Resection of lung metastases. Results and prognostic factors

249 thoracotomies for lung-metastases were performed in 202 patients at the 2nd Dept. of Surgery of the Vienna University Clinic till 1989. Age ranged from 2 to 78 years, 14 patients were younger than 18 years. The primary tumour was a carcinoma in 143 cases, a sarcoma in 45 cases and a melanoma in 14 patients. The primary tumour in the young patients was osteosarcoma in 8 cases, Ewing sarcoma in 2 cases and Wilms tumour in 2 patients. With a minimal follow up period of 2.5 years the 5-years-survival after metastasectomy was 42% for patients with carcinoma and 29% for the sarcoma patients. None of the patients with melanoma survived 5 years. A significant difference was found between the carcinoma and sarcoma groups with respect to survival rate. A prognostic factor was the disease-free interval in carcinoma patients. Actuarial post-thoracotomy survival in patients with osteogenic sarcoma was 34% at 5 years and 18% in the soft-tissue sarcoma group. Size of lesion, vitality of the metastases and the disease free interval correlated with survival in the osteogenic group, whilst the number of lesions was of importance in the soft-tissue group. On account of the lesser functional morbidity and the enablement to assess both lungs for treatment, the median sternotomy is recommended for cases with bilateral lung metastases. The results justify an aggressive surgical approach for the treatment of lung metastases.     

Personal experience in surgical management of pulmonary pleomorphic carcinoma

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.     

A case of carcinosarcoma arising in the submandibular gland.

A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of the left submandibular area. Total excision of the left submandibular gland with radical neck dissection was performed under a diagnosis of a submandibular tumor, probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma consisting of carcinomatous and sarcomatous elements. The epithelial component was composed of squamous cell carcinoma, undifferentiated carcinoma, and adenocarcinoma. The nonepithelial component was composed of chondrosarcoma, osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the central area of the tumor, a few remnants of benign pleomorphic adenoma were identifiable. The finding suggested that in our patient, the carcinosarcoma arose from a preexisting pleomorphic adenoma. In view of the expected aggressive nature of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well and free of disease 24 months after treatment.     

Carcinosarcomas of the lung: a clinicopathologic study of 66 patients

Carcinosarcoma is a malignant tumor having a mixture of carcinoma and sarcoma containing differentiated mesenchymal elements, such as malignant cartilage, bone, and skeletal muscle. These tumors have been linked histogenetically to pleomorphic carcinomas; it is unclear whether their clinical behavior is significantly different. To investigate this issue, we studied 66 cases of carcinosarcomas of the lung and compared them with cases from a previously published series of pleomorphic carcinomas. Carcinosarcomas show a male-to-female ratio of 7.25:1, with a mean and median age of 65 years. They most often present as solitary masses in the upper lobes and average 7 cm in diameter. Most (62%) were endobronchial or central tumors, whereas 38% were described as peripheral. The most frequent epithelial component was squamous cell carcinoma (46%), followed by adenocarcinoma (31%) and adenosquamous carcinoma (19%), whereas sarcomatous elements most frequently included rhabdomyosarcoma, chondrosarcoma, osteosarcoma, or combinations of these elements. Survival of patients with carcinosarcomas of lung was poor, with a 5-year survival rate of 21.3%. Of several clinical and pathologic parameters, only increased tumor size (with 6 cm as the optimal cutoff point) appeared to be related to reduced survival (p = 0.0195). In comparison with patients with pleomorphic carcinoma, patients with carcinosarcomas had no significant difference in the size of their tumors (p = 1.0), stage at presentation (p = 0.883), location in the lung (p = 0.073), or their overall survival (21.3% vs 15.0%) (p = 0.1038). A significantly greater proportion of patients with carcinosarcoma had squamous cell (p = 0.004) or adenosquamous (p = 0.016) carcinoma, whereas patients who had pleomorphic carcinoma showed a significantly greater frequency of adenocarcinoma (p = 0.029) and large cell carcinoma. The histologic differences between these two types of tumor suggest that they may be different entities with similar behavior, but additional studies are warranted to investigate this hypothesis.     

Collision malignant melanoma and medullary carcinoma of the thyroid

This report presents the case of a 54‐year‐old woman with a collision tumour of malignant melanoma and medullary thyroid carcinoma in the thyroid. Twenty four of 25 neck lymph nodes contained metastatic melanoma, with the rest having both metastatic melanoma and medullary carcinoma. Systemic chemotherapy was administered for the malignant melanoma, and a complete response was thus obtained. However, just after having the chemotherapy, multiple lung and brain metastases emerged. The simultaneous occurrence of malignant melanoma and medullary carcinoma in the same thyroid has not been previously reported in the literature. Collision tumour of malignant melanoma and medullary carcinoma of the thyroid might imply bad prognosis.     

A malignant mixed gonadal stromal tumour of the testis with heterologous components

We report a case of malignant mixed gonadal stromal tumour in the testis, which consisted of epithelial heterologous components and metastasized to the retroperitoneal lymph nodes. The primary lesion and biopsy of the retroperitoneal metastases showed predominance of the Sertoli cell component. The patient was put on chemotherapy.     

Alveolar soft-part sarcoma

Alveolar soft-part sarcoma is a slow-growing but nevertheless malignant soft tissue tumour arising in muscle. It occurs most frequently in young women and often presents as a painless swelling in an upper or lower limb. The swelling, which may have been present for a considerable time, is firm and appears to be well circumscribed but it may recur locally after excision. Blood-borne metastases to the lung are common and this is frequently the mode of presentation. Lymphatic metastases are unusual. The tumour is composed of nests of large cells and the histological appearances may resemble those of a renal adenocarcinoma (hypernephroma). Six new cases of this very rare tumour are presented and the published reports are reviewed.     

Ultrastructural contributions to the study of morphological differentiation in malignant mixed (pleomorphic) tumors of salivary gland

Ultrastructural studies of pleomorphic adenoma have shown a coordinated differentiation of luminal epithelial and modified myoepithelial cells with the latter cells related to processes resulting in the myxochondroid stroma. Five examples of various histologic types of malignant mixed tumor of parotid origin were examined by electron microscopy to see if underlying patterns of tumor cell differentiation and organization matched those of pleomorphic adenoma. Whether they were intracapsular tumors (with or without identifiable pleomorphic adenoma), carcinomas ex pleomorphic adenoma, or a true malignant mixed tumor, all lesions had cell types and organizations either identical to those in pleomorphic adenoma or, as in less-differentiated examples, displayed features suggesting origin from luminal cells, myoepithelial cells, or both. Even the chondroid cells in the true malignant mixed tumor expressed ultrastructural features indicating their epithelial derivation. On the basis of these findings, some alterations to the classification and terminology of the subtypes of malignant mixed tumor are suggested.     

'True' sarcomatoid carcinoma of the renal pelvis. First case report with immunocytochemical study

A case of sarcomatoid carcinoma of the renal pelvis is reported. The neoplasm showed polypoid configuration and was composed exclusively of plump, spindle and pleomorphic cells. Light microscopy did not reveal any epithelial differentiation of the neoplastic cells. Immunoperoxidase staining for keratins and for epithelial membrane antigen was strongly positive in the spindle elements and showed the epithelial nature of the proliferation. The present case suggests that pleomorphic tumors, when occurring in visceral organs, should be carefully sampled and immunocytochemical markers for epithelial and sarcomatous differentiation studied, before diagnosis of carcinosarcoma or sarcoma may be accepted.     

Concurrent metastatic thymic carcinoma and postirradiation sarcoma

We present a case of concurrent metastatic thymic carcinoma and postirradiation sarcoma in the same lobe of the lung in a woman who had received partial resection of thymic carcinoma with chemoradiotherapy 11 years ago. One tumor showed similar histology to the previous carcinoma. The other tumor was a pleomorphic sarcoma, suggestive of a postirradiation sarcoma. Irradiation-induced sarcomas are rare and have not been reported in patients with thymic carcinoma. This case may serve as a model in considering the possibility of postirradiation sarcoma for patients encountering recurrent masses with the history of radiotherapy for thymic carcinoma several years ago.     

Palmar localization of epithelioid sarcoma mimicking Dupuytren's disease

A case of epithelioid sarcoma localized in the palm of the left hand in a 32-year-old woman is reported. The tumor evolved for many years, clinically and microscopically simulating palmar fibromatosis. Epithelioid sarcoma is an uncommon malignant tumor, often misdiagnosed by surgeons and pathologists. It occurs in young patients and is often localized at the upper distal extremity. Microscopically, epithelioid sarcoma shows nodules manifesting fibrous hyaline cores with central necrosis. It contains epithelioid and spindle cells immunoreactive to keratin, epithelial membrane antigen and vimentin. Recurrences, lymph node metastases and lung metastases are frequent. Surgical literature tends to recommend wide "en bloc" excision or amputation, combined or not with adjuvant radiation therapy.     

Surgical treatment for small bowel metastasis of pleomorphic carcinoma 6 months after pulmonary resection

The prognosis of patients with distant metastases of pulmonary pleomorphic carcinoma is poor. We report a case of pulmonary pleomorphic carcinoma patient who underwent surgical resection of small bowel metastasis. A 69-year-old man developed anemia secondary to melena 6 months after right upper lobectomy for pulmonary pleomorphic carcinoma and small bowel metastasis was detected endoscopically. He underwent laparoscopic ileocecal resection and has survived for 2 years after lung cancer resection without any other recurrence or metastasis.     

Giant submandibular gland tumor: mucoepidermoid carcinoma within the pleomorphic adenoma (mixed tumor)

Pleomorphic adenoma (mixed tumor) is the most common type of salivary gland tumors, most often involving the parotid glands. The study presented a case of a giant pleomorphic adenoma of the submandibular gland in a 78-year old woman. Due to the initially slow and progressive growth (during a period of 25 years) without treatment, the tumor attained a size of 25×19×16 cm and a weight of 4 kg. The patient underwent surgery. The histopathological examination showed that the tumor was subject to malignant transformation: within the pleomorphic adenoma one observed mucoepidermoid carcinoma lesions of high-degree malignancy. In spite of the good postoperative esthetic and functional effect the patient was diagnosed with distant metastases to the lungs.     

Long-term results of surgical resection of lung metastases

Between 1990 and 2000, 56 consecutive patients underwent lung resection for removal of metastatic disease. Mortality, disease-free interval, and overall survival were studied. Only patients with a complete follow-up were included and data were collected conform the protocol of the International Registry of Lung Metastases. The primary tumour in our series was an epithelial tumour in 25 patients (45%), sarcoma in 15 (27%), germ cell tumours in 11 (19%) and melanoma in 5. Operative mortality was 1.4% (1 out of 73 procedures). Germ cell tumours had the best survival (76% at 5 years), and melanoma the worst (0% at 5 years). Multivariate analysis showed that survival for patients who underwent 2 or more metastasectomies was surprisingly good with a 5-year survival rate of 46%. Survival was not related to disease-free interval, multiple lung metastases, or pneumonectomy. It is in accordance with some reports that a short disease-free interval, numerous lung metastases, or recurrence after the first metastasectomy should not preclude patients from operation.     

The value of prognostic factors in patients who underwent a resection of pulmonary metastases

155 patients were operated on pulmonary metastases in Jena during the period from 1.1.1984 to the 31.12.1994. The findings of 151 patients were analysed. 128 patients suffered from a carcinoma, 15 from a sarcoma, 6 from a malignant melanoma and 2 from a Wilms-tumor. The prognostic factors discussed in the international publications at present were investigated in those patients. Significant differences in the long-term survival were found for the following features: a possible radical resection, the tumor entity, the site, the histology and the grading of the primary tumor, the size and the site of the metastases and the resection of recurrent metastases. Tendencies are described for the type of dissemination and the staging of the primary tumor, the site of the pulmonary metastases in the lung lobes, solitary extrapulmonary metastases and more than 6 lung metastases. In addition patients who showed metastases of a renal cell carcinoma are considered separately.     

Pleomorphic carcinoma of the lung arising in a patient with Li-Fraumeni syndrome: Report of a case

We herein report the case of a patient with Li-Fraumeni syndrome (LFS) who developed lung pleomorphic carcinoma. A 28-year-old female patient with a family history of early-onset malignancies was diagnosed with lung carcinoma and treated by surgical resection. Histological examination revealed a heterogeneous tumor with epithelial and mesenchymal components. The final pathological diagnosis was pulmonary pleomorphic carcinoma. In this patient, a constitutional mutation at codon 213 in exon 6 of the p53 gene was identified in the peripheral lymphocytes and the resected tumor, and LFS was suspected. This mutation causes a nonsense mutation (Arg-to-Stop codon) that has been shown to attenuate p53 function. This is the first report of pulmonary pleomorphic carcinoma developing in an LFS patient, and may suggest a relationship between germline p53 mutation and carcinogenesis in pulmonary pleomorphic carcinoma.     

Results and prognostic factors after resection of pulmonary metastases

One hundred and fifty-nine thoracotomies were performed in 122 patients with pulmonary metastases. The patients' ages ranged from 2 to 76 years, and 13 patients were younger than 18 years. The primary tumour was carcinoma in 83 cases, sarcoma in 29 cases and melanoma in 10 cases. The primary tumour in children was osteogenic sarcoma (6 patients), Ewing's sarcoma (2 patients) and Wilms' tumour (2 patients). With a minimum follow-up of 2 years, an actuarial 5-year survival rate of 38% was observed for carcinoma and 28% for sarcoma. Four of the children survived disease-free for 3 years or more after pumonary metastasectomy. The primary tumour in these cases was osteogenic sarcoma and Ewing's sarcoma. A statistically significant difference in survival was found between the groups of carcinoma and sarcoma, but the prognosis for melanoma patients was markedly worse. In carcinoma patients the main prognostic factor was the duration of the disease-free interval. The actuarial postthoracotomy survival in patients with osteogenic sarcomas was 31% at 5 years, and 18% at 5 years in soft-tissue sarcomas. The size of the lesions, activity and disease-free interval correlated with survival in the osteogenic sarcoma group, and the number of lesions in the soft-tissue sarcoma group. An aggressive surgical approach towards pulmonary metastatic disease thus appears to be justified.     

Pleomorphic carcinoma of the lung; report of a case

Pleomorphic carcinoma is a rare primary lung cancer with a poor prognosis. We report a surgically treated case of pleomorphic carcinoma of the lung. An abnormal shadow was incidentally detected by computed tomography (CT) scan for an 80-year-old male. CT scan performed 1 month before the detection of tumor was normal. Right upper lobectomy with ND2a was performed after 5 months follow-up by CT scan because of the enlargement of the tumor. Histological examination showed numerous atypical spindle cells with massive necrosis, diagnosing as pleomorphic carcinoma. Only 2 months after operation, multiple metastases to the lung, chest wall, pleura, and small intestine were found.     

Malignant mesothelioma of the pleura: relation between histological type and clinical behaviour.

The differing clinical behaviour of malignant mesothelioma of different cell types was studied in 115 cases of pleural mesothelioma, classified histologically into epithelial (60), sarcomatous (25), and mixed (30). Epithelial mesotheliomas were associated with clinical features characteristic of carcinomas rather than sarcomas, including spread of tumour by direct extension, large pleural effusions, contralateral pleural effusions, ascites, metastases in regional lymph nodes, and occasional response to radiotherapy. Sarcomatous mesotheliomas were associated with clinical features more characteristic of sarcomas, with more frequent distant metastases, little or no effusion, and shorter survival. Mixed tumours had features of both, large pleural effusions occurring as frequently as with epithelial tumours, but survival being almost as poor as in sarcomatous cases. Despite these differences there is evidence from published reports that epithelial, sarcomatous, and mixed mesotheliomas have a common origin from mesothelial cells or their precursor cells.     

A report of two cases of Werner's syndrome and review of the literature

Two cases of Werner's syndrome are reported. The first case is that of a man with grey hair since his 20s, and alopecia since aged about 50 years. At the age of 53 years, Werner's syndrome was diagnosed, along with a malignant soft tissue tumour of the hand. The patient underwent ray amputation for the tumour. The subsequent histopathological diagnosis was synovial cell sarcoma, and the patient died of lung metastasis at 15 weeks postsurgery. The second case is that of a woman diagnosed with diabetes mellitus when aged 34 years. At 39 years, a bilateral cataract was diagnosed and at 40 years, diabetic gangrene of the left calcaneal region and calcaneal osteomyelitis necessitated left below-knee amputation. The incidence of Werner's syndrome in Japan is extremely high (1000 of the around 1300 cases reported worldwide) compared to other countries. Most patients develop malignant tumour or arteriosclerosis, the most important complications of this syndrome. The average life expectancy for patients with Werner's syndrome is 46 years. The incidence of epithelial cancer and mesenchymal sarcoma is 10 times that of the general population. The onset of symptoms of Werner's syndrome generally precedes any later symptoms of associated conditions, such as malignant tumour. Therefore, early recognition of Werner's syndrome is important to assist identification of malignant tumours at an early stage in this patient group.