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Biomedical subjects

J M Corson

Publications and source records attributed to J M Corson.

At least 19 recordsLinked to original sources

Long-term salvageability for patients with locally recurrent soft-tissue sarcomas.

Between 1971 and 1988, 39 patients were referred because of local recurrence of soft-tissue sarcomas and data from their patient records were analyzed to determine the parameters governing local recurrence. Mean follow-up was 11.1 years, with a mean time to local recurrence of 22 months. Twenty-one patients had local recurrence only, without metastatic disease. Salvage was provided for 14 (67%) of these patients after reexcision of local recurrence, and all 14 patients remained free of disease (mean follow-up, 112 months). We conclude that (1) excisional biopsy of tumors larger than 3 cm leads to potential contamination of clean tissue planes, limits ability to achieve an adequate margin of resection, and may compromise the definitive excision, and (2) in patients with local recurrence only, there is a high rate of long-term salvage (67% for follow-up of 9.3 years) after radical compartmental excision with or without postoperative radiation therapy.

Adolescent

Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis.

OBJECTIVE: To evaluate the utility of real-time, high-resolution ultrasound of the shoulder in the diagnosis of dialysis-related amyloidosis. METHODS: We performed a case series study of 2 groups of patients seen at a referral-based clinic in a tertiary care hospital. The shoulders of 13 patients with normal renal function and of 38 patients receiving long-term hemodialysis were studied by real-time, high-resolution ultrasound. All hemodialysis patients were evaluated clinically for the presence of dialysis-related amyloidosis. Surgical specimens of joints were available for all 13 patients with normal renal function and for 17 of the 38 hemodialysis patients. These specimens were evaluated for the presence of beta 2-microglobulin (beta 2m) amyloid by Congo red and immunohistochemical staining. RESULTS: Two ultrasonographic findings were selectively observed in the dialysis patients with clinical and histologic evidence of beta 2m amyloid in comparison with patients with normal renal function and no evidence of amyloid: rotator cuffs greater than 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff. The presence of at least 1 of these 2 findings corresponded to the presence of clinically and histologically evident beta 2m amyloid with a sensitivity of 79% and a specificity of 100%. When additional patients without surgical specimens for histologic confirmation of amyloidosis were included, the sensitivity of these 2 sonographic findings was 72% and the specificity was 97%. CONCLUSION: Real-time, high-resolution ultrasound is a relatively sensitive and highly specific noninvasive adjunct to the clinical diagnosis of beta 2m amyloidosis in patients receiving long-term hemodialysis.

Adult

Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors.

BACKGROUND: Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established. METHODS: We attempted to determine the karyotypes of a series of 62 consecutive, unselected malignant spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16 children) after direct harvesting of cells or short-term culture. All tumors were examined independently by immunohistochemical staining in addition to routine light-microscopical evaluation, and all but two tumors were examined by electron microscopy. RESULTS: Metaphases were obtained from 61 of the 62 tumors, and clonal chromosome aberrations were identified in 55 (89 percent). In the six tumors that yielded metaphases but lacked apparent clonal aberrations, the normal metaphases were found to originate from non-neoplastic stromal elements within the tumor specimens. Thus, all tumors in which karyotyping was successful contained clonal chromosome aberrations. Forty of 62 tumors (65 percent) contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis; in 15 of these tumors (24 percent of all tumors), the aberrations were important in establishing the final diagnosis. Cytogenetic analyses were particularly informative about small round-cell tumors from children: 8 of 14 round-cell tumors contained diagnostically important chromosome aberrations. Using the combined approaches of light and electron microscopy, immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis for 60 of 62 tumors. CONCLUSIONS: Cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft-tissue tumors. These clonal chromosome aberrations, particularly in small round-cell tumors in children, often have diagnostic relevance.

Adult

Cytogenetic evidence of clonality in a case of pigmented villonodular synovitis.

Pigmented villonodular synovitis is an uncommon benign lesion that is characterized by diffuse synovial proliferation. Based on animal models, this lesion has been conjectured previously to be reactive in nature. In this report, the authors present the histologic and cytogenetic findings for a pigmented villonodular synovitis that was excised from the right knee of a 47-year-old man. Trisomy 7 was observed in 24 of 75 (35%) metaphases obtained from short-term culture of cells from this tumor. These findings suggest that some cases of pigmented villonodular synovitis represent clonal, neoplastic proliferations.

Chromosomes, Human, Pair 7

Radiographic detection of metal-induced synovitis as a complication of arthroplasty of the knee.

Radiographs of eighteen patients who had had a diagnosis of metal-induced synovitis subsequent to a knee-replacement arthroplasty were retrospectively reviewed. The presence of a dense line outlining a portion of the capsule or articular surface of the knee joint (the so-called metal-line sign) was noted in association with wear in eleven patients. In the nine patients who had a positive sign and also had specimens available for histological examination, there was dense deposition of metal particles, whereas in the six patients who did not have a metal-line sign and had specimens available for histological examination, five had only a slight amount of metal in the synovial tissue and one, a moderate amount. The presence of the metal-line sign was associated with metal-induced synovitis in eleven of the eighteen patients. The sign should be useful in helping to make this diagnosis preoperatively in many patients.

Chromium Alloys

Diagnosis of diffuse malignant mesothelioma: experience of a US/Canadian Mesothelioma Panel.

The experience of the US/Canadian Mesothelioma Panel with its first 200 cases is reviewed. The light microscopic diagnosis, histochemical findings, immunohistochemical findings, and electron microscopic features of malignant mesotheliomas are reviewed in the context of differential diagnosis. Reasons for referral of case material to the panel and lessons from follow-up of difficult and controversial cases are reported. Recommendations to general pathologists are made regarding evaluation and review of possible mesotheliomas.

Adenocarcinoma

Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma.

Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach.

Antineoplastic Combined Chemotherapy Protocols

Melanoma and soft tissue sarcoma in seven patients.

Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between melanoma and sarcoma, the nature of which remains unknown.

Female

Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B.

Carboplatin (400 mg/m2) was given at 28-day intervals to 41 patients with malignant mesothelioma. In all, 40 patients were eligible and evaluable for response. Partial responses were seen in 2 cases (5%); regression of evaluable disease, in 1 patient (2%); and stable disease, in 19 subjects (48%). A median of two doses of carboplatin per patient resulted in mild toxicity. Leukopenia (less than or equal to 2,000 cells/microliters) and thrombocytopenia (less than 100,000 cells/microliters) were seen in only 6% and 20% of the patients, respectively. Median survival from study entry was estimated at 7.1 months, with a 1-year survival of 25% +/- 7%. Carboplatin given at a dose of 400 mg/m2 at 28-day intervals shows minor activity against malignant mesothelioma.

Adult

Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome.

The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential.

Antibodies

ME1. A monoclonal antibody that distinguishes epithelial-type malignant mesothelioma from pulmonary adenocarcinoma and extrapulmonary malignancies.

ME1 is a monoclonal antibody reactive in frozen tissue sections with normal mesothelial cells and malignant mesotheliomas. In this immunoperoxidase study, ME1 reacted with all 40 epithelial type malignant mesotheliomas. Fifty percent or more of the mesothelioma cells were stained in all cases and the staining intensity was strong in 32 and moderate in eight. In contrast, all 19 well- and moderately differentiated pulmonary adenocarcinomas were completely negative, and of the total 88 non-mesotheliomatous malignancies studied, staining comparable to the mesotheliomas was seen in only 6 tumors (2 pulmonary adenocarcinomas, 2 adenocarcinomas of the breast, 1 adenocarcinoma of the pancreas, and 1 melanoma), although limited, weaker staining was seen in additional cases. Five of the six strongly to moderately positive nonmesotheliomatous tumors had immunoreactivity for complementary immunoreactants (CEA, Leu-M1, S-100 protein, HMB-45). Our results with ME1, the first monoclonal antibody that recognizes malignant mesothelial cells, provides a basis for using this reagent in the differential diagnosis of tumors of the pleura and peritoneum.

Adenocarcinoma

Keratin protein immunoreactivity of sarcomatoid and mixed types of diffuse malignant mesothelioma: an immunoperoxidase study of 30 cases.

To define the role of keratin protein immunohistochemistry in the pathologic diagnosis of the sarcomatoid type of diffuse malignant mesothelioma (DMM), we examined 30 DMM (16 pure sarcomatoid type and 14 mixed sarcomatoid-epithelial type) by an indirect immunoperoxidase technique using three commercially available antibodies to keratin proteins. The sarcomatoid (spindle-cell) areas of all 30 cases of sarcomatoid DMM were immunoreactive for keratin proteins. In 14 of 16 cases of sarcomatoid DMM, 50% or more of the tumor cells were reactive with one or more antibodies; however, polyclonal bovine muzzle and monoclonal AE1/AE3 antibodies were distinctly superior to polyclonal human callus keratin antibody in the detection of spindle tumor cells. In contrast with the staining patterns observed for DMM, 39 spindle-cell malignancies and tumor-like processes of 10 histogenetic types were unreactive with the three antibodies. Those spindle-cell tumors and reactive mesothelial proliferations that may enter into the differential diagnosis of sarcomatoid DMM are discussed. We conclude that keratin protein immunohistochemistry is a sensitive and highly useful method for the pathologic diagnosis of the sarcomatoid type of DMM and its distinction from other spindle-cell neoplasms.

Adult

The distinction of adenocarcinoma from malignant mesothelioma in cell blocks of effusions: the role of routine mucin histochemistry and immunohistochemical assessment of carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, and milk fat globule-derived antigen.

The immunohistochemical profile (i.e., carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, human milk fat globule-derived antigen, and mucin) of paraffin-embedded cell blocks of 20 malignant effusions from patients with malignant mesothelioma was compared with that of 39 malignant effusions from patients with metastatic adenocarcinoma to determine whether these markers distinguished between these tumor types. Twenty-three adenocarcinomas (59 per cent) stained for mucin. Immunoreactivity for carcinoembryonic antigen (CEA) was observed in 28 adenocarcinomas (72 per cent). All were immunoreactive for keratin proteins, and 29 adenocarcinomas (74 per cent), including seven that were mucin and CEA negative and exhibited a "peripheral predominant" staining pattern for keratin proteins. By contrast, none of the mesotheliomas stained for mucin or for CEA, and, although all were immunoreactive for keratin proteins, none demonstrated a peripheral predominant pattern of staining. Epithelial membrane antigen and milk fat globule-derived antigen were identified in the majority of both mesotheliomas and adenocarcinomas. Neither staining intensity nor pattern of reactivity of these markers clearly distinguished the tumors. This study of cell blocks of serous effusions suggests that staining for mucin, immunoreactivity for carcinoembryonic antigen, and a peripheral predominant pattern of reactivity for keratin proteins represent highly characteristic markers of adenocarcinomas, which identify the majority of these tumors (38 of 39) and allow their distinction from malignant mesotheliomas.

Adenocarcinoma

Keratin protein immunohistochemistry in surgical pathology practice.

Keratin protein immunohistochemistry is a powerful diagnostic tool whose role has already been firmly established in many surgical pathology laboratories. Recent studies of the biology of keratin proteins have defined the heterogeneity of keratin protein expression among various epithelial tissues and their tumors and provide the basis for understanding the immunoreactivity of epithelial tumors with various keratin antibodies. Successful execution of the procedure requires attention to technical details such as the fixation of tissue, use of proteolytic enzymes such as trypsin for formalin-fixed tissues, and the choice of the appropriate antibody and controls. Broadly reactive polyclonal and monoclonal antibodies to keratins have been remarkably useful in identifying poorly differentiated and undifferentiated carcinomas. Monoclonal antibodies of restricted specificity and monospecific antibodies to keratin are under development and may prove helpful in defining the organ of origin of metastatic carcinomas. Keratin protein immunohistochemistry supplements existing information used by pathologists in diagnosis, and the immunohistochemical results should be interpreted in the light of the clinical findings, gross and microscopic pathology, and the results of any other special studies.

Animals

Early peritoneal mesothelioma: a treatable malignancy.

37 patients with malignant peritoneal mesothelioma were studied to assess the efficacy of combined therapy. 14 patients presented after 1982. Of 6 patients treated intensively, all remain alive with no evidence of disease by computed tomographic scan at 9-36 months. Of 8 patients treated palliatively, 5 are dead. (5 had stable disease, 1 has progressed despite all treatment, and 2 were not treated.) Survival of the intensively treated group is significantly better than that of other stage I patients in this series. Patients under 40 had a significantly better survival rate than older patients.

Adolescent

Optimal immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissue requires preliminary trypsinization. An immunoperoxidase study of various tumours using polyclonal and monoclonal antibodies.

The effect of preliminary trypsinization on the immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissues of a variety of tumors (squamous cell carcinomas, adenocarcinomas, mesotheliomas, and transitional cell carcinomas) was evaluated. Three types of trypsin (Type II and Type IX porcine trypsin and Type III bovine trypsin) and varying concentrations of trypsin were assessed. Immunoreactivity of keratin proteins was determined using rabbit anti-keratin antibodies and monoclonal antibodies (combination of AE1 and AE3) and immunoperoxidase techniques. Preliminary trypsinization was mandatory for optimal immunoreactivity of keratin proteins using either polyclonal or monoclonal antibodies. Excellent results were obtained using Type II porcine trypsin at concentrations of 25 mg/dl for 30-45 min or 50 mg/dl for 20 min, at 37 degrees C. Trypsin treatment with excessive concentrations of enzyme and/or extended incubation times promoted tissue digestion and in some cases, yielded decreased immunoreactivity and altered staining patterns.

Adenocarcinoma