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Biomedical subjects

D M Menke

Publications and source records attributed to D M Menke.

At least 19 recordsLinked to original sources

Chymase expressing bone marrow mast cells in mastocytosis and myelodysplastic syndromes: an immunohistochemical and morphometric study.

BACKGROUND: Two cell specific neutral proteases, tryptase and chymase, are produced by human mast cells (MC). Tryptase is constitutively expressed by all MC, whereas chymase is found only in an MC subset. Very little is known about chymase expression in MC proliferative disorders (mastocytosis). AIMS AND METHODS: Routinely processed, formalin fixed, and paraffin wax embedded bone marrow trephine biopsy specimens obtained from patients with various subtypes of mastocytosis (n = 47) and myelodysplastic syndromes (MDS; n = 28) were immunostained with antibodies against chymase and tryptase. Normal/reactive bone marrow specimens with intact haemopoiesis (n = 31) served as controls. The numbers of chymase expressing (C+) and of tryptase expressing (T+) MC were assessed morphometrically using a computer assisted video camera system. RESULTS: In normal/reactive bone marrow, the numbers of C+ MC (median, 8/mm(2); maximum, 159/mm(2)) were in the same range as those of T+ MC (median, 4/mm(2); maximum, 167/mm(2)). Because normal MC express both chymase and tryptase, these findings indicate that the common phenotype of bone marrow MC in normal/reactive states is MC(TC) (MC expressing both tryptase and chymase). In contrast, in MDS and mastocytosis, the bone marrow exhibited far more T+ MC than C+ MC in almost all cases. CONCLUSIONS: According to these findings, the predominant MC type in the bone marrow in neoplastic states such as MDS and mastocytosis is MC(T) (MC expressing only tryptase). Although the pathophysiological basis of this apparent lack of chymase expression in most neoplastic MC in mastocytosis and MC involved in MDS remains unknown, this study has produced further evidence of the superior value of antitryptase antibodies in the diagnosis of mastocytosis.

Bone Marrow Cells↗

Agnogenic myeloid metaplasia associated with Klinefelter syndrome: a case report.

Klinefelter syndrome is the most commonly diagnosed sex chromosome disorder among males. It is usually associated with 47 chromosomes, including two Xs and one Y. The formal cytogenetic designation for Klinefelter syndrome is 47, XXY; the extra sex chromosome is due to meiotic chromosomal nondisjunction. Increased risk of various malignant diseases has been recognized among patients with different congenital chromosomal abnormalities. Since the early 1960s, numerous reports have appeared of an increased risk of malignant neoplasms among patients with Klinefelter syndrome. Evidence suggests a correlation with increased incidences of germ cell tumors and breast cancers. Whether these patients are at an increased risk of hematologic malignant disease, especially acute leukemia, is still uncertain. This report describes a patient with agnogenic myeloid metaplasia and Klinefelter syndrome, an association not previously reported.

Cytogenetic Analysis↗

Primary lymph node plasmacytomas (plasmacytic lymphomas).

To determine whether primary lymph node plasmacytoma (PLNP) is a distinct entity among other types of plasma cell neoplasia, we analyzed a large series of PLNPs from 2 large lymphoma registries to compare histologic, immunophenotypic, and clinical features of PLNPs, nonnodal extramedullary plasmacytomas, and multiple myeloma. Twenty-five PLNPs (clinical data on 15 cases) were compared with 10 non-lymph node plasmacytomas and 51 cases of multiple myeloma; 36 cases of reactive plasmacytoses were used as controls. The histologic features of PLNP and other extramedullary plasmacytomas were similar. The histologic features of PLNPs were more immature than those of reactive plasmacytoses and less immature than in multiple myeloma. The immunophenotype of PLNPs significantly differed from that of reactive plasmacytoses, other extramedullary plasmacytomas, and multiple myeloma. PLNPs did not progress to multiple myeloma, unlike other extramedullary plasmacytomas, even though survival in PLNPs and other extramedullary plasmacytomas was similar. Our findings suggest that PLNPs may be distinct from other plasma cell dyscrasias.

Adolescent↗

Lack of cytogenetic abnormalities in Castleman's disease.

BACKGROUND: Castleman's disease (CD) is a distinctive type of atypical lymph node hyperplasia that is often clonal. In a previously reported series of CD, clonal populations of plasma cells were detected by immunohistology in 4 of 39 cases (10%, lambda restricted), and immunoglobulin gene rearrangements were detected by paraffin polymerase chain reaction (PCR) analysis in 10 of 37 cases (27%). Cytogenetic analysis has been used to detect clonal proliferations of plasma cells in myeloma and clonal proliferations of lymphocytes in lymphomas and has identified critical gene loci that are important in the histopathogenesis of these disorders. Cytogenetic studies have not been done on a large series of patients with CD. Thus, we reviewed the archives of our institution for cases of CD and lymphoma that had had cytogenetic analysis. METHODS: The cytogenetic and lymphoma archives of our institution (a tertiary care center) from 1985 to 1998 were reviewed for the diagnoses of CD and lymphoma. There were 21,006 lymphomas, 701 of which had cytogenetic analysis (400 abnormal). There were 162 cases of CD, 7 of which had cytogenetic analysis. The frequency of cytogenetic abnormalities in CD was compared with that in lymphoma. The sensitivity of cytogenetics for defining clonality in CD was compared with immunohistology and paraffin PCR-amplified immunoglobulin heavy-chain gene rearrangement. RESULTS: From 1985 to 1998, 162 cases of CD and 21,006 cases of lymphoma were diagnosed. Cytogenetic analysis yielded adequate numbers of metaphases for analysis of 4 cases of CD and 701 lymphomas. Cytogenetic abnormalities were not identified in CD but were identified in 400 lymphomas (57%). Although 1 of 4 cases of CD was clonal by immunohistology (lambda restricted), no immunoglobulin gene rearrangements were detected by paraffin PCR analysis. CONCLUSIONS: The frequency of cytogenetic abnormalities in lymphomas and the lack of cytogenetic abnormalities in CD suggest that cytogenetic abnormalities, as detected by conventional cytogenetic analysis, are important in the pathogenesis of lymphoma but not CD. The lack of cytogenetic abnormalities in CD supports the hypothesis that CD is an interleukin-6-driven lymphoproliferative disorder.

Castleman Disease↗

Tarsal fibroma.

PURPOSE: To report a case of an isolated tarsal fibroma. METHODS: Case report. Excisional biopsy and histopathological evaluation were performed on a solid lesion originating from the tarsal conjunctival surface of an upper eyelid. RESULTS: Histopathological evaluation, including positive trichrome stains, was consistent with fibroma of the left upper tarsus. No recurrence has developed after a follow-up interval of a year. CONCLUSION: Tarsal fibroma is a rare condition that should be considered in the differential diagnosis of tarsal lesions.

Aged↗

Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.

Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.

Adolescent↗

Pheochromocytoma in an incidentally discovered asymptomatic cystic adrenal mass.

Cystic adrenal lesions can be either cortical or medullary, and distinguishing between these 2 types of lesions may be important in patient management. Pheochromocytomas, which are adrenal medullary neoplasms, typically manifest with hypertension, headaches, palpitations, tachycardia, sweating, and anxiety symptoms; however, 10% to 17% of patients with pheochromocytomas are asymptomatic. We describe a 67-year-old woman with lifelong headaches and recent persistent cough in whom a left cystic adrenal mass was incidentally discovered by computed tomography of the chest. A moderate increase in normetanephrine and total metanephrine values in two 24-hour urine samples suggested a pheochromocytoma. Computed tomography with use of contrast medium revealed ring enhancement of the cyst wall, a finding consistent with an adrenal medullary tumor. This report demonstrates the importance of repeated 24-hour urine samples to determine the metanephrine values together with contrast-enhanced computed tomography in a patient with nonspecific symptoms.

Adrenal Cortex Function Tests↗

Hodgkin's disease of the esophagus: report of a case.

Most esophageal malignancies are either squamous carcinomas or adenocarcinomas arising in the background of Barrett's esophagus. We describe a case of an 85-yr-old woman in whom the diagnosis of esophageal malignancy was difficult to confirm despite its endoscopic appearance and previous biopsies. This case illustrates the difficulty in diagnosing Hodgkin's disease of the esophagus. Despite the rarity of this entity, if clinically indicated by symptoms, large, deep biopsies by rigid esophagoscopy should be considered.

Aged↗

Intravascular lymphomatosis. A report of ten patients with central nervous system involvement and a review of the disease process.

The clinical, radiographic, and pathological findings in ten cases of intravascular lymphomatosis with central nervous system involvement seen at our institution over a 15-year period are presented. Nine patients presented with a subacute, progressive multifocal neurologic disorder. Most patients had fever, anemia, and elevation of the erythrocyte sedimentation rate. As the illness evolved, computerized tomography scanning and magnetic resonance imaging showed evidence of multifocal central nervous system disease. Angiography was nondiagnostic but suggested vasculitis in six cases. A response to empiric corticosteroid treatment was typical but usually transient. In six patients, the diagnosis was made antemortem by brain biopsy. The prognosis of patients was primarily dependent on early diagnosis and treatment, before massive central nervous system damage occurred. Treatment with chemotherapy, with or without radiotherapy, was associated with stabilization of the disease in three of five patients.

Aged↗

Localized lymphoplasmacellular pancreatitis forming a pancreatic inflammatory pseudotumor.

Inflammatory pseudotumors (IPTs) of the pancreas are rare. To our knowledge, we report the first case of a pancreatic IPT composed of dense lymphocytic and plasmacellular infiltrates that histologically resembled a primary lymphoplasmacytic lymphoma of the pancreas. In addition, it is the first pancreatic IPT analyzed for latent Epstein-Barr virus, an agent implicated in the pathogenesis of IPTs of the liver and spleen.

Granuloma, Plasma Cell↗

Immunophenotypic and genotypic characterisation of multiple myelomas with adverse prognosis characterised by immunohistological expression of the T cell related antigen CD45RO (UCHL-1).

AIMS: To investigate whether plasma cell expression of early B cell, late B cell/preplasma cell, T cell, and myelomonocytic antigens or myeloma associated lymphocytic infiltrates correlated with prognosis in bone marrow biopsy specimens of patients with multiple myeloma. METHODS: Bone marrow biopsy specimens of 23 patients with multiple myeloma were investigated for plasma cell expression and interstitial lymphocyte expression of T cell related antigen CD45RO (UCHL-1). RESULTS: Eight patients showed plasma cell expression of CD45RO and 16 showed increased tumour infiltrating CD45RO positive lymphocytes, which were correlated with poor survival by multivariate analyses (p = 0.005 and p = 0.04, respectively). B cell antigens (MB2, CD20) but no T cell specific antigens (CD3) or T cell receptor gene rearrangements were expressed by plasma cells in CD45RO positive myelomas. Of 16 patients with myeloma who had increased tumour infiltrating CD45RO positive lymphocytes, four had interstitial lymphocyte expression of B cell antigens and two had interstitial lymphocyte expression of the T cell specific antigen CD3. CONCLUSIONS: The recognition of plasma cell expression of CD45RO and increased interstitial CD45RO lymphocytes in bone marrow biopsy specimens of patients with multiple myeloma is an adverse prognostic finding not indicative of an aberrant T cell phenotype or genotype; it is consistent with B cell/pre-plasma cell antigen expression by myeloma cells and their lymphocytic precursors.

Adult↗

Hand-assisted laparoscopic distal pancreatectomy for pancreatic cystadenoma.

A cystic lesion in the body of the pancreas was detected during staging workup of a 59-year-old woman with T-cell lymphoma of the tongue. After six cycles of chemotherapy the pancreatic lesion was unchanged. Suggestive ulceration of the vulva with edema appeared at the end of chemotherapy. After right vulvar excision, distal pancreatic resection with splenectomy was carried out by a hand-assisted laparoscopic technique utilizing a small muscle-splitting right lower quadrant incision. This allowed for palpation of the peritoneal cavity for evidence of tumor and allowed for safe and expeditious pancreatectomy. The pancreatic tumor was found to be a serous cystadenoma without evidence of malignancy. T-cell lymphoma was identified in the spleen and the vulva. The patient was discharged home on the fifth postoperative day and returned to normal activity within 2 weeks after operation. Two months after the surgery, computed tomography demonstrated a 3-cm pseudocyst in the region of the tail of the pancreas. As the patient was asymptomatic, this required no further therapy. Minimally invasive surgery together with hand assistance combines the advantages of both laparotomy and laparoscopy in the surgical management of selected lesions in the pancreas.

Cystadenoma↗

Mastocytosis: reactive or neoplastic?

Mast cells are now known to derive from CD34+ haemopoietic stem cells in the bone marrow. However, it has not yet been established whether the various types of mastocytosis, which involve tumour-like proliferation of mast cells, are true neoplastic disorders or reactive/hyperplastic conditions. In this study, tissue specimens (five bone marrow, two spleen, one skin) from female patients with histologically confirmed mastocytosis were investigated with a recently developed polymerase chain reaction assay for the determination of clonality of female cells using the human androgen receptor gene (HU-MARA). Mast cells purified to near homogeneity from hysterectomy specimens served as a control. The findings in bone marrow and skin either were not reproducible, or indicated polyclonality. However, both spleen specimens exhibited monoclonality. In addition, DNA analysis by flow cytometry was performed and revealed a diploid chromosome content with proliferation indices of under 8% in all the specimens. This is the first molecular biological study to indicate that mastocytosis is indeed neoplastic in nature.

Case-Control Studies↗

Neoplastic human tissue mast cells express the adhesion molecule CD44/HCAM.

Expression of the homing-associated cell adhesion molecule/HCAM (CD44) in normal/reactive and neoplastic human tissue mast cells (TMC) was determined immunohistochemically using the antibody DAKO-DF1485, which detects all isoforms of CD44. Studies were performed on 30 routinely processed specimens. Twenty of these, from bone marrow, skin, spleen, liver, lymph node and jejunal mucosa, contained infiltrates of TMC. These represented various types of generalized mastocytosis/systemic mast cell disease, including benign systemic mastocytosis. Ten specimens consisted of tissue with a marked reactive increase in TMC; most of these were lymph nodes with chronic nonspecific lymphadenitis and benign or malignant solid tumours. In all 30 specimens TMC exhibited an annular pattern of immunostaining, which was usually very strong. Both normal/reactive and neoplastic TMC exhibited consistent immunoreactivity with the antibody DAKO-DF1485, and this antibody may be of diagnostic value in the detection of atypical TMC associated with malignant mastocytosis. TMC and their neoplastic derivatives belong to a large family of mesenchymal and epithelial cells containing the principal surface receptor for hyaluronan.

Humans↗