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Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 217 records · Page 12Linked to original sources

Lipoblastoma and lipoblastomatosis: a clinicopathological study of 14 cases.

The clinicopathological features of 14 cases of lipoblastoma and lipoblastomatosis are presented. The age of the patients at presentation ranged from 5 days to 6 years (mean 2.7 years); nine patients were male. Histologically, six cases were circumscribed (lipoblastoma) while eight were diffuse and ill-defined (lipoblastomatosis). In both groups and in individual cases there was distinct lobulation, as well as a spectrum of adipocytic maturation. Cytologically, the 10 most mature lesions were composed of uniform adipocytes intermixed with only scattered lipoblasts and primitive mesenchymal cells. A notable feature in the other four cases was a prominent myxoid stroma producing a very close resemblance to myxoid liposarcoma. Mitotic figures were rare and always normal in appearance. Atypical nuclei were not evident. Follow-up in eight patients revealed local recurrence in two. Liposarcoma in patients under 10 years is exceedingly rare, and, in myxoid form, may be almost impossible to distinguish histologically from lipoblastoma. Helpful clues are the lack of lobulation, variable growth pattern and increased nuclear atypia in liposarcoma.

Child↗

Lipoprotein(a) and postmenopausal oestrogen.

Epidemiological studies have shown that postmenopausal oestrogen therapy substantially reduces the risk of cardiovascular and cerebrovascular disease and this is partly mediated by oestrogen-associated changes in lipoproteins, particularly high-density lipoprotein. In this study, we investigated whether changes in lipoprotein(a) might help to account for the reduction in coronary heart disease and stroke associated with postmenopausal oestrogen therapy. The study group consisted of 18 women who had hysterectomy and bilateral oophorectomy at least 2 months prior to recruitment and had received no previous hormonal therapy. Serum samples were collected for measurement of lipoprotein(a) before and after 4 months of treatment with oestradiol valerate (2 mg/day). Lipoprotein(a) levels ranged from 35 to 720 mg/l (median 180 mg/l) before treatment and from 55 to 780 mg/l (median 130 mg/l) after oestradiol treatment and showed no consistent pattern of change. It would appear, therefore, that treatment with unopposed oestrogen in relatively low doses not have a marked effect on lipoprotein(a), at least in the short term.

Adult↗

Expression of adhesion molecules on the endothelium of normal tissue vessels and vascular tumors.

BACKGROUND: Endothelial cells are important in initiating adhesive processes between circulating cells and extracellular structures and changes in their distribution are believed to be important in many pathologic conditions. Since little is known about the detailed distribution of adhesion molecules in human endothelium in different sites and circumstances, the present study has undertaken a detailed analysis of 5 of the putative most important adhesion molecules on a wide range of normal tissue endothelium. We have compared this reactivity with that seen in a comprehensive range of vascular tumors both benign and malignant. EXPERIMENTAL DESIGN: Fresh samples of a wide range of normal tissues and vascular tumors were stained by antibodies against the following adhesion molecules; intercellular adhesion molecule-1 (CD54), E-selectin (endothelial cell adhesion molecule-1), vascular cell adhesion molecule-MUC-1, P-selectin (platelet activation-dependent granule to external membrane protein, CD62) and MUC-18 using either the APAAP immuno-alkaline phosphatase or an immunoperoxidase method. RESULTS: Labeling of the endothelial cells in different normal tissues with intercellular adhesion molecule-1, P-selectin, and MUC-18 was heterogeneous both in terms of vessel size and strength of staining. Vascular cell adhesion molecule-1 and E-selectin were largely absent. The vascular tumors were likewise variable in their staining patterns which frequently differed from the immunophenotype of the reactive vessels surrounding the tumor. CONCLUSIONS: This study demonstrates that the expression of adhesion molecules of the immunoglobulin and selectin family on normal tissue endothelium, and vascular tumors is much less predictable than that obtained with other vascular markers such as F8 RA, CD31, CD34, and CD36. Adhesion molecules show considerable heterogeneity of expression on vascular endothelium which presumably reflects their varied functions on different types of vessel. In general their expression is markedly reduced on vascular tumors.

Antibodies, Monoclonal↗

Pleomorphic rhabdomyosarcoma in adulthood. Analysis of 11 cases with definition of diagnostic criteria.

Currently, pleomorphic rhabdomyosarcoma (RMS) in adults is considered to be extremely rare or nonexistent. The authors have identified 11 cases of pleomorphic RMS using the following criteria: pleomorphic sarcoma occurring within voluntary muscle, large polygonal or strap-like cells with copious eosinophilic cytoplasm, desmin and myoglobin immunoreactivity, or ultrastructural evidence of sarcomeric differentiation. Ten patients were male, the median age at presentation was 56 years (range, 27-84), and the thigh (seven cases) was the most common site. Of eight cases with clinical follow-up, one patient is alive at 20 months, and seven died 2 to 28 months following diagnosis. The tumors were generally patternless, but several had storiform areas. Cross-striations were not identified. Immunostaining for muscle-related antigens was positive as follows: desmin (in 10 of 11 cases), myoglobin (in 10 of 11 cases), actin HHF-35 (in all 11 cases), smooth-muscle actin (in six of eight cases), sarcomeric actin (in six of nine cases), and fast myosin (in five of five cases). Staining for S-100 protein was negative in all cases. On electron microscopy (six cases), two tumors had well-differentiated rhabdomyoblasts with sarcomeres, Z-disks, and hexagonal arrays of myofilaments; three were poorly differentiated; and one contained immature mesenchymal cells only. Pleomorphic RMS can be distinguished from other pleomorphic sarcomas provided that well-fixed tumor tissue is available for immunohistochemical staining and electron microscopy. We consider that this distinction is important in view of the poor prognosis associated with pleomorphic RMS in this series.

Adult↗

A comparison of proliferating cell nuclear antigen (PCNA) immunostaining, nucleolar organizer region (AgNOR) staining, and histological grading in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours are lesions in which it is difficult to predict clinical outcome from the histological appearances. Sixty cases were studied using three different methods of assessing aspects of cellular proliferation; these were (i) immunostaining for proliferating cell nuclear antigen (PCNA), (ii) interphase nucleolar organizer region staining (AgNORs), and (iii) a histological grading system based on mitotic counts. Both PCNA immunostaining and AgNOR counts were found to correlate well with histological grading and all three methods independently showed good correlations with survival. This suggests that these proliferation-associated markers may be used as additional features to support histological grading in this relatively uncommon group of tumours.

Antigens, Neoplasm↗

TDM35--a new monoclonal antibody to the XH1 cervical carcinoma cell line. Characterization and immunoperoxidase localization in benign and malignant tissues.

The murine monoclonal IgG1 kappa antibody TDM35 was raised against the cervical carcinoma cell line XH1. The antibody recognizes 18.5-66 kDa NCA-like glycoproteins and immunostains a variety of formalin-fixed, paraffin-embedded normal, benign, and malignant tissues. It is of value in the diagnosis of carcinoma of the exocrine pancreas and it identifies foci of squamous and glandular differentiation in other tumours. TDM35 should form a useful addition to a panel of antibodies for the evaluation of epithelial lesions.

Adenocarcinoma↗

Malignant paraganglioma of the uterus.

We report a malignant uterine paraganglioma in a 40-year-old female, who died 7 months after the initial diagnosis. On light microscopy the tumour showed a typical zellballen pattern as well as a pronounced cellular pleomorphism. In many tumour cells hyaline globules were demonstrated within the cytoplasm. Immunohistochemically the lesion was characterized by the presence of neuron-specific enolase, protein gene product 9.5 and synaptophysin, and electron microscopically by the occurrence of neurosecretory granules.

Adult↗

Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature.

Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood.

Abdominal Neoplasms↗

Primary vascular tumors of lymph nodes other than Kaposi's sarcoma. Analysis of 39 cases and delineation of two new entities.

Primary vascular tumors of lymph nodes other than Kaposi's sarcoma are very rare, as attested to by only a handful of case reports in the literature. Based on an analysis of 39 such cases, we could distinguish five major groups. Hemangiomas of capillary/cavernous, lobular capillary, and cellular types were composed of compact aggregates of blood-filled vessels, variable in size, that replaced the nodal architecture partly or almost completely; some appeared to have originated in the hilum or medulla. These hemangiomas either represented incidental findings in lymph nodes or were seen with solitary lymph node enlargement; the evolution was benign with no recurrence. A distinctive benign lesion occurring exclusively in inguinal lymph nodes, which we propose designating "angiomyomatous hamartoma," showed replacement of the nodal parenchyma by smooth muscle cells and fibrous tissue, in continuity with exuberant proliferation of muscular vessels in the hilum. Epithelioid vascular tumors, characterized by plump endothelial cells with dense eosinophilic cytoplasm and numerous vacuoles, exhibited a range of differentiation, from hemangioma with well-formed vascular channels (with or without tissue eosinophilia) to hemangioendotheliomas composed predominantly of cords and sheets of tumor cells lying in a hyaline-myxoid matrix. Epithelioid hemangioendothelioma was particularly likely to be mistaken for metastatic carcinoma, and local recurrence could occur. A variant, the spindle and epithelioid hemangioendothelioma, was characterized by the presence of an additional component of spindle cells. Another tumor we found, polymorphous hemangioendothelioma, is a previously uncharacterized borderline malignant vascular tumor exhibiting solid, primitive vascular and angiomatous patterns and relatively bland cytologic features. Lymphangiomas of lymph nodes usually showed simultaneous multifocal and extra-nodal involvement and were characterized by cystic endothelium-lined spaces filled predominantly with lymph fluid. It is important to recognize these primary vascular tumors of lymph nodes to avoid mistaking them for a variety of benign vasoproliferative lesions, Kaposi's sarcoma, angiosarcoma, and metastatic cancer.

Adolescent↗

Angiomyofibroblastoma of the vulva. A benign neoplasm distinct from aggressive angiomyxoma.

Aggressive angiomyxoma of pelvic soft parts is a rare lesion with a high risk of recurrence. We report 10 cases of angiomyofibroblastoma, a hitherto uncharacterized benign tumor of the vulva histologically mimicking aggressive angiomyxoma. All patients had a vulval mass, often clinically diagnosed as a Bartholin's cyst. There was no recurrence after excision. The tumors were well circumscribed, measuring 0.5-12 cm in maximum dimension. They were characterized by alternating hypercellular and hypocellular edematous zones in which abundant blood vessels (predominantly of the capillary type) were irregularly distributed. Spindled, plump spindled, and oval stromal cells were aggregated around the blood vessels, sometimes forming solid compact foci, or were loosely dispersed in the hypocellular areas. Their nuclei were bland, but rare ones were enlarged and hyperchromatic in four cases. Some cells had abundant eosinophilic hyaline cytoplasm and eccentrically placed nuclei. Mitotic figures were absent or very sparse. Scattered throughout were thin, wavy strands or thick bundles of collagen. Mast cells were readily seen in eight cases. Immunohistochemically, the stromal cells were reactive for vimentin and desmin, but not cytokeratin, muscle-specific actin, alpha-smooth muscle actin, or S-100 protein. Ultrastructural studies showed well-developed rough endoplasmic reticulum, Golgi apparatus, abundant intermediate filaments, and pinocytotic vesicles in the stromal cells. Angiomyofibroblastoma can be distinguished from aggressive angiomyxoma by its circumscribed borders, much higher cellularity, more numerous blood vessels (which lack prominent hyalinization), frequent presence of plump stromal cells, minimal stromal mucin, and rarity of erythrocyte extravasation.

Adult↗

Pseudosarcomatous myofibroblastic proliferations of the spermatic cord ("proliferative funiculitis"). Histologic and immunohistochemical analysis of a distinctive entity.

Pseudosarcomatous myofibroblastic proliferations have been recognised at a variety of sites. We describe five lesions of the spermatic cord, four of which were incidental findings at inguinal herniorrhaphy. The patients' age range was 52-76 years. In all cases, sarcoma was suspected histologically, but each lesion showed morphologic features in keeping with fasciitis-like lesions described at other sites. Two cases showed actin positivity, supporting this interpretation. All were marginally or incompletely excised. One recurred locally. We believe that ischemia or torsion is of pathogenetic importance at this site. We propose that the term "proliferative funiculitis" be used to describe this type of reactive process when it presents in the spermatic cord.

Aged↗

Cellular 'neurothekeoma': an epithelioid variant of pilar leiomyoma? Morphological and immunohistochemical analysis of a series.

Cellular neurothekeoma is a recently recognized benign cutaneous neoplasm, which is currently regarded as being of nerve sheath origin and is thought to represent a variant of conventional neurothekeoma (dermal nerve sheath myxoma). Nine new cases presenting predominantly in adolescents or young adults are described. Morphologically they were characterized by short fascicles or small nests of palely eosinophilic epithelioid or spindle-shaped cells which ramified in an ill-defined manner between dermal collagen bundles. Myxoid matrix was absent or sparse. Scattered normal mitoses and multinucleate giant cells were often present. Immunohistochemically all nine cases were strongly NK1/C3 positive, seven were weakly NSE positive and three were smooth muscle actin positive. Staining for S-100 protein, PGP 9.5, epithelial membrane antigen and desmin was negative in all cases. In view of its distinctive architecture and immunophenotype, both of which are totally different from conventional neurothekeoma, it is proposed that cellular 'neurothekeoma' is a separate discrete entity which may represent an epithelioid variant of pilar leiomyoma.

Adolescent↗

Primary biphasic synovial sarcoma of the orbit.

Synovial sarcoma is one of the most common soft tissue malignancies of adolescents and young adults. Despite its name, it is no longer thought to be histogenetically derived from the synovium. What seems to be the first case of synovial sarcoma to arise in the orbit presented in a 21 year old woman as a slowly enlarging subconjunctival mass. Although this tumour was typically biphasic, the monophasic spindle cell variant arising at this site could easily be confused with less aggressive orbital connective tissue neoplasms.

Adult↗

Reversible menopause induced by the GnRH analogue buserelin: effects on lipoprotein metabolism.

GnRH agonists can induce a reversible pharmacological menopause and can be used to treat endometriosis, a fairly common gynaecological problem which responds well to oestrogen deprivation. Premature menopause is associated with adverse lipid changes and an increased risk of coronary heart disease. Therefore we set out to investigate changes in lipoprotein metabolism in a group of premenopausal women being treated with the GnRH analogue buserelin for active endometriosis. We monitored lipoprotein levels, high density lipoprotein subfractions and apolipoproteins AI, AII and B during a 12-month course of treatment and for 6 months afterwards. Treatment caused a sustained increase in HDL3 cholesterol levels and a small increase in low density lipoprotein cholesterol, which was significant at the six-month visit only. Apolipoprotein B levels rose significantly and there were marginal increases in apolipoproteins AI and AII. All changes and trends were reversed after cessation of treatment. We conclude that the treatment did not profoundly affect lipoprotein metabolism, neither LDL nor HDL cholesterol, the established important risk markers for coronary heart disease appreciably altered.

Adult↗