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Biomedical subjects

F Askin

Publications and source records attributed to F Askin.

At least 19 recordsLinked to original sources
PubMed1999

Congenital cystic adenomatoid malformation of the lung (CCAM): evaluation of the cellular components.

Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital lesion whose pathogenesis is not well defined. It is generally accepted that the various types of CCAMs originate at different levels of the tracheobronchial tree. To further define the pathogenesis of CCAM, we evaluated the cellular composition of different CCAM types by immunohistochemistry. Twenty-two CCAMs (17 CCAM type 1, two type 2, one type 3, and two type 4) were collected. The cellular composition was determined using immunohistochemical stains for type I cell-associated antigen (T1 cell-Ag), surfactant proteins and surfactant protein precursors (SP-A, SP-B, proSP-B, and proSP-C), neuroendocrine cells (GRP), Clara cells (UP-1), and the adhesion molecule CD44v6, a glycoprotein thought to be involved in cell-matrix and cell-cell interactions. Eleven fetal lungs also were analyzed to compare cytodifferentiation of the epithelial-lined cysts of the different types of CCAM with the stages of normal lung development. Our results indicate that CCAM is caused by an arrest in lung development, and, on the basis of cytodifferentiation, two major subtypes can be distinguished. One subtype consisting of CCAM types 1, 2, and 3 that shows a bronchiolar type of epithelium and a second subtype, consisting of CCAM type 4, that has an acinar-alveolar type of epithelium. Our findings also suggest that these two subtypes may arise at different stages of the branching of the bronchopulmonary tree, the first at the pseudoglandular stage and the second at the saccular stage.

Antigens, Neoplasm↗
PubMed1999

Clinical and pathologic predictors of survival in patients with thymoma.

OBJECTIVE: To evaluate the Johns Hopkins Hospital experience with 136 thymomas over the past 40 years. This number of patients allowed quantitative estimation of the independent influence of common clinicopathologic risk factors using multivariate analysis. SUMMARY BACKGROUND DATA: Thymomas vary widely in terms of recurrence and influence on overall survival. Several series have indicated the importance of initial tumor invasion, as well as the extent of surgical resection, as predictors of recurrence and survival after thymoma resection. However, findings have been equivocal when other predictors of prognosis were examined. METHODS: The authors evaluated 136 patients seen at the Johns Hopkins Hospital between 1957 and 1997 with a pathologic diagnosis of thymoma. Demographic information, clinical staging data, surgical and adjuvant treatment details, and patient follow-up data were obtained from the patient record and from detailed patient or family interviews. Microscopic sections of all 136 patients were reviewed by two pathologists blinded to the clinical data. All data were analyzed by multivariate Cox regression analysis, which allowed the quantification of the independent predictive value of 12 putative clinicopathologic prognostic indicators. RESULTS: Completeness of follow-up was 99%, 99%, and 98% of eligible patients at 5, 10, and 15 years, respectively. Forty percent of the patients had associated myasthenia gravis and 27% had a secondary primary malignancy. Overall patient survival rates were 71%, 56%, 44%, 38%, and 33% at 5, 10, 15, 20, and 25 years, respectively. Overall, the thymoma-related mortality rate was 14%; the nonthymoma-related mortality rate was 26%. Incomplete resection, preoperative absence of myasthenia gravis, and advanced Lattes/Bernatz pathologic class were found to be independent predictors of poorer overall survival. CONCLUSIONS: These findings support a policy of aggressive, complete surgical resection of all thymomas when feasible. Thymoma behaves as a rather indolent tumor, with most deaths from causes unrelated to thymoma or its direct treatment. Clinicians should have an increased awareness of the possibility of second primary malignancies in patients with thymoma.

Adolescent↗
PubMed1999

Pulmonary infiltrates after cytokine therapy for stem cell transplantation. Massive deposition of eosinophil major basic protein detected by immunohistochemistry.

Interleukin-2 (IL-2), a product of activated T-cells, is now being used in a number of protocols for cancer immunotherapy. In one stem cell transplantation protocol for breast cancer, IL-2 is used together with interferon-gamma (IFN-gamma) and cyclosporine to stimulate a graft-versus-tumor response and improve the likelihood of a prolonged remission. We present the case of a patient who developed peripheral eosinophilia, perihilar infiltrates, and hypoxemia after autologous stem cell transplantation and the use of recombinant IL-2 and IFN-gamma. Histologic analysis of transbronchial lung biopsies demonstrated a few eosinophils within the bronchial submucosa. Immunostaining using antibodies directed against eosinophil major basic protein (MBP), however, revealed massive extracellular deposition of this toxic granule protein throughout the lung parenchyma. IL-2 therapy is well known to induce a peripheral eosinophilia and to be associated with the capillary leak syndrome characterized by weight gain, edema, and oliguria. The findings noted in this case report suggest that the eosinophil activation that accompanies immunologic therapy with IL-2 can result in direct toxicity to the lung and a localized vascular leak syndrome. This syndrome should be considered in the differential diagnosis of pulmonary infiltrates that occur acutely after bone marrow transplantation with cytokine augmentation.

Blood Proteins↗
PubMed1999

Pulmonary manifestations of ulcerative colitis mimicking Wegener's granulomatosis.

We describe 2 patients with quiescent ulcerative colitis who developed clinical syndromes suggesting Wegener's granulomatosis. Both patients had features of systemic illnesses, nodular lung lesions, and antineutrophil cytoplasmic antibodies. Although the inflammatory bowel disease of both patients was quiescent at the time of their pulmonary presentations, lung biopsy results were consistent with pulmonary complications of ulcerative colitis, an unusual manifestation of that disorder. These cases illustrate that pathological confirmation of the diagnosis is essential in cases of suspected vasculitis. The patients' pulmonary lesions resolved promptly after treatment with corticosteroids.

Adult↗
PubMed1995

Congenital cystic adenomatoid malformation of the lung: insights into the pathogenesis utilizing quantitative analysis of vascular marker CD34 (QBEND-10) and cell proliferation marker MIB-1.

Congenital cystic adenomatoid malformation (CCAM) encompasses a spectrum of variably cystic developmental anomalies of the lung histologically characterized by immature lung tissue. The pathogenesis is uncertain, but many investigators favor a maturation arrest in bronchopulmonary development. To investigate this hypothesis, the vascular development and proliferation capacity of lung tissue with CCAM type I from nine infants ranging in age from 20 weeks gestation to 42 days old were studied immunohistochemically utilizing CD34 for the former and MIB-1 for the latter. Both markers were quantitated on an image analysis system. CCAM was hypovascular with a mean vascular index of 20.05% +/- 6.58 compared to 40.06% +/- 4.19 for the age-matched controls (P < 0.000001). The proliferation index of both epithelial and mesenchymal components was higher in CCAM (10.46 +/- 3.48) than in control tissue (7.14 +/- 1.88; P < 0.012). In contrast to the control lung tissue which showed a remarkable synchrony between the vascular development and proliferation throughout the parenchyma, focal asynchrony between the proliferation of the epithelial and stromal components was noted in CCAM. The vascularity in CCAM corresponds to that seen in early gestation. The cellular proliferation in CCAM is higher than in full-term infants and corresponds to late second trimester or early third trimester fetuses. These findings support the proposed pathogenesis of a maturation defect in lung embryogenesis.

Antigens, CD34↗
PubMed1994

Microsatellite alterations as clonal markers for the detection of human cancer.

Microsatellite instability has been reported to be an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. The recent discovery of genetic instability in small cell lung carcinoma, a neoplasm not associated with HNPCC, led us to investigate the possible presence of microsatellite alterations in other tumor types. We examined 52 microsatellite repeat sequences in the DNA of normal and tumor pairs from 100 head and neck, bladder, and lung cancer patients by the polymerase chain reaction. Although alterations were rare in dinucleotide repeats, larger (tri- or tetranucleotide) repeats were found to be more prone to expansion or deletion. We screened 100 tumors with a panel of nine tri- and tetranucleotide repeat markers and identified 26 (26%) that displayed alterations in at least one locus. This observation prompted us to examine the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in pathologic samples. The identical microsatellite alterations detected in the primary tumors were successfully identified in corresponding urine, sputum, and surgical margins from affected patients. This study demonstrates that appropriately selected microsatellite loci are commonly altered in many cancers and can serve as clonal markers for their detection.

Base Sequence↗
PubMed1994

Frequent loss of chromosome 9 in human primary non-small cell lung cancer.

We analyzed the pattern of allelic loss on chromosome 9 in 40 primary human non-small cell lung cancers including 16 squamous cell, 18 adeno-, and 6 large cell carcinomas. Using 24 polymorphic microsatellite markers spanning chromosome 9, we found that 27 of 40 (67.5%) of these neoplasms displayed loss of heterozygosity (LOH) on chromosome 9. Most tumors showed LOH for all informative markers on both chromosomal arms, whereas five tumors demonstrated partial LOH on chromosome 9. In four of these tumors, allelic loss was limited to the 9p arm, whereas in the remaining specimen, LOH extended from 9p21-22 to terminal 9q. These five tumors delineate a minimal area of loss at 9p21-22, which includes a previously defined tumor suppressor gene locus. We have identified a distinct region of loss on chromosome 9p commonly involved in non-small cell lung cancer tumorigenesis.

Aged↗
PubMed1988

Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer.

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.

Carcinoma↗
PubMed1987

Granulocytic sarcoma presenting as pulmonary nodules and lymphadenopathy.

A patient presented with anterior and posterior cervical lymphadenopathy as well as widespread intrapulmonary nodules. Histologic sections of both lymph node and lung revealed dense infiltration by sheets of cells which were cytochemically positive for chloroacetate esterase and myeloperoxidase, thus suggesting a diagnosis of granulocytic sarcoma. The patient was initially treated with daily hydroxyurea. After 6 weeks, when progression of the disease was apparent, hydroxyurea was discontinued and the patient was placed on mithramycin, an agent reported to induce differentiation of myeloid precursor cells both in vitro and in vivo. On this latter agent, a dramatic response has been noted with a decrease in the pulmonary symptoms, and a marked reduction in the size of the lymph nodes and lung nodules. The authors report this case because it represents a rare presentation of an uncommon disease and because of the striking improvement that followed the initiation of a novel therapeutic modality.

Aged↗
PubMed1985

Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones.

This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) had a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regimen I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The mean diameter of the pelvic primaries was comparable to the nonpelvic, however, one half of the pelvic cases were in the range 10-15 cm. The median time to relapse of the 241 non-pelvic patients on IESS I was 222 weeks as contrasted with the median time to relapse of 92 weeks in the 62 pelvic patients on the same study (p = 0.002). The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

Adolescent↗
PubMed1985

S-100 staining in the diagnosis of eosinophilic granuloma of lung.

The authors used immunohistochemical staining for S-100 protein to search for Langerhans cells in 7 cases of pulmonary eosinophilic granuloma (EGL) and in 18 cases of other pulmonary processes (including reactive eosinophilic pleuritis, chronic interstitial pneumonias, eosinophilic pneumonia, and nonspecific scars), which can produce diagnostic confusion with EGL. Qualitatively, Langerhans cells were found in almost every disease. However, cases of active or resolving EGL showed greater than 75 such cells/10 high-power fields (hpf), often appearing as densely packed aggregates (a virtually diagnostic feature), while all other conditions, including completely scarred EGL, showed fewer than 35 Langerhans cells/10 hpf, and the cells were scattered through the parenchyma. The authors conclude the following: (1) Langerhans cells participate in many types of inflammatory process in the lung, and hence the mere presence of Langerhans cells is not diagnostic of EGL; (2) S-100 staining with quantitation of Langerhans cells is a useful adjunct in the diagnosis of active and resolving EGL.

Eosinophilic Granuloma↗
PubMed1985

The pathologic spectrum of small cell carcinoma of the cervix.

Small cell carcinoma of the cervix is a term used to describe several entities including cervical carcinoid, "oat cell" carcinoma, reserve cell carcinoma, and poorly differentiated nonkeratinizing squamous cell carcinoma. The light microscopic, ultrastructural, and clinical features of seven small cell cervical carcinomas are presented in this report. Five tumors in our report were diagnosed as small cell anaplastic or oat cell carcinoma by light microscopy. This diagnosis was associated with a poor prognosis, and four of these patients were dead of disease within 24 months. The ultrastructural features of these tumors were similar, but neurosecretory granules were demonstrable in only three of the five cases. Evidence of glandular differentiation was present in one of the five cases, and dual differentiation, i.e., neuroendocrine and squamous, was noted in another. The similarities between pulmonary small cell carcinoma and these cervical lesions are discussed and the literature is reviewed. Also included in the study is a well-differentiated neuroendocrine lesion, a carcinoid that behaved in an aggressive fashion. The final case was a carcinoma putatively derived from reserve cells. The features that help make the diagnosis of reserve cell carcinoma and that distinguish this lesion from other small cell carcinomas are presented.

Adult↗
PubMed1984

Bioelectric properties and ion flow across excised human bronchi.

Bioelectric properties and ion transport of excised human segmental/subsegmental bronchi were measured in specimens from 40 patients. Transepithelial electric potential difference (PD), short-circuit current (Isc), and conductance (G), averaged 5.8 mV (lumen negative), 51 microA X cm-2, and 9 mS X cm-2, respectively. Na+ was absorbed from lumen to interstitium under open- and short-circuit conditions. Cl- flows were symmetrical under short-circuit conditions. Isc was abolished by 10(-4) M ouabain. Amiloride inhibited Isc (the concentration necessary to achieve 50% of the maximal effect = 7 X 10(-7) M) and abolished net Na+ transport. PD and Isc were not reduced to zero by amiloride because a net Cl- secretion was induced that reflected a reduction in Cl- flow in the absorptive direction (Jm----sCl-). Acetylcholine (10(-4) M) induced an electrically silent, matched flow of Na+ (1.7 mueq X cm-1 X h-1) and Cl- (1.9 mueq X cm-12 X h-1) toward the lumen. This response was blocked by atropine. Phenylephrine (10(-5) M) did not affect bioelectric properties or unidirectional ion flows, whereas isoproterenol (10(-5) M) induced a small increase in Isc (10%) without changing net ion flows significantly. We conclude that 1) Na+ absorption is the major active ion transport across excised human bronchi, 2) Na+ absorption is both amiloride and ouabain sensitive, 3) Cl- secretion can be induced by inhibition of the entry of luminal Na+ into the epithelia, and 4) cholinergic more than adrenergic agents modulate basal ion flow, probably by affecting gland output.

Acetylcholine↗
PubMed1981

Endometrial extension of carcinoma of the uterine cervix: a prognostic factor that may modify staging.

A retrospective review was done of 473 patients with histologically proven primary carcinoma of the uterine cervix on whom a dilatation and curettage (D & C) was performed during the initial workup. The pathologic features of the D & C specimens were classified as: (1) endometrial stomal invasion of cervical carcinoma; (2) tumor only, cervical carcinoma in D & C, normal endometrium absent; (3) admixture of normal endometrium and cervical carcinoma (contamination); (4) D & C negative for tumor. The patients were staged according to the FIGO classification. Eighty-two percent (388) of the patients were treated with radiation alone and the rest with a combination including surgical procedures (usually radical hystrectomy with lymphadenectomy). The three- and five-year survival rates were 10% to 20% lower for patients with D & C showing stromal invasion or tumor only than in patients with admixture or negative D & C. These results were coupled with an appreciably higher number of distant metastases in the patients with positive D & C and a lower incidence in patients with negative D & C. The authors suggest that endometrial extension of carcinoma of the uterine cervix may be an important factor in the staging classification of these patients and recommend that D & C always be done in the initial evaluation. Because of the high incidence of distant metastasis, effective adjuvant therapy must be developed to improve the present therapeutic results.

Adenocarcinoma↗