bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology and immunohistochemistry of carcinoma in situ adjacent to testicular germ cell tumours in adults and children: implications for histogenesis
Authors: SOOSAY G.N. , BOBROW L. , HAPPERFIELD L. , PARKINSON M.C.
Published: April 2007

Observations differ on the pre‐invasive malignant lesions associated with the various categories of testicular germ cell tumours. Such lesions have been found to be similar in appearance and are assumed to be composed of multipotent cells, or conversely a distinctive pre‐invasive stage has been reported in association with each form of germ cell neoplasm. This study was undertaken to see whether distinctive morphological and immunohistochemical features of carcinoma in situ adjacent to various categories of germ cell tumours could be established. Carcinoma in situ adjacent to seminomas, teratomas and mixed germ cell tumours in 18 adults was indistinguishable morphologically. Placental alkaline phosphatase was demonstrated immunohistochemically but vimentin and low molecular weight cytokeratins were uniformly absent in these abnormal germ cells from all three groups. These findings support the concept of a multipotent pre‐invasive malignant cell for both seminoma and teratoma in the adult. Carcinoma in situ was not seen adjacent to 1 5 spermatocytic seminomas, nor was placental alkaline phosphatase demonstrated in tubules adjacent to these tumours. These negative findings are additional evidence that spermatocytic seminoma differs from classical seminoma in its histogenesis. Carcinoma in situ, as defined morphologically and immunohistochemically in adults, was not identified adjacent to yolk sac tumours and differentiated teratomas in 20 prepubertal testes. The possibility that pre‐invasive malignancy in children may not resemble that in adults must be considered when assessing the malignant potential of cryptorchid testes on biopsies taken during orchidopexy.
Ki‐67 immunostaining and survival in operable lung cancer
Authors: TUNGEKAR M.F. , GATTER K.C. , DUNNILL M.S. , MASON D.Y.
Published: April 2007

One hundred and eighty‐seven operable lung tumours were immunostained with the monoclonal antibody Ki‐67 and divided into groups of high, moderate or low proliferation. Patients have been followed clinically for up to 7 years to ascertain whether this immunocytochemical measurement reflected tumour behaviour in terms of survival. The majority of the tumours were squamous cell carcinomas (104 cases) and adenocarcinomas (60 cases). These were divided into three groups of low, intermediate and high growth fraction, in which survival was better for tumours of lower proliferative rate up to approximately 2 years after operation. By 5 years these differences had largely disappeared and all tumours of a particular type showed a similar survival curve. Small cell carcinomas (13 cases) had high Ki‐67 labelling indices, with more than 60% of patients dead in the first year, whereas carcinoid tumours (10 cases) had low labelling rates and all but one are still alive. We conclude that measurement of lung tumour growth rate with the monoclonal antibody Ki‐67 shows promise as a possible indicator of short‐term survival and perhaps as a means of choosing a group of patients with adenocarcinomas and squamous cell carcinomas for post‐operative chemotherapy.
Evaluation of endothelial markers in detecting blood and lymphatic channel invasion in pT1 transitional carcinoma of bladder
Authors: RAMANI P. , BIRCH B.R.P. , HARLAND S.J. , PARKINSON M.C.
Published: April 2007

In a study of 40 patients with high‐grade (G2 and G3) transitional cell carcinoma of bladder invading the lamina propria—stage pT1, retraction artifact was often misdiagnosed as vascular/lymphatic tumour invasion. Vascular/lymphatic infiltration was diagnosed in five cases based on haematoxylin and eosin stained sections, but confirmed in only two of these using immunohistochemical techniques to demonstrate endothelial markers. Of the latter, these preparations demonstrating von‐Willebrand factor and binding the monoclonal antibody QBEND/10 were technically superior to those in which Ulex europaeus agglutinin 1 was used. It is unlikely that the demonstration of vascular/lymphatic infiltration, a rare feature, will prove of value in defining prognostic groups for treatment.
Localized amyloidosis of the lower genitourinary tract: a clinicopathological and immunohistochemical study of nine cases
Authors: KHAN S.M. , BIRCH P.J. , BASS P.S. , WILLIAMS J.H. , THEAKER J.M.
Published: April 2007

A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50‐79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non‐reactive with antibodies to serum amyloid A protein, prealbumin and β2 microglobulin, while equivocal immunoreactivity was seen with anti‐light chain antibodies.
Thymic carcinosarcoma associated with a spindle cell thymoma: an immunohistochemical study
Authors: VILELA D.SUAREZ , VALIEN J.S.SALAS , MORAN M.A.GONZALEZ , GARCIA F.IZQUIERDO , VELASCO J.R.RIERA
Published: April 2007

A case of thymic carcinosarcoma associated with a spindle cell thymoma in a 71‐year‐old woman is reported. Histological and immunohistochemical studies of the carcinosarcoma showed two quite different components: the sarcomatous component included cells with myoid differentiation which stained for desmin and muscle specific actin, and some isolated cells which stained positively for low molecular weight cytokeratin, while the carcinomatous component, which formed less than 10% of the tumour, showed an epithelial phenotype, being positive for low and high molecular weight cytokeratin and epithelial membrane antigen. The thymoma cells showed epithelial markers, and a few cells were also positive for desmin and muscle specific actin. The rarity of this tumour and its possible histogenesis are discussed.
p53 expression is common in malignant mesothelioma
Authors: KAFIRI G. , THOMAS D.M. , SHEPHERD N.A. , KRAUSZ T. , LANE D.P. , HALL P.A.
Published: April 2007

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM‐1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.
Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger–Ellison syndrome during omeprazole treatment
Authors: CARUANA P. , AZZONI C. , BERTELÉ A. , ANNIBALE B. , FRANZÉ A. , FAVE G. DELLE , BORDI C.
Published: April 2007

Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the Zollinger–Ellison syndrome undergoing long‐term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non‐atrophic mucosa. The possible relationship of these changes to long‐standing pharmacological therapy for gastric acid suppression is discussed.
Sporadic medullary microcarcinoma of the thyroid
Authors: MIZUKAMI Y. , KURUMAYA H. , NONOMURA A. , MICHIGISHI T. , TERAHATA S. , NOGUCHI M. , HASHIMOTO T. , MATSUBARA F.
Published: April 2007

Two cases of medullary microcarcinoma of the thyroid are reported. The tumours were identified incidentally in a 60‐ and a 66‐year‐old woman each with a thyroid adenoma. These tumours were 0.8 cm and 0.5 cm in size, respectively, and located in the central portion of the right lateral lobe. In neither patient was there a family history of medullary thyroid carcinoma. Although medullary microcarcinoma with associated C‐cell hyperplasia in familial form has been reported, sporadic medullary microcarcinoma is rare.
Histological examination of first trimester spontaneous abortions: the impact of materno‐embryonic interface features
Authors: JAUNIAUX E. , HUSTIN J.
Published: April 2007

Cytogenetic findings and placental histological features of 319 consecutive first trimester spontaneous abortions were retrospectively investigated. Correlation of cell culture results and microscopic examination based on conventional villous histological criteria showed an overall sensitivity of 45.1% for histology in detecting chromosomal anomalies. Discrepant cases, i.e. normal histology with unequivocal chromosomal anomaly and abnormal histological features suggesting a chromosomal anomaly according to the classical criteria but with a normal karyotype, were reviewed by two independent observers using extended histological criteria including features of the materno‐embryonic interface. There was a significant (P < 0.001) increase of the sensitivity of histology to 66.4% for both observers after the second histological examination. Macerated specimens or incomplete specimens made of chorion laeve or maternal decidua only are difficult to evaluate, and represent the main cause of discrepancy between cytogenetics and morphology. The results of this study indicate that the sensitivity and specificity of microscopic examination in cases of early spontaneous abortion may be improved by adding features of the materno‐embryonic interface to classical villous histological criteria.
The lymphoepithelial lesion of gastric low‐grade B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT): an ultrastructural study
Authors: PAPADAKI L. , WOTHERSPOON A.C. , ISAACSON P.G.
Published: April 2007

Lymphoepithelial lesions are a characteristic feature of primary, gastric low‐grade lymphomas of mucosa‐associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte‐like (CCL) B‐cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated.
Benign epithelial neoplasms of the appendix: classification and clinical associations
Authors: WILLIAMS G.R. , BOULAY C.E.H.DU , ROCHE W.R.
Published: April 2007

The nomenclature of non‐carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well‐established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions.

All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow‐up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post‐appendicectomy respectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel.
Thymic pathology in primary and secondary immunodeficiencies
Authors: NEZELOF C.
Published: April 2007

For the sake of clarity and in agreement with the World Health Organization immunodeficiency classification, it is important to distinguish the congenital, inherited malformative lesions called generically ‘thymic dysplasia’ from the secondary, acquired changes, designated under the broad term of ‘severe thymic atrophy’. Thymic dysplasia represents the archetype of thymic changes in cellular immunodeficiency, since there is no example of a thymic dysplasia associated with a normal T‐cell function. Thymic dysplasia is observed in several inherited diseases, the most frequent of them being severe combined immunodeficiency. More than the depletion of lymphoid cells, the lack of differentiation of the thymic epithelium, responsible for the absence of Hassal's corpuscles, is the main and constant feature of this condition. Thymic dysplasia underscores the crucial role of the thymic epithelium in the normal differentiation of the T‐cell population. Severe thymic atrophy is secondary to various causes, including prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction and, chiefly today, chronic viral infection, especially with HIV‐1. The morphological changes are similar and are characterized by a partial lymphoid depletion, involving mainly the CD1 + population, necrosis and calcification of epithelial cells, the frequent presence of plasma cells and, more significantly, fibrohyaline changes of the basement membrane of the vessels and thymic epithelium. The severity of the atrophic changes and the immunodeficiency‐related manifestations depend on the duration of the aetiological factors and, more significantly, with their early occurrence, within the first months of life. The mechanisms underlying thymic atrophy are poorly understood. A primary impairment of lymphoid cells seems at present to be the most likely hypothesis.
Epidermal damage in skin of allogeneic marrow recipients: relative importance of chemotherapy, conditioning and graft v. host disease
Authors: NORTON J. , SLOANE J.P.
Published: April 2007

The relative importance of previous chemotherapy, conditioning and graft v. host disease in producing the epidermal damage associated with allogeneic bone marrow transplantation was investigated by enumerating individually necrotic cells. A small number was seen in many pre‐transplant biopsies and was related to the time interval between biopsy and the last dose of chemotherapy. Their presence did not predispose patients to develop graft v. host disease in the post‐transplant period. In post‐transplant patients without rashes the degree of epidermal damage at 14 days was similar to that seen in the pre‐transplant period indicating that the effects of the conditioning regime were insignificant. In patients with rashes clinically classical of graft v. host disease, necrotic cells were increased above the pre‐transplant levels even in the absence of a lymphocytic infiltrate. Lymphocytic infiltration was seen more frequently in biopsies taken later after transplantation and after the onset of the rash and was associated with the maximal amount of epidermal damage. Comparison of the degree of epidermal damage in pre‐ and post‐transplantation specimens lacking a lymphocytic infiltrate resulted in the correct identification of the majority of patients with clinical evidence of graft v. host disease. This approach may, thus, be useful in diagnosing early graft v. host disease especially if combined with keratinocyte HLA‐DR staining.
Primary gastrointestinal malignant lymphomas associated with Epstein‐Barr virus after heart transplantation
Authors: GUETTIER C. , HAMILTON‐DUTOIT S. , GUILLEMAIN R. , FARGE D. , AMREIN C. , VULSER C. , HOFMAN P. , CARPENTIER A. , DIEBOLD J.
Published: April 2007

Gastrointestinal involvement has been reported in 12–21% of post‐transplant lymphoproliferative disorders but is unusual in the setting of heart transplantation. We report four post‐transplant lymphoproliferative disorders observed among the 174 heart transplant recipients of our series, all of which were primary malignant lymphomas of and confined to the digestive tract. The mean onset time from transplantation was 22 months. Small intestine lesions were present in all four patients, with gastric involvement in one. Histologically, the tumour was monomorphic of immunoblastic type in one case and polymorphic in the three other cases. Analysis of cytoplasmic immunoglobulins demonstrated the presence of a major monoclonal subset in all patients. Epstein‐Barr virus genome was found in numerous tumour cells by in situ hybridization. The exclusive localization to the digestive tract and the lymphoepithelial lesions observed in two cases suggest that these lymphoproliferations might originate from mucosa‐associated lymphoid tissue.
An assessment of involucrin as a diagnostically useful immunohistochemical marker in lung tumours
Authors: MAYALL F.G. , GODDARD H. , GIBBS A.R.
Published: April 2007

A previous report has described involucrin as a specific immunohistochemical marker of squamous differentiation in lung carcinomas. The aim of our study was to examine the expression of this antigen in a wide variety of lung tumours, with particular attention to its potential value in the typing of biopsy specimens. We found that immunostaining for involucrin was common in squamous carcinomas but was also found in adenocarcinomas, adenosquamous carcinomas, large cell carcinomas and carcinosarcomas. Small cell carcinomas, carcinoid tumours and mesotheliomas were negative. Contrary to previous claims, this marker appears to have little diagnostic utility in the typing of lung tumours.
Carcinoma of the thyroid at a young age—a review of 23 patients
Authors: MIZUKAMI Y. , MICHIGISHI T. , NONOMURA A. , HASHIMOTO T. , NOGUCHI M. , MATSUBARA F. , WATANABE K.
Published: April 2007

Twenty‐three children and adolescents with thyroid carcinoma who were 20 years old or younger at the time of initial treatment were followed for a mean time of 9.5 years. Of the tumours, 21 were papillary and two follicular carcinomas. The majority (91%) of the 23 cases showed extra‐thyroidal extension of the tumour. An association with chronic thyroiditis was observed in 30% of the cases. There was no history of irradiation of the head and neck in any patients. Relapse occurred in eight patients, lung metastases in two and local recurrences in six; one patient died from lung metastases 3 months after initial treatment. Male patients, advanced stage of tumour, less differentiated histological features and DNA aneuploidy were associated with a higher frequency of relapse. The prognosis of thyroid carcinomas in children and adolescents is not so good as is generally believed.
Micro‐invasive breast carcinoma with granulomatous stromal response
Authors: COYNE J. , HABOUBI N.Y.
Published: April 2007

Two cases of micro‐invasive breast carcinoma with granuloma formation associated with invasive foci are presented. This is an unusual feature which may aid in the recognition of stromal micro‐invasion. Micro‐invasive carcinomas are defined as predominantly non‐invasive tumours in which there are one or more foci of infiltration, none measuring more than 1 mm in maximum diameter1.
Pathological variables determining the prognosis of non‐Hodgkin's lymphomas
Authors: KELLY S.A. , HARKIN P.J.R. , JACK A.S.
Published: April 2007

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non‐Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18‐month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high‐grade and intermediate‐grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate‐grade tumours, when subdivided into Kiel low‐ and high‐grade types, differed in survival from tumours graded as low‐ or high‐grade by both methods. However, NCI working formulation high‐grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.
Expression of mutant p53 gene in squamous carcinoma arising in patients with recessive dystrophic epidermolysis bullosa
Authors: SLATER S.D. , McGRATH J.A. , HOBBS C. , EADY R.A.J. , McKEE P.H.
Published: April 2007

J.A.M. is currently receiving a research fellowship from the Dystrophic Epidermolysis Bullosa Research Association (DEBRA).

Epidermolysis bullosa, a rare genodermatosis, is characterized by increased skin fragility manifest as blistering and sometimes accompanied by scarring. The latter is particularly severe in the recessive dystrophic variant and may be complicated by the development of squamous carcinoma in up to 30% of patients. We have studied 23 such tumours in six patients with this variant, with an anti‐serum to p53 protein. Twenty‐six per cent of the squamous carcinomas labelled positively for mutant‐type p53 protein. This low figure, however, reflects the large number of well‐differentiated tumours in this series, where 14 out of 15 were negative. In the moderate to poorly differentiated examples the positivity rate was 63%. Of the three patients in the latter category, one has died from disseminated tumour and another has widespread metastases. The findings support the hypothesis that mutant p53 protein expression correlates with poorer tumour differentiation. They also suggest a possible correlation between p53 protein expression and tumour behaviour.
Papillary thyroid carcinoma in Kanazawa, Japan: prognostic significance of histological subtypes
Authors: MIZUKAMI Y. , NOGUCHI M. , MICHIGISHI T. , NONOMURA A. , HASHIMOTO T. , OTAKE S. , NAKAMURA S. , MATSUBARA F.
Published: April 2007

A retrospective analysis of 183 papillary thyroid carcinomas was made in order to assess the prognostic factors related to survival. The following factors were found to adversely affect the prognosis: trabecular subtype of papillary carcinoma, the extent of the primary tumour, regional lymph node involvement, the presence of distant metastases, old age, male sex and the extent of the neck dissection. The presence of the follicular variant of papillary carcinoma and the extent of the thyroidectomy did not influence the prognosis. The trabecular subtype of papillary carcinoma is characterized by a trabecular or solid arrangement of follicular cells with nuclei of ground‐glass appearance. Univariate and multivariate analysis indicated that patients with this type of thyroid tumour had a poorer prognosis than those with the well‐differentiated or follicular variants of papillary carcinoma. In our opinion the trabecular subtype of papillary carcinoma should be included as a separate entity in the WHO classification of thyroid tumours.
Disseminated Penicillium marneffei infection in HIV‐infected subject
Authors: TSUI W.M.S. , MA K.F. , TSANG D.N.C
Published: April 2007

Penicillium marneffei is a rare human pathogen predominantly affecting residents of South‐east Asia. We report four fatal cases from Hong Kong in human immunodeficiency virus‐infected patients. The diagnosis was established by histological examination and confirmed by isolation of the fungus. The infection was disseminated with involvement of lymph nodes, liver, spleen, lung, intestine and bone marrow. The involved organs showed an exclusively anergic tissue reaction characterized by a diffuse infiltrate of fungi‐laden macrophages, multiple co‐existing opportunistic infections and lymphoid cell depletion. This organism has to be distinguished from Histoplasma capsulatum and Pneumocystis carinii. Establishment of the diagnosis is important not only because this infection is potentially curable, but also it is a likely indicator disease of AIDS in South‐east Asia. Penicilliosis marneffei should be suspected in any symptomatic HIV‐positive patient who comes from or has visited endemic areas of South‐east Asia.
Gastrointestinal autonomic nerve tumours: a case report with ultrastructural and immunohistochemical studies
Authors: MORALEDA F.PINEDO , GONZÁLEZ M.A.MARTÍNEZ , CARCAVILLA C.BALLESTÍN , CASTRILLÓN J.VARGAS
Published: April 2007

A case of gastrointestinal autonomic nerve tumour with light microscopic, immunohistochemical and ultrastructural examination is reported. The tumour was composed of spindle cells or large cells with clear cytoplasm and showed intense staining for vimentin and focal staining for neuron‐specific enolase, chromogranin, synaptophysin, gastrin, P substance and S‐100 protein. Ultrastructural examination showed long processes with dense core granules and the absence of features characteristic of other gastrointestinal stromal tumours. In addition we noted small traces of basal lamina and the absence of synaptic vesicles. It seems that the biological behaviour of gastrointestinal autonomic nerve tumours is aggressive but there are too few reports on which to conclude anything about their prognosis. Our findings suggest the tumour has a neuroectodermal differentiation.
Immunohistochemical detection of p53 and bcl‐2 proteins in non‐Hodgkin's lymphoma
Authors: PEZZELLA F. , MORRISON H. , JONES M. , GATTER K.C. , LANE D. , HARRIS A.L. , MASON D.Y.
Published: April 2007

We have investigated the immunohistochemical expression of p53 protein in 96 cases of non‐Hodgkin's lymphoma using a panel of five antibodies. Positive neoplastic cells were found in 30 (31.2%) cases, which could be divided into two groups according to their patterns of reactivity with the different antibodies; i.e. those positive with both polyclonal and monoclonal antibodies, and those which were stained only by monoclonal antibodies PAb1801 and/or PAb240. Positivity was nuclear in all but six cases in which cytoplasmic staining was found. In view of the hypothesis recently raised that p53 protein induces apoptosis we have compared our results with parallel staining for bcl‐2 protein since bcl‐2 is believed to be important, at least in lymphomas, in suppression of apoptosis. Staining for bcl‐2 protein was performed on 83 cases and it was shown that p53‐positive cases accounted for 10 out of 17 (59%) of the bcl‐2‐negative lymphomas but only for 15 out of the 66 (23%) bcl‐2‐positive cases, suggesting a possible relationship between the expression of these two proteins. Thus, our data show that p53 protein is abnormally expressed in a substantial proportion of non‐Hodgkin's lymphomas and bears a significant inverse relationship to bcl‐2 protein expression. However the molecular basis of this expression remains to be elucidated.
Nucleolar organizer regions and glycoprotein‐hormone α‐chain reaction as markers of malignancy in endocrine tumours of the pancreas
Authors: ÜSCHOFF J.P. , WILLEMER S. , BRUNZEL M. , TRAUTMANN M.E , FRANK M. , ARNOLD R. , KLÖPPEL G.
Published: April 2007

The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin α‐chain reaction (HCG‐α) as markers of malignancy was investigated in 60 primary pancreatic endocrine tumours, 37 of which had metastasized at the time of surgery, and in one of which metastases developed 4 years after surgery. Assessment of AgNORs by digital image analysis revealed few but large AgNORs (mean number 2.5 ± 1.1; mean area ± in the 22 benign tumours and many but small AgNORs (mean number 5.1 ± 1.9, P<0.05; mean ± 9 μm2. P<0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG‐α immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG‐α scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG‐α status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG‐α scores, were negative. Thus, investigation of AgNORs HCG‐α is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.
Legionnaire's disease mimicking pulmonary miliary tuberculosis in the immunocompromised
Authors: CLUROE A.D.
Published: April 2007

Two siblings with systemic lupus erythematosus, whose presentation suggested food poisoning, had pulmonary Legionella infection which, at autopsy, mimicked miliary tuberculosis.
A histochemical and immunohistochemical study of extra‐ocular sebaceous carcinoma
Authors: ANSAI S. , HASHIMOTO H. , AOKI T. , HOZUMI Y. , ASO K.
Published: April 2007

A histochemical and immunohistochemical study of five cases of extra‐ocular sebaceous carcinoma was performed using formalin‐fixed and paraffin‐embedded tissue specimens. Histochemically, the clear cells of sebaceous carcinomas were negative with periodic acid‐Schiff and alcian blue staining. Immunohistochemically, the tumour cells of sebaceous carcinomas showed positive reactions for epithelial membrane antigen, human milk fat globules subclass 1, human milk fat globules subclass 2 and Leu M1, but did not express carcinoembryonic antigen, breast carcinoma associated antigen, S‐100 protein, gross cystic disease fluid protein‐15 or Dako M1. These histochemical and immunohistochemical findings were compared with those of other skin cancers which must be distinguished histopathologically from sebaceous carcinoma. We conclude that sebaceous carcinoma can be distinguished from eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease, malignant trichilemmoma, squamous cell carcinoma and basal cell carcinoma by histochemical and immunohistochemical techniques using formalin‐fixed and paraffin‐embedded tissue specimens.
Seminal vesicle amyloidosis: morphological, histochemical and immunohistochemical observations
Authors: COYNE J.D. , KEALY W.F.
Published: April 2007

Subepithelial deposits of amyloid were detected within the seminal vesicles of 13 males from a total of 143 unselected autopsies (9%). The incidence increased with increasing age. The amyloid was classified using histochemistry, immunohistochemistry and clinical features. Eight cases were categorized as senile vesicle amyloid, two as systemic AA amyloid with secondary involvement of the seminal vesicle, and three as mixed amyloidosis. The morphological appearances of the different categories of seminal vesicle amyloidosis are similar but a different distribution is common. The staining characteristics of senile vesicle amyloid suggest that this is a different amyloid protein, perhaps locally derived within the seminal vesicle.
Chronic hepatitis in multiple virus infection: histopathological evaluation
Authors: COLOMBARI R. , DHILLON A. P. , PIAZZOLA E. , TOMEZZOLI A. A. , ANGELINI G. P. , CAPRA F. , TOMBA A. , SCHEUER P. J.
Published: April 2007

The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty‐nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The δ‐5‐virus (HDV) was not associated with severe necro‐inflammatory lesions, but HDV‐positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non‐specific for HCV infection, or that these cases represent HCV infection with false‐negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co‐infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear.
Expression of tumour necrosis factor‐α in cryptogenic fibrosing alveolitis
Authors: NASH J. R. G. , MCLAUGHLIN P. J. , BUTCHER D. , CORRIN B.
Published: April 2007

We have studied 15 cases of cryptogenic fibrosing alveolitis stained with a monoclonal antibody reactive with human tumour necrosis factor‐α (TNFα), a cytokine that has been implicated in inflammation and fibrosis. Seven were examples of lone cryptogenic fibrosing alveolitis and eight were examples of cryptogenic fibrosing alveolitis in patients with systemic sclerosis. There was widespread staining of epithelial cells, particularly hyperplastic type II pneumocytes. Macrophages stained only weakly. In a control group of 10 patients dying of unrelated conditions, staining for TNFα was weak and, in the alveolar epithelium, was confined to a very occasional type II pneumocyte. The strong expression of TNFα in hyperplastic type II pneumocytes suggests that TNFα produced during alveolar epithelial regeneration may play a part in the fibrosis seen in this disease.
Detection of the Ki‐67 antigen in fixed and wax‐embedded sections with the monoclonal antibody MIB1
Authors: McCORMICK D. , CHONG H. , HOBBS C. , DATTA C. , HALL P. A.
Published: April 2007

Novel antibodies have been generated by immunizing with bacterially expressed fragments of the repetitive motif of the Ki‐67 gene. One such antibody, MIB1, recognizes a fixation and embedding resistant epitope on the Ki‐67 protein if sections are previously microwaved in a citrate buffer. We have investigated the utility of this antibody as a marker of cell proliferation in archival material. The microwave technique is simple but requires careful monitoring since different tissues and fixatives require different irradiation times. Strong nuclear immunoreactivity was detected with all fixatives studied. Cytoplasmic staining was not identified. In a wide range of normal tissues the distribution and number of MIB1 immunoreactive cells matched that of cryostat sections stained with Ki‐67. In nude mouse xenografts in which the growth fraction had been defined using a fraction of labelled mitosis method, the labelling index with MIB1 matched that previously determined for Ki‐67 and correlated well with the growth fraction. Other markers of proliferation (e.g. proliferating cell nulcear antigen) have been shown to be expressed in DNA repair, thus we investigated expression of MIB1 immunoreactivity in situations of DNA repair in vivo—ultraviolet irradiated human skin. MIB1 staining correlated with semi‐conservative DNA synthesis rather than excision repair DNA synthesis. Finally, the morphological and cell cycle distribution of MIB1 expression is identical to that of Ki‐67. Thus, MIB1 represents a new anti‐Ki‐67 antibody which appears to be a robust marker of cell proliferation easily applicable to archival material.
The histopathology of transcervical resection of the endometrium: an analysis of 200 cases
Authors: HELLEN E. A. , COGHILL S. B. , SHAXTED E. J.
Published: April 2007

The results of a series of 200 patients treated by transcervical resection of the endometrium are presented. The failure rate was 20% with a minimum follow up period of 18 months, although seven women (3.5%) had treatment beyond this interval. A second resection was performed in 14 patients with two later requiring a hysterectomy. An additional 26 women proceeded to hysterectomy following the initial resection. Specimen weight was inversely related to the need for further surgery with no secondary operations performed when more than 12 g of endometrium and myometrium had been resected. Age was also correlated with clinical outcome with patients under 35 years of age more likely to require further operative treatment. No histological feature could be identified which predicted failure of the procedure. The main role for histopathological assessment of transcervical resection specimens is in the provision of an accurate weight and the identification of the relatively rare cases harbouring endometrial or myometrial malignancy. Although endometrial resection appears to have resulted in fewer hysterectomies in the treatment of dysfunctional uterine bleeding, long‐term follow‐up is required before an accurate assessment of success can be established.
Comparison of bone marrow sections, smears and immunohistological staining for immunoglobulin light chains in the diagnosis of benign and malignant plasma cell proliferations
Authors: THIRY A. , DELVENNE P. , FONTAINE M.‐A. , BONIVER J.
Published: April 2007

Bone marrow specimens from 118 patients with clinical suspicion of multiple myeloma were studied to assess the diagnostic reliability of histological and cytological criteria. Plasma cell clonality was assessed by demonstrating light chain restriction. In most cases of multiple myeloma, the classical cytological and histological criteria were found. In eight cases in which the marrow contained less than 10% of plasma cells, there was discordance between the light microscopic and immunohistochemical findings. In six cases without evidence of multiple myeloma and with polyclonal plasma cells in bone marrow, abnormal plasma cells resembling a malignant proliferation were found. These findings indicate that comparison of histological and cytological results with immunohistological studies for immunoglobulin light chains in bone marrow biopsy sections can be helpful in the evaluation of patients with a susicion of multiple myeloma and when the marrow contains less than 10% of plasma cells.
Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB‐45‐positive smooth muscle
Authors: CHAN J.K.C. , TSANG W.Y.W. , PAU M.Y. , TANG M.C. , PANG S.W. , FLETCHE C.D.M.
Published: April 2007

Angiomyolipoma is a hamartomatous condition which can occur as a component of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long been suspected to be related to angiomyolipoma and tuberous sclerosis because of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two entities. Five cases of lymphangiomyomatosis and 20 case of angiomyolipoma were retrieved for histological review and immunohistochemical studies. The antibodies used were anti‐muscle specific actin (HHF‐35), anti‐desmin (D33) and antimelanoma (HMB‐45). Lesions featuring smooth muscle proliferation were used as controls. The proliferated smooth muscle cells in both lymphangiomyomatosis and angiomyolipoma were much plumper and paler or even clear, when compared with the deeply eosinophilic cytoplasm of the normal spindly smooth muscle cells and those of leiomyomas. Their nuclei were round to oval and pale rather than elongated and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomyolipoma there were foci indistinguishable from lymphangiomyomatosis, i.e. plump spindle cells arranged in short fascicles around ramifying endothelium‐lined spaces. All five cases of lymphangiomyomatosis stained for muscle‐specific actin, desmin and HMB‐45. For angiomyolipomas, the positivity rates for these markers were: 20/20, 17/20 and 18/20, respectively, including one case that was negative for both desmin and HMB‐45. The various smooth muscle proliferations and tumours selected as controls were uniformly HMB‐45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all support a close relationship between lymphangiomyomatosis and angiomyolipoma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB‐45‐positive smooth muscle.
Expression of alpha‐amylase isoenzymes and trypsin by the proliferating epithelium of large intrahepatic bile ducts and intrahepatic peribiliary glands in hepatolithiasis
Authors: TERADA T. , NAKANUMA Y.
Published: April 2007

The expression of alpha‐amylase isoenzymes (pancreatic and salivary) and trypsin by the epithelium of large intrahepatic bile ducts and peribiliary glands was examined immunohistochemically in hepatolithiasis (n= 22), extrahepatic biliary obstruction (n= 20) and normal liver (n= 22). Hepatolithiasis was associated with marked proliferation of bile duct cells and peribiliary glands. Expression of pancreatic and salivary amylase was observed in the proliferating bile duct cells and peribiliary glands of all livers, and trypsin was found in 68% of the livers. In extrahepatic biliary obstruction, proliferation of the biliary epithelium was less marked, but expression of amylase isoenzymes was observed in all livers and trypsin was found in 50%. All normal livers showed expression of amylase isoenzymes in large intrahepatic bile ducts, septal bile ducts and peribiliary glands, and trypsin was found in 73%. The density of enzyme‐containing acini was highest in hepatolithiasis, intermediate in extrahepatic biliary obstruction and lowest in normal liver. These results show that the proliferating biliary epithelium in hepatolithiasis contains amylase isoenzymes and trypsin and that biliary epithelium retains the ability to produce these enzymes after proliferation, suggesting that a large amount of amylase isoenzymes and trypsin may be secreted into the bile ducts in hepatolithiasis. These enzymes may play an important role in the pathophysiology of hepatolithiasis.
Mechanism of pain in osteoid osteomas: an immunohistochemical study
Authors: HASEGAWA T. , HIROSE T. , SAKAMOTO R. , SEKI K. , IKATA T. , HIZAWA K.
Published: April 2007

Osteoid osteoma is a benign bone tumour characterized by pain which is relieved by non‐steroidal anti‐inflammatory drugs (NSAIDs), such as aspirin. To clarify the mechanism of the pain, five osteoid osteomas were studied immunohistochemically using polyclonal antibodies against prostaglandin E2 (PGE2), S‐100 protein and protein gene product 9.5 (PGP 9.5). In all five cases, the pain had been relieved by NSAIDs. Nerve fibres positive for S‐100 protein and PGP 9.5 were observed in the fibrous zone, especially close to the blood vessels, around the nidus in all the lesions and also within the nidus in three lesions. PGE2 immunoreactivity was variably positive in the nidus of three lesions. In one case a large number of actively proliferating osteoblasts reacted with this antibody. The other cases showed unevenly distributed PGE2 positivity which tended to be prominent in the plump osteoblasts. As control material we examined fibrous dysplasia (3 cases), osteosarcomas (3) and giant‐cell tumours of bone (3). The plump osteoblastic tumour cells of three osteosarcomas and the bone‐forming cells in two cases of fibrous dysplasia gave a positive reaction for PGE2. No S‐100 or PGP 9.5 immunoreactive nerve fibres were seen in these lesions. It is concluded that the presence of nerve fibres alone might play a more important role in mediation of pain in osteoid osteomas than some effects of osteoblast‐produced PGE2 on the nerves and proliferated blood vessels.
The value of histomorphological features of chorionic villi in early spontaneous abortion for the prediction of karyotype
Authors: LIJNSCHOTEN G.VAN , ARENDS J.W. , LEFFERS P. , DE LA FUENTE A.A. , LOOIJ H.J.A.M. VAN DER , GERAEDTS J.P.M.
Published: April 2007

This study was conducted to evaluate the value of histomorphological features of chorionic villi, such as size, shape, vascularity, trophoblast proliferation and trophoblastic pseudo‐inclusions, for the prediction of chromosomal abnormality. Slides of 83 early spontaneous abortions were assessed by three observers. Assessments and karyotype were compared and likelihood ratios computed. Likelihood ratios of ≤0.40 or ≥2.50 were not obtained by all three observers for any of the features. One or two observers obtained likelihood ratios of ≥2.50 for lacunar stromal hydrops, presence of trophoblastic hyperplasia. moderate to abundant trophoblastic hyperplasia, presence of trophoblastic lacunae, few intervillous fibrin deposits and few intervillous trophoblastic buds. Likelihood ratios of ≥0.40 were found for small chorionic villi and presence of basophilic staining. Lacunar stromal hydrops and trophoblastic lacunae were predictive of triploid karyotype, but not specific for any other type of chromosomal abnormality. After application of data previously obtained on Cohen kappas, lacunar stromal hydrops, moderate to abundant trophoblastic hyperplasia and presence of trophoblastic lacunae remained as possibly useful features, again mainly for identifying triploidy. Most of the items claimed to be related to abnormal karyotype, however, were not predictive at all.
Pustular drug eruptions: a histopathological spectrum
Authors: BURROWS N.P. , JONES R. RUSSELL
Published: April 2007

We have reviewed the histopathological features of 11 patients with pustular drug eruptions. Two main histological patterns were seen. Eight cases revealed features of toxic pustuloderma with the presence of spongiform intra‐epidermal pustules in association with papillary oedema and a mixed inflammatory cell infiltrate around upper dermal blood vessels. Pustules were present at different levels within the epidermis. The other three cases exhibited leucocytoclastic vasculitis with neutrophil collections both below and within the epidermis. One case showed continuity between the subepidermal and intra‐epidermal pustules. These findings suggest a dynamic process in which neutrophils collect around upper dermal blood vessels and are then eliminated via the overyling epidermis. The presence of extravasated red blood cells within the intra‐epidermal pustules indicates that this process is passive rather than the result of specific chemotaxis or cell migration.
Combined cytological and histological diagnosis of hepatocellular carcinoma in ultrasonically guided fine needle biopsy specimens
Authors: ZAINOL H. , SUMITHRAN E.
Published: April 2007

This study evaluates the usefulness of a combined cytological and histological approach to the diagnosis of hepatocellular carcinoma (HCC) when applied to fine needle biopsy specimens obtained under ultrasonic guidance. The material, aspirated from 51 focal liver lesions, was handled in such a way that there was sufficient material for both cytological and histological (cell block) assessment. Of the 29 cases of HCC studied, a confident cytological diagnosis was made in 23 (79%). In the remaining six cases, the cytological features were considered to be suspicious but not diagnostic of HCC. Examination of cell blocks in the six cases enabled a confident diagnosis of HCC to be made in all cases. This was due to the supplementary visual information provided by the histological features, particularly the pattern of arrangement of the tumour cells.