Pulmonary Carcinomas With Pleomorphic, Sarcomatoid, or Sarcomatous Elements

Abstract

We collected 75 primary pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements to better define their clinical, histologic, and immunohistochemical profile. The patient's age ranged from 42 to 81 years (mean 65 years), and the male-to-female ratio was 9.7:1. Sixty-nine patients (92%) were smokers. Cough and hemoptysis were the most frequent presenting symptoms. Fifty-nine patients (65%) died of disease: only stage significantly predicts overall survival (p ‫ס‬ 0.0273). Microscopically, based on the WHO criteria, 58 cases were classified as pleomorphic carcinoma (51 with an epithelial component, 7 composed exclusively of spindle and giant cells), 10 as spindle cell carcinoma, 3 as giant cell carcinoma, 3 as carcinosarcoma, and 1 as pulmonary blastoma. Immunohistochemically, in the tumors composed exclusively of spindle and/or giant cells, thyroid transcription factor-1 (TTF-1) and cytokeratin 7 were positive in 55% and 70% of the cases, respectively, whereas surfactant protein-A was always negative. In pleomorphic carcinomas with an epithelial component, cytokeratin 7, TTF-1, and surfactant protein-A were positive in the sarcomatoid component in 62.7%, 43.1%, and 5.9% of the cases, respectively, whereas they were always negative in the sarcomatous part of carcinosarcomas and blastoma. In the epithelial component of pleomorphic carcinomas, cytokeratin 7, TTF-1, and surfactant protein-A were positive in 76.4%, 58.8%, and 39.2% of the cases, respectively, whereas the same antibodies did not react with the epithelial component of carcinosarcomas; in the case of blastoma, the epithelial part of the tumor was positive for cytokeratin 7 and TTF-1, whereas it was negative for surfactant protein-A. Cytokeratin 20 was always negative. In our opinion, this study: 1) supports the metaplastic histogenetic theory for this group of tumors; 2) shows that cytokeratin 7 and TTF-1, but not surfactant protein-A, are useful immunohistochemical markers in this setting; 3) confirms that stage is at the moment the only significant prognostic parameter, as in conventional non-small cell lung carcinomas; and 4) shows that this group of tumors has a worse prognosis than conventional non-small cell lung carcinoma at surgically curable stages I, justifying their segregation as an independent histologic type in the WHO classification.

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung

“…Therefore, we speculate that biphasic pleomorphic carcinomas may either be metaplastic carcinomas derived from trans-differentiation of malignant epithelial cells into sarcomalike cells (according to the conversion theory) or arise from a common progenitor that shows an early divergent bi-directional differentiation (according to the combination theory). Our hypothesis of a metaplastic origin of biphasic pleomorphic carcinomas is also supported by three other recent studies, two immunohistochemical dealing with pleomorphic carcinomas 19,22 and another genetic dealing with carcinosarcomas of the lung. 28 In the latter, a multistep progression of the sarcomatous component from a common totipotent ancestor through an intermediate stage of carcinoma was prospected, as these tumors showed a greater amount of genetic damages in the mesenchymal than in the epithelial component.…”

“…These tumors have been variously designated in the past as biphasic and monophasic sarcomatoid carcinoma, pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pseudosarcoma, pulmonary blastoma and carcinosarcoma. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] The latest recommendations of the World Health Organization have eliminated most of these terms, 1 confirming the designation of pleomorphic carcinomas to either pure neoplasms consisting of sarcomatoid spindle and giant tumor cells or biphasic neoplasms containing sarcomatoid spindle and/or giant cell components (accounting for at least 10% of the tumor mass) and conventional non-small-cell lung carcinoma, including squamous cell carcinoma, adenocarcinoma or large-cell carcinoma. These tumors may be differentiated from carcinosarcomas for the lack of a true malignant heterologous mesenchymal component, such as bone, cartilage, vessels or skeletal muscle, 10 and from pulmonary blastomas for the lack of primitive mesenchymal and epithelial tumor cells.…”

“…1,20 Pleomorphic carcinomas are basically thought to be epithelial tumors in which neoplastic cells undergo an epithelial-mesenchymal transition 21 and express vimentin and other mesenchymal proteins. 3,7,[13][14][15]17,19,22 In different anatomical sites, most, but not all, of these tumors composed of carcinoma and sarcoma or sarcoma-like components are considered monoclonal growths (the so-called divergent hypothesis) rather than true collision tumors (convergent hypothesis). 20,[23][24][25][26][27][28][29][30][31] In turn, these monoclonal growths may originate from a single ancestor undergoing divergent epithelial and mesenchymal differentiation early during the neoplastic transformation (combination theory), or the full-blown carcinoma cells undergo sarcomatoid changes during tumor progression (conversion theory).…”

Air bronchogram in pleomorphic carcinoma of the lung is associated with favorable prognosis

“…Pleomorphic carcinoma of the lung usually presents as a large, necrotic mass and mainly involves the upper lobe 5. Likewise, in this study, 24 out of 35 (68.6%) tumors with a mean diameter of 37.9 mm were located in the upper lobes.…”

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

“…17 Furthermore, thyroglobulin and surfactant protein are completely negative in all anaplastic thyroid carcinomas and pulmonary pleomorphic carcinomas. [18][19][20] Even the transcription factor TTF-1 is expressed only in 5.7% 21 of anaplastic thyroid carcinomas, and 55% of lung pleomorphic carcinomas. 20 The diagnosis of anaplastic carcinomas, which is the least differentiated thyroid epithelial neoplasm, is conventionally based, similarly to undifferentiated carcinomas of other organs such as upper aerodigestive tract and uterus, on: (1) a presence of differentiated thyroid carcinoma componentusually papillary carcinomas but also follicular carcinomas and poorly differentiated carcinomaswhich can be found in 50-89% of well-sampled cases; (2) involvement of the bulk of the tumor in the thyroid gland; (3) exclusion of undifferentiated tumor by metastasis or direct invasion from a neighboring organ, such as larynx.…”