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B J Addis

Publications and source records attributed to B J Addis.

At least 37 records · Page 2Linked to original sources

Non-small cell lung carcinomas with neuroendocrine features. A light microscopic, immunohistochemical and ultrastructural study of 11 cases.

Eleven resected primary lung carcinomas classified as large cell carcinomas or squamous cell carcinomas, but showing some microscopic resemblances to bronchial carcinoid and small cell carcinoma, were studied. All cases were neurone-specific enolase and protein gene product 9.5 positive, indicating neuroendocrine differentiation. Staining for bombesin, C-terminal peptide of human pro-bombesin and chromogranin was positive in some cases. Electron microscopy showed dense-core granules in six of seven cases investigated, the remaining case showing small granules of uncertain nature. All but one patient died within 15 months after operation. These data indicate that neuroendocrine differentiation in non-small cell carcinomas of the lung may in some cases be suspected on routine histology. The follow-up data suggest that the identification of these cases might have implications for prognosis and therapy, and consequently for diagnostic lung tumour classification.

Adult↗

Peripheral T-cell lymphoma presenting with angioedema and diffuse pulmonary infiltrates.

Peripheral T-cell lymphoma is becoming increasingly recognized as a clinical entity despite its protean clinical manifestations and morphological features. Pulmonary involvement is evident in 20% of patients at initial diagnosis and develops in a further 20% during the course of their disease. Angioedema resulting from immune-mediated complement depletion is a rare complication of B-cell tumors. It has not been reported in T-cell lymphoma. We describe a patient with peripheral T-cell lymphoma who presented with angioedema and diffuse pulmonary infiltrates. Normal serum complement levels suggest that this patient developed angioedema independent of abnormalities in the complement cascade.

Angioedema↗

The human thymus contains a novel population of B lymphocytes.

A study of thymus glands from fetuses, newborn babies, children, and adults has shown a prominent intramedullary B-cell population. These cells have a distinctive phenotype, show evidence of activation, and specifically cluster around Hassall's corpuscles. The thymus can no longer be regarded as an organ exclusively concerned with T-cell function.

Adolescent↗

Epidermal growth factor receptors in lung tumours.

Immunocytochemical analysis of epidermal growth factor (EGF) receptor expression was carried out on frozen sections of 109 primary lung tumours resected at the Brompton Hospital from February 1984 to May 1985. Tumours with detectable levels of this proto-oncogene protein were significantly more frequent among squamous cell carcinomas than among other types of lung tumour. No truncated EGF receptors were detected in the tumours using two monoclonal antibodies (Mabs) directed against different portions of the receptor (EGFR1 and F4). Mab F4 is the first antibody to the EGF receptor to show reactivity in paraffin sections. Southern blot analysis of a subset of the tumours detected amplification of the EGF receptor gene in squamous cell carcinomas but not in adenocarcinomas. The one carcinosarcoma examined had a re-arranged and amplified EGF receptor gene. Measurement of EGF receptor expression in lung tumours can be of diagnostic value and may prove to be useful in the development of antibody-directed therapy.

Adenocarcinoma↗

Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung.

A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma.

Biomarkers, Tumor↗

Expression of the C-terminal peptide of human pro-bombesin in 361 lung endocrine tumours, a reliable marker and possible prognostic indicator for small cell carcinoma.

Small cell carcinoma of the lung is a highly malignant tumour. Its known biological products which include bombesin, do not allow the prediction of tumour behaviour. Molecular biology has revealed the amino acid sequence of human pro-bombesin, which consists of a signal peptide, the bioactive bombesin molecule and a C-terminal peptide. We have raised a rabbit antiserum to the first (N-terminal) 21 amino acids of the predicted C-terminal peptide. A total of 505 (361 neuroendocrine) surgically resected pulmonary tumours were evaluated for the presence of immunoreactive bombesin and C-terminal peptide. Strong immunostaining was obtained with the antiserum to the C-terminal peptide of human pro-bombesin in 70% of the small cell carcinomas (175/250), in 63% of atypical (aggressive) carcinoids (31/49) but only in 16% of benign carcinoids (10/62). In contrast, bombesin immunostaining was focal and only moderately strong and the relative proportion of positive cases was quite evenly distributed amongst the neuroendocrine tumours: 35% of carcinoids (22/62), 22% of atypical carcinoids (11/49) and 25% of small cell carcinoma (62/250). None of the squamous, adeno, or large cell undifferentiated carcinomas were immunoreactive for bombesin or the C-terminal peptide. Radioimmunoassay and chromatography of extracts of tumours recovered from wax blocks revealed high concentrations of C-terminal peptide immunoreactivity (241 +/- 66 pmol/g of tissue) in all 12 small cell carcinomas studied, moderate concentrations in carcinoid tumours (50 +/- 7 pmol/g) and none in non-small cell carcinomas. Patients with tumours showing immunoreactivity to the C-terminal peptide of human pro-bombesin had a significantly shorter survival time than those without immunoreactive peptide (185 +/- 16.49 days, mean +/- SEM, and with 1128 +/- 226 days, respectively P greater than 0.02). The apparent presence of the C-terminal peptide of human pro-bombesin in higher concentrations than bombesin in the more malignant class of endocrine tumours, mainly small cell carcinomas associated with the poorest prognosis, suggests that the antiserum to this C-terminal peptide is not only a useful pathological marker but may prove to be of value in investigating the biological behaviour of small cell carcinomas and predicting the clinical course of the disease.

Bombesin↗

Epithelial hyperplasia and malignant change in congenital lung cysts.

Patients with congenital lung cysts are at increased risk of developing carcinoma, but the mechanisms concerned are not clear. The case of a young adult who developed a bronchioloalveolar carcinoma associated with a cystic congenital adenomatoid malformation is reported. The adjacent lung showed an unusual intra-alveolar hyperplasia of mucous cells. Two further cases of congenital adenomatoid malformation are also described; both patients presented in infancy and showed similar mucous cell hyperplasia in alveoli surrounding the cysts. In all three cases the staining characteristic of the mucus was identical with that of normal bronchial mucous glands. It is suggested that the benign proliferation represents a premalignant lesion. Its presence in infants shows that it may occur at an early age and reinforces the need for early removal of congenital lung cysts.

Adenocarcinoma↗

Thymoma: an integrated clinicopathological and immunohistochemical study.

The clinicopathological features of 32 thymomas were reviewed and tumours were staged according to their degree of invasion. Their antigenic profiles were studied using monoclonal antibodies to cytokeratins (CAM 5.2 and DAKO-CK1), HNK-1 (Leu 7), and HLA-DR (TAL-IB5). Stage I (non-invasive) tumours were mainly of the spindle cell (SC) or predominantly lymphocytic (PL) types, whilst all the predominantly epithelial (PE) tumours were either locally invasive (stage II) or showed more extensive spread (stage III). Neoplastic epithelial cells all expressed cytokeratin, but varied in their degree of positivity. CAM 5.2 was more uniformly positive with cells at the periphery of tumour nodules and lining tubulo-cystic areas staining most strongly. DAKO-CK1 gave less uniform positivity but highlighted areas of medullary differentiation. HNK-1 was variably expressed in all tumour groups but was found more often in the invasive tumours (73 per cent stage III, 62 per cent stage II, 50 per cent stage I), particularly those of PE or mixed (M) type. In general, TAL-IB5 expression was lost in the more invasive thymomas. Focal medullary differentiation in tumours suggests a common origin for cortical and medullary epithelium, indicating that sub-division of tumours into cortical or medullary types is not valid. Immunohistochemistry may usefully complement clinical and macroscopic findings in the assessment of malignancy in thymoma.

Adolescent↗

Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin.

Fifteen cases of non-Hodgkin's lymphoma of the anterior mediastinum are reported. In the first group of four, fresh tissue was available and immunohistochemical studies demonstrated their B-cell origin, with monotypic immunoglobulin production in two. Only fixed tissue was available in the second group of 11 patients. All stained with antibody to leucocyte common antigen (PD7/26) and three showed monotypic immunoglobulin production. If the two groups are combined seven of the 15 tumours were clearly of B-cell origin. Classification on morphological grounds was difficult, with most tumours showing mixtures of centroblasts and large centrocytes, and the original diagnoses had included Hodgkin's disease (three), thymoma (one) and undifferentiated carcinoma (two). None of the patients had evidence of extra-thoracic disease at presentation and when this developed the organs involved were liver (one), kidney (two) and thyroid (one). Direct extension within the chest led to infiltration of chest wall, sternum, lung, superior vena cava and other structures. The site of origin, lack of nodal involvement and, in one case, presence of residual thymus around the tumour indicate an origin in thymic B-cells.

Adolescent↗

Secretory component in pulmonary adenocarcinoma and mesothelioma.

The distribution of secretory component was examined by an immunoperoxidase method in 40 pulmonary adenocarcinomas, 11 malignant pleural mesotheliomas and areas of normal lung adjacent to the tumours. Secretory component was demonstrated in tumour cells in 25 (67%) adenocarcinomas. Its presence correlated with the degree of differentiation but was not related to tumour pattern. In the normal lung secretory component can be demonstrated in bronchial ciliated cells, bronchial gland serous cells, bronchiolar epithelium and hyperplastic alveolar epithelium. Although not usually detectable in normal mucous cells it was frequently present in mucin-producing tumours. None of the mesotheliomas examined contained secretory component and this may be an additional useful feature in the differential diagnosis between mesothelioma and adenocarcinoma.

Adenocarcinoma↗

Pulmonary blastoma, carcinosarcoma and spindle-cell carcinoma: an immunohistochemical study of keratin intermediate filaments.

We have examined 18 primary malignant lung tumours categorized as either carcinosarcoma, blastoma or spindle-cell carcinoma according to accepted criteria. Two monoclonal antibodies to keratins, CAM 5.2 and LP 34, were used to determine whether the non-epithelial or spindle-cell components of each tumour showed evidence of keratin expression. By this means the epithelial nature of the five tumours classified as spindle-cell carcinomas was confirmed. In all four pulmonary blastomas and in five of nine carcinosarcomas, the sarcomatous elements failed to stain for keratin but in the remaining four carcinosarcomas there was focal staining. The histogenesis of these tumours is discussed and it is suggested that the sarcomatous component of a carcinosarcoma may be derived from malignant epithelial cells by a process of mesenchymal metaplasia with a switch in intermediate filament type. It remains uncertain whether blastomas are derived from both endoderm and mesoderm, or from either one of these tissues, with one component representing complete metaplastic transformation.

Aged↗

Papillary mesothelioma of ovary.

A case of primary papillary mesothelioma of the ovary is reported and its microscopic and ultrastructural features described. This tumour was an incidental surgical finding and was accompanied by multiple, partially cystic, peritoneal lesions with similar microscopic features. The histological pattern was predominantly papillary with well-differentiated mesothelial cells and a prominent stromal infiltrate that included large numbers of lymphocytes and lipid-filled macrophages. A comparison is made with adenomatoid tumours and with other tumours of ovarian epithelium and it is suggested that this tumour may represent the benign counterpart of one form of clear cell carcinoma of the ovary. The presence of multiple peritoneal lesions may indicate limited malignant potential comparable to some other papillary epithelial neoplasms of the ovary.

Aged↗

Plasmacytoma of lymph nodes.

A case of primary plasmacytoma in a lymph node accompanied by IgG Kappa paraproteinemia is described. Eight months after the plasmacytoma's removal, the paraprotein was undetectable in the serum and the patient has remained well for a year. Abundant crystalline inclusions were present in the tumor and the immunoperoxidase technique was used to show that these consisted of monotypic immunoglobulin are were contained predominantly within macrophages. Reported cases of plasmacytoma in lymph nodes are reviewed and the natural history of this group of tumor is discussed.

Adult↗