Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases

Abstract

Background. The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. Methods. Seventy‐eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow‐up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. Results. The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow‐up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23‐month mean survival (median, 10 months) (Kaplan‐Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. Conclusions. The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma. Cancer 1994; 73:2936–45.

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma 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. 28 The association between smoking and pulmonary pleomorphic carcinomas is very strong, 7,14,15,17,32 as re-emphasized also by the current series of patients, in whom all but one were smokers. All K-ras mutations detected in our tumors were transversions, namely G:C-T:A in four cases and G:C-C:G in two cases, exactly paralleling the findings of previous reports showing a higher prevalence of G:C-T:A (67%) than G:C-C:G transversions (33%).…”

“…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).…”

The new World Health Organization classification of lung tumours

“…Spindle and giant cell carcinoma and carcinosarcoma comprise only 0.4% and 0.1% of all lung malignancies, respectively [23]. The tumours described under which name represent overall a continuum of epithelial and mesenchymal differentiation [47,48]. Whether these tumours have a worse prognosis than other NSCLC is intuitively likely, but has not been firmly demonstrated on large series.…”

Clinicopathological factors influenced the prognosis of surgically resected pulmonary pleomorphic carcinoma

“…In 1999, WHO defined PC is a poorly differentiated non-small cell lung carcinoma (NSCLC) namely a squamous cell carcinoma, adenocarcinoma, or undifferentiated non-small cell carcinoma that contains at least 10% spindle and/or giant cells or a carcinoma consisting only of spindle and giant cells (2). According to the WHO report, PC makes an unfavorable prognosis because of its properties of resisting radiation and chemotherapy, and its aggressive growth (3)(4)(5)(6).…”