Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute.
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Carcinoid Tumor↗
Biomedical subjects
W D Travis
Publications and source records attributed to W D Travis.
Immunohistochemical study of matrix metalloproteinases and their tissue inhibitors in pulmonary Langerhans' cell granulomatosis.
OBJECTIVE: To evaluate the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of the lesions of pulmonary Langerhans' cell granulomatosis. DESIGN: Immunohistochemical and confocal microscopic studies were made of lung biopsy specimens from five patients with pulmonary Langerhans' cell granulomatosis. RESULTS: The reactivity of Langerhans' cells was moderate to intense for MMP-2, weaker for MMP-9, and faint for TIMP-1 and TIMP-2. Type IV collagen colocalized with MMP-2 in areas of damage to epithelial basement membranes, a finding that emphasizes the potential importance of this enzyme in the pathogenesis of the destructive lesions of pulmonary Langerhans' cell granulomatosis. In the more advanced fibrotic lesions, TIMP-2 colocalized with basement membranes and with fibrillar collagen, suggesting that it contributes to the permanence of the fibrosis. CONCLUSION: These results indicate an important role for MMPs and TIMPs in pulmonary Langerhans' cell granulomatosis.
Adult↗
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.
Antigens, Neoplasm↗
United States lung carcinoma incidence trends: declining for most histologic types among males, increasing among females.
BACKGROUND: Lung carcinoma is now the most frequently diagnosed major cancer in the world and is also the most common cause of cancer deaths in males and females in the United States and worldwide. Based on trends in cigarette smoking and on analysis of lung cancer rates by birth cohort, it was predicted that a decline would occur in age-adjusted lung cancer rates, initially in males, and approximately 10 years later in females. We evaluated age-adjusted lung cancer incidence rates for changes in trends by race, sex and histologic type to determine if and when rates may have started declining. METHODS: We analyzed population-based incidence data from the National Cancer Institute's Third National Cancer Survey conducted between 1969 and 1971 and from the Surveillance, Epidemiology and End-results (SEER) program conducted between 1974 and 1991. Age-adjusted rates were plotted by time period using a logarithmic scale for the ordinate. We used regression methods for grouped time-to-response data to fit a model to the disease rate for age, and calendar year to estimate the calendar year of maximum disease rate. RESULTS: During this period, the overall age-adjusted lung cancer incidence rate rose from 37.8 to 68.2 per 100,000. Lung cancer rates in both white and black males climaxed around 1984 and declined subsequently. Furthermore, among white and black males, the rates of squamous cell carcinoma, small cell carcinoma, and large cell carcinoma declined after peaks in 1981 and 1982, 1986 and 1987, and 1986 and 1988, respectively. The rates for adenocarcinoma in black males peaked in 1987 whereas the rates in white males appeared to have plateaued between 1989 and 1991. Total lung cancer rates in males exceeded those in females, with rates in black males exceeding rates in white males. Age-adjusted lung carcinoma rates among white and black females continued to increase for all histologic types with the exception of large cell carcinoma among whites, bronchioloalveolar carcinoma among whites and blacks, and adenosquamous carcinoma among blacks. CONCLUSIONS: The cumulative effect of these trends has resulted in a plateau of total lung carcinoma incidence in all persons combined, and a decline might be expected soon, as has already been observed among males. Most of these changes reflect past cigarette smoking patterns. Demonstration of declines and tapering increases among several population subgroups suggests impending reductions in the incidence and mortality rate for this highly fatal cancer.
Carcinoma, Non-Small-Cell Lung↗
Post-irradiation malignant mesothelioma.
BACKGROUND: Approximately 30 patients with malignant mesothelioma following radiotherapy have been described. Population-based studies of this occurrence have not been reported. METHODS: Patients with malignant mesothelioma of the pleura were collected. All of the patients had a prior cancer and had received radiotherapy to the region in which the malignant mesothelioma developed. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program and the Connecticut Tumor Registry were evaluated for cases of malignant mesothelioma of the pleura occurring in patients with a previous cancer. The literature on post-irradiation malignant mesotheliomas was reviewed. RESULTS: Eight patients (4 men, 4 women) with malignant mesothelioma occurring in sites of radiotherapy for a prior tumor were identified. The mean age at diagnosis of mesothelioma was 45 years (range: 22-78 years), and the average interval between radiotherapy and the mesothelioma was 21 years (range: 11-29 years). Three of the patients had also received chemotherapy. Histologically, the mesotheliomas were epithelial in five cases, biphasic in one, and sarcomatous in one. One hundred forty-two patients were identified in the epidemiologic survey. The majority were men (89%), with a mean age for all patients of 68.5 years (range: 35-86 years) and a median latency between first cancer and mesothelioma of 4.3 years (range: 2 months-29.9 years). CONCLUSIONS: Mesotheliomas rarely develop as second malignant neoplasms. Within a large, population-based survey of patients with cancer, temporal patterns and demographic features of most second primary mesotheliomas were similar to asbestos-related tumors, although the late effects of cancer treatment might have contributed to the occurrence of cancer in some patients.
Adult↗
Bladder calcifications after photodynamic therapy: analysis of a rare complication.
OBJECTIVES: We analyzed bladder calcifications occurring after photodynamic therapy administered for the treatment of superficial bladder cancer, a finding not previously reported after this treatment. METHODS: Bladder biopsies from 20 patients undergoing photodynamic therapy were evaluated. Bladder calcifications were identified in 2 patients and analyzed for composition. RESULTS: One patient had diffuse microcrystalline deposition in two biopsies composed of calcium oxalate monohydrate A. A second patient had a focal stone at a healing biopsy site composed of monoclinic calcium hydrogen phosphate dihydrate (brushite) (66%), calcium oxalate (25%), hydroxyapatite (6%), and protein (3%). CONCLUSIONS: Rare calcium oxalate and brushite calcifications were identified after photodynamic therapy and presumed to occur because of tissue injury associated with treatment.
Aged↗
Lung tumors with a rhabdoid phenotype.
Six malignant tumors of the lung with a rhabdoid phenotype are described. All presented as lung masses in middle-aged to elderly adults (mean age 51 years), with no sex predilection. The tumors ranged from 1.3 cm to 8.0 cm in size and were generally associated with locally advanced disease. The distinctive (and defining) histologic feature was the presence of macronucleolated tumor cells with a large eosinophilic globular cytoplasmic inclusion. These "rhabdoid" elements comprised at least 10% of the neoplastic population. Immunohistochemistry revealed diffuse vimentin positivity in all cases. Epithelial and neuroendocrine markers were at least focally positive in five and in all six cases, respectively. Electron microscopy was performed in one case and it showed paranuclear aggregates of intermediate filaments, dense core granules, and intercellular attachments. Malignant tumors of the lung with a rhabdoid phenotype are very rare. The majority are poorly differentiated carcinomas, and they frequently show features suggesting a neuroendocrine differentiation.
Adult↗
Calcifying fibrous pseudotumor of pleura. A report of three cases of a newly described entity involving the pleura.
A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissues of the extremities, trunk, scrotum, groin, neck, or axilla. To date, CFPT has not been described in the pleura. The authors reviewed the clinical, radiologic, and pathologic features of three cases. A 23-year old woman and 34-year old man who presented with chest pain, and a 28-year old woman without chest symptoms were found to have a pleural mass on chest radiographs. Computed tomography (CT) scans of each patient revealed pleural-based nodular masses with central areas of increased attenuation due to calcifications. Each lesions consisted of circumscribed, but unencapsulated masses of hyalinized collagenous fibrotic tissue interspersed with lymphoplasmacytic infiltrates and calcifications, many of which had psammomatous features. The lesions were limited to the pleura and did not involve the underlying lung parenchyma. Electron microscopy in one case showed fibroblasts scattered in dense collagenous tissue. Calcifying fibrous pseudotumor is distinct from other pleural lesions such as fibrous tumor of pleura, calcified granulomas, calcified pleural plaques, and chronic fibrous pleuritis as well as intrapulmonary lesions such as hyalinizing granuloma, inflammatory pseudotumor, and amyloid. As in the soft tissues, local excision appears adequate therapy for CFPT of the pleura. If these lesions behave in a similar fashion to CFPT of soft tissues, one might expect a low frequency of local recurrence.
Adult↗
Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X; 18).
The authors report an unusual spindle cell sarcoma that arose in the lung of a 12-year-old girl. This tumor had histologic, immunophenotypic, and ultrastructural features consistent with monophasic fibrous synovial sarcoma. These features included a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin immunoreactivity, and focal expression of epithelial membrane antigen and S100 protein. This diagnosis was further supported by cytogenetic studies showing the specific t(X; 18) chromosomal translocation associated with synovial sarcoma. This balanced translocation appears to be an essentially universal characteristic of these sarcomas, regardless of histologic subtype or site of origin. The constellation of morphologic and cytogenetic findings in this case firmly establishes synovial sarcoma as a subtype of pulmonary spindle cell sarcomas. The distinctive features of these neoplasms allow them to be distinguished from a variety of primary and metastatic malignancies in the lung.
Child↗
Biphasic synovial sarcomas arising in the pleural cavity. A clinicopathologic study of five cases.
Five cases of primary synovial sarcoma of the pleura are presented with a discussion of differentiation from other biphasic malignant neoplasms, most notably malignant mesothelioma. The cases have clinical, histologic, and immunohistochemical features consistent with synovial sarcoma of soft tissue. The average age at initial presentation of the reported patients was 25 years with an approximate range of 9 to 50 years. A large pleural-based intrathoracic mass was identified in each case. Histologic analysis showed a biphasic (mixed) pattern composed of epithelial and spindle cells. The epithelial cells showed cleft-like to tubulopapillary growth with focal intraluminal periodic acid Schiff's (PAS)-positive, diastase-resistant secretions identified in four of the five cases. The spindle cell component was composed predominantly of densely packed, elongated, fusiform cells. Immunohistochemical staining showed positivity with antibodies against cytokeratin, BER.EP4, epithelial membrane antigen, and vimentin in all cases. The patients seem to have an aggressive course, with four deaths reported within 3 years from initial surgery. These cases represent the first reported cases of primary synovial sarcoma of the pleura and lend further credence to the theory that synovial sarcomas are derived from immature mesenchymal elements, not from synovium.
Adolescent↗
Adenomatoid tumors of the pleura.
We report two cases of small pleural nodules showing the distinctive histologic appearance of adenomatoid tumor. Both lesions were discovered incidentally during surgery in patients undergoing lung resection for unrelated intrapulmonary masses: lung carcinoma in one case and histoplasmosis in the other. The tumors were composed of a focal proliferation of epithelioid cells forming vacuoles and tubular spaces in a fibrous stroma, as seen in adenomatoid tumors from other sites. The differential diagnosis in both cases included metastatic signet ring cell carcinoma. The mesothelial nature of the lesions was supported by immunohistochemical and ultrastructural evidence. The tumor cells in both cases were positive for cytokeratin but negative for carcinoembryonic antigen and LeuM1. One case was also negative for BER-EP4, B72.3, CD34, and Factor VIII. Electron microscopy in this case demonstrated well-developed basal laminae, desmosomes, and numerous slender microvilli along the luminal surfaces of the tumor cells. Adenomatoid tumors are regarded as a benign variant of mesothelioma. Despite the abundance of mesothelial cells in the pleura, adenomatoid tumors are apparently extremely rare in this location. Separation from malignant lesions such as adenocarcinoma and epithelioid hemangioendothelioma is important.
Adenomatoid Tumor↗
Sodium polystyrene sulfonate (kayexalate) aspiration: histologic appearance and infrared microspectrophotometric analysis of two cases.
OBJECTIVE: Sodium polystyrene sulfonate (kayexalate) is a cation-exchange resin given enterally for the treatment of hyperkalemia. Aspiration of this material is a rare occurrence, but when visualized in the alveolus, it has a characteristic microscopic appearance that is virtually diagnostic. In two cases, recognition of the characteristic morphology of the foreign material raised the question of sodium polystyrene sulfonate. DESIGN: We used infrared spectroscopy to demonstrate the presence of this material in lung biopsies of two patients by identifying foreign body particles. Histories of the patients were reviewed for exposure to sodium polystyrene sulfonate. SETTING: Two lung specimens were referred to the Armed Forces Institute of Pathology with an unknown foreign material identified within the air spaces. PATIENTS: The lung biopsies were from two children, one postterm female infant who died at 3 days of life and a 4-year-old girl who underwent lung biopsy during surgical repair for tetralogy of Fallot. Both patients had received sodium polystyrene sulfonate previously for control of hyperkalemia. RESULTS: The lung specimens showed characteristic basophilic, amorphous foreign material in airspaces on histologic sections. The identity of this material was confirmed by Fourier transform infrared microspectrophotometry. CONCLUSIONS: To our knowledge, we report the first two cases of sodium polystyrene sulfonate aspiration in children. This material has a distinctive morphologic appearance on histologic sections, and its identity can be confirmed by Fourier transform infrared microspectrophotometry.
Cation Exchange Resins↗
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.
Carcinoid Tumor↗
Simian virus 40 and pleural mesothelioma in humans.
It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification. beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV40 with mesothelioma.
Adult↗
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.
Adolescent↗
Pathology of pulmonary granulomatous vasculitis.
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Biopsy↗
Interstitial lung disease.
Because the list of interstitial lung diseases is so extensive, encompassing more than 180 chronic lung diseases in which the interstitium is altered by inflammation and/or fibrosis, this chapter focuses on several inflammatory lung diseases of unknown etiology: usual interstitial pneumonitis, respiratory bronchiolitis, idiopathic bronchiolitis obliterans with organizing pneumonia, pulmonary Langerhans' cell granulomatosis, hypersensitivity pneumonitis, and lymphangioleiomyomatosis.
Alveolitis, Extrinsic Allergic↗
Vasculitis of the lung.
Many conditions are known to produce vasculitis of the lung but only a few major idiopathic vasculitis syndromes are clinically encountered-- and their diagnosis is very difficult. The authors provide in-depth coverage of these syndromes, focusing on clinical features, pathologic features, and diagnosis and differential diagnosis.
Churg-Strauss Syndrome↗