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Background. Smooth muscle tumors presenting as mediastinal soft tissue masses are extremely rare and often are mistaken for other neoplastic conditions. Methods. Ten cases of patients with malignant smooth muscle tumors presenting as mediastinal soft tissue masses were studied and correlated with their clinical behavior. Tissues were examined histologically and with immunohistochemical stains in all cases, and by electron microscopy in two cases. Results. The patients' ages ranged from 26 to 71 years (mean, 56 years); three were women, and seven were men. Three cases were located in the anterior mediastinum and seven in the posterior mediastinum. The patients with anterosuperior mediastinal tumors all presented with signs and symptoms referable to their lesions; the patients with posterior mediastinal masses (with the exception of one) were all asymptomatic. Grossly, the lesions were well circumscribed and unencapsulated, ranging from 6 to 18 cm in greatest dimension and showed a homogeneous, rubbery cut surface with prominent cystic and myxoid areas. The tumors in all patients appeared to arise from the soft tissues within the mediastinum and were unrelated to adjacent structures. In three patients, the tumors compressed and displaced the esophagus without infiltrating its wall, and in one patient, the tumor was found in close proximity, although unattached, to a large vessel. Histologically, the lesions exhibited a spectrum of morphologic appearances that ranged from low grade leiomyosarcoma with mild-to-moderate nuclear atypia and low mitotic activity < 3/10 high power fields [HPFs]), to high grade tumors with marked nuclear pleomorphism, extensive areas of necrosis, and high mitotic activity (> 10 mitoses/10 HPFs). One case was characterized by a striking epithelioid morphology with large, round cells arranged in small clusters; another was associated with an incidental microscopic focus of thymic seminoma in the adjacent thymus. Immunohistochemical stains in all cases showed positive labeling of the tumor cells with smooth muscle actin, desmin, and vimentin antibodies. Electron microscopy in two cases showed features of smooth muscle differentiation, i.e., spindle cells surrounded by basal lamina material, immature cell junctions, and abundant intracytoplasmic filaments with focal condensations. All patients were treated with surgical excision. On follow-up, three patients with Stage IIIb and IVa tumors died 2-7 years after surgery, and two patients with Stage Ib and IIb were alive and well 4 and 6 years after surgery, respectively. Conclusion. Leiomyosarcomas may arise as primary tumors originating from mediastinal soft tissues in both anterior and posterior compartments. Because of their large size and frequent areas of cystic and myxoid degeneration, they may be confused histologically with neural or other neoplasms. As with their counterparts in other soft tissue locations, histologic grade and clinical stage are the most useful parameters for assessing prognosis. Cancer 1994; 74:2251-60.

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 Ill 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. Key words: pleomorphic carcinoma, giant cell carcinoma, spindle cell carcinoma, sarcomatoid carcinoma.

Background. Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare. Methods. Eight patients with primary lung neoplasms showing light microscopic and immunohistochemical features of salivary gland-type mixed tumors were studied. Results. The patients were six women and two men, ages 35-69 years (mean, 52.5 years). The tumors ranged from 2 to 16 cm in greatest diameter. In two patients the lesions presented as polypoid endobronchial lesions obstructing the lumen; in another two patients the lesions were found in close proximity or in continuity with a bronchus; in three patients, the lesions presented as peripheral parenchymatous nodules unrelated to a bronchus; and in one patient, the relationship to the bronchus could not be determined. Histologically, the lesions were biphasic, showing admixtures in varying proportions of epithelial elements containing a predominant myoepithelial cell population with a stromal component containing an abundant myxoid or focally chondroid matrix. Immunohistochemical studies showed strong positivity of the cells in the epithelial component with low molecular weight keratins (CAM 5.2), and to a lesser extent with broad spectrum keratin, actin, and vimentin antibodies. The cells also showed variable reactivity in the epithelial and nonepithelial elements with S-100 protein and glial fibrillary acidic protein. Six tumors were grossly and histologically benign; in two patients, the tumors were larger, locally invasive, and showed more atypical histologic features. All patients were treated with surgical excision. On follow-up, of the six patients with histologically benign-appearing tumors, one was alive and well 6 years after surgery; another died 4 years after surgery of a second unrelated malignancy; one died during the immediate postoperative period of myocardial infarction; and three have been lost to follow-up. In the two patients with histologically atypical lesions, the tumors recurred and metastasized after 2 and 3 years, respectively, with one of them leading to death caused by widespread metastases and superior vena cava syndrome. Conclusions. Review of the literature and the findings in the current series indicate that salivary gland-type mixed tumors of the lung may present with a spectrum of histologic features and clinical behavior, ranging from benign to frankly malignant, similar to that observed for their salivary gland counterparts. Size of the lesion at the time of presentation, extent of local infiltration, and degree of mitotic activity appear to be the most reliable prognostic features of these tumors. Cancer 1994; 73:2481-90.

Background. The spectrum of pulmonary fibrohistiocytic lesions (PFL) ranges from benign fibrohistiocytoma or inflammatory pseudotumor, fibrohistiocytic type (IP), to fibrohistiocytic lesions of borderline malignant appearance (B), to unequivocal malignant fibrous histiocytoma (MFH). The authors reviewed a spectrum of PFL in an attempt to define their natural history and establish independent factors of prognostic significance. Methods. Thirty-one fibrohistiocytic lesions were analyzed by multiple clinical, gross, and microscopic factors. Prognostic factors were evaluated by univariate and multivariate Cox proportional hazards models. Results. After histopathologic review, the cases were classified into IP (15 cases), B (3 cases), and MFH (13 cases). IP tended to occur in younger patients (median age, 30 years; range, 11-64 years) than did MFH (median age, 54 years; range, 12-81 years) (P = 0.03). All 15 patients with IP and 3 patients with B survived. Local recurrence developed in 2 patients with IP and 6 patients with MFH. Distant metastases occurred in 7 patients with MFH. Eight of 13 patients with MFH died of disease, with a median survival time of 16 months (range, 6-36). For all pulmonary fibrohistiocytic lesions, univariate Cox regression analysis disclosed several statistically significant prognostic factors associated with mortality: metastasis (P = 0.0005), significant necrosis (P = 0.0015), local recurrence (P = 0.003), bizarre giant cells (P = 0.0282), mitoses greater than or equal to 3 per 50 high-power fields (P = 0.0286), stage at surgery (P = 0.002), high cellularity (P = 0.0267), and poor circumscription (P = 0.0294). Other parameters (age, sex, symptoms, laterality, location, atypical mitoses, nuclear pleomorphism, degree of fibrosis, and size) were not significant prognostic factors. By multivariate Cox regression analysis, metastasis was the most significant individual parameter (P = 0.002), overriding all other prognostic factors. With metastasis removed from the model, local recurrence (P = 0.0199) and necrosis (P = 0.037) were the other significant independent prognostic factors. Conclusions. Certain individual clinical, gross, and microscopic features have prognostic relevance in determining survival time in pulmonary fibrohistiocytic lesions. Cancer 1994; 73:1817-24. Key words: lung, inflammatory pseudotumor, plasma cell granuloma, fibrohistiocytoma, malignant fibrous histiocytoma, Cox proportional hazards model, survival, prognostic factors.

Background. Adenoid cystic carcinoma (ACC) is a rare but distinctive salivary gland-type malignant neoplasm that arises infrequently as a primary tumor in the lung. Methods. The clinical and pathologic features in 16 cases of primary ACC of the lung were reviewed, and immunohistochemical stains on paraffin sections were performed in 7 cases. Results. The patients' ages ranged from 29 to 79 years (mean age, 54 years); 11 were men and 5 were women. Clinically, most patients were seen initially with obstructive symptoms, including cough, wheezing, shortness of breath, and hemoptysis. Eight tumors were in the left lung and eight in the right lung. The lesions were treated by pneumonectomy in seven patients, lobectomy in six, and lobectomy plus chemotherapy in two. One patient was treated with chemotherapy alone after undergoing a diagnostic biopsy that revealed advanced disease. Grossly, most lesions were described as endobronchial and measured from 0.9 to 4.0 cm in greatest dimension; two cases, however, showed poorly circumscribed infiltrative tumors. Histologically, three main growth patterns were identified admixed in various proportions: cribriform (cylindromatous), tubular, and solid. Immunohistochemical study in six of seven cases showed a prominent myoepithelial cell component, as evidenced by immunoreactivity for keratin, actin, and S-100 protein in numerous tumor cells. Clinical follow-up ranging from 2 to 15 years in six patients showed that three were alive and well without evidence of recurrence or metastases at 5, 10, and 12 years, respectively, and three were alive with recurrence at 2, 5, and 15 years, respectively. Three other patients died of unrelated conditions at 2, 7, and 9 years, respectively, after diagnosis. Two patients in the study were seen initially with metastatic spread at the time of initial diagnosis and died 2 months and 1 year later with widespread metastases to lymph nodes, liver, spleen, kidney, and bone despite intensive chemotherapy. Conclusions. Disease stage at the time of diagnosis may play an important role in predicting the clinical outcome of patients with these tumors. Despite their generally slow and indolent growth in other locations, ACC arising in the lung may in certain cases be more aggressive. Cancer 1994; 73:1390-7.

Background. Paragangliomas of the mediastinum are rare neoplasms. Because of their rarity, the spectrum of morphologic and immunohistochemical features and biologic behavior of these tumors in this location has not been delineated. Methods. A retrospective study of 16 cases of mediastinal paragangliomas was undertaken to evaluate their clinicopathologic and immunohistochemical features. Results. The patients were 10 men and 6 women whose ages ranged from 16-69 years of age (mean, 42.5 years). Twelve tumors were located in the posterior mediastinum, and three tumors were located in the anterior mediastinum. In one case, the exact location of the tumor within the mediastinum was not available. Microscopically, the nesting pattern (zellballen) was the most commonly encountered. Areas of stromal hyalinization were also frequent and were marked in two tumors. In two cases there was a prominent spindle cell component, and two cases showed granular cell changes in the cytoplasm of the tumor cells. Cellular pleomorphism was observed in the majority of cases. Occasional mitoses were seen in a few cases. Immunohistochemical studies in 10 cases showed chromogranin reactivity in 10 of 10 cases, S-100 protein in 9 of 10 cases, leu-enkephalin in 6 of 10 cases, and neurofilament protein in 5 of 10 cases. Keratin was negative in all cases studied. All patients underwent surgical resection of their tumors, and one patient underwent adjuvant radiation therapy. Follow-up information ranging from 1-168 months (mean, 84.5 months) was obtained in 12 patients. Nine patients (75%) were alive and well at last follow-up. In one patient the tumor metastasized to spinal space and bone marrow, and another patient died with metastases to lymph node, lung, and pelvis 14 years after initial diagnosis. Conclusions. The only parameter found to correlate with aggressive behavior was the extent of circumscription and/or local infiltration of the tumor at initial resection. No clinical, histologic, or immunohistochemical features were otherwise found to separate aggressive from indolent clinical behavior. Regular follow-up is recommended in these patients due to the potential for these tumors to metastasize.