC. The H-FLAC needs to be distinguished from L-FLAC. Both forms may have stromal components, so both have been referred to as blastomas. The H-FLAC represents the prototype of so-called pulmonary blastoma predominantly seen in the elderly, whereas L-FLAC and its biphasic form predominate in the middle-aged population.

We describe the expression of 18 different cell adhesion molecules, intermediate filaments and Ki-67 antigen in embryonal childhood tumors. 5 microns frozen sections from 15 nephroblastomas, 13 neuroblastomas, six rhabdomyosarcomas, one Ewing sarcoma and one pulmonary blastoma were analyzed by the alkaline phosphatase anti-alkaline phosphatase (APAAP) method using murine monoclonal antibodies. All tumors exhibited high proliferation rates as did, surprisingly, the nephroblastoma specimens despite pre-treatment with chemotherapy. Polysialylated NCAM was demonstrated on all tumor types, but Ewing sarcoma and expression correlated inversely with cell differentiation. In contrast, E-cadherin was present solely on tubulus like cells in nephroblastomas. This cell type showed a coexpression of cytokeratin and vimentin, giving evidence of its intermediate position between the mesenchyme and epithelium. In neuroblastomas, CD44s (hyaluronate receptor) expression was increased with cell differentiation. ICAM-1, VCAM-1 and E-selectin were mostly expressed in regressive areas of pretreated nephroblastoma specimens where a considerable infiltration of leukocytes was noted as well. Since endothelial and leukocyte adhesion molecules were distinctly less expressed in all other tumors investigated, these findings may indicate immunological processes as a consequence of or as supplement to the chemotherapeutical effect on nephroblastoma cells. Integrin receptors were not found on the surface of tumor cells, and therefore, at least those investigated seem to be of secondary importance to the biology of the tumors studied herein. In conclusion, our investigations demonstrate that, besides achieving a secure and prompt differentiation between various embryonal tumors, applying the panel of monoclonal antibodies proposed herein gives interesting insights into the histogenesis, biology and metastatic potential of pediatric malignancies.

Pulmonary blastomas (PBs) are rare primary malignancies that include adult types: biphasic pulmonary blastoma (BPB) and well-differentiated fetal adenocarcinoma (WDFA); and childhood type: pleuropulmonary blastoma (PPB). Their pathogenesis and relationship to bronchogenic carcinoma (BCA) are controversial. To determine whether or not PB share molecular pathological features with BCA, the authors immunostained three BPB, three WDFA, three PPB, and 80 standard BCA for p53 protein and MDM2 protein, gene products believed to be significant in the pathogenesis of BCA. Paraffin-embedded tissue sections were immunostained with monoclonal antibody to p53 and MDM2 proteins. Strong intranuclear staining in greater than 10% of cells was considered positive. Three (50%) BPB and WDFA stained for p53 and five (83%) for MDM2. None of the PPB stained for p53, and one PPB did not stain for either p53 or MDM2. Five of six adult type PB occurred in smokers, whereas none of the PPB was associated with smoking. Seventy-five (94%) of the BCA stained for MDM2 and 46 (61%) for p53. Immunostaining patterns for p53 and MDM2 in adult types of PB, and not PPB, appear similar to those for BCA. This may suggest that adult type PB, but not childhood PB, have a similar pathogenesis to BCA.

A case is presented of pulmonary blastoma occurring in the right upper lobe of a 25-year-old man without distinct clinical features and laboratory abnormality. Light microscopic analysis revealed that the tumor was composed of branching glands and morulae embedded in a primitive but bland mesenchyme. Immunohistochemically the epithelial cells were immunoreactive for cytokeratins, S-100 protein, protein gene product 9.5, chromogranin A, calcitonin, and Ki-67 (MIB-1); the mesenchymal cells were immunoreactive for vimentin, actin, cytokeratins, and Ki-67; and all the tumor cells were negative for p53, estrogen receptor protein, and human chorionic gonadotropin beta. Characteristically, many epithelial cells contained optically clear nuclei which were immunoreactive for biotin (M743). Electron microscopic analysis revealed that the optically clearing change was due to replacement of the central area of the nuclei by a mass of parallel-arranged 7- to 10-nm filaments, and biotin-immunoreactive products were mainly localized in the nuclear matrix. Additionally, spherical bodies were identified in the cytoplasm of the nuclear filament-aggregated cells, suggestive of an intimate pathogenetic association of the two morphological abnormalities. The similarity of the aggregated nuclear filaments to those observed in gestational endometrium and ovarian endometrioid carcinoma implies that a similar mechanism plays a role in the pathogenesis of these abnormalities.