Primary intrapulmonary thymoma. A clinicopathologic and immunohistochemical study of eight cases.

We describe eight cases of primary intrapulmonary thymoma occurring in seven women and one man between the ages of 25 and 77 years. Clinically, all patients had initial radiographic findings of a parenchymatous intrapulmonary mass without evidence of mediastinal involvement either radiologically or at surgery. The lesions varied from 0.5 to 10 cm in greatest diameter. Five tumors were located close to the hilum, while the other three were discovered deep within the lung and in subpleural locations. In one case, the lesion appeared to arise endobronchially and infiltrate the surrounding parenchyma. In another case, in addition to the main hilar mass, there were two smaller tumor nodules found deep within the same lung. Histologically, the lesions were characterized by the classic biphasic cellular composition of thymomas, i.e., an admixture in varying proportions of epithelial cells and lymphocytes. Four cases were characterized by sheets of lymphocytes admixed with scattered epithelial cells that were separated by fibrous bands into lobules. Three cases were composed predominantly of sheets of epithelial cells admixed with scattered small lymphocytes and containing prominent perivascular spaces. In two of these cases, focal areas of spindling of the cells were noted. One case was composed predominantly of a spindle cell proliferation with perivascular spaces and numerous small lymphocytes. Immunohistochemical stains for keratin and epithelial membrane antigen in six cases highlighted the epithelial cells scattered against the lymphoid cell background. Seven patients were treated by surgery. In one patient the tumor was deemed inoperable at the time of exploration owing to extensive pleural infiltration and was treated by postoperative radiation; the lesion recurred locally in the pleura 8 years later. Clinical follow-up in three patients after surgical incision showed them to ba alive and well without evidence of disease at 10 months, 2 years, and 8 years, respectively. Two of the patients had been followed clinically for 2 and 4 years following discovery of their lung masses on routine chest radiograph before resection of their tumors. Two patients died of unrelated conditions; in one of them, the lesions had been followed clinically for 6 years before surgery; this patient died 6 months later from coronary artery disease, without evidence of recurrence or metastasis. Our findings suggest that intrapulmonary thymomas are slow-growing tumors that may respond well to surgical resection when confined to the lung. As with their mediastinal counterparts, invasive tumors will require additional treatment for the possibility of recurrence of metastasis.

Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases.

We present 25 cases of a primary pulmonary sarcoma bearing histological, immunohistochemical, and ultrastructural features indistinguishable from those of monophasic synovial sarcoma of soft tissue. The patients were 11 men and 14 women between the ages of 16 and 77 years. Clinically, the most common symptoms were chest pain, cough, shortness of breath, and hemoptysis. The lesions involved all lung segments. Grossly, they varied in size from 0.6 to 20 cm and were described as soft to rubbery tumors with areas of necrosis and hemorrhage, some with cystic changes. Two lesions involved the bronchial wall and in one case the tumor was described as encircling the bronchial tree. Histologically, all of the lesions were characterized by an atypical spindle cell proliferation with a solid growth pattern. Areas of myxoid, neural, hemangiopericytic, and epithelial-like growth pattern were observed. Mitoses, necrosis, and hemorrhage were seen in all lesions in varying proportions. Immunohistochemical studies for epithelial membrane antigen (EMA) and keratin showed strong focal positivity in 25 of 25 and 23 of 25 lesions, respectively. Immunohistochemical study for vimentin showed diffuse strong positivity in all lesions. Other immunostains, including desmin, smooth muscle actin, and S-100 protein, were negative. Electron microscopy in three cases showed spindle cells with elongated nuclei containing abundant cytoplasmic rough endoplasmic reticulum and well developed desmosome type intercellular junctions. Follow-up information ranging from 2 to 20 years was obtained in 18 patients. Six patients died of their tumors, whereas four patients died of unrelated causes without evidence of recurrence or metastases. Eight patients were alive with disease (recurrence and/or metastases) from 1 to 7 years after diagnosis. Four patients were alive and well without evidence of recurrence or metastases from 2 to 20 years (mean follow-up, 12.5 years). The present group of lesions appears to constitute a distinctive and as yet previously undescribed primary sarcoma of the lung, which probably represents the visceral counterpart of monophasic synovial sarcoma of soft tissue in a pulmonary location. Because of their distinctive biology these lesions should be distinguished from a variety of primary and metastatic malignancies of the lung.

The spectrum of immunohistochemical staining of small-cell lung carcinoma in specimens from transbronchial and open-lung biopsies.

Immunohistochemistry is increasingly used as an aid in the diagnosis of small-cell lung carcinoma (SCLC). Previous studies have investigated immunohistochemical staining of SCLC with small numbers of antibodies, but few have examined large series with a broad panel of antibodies. For this reason, the authors examined the distribution and intensity of staining of 20 open-lung biopsy (OLB) and 21 transbronchial biopsy (TBB) specimens of SCLC with a panel of epithelial, neuroendocrine, and hormonal markers. Small-cell lung carcinoma stained most frequently with epithelial markers, followed by neuroendocrine and hormonal markers. Similar percentages of OLB and TBB specimens stained for keratin (100% each) and epithelial membrane antigen (100% and 95%, respectively). Unexpectedly, BER-EP4 stained 100% of OLB specimens. Chromogranin A was the most frequent neuroendocrine marker in OLB and TBB specimens (60% and 47%, respectively) followed by neuron-specific enolase (60% and 33%), Leu-7 (40% and 24%), and synaptophysin (5% and 19%). No neuroendocrine immunohistochemical reactivity was found in 24% of TBB specimens and 20% of OLB specimens. Bombesin was the most sensitive hormonal marker (45% of OLB specimens). These results show that keratin, epithelial membrane antigen, and BER-EP4 are reliable epithelial markers for SCLC in both TBB and OLB specimens. In addition, negative staining for neuroendocrine markers, because it can occur in as many as 25% of cases, should not deter the diagnosis of SCLC.

Occult metastatic mesothelioma--diagnosis by fine-needle aspiration. A case report.

Fine-needle aspiration biopsy of an enlarged right axillary lymph node was performed on a 33-year-old woman with Ebstein's cardiac anomaly. Microscopic examination of the cytologic material revealed large discohesive cells with abundant pale cytoplasm, "ruffled" cytoplasmic borders, and prominent central nucleoli. Immunocytochemical analysis of the aspirate confirmed the mesothelial origin of these cells and prompted the diagnosis of metastatic mesothelioma. Autopsy examination revealed a large pericardial mesothelioma with metastases to mediastinal and axillary lymph nodes. This case report demonstrates the usefulness of fine-needle aspiration biopsy in the diagnosis of metastatic mesothelioma.

Extramedullary plasmacytomas presenting as mediastinal masses: clinicopathologic study of two cases preceding the onset of multiple myeloma.

We present two cases of extramedullary plasmacytoma presenting as a mediastinal mass and preceding the onset of full-blown multiple myeloma. The patients are a 62-year-old woman who presented with progressive dyspnea and left-sided chest pain and a 59-year-old asymptomatic man. In both patients, radiographic studies revealed a posterior and anterior mediastinal mass, respectively. Surgical resection of the tumor was performed in the two cases. The tumors were characterized by a well-circumscribed proliferation of plasma cells surrounded by residual lymph nodal tissue. Immunohistochemical studies on paraffin sections demonstrated lambda light chain restriction. Follow-up in our patients revealed that both of them developed multiple myeloma after 6 months and 2 years, respectively. One patient received treatment with melphalan and prednisone and is currently alive and well without evidence of disease, 2 years after diagnosis. The second patient died 4 years after resection of his tumor with evidence of disease in lumbar spine, skull, and lungs. Extramedullary plasmacytoma presenting as a mediastinal mass may precede the onset of full-blown multiple myeloma; therefore, institution of early systemic therapy in these patients may be of value in preventing further progression of the disease.

Thoracic sarcoidosis: radiologic-pathologic correlation.

Sarcoidosis is a systemic disease of unknown etiology with variable presentation, prognosis, and progression. At diagnosis, about 50% of patients are asymptomatic, 25% complain of cough or dyspnea, and 25% have skin lesions (erythema nodosum, lupus pernio, or plaques or scars) or eye symptoms (or develop them during the course of the disease). Bilateral hilar adenopathy is the most common radiographic finding. Other characteristic findings include interstitial lung disease, occasional calcification of affected lymph nodes, and pleural effusions and thickening. Computed tomography is more sensitive than radiography in the detection of adenopathy and subtle parenchymal disease; gallium-67 scintigraphy is useful in identifying extrathoracic sites of involvement, detecting active disease, and assessing response to treatment. The diagnosis is established most securely when clinicoradiologic findings are supported by histologic evidence of widespread noncaseating granulomas. The disease ranges from a self-limited subclinical process to chronic debilitation and death, with the major complications being fibrosis, mycetoma formation, and cor pulmonale. Because the disease so often involves thoracic structures, chest radiography plays a crucial role in the diagnosis, staging, and follow-up of sarcoidosis.

The alphabet soup revisited: the chronic interstitial pneumonias in the 1990s.

Liebow classified the idiopathic interstitial pneumonias as usual (UIP), desquamative (DIP), bronchiolitis obliterans (BIP), lymphoid (LIP), and giant cell (GIP) interstitial pneumonias. This classification was modified to exclude LIP and GIP. UIP, the most common type, is characterized by synchronous foci of inflammation, collagen deposition, and fibrosis with interspersed normal lung. It usually affects men 40-60 years old and manifests radiologically with bilateral, basilar irregular opacities and volume loss. In most cases, a confident diagnosis can be made at high-resolution computed tomography because of characteristic subpleural irregular linear opacities, ground-glass opacities, honeycombing, and traction bronchiectasis. DIP affects younger patients and is characterized by diffuse intraalveolar macrophage aggregation. Typical radiologic features include bilateral, basilar ground-glass opacities and preserved lung volumes. BIP, renamed bronchiolitis obliterans with organizing pneumonia, affects middle-aged patients and manifests with multifocal plugs of immature fibroblasts in the air spaces. Typical radiologic features include bilateral consolidations and normal lung volumes. Recently described entities include acute (AIP) and nonspecific (NIP) interstitial pneumonias and respiratory bronchiolitis with interstitial lung disease (RB-ILD). AIP is a rapidly progressive, often fatal, illness characterized by diffuse alveolar damage and manifests with clinical and radiologic features of adult respiratory distress syndrome. NIP is a heterogeneous group of fibrosing disorders that cannot be otherwise classified. RB-ILD is a disease of smokers with a good prognosis.

Castleman disease of the thorax: radiologic features with clinical and histopathologic correlation.

PURPOSE: To correlate the radiologic manifestations of thoracic Castleman disease with the clinical and histopathologic features. MATERIALS AND METHODS: The clinical, surgical, and histopathologic records; chest radiographs; and computed tomographic (CT) and magnetic resonance (MR) images in 30 pathologically proved cases of thoracic Castleman disease were reviewed. RESULTS: Patients with localized Castleman disease (n = 24) typically had the hyaline-vascular type (n = 23), were asymptomatic (n = 14), and had solitary, well-circumscribed mediastinal masses (n = 24). All lesions at contrast material-enhanced CT (n = 13) enhanced. All lesions at MR imaging (n = 5) were heterogeneous and had increased signal intensity on T1- and T2-weighted images. Three patterns were observed on CT or MR images in 20 patients: a solitary, noninvasive mass (n = 10); a dominant infiltrative mass with associated lymphadenopathy (n = 8); or matted lymphadenopathy without a dominant mass (n = 2). Patients with disseminated Castleman disease (n = 6) typically had the plasma cell type (n = 4), were symptomatic at presentation (n = 5), and had bilateral mediastinal masses on chest radiographs (n = 4). At CT, all lesions manifested with diffuse mediastinal lymphadenopathy. All lesions at contrast-enhanced CT (n = 5) enhanced. CONCLUSION: Localized Castleman disease manifests as either a solitary, well-circumscribed mediastinal mass or an infiltrative mass with associated lymphadenopathy on CT or MR images. Disseminated Castleman disease manifests with diffuse mediastinal lymphadenopathy.

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

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.

Comparison of DNA topoisomerase II alpha expression in small cell and nonsmall cell carcinoma of the lung. In search of a mechanism of chemotherapeutic response.

BACKGROUND: Small cell carcinoma of the lung (SCLC) is distinguished from nonsmall cell carcinoma (NSCLC) by its exquisite initial sensitivity to chemotherapy. Antineoplastic drugs effective against SCLC include doxorubicin, etoposide, and others. Recently, the molecular target of these drugs has been identified as the alpha form of DNA topoisomerase II, which is important in DNA replication and in the separation of chromosomes during normal cellular division. In this study we compared DNA topoisomerase II alpha expression in SCLC and NSCLC by immunohistochemistry. We hypothesized that the sensitivity of SCLC and relative insensitivity of NSCLC to these chemotherapeutic agents stem from different frequencies of DNA topoisomerase II alpha expression. METHODS: DNA topoisomerase II alpha expression was analyzed in 17 cases of SCLC and 24 cases of NSCLC by immunohistochemistry utilizing a monoclonal antibody recognizing the alpha isoform of DNA topoisomerase II. A topo II index was determined by dividing the number of tumor nuclei expressing DNA topoisomerase II by the total number of tumor nuclei counted. RESULTS: A significantly higher frequency of DNA topoisomerase II alpha expression was identified in SCLC (P < 0.001). The average topo II index for SCLC was 0.60 (range: 0.45-0.76) compared with NSCLC, 0.31 (range: 0.05-0.75). CONCLUSIONS: We conclude that DNA topoisomerase II alpha is expressed at a higher frequency in SCLC than in NSCLC, and that this expression is possibly involved in the response of SCLC to chemotherapeutic agents.