Vein patch angioplasty with non-penetrating titanium clips. Comparison to standard suture technique.

Our purpose was to compare the Vascular Closure Staples (VCS) clips to a standard suture technique for vein patch angioplasty in a porcine model. Six female pigs underwent vein patch angioplasty of the common iliac arteries with either VCS clips or continuous suturing. The reconstructed vessels were evaluated macroscopically, angiographically and histologically after two months by re-operation. There was a non significant trend towards shorter reconstruction (6.5 +/- 1.8 min. for clips vs. 8.5 +/- 1.7 min. for sutures, p = 0.15) and clamp times when clips were used (8.4 +/- 1.5 min. vs. 10.1 +/- 1.3 min., p = 0.15). At re-operation all vessels were found patent without significant histological differences regarding the intimal reaction. VCS clips are a reliable alternative to sutures for vein patch angioplasty.

Arterial repair with synthetic patch by using titanium clips.

BACKGROUND: Vascular closure staple (VCS) clips made of titanium were originally developed for microvascular anastomoses. There is limited experience with their applicability to vascular reconstruction in larger vessels. This study compares VCS clips to standard sutures in arterial repair using a synthetic patch. METHODS: In an experimental study with pigs, two sequential 10-mm abdominal aortotomies were allocated randomly to synthetic patch (polytetrafluoroethylene) repair with VCS clips or continuous 6-0 polypropylene sutures. Angiographic, macroscopic, and microscopic results were assessed after 2 months. RESULTS: There were no significant differences in the patency rate, vessel diameter at the repair site, or healing indices. The mean (SD) clamp time was 8.7 (3.0) minutes for clip repair and 14.3 (7.4) minutes for suture repair (p = 0.04), and the times required for the vessel reconstruction were 5.3 (1.3) and 9.3 (3.0) minutes, respectively (p = 0.009). CONCLUSION: Patched arterial repair with VCS clips is faster than sutured reconstruction with comparable results after 2 months of follow up.

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.

Ureteral repair with titanium staples: comparison with suture closure.

OBJECTIVES: Vascular closure staple (VCS) clips made of titanium were initially developed for microvascular anastomoses with little knowledge of their effectiveness in larger tubular tissue structures. This study compares VCS clips and sutures in the closure of longitudinal ureterotomy incisions. METHODS: In 9 pigs, 1-cm-long anterior, longitudinal ureterotomy incisions were randomly assigned to closure with either 4-0 interrupted polyglactin sutures or VCS clips. RESULTS: Clip closure was significantly faster (74+/-28 versus 534+/-182 seconds). All 18 ureters were patent and without signs of leakage, calculus formation, or stenoses after 3 months. Clip closure resulted in slightly but not statistically significantly less narrowing of the duct lumen, but there was no difference in wall thickness at the repair site. At histologic examination, all 18 incisions healed without signs of acute inflammation or marked fibrosis. CONCLUSIONS: Ureterotomy closure with VCS clips results in wound healing that is as effective as suture closure, with a comparable degree of narrowing. The time required for clip closure is only about 1/7 that required for suture closure.

Arterial reconstruction with vascular clips is safe and quicker than sutured repair.

BACKGROUND: Non-penetrating, arcuate-legged vascular-closure staple clips made of titanium were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare vascular-closure staple clips to sutured anastomoses in common iliac arteries in a porcine model. METHODS: In an experimental study, transected iliac arteries on both sides of 11 pigs were randomly assigned to end-to-end anastomosis performed with vascular-closure staple clips or interrupted 6-0 polypropylene sutures. Angiographic, macroscopic and microscopic results were assessed after 2 months. RESULTS: There was no significant difference in the patency rate, tensile strength of the anastomoses, vessel diameter at the repair site, intimal thickness or wall thickness of the arteries after either method of closure. The mean (s.d.) clamp time was 19.8 (6.1) minutes for clip repair, and 36.0 (6.9) seconds for suture repair (P < 0.001). The times required for the reconstruction of the anastomoses were 17.4 (6.1) and 35.5 (7.1) minutes, respectively (P < 0.001). CONCLUSIONS: Arterial anastomoses performed with vascular-closure staple clips are faster than sutured anastomoses, and result in comparable wound healing when assessed for patency, tensile strength, degree of narrowing and intimal reaction.

Arterial and venous repair with vascular clips: comparison with suture closure.

PURPOSE: Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS) clips were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare the VCS clips with standard suture closure of arteriotomies and venotomies in common iliac vessels of pigs. METHODS: In nine pigs, longitudinal 1 cm iliac arterial and venous incisions were repaired with VCS clips on one side and continuous 6-0 polypropylene suture on the other, and the macroscopic and microscopic results were assessed after 3 months. RESULTS: The time required for vessel repair was significantly shorter with clips than with sutures both in arteries (51 +/- 9 vs 414 +/- 36 seconds) and in veins (100 +/- 32 vs 439 +/- 45 seconds). There was no significant difference in the inner diameter, intimal thickness, or intima-to-media height ratios of the arteries or veins after either method of closure. CONCLUSIONS: Repair of 1 cm incisions in small-diameter arteries and veins with VCS clips results in wound healing as good as that achieved with standard suture closure, when assessed for patency, leakage, degree of narrowing, and intimal reaction. The time required for clip closure is considerably shorter than for suture closure.

Common bile duct repair with titanium staples. Comparison with suture closure.

BACKGROUND: Vascular Closure Staple (VCS) clips made of titanium were initially developed for microvascular anastomoses with little experience of their use in larger tubular structures. This study compares VCS clips and sutures in the closure of supraduodenal choledochotomy. METHODS: In nine pigs, two longitudinal incisions of the common bile duct (CBD) were randomly assigned to closure with 4-0 interrupted polyglactin sutures or VCS clips. RESULTS: Clip closure was significantly faster (116 +/- 28 vs 581 +/- 88 s). All nine CBDs were patent and without signs of calculus formation after 3 months. Clip closure resulted in slightly less narrowing of the duct lumen and thinner scar at the repair site. At histological examination, all 18 incisions had healed without signs of fistula formation or marked fibrosis. CONCLUSIONS: Choledochotomy closure with VCS clips results in as good or better wound healing than suture closure, with a comparable degree of narrowing. The time required for clip closure is only about one-fifth that of suture closure.

Pleomorphic (giant and spindle cell) carcinoma is genetically distinct from adenocarcinoma and squamous cell carcinoma by K-ras-2 and p53 analysis.

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.

Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Immunohistochemical and confocal microscopic studies of the localization of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen were made in lung tissues from patients with normal pulmonary histology (n = 3), diffuse alveolar damage (n = 14), and idiopathic pulmonary fibrosis (n = 12). Pretreatment with pepsin revealed otherwise undetectable MMP- and TIMP-immunoreactive sites. In normal lung, MMP-2, MMP-9, TIMP-1, and TIMP-2 were localized in ciliated cells, endothelial cells, pneumocytes, macrophages, and smooth muscle cells; fibroblasts showed a strong reaction only for MMP-2. Only TIMP-2 showed co-localization with type IV collagen. Myofibroblasts and epithelial cells expressed increased reactivity for MMPs and TIMPs in both disorders. The reactivities for MMPs and TIMPs were stronger in diffuse alveolar damage. MMP-2 showed focal co-localization in capillary endothelial and disrupted epithelial basement membranes, suggesting activation of collagenolysis. A protective effect against this lysis was suggested by the extensive co-localization of TIMP-2 with type IV collagen and fibrillar collagens. Alveolar buds showed increased reactivity for MMPs and TIMPs in their lining epithelial cells, myofibroblasts, and their basement membranes; however, their matrices were mostly unreactive. These findings emphasize the complexity of the roles of MMPs and TIMPs in collagen turnover in diffuse alvcolar damage and idiopathic pulmonary fibrosis.

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.

Update on lymphoid interstitial pneumonitis.

Lymphoid interstitial pneumonitis (LIP) involves a clinicopathologic pattern of pulmonary disease characterized by diffuse interstitial reactive lymphoid infiltrates. In adults, it occurs most commonly in autoimmune diseases, such as Sjögren's syndrome (0.9% of these patients) and primary biliary cirrhosis, whereas in children it is usually seen in HIV infection. Dysproteinemias (hyper- and hypogammaglobulinemia) are found in more than 60% of patients. Children can show CD8-lymphocytosis in bronchoalveolar lavage fluid, lung tissue, peripheral blood, and salivary gland, associated with HLA-DR5 haplotype. Radiographically, most patients with LIP have reticulonodular infiltrates, with or without patchy areas of consolidation. CT scans can show both small nodular and ground glass patterns, patterns that are diagnostically nonspecific. Reduced lung volumes and diffusing capacities are consistent and sensitive indicators of disease in LIP. In an experimental model, diffusing capacity was the single most sensitive functional index of disease progression. Microscopically, LIP is part of a spectrum of pulmonary lymphoid proliferations, ranging from follicular bronchitis-bronchiolitis and pulmonary lymphoid hyperplasia (the latter in AIDS patients), proliferations largely limited to airways, to low-grade malignant lymphoma. These patterns may be difficult to differentiate from each other. It appears that LIP sometimes evolves to lymphoma; the frequency of this evolution is probably low but is difficult to assess because low-grade lymphomas may mimic LIP. A relatively high frequency of LIP patients have Epstein-Barr virus DNA in their lungs but not all patients with LIP show this finding, suggesting other possible etiologies.

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.

A quick and simple method to close vascular, biliary, and urinary tract incisions using the new Vascular Closure Staples: a preliminary report.

Traditional suture reconstruction of tubular organs creates a perforating needle injury, leaves suture material on the endothelial or mucosal surfaces, and is cumbersome when done endoscopically. One alternative method of reconstruction of tubular organs could use the new nonpenetrating clip to create an everted closure. In five pigs, a longitudinal incision of the infrarenal aorta, inferior vena cava, left ureter, gallbladder, and the common bile duct (in two) was closed with Vascular Closure Staples (VCS-clips). Four weeks after surgery, all ten blood vessels remained patent with no thrombosis. There was a well-healed wound with continuous intimal layer. The ureteral, gallbladder, and common bile duct wounds healed without leakage or obstruction in all animals. There was complete mucosal bridging of the wound, although in some specimens one or two clips were exposed to the lumen. The VCS-clips are easily and quickly applied and are safe insofar as can be determined by short-term follow-up.

Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome.

Neuroendocrine tumors of lung, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC) constitute a spectrum of malignancies in which the pathologist at times has difficulty in discerning tumor subtype and aggressiveness in a reproducible fashion. Therefore, 59 primary neuroendocrine lung tumors including 10 TCs, 26 ACs, 15 LCNECs, and 8 SCLCs were selected from cases collected from 1976 to 1988 and immunostained for p53 protein. All of these tumors were also genotyped for specific point mutational damage affecting p53 (exons 5, 7, and 8; with ACs additionally sequenced for p53 exon 6); 13 tumors for K-ras-2 (exon 1); and 31 tumors for c-raf-1 (exon 15) growth-regulatory genes. Genotyping was performed on topographically selected, minute tumor samples removed from unstained formalin-fixed, paraffin-embedded tissue sections (topographic genotyping) using polymerase chain reaction and direct sequencing. The distribution of p53 immunohistochemical staining had four patterns: negative in TCs, one-half of ACs, 3 of 15 LCNECs, and 1 of 8 SCLCs; less than 10% but more than five tumor cells per 10 high power fields (focal) in a subset (7 of 26) of aggressive ACs; 10 to 49% of tumor cells (patchy) in a subset (6 of 26) of ACs with a higher grade of aggressiveness; and 50 to 100% of tumor cells (diffuse), exclusively seen in LCNECs (12 of 15) and SCLCs (7 of 8). Three patterns of immunohistochemical staining intensity of p53 protein were seen: negative, weak or mild, and moderate to marked. SCLCs and LCNECs accounted for cases of moderate to marked staining and were the only ones to have mutations in p53 exons 5, 7, or 8. No mutations were found in AC and TC, showing absent to weak staining and no staining, respectively. The difference in distribution and staining intensities between LCNEC and SCLC compared with AC and TC was statistically significant (P < 0.001). Patients having AC with patchy p53 immunostaining usually had survival limited to 3 years, whereas those having AC with focal p53 immunostaining subsequently developed metastatic or recurrence of AC disease (P < 0.05). The absence of point mutations in cases with patchy or focal immunostaining suggests increased expression of wild-type p53 tumor suppressor protein likely in response to growth deregulation in a more aggressive subtype of AC. A novel hypothesis is presented in regard to these findings. K-ras-2 and c-raf-1 gene sequence analysis showed no evidence of point mutational change in any of the tumors studied. The TC and AC categories are therefore genetically distinct from the higher grade neuroendocrine SCLC and LCNEC. Immunohistochemistry for p53 on AC lung tumors may be helpful to delineate cases at higher risk for aggressive behavior. Additionally, although LCNEC is categorized as a non-small-cell carcinoma, it is more akin genetically and immunohistochemically to SCLC.

Pulmonary involvement in systemic lupus erythematosus.

Pulmonary disorders in systemic lupus erythematosus involve a variety of clinical presentations and pathologic patterns, which can be difficult to diagnose due to systemic dysfunction, infection, or complications of therapy. The causes of dyspnea in systemic lupus erythematosus are multifactorial, and the clinical manifestations of lung disease widely vary. Biopsy is frequently relied on to evaluate and diagnose pulmonary disease in systemic lupus erythematosus. The patient who has systemic lupus erythematosus-associated lung disease is effectively treated with various immunosuppressive drugs, in conjunction with careful evaluation of the patient's systemic involvement, drug-induced complications, and the ever-present threat of infection.

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.

Extramedullary hematopoiesis presenting as posterior mediastinal mass: a study of four cases.

We present four cases of extramedullary hematopoiesis occurring in the posterior mediastinum. The patients are two women and two men between the ages of 20 and 87 years. Two patients presented with a history of thalassemia, and one had a history of anemia of undetermined etiology. One patient was asymptomatic, and the posterior mediastinal mass was detected during a routine chest radiographs. Surgical resection of the mass was performed in one patient, whereas a biopsy was performed in the other three. Histologically, all the cases showed the typical features of extramedullary hematopoiesis, namely the presence of numerous lymphocytes admixed with megakaryocytes and red cell precursors. Follow-up information ranging from 2 mo to 3 years showed that all patients are alive and well.

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.

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.

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.