BACKGROUND & OBJECTIVE: Lung pleomorphic (spindle/giant cell) carcinoma is a rare epithelial malignant tumor. This study was to investigate its clinicopathologic and prognostic characteristics. METHODS: Clinicopathologic records of 17 patients with lung pleomorphic (spindle/giant cell) carcinoma were reviewed and compared with those of the patients with other histopathologic types of lung cancer treated in the same period. All patients underwent surgical resection. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for prognostic analysis. RESULTS: The 17 patients consisted of 15 men and 2 women with median age of 58 (45-78)û 5 at stage I, 3 at stage II, and 9 at stage III by pathologic TNM staging. Of the 17 cases of lung pleomorphic (spindle/giant cell) carcinoma, 2 were lung exclusive spindle cell carcinoma, 5 were lung carcinoma with spindle cells (combined with one kind of epithelial components, such as squamous cell carcinoma in 3 cases, adenocarcinoma in 1 case, and large cell carcinoma in 1 case), 10 were lung carcinoma with giant cell carcinoma (combined with one kind of epithelial components in 5 cases, two kinds in another 5 cases). Four patients at stage I survived free of tumor for more than 5 years. The median survival time was significantly shorter in lung pleomorphic (spindle/giant cell) carcinoma patients than in lung squamous cell carcinoma patients (36 months vs. 61 months, P=0.027), and was also significantly longer in patients with carcinoma containing spindle cells (including spindle cell carcinoma) than in patients with carcinoma containing giant cells (64 months vs. 18 months,P=0.026). Lymph node metastasis and carcinoma containing giant cells were poor prognostic factors of lung pleomorphic (spindle/giant cell) carcinoma. CONCLUSION: Lung carcinoma containing giant cells has multiple cells components, and has worse prognosis than lung carcinoma containing spindle cells and spindle cells carcinoma do.

Pulmonary pleomorphic carcinoma.Kyobu Geka. 2005 Nov;58(12):1043-8.

Pleomorphic carcinoma is a rare primary pulmonary malignancy. We report 2 surgical cases of pulmonary pleomorphic carcinoma. The first case was a 71-year-old male. Chest computed tomography (CT) showed a rapidly growing tumor with irregular density. Transbronchial lung biopsy revealed the tumor to be malignant. Left lower lobectomy was performed. Pathological diagnosis was pleomorphic carcinoma (pT2N2M0, stage IIIA). He died 8 months after surgery due to brain metastasis and mediastinal lymph node metastasis. The second case was a 74-year-old male who complained of bloody sputum. Chest CT showed a tumor with cavity in the right middle lobe. Brushing cytology under bronchofiberscopy revealed atypical cell. Right middle lobectomy and partial resection of the right lower lobe were performed. Pathological diagnosis was also pleomorphic carcinoma (pT2N0M0, stage IB). He has no findings of recurrence nor metastasis 15 months after the operation.

Pulmonary pleomorphic carcinoma; report of 2 cases. Kyobu Geka. 2006 Jul;59(7):585-9.

The 1st case was a 74-year-old male diagnosed as femoral neck fracture. Biopsy of the bone revealed metastatic adenocarcinoma. Chest computed tomography (CT) showed a mass lesion located in the right lower lobe. With a diagnosis of primary lung cancer (cT2N1M1), two-staged operation was performed. Pathological diagnosis was pleomorphic carcinoma [pT2N1M1 (OSS), stage IV]. He died 8 months after surgery due to metastasis to the thoracic spine. The 2nd case was a 80-year-old female who complained of lateral chest pain. Chest CT revealed a tumor in the right hilar region, which was diagnosed as adenocarcinoma by transbronchial lung biopsy. Only thoracic drainage was performed since metastases to the brain and the rib were demonstrated. She died 2 months after admission. Autopsy revealed pleomorphic carcinoma of the lung with metastasis to the brain, costa and mediastinal lymph nodes.

Pathological study of pulmonary carcinomas with spindle and/or giant cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2006 Jun;28(3):391-4.

OBJECTIVE: To study the pathologic features of pulmonary carcinomas with spindle and/or giant cells. METHODS: Twenty cases of pulmonary carcinomas with spindle and/or giant cells were studied by using lightmicroscopy and immunohistochemical staining. RESULTS: Of 20 cases, 15 cases were pleomorphic carcinoma (10 cases with adenocarcinoma, 3 cases with large cell carcinoma, 1 case with squamous cell carcinoma and 1 case with giant cell carcinoma) , 4 cases were spindle cell carcinoma, and 1 case was giant cell carcinoma. Immunohistochemical results showed AE1/AE3 was positive in the spindle and/or giant cell component of 19 cases, Vimentin was positive in the spindle and/or giant cell component of 20 cases, P53 was positive in 10 cases and thyoid transcription factor-1 (TTF-1) was negtive in all cases. CONCLUSIONS: Pulmonary carcinomas with spindle and/or giant cells is defined as a group of poorly differentiated non-small cell carcinoma that contains a component of spindle and/or giant cells. The diagnosis is based on histopathology and immunohistochemical staining of AE1/AE3 and Vimentin.

Cavitating pleomorphic carcinoma of the lung; report of a case. Kyobu Geka. 2006 Sep;59(10):959-61.

We report a case of a previously healthy 76-year-old male with cavitating pleomorphic carcinoma of the lung. He was admitted because of an abnormal lung shadow on chest X-ray. Computed tomography (CT) showed a well-demarcated nodular shadow within thin-walled cavity in the right upper lobe. Because the lesion was revealed as adenocarcinoma by transbronchial lung biopsy, right upper lobectomy was performed. By histopathologic examination of the resected specimen, the nodule contained a component of spindle cell features and the cavity wall was composed of adenocarcinoma. The final diagnosis was pleomorphic carcinoma. Postoperative course has been uneventful for 12 months after surgery.

Pulmonary pleomorphic carcinoma; report of a case.Kyobu Geka. 2005 Oct;58(11):1013-6.

We report a case of a 64-year-old man with pleomorphic carcinoma of the lung and thymic cyst. He was admitted to our hospital because of an abnormal shadow observed on chest X-ray. Computed tomography (CT) showed a mass lesion located in the right upper lobe and a non-invasive anterior mediastinal tumor adjacent to the left brachiocepharic vein. On enhanced CT, the lung mass showed central low-attenuation areas with a substantial enhancement in the periphery. Preoperative transbronchial blushing cytology of the mass revealed adenocarcinoma. With a diagnosis of primary lung cancer (cT3N0M0) and mediastinal tumor, an operation was performed through a median sternotomy. The mediastinal tumor was excised and a right upper lobectomy and were also accomplished, because the lung tumor did not show adhesion or pleural invasion. Histopathologic examination of the resected specimen revealed that the lung tumor composed of a mixture of spindle and giant cell features and contained a component of adenocarcinoma and squamous cell carcinoma. This finding yielded a pathological diagnosis of pleomorphic carcinoma (pT2N0M0). The mediastinal tumor was diagnosed as thymic cyst. The postoperative course was uneventful, and he is currently well 6 months after surgery.

Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases. Cancer. 1994;73(12):2936-45.

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.

Pleomorphic (giant and/or spindle cell) carcinoma of lung shows a high percentage of variant CYP1A12.Mol Diagn. 2001 Jun;6(2):109-15.

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is an aggressive epithelial neoplasm composed of giant and/or spindle tumor cells and associated with short survival. Most patients are cigarette smokers. The tumor susceptibility gene P-450 1A1 (CYP1A1) is involved in the activation of polycyclic aromatic hydrocarbons, including benzo[a]pyrene, producing DNA-damaging epoxides that lead to G:C-->T:A point mutations. Isoleucine (Ile)-valine (Val) and Val-Val genotypes of the CYP1A1 exon 7 polymorphism are associated with an increased risk for lung cancer in certain populations. METHODS AND RESULTS: We sought to determine whether 25 archival, formalin-fixed, paraffin-embedded PC samples had a modified CYP1A1 gene profile at exon 7 using allele-specific PCR amplification. KRAS mutation status was available for all samples. Previous investigations have shown 0.88 Ile-Ile, 0.12 Ile-Val, and rarely, Val-Val as normal baseline population frequencies. Conversely, the markedly different PC CYP1A1 population frequencies were more likely to have the heterozygote variant alleles: 0.24 (six cases, Ile-Ile) and 0.76 (19 cases, Ile-Val; P <.001). CYP1A1 genotypes were found to be similar in both tumor and nontumor samples in a given case. All KRAS-mutated cases were Ile-Val heterozygotes. CONCLUSION: The increased propensity for the variant CYP1A1 allele may be the contributing factor to PC pathogenesis and may also result from KRAS mutations in these tumors.

Personal experience in surgical management of pulmonary pleomorphic carcinoma. Ann Thorac Surg. 2004 Nov;78(5):1742-7.

BACKGROUND: Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. METHODS: Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. RESULTS: We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. CONCLUSIONS: The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

Sarcomatoid carcinoma of the lung: a clinicopathologic study of 37 cases.Cancer. 1999 Aug 15;86(4):608-16.

BACKGROUND: Spindle and giant cell carcinomas of the lung are rare subtypes and are regarded as one type of lung carcinoma, termed pleomorphic carcinoma in the Armed Forces Institute of Pathology classification. This classification is different from the World Health Organization classification. METHODS: Thirty-seven cases of sarcomatoid (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy, conventional histochemistry, and immunohistochemistry to establish their clinical and histologic characteristics. RESULTS: The patient population was comprised of 29 men and 8 women ages 33-81 years. Seventeen patients died of their disease and there was no statistically significant difference in patient prognosis between sarcomatoid carcinoma and nonsarcomatoid carcinoma of the lung. Using light microscopy, 5 cases (13.5%) comprised entirely of sarcomatoid components without carcinomatous elements were classified as Group A. In the remaining 32 cases (86. 5%), classified as Group B, carcinomatous components were present (adenocarcinoma [18 cases; 48.7%], squamous cell carcinoma [8 cases; 21.6%], and large cell carcinoma [6 cases; 16.2%]). Sarcomatoid components were divided further into three categories: spindle cell type, giant cell type, and mixed spindle and giant cell type. Immunohistochemically, the sarcomatoid components of all 37 cases were positive for cytokeratins. Statistically, there was no significant prognostic difference between the 37 cases of sarcomatoid carcinoma and 647 cases of nonsarcomatoid, nonsmall cell carcinoma of the lung (P = 0.8537). CONCLUSIONS: The sarcomatoid portions in all sarcomatoid carcinomas in the current study showed an epithelial differentiation, and there was no apparent difference in biologic behavior between sarcomatoid carcinoma and ordinary lung carcinoma.

Pulmonary giant cell carcinoma: pathological entity or morphological phenotype?Histopathology. 1998 Mar;32(3):225-31.

AIMS: To evaluate the morphological spectrum and clinical significance of giant cell carcinoma and to assess the frequency of tumour giant cell production in a consecutive series of primary (non-giant cell) lung tumours. METHODS AND RESULTS: Forty-six cases of giant cell carcinoma of the lung were collated from two centres over a 12-year period. Giant cell carcinoma was found to be associated with areas of clear cell carcinoma, spindle cell carcinoma and showed trophoblastic differentiation (syncytiotrophoblastic giant cells and beta-human chorionic gonadotrophin immunopositivity) in 57%, 34% and 26% cases, respectively. 'Pure' giant cell carcinoma was identified in five (11%) cases. Eleven of the tumours contained diastase-resistant periodic acid-Schiff positive material and were separately designated as giant cell adenocarcinomas. Areas of squamous cell and neuroendocrine differentiation (as determined by chromogranin A and Leu-7 immunopositivity) were not found. The median survival for giant cell carcinoma (excluding the giant cell adenocarcinomas) was 18 months. Median survival was not adversely affected by the extent of tumour giant cell formation or by the presence of trophoblastic differentiation. Of 200 consecutive non-small cell lung carcinomas, tumour giant cells constituting < 10% of the tumour were identified in 32% of adenocarcinomas and 26% of squamous cell carcinomas. CONCLUSIONS: The presence of tumour giant cells in lung carcinoma does not, in itself, indicate a more aggressive tumour type, Giant cell carcinoma of the lung does not appear to be a distinct entity but a morphological phenotype expressed by a heterogenous group of tumours. We support and advocate the use of an encompassing term such as 'pleomorphic' or 'anaplastic' carcinoma for those tumours showing no specific differentiation pattern but which express diverse morphological features such as giant cell formation, clear or spindle cell change.

Pleomorphic (giant and spindle cell) carcinoma is genetically distinct from adenocarcinoma and squamous cell carcinoma by K-ras-2 and p53 analysis.Am J Clin Pathol. 1996 Oct;106(4):487-92.

Pleomorphic carcinoma (PC) of lung is a poorly differentiated epithelial neoplasm predominantly composed of pleomorphic giant and/or spindle tumor cells. The WHO classification of lung cancer recognizes spindle cell carcinoma and giant cell carcinoma as separate neoplasms related to squamous cell carcinoma (SqC) and large cell carcinomas, respectively. Further, the presence of foci of SqC or adenocarcinoma (AdC) in, respectively, 10% and 45% of PC produces additional uncertainty as to the distinctive nature of this tumor type. In this study, the authors tested the hypothesis that PC is an entity separate from SqC or AdC by evaluating the mutational spectrum seen in these tumor types. This is performed by documenting and comparing mutation type and rate of K-ras-2 and p53 genes in PC, SqC, and AdC. Comparative DNA sequence and immunohistochemical analysis were performed on 22 PC, 42 SqC, and 97 AdC. Archival formalin-fixed, paraffin-embedded tissues formed the basis of the study. Immunohistochemical staining with p53 antibody (DO-7) revealed statistically significant differences in the intensity and frequency of staining of PC (weak, 86% of cases) versus SqC (strong, 52% of cases) and AdC (strong, 27% of cases) (P < .001). Topographic genotyping with subsequent polymerase chain reaction (PCR) and sequence analysis of K-ras-2 showed mutations in significantly fewer cases of PC (9%, 2 of 22 cases) than in AdC (36%, 35 of 97 cases) or SqC (0%, 0 of 42 cases) (P < .001). Pleomorphic carcinoma also showed significantly fewer p53 point mutations (14%, 3 of 22 cases) than did AdC (27%, 26 of 97 cases) of SqC (43%, 18 of 42 cases) (P < .01). Finally, the p53 mutations in PC were more common in exon 7, whereas those in SqC and AdC were more frequent in exon 8. These findings reveal significant differences in the pattern and frequency of genetic mutations between PC and pulmonary SqC and AdC and are in keeping with the separate histopathologic classification of these tumors.

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