Fine-needle aspiration cytology of pulmonary adenocarcinoma of fetal type: report of a case with immunohistochemical and ultrastructural studies.

This report describes the fine-needle aspiration (FNA) cytology of a case of adenocarcinoma resembling fetal lung in a 53-yr-old male, a very uncommon malignant tumor of the lung that is similar to an early stage of lung differentiation. FNA smears revealed relatively small, fairly uniform tumor cells appearing as cohesive cell groups and scattered, isolated cells, some of them showing a rosette or acinus pattern. In addition, clusters of larger cells with eosinophilic cytoplasm and prominent nucleoli existed contiguously with the small cells or separately. The possibilities of an unusual type of adenocarcinoma, carcinoid tumor, and pulmonary blastoma were suggested by the cytologic findings. Immunohistochemical studies performed on a resected tumor tissue showed immunoreactivity for alpha-fetoprotein, neuron-specific enolase, and somatostatin, and endocrine-type granules were found ultrastructurally. This type of adenocarcinoma is considered to have a histogenesis similar to that of pulmonary blastoma. To our knowledge this is the first reported case in the cytologic literature.     

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 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.     

Pleuro-pulmonary blastoma in a 45 year-old woman after Hodgkin’s lymphoma: a case report

Pleuro-pulmonary blastoma is a rare and aggressive intrathoracic mesenchymal tumor occurring in childhood. We report the exceptional case of a forty-five year-old woman, presenting with respiratory distress. She had previously been treated with chemotherapy and radiotherapy for Hodgkin lymphoma. Chest X rays and computed tomography scan showed a left lung lower lobe mass and pleural effusion. Biopsy cores revealed a pleura-pulmonary blastoma tumor with mixed components. Neoadjuvant chemotherapy was decided in multidisciplinary round. Because of the rarity of these tumors, no consensus for the treatment exists.     

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.     

Well-differentiated fetal adenocarcinoma of the lung: cytomorphologic features on fine-needle aspiration with emphasis on use of beta-catenin as a useful diagnostic marker

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.     

The cytomorphology of pleuropulmonary blastoma

Pleuropulmonary blastoma is a rare, primitive primary neoplasm of the thorax in young children. The tumor, which is often but not always associated with cystic lung lesions, may arise in pulmonary parenchyma, the mediastinum, and pleura. Histologically, it is characterized by a biphasic neoplastic population of undifferentiated-appearing small round cells and larger spindle-shaped cells. A proportion of these cancers may also manifest more specific mesenchymal differentiation. In contrast to the pulmonary blastoma of adults, a malignant epithelial component does not occur. We present herein the third known case of a fine needle aspiration biopsy of a pleuropulmonary blastoma in a 5-year-old girl. The smears were moderately cellular and included an admixture of the characteristic small ovoid blastemal elements and scattered spindled mesenchymal tumor cells.     

Infant pleuropulmonary blastoma: report of a rare case and review of literature

In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small cells, usually observed in sheets. So as to provide proper and timely treatment, the differential diagnosis includes pulmonary blastoma, sarcomatoid mesothelioma, fetal rhabdomyoma, synovial sarcoma, and primitive neuroectodermal tumor. Herein, we will present one male pediatric patient with pleuropulmonary blastoma. The patient was a 4-month-old male infant, who had a prolonged cough and dyspnea for 4 months that was complicated by cyanosis for 3 days. A physical examination revealed a solid mass in the right lung that was sized 9.0 × 6.0 × 4.0 cm and had a grayish-white cross section. The boundary between the mass and lung tissue was clear; the mass already occupied a great portion of the lung. A microscopic examination suggested that the tumor was composed of round or orbicular-ovate primitive fetal cells. The cells were medium sized, having little cytoplasm, but had a clearly visualized nucleolus and active karyokinesis. The tumor mass was biphasic, namely, fasciculated sarcoma (composed of spindle-shaped cells and short spindle-shaped cells) and malignant fibrous histiocytoma containing well-differentiated cartilage islands or cartilaginous nodes. Immunohistochemistry was performed for further detection: vimentin (+), S-100 protein (+), CK (AE1/AE3), EMA and TTF-1 in residual epithelial components (+), NSE (focal +), SMA (mesenchymal cells, focal +), CD99 (weak +), Bcl-2 (weak +), desmin (-), myoglobin (-), calretinin (-), calponin (-), FLI (-), MyoD-1 (-), and CD34 (-). Pleuropulmonary blastoma is extremely rare but highly aggressive neoplasm in children. Its typical histopathological presentation is the aggregation of primitive malignant small cells. Combining imaging and histopathological examinations and clinical data should help in determining the diagnosis of pleural pulmonary blastoma.     

胸膜肺母细胞瘤1例报道及文献复习

目的：阐明胸膜肺母细胞瘤的病理形态特征及鉴别诊断要点。方法：对1例小儿胸膜肺母细胞瘤进行了组织形态学,免疫组织化学分析。结果：胸膜肺母细胞瘤是一种纯间质性恶性肿瘤,好发于12岁以下的儿童及婴幼儿,起源于肺、胸膜或纵隔的原始细胞,镜下可见原始胚胎性的圆形或短梭形细胞,瘤细胞有呈巢趋势,酷似肾母细胞瘤,肝母细胞瘤等肿瘤原始胚基成分,免疫组化未见有上皮细胞及其他间叶成分标志的表达,另一种成分为梭形细胞,除表现为纤维肉瘤特点外,还向横纹肌肉瘤分化,结论：胸膜肺母细胞瘤是一种极为罕见的恶性肿瘤,应与肺母细胞瘤,原始神经外胚叶肿瘤及胚胎性横纹肌肉瘤等鉴别。     

Pleuropulmonary blastoma: Diagnosis by fine-needle aspiration cytology: A case report

Pleuropulmonary blastoma (PPB) is an unusual pleural-based blastoma presenting in childhood composed by undifferentiated sarcomatous tissue with divergent differentiation and occasional benign epithelial-lined structures. We are presenting the cytologic features of PPB as diagnosed by fine-needle aspiration cytology (FNAC) of the lower lobe of the right lung in a 4-year-old girl. The smears showed highly malignant cells with hyperchromatic oval or multilobulated pleomorphic nuclei strongly suggesting an aggressive sarcoma. Histology of the aspirated material also revealed small fragments of a myxoid sarcoma with some pleomorphic anaplastic cells. Lobectomy and surgical pathologic investigation confirmed the diagnosis. PPB seems to be another tumor in which accurate diagnosis may be achieved by FNAC. Diagn. Cytopathol. 1998;19:303–305. © 1998 Wiley-Liss, Inc.     

Pulmonary blastoma in a child: Report of a case with cytological findings

Pulmonary blastoma is an uncommon tumour. It constitutes <0.1% of all resected lung cancers. It is even more rare in children with only a few case reports describing this entity in them. Pulmonary blastoma should not be confused with pleuropulmonary blastoma which is a paediatric lung tumour with different morphology and better outcome. Here we take the opportunity of describing pulmonary blastoma in a 3 years old child along with its cytological findings.     

Pulmonary blastoma: a light-microscopic, immunohistochemical and electron-microscopic study of six cases in childhood]

Pulmonary blastoma is a very rare primary tumor of the lung, which mostly occur at a late age in adults. Six cases in children under four years of age are reported in this series. The light-microscopic, immunohistochemical and electron-microscopic characteristics revealed that the elements of P.B. in childhood consist mainly of mesenchymal components, including undifferentiated large cells and small round cells, which tend to differentiate toward rhabdomyosarcoma. The epithelial components comprise only a small portion of the total tumor, and most appear as the well-demarcate branching tubular structures lined with columnar or cubiodal epithelium merging with the stroma. The degree of differentiation of mesenchymal elements is closely related to the prognosis.     

Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations

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.     

Adrenocortical blastoma.

We report a previously undescribed virilizing malignant adrenocortical tumor in an 21-month-old infant with elevated serum alphafetoprotein. The tumor consists of a peculiar mixture of immature epithelial and mesenchymal elements as well as slit-like spaces partially lined by primitive epithelial cells. Focally, the tumor has features reminiscent of the normal embryologic development of the adrenal cortex. A panel of immunohistochemical stains revealed only vimentin reactivity. We propose the term "adrenocortical blastoma" for this unusual neoplasm.     

DICER1 mutations in a patient with an ovarian Sertoli-Leydig tumor,well-differentiated fetal adenocarcinoma of the lung,and familial multinodular goiter

DICER1 syndrome, a recently described tumor-predisposition syndrome, often involves multiple organs and is characterized by pleuropulmonary blastoma (PPB), cystic nephroma, ovarian Sertoli-Leydig tumors, familial multinodular goiter, etc. Germline DICER1 mutations have been identified in individuals with a variety of malignant conditions. However, in a review of the reported DICER1 syndrome cases that feature an unusual array of neoplastic and hyperplastic phenotypes, no mentions are made of these patients also presenting well-differentiated fetal adenocarcinoma of the lung.Here, we present a 16-year-old Chinese adolescent suffering from an ovarian Sertoli-Leydig cell tumor, well-differentiated fetal adenocarcinoma of the lung, and familial multinodular goiter with a nonsense mutation (c.3540C > A; p.Tyr1180*) in exon 21 of DICER1. This report presents the first case in which the clinical features of DICER1 syndrome appear in combination with well-differentiated fetal adenocarcinoma of the lung. We hypothesize that this case may suggest that well-differentiated fetal adenocarcinoma of the lung falls within the wide spectrum of manifestations of the DICER1 syndrome. Remarkably, this mutation is reported in a patient from The International PPB Registry.     

Fine-needle aspiration cytology of pleuropulmonary blastoma: Case report and review of the literature

This report describes the fine-needle aspiration (FNA) cytology of a case of pleuropulmonary blastoma in a 3-yr-9-mo-old male. Pleuropulmonary blastoma is considered by most authors to be distinct from pulmonary blastoma and is a rare malignant tumor of the intrathoracic cavity. FNA smears were cellular with numerous small ovoid to spindled cells with oval to elliptical nuclei exhibiting finely granular chromatin and inconspicuous nucleoli. The cytoplasm was scant and cosinophilic with indistinct borders. Focal chondroid material and blastema-like cells were noted. The differential diagnosis suggested by the cytologic findings included rhabdomysosarcoma, teratoma, neuroblastoma, malignant mesenchymoma, pleuropulmonary blastoma, and metastatic tumor. To our knowledge, this is the first report of the cytology of this tumor. Diagn. Cytopathol. 16:336–340, 1997. © 1997 Wiley-Liss, Inc.     

Nasal Blastoma: A Light and Electron Microscopic Study

The first light and electron microscopic study of a nasal blastoma is reported. Analogous to a pulmonary blastoma, the tumor is composed of well-differentiated squamous and glandular epithelial elements surrounded by a spindle cell stroma. The spindle stromal cell is a myofibroblast. Eighteen months after complete surgical removal of the tumor and radiation therapy, the patient is clinically free of disease.     

Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium.

Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung-type adenocarcinoma, were examined by immunohistochemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present; they were argyrophilic and expressed pan-NE markers, neurosecretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated Lewis X was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha-fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium.     

Intratubular embryonal carcinoma

Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and alpha-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.