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M J Kornstein

Publications and source records attributed to M J Kornstein.

At least 19 recordsLinked to original sources
PubMed2001

Neuroendocrine tumors of the thymus: a clinicopathological and prognostic study.

BACKGROUND: Neuroendocrine tumors of the thymus are rare, histologically diverse neoplasms with an unpredictable clinical behavior. This study provides a useful clinicopathological classification and determines the relevance of specific prognostic factors. METHODS: Ten neuroendocrine tumors of the thymus were analyzed for specific clinical and pathological features. Prognostic factors of these cases and 71 previously published cases were evaluated by Kaplan-Meier survival curves and Cox multivariate hazard model. RESULTS: There were 7 males and 3 females, with ages ranging from 26 to 77 years. Cases were classified as carcinoid tumor (2), atypical carcinoid tumor (6), and small cell carcinoma (2). An advanced clinical stage was evident in all instances with frequent recurrence (4) and metastases (8), and a short disease-free survival. Overall mortality was 60%. Statistical analysis of current and previously published cases (n = 81 total) revealed that unresectability (p = 0.0001), extent of surgical resection (p = 0.0002), and advanced clinical stage at presentation (p = 0.03) were associated with higher mortality. By multivariate Cox regression analysis, unresectability (p = 0.02) and advanced clinical stage (p = 0.03) were associated with decreased survival. CONCLUSIONS: Neuroendocrine tumors of the thymus can be classified into distinct clinicopathological entities, and specific factors have prognostic relevance.

Adult↗
PubMed2000

Kaposiform hemangioendothelioma of the thymus.

Kaposiform hemangioendothelioma is a rare pediatric neoplasm that presents most commonly in the soft tissues. We report the case of a 1-month-old infant who presented with stridor and was found to have a diffusely infiltrating tumor in the thymus that extended into the pericardium and up the carotid sheaths. Histologic examination revealed a vascular tumor infiltrating among the lobules of the lymphocyte-depleted thymus. The lesion had features of both a capillary hemangioma and Kaposi sarcoma. Immunoperoxidase studies on formalin-fixed, paraffin-embedded tissue demonstrated the neoplastic endothelial cells to be positive for vascular markers CD31 and CD34. Antibody to factor VIII-related antigen labeled feeding vessels, but failed to stain the lobules of tumor. Although these tumors have been treated in a fashion similar to capillary hemangiomas in the past, it may be important to differentiate Kaposiform hemangioendotheliomas because of their association with Kasabach-Merritt syndrome and recent success with more aggressive chemotherapy regimens.

Biomarkers, Tumor↗
PubMed2000

Primary T-cell-rich B-cell lymphoma masquerading as a meningioma.

Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case of T-cell-rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques.

Antigens, CD↗
PubMed2000

CD10 expression in follicular lymphoma versus reactive follicular hyperplasia: evaluation in paraffin-embedded tissue.

The differentiation of reactive follicular hyperplasia (RFH) from follicular lymphoma (FL) may be a diagnostic challenge and require the use of adjuvant studies. Antibodies to CD10 have been used with flow cytometry and frozen tissue sections and recently have become available for use with paraffin-embedded tissue. We sought to investigate the utility of CD10 in the differentiation of RFH from FL in paraffin-embedded tissue. Twenty-three cases of FL and 19 cases of RFH were evaluated after immunostaining with antibodies to CD3, CD20, BCL2, and CD10 antigens. Intensity of CD10 expression was graded. CD10 expression was present in 87% of cases of FL. Follicles demonstrated strong positivity in 70%. One CD10-positive case of FL showed equivocal staining for BCL2 and one an absence of staining for BCL2. Weaker but definite staining was present in 17%, and 13% were negative for CD10. In contrast, none of the cases of RFH was strongly positive for CD10 expression, with 26% demonstrating weak immunostaining, one case showing equivocal staining, and 68% being entirely negative. CD3, CD20, and BCL2 stained appropriately in all cases. These findings indicate that immunohistochemical staining of paraffin-embedded tissue sections for CD10 may help differentiate reactive from neoplastic follicular lesions.

Antigens, CD20↗
PubMed1998

CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms.

We studied 109 thymic tumors and 423 other neoplasms for immunocytochemical expression of CD5 in paraffin-embedded tissue using 2 monoclonal antibodies. One of the antibodies (clone CD5/54/B4) labeled 7 (29%) of 24 thymic carcinomas but did not stain any of the other neoplasms. In contrast, the other antibody (clone 4C7) labeled 15 (62%) of 24 thymic carcinomas, 2 (2%) of 84 thymomas, 3 (8%) of 37 lymphomas, and 14 (4%) of 386 other tumors. Among the lymphomas, 4C7 labeled 2 of 4 peripheral T-cell lymphomas and 1 of 4 anaplastic large cell lymphomas. Clone 4C7 produced strong labeling of reactive T lymphocytes, whereas CD5/54/B4 staining of these cells was weak or absent. No other normal cells seemed to stain with either antibody. In conclusion, one CD5 antibody clone (CD5/54/B4) specifically identified 30% of thymic carcinomas. The other CD5 antibody (clone 4C7) identified 62% of thymic carcinomas but also labeled occasional other neoplasms.

Antibodies, Monoclonal↗
PubMed1996

Malignant lymphoma can present as hepatobiliary disease.

BACKGROUND: Liver involvement by non Hodgkin's lymphoma usually represents systemic progression of a low grade lymphoma. Sixteen patients without palpable lymphadenopathy who presented with features suggesting hepatic inflammation were found to have non Hodgkin's lymphoma involving the liver. METHODS: Tissue sections stained with hematoxylin and eosin were examined by light microscopy. Immunohistochemical studies were performed on formalin-fixed paraffin embedded tissue to determine phenotype. Patients' medical records were reviewed for clinical details. RESULTS: Clinical presentation included fever, jaundice, and elevated liver enzymes. Peripheral lymphadenopathy was absent. Hepatomegaly and splenomegaly were common. Imaging studies revealed a homogeneous pattern of liver involvement without a discrete mass. Histologically, infiltration of the liver was predominantly portal consisting of large, atypical cells scattered within a background of small lymphoid cells. By immunohistochemistry, it was determined that eight were T-cell and eight were B-cell lymphomas. Of the eight patients who had lymph node sampling, three showed involvement by diffuse mixed, small cleaved, and large cell lymphomas. Each of these three involved lymph nodes was located near the liver. Bone marrow infiltration was demonstrated in 10 of the 11 patients in whom it was sampled. Eleven of the 16 patients died 2 days to 31 months after diagnosis, and at last follow-up, 5 patients were alive 2 weeks to 13 months after diagnosis. CONCLUSIONS: Patients with non-Hodgkin's lymphoma can present with hepatic dysfunction and without peripheral lymphadenopathy. This presentation of lymphoma is associated with extensive disease and an aggressive course.

Adolescent↗
PubMed1996

Antibody NCL-CD5 fails to detect neoplastic CD5+ cells in paraffin sections.

Many low grade B-cell lymphomas, and most T-cells lymphomas, express CD5 on their surface. This expression has been demonstrated in fresh cells or frozen sections. Recently, a new monoclonal antibody to CD5, NCL-CD5, has been introduced that detects CD5 in paraffin-embedded tissues. Paraffin-embedded tissues from five patients with small lymphocytic lymphoma (SL), four patients with chronic lymphocytic leukemia (CLL), and one patient each with large granular lymphocytic leukemia, diffuse large cell lymphoma (T cell), and mycosis fungoides were stained with the NCL-CD5 antibody after unmasking the antibody with the steam/citrate technique. All these cases had CD5 positivity demonstrated by flow cytometry or on cytospin or frozen section preparations. In addition, one case of angiofollicular lymph node hyperplasia (CD5+), two cases of SL/CLL (CD5-), and one case CD5- T-cell lymphoma were also investigated. Of the 12 CD5+ malignancies, only 1, an SL, was positive with the NCL-CD5 antibody. In seven of these cases, both B-5 and formalin-fixed tissues were tested; the one positive case was positive only in the formalin tissue. The three CD5- malignancies were also negative in paraffin sections (P = .001; McNemar test). However, reactive T cells did stain in these biopsy sections. The case of Castleman's disease showed many CD5+ cells with the NCL-CD5 antibody. Although NCL-CD5 does indeed stain reactive T cells in paraffin sections, it does not appear to stain neoplastic CD5+ cells.

Antibodies, Monoclonal↗
PubMed1996

CD5 immunoreactivity of epithelial cells in thymic carcinoma and CASTLE using paraffin-embedded tissue.

Because the histologic features may resemble those of other mediastinal malignancies, thymic carcinoma can be difficult to diagnose, particularly if the primary site is uncertain. In an effort to facilitate this diagnosis, the authors have evaluated the use of immunohistochemistry with an antibody to CD5 (NCL-CD5). Nine thymic carcinomas, 15 thymomas, 8 lymphomas, 10 poorly differentiated lung carcinomas, 10 breast carcinomas, 1 mediastinal seminoma, and 1 thyroid carcinoma showing thymus-like differentiation (CASTLE) were studied. Four of 9 poorly differentiated carcinomas of the thymus were CD5 positive. The one CASTLE was CD5 positive. All other tumors were negative. CD5-positive lymphocytes were internal controls in every case. CD5 labels some thymic carcinomas in paraffin-embedded tissue, whereas other tumors studied were negative. CD5 immunoreactivity of CASTLE appears to support thymic derivation of this tumor.

Adult↗
PubMed1996

Long-term results of breast conservation therapy for breast cancer.

OBJECTIVE: This study was done to determine the long-term outcome of breast conservation therapy (BCT) for patients with early-stage breast cancer during a period of treatment evolution at a single institution. SUMMARY BACKGROUND DATA: Breast cancer treatment has evolved from extensive surgical extirpation of the breast to treatment options that conserve the breast. Prospective and retrospective studies have confirmed the efficacy of BCT and justify its use for many patients with early breast cancer, but there is no universally accepted consensus as to who benefits from more aggressive application of surgery or radiotherapy in BCT. Prognostic variables for breast cancer and information on factors that contribute to local recurrence help predict BCT results. Continued analysis of BCT still is necessary to improve patient outcome. METHODS: Eighty-five patients treated with BCT (lumpectomy with adjuvant radiation therapy) at the Medical College of Virginia from 1980 to 1990 were identified. Clinicopathologic parameters and treatment details were analyzed for relationship to development of local recurrence, distant metastasis, and survival. Fisher's exact test was used for comparisons. Actuarial survival curves were plotted. The earlier treatment period (1980-1985) was compared with the later treatment period (1985-1990). RESULTS: Median follow-up was 5 years. Actuarial overall survival was 83% at 5 years (69% at 10 years), and 5-year distant metastasis-free survival was 79%. The 5-year actuarial local recurrence rate was 6.6% (crude rate 10.6%, 9/85). Young patients (age < 40 years) were found to be at increased risk for local recurrence (24% < 40 years vs. 6% > or = 40 years, p < 0.05). Tumor margins < or = 3 mm were more frequently found, and lumpectomy site radiation boost was used increasingly from 1986 to 1990. Almost half of all local recurrences occurred after 5 years. CONCLUSIONS: Survival and local recurrence rates were comparable to other series. Young patients were found to be at increased risk for local recurrence. Negative microscopic margins, even when close, can provide low local recurrence rates when adjuvant radiation therapy is administered.

Adult↗
PubMed1996

Cytokeratins 7 and 20 and carcinoembryonic antigen in ovarian and colonic carcinoma.

The histologic distinction between adenocarcinoma primary to the ovary and metastatic to the ovary can be difficult. In an effort to facilitate this distinction, we have evaluated the use of immunohistochemical techniques with antibodies to cytokeratins 7 and 20, along with antibodies to carcinoembryonic antigen. We studied 24 primary ovarian adenocarcinomas, 11 colonic adenocarcinomas metastatic to the ovary, and 10 primary adenocarcinomas of the colon. Four ovarian adenocarcinomas metastatic to the colon were also studied. All but one of the primary and metastatic colonic carcinomas were negative for cytokeratin 7, whereas all the primary and metastatic ovarian carcinomas were positive for cytokeratin 7. The tumors metastatic to the ovary were all positive for cytokeratin 20 and carcinoembryonic antigen. Among the primary ovarian carcinomas, none of six serous tumors, three of seven endometrioid tumors, and three of 11 mucinous tumors were positive for cytokeratin 20. Ten of the primary ovarian tumors were negative for carcinoembryonic antigen using both monoclonal and polyclonal antibodies. One of the ovarian tumors was negative for carcinoembryonic antigen with the monoclonal antibody but positive using the polyclonal antibody. Cytokeratin 7 is the most helpful marker in the distinction between primary ovarian carcinoma and colonic carcinoma metastatic to the ovary.

Adenocarcinoma↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Acetylcholine receptor alpha-subunit and myogenin mRNAs in thymus and thymomas.

Myasthenia gravis is an autoimmune disorder characterized in most cases by serological antibody against the acetylcholine receptor (AChR). Evidence for intrathymic localization of AChR suggests that the thymus has an important role in the pathogenesis of this disorder. Using reverse transcription followed by the polymerase chain reaction, we have demonstrated AChR alpha-subunit mRNA in thymuses and thymomas from patients with and without myasthenia gravis. We have also studied the expression of myogenin which is known to be involved in the regulation of AChR expression. By using the reverse transcription polymerase chain reaction, we found myogenin mRNAs in all of the thymuses and thymomas. Thus, both AChR alpha-subunit and myogenin mRNA are present in all of these specimens. By immunohistochemistry myoid cells (desmin and myoglobin positive) were present in all (four of four) thymuses studied and in two of five thymomas. Thus, in thymomas, nonmyoid cells might express both AChR and myogenin. These results indicate that cells within the thymus and thymoma express AChR and its regulatory protein myogenin and that such cells, under certain conditions, might play a role in the triggering of myasthenia gravis.

Adolescent↗
PubMed1994

Staining for Bcl-2 protein helps to distinguish benign from malignant lymphoid aggregates in bone marrow biopsies.

Lymphoid nodules in a bone marrow biopsy may be either benign or malignant. Morphological clues may help to differentiate the benign from the malignant nodules. However, it is sometimes difficult, if not impossible, to make this distinction, especially in patients with a known low-grade lymphocytic malignancy. This study was undertaken to determine whether staining bone marrow biopsies with an antibody to the bcl-2 protein might aid in making this differentiation. Using a monoclonal antibody to bcl-2, we stained 26 bone marrows with benign lymphoid aggregates, 19 with a follicular lymphoma, 10 with small lymphocytic lymphoma/chronic lymphocytic leukemia, three with other non-Hodgkin's lymphomas, and three with other miscellaneous hematopoietic lesions. Only one of the 26 benign lymphoid aggregates had moderate to intense staining with this antibody; in contrast, 79% of the follicular lymphomas stained positively. Eight of the 10 small lymphocytic lymphoma/chronic lymphocytic leukemia cases stained with moderate to intense intensity; the other two cases had weak staining. No consistent pattern was seen with the other six lesions. Based on this data, we conclude that lack of staining of small lymphoid aggregates within the bone marrow with the antibody to the bcl-2 protein is suggestive of a benign aggregate, whereas moderate to strong staining intensity is most consistent with a malignant process.

Bone Marrow↗
PubMed1994

Small cell carcinomas of the lung express the Bcl-2 protein.

In our laboratory, we observed that a case of small cell carcinoma of the lung (SCLC) stained with a monoclonal antibody (Dako Corp., Bcl-2-124) against the Bcl-2 protein. To determine how common this reaction was, and whether it was specific for SCLC, we stained formalin-fixed, paraffin-embedded tissues from 23 cases of SCLC and 20 cases of squamous cell carcinoma of the lung for Bcl-2. Fifteen of the 23 SCLC cases stained positively for the Bcl-2 oncogene protein. In contrast, weak staining was observed in only three of the squamous cell carcinomas (chi 2-test; P = 0.001). In addition, four small cell carcinoma cell lines (H69, H146, H209, and WB) were tested by immunohistochemistry and flow cytometry for expression of this protein; all four were positive. In these and three other (H128, H432, and H510) SCLC lines, Northern blots of polyadenylated RNA revealed expression of the 6-kb Bcl-2 mRNA. Moreover, Western blots of extracts from these cell lines revealed the characteristic 26-kd band for Bcl-2 protein. In a single cell line, H82, which has previously been characterized as a variant SCLC, we failed to detect expression of the Bcl-2-specific mRNA and protein. We therefore conclude that most cases of SCLC of the lung express the Bcl-2 oncoprotein, which could play a role in the pathogenesis of this disease.

Antibodies, Monoclonal↗
PubMed1993

Malignant lymphoma imitating hepatitis.

BACKGROUND: Involvement of the liver is common in low-grade lymphomas and usually occurs as disseminated disease. Less common causes include primary liver lymphoma, usually of B-cell origin, and hepatosplenic lymphoma, a recently described T-cell lymphoma. METHODS: The medical records of three patients with clinical features of hepatitis who were found at autopsy to have lymphoma involving primarily the liver and spleen were reviewed. Tissue sections were stained with hematoxylin and eosin after fixation. Immunohistochemistry evaluation was performed by the immunoperoxidase technique on tissue fixed in formaldehyde solution and embedded in paraffin. Frozen tissue was available for additional immunophenotypic studies in one patient (Patient 1). RESULTS: Presenting signs included fever, jaundice, hepatomegaly, and elevated liver enzyme levels, especially serum alkaline phosphatase and bilirubin. Palpable lymphadenopathy was absent. Clinical evaluation indicated hepatitis. Lymphoma was the unexpected finding at postmortem examination after a rapidly deteriorating clinical course. The entire liver in each patient showed a predominant portal lymphomatous infiltration. Two patients had small cleaved cell lymphomas, and one had a large cell lymphoma. Immunologically, one of the small cleaved cell lymphomas was of B-cell phenotype and one was of T-cell origin. The large cell lymphoma showed immunologic staining only with the CD15 antibody (LeuM1). CONCLUSIONS: Lymphoma diffusely involving the liver frequently is associated with splenic involvement and may present as primary hepatic dysfunction. In contrast to previous reports of hepatosplenic T-cell lymphoma, this series suggests that lymphoma involving primarily the liver and spleen can be diverse in cytologic and immunologic characteristics.

Aged↗