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Biomedical subjects

K Hollowood

Publications and source records attributed to K Hollowood.

35 records · Page 2Linked to original sources

Germinal centre cell kinetics.

The germinal centre is a fundamental component of the humoral immune response, representing a unique microenvironment where antigen-activated B lymphocytes undergo clonal expansion, mutate their immunoglobulin, and are subject to a stringent selection process based on their antigen affinity. This review highlights recent advances in the understanding of the cell kinetic process of activation, proliferation, differentiation, and death of germinal centre cells, which are beginning to provide important insights into the regulation of this highly complex reaction. Their definition may have considerable pathological import given the involvement of the germinal centre in non-Hodgkin's lymphomas and recent evidence suggesting that abnormal germinal centre reactions may be involved in the pathogenesis of Hodgkin's disease and some autoimmune diseases.

Animals↗

Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract. Morphologic, immunohistochemical and ultrastructural analysis of two cases.

Tumors showing differentiation toward follicular dendritic cells are rare and usually occur in lymph nodes. Their occurrence at extranodal sites was recognized recently. This report documents two further extranodal cases, one arising in the small intestine of a 23-year-old woman and the second in periduodenal retroperitoneal soft tissue of a 63-year-old man. Both neoplasms displayed a typical biphasic morphologic pattern, composed of large cells with indistinct cytoplasmic borders creating a syncytial appearance, admixed with spindle cell areas resembling malignant fibrous histiocytoma, and infiltrated by numerous small T lymphocytes. Expression of CD21 and CD35, together with ultrastructural demonstration (in one case) of long cytoplasmic processes connected by desmosomes, confirmed follicular dendritic cell differentiation. One case also expressed HLA-DR, and both showed aberrant epithelial membrane antigen staining. Neither tumor showed CD45 expression. In both cases the tumors were treated by local excision. Case 1 has shown an unusually aggressive course with extensive intraperitoneal recurrence. The biphasic morphologic pattern and tumor immunophenotype are discussed in relation to increasing evidence of immunophenotypic and morphologic heterogeneity of normal follicular dendritic cells.

Adult↗

Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases.

Pseudosarcomatous proliferation of myofibroblasts, fibroblasts and inflammatory cells have been reported in a wide variety of sites and are most commonly termed inflammatory pseudotumours. Despite increasing recognition, the occurrence of inflammatory pseudotumour in somatic soft tissue is poorly documented, such that these lesions are commonly mistaken for a variety of benign and malignant neoplasms. This report documents our experience of 18 cases of soft tissue inflammatory pseudotumour. All arose in adults (median age 54.5 years; range 28-83 years) and showed no sex predilection. Anatomical location was varied but the head and neck region and abdominal cavity were most common. They displayed a spectrum of histological appearances but all were characterized, to a greater or lesser extent, by an admixture of myofibroblasts and fibroblasts, most commonly arranged in short interwoven fascicles, together with a polymorphic inflammatory cell component, consisting principally of lymphocytes and plasma cells. In some cases xanthoma cells were prominent. Simple surgical excision appeared to be curative. The importance of recognizing the presence of a wide clinicopathological spectrum is emphasized and the differential diagnosis, especially from fibrohistiocytic neoplasms or Hodgkin's disease, is discussed.

Adult↗

Soft tissue sarcomas that mimic benign lesions.

Although it is well known that a variety of benign mesenchymal neoplasms and reactive proliferations may mimic sarcomas, the fact that some types of sarcoma commonly are misinterpreted as benign is less widely appreciated. This review considers five such lesions in soft tissue: low grade fibromyxoid sarcoma, low grade myxofibrosarcoma (myxoid "MFH"), well differentiated liposarcoma (atypical lipoma), epithelioid sarcoma, and so-called inflammatory fibrosarcoma. Principal reasons for their underrecognition are their generally bland cytology, often relative hypocellularity, and indolent clinical course. Common to several of these lesions, however, is a tendency for histological and hence biological progression in local recurrences, underlining the importance of accurate diagnosis and adequate treatment of the primary lesion. This review considers the principal clinicopathologic features, differential diagnosis and (where appropriate) nosologic status of this treacherous group of neoplasms.

Connective Tissue↗

Malignant fibrous histiocytoma: morphologic pattern or pathologic entity?

Since the concept of malignant fibrous histiocytoma (MFH) was introduced and subsequently popularized in the 1960's and 1970's, it has become widely regarded as the commonest soft-tissue sarcoma of adulthood. Although the initial notion that MFH was a true histiocytic tumor showing faculative fibroblastic differentiation has been disproved, and despite the lack of definable, reproducible diagnostic criteria and considerable immunophenotypic, ultrastructural and karyotypic heterogeneity, MFH is still accepted widely as a discrete clinicopathologic entity. On the other hand several recent studies have expressed considerable doubts about MFH, or at least pleomorphic MFH, as an "entity" and have suggested that it represents a common morphologic manifestation of a host of poorly differentiated sarcomas and, more rarely, other neoplasms. This article reviews the clinicopathologic features of MFH and its established variants in the context of this debate and considers the evidence for and against their continued acceptance as distinct entities or as a cohesive group. We conclude that the pleomorphic, giant cell and inflammatory variants each represent heterogeneous diagnostic groups which are hard to defend as cohesive entities, while the myxoid ("myxofibrosarcoma") and angiomatoid types are distinct, reproducible tumor types.

Desmin↗

Gastric telangiectasis: a rare cause of severe blood loss in CREST syndrome.

A 46 year old woman presented with the CREST variety of systemic sclerosis and occult gastrointestinal bleeding due to vascular malformations of her stomach. Partial gastrectomy cured her anaemia. In systemic sclerosis, visceral angiography should be performed early when initial investigations have been negative.

CREST Syndrome↗

Rhabdomyosarcoma in adults.

Rhabdomyosarcomas occur in adults in one of two forms; as sporadic cases of the juvenile histological types and more commonly, if controversially, as the major adult form, pleomorphic rhabdomyosarcoma. This review documents the historical background to the fluctuating diagnostic popularity of pleomorphic rhabdomyosarcoma, together with a presentation of its defining clinicopathologic characteristics, and presents the clinicopathologic features of the juvenile types as they occur in adults. The concept of pleomorphic rhabdomyosarcoma as a distinct clinicopathologic entity, presenting as an aggressive, predominantly spindle-cell tumor arising in the skeletal musculature of middle-aged adults and defined by the presence of large, pleomorphic tumor cells, which show, at least focally, immunophenotypic or ultrastructural sarcomeric muscle differentiation, is discussed and supported.

Adult↗

Cell kinetics of the germinal center reaction--a stathmokinetic study.

The changes in splenic germinal center (GC) cell proliferation were measured during primary and secondary responses to a T-dependent antigen in vivo to examine the regulation of the GC reaction. Adult C3H/HeN mice were immunized with sheep red blood cells and boosted 7 or 21 days later. GC cell proliferation was assessed by measurement of GC cell birth rates using a stathmokinetic technique. Actual GC growth and regression were assessed in terms of total splenic volume and number. Pre-existing GC had a mean cell birth rate of 33 cells/1000 cells/h. The GC reactions following each immunization showed a biphasic pattern of changes in cell birth rate, comprising an initial fall immediately succeeded by a transient, but significant, increase. These fluctuations occurred earlier in secondary compared to primary responses. Significant increases in total GC volumes succeeded the peaks of cell birth rate following both primary and early secondary immunization. However, there was a substantially smaller increase following later secondary immunization. We propose that the initial cell birth rate reduction is due to inhibition of pre-existing GC clones and represents one component of the phenomenon of GC dissociation. The succeeding peak birth rate represents early, massive proliferation of newly activated antigen-specific clones. The different patterns of GC expansion, despite similar proliferative responses, may reflect different pathways of differentiation dependent on the timing of antigenic stimulation.

Animals↗

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↗

Rheumatoid arthritis: an association with pemphigus foliaceous.

We have observed a high incidence of pemphigus foliaceous, in the absence of therapy with penicillamine, within a small population of patients with rheumatoid arthritis. We suggest that penicillamine as well as inducing autoimmune disease might exacerbate subclinical pemphigus foliaceous in this group, accounting for those few patients whose skin disease fails to resolve following drug withdrawal. Pemphigus and rheumatoid arthritis have both been associated with HLA DR4, which was present in all three of our patients who were tested.

Adult↗

Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation.

Putative sarcomas of follicular dendritic cells are extremely uncommon and only small case numbers have been clearly documented. A major difficulty in their delineation has been the persistent controversy over the phenotype and ontogeny of normal follicular dendritic cells. Two new cases arising in adult females are presented herein, both of which had initially been mistaken for metastases from a true soft tissue sarcoma. Their morphology, immunophenotype, and ultrastructure (in one case) are described in order to aid their wider recognition. In the light of these findings, the nature and origin of follicular dendritic cells are discussed.

Adult↗

Reduced apoptotic cell death in follicular lymphoma.

It has been hypothesized that inhibition of germinal centre cell apoptosis may underlie the development of follicle centre cell lymphomas. We have performed a comparative, quantitative study of apoptotic cell death in germinal centres and in the neoplastic follicles of centroblastic-centrocytic, follicular, non-Hodgkin's lymphoma (Cb/Cc NHL). Ten cases each of reactive follicular hyperplasia and Cb/Cc NHL were analysed. One-micrometre-thick resin-embedded sections were examined at x 1000 magnification. The total numbers of cells, nuclear containing apoptotic bodies, and mitoses were counted in each follicle and the apoptotic and mitotic indices were derived. Transmission electron microscopy was performed on selected cases to confirm the typical features of apoptosis. The mean apoptotic (4.9 per cent) and mitotic indices (0.9 per cent) for the germinal centres were significantly higher (P much less than 0.001) than those for the neoplastic follicles (0.9 and 0.14 per cent). These results lend support to the recent proposal that reduced apoptotic cell death may be important in the pathogenesis of follicular lymphomas.

Cell Survival↗

Plexiform fibrohistiocytic tumour: clinicopathological, immunohistochemical and ultrastructural analysis in favour of a myofibroblastic lesion.

Plexiform fibrohistiocytic tumour is a recently described, seemingly benign neoplasm of superficial soft tissue which is poorly recognized and the differentiation pattern of which remains obscure. Fourteen new cases are presented here. These presented predominantly in the upper limb of infants and children, although the age-range was wide. A morphological spectrum depending on the relative proportions of the spindle cellular and nodular histiocyte-like components was evident. Immunohistochemical analysis revealed positivity of tumour cells in both components for smooth muscle actin, suggestive of myofibroblastic differentiation, as was borne out ultrastructurally in two cases. In addition, a minority of the histiocyte-like cells were also CD68 positive but negative for leucocyte common antigen, HLA-DR, Mac387 and lysozyme. In view of the ultrastructural and other immunohistochemical results, this is regarded as further evidence that the CD68 epitope recognized by KP-1 is not confined to cells of monocyte/macrophage or myeloid lineage. Plexiform fibrohistiocytic tumour appears to be a clinicopathologically distinctive myofibroblastic neoplasm which may warrant reclassification in due course.

Actins↗

DNA flow cytometry of follicular non-Hodgkin's lymphoma.

S-phase fraction, an index of cellular proliferation, and DNA ploidy were measured by DNA flow cytometry in a retrospective study of lymph node biopsy specimens from 83 cases (before treatment) of follicular non-Hodgkin's lymphoma, Working Formulation categories B and C. The correlations between these measures and survival, clinical stage, symptoms and histopathological factors were investigated. Aneuploidy was rare (n = 16) and had no effect on length of survival or transformation to high grade lymphoma. The overall mean S-phase fraction was 3.6%; for the whole series increasing S-phase fraction was associated with decreased survival. A high S-phase fraction (more than 5%) in initial biopsy specimens was also associated with an increased risk of subsequent high grade transformation at relapse. There was no difference between the survival or proliferative activity of tumours composed of mainly small cleaved cells compared with those composed of mixed small and large cells. There was no difference in survival or proliferative activity between tumours showing a pure follicular growth pattern and those with a mixed follicular and diffuse growth pattern. Multifactorial analysis showed that an S-phase fraction of more than 5% and B symptoms were the most important factors determining survival in these follicular non-Hodgkin's lymphomas.

Adult↗