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Biomedical subjects

B C Wolf

Publications and source records attributed to B C Wolf.

At least 37 records · Page 2Linked to original sources

An evaluation of immunohistologic stains for immunoglobulin light chains in bone marrow biopsies in benign and malignant plasma cell proliferations.

Bone marrow specimens from 226 patients with a variety of benign and malignant plasma cell proliferations were studied to assess the reliability of immunohistologic studies in their evaluation. The clonality of the bone marrow plasma cells was compared with results of serum and urine electrophoreses. Discordance was observed most frequently in cases in which a paraprotein was demonstrated, but no monoclonality was detected by immunoperoxidase (16 cases). Of these 16 cases, 9 had 5% or less bone marrow plasma cells. In only one case was the light chain class of the bone marrow plasma cells different from that of the paraprotein. If discordant cases with 5% or less plasma cells are eliminated, the overall concordance was 97%. The authors' findings indicate that immunohistologic studies for immunoglobulin light chains in Zenker-fixed decalcified bone marrow biopsy sections are reliable in the evaluation of patients with plasma cell proliferations when the marrow contains more than 5% plasma cells.

Biopsy↗

The detection of Epstein-Barr virus in hairy cell leukemia cells by in situ hybridization.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several B-cell lymphoid proliferations. Because patients with hairy cell leukemia (HCL) have a high incidence of seropositivity for EBV antigens, we studied the cells of HCL for evidence of EBV infection using in situ hybridization techniques. EBV mRNA was detected in the tumor cells in four of six cases using a radiolabeled RNA probe. Confirmatory serologic data were available in three cases in which the viral DNA was detected and in one negative case. Our results suggest that EBV infection may have a pathogenetic role in this disorder.

Adult↗

Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colon cancer cell line.

We characterized the tumorigenic and metastatic potential of a poorly differentiated, non-CEA-producing colon cancer cell line, MIP-101, after injection at different sites in athymic mice. After subcutaneous and intrasplenic injection tumor grew locally in 100 and 50%, respectively, but no metastases were found, even after intravenous injection. Intraperitoneal implantation, however, resulted in a high tumor take (10/10) and subsequent liver colonization (8/10 mice). Exogenous CEA prior to intrasplenic injection induced metastasis in 7/8 mice (in 2 mice to the liver and in 5 mice to the lung). Intrasplenic injection of CX-1, a good CEA producer, resulted in hepatic metastases in 100% of the animals. These data suggest a direct or indirect role of CEA in the metastatic process. We conclude that MIP-101 has a high tumorigenic and invasive potential but a low metastatic proclivity, except when grown in the peritoneum, and that pretreatment of tumor-bearing animals with CEA affects the metastatic proclivity.

Adenocarcinoma↗

Detection of the tumor-associated glycoprotein antigen (TAG-72) in premalignant lesions of the colon.

We used monoclonal antibody B72.3 to study the expression of the colorectal carcinoma-associated antigen TAG-72 in premalignant colonic lesions with the immunoperoxidase technique. This antigen, which is rarely detectable in the normal colonic epithelium, was expressed in 13 of 19 adenomas with moderate to severe dysplasia and nine of nine cases of inflammatory bowel disease. The antibody reacted with the normal-appearing mucosa adjacent to a carcinoma in 10 of 12 cases, although only eight of the tumors expressed the antigen. The expression of the TAG-72 antigen in the colonic epithelium may be an early marker of malignant transformation.

Antibodies, Monoclonal↗

The pathogenesis of splenic extramedullary hematopoiesis in metastatic carcinoma.

Splenic extramedullary hematopoiesis (EMH) is a characteristic finding in agnogenic myeloid metaplasia (AMM) and in the spent phase of polycythemia vera (PV). Evidence from our laboratory has suggested that splenic EMH in these conditions results from the filtration of circulating hematopoietic cells from the peripheral blood and does not arise de novo from splenic stem cells. To further test this hypothesis, 31 autopsy and 26 surgical cases of carcinoma metastatic to the bone marrow were studied. The presence of leukoerythroblastosis (LEB) correlated with intravascular hematopoiesis (IVH) in the bone marrows associated with reticulin fibrosis, and with splenic EMH in the autopsy cases. These studies provide evidence that stromal changes in the bone marrow with resulting IVH, LEB, and splenic EMH are not unique to AMM and PV but also occur in such unrelated conditions as metastatic carcinoma, and suggest that these phenomena are causally related.

Adult↗

Reversal of bone marrow fibrosis and subsequent development of polycythemia in patients with myeloproliferative disorders.

Bone marrow fibrosis is a characteristic finding in agnogenic myeloid metaplasia and in the spent phase of polycythemia vera. It is commonly believed that the reticulin deposition is irreversible. However, we report four patients who demonstrated clinical and laboratory evidence of transition from myelofibrosis to polycythemia. The transition was documented by improvement in the hemoglobin concentration and by determination of the Cr51 red blood cell mass, accompanied by a resolution of the fibrosis on serial bone marrow biopsies. Two of the patients had been treated with alkylating agents and splenectomy, one with myelosuppressive therapy without splenectomy, and one with splenectomy alone. These findings indicate that bone marrow fibrosis in the chronic myeloproliferative disorders is not always an irreversible phenomenon. Pathogenetic implications will be discussed.

Aged↗

The expression of colorectal carcinoma-associated antigens in the normal colonic mucosa. An immunohistochemical analysis of regional distribution.

Immunohistologic studies were performed to evaluate the expression and regional distribution of 20 colorectal carcinoma-associated antigens in the colonic mucosa of 12 normal adults. A distinct regional variation was seen in the expression of blood group A, B, Lewis(b), and extended Lewis(y) antigens, which were expressed predominantly in the right colon, whereas Lewis(a), Lewis(y), and H-type 2 were prevalent throughout. Lewis(x) and X-like antigens were only occasionally expressed. Two antibodies against sialylated Lewis(a) showed different staining patterns, with CA19.9 positive in only two biopsies and CO29.11 intensely positive in most. Two of the three antibodies detecting carcinoembryonic antigen epitopes (3d6 and COL-4) stained many biopsies, whereas COL-12 was rarely detected. No regional gradient was found in the expression of the other antigens studied (B72.3, ME491; GA73.3, ND1, and ND4). This mapping data will provide an important baseline for future studies of epitope distribution in the colon in premalignant and neoplastic conditions.

ABO Blood-Group System↗

Small lymphocytic lymphoma: a clinicopathologic analysis of 268 cases.

We analyzed specimens from 268 patients with small lymphocytic lymphoma (SL) to identify prognostic factors significant for survival. These patients were staged and treated according to the protocols of the Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southeastern Cancer Study Group, and the Southwest Oncology Group. Univariate analysis showed that a large-cell grade greater than I, WBC greater than 10,000/microL, hemoglobin (Hgb) less than 11 g/dL, age greater than or equal to 55 years, and failure to respond to treatment were all poor prognostic factors. Multivariate analysis showed that large-cell grade, age, degree of capsular invasion, and symptom type were independently associated with survival. Separate analyses of cases with and without leukocytosis indicated differences in survival. In patients without leukocytosis, age, presence or absence of anemia, and treatment response were significant prognostic variables; in patients with leukocytosis, large-cell grade, presence or absence of anemia, symptom type, and treatment response were significantly related to survival. Multivariate analysis showed that age was the only significant independent prognostic variable in patients without leukocytosis; in patients with leukocytosis, symptom type, large-cell grade, and bone marrow involvement were independently associated with survival. We conclude that several parameters, both clinical and pathologic, should be assessed at the initial diagnosis of SL to predict prognosis better.

Age Factors↗

A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors.

A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen. This antibody, ND4, is an IgG2a which does not cross-react with carcinoembryonic antigen (CEA), non-specific cross-reacting antigen, or blood group substances A, B, and H. Immunoprecipitation using lysates of cells grown in [35S]methionine or [3H]glucosamine and lysates of cells surface labeled with 125I showed binding to a cell surface glycoprotein with a molecular weight of approximately 160,000. Indirect immunofluorescence showed binding to the cell surface of 14 of 15 human colorectal carcinoma cell lines including six of six that do not secrete CEA. Two of seven human noncolorectal carcinoma lines and one of six nonhuman cell lines also bound antibody. Immunoperoxidase staining of formalin-fixed tissues showed prominent antibody binding with 19 of 33 (58%) human colorectal carcinomas, including five of six poorly differentiated tumors, five of 43 (12%) normal colonic mucosal biopsies, and one of 17 (6%) normal noncolonic tissues. One of 11 (9%) noncolonic tumors, a gastric adenocarcinoma, stained with ND4. Preliminary data obtained by a nonquantitative nitrocellulose dot-immunoassay have tentatively identified this glycoprotein in the serum of 15 of 37 (41%) patients with colorectal cancer. Three of the 15 patients had early stage disease and normal CEA levels (less than 2.5 ng/ml). Three patients had circulating antigen detectable preoperatively but not after tumor resection. Only one of 11 (9%) sera samples from normal subjects was positive. The characteristics of ND4 suggest that it may be of value in monitoring patients with colorectal carcinomas who do not have plasma CEA elevations. It may also be of value in the differential diagnosis of metastatic, poorly differentiated adenocarcinomas of unknown primary origin.

Animals↗

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Clinical Trials as Topic↗

Statistical and empirical evaluation of histopathologic reviews for quality assurance in the Eastern Cooperative Oncology Group.

Central pathology review for quality assurance in cooperative clinical cancer trials has been an accepted practice for over a decade. However, the actual value of such pathology review has never been statistically evaluated or the need defined in a comprehensive manner. Pathology exclusions in 35 completed and ongoing Eastern Cooperative Oncology Group (ECOG) trials were analyzed. Ineligibility rates ranged from 0% to 16.9%. The lowest ineligibility rates occurred in breast cancer, small cell and non-small cell lung cancer, squamous cell carcinoma of head and neck, and gastrointestinal carcinoma protocols. The highest rates occurred in rare cancers such as malignant thymoma, endocrine carcinomas, and in the sarcoma-mesothelioma area. Simulated prototypical trials involving an aggressive and an indolent cancer were examined to evaluate the precision with which treatment differences would be measured when pathologically ineligible cases were included. Analysis of these models indicated that in trials in which the pathology exclusion rate is greater than 10%, slide review is prudent. When the exclusion rate is 5% to 10%, the necessity for pathology confirmation depends on the scientific objective of the trial. If less than 5% pathology exclusions characterize a clinical trial, routine pathology review is not justified. Routine histopathologic review for quality assurance in cooperative groups is not always necessary and may be eliminated in studies of the more common cancers. The practical value of reallocating limited pathology resources for investigative studies in cooperative groups is significant.

Costs and Cost Analysis↗

Inflammatory pseudotumor of the spleen: a clinicopathology study of three cases.

The clinical and pathologic findings of three cases of splenic inflammatory pseudotumor are described, and differential diagnostic features are discussed. This benign lesion is extremely rare, only four having been previously reported. Inflammatory pseudotumors often pose diagnostic difficulties because they form infiltrative masses which have clinical and gross pathologic features that suggest malignancy. Although these lesions are usually easily recognizable microscopically as benign processes, the admixed component of lymphoid and other hematopoietic cells may sometimes raise the question of a lymphoreticular malignancy, requiring immunohistologic studies for resolution in some cases. Alternatively, pseudotumors may be mistaken for infectious granulomatous processes, sarcoidosis, or hamartomas.

Adult↗

Benign lesions mimicking malignant tumors of the esophagus.

Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies.

Adult↗

Splenic hematopoiesis in polycythemia vera. A morphologic and immunohistologic study.

Spleens from 42 patients with polycythemia vera were studied with immunohistologic technics to assess the degree of hematopoietic cellularity in an attempt to clarify the pathogenesis of the splenomegaly characteristic of this disorder. The 22 spleens obtained in the erythrocytotic phase showed striking congestion with mature erythrocytes but no significant extramedullary hematopoiesis. However, the 20 spleens obtained in the spent phase showed prominent trilinear extramedullary hematopoiesis. Increasing splenomegaly with extramedullary hematopoiesis correlated with the development of increased medullary reticulin and peripheral blood leukoerythroblastosis. Splenic myeloid metaplasia is not a feature of uncomplicated polycythemia vera, and its presence indicates progression to the spent phase, or postpolycythemic myeloid metaplasia. The authors' findings indicate that the presence of hematopoietic precursors in the spleen in the spent phase of polycythemia vera and in agnogenic myeloid metaplasia is a result of their filtration from the peripheral blood.

Adult↗

The bone marrow in myeloproliferative and dysmyelopoietic syndromes.

The myeloproliferative and dysmyelopoietic syndromes are complex disorders that are interrelated and not always easily diagnosed on morphologic grounds alone. In particular, in the case of the myeloproliferative diseases, the diagnostic pathologist should avoid the pitfall of attempting to make a definite diagnosis in the absence of appropriate laboratory and clinical data. The morphologic features in given myeloproliferative diseases are not always specific; and, as the disorders evolve, they may closely mimic one another. With respect to the dysmyelopoietic syndromes, care must be taken not to confuse them with megaloblastic anemias or other conditions that do not have the same ominous prognosis. Distinction between the varying syndromes may frequently also be difficult, and on occasion one may have difficulty placing them within the appropriate context. Only careful correlation with clinical laboratory findings and history will result in accurate diagnoses.

Bone Marrow↗

The histologic features of hyperplastic lymphadenopathy in AIDS-related complex are nonspecific.

Follicular hyperplasia is the most common histologic finding in lymph nodes of patients with AIDS-related complex (ARC) and persistent generalized lymphadenopathy. To determine the specificity of the published features considered characteristic of this condition, we compared two sets of lymph-node biopsy specimens with follicular hyperplasia. Thirty-eight specimens were from human immunodeficiency virus (HIV/HTLV3/LAV) positive homosexual men with persistent generalized lymphadenopathy, and 87 specimens were from patients free of AIDS risk. Polykaryocytes, epithelioid histiocytes, and follicle mantle zone effacement were significantly more common in the ARC group. Dermatopathic change and so-called follicle lysis were significantly more common in control, non-ARC nodes. No statistically significant difference between the two groups could be demonstrated for the following features: irregularity of follicles, burnt-out follicles, sinus monocytoid cells, marked plasmacytosis, and the toxoplasmosis triad. Most importantly, no feature was seen exclusively in either of the two groups. Although some features considered characteristic of the hyperplastic form of ARC lymphadenopathy are seen more commonly in this condition than in lymph nodes showing follicular hyperplasia unrelated to ARC, none of these features is specific for ARC and there is no histologic picture diagnostic of this condition.

AIDS-Related Complex↗