bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective randomized trial of the effect of preoperative endometrial inhibition on the long‐term outcome of transcervical endometrial resection
Authors: Sowter M.C. , Bidgood K. , Richardson J.A.
Published: November 2003

Objective To determine the effect of preoperative hormonal inhibition of the endometrium on the long‐term results of transcervical endometrial resection.

Design A prospective randomized trial.

Setting Gynaecology department of a district general hospital.

Subjects 77 women undergoing transcervical endometrial resection between January 1992 and December 1993 were randomized to either no endometrial preparation or pretreatment with two injections of goserelin, 3.6 mg, 4 weeks apart prior to surgery. Another 58 women who declined entry into the trial were given danazol, 800 mg per day, for 6 weeks preoperatively, and were also contacted postoperatively to assess the outcome of surgery.

Main outcome measures Postoperative menstrual loss, dysmenorrhoea, patient satisfaction and the need for any further surgery were assessed by postal or telephone questionnaire at between 12 and 33 months after surgery.

Results A significantly higher proportion of women treated preoperatively with goserelin had amenorrhoea postoperatively when compared with those who had no pretreatment (57.1 vs. 22.5%; P<0.01). Overall postoperative menstrual loss was also significantly less in the pretreatment group. The proportion of women with no postoperative dysmenorrhoea was greater in those who had received preoperative goserelin (57.1 vs. 35.0%) but did not reach significance (P=0.08). Patients treated with danazol preoperatively showed a similar but nonsignificant pattern when compared with women receiving no pretreatment. Patient satisfaction and the proportion of women subsequently having a hysterectomy was similar in each of the three groups.

Conclusions Endometrial inhibition with goserelin prior to transcervical endometrial resection results in significantly higher rates of postoperative amenorrhoea. It may also reduce postoperative dysmenorrhoea and overall postoperative menstrual loss. However, patient satisfaction and subsequent hysterectomy rate is unaffected by preoperative endometrial inhibition.
Uterine rupture during labour after hysteroscopic myomectomy
Authors: Abbas A. , Irvine L. M.
Published: November 2003

In this case a patient with submucous fundal fibroid subsequently underwent hysteroscopic myomectomy. During the procedure the uterus was perforated and laparoscopy was performed. Bipolar coagulation was applied at the edges of the perforation to secure haemostasis. The patient 5 years later became pregnant and was admitted in labour at 41 weeks' gestation. She required an emergency laparotomy for fetal bradycardia. A live baby was delivered through a lower segment incision. On inspection of the uterus a circular defect was noted at the fundus. The uterus was repaired and haemostasis was eventually achieved. The lower segment was closed separately. The postoperative course, for both mother and baby was satisfactory.
Counselling guidelines for managing musculoskeletal problems in haemophilia in the 1990s
Authors: MILLER R. , BEETON K. , GOLDMAN E. , RIBBANS W.J.
Published: November 2003

Complex medical, psychological and social factors affect how patients with haemophilia and their families respond to bleeding episodes. Prompt, adequate treatment for bleeds remains the best way to preserve optimal musculoskeletal health. Untreated and under treated bleeding episodes into muscles and joints can cause pain, deformity and severely limit the daily activities of patients with haemophilia. Viral infections over the last decade have, to some extent, diverted attention away from musculoskeletal problems. The orthopaedic contribution to haemophilia care remains important and can be enhanced through regular review clinics and developing focused approaches to identifying and addressing musculoskeletal problems.
Multifocal pseudotumour in a single limb
Authors: HEIM M. , HOROSZOWSKI H. , SCHULMAN S. , VARON D. , BARZILAI A. , ENGELBERG S. , MARTINOWITZ U.
Published: November 2003

A 13‐year‐old boy with severe haemophilia presented at the National Centre with gross swelling of his foot and infrapatella area, and reported that several months previously he had kicked a football and had instantly developed a bleed in his foot. Despite replacement factor the swelling failed to subside. He had ambulated for a while using crutches and when he eventually presented himself the X‐rays revealed two separate pseudotumours. The patient underwent a transfemoral amputation.
Emotional adjustment of children and adolescents with haemophilia in relation to the HIV threat
Authors: BOSWERGER M. G. C. , FIJNVANDRAAT K. , VAN VELDHUIZEN A. M. H. , ROSENDAAL F. R. , PETERS M.
Published: November 2003

A Dutch nation‐wide study on young haemophilia patients, whose former treatment placed them at risk for HIV infection, was done to examine the effect of HIV testing, HIV status, disclosure of HIV status and the child's experiences with disease‐related information on emotional adjustment. In the Netherlands HIV tests are not routinely performed for paediatric haemophilia patients, but the number of HIV‐infected children is estimated to be low (8%). Seventy‐two boys with haemophilia, five HIV positive, 51 HIV negative and 16 not tested, and their mothers were interviewed and administered standardized questionnaires. Multiple regression analyses showed no differences in anxiety and depression between HIV‐positive, HIV‐negative or untested boys, nor between children who were informed or not informed about their HIV status. Conversely, children who experienced more difficulties to obtain information about the their disease were significantly more anxious and tended to be more depressed. No significant differences in emotional distress were found between the patients and a standardization sample of healthy peers. The data provide evidence that children and adolescents with haemophilia cope effectively with their disease and the emotional impact of the HIV threat. There seems to be no reason to protect children from testing or knowing their HIV status. In the absence of compelling medical reasons, however, health care workers should not forcefully advocate testing or early disclosure. Distinct disease and treatment‐related factors as well as social factors modify disclosure practices.
Lack of immune response to mouse IgG in previously untreated haemophilia A and haemophilia B patients treated with monoclonal antibody purified factor VIII and factor IX preparations
Authors: DAVIS H. M. , NASH D. W. , CLYMER M. D. , FRIGO M. L. , BERGMAN G. E.
Published: November 2003

Immunoaffinity purification of factor VIII and factor IX results in the inclusion of trace quantities (50 ng 100 IU−1) of mouse protein in the final product. It is possible that infusion of extremely low levels of proteins might induce human antimouse antibody (HAMA) responses. To test this possibility, IgG, IgM and IgE antibodies to mouse IgG were assessed in previously untreated haemophilia A and haemophilia B patients (n = 9 and n = 11, respectively) who received monoclonal antibody (MAb) purified factor VIII (Monoclate‐P® Antihaemophilic Factor [Human] Centeon, King of Prussia, PA) or factor IX (Mononine® Coagulation Factor IX [Human] Centeon). HAMA were evaluated prior to and 2–42 months after initial treatment. IgE antibodies to mouse IgG were undetectable (< 19 ng ML−1) at all time points. Antimouse IgG levels for Monoclate‐P‐treated patients averaged (mean±SD) 0.40±0.18 μg mL−1 prior to treatment, and 0.64±0.43 μg mL−1 at the time of last observation (P > 0.05, not significant [n.s.]). Respective values for antimouse IgM in these patients were 2.48±1.20 μg mL−1 and 2.85±1.63 μg mL−1 (P > 0.05, n.s.). Antimouse IgG levels for Mononine‐treated patients averaged 0.48±0.52 μg mL−1 prior to treatment, and 0.66±0.59 μg mL−1 after 3 months of therapy (P > 0.05, n.s.). Respective values for antimouse IgM in these pa‐tients were 1.94±1.52 μg mL−1 and 1.77±0.99 μg mL−1 (P > 0.05, n.s.). Lack of immunogenicity of traces of mouse protein in these preparations is supported in that none of the patients assessed developed anaphylactoid reactions during treatment.
Improved cost‐effectiveness by pharmacokinetic dosing of factor VIII in prophylactic treatment of haemophilia A
Authors: CARLSSON M. , BERNTORP E. , BJÖRKMAN S. , LETHAGEN S. , LJUNG R.
Published: November 2003

The aim of the study was to investigate the feasibility of optimizing prophylactic dosing of factor VIII by the use of individual pharmacokinetic data. Twenty‐one patients were enrolled in a randomized cross‐over study on standard dosage regimens vs. dosing according to pharmacokinetic principles. The study period was 2×6 months. Using single‐dose pharmacokinetic data for each patient, plasma factor VIII procoagulant activity (FVIII:C) curves following various doses and intervals were computer‐simulated. From these calculations, a suitable dosage was chosen. FVIII:C was also repeatedly measured during study periods. Trough levels of FVIII:C, numbers of spontaneous joint bleedings and amounts of factor concentrate used during the two study periods were compared for each patient.

There was a close correlation between predicted and measured values of FVIII:C. As the half‐lives of FVIII:C in the patients varied from 7.8 to 18.3 h, it was obviously beneficial to base the dosage on individual pharmacokinetic data. Fourteen patients completed both study periods. Mean trough level of exogenous FVIII:C was raised from 0.89 (SD 0.73) U dL−1 during standard dosage to 2.2 (1.5) U dL−1 during pharmacokinetic dosage. Concomitantly, mean 6‐month consumption of factor VIII was decreased from 124 000 (SD 30 000) units to 84 000 (31 000) units. Numbers of reported bleedings were generally similar during both periods.

The study demonstrates the usefulness of individual pharmacokinetics as a tool for cost‐effective utilization of factor VIII in the prophylactic treatment of haemophilia A.
Identifying carriers at high risk for negative reactions when performing prenatal diagnosis of haemophilia
Authors: TEDGÅRD U. , LJUNG R. , MCNEIL T. F. , TEDGÅRD E.
Published: November 2003

The aim of the current study was to determine which pregnant carriers of haemophilia are at particularly high risk for having notably negative psychological reactions in association with prenatal diagnosis (PND) by fetal blood sampling of offspring haemophilia. Among 29 carriers of haemophilia A or B, notable psychiatric or psychosomatic symptoms in association with PND were significantly related to the woman’s having a negative view of herself in general and of being a gene carrier, a planned pregnancy, high education, a good general knowledge of haemophilia and a guiding philosophy of life. Women with strong negative reactions significantly more often reported signs of depressive mood at follow‐up. The results suggest that giving more information and promoting increased knowledge about the disease and the PND procedure will, by itself, not help women to cope better emotionally. Provision of prospective psychosocial support is recommended.
Incidence of hereditary bleeding disorders in Bradford, UK: variation with ethnic group
Authors: MACHETA M. P. , MINFORD A. M. B. , PARAPIA L. A.
Published: November 2003

We have studied the number of patients registered with congenital bleeding disorders at the Haemophilia Centre, Bradford, UK, according to ethnic group. The large Pakistani population in Bradford presents a different spectrum of disorders compared with the indigenous Caucasian population with a significantly higher number of cases of factor VII deficiency and platelet disorders. Other haemophilia centres in the developed world serving large immigrant communities may also manage increased numbers of these rarer disorders with similar implications for resource allocation.
Identification and eradication of Helicobacter pylori infection in haemophilic patients
Authors: LEE C. K. , WYETH J. , SERCOMBE J. C. , PASI K. J. , LEE C. A. , POUNDER R. E.
Published: November 2003

The aim of this study was to identify and eradicate H. pylori infection in patients with haemophilia. Patients were screened for IgG antibodies against H. pylori; active infection was determined using a 13C‐urea breath test and infected patients were given combination therapy with antibiotics to eradicate infection. Seventy‐eight of 219 (36%) patients with haemophilia were found to have an elevated serum antibody titre against H. pylori; of 36 antibody‐positive patients with confirmatory testing, 14 were found to have active H. pylori infection. H. pylori infection was successfully eradicated in every infectedpatient using acombination of ranitidine plus two antibiotics (usually amoxycillin and metronidazole). It is concluded that eradication of H. pylori infection is likely to be a cost‐effective screening strategy in patients with haemophilia, to prevent complications of peptic ulcer disease.
Membranous fat necrosis of the breast
Authors: COYNE J.D. , PARKINSON D. , BAILDAM A.D.
Published: November 2003

To investigate the pattern and prevalence of membranous fat necrosis of the breast we examined 25 breast biopsies or mastectomy specimens performed for recurrent lumps following conservative surgery and radiation therapy. In addition, we examined 41 consecutive cases taken from our files coded as fat necrosis which were associated with several aetiologies. Our results demonstrate that membranous fat necrosis of the breast occurs in association with several aetiologies but in its florid form is most often due to radiation therapy.
Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease
Authors: BISCHOFF S.C. , WEDEMEYER J. , HERRMANN A. , MEIER P.N. , TRAUTWEIN C. , CETIN Y. , MASCHEK H. , STOLTE M. , GEBEL M. , MANNS M.P.
Published: November 2003

Previous studies on the frequency of intestinal mast cells and eosinophils in patients with inflammatory bowel disease yielded conflicting results. In the present morphometric study, we quantified mast cells and eosinophils in the lamina propria by histological and immunohistochemical methods in 64 patients suffering from Crohn’s disease (33 cases) or ulcerative colitis (31 cases), and in 29 controls. Histological data from 206 biopsies were related to the presence of mucosal inflammation and clinical parameters. The number of eosinophils was increased in patients with inflammatory bowel conditions (mean ± SE: 331 ± 44/mm2) as compared to controls (258 ± 27/mm2), and was dependent on disease activity and drug treatment. Mean mast cell numbers did not differ between patients and controls. However, a reduced mast cell number was found in toluidine blue‐stained sections of actively inflamed tissue areas (143 ± 16/mm2, versus 206 ± 18/mm2 in non‐inflamed tissue). Immunohistochemical studies using antibodies against the granule proteins tryptase and chymase suggest that this decrease in mast cell numbers is due to mast cell degranulation. The present data show that the number of intestinal mast cells and eosinophils is altered in patients with inflammatory bowel diseases, suggesting that both cell types are involved in the pathogenesis of chronic intestinal inflammation.
T‐cell rich B‐cell non‐Hodgkin's lymphoma: a progressed form of follicle centre cell lymphoma and lymphocyte predominance Hodgkin's disease
Authors: DE JONG D. , VAN GORP J. , SIE‐GO D. , VAN HEERDE P.
Published: November 2003

T‐cell rich B‐cell non‐Hodgkin's lymphoma (T‐cell rich B‐cell lymphoma) is a morphological variant of diffuse large B‐cell lymphoma. It is important to recognize this variant in the differential diagnosis of T‐cell non‐Hodgkin's lymphoma. The main differential diagnosis of T‐cell rich B‐cell lymphoma, nodular and diffuse lymphocyte predominance Hodgkin's disease (lymphocyte predominance Hodgkin's disease), is, however, even more difficult and differentiating criteria are still not satisfactorily defined. Moreover, T‐cell rich B‐cell lymphoma may not represent a clinicopathological entity. Twelve cases of T‐cell rich B‐cell lymphoma, selected on the basis of morphology and limited immunohistochemistry without previous knowledge of clinical data, were studied by immunohistochemistry and polymerase chain reaction for bcl‐2 rearrangements to investigate the histogenetic background. In three of 12 cases, bcl‐2 rearrangements were found, strongly suggesting a follicle centre cell origin. In three other cases, a documented history of definite nodular lymphocyte predominance Hodgkin's disease 29 months to 20 years prior to the diagnosis of the lymphoma was present. No differences in growth pattern, residual nodularity, tumour cell distribution, cellular morphology and composition, or immunophenotypical differences were noted in these six cases as compared to the remaining cases. These data underscore the histogenetic diversity in T‐cell rich B‐cell lymphoma and identify it as a progressed form of lymphoma derived from entities as diverse as follicle centre cell lymphoma and nodular lymphocyte predominance Hodgkin's disease. Moreover, it shows a complete morphological overlap with the diffuse form of lymphocyte predominance Hodgkin's disease and may actually encompass this disease entity.
Cadherins in reactive lymph nodes and lymphomas: high expression in anaplastic large cell lymphomas
Authors: ASHTON‐KEY M. , COWLEY G.P. , SMITH M.E.F.
Published: November 2003

Using a polyclonal pan‐cadherin antibody and a monoclonal E‐cadherin antibody (HECD‐1) we have investigated cadherin expression in lymphomas and reactive lymph nodes. Routinely processed tissue from nine reactive lymph nodes and 48 lymphomas (six T‐cell, six high‐grade B‐cell, 15 low‐grade B‐cell, 13 anaplastic large cell and eight Hodgkin’s disease) were immunostained. The reactive cases showed pan‐cadherin membrane associated staining of endothelium and epithelioid granulomas. No staining of lymphoid cells was seen. Pan‐cadherin immunostaining was present in three of six T‐cell lymphomas, two of six high‐grade B‐cell lymphomas, 12 of 13 anaplastic large cell lymphomas and three of eight cases of Hodgkin’s disease. No staining of low‐grade B‐cell lymphomas was identified with the pan‐cadherin antibody. E‐cadherin was not detected in any of the lymphomas that showed pan‐cadherin expression. The frequent and strongest cadherin expression in anaplastic large cell is noteworthy. The tumour cells of this lymphoma subtype are characterized by copious cytoplasm and a cohesive appearance, features which impart a superficial resemblance to carcinoma cells. Since cadherin molecules are known to have major morpho‐regulatory functions our data suggests that the expression of cadherin molecules by anaplastic large cell lymphomas may play an important role in determining their characteristic epithelioid phenotype.
Papillary endothelial hyperplasia of adnexal vasculature
Authors: SAFNECK J.R. , ALGUACIL‐GARCIA A. , PARASKEVAS M.
Published: November 2003

Papillary endothelial hyperplasia is an exuberant predominantly intravascular endothelial proliferation which may simulate angiosarcoma both clinically and histopathologically. This report describes what, to the best of our knowledge, is a unique case of papillary endothelial hyperplasia within para‐ovarian and paratubal veins in relation to a multicystic mesothelial and haemorrhagic ovarian mass. Papillary endothelial hyperplasia should be included in the differential diagnosis of vascular lesions in this site.
A study of the value and prognostic significance of mucin staining in squamous cell carcinoma of the uterine cervix
Authors: LANGLOIS N.E.I. , ELLUL B. , MILLER I.D.
Published: November 2003

One hundred and eighty‐one cases of squamous carcinoma of the uterine cervix, which had been retrieved from the archives of Aberdeen Royal Hospital, from 1974 to 1988, were stained with periodic acid‐Schiff following diastase and alcian blue to ascertain the value and prognostic significance of demonstrating the presence of mucin. Each case was typed and graded on a representative haematoxylin and eosin section, while the age at diagnosis, stage and survival (within a minimum five year follow‐up) was obtained from examination of hospital case notes and death certificates. The data was analysed by Cox regression which revealed that the demonstration of mucin, either by both stains or only one method, had no bearing on prognosis. On this basis, it is concluded that routine mucin staining of squamous carcinomas of the uterine cervix is not justified.
Histopathology of the liver in non‐cirrhotic portal hypertension of unknown aetiology
Authors: NAKANUMA Y. , HOSO M. , SASAKI M. , TERADA T. , KATAYANAGI K. , NONOMURA A. , KURUMAYA H. , HARADA A. , OBATA H.
Published: November 2003

Non‐cirrhotic, long‐standing portal hypertension of unknown aetiology is being re‐evaluated histopathologically and clinically. In this study, we examined 107 livers with this condition (92 wedge biopsy and 15 autopsy specimens) from five institutions in Japan. These cases were histologically categorized into four groups: idiopathic portal hypertension (66 cases), nodular regenerative hyperplasia (14 cases), partial nodular transformation (two cases), and incomplete septal cirrhosis (25 cases). These four groups shared several histological features: dense portal fibrosis with portal venous obliteration and intralobular slender fibrosis. In addition, the histopathological features characteristic of one group were also found to a mild degree in other groups. The histopathological lesions preceding portal venous obliteration remain speculative. However, the portal venous obliteration may be responsible for the occurrence of sustained portal hypertension and several of the pathological changes in these livers. It seems likely that idiopathic portal hypertension, nodular regenerative hyperplasia, partial nodular transformation and incomplete septal cirrhosis comprise a family of non‐cirrhotic, long‐standing portal hypertension in Japan, and the histological differences between them may reflect chronological progression of a single disease.
GRANULOMAS AND HEPATITIS C
Authors: GOLDIN R.D. , LEVINE T.S. , FOSTER G.R. , THOMAS H.C.
Published: November 2003

Hepatitis C (HCV) is associated with a number of characteristic histological features.. A recent paper has identified an increased frequency of granulomas in resection specimens from cases of HCV. We have carried out a retrospective study of 155 cases of HCV to assess the frequency of granulomas in biopsy specimens. We had two control groups: 151 cases of hepatitis B (HBV) and 129 cases of alcohol induced liver disease. Granulomas were found in 14 cases of HCV (10%), three cases of HBV (2%) and three cases of alcohol induced liver disease (2%). Granulomas were significantly commoner in cases of HCV than in the other two groups. Of the 14 cases of HCV, the granulomas could be ascribed to another cause in seven cases. When the analysis was carried out, excluding those granulomas which could be ascribed to another cause, they were still significantly commoner in cases of HCV. We conclude that granulomas are more frequent in HCV but that in half of cases in which they are found another cause can be identified. This means that if granulomas are seen in association with hepatitis C another aetiology should be sought before ascribing them to HCV.
EBV latent membrane protein (LMP‐1) and bcl‐2 protein expression in Reed‐Sternberg‐like cells in post‐transplant lymphoproliferative disorders
Authors: CHETTY R. , BIDDOLPH S.C. , KAKLAMANIS L. , CARY N. , STEWART S. , GIATROMANOLAKI A. , GATTER K.C.
Published: November 2003

An inconsistent association exists between EBV‐LMP‐1 and bcl‐2 protein expression in Reed‐Sternberg cells seen in Hodgkin’s disease. In fact, many studies have concluded that there is no correlation between EBV‐LMP and bcl‐2 expression in Hodgkin's disease. We undertook an analysis of post‐transplant lymphoproliferative disorders to explore the relationship between EBV‐LMP and bcl‐2 in Reed‐Sternberg‐like cells found in this condition, given the strong association between this disorder and EBV. Reed‐Sternberg‐like cells were found histologically in 11 of 28 cases of renal, heart and heart‐lung post‐transplant lymphoproliferative disorders. Formalin‐fixed, paraffin‐embedded sections were stained with monoclonal antibodies to EBV‐LMP‐1 and bcl‐2 proteins. Reed‐Sternberg‐like cells in all 11 cases co‐expressed EBV‐LMP and bcl‐2. A similar relationship was noted with large, mononuclear cells and occasional small lymphoid cells. The staining pattern seen with both antibodies was of similar intensity and both displayed cytoplasmic Golgi accentuation. In the setting of post‐transplant lymphoproliferative disorders, Reed‐Sternberg‐like cells exhibit strong co‐expression of EBV‐LMP‐1 and bcl‐2 proteins, supporting a positive correlation between them. This is in contrast to the findings in Hodgkin's disease. The reason for this discrepancy may be due to the iatrogenic immunosuppression and resultant severe EBV infection, together with other cellular events.
Alkaline encrusted cystitis associated with malakoplakia
Authors: BERNEY D.M. , THOMPSON I. , SHEAFF M. , BAITHUN S.I.
Published: November 2003

Alkaline encrusted cystitis is a rare inflammatory condition of the bladder which has been reported sporadically over the past 80 years. It is caused by infection with urea splitting organisms leading to the deposition of inorganic salts on to the surface of the bladder. We present three cases of alkaline encrusted cystitis. In two cases the encrusted area was associated with foci of malakoplakia. The third case occurred in a patient who had received chemotherapy for acute lymphoblastic leukaemia. To our knowledge, these are the first cases of malakoplakia associated with alkaline encrusted cystitis. These two conditions have a number of clinical and aetiological similarities, and may have more in common than has been previously thought.
Malignant lymphomas with a follicular growth pattern
Authors: ISAACSON P.G.
Published: November 2003

Given the pivotal role of the B‐cell follicle in B‐cell proliferation, and the fact that the follicle centre has the highest proliferation fraction of any structure in the body, it would be reasonable to expect that the potential for the development of aberrant (neoplastic) growth within it would be relatively high, especially when compared to other lymphoid compartments. However, in all current lymphoma classifications only one entity, namely follicular lymphoma, is acknowledged as having any relation to the follicle. As knowledge of the immunophenotype and function of the normal follicle has increased, it has become evident that many lymphomas, including some examples of Hodgkin’s disease, are related to the B‐cell follicle and as a consequence manifest a follicular growth pattern. This has implications for the pathogenesis of these tumours and may point the way to novel therapeutic options.
Peroxisome proliferation associated with fibrinogen storage in the liver
Authors: DE CRAEMER D. , PIPELEERS‐MARICHAL M. , VANDENPLAS Y. , VAN DEN BRANDEN C.
Published: November 2003

We report a patient with fibrinogen storage disease in which there was proliferation of normal‐sized peroxisomes in the hepatocytes. This phenomenon has previously been described in several acquired liver diseases. We believe that this is an adaptation response due to decreased microsomal isoenzyme activity as a result of the excess accumulation of fibrinogen in the endoplasmic reticulum.
HETEROGENEITY OF MITOTIC ACTIVITY IN BREAST CANCER
Authors: Jannink I. , Risberg B. , Diest P.J.van , Baak J.P.A.
Published: November 2003

The aim of this study was to investigate to what extent mitotic activity index assessments are influenced by tumour heterogeneity. Ten invasive breast carcinomas of varying size were completely embedded, yielding 2–7 paraffin blocks per tumour. From each block, three H&E stained skip sections were cut and, in all sections, the mitotic activity index (MAI) and the mitoses per volume (M/V‐)index were assessed. Coefficients of variation were calculated for the three different sampling levels (tumours, blocks, sections). In addition we recorded in how many tumours threshold discrepancies (values on both sides of the prognostic thresholds) occurred. Nested analysis of variance showed that most of the total variance occurred between the tumours. Threshold discrepancies occurred in four (40%) and five tumours (50%) for mitotic activity index and the mitoses per volume index, respectively. However, when grouping all sections from the same tumour and subjectively selecting the one showing the highest proliferation, the section with the highest mitotic activity was selected in nine of the 10 cases. In the other single case a prognostically correct value was still obtained. Thus, there is a noteworthy intra‐tumour heterogeneity in mitotic activity in invasive breast cancer. We therefore propose the need to take multiple blocks per tumour and carefully scan all sections for the highest proliferative area.
Chondromyxoid fibroma‐like osteosarcoma: a distinct variant of low‐grade osteosarcoma
Authors: CHOW L.T.C. , LIN J. , YIP K.M.H. , KUMTA S.M. , AHUJA A.T. , KING W.W.K. , LEE J.C.K.
Published: November 2003

Chondromyxoid fibroma‐like osteosarcoma is a recently described, extremely rare subtype of low‐grade osteosarcoma. Two such cases were encountered among 102 cases of osteosarcoma seen in the Prince of Wales Hospital, Hong Kong, between 1984 and 1994. The first patient, a 39‐year‐old woman, presented with a mass in her right maxilla which was resected and mistaken as a myxoma. The tumour recurred locally four years later and she now has extensive local recurrent disease six years after initial presentation and is amenable to support treatment only. The second patient, a 28‐year‐old man, had a pelvic tumour which recurred in the form of a polypoid left atrial tumour and pulmonary nodules six years after operation. The left atrial tumour recurred one year after operation, and led to sudden death of the patient seven years after initial presentation. Radiologically, the tumours in both cases appeared as expansile osteolytic lesions with erosion of adjacent bone and infiltration into soft tissue. Histologically, they consisted of lobules of spindle, stellate or polygonal tumour cells showing mitotic activity and with moderate nuclear pleomorphism and hyperchromatism, set in a highly myxoid stroma superficially mimicking chondromyxoid fibroma. The histological hallmark was the direct production of osteoid by tumour cells. Chondromyxoid fibroma‐like osteosarcoma merits recognition as a distinct variant of low‐grade osteosarcoma for which early appropriate surgery is indicated.
T‐cell lymphoma in Hashimoto’s thyroiditis
Authors: ABDUL‐RAHMAN Z.H. , GOGAS H.J. , TOOZE J.A. , ANDERSON B. , MANSI J. , SACKS N.P. , FINLAYSON C.J.
Published: November 2003

An elderly Caucasian woman with a 2‐year‐history of hypothyroidism, treated with thyroxine, presented with a rapidly growing mass in the thyroid. The morphological and immunological features of this thyroid tumour were those of a peripheral T‐cell lymphoma with an immunophenotype commonly associated with HTLV‐1 positive‐adult T‐cell leukaemia/lymphoma, although serology for HTLV1 antibody was negative. Monoclonal gene rearrangements were demonstrated with T‐cell receptor beta‐ and gamma‐specific primers. There are several interesting features in this case (i): although primary B‐cell lymphomas (MALT‐associated lymphomas) of thyroid are a well‐recognized sequel to thyroiditis, primary T‐cell lymphomas are rare, even in areas of the world where adult T‐cell lymphomas predominate; (ii) the tumour showed the typical immunophenotype of an HTLV‐1 positive T‐cell lymphoma but the patient is English, has not visited endemic areas, and is serologically negative for HTLV–1; (iii) the residual thyroid gland showed a florid lymphocytic thyroiditis with Hu¨rthle cell change, typical of Hashimoto’s thyroiditis; (iv) unlike other reports of thyroid T‐cell lymphoma, which have presented with stage III‐IV disease, this tumour presented in the favourable clinical stage of IE.
Pitfalls in the diagnosis of ectopic hamartomatous thymoma
Authors: MICHAL M. , ZÁMEČNÍK M. , GOGORA M. , MUKENŠNABL P. , NEUBAUER L.
Published: November 2003

We describe four cases of ectopic hamartomatous thymoma with unusual morphological features. In cases 1 and 2 we found a dysplastic glandular component which was often arranged in a cribriform pattern bridging several glandular spaces. In case 2 we found solid adenocarcinomatous areas with infiltrative edges. Case 3 showed widespread smooth muscle differentiation within the spindle epithelial cell component, the presence of multiple clear cell glands which contained a distinct myoepithelial layer and an overall picture which vaguely resembled a sclerosing adenosis of the breast. Case 4 contained frequent foci of multinucleated giant epithelial cells within the markedly cellular spindle cell component; it also showed multiple, hypocellular, myxoid areas containing eosinophilic cords and pearls of squamous cells, and resembled squamous cell carcinoma with a sarcomatoid spindle cell component. We could not find any evidence of a thymic origin or of thymic differentiation in our four cases or in any other reported cases of ectopic hamartomatous thymoma. We believe that ectopic hamartomatous thymomas manifest salivary gland differentiation.
Mammary mucinous lesions: congeners, prevalence and important pathological associations
Authors: CHINYAMA C.N. , DAVIES J.D.
Published: November 2003

A retrospective histopathological study was undertaken to determine the prevalence of mucin filled ducts and their associated mucinous proliferation in 962 breast cancers and 335 benign lesions. A total of 38 (3%) cases with mucin filled ducts was identified and 27 (2%) of these showed mucin extravasation into the adjacent stroma, changes characteristic of mucocoele‐like lesions. This constitutes the largest series reported to date. Of the mucocoele‐like lesions 12 were prototypic screen‐detected cases; 11 of which were mammographically detected on account of suspicious microcalcification and eight cases (67%) exhibited mucinous atypical ductal hyperplasia without overt malignancy. A further 12 mucocoele‐like lesions were incidental findings in screen‐detected (11) and symptomatic (one) cancers, the majority of which were invasive ductal carcinomas of no special type. In six of these cases (50%), mucinous atypical ductal hyperplasia or ductal carcinoma in situ was present. Thirty mucinous carcinomas constituted 3% of all cancers and three cases had associated mucocoele‐like lesions. Mucinous atypical ductal hyperplasia or ductal carcinoma in situ was also associated with 11 cases of mucinous carcinoma. In six mucinous carcinomas, amorphous microcalcification with a similar appearance to that of benign mucocoele‐like lesions was identified in the mucin, suggesting a possible link between the two lesions. Mucin‐filled ducts or mucocoele‐like lesions were almost twice as frequent in screen‐detected as in symptomatic lesions. The presence of mucinous atypical ductal hyperplasia in screen‐detected mucocoele‐like lesions, a decade earlier than the peak of mucinous carcinoma, is a possible risk factor for subsequent invasive malignancy. Mucin‐filled ducts, mucocoele‐like lesions, mucinous atypical ductal hyperplasia or ductal carcinoma in situ and mucinous carcinoma may represent different stages of the same disease process. Our findings suggest that patients with mucin‐filled ducts of mucocoele‐like lesions merit close follow‐up.
Expression of metastasis suppressor gene product, nm23 protein, is not inversely correlated with the tumour progression in human malignant melanomas
Authors: SAITOH K. , TAKAHASHI H. , YAMAMOTO M. , KISHI H. , PARSONS P.G.
Published: November 2003

An inverse correlation between the nm23 RNA level and tumour progression of melanocytes has been reported. To elucidate whether the expression of nm23 gene product in malignant melanoma is also inversely correlated with metastatic potential, conventional prognostic parameters or the tumour suppressor protein p53, immunohistochemical studies using a monoclonal antibody against nm23‐H1 protein were performed on 138 benign and malignant melanocytic tumours. The expression of nm23 protein was compared with that of p53 protein and conventional clinicopathological prognostic factors. The nm23 protein level in benign melanocytes and metastatic melanoma cells was also studied by Western blot analysis. No significant difference regarding the protein was observed between naevi and melanomas, either at histological or protein levels. The expression correlated with local recurrence within 1 year after surgery, level of invasion and tumour thickness, but no parallels were observed between the nm23 and p53 proteins, suggesting that gene is regulated by independent mechanisms, although located on the same chromosome. There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.
Vimentin‐positive adenocarcinomas of the stomach: co‐expression of vimentin and cytokeratin
Authors: UTSUNOMIYA T. , YAO T. , MASUDA K. , TSUNEYOSHI M.
Published: November 2003

Recently, the expression of vimentin has been reported in some carcinomas. This study was designed to clarify the significance of vimentin expression in solid type poorly differentiated adenocarcinomas of the stomach. Immunohistochemically, 239 poorly differentiated adenocarcinomas with solid components of the stomach were stained for vimentin. Vimentin‐positive cases were also stained by CAM 5.2 using serial mirror sections. We found 15 (6.3%) vimentin‐positive cases. Twelve of them demonstrated varying amounts of rhabdoid‐like cells. Eight cases diffusely co‐expressed vimentin and cytokeratin simultaneously. In addition, four co‐expressing cases showed positive staining with Keratin‐903 which recognizes the high molecular‐weight cytokeratin. Most of the co‐expressing cases showed a diffuse proliferation of polygonal tumour cells with focal cell‐to‐cell contact. The prognosis of the co‐expressing cases was poor in comparison with that of the 89 vimentin‐negative tumours (P < 0.05).
Large cell neuroendocrine carcinoma of the thymus
Authors: CHETTY R. , BATITANG S. , GOVENDER D.
Published: November 2003

Aim:

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.

Case details:

A 68‐year‐old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later. Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high‐power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron‐specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot‐like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma.

Conclusions:

Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.
Thyroid carcinoma associated with familial adenomatous polyposis
Authors: CETTA F. , TOTI P. , PETRACCI M. , MONTALTO G. , DISANTO A. , LORÈ F. , FUSCO A.
Published: November 2003

Aims:

Thyroid carcinoma is an extracolonic manifestation that is present in about 1% to 2% of patients with familial adenomatous polyposis (FAP). Less than 100 cases have been reported in detail. We have investigated the suggestion that FAP associated thyroid carcinoma is significantly different morphologically from both papillary and follicular types and can be considered as a separate entity.

Methods and results:

Specimens from three patients with FAP associated thyroid tumours, all but one having single nodules, have been analysed. All three patients belonged to an extended kindred (23 siblings in four generations) who had genetic analysis and intensive screening for thyroid nodules. Seven patients had the same APC mutation at codon 1061. Pathological examination revealed a typical papillary carcinoma, encapsulated variant, in all patients, with follicular areas in one case. All thyroid specimens, in addition to histological and immunohistological examinations, were also specifically studied for activation of the RET‐PTC oncogene, that seems to be restricted to papillary thyroid carcinoma. Two of the three patients had RET‐PTC activation (PTC1 isoform).

Conclusions:

The findings suggest that the tumours were certainly papillary, at least in the present kindred. Further studies in different families are required for a better understanding of this peculiar tumour and of its biological behaviour.
Carcinosarcoma of the oesophagus showing neuroendocrine, squamous and glandular differentiation
Authors: ROBERTSON N.J. , RAHAMIM J. , SMITH M.E.F.
Published: November 2003

Aim:

A case of oesophageal carcinosarcoma occurring in a previously fit, 64‐year‐old man is reported.

Case summary:

The carcinomatous component displayed neuroendocrine, squamous and glandular differentiation; the sarcomatous component showed no specific features of differentiation. In‐situ squamous carcinoma was present in the adjacent squamous mucosa. The most superficial part of the invasive tumour consisted of carcinosarcoma with a predominant neuroendocrine epithelial component. Squamous carcinoma without an accompanying sarcomatous component occupied most of the deeper part of the tumour, suggesting outgrowth of this tumour type by a selective growth advantage.

Conclusion:

We speculate that further tumour growth might have led to complete replacement of the tumour by pure squamous carcinoma, and that other advanced oesophageal squamous carcinomas might have had their origin in a short‐lived carcinosarcomatous phase.
Granular cell dermatofibroma
Authors: ZELGER B.G. , STEINER H. , KUTZNER H. , RÜTTEN A. , ZELGER B.
Published: November 2003

Aims:

To describe a series of five granular cell dermatofibromas as an unusual and rare manifestation of fibrohistiocytic tissue response.

Methods and results:

Five granular cell dermatofibromas were collected out of 136 tumours filed as granular cell tumours. Clinically, all lesions occurred on the shoulder or back of middle‐aged adults (two women, three men), mostly with the clinical diagnosis of a fibrohistiocytic lesion. Histology revealed well‐circumscribed, dermal to subcutaneous lesions dominated by periodic acid–Schiff (PAS) positive, granular cells. Acanthosis above, as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lymphohistiocytic infiltrate at the periphery of the lesion, indicated the fibrohistiocytic origin. Lesions showed prominent reactivity with NK1C3 (CD57), as well as for macrophage markers KiM1p and KP1 (CD68). In contrast to classic Schwannian/neurogenic granular cell tumours, granular cell dermatofibromas were S100 protein negative, but showed variable reactivity for factor XIIIa (10–50%) in 4/5, for smooth muscle specific actin (10–50%) in 2/5 and with E9 (10–30%) in 3/5 lesions. Electron microscopy in one case revealed large pools of phago‐lysosomes and variably sized glycogen granules in granular cells.

Conclusion:

Our series delineates granular cell dermatofibroma as a distinct clinicopathological variant of fibrohistiocytic tissue response which needs to be distinguished from other tumours with granular cell features.
Prognostic value of high serum levels of CA‐125 in malignant secretory peritoneal mesotheliomas affecting young women. A case report with differential diagnosis and review of the literature
Authors: ALMUDÉVAR BERCERO E. , GARCÍA‐ROSTÁN Y PÉREZ G.MA , GARCÍA BRAGADO F. , JIMÉNEZ C.
Published: November 2003

Aims:

Very few cases of diffuse, malignant, peritoneal mesothelioma have been reported in young women. Distinction between peritoneal mesothelioma and serous epithelial tumours, including papillary serous carcinomas and borderline serous tumours, can be difficult. Differential diagnosis based on clinical appearance and imaging techniques is broad and inconclusive, thus the diagnosis must be confirmed by histological examination. Because the vast majority of tumours involving the peritoneal and serosal surfaces are due to primary or metastatic serous epithelial tumours, there is a tendency on the part of pathologists to disregard the possibility of mesothelioma when examining a biopsy or excision specimen. This is especially likely to occur when mesothelioma is associated with highly elevated serum levels of CA‐125, which is the typical tumoral marker of epithelial serous tumours from the ovary. The association between peritoneal mesothelioma and high serum levels of CA‐125 has been reported in the literature only in two cases.

Case details:

In order to avoid a misdiagnosis of this neoplasm we describe a new case of peritoneal mesothelioma in an 18‐year‐old woman with high serum levels of CA‐125.

Conclusions:

Besides its clinicopathological characteristics and its histological, immunohistochemical and ultrastructural features, we describe its biological behaviour, which seems to be worst when CA‐125 levels are high.
Enteropathy‐associated T‐cell lymphomas have a cytotoxic T‐cell phenotype
Authors: DE BRUIN P.C. , CONNOLLY C.E. , OUDEJANS J.J. , KUMMER J.A. , JANSEN W. , MCCARTHY C.F. , MEIJER C.J.L.M.
Published: November 2003

Aims:

Enteropathy‐associated T‐cell lymphoma (EATCL) is a rare complication of coeliac disease. We investigated whether EATCLs are the neoplastic counterparts of activated cytotoxic T‐cells (CTLs).

Methods and results:

Eight cases, clinically and histologically defined, were stained with monoclonal antibodies against components of the cytotoxic granules of CTLs, granzyme B and T‐cell restricted intracellular antigen (TIA‐1). It was found that all cases had a cytotoxic phenotype, i.e. expression of TIA‐1 in most of the tumour cells, whereas granzyme B was found in six of eight cases, mostly in a smaller number of tumour cells compared to TIA‐1. Since TIA‐1 and granzyme B are expressed at different stages of activation of CTLs it is hypothesized that differences in expression between granzyme B and TIA‐1 in EATCL represent different stages of activation in which the tumour cells are arrested. Clinically, seven of the eight patients died within 10 months after diagnosis of EATCL.

Conclusions:

EATCL is a clinicopathological entity with a grim prognosis and with tumour cells representing a unique neoplastic equivalent of CTLs arrested in varying stages of activation.