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Biomedical subjects

M J Kornstein

Publications and source records attributed to M J Kornstein.

At least 19 recordsLinked to original sources

Fine-needle aspiration biopsy and imprint cytology of small non-cleaved cell (Burkitt's) lymphoma.

We reviewed 13 cases of small non-cleaved cell (Burkitt's) lymphoma diagnosed by fine-needle aspiration biopsy (FNAB) and four cases where that diagnosis was made from touch imprints from surgical biopsy specimens. The most common site was intraabdominal. Histologic confirmation was present in 14/17 cases. General microscopic features on smears included high cellularity and an individual cell pattern. Extracellular lymphoglandular bodies were abundant and tingible body macrophages were prominent. Nuclei were intermediate in size and round with a finely dispersed chromatin pattern on May-Grünwald-Giemsa stained smears. Cytoplasm was basophilic and scant with prominent vacuoles. Extracellular vacuoles and vacuoles within lymphoglandular bodies occurred in all patients. Immunocytochemistry performed on 16/17 cases demonstrated a B cell phenotype in 15. Nine cases were kappa light chain positive and six were lambda light chain positive. Flow cytometry performed in five cases demonstrated diploid cells with a high S phase. We conclude that Burkitt's lymphoma can be diagnosed using combined FNAB and immunophenotyping.

Adolescent

Condyloma and cervical intraepithelial neoplasia of the endometrium.

Many studies have shown the presence of squamous metaplasia, dysplasia, carcinoma in situ and squamous cell carcinoma of the endometrium, whether they arose de novo or from direct extension from the cervix. Condyloma associated with squamous metaplasia or dysplasia of the endometrium is rare. We report a case of cervical intraepithelial neoplasia (CIN I) and condyloma of the endometrium. A 58-year-old woman presented with high-grade dysplasia on two successive pap smears. A total vaginal hysterectomy showed extensive CIN I and condyloma involving the entire endometrium. DNA in situ hybridization and polymerase chain reaction documented the presence of condyloma.

Base Sequence

Coexpression of the c-kit and stem cell factor genes in breast carcinomas.

Expression of the c-kit tyrosine kinase growth factor receptor has been reported in some breast tumors; however, no data exist concerning expression of its ligand, stem cell factor. The aim of this study was to determine how frequently the c-kit and stem cell factor genes were coexpressed in breast tumors and tumor-derived cell lines and to determine whether coexpression of c-kit and stem cell factor could result in growth stimulation of breast tumor cells. Expression of the c-kit and stem cell factor genes in tissue specimens and cell lines was determined using an RNase protection assay, with confirmation of c-kit protein expression by immunohistochemistry and Western blotting in tumor tissue and cell lines, respectively. Of 11 tumor specimens studied, 9 expressed variable but detectable quantities of c-kit; 7 of 13 tumor-derived cell lines also expressed c-kit. All tumor specimens and cell lines expressed detectable stem cell factor mRNA, suggesting that an autocrine growth loop could exist in the majority of breast carcinomas. To determine the biological effects of coexpression of c-kit and stem cell factor, the MCF-7 cell line, which expresses only stem cell factor, was transfected with a c-kit expression vector. Coexpression of c-kit and stem cell factor in MCF-7 cells resulted in an enhanced growth rate and cloning efficiency but not a loss of the dependence of this cell line upon estrogen. Analysis of subclones expressing different amounts of c-kit protein revealed that, although they all showed enhanced growth relative to control transfectants in serum-free medium containing IGF-1, only the highest c-kit expressor responded with additional growth to exogenous soluble stem cell factor. However, all c-kit-expressing clones, but not control clones, showed growth inhibition when exposed to a blocking anti-c-kit antibody. This blocking antibody also significantly inhibited the growth of the established ZR75-1 cell line in serum-free medium containing IGF-1. Taken together, these data suggest that coexpression of stem cell factor and c-kit could be responsible for growth deregulation in a significant number of breast carcinomas.

Adenocarcinoma

Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis.

Fifty consecutive patients who underwent 52 formal hepatic resections (excluding isolated wedge resections) for metastatic colorectal cancer were analyzed to determine whether DNA content was of prognostic significance. The Dukes' stages of the colorectal primaries were: A (10%), B (20%), C (40%), D (28%), and unknown in 2%. Four patients whose liver metastases were discovered at the time of resection of the primary bowel cancer underwent concomitant liver resection, and the remaining patients underwent delayed resections. The hepatic resections performed were right lobectomy (50%), extended right lobectomy (19%), left lobectomy (13%), left lateral segmentectomy (6%), left lobectomy and right wedge (6%), extended left lobectomy (4%), and right lobectomy and left wedge (2%). The overall morbidity rate was 29%. The in-hospital mortality rate was 9%. As of November 1991, 36 patients have recurred. The 5-year actuarial survival was 28%. Flow cytometry could be performed on 37 archival specimens, 15 of which were found to be diploid whereas 22 were aneuploid. All metastases from Dukes A colorectal primaries demonstrated a diploid DNA content. In addition, there was no difference in actuarial survival between diploid and aneuploid tumors. These data suggest that in selected patients, formal hepatic resection of colorectal liver metastases can be performed with an acceptable morbidity rate, mortality rate, and survival, but ploidy of the resected tumor is not of prognostic significance.

Adult

The utility of CD20 and CD43 in subclassification of low-grade B-cell lymphoma on paraffin sections.

To identify phenotypic differences among the low-grade lympho-proliferative disorders in paraffin-embedded tissue, we studied 49 cases. All 22 follicular small cleaved cell lymphomas (FSC) were CD43 negative and CD20 positive. In contrast, of 20 small lymphocytic lymphomas (SL), 90% were CD20 positive, 85% were CD43 positive, and 75% were positive for both. Of three lymphomas of intermediate differentiation (IDL), two were CD20 positive and two were CD43 positive. All four monocytoid B-cell lymphomas were positive for CD20 and 50% (two cases) were positive for CD43. Some 86% of 14 chronic lymphocytic leukemias (CLL) (on cytospins) were positive for CD43; all nine of the CLL studied for CD20 were positive and 89% (8/9) expressed both antibodies CD5 expression (on frozen sections or cytospin preparations) was compared to CD43 in 21 cases of SL and CLL. Some 77% were positive for both CD5 and CD20. All seven of the CD5-positive SL also expressed CD43. The antibody MT2 was also examined with the following results: FSC, 16/20 (80%) positive; SL, 18/19 (94%) positive; MBC, 3/3 positive; and ILL, 2/3 positive. All 56 cases tested were CD45RO (UCHL1) negative. We conclude that CD43 is expressed on most cases of low-grade lymphoproliferative disorders with the exception of FSC. Its pattern of expression seems similar to CD5; however, unlike CD5, CD43 can be studied in formalin-fixed tissue. MT2 is not helpful in distinguishing among these lesions.

Antigens, CD

Unusual biclonal plasma cell dyscrasia with crystallike inclusions producing colonic tumors (plasma cell polyposis) and terminating in T-cell lymphoma.

A 62-year-old man underwent a partial colectomy for persistent rectal bleeding. Multiple submucosal lesions up to 7 cm in diameter were identified and were composed of plasmacytoid and histiocytoid cells with crystallike inclusions. Ultrastructurally, inclusions were bounded by rough endoplasmic reticulum. Immunohistochemical studies demonstrated a monoclonal population of IgA kappa-positive plasma cells. Immunofixation using a saline extract of the tumor revealed two distinct bands: one for IgG kappa and another for IgA kappa. Southern blotting revealed a germline configuration for the immunoglobulin heavy-chain gene and the T-cell antigen receptor beta-chain gene. A bone marrow aspirate contained 12% plasma cells, some of which had cytoplasmic inclusions. Eight months after surgery, the patient developed a large mediastinal mass. Histologic and immunohistochemical studies indicated that this mass was an undifferentiated neoplasm. However, gene rearrangement studies indicated a T-cell lymphoma. This patient illustrates a rare association between a plasma cell neoplasm and a T-cell lymphoma.

Blotting, Southern

Angiofollicular lymph node hyperplasia (Castleman's disease) in an adolescent female. Clinical and immunologic findings.

Angiofollicular lymph node hyperplasia is a heterogeneous disorder of unclear etiology and has a wide spectrum of systemic symptoms. This report describes a case of this disorder in a 15-year-old girl and examines the response of the primary mass, systemic symptoms, and alterations of selected immune parameters at diagnosis, as a result of steroid therapy and radiation therapy (RT). The patient had a 1-year history of growth failure, delayed puberty, and refractory iron deficiency anemia. Computed tomography scan showed a posterior mediastinal mass. Biopsy revealed angiofollicular lymph node hyperplasia of mixed hyaline-vascular and plasma cell type histologic type. Immunoperoxidase studies showed polyclonal B-cells, predominance of T-helper cells (CD4) over cytotoxic/suppressor T-cells (CD8), and the presence of natural killer (NK) cells. Southern blot analysis demonstrated germ line gene configuration for the T-cell antigen receptor and Ig heavy chain. The patient clinically improved with RT after failing to respond to steroids. Immunophenotyping of peripheral blood lymphocytes before therapy revealed a CD4:CD8 ratio of 0.8 with decreased numbers of circulating T-cells; this increased to 1.4 after steroid therapy. The patient's T-lymphocytes had no proliferative response to phytohemagglutinin (PHA) or concanavalin A (Con A) before RT. After RT, a small but significant mitogenic response to these reagents was noticed. The proliferative response to recombinant interleukin-2 (rIL-2) remained similar to that of control lymphocytes. Induction of second messenger signals by activation of protein kinase C (PKC) and elevation of free cytosolic calcium through the use of the phorbol ester, phorbol 12, 13-dibutyrate (PDBu), and ionomycin (Io) resulted in a strong proliferative response at diagnosis and after RT. In vitro cytotoxicity assays revealed diminished NK activity before and after therapy. Lymphokine-activated killer (LAK) activity remained comparable with that of control cells and was not affected by therapy. Before RT patient lymphocytes maintained cytotoxic capabilities after coincubation with rIL-2 and PDBu plus Io, whereas coincubation with these reagents abrogated cytotoxic function of normal cells. This case demonstrates a clinical response to RT as well as improvement in immune parameters. Intact signal transduction mechanisms through PKC activation and elevation of cytosolic calcium were also demonstrated in the circulating lymphocytes.

Adolescent

Dendritic reticulum cells and immunophenotype in aspiration biopsies of lymph nodes. Value in the subclassification of non-Hodgkin's lymphomas.

Twenty-seven lymph node aspirates were identified for which histologic confirmation of non-Hodgkin's lymphoma was subsequently obtained. Fifteen aspirates interpreted as reactive hyperplasia were also examined. All aspirates were studied by immunoperoxidase on cytospin preparations with the use of antibodies DRC1, kappa, lambda, CD3, CD5, and CD20. The follicular lymphomas could not be identified reliably by morphologic examination of aspirate smears. Clusters of DRC1-positive (DRC1+) cells were present in seven of seven follicular lymphomas, one of one mantle zone lymphoma, and one of seven small lymphocytic lymphomas. Rare DRC1+ cells were present in one of one diffuse mixed and one of seven large cell lymphomas. One lymphoblastic, one Burkitt's, and two diffuse small cleaved cell lymphomas had no DRC1+ cells. None of the seven follicular lymphomas was CD5 positive (CD5+), whereas five of the seven small lymphocytic lymphomas were CD5+. Conversely, all seven follicular lymphomas were CD20-positive (CD20+), but only one of seven small lymphocytic lymphomas was CD20+. Nineteen of the lymphomas, including all 7 of the follicular lymphomas, were either kappa or lambda positive. The other eight lymphomas were T-cell (1), B-cell (1), true histiocytic (1), or "null" cell (5). The reactive aspirates had both kappa- and lambda-positive B-cells. Seven of the 15 had clusters of DRC1+ cells. To further evaluate these antibodies, the authors studied 29 additional, surgically biopsied, non-Hodgkin's lymphomas that had not been aspirated. Similar results were obtained, except that three of five diffuse small cleaved cell lymphomas had DRC1+ cells. DRC1, in conjunction with antibodies to CD5, CD20, kappa, and lambda, helps to distinguish follicular lymphoma from small lymphocytic lymphoma. DRC1 is not useful in separating reactive hyperplasia from follicular lymphoma.

Antibodies, Monoclonal

Fine needle aspiration biopsy of extramedullary plasma cell tumors.

Fourteen fine needle aspiration (FNA) biopsies of extramedullary plasma cell tumors (PCT) from 11 patients were reviewed and correlated with histology in eight patients. This series comprised seven men and four women ranging in age from 46 to 83 yr (median 69 yr). Discrete masses were located in lymph nodes (three patients), pleura (one patient), soft tissues of the neck (two patients), thorax (six patients), axilla (one patient), and inguinal region (one patient). A spectrum of cytologic findings was demonstrated which led to the clinical confirmation of myeloma in four of 11 patients and of solitary plasmacytoma in two of 11 patients. In addition, FNA biopsies confirmed the presence of extramedullary disease in four of 11 patients with previously diagnosed myeloma. In another patient with a poorly differentiated plasma cell neoplasm, excisional biopsy was recommended to confirm the presence of a plasma cell tumor. Clinical follow-up was available on ten patients; of these, nine were treated with aggressive chemotherapy and, in five instances, additional radiotherapy. The 10th patient succumbed to infection prior to treatment. Nine of the ten patients were dead of disease 3 days to 4 yr following clinical diagnosis of a plasma cell dyscrasia. One patient (Case 1) was lost to follow-up after biopsy confirmation of plasmacytoma. The cytomorphologic appearance of neoplastic plasma cells in FNA of solitary masses necessitates clinical evaluation for bone marrow disease, i.e., myeloma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

B cells in thymomas.

Although previous studies demonstrated thymoma-associated lymphocytes to be T cells, six thymomas were identified with germinal centers (GC) inside the tumor capsule. Three were mixed lymphocytic and epithelial thymomas. These tumors contained GC interspersed throughout and were not associated with myasthenia gravis (MG) or with GC in adjacent thymus. Three other tumors were lymphocytic thymomas with subcapsular GC. These thymomas occurred in MG patients and were associated with GC in adjacent non-neoplastic thymus. Immunoperoxidase studies using antibodies LN1, LN2, and L26 confirmed the presence of B cells in thymomas, particularly those with germinal centers. The presence of B cells in certain thymomas must be considered when studying the association of Epstein-Barr virus with thymic tumors. Germinal centers in a thymoma are not necessarily associated with myasthenia gravis.

Antibodies, Monoclonal

Extrarenal Wilms' tumor: an analysis of four cases.

During a review of Wilms' tumor, four located external to the kidney were identified. Patient age ranged from 7 months to 4 years; three were female. One neoplasm was located in the parametrial connective tissue to the left of the uterus; both kidneys were radiographically normal. Three neoplasms were located in the right retroperitoneum adherent to the surface of the ipsilateral kidney, but separated from the parenchyma by a thick fibrous capsule. Two were attached to the upper pole, while the third was attached to the midportion of the kidney. Radiologic studies showed displacement of all three kidneys, but intravenous pyelogram (IVP) revealed no calyceal distortion. All four neoplasms were favorable histology Wilms' tumor: one was monophasic epithelial type, one was monophasic blastemal type, and two had a mixture of stromal, epithelial, and blastemal tissue. No teratomatous elements were present. Immunoperoxidase staining for cytokeratin (AE-1, AE-3, CAM 5.2), vimentin, and epithelial membrane antigen (EMA) showed the strongest focal positive staining of tubular structures with CAM 5.2, and slight staining with EMA. Staining reaction to vimentin was variable, but negative in most areas. Three tumors extracted from paraffin were diploid by quantitative flow cytometric DNA analysis; in one case, flow cytometry could not be performed. Clinical follow-up from 2 years to 6 years showed all children to be alive without evidence of disease. Based on the similarity to conventional renal Wilms' tumor, these findings support the hypothesis of displaced mesonephric/metanephric rests for the origin of extrarenal Wilms' tumor.

Child, Preschool

Epstein-Barr virus-associated lymphoproliferative disorder. Applications of immunoperoxidase and molecular biologic techniques.

A 17-year-old boy with fever and cervical lymphadenopathy developed multiple-organ failure and died three weeks after hospital admission. A lymph node biopsy specimen demonstrated a florid immunoblastic infiltrate that was suspicious for a malignant lymphoma. By using immunoperoxidase and molecular biologic techniques, evidence was presented for an Epstein-Barr virus-associated lymphoproliferative disorder.

Adolescent

New techniques in diagnosing malignancy: morphology and beyond.

New pathologic techniques are improving the ability to detect malignancy and determine treatment modes. With immunohistochemistry the pathologist can make important distinctions, such as differentiating between carcinomas and lymphomas. With the flow cytometer various cell parameters and fluorescent labels can be measured. Still investigational are techniques for the detection of activated oncogenes and early viral infections.

Biomarkers, Tumor

Cortical versus medullary thymomas: a useful morphologic distinction?

We have tested the hypothesis that thymomas can be classified solely on the basis of epithelial cell morphology and that this distinction is prognostically useful. One hundred thymic epithelial tumors were classified according to the morphologic resemblance to cortical or medullary thymic epithelium and to the traditional classification (lymphocytic, epithelial, mixed, and spindled). Follow-up data was obtained on 78 patients. Fifty-eight percent of the tumors were invasive. Nineteen of the invasive tumors relapsed and none of the non-invasive tumors relapsed (P less than .0001). Four of nine tumors with microscopic invasion through the capsule recurred. Statistical analysis showed no significant differences in relapse-free survival for any of the histologic categories. Ninety-four percent of the tumors studied were keratin positive and all were chromogranin negative. Carcinoembryonic antigen was negative for all but one cytologically malignant tumor; of the tumors 75% were epithelial membrane antigen positive, 80% were Leu-7 positive, and 11% were neuron specific enolase positive. Seven of 12 tumors tested expressed HLA-DR. There was no correlation between immunoreactivity and classification. The morphologic cortical/medullary distinction is conceptually attractive but appears clinically to be no more advantageous than the traditional classification.

Adult

Immunohistology of the benign lymphoepithelial lesion in AIDS-related lymphadenopathy: a case report.

We report a case of a benign lymphoepithelial lesion of the parotid gland in a patient with progressive generalized lymphadenopathy (PGL) related to human immunodeficiency virus. Serologic studies and immunoperoxidase studies for lymphocyte subsets, which have not previously been reported in this lesion, suggest involvement of an intraparotid lymph node by PGL rather than Sjogren's syndrome.

AIDS-Related Complex