Ex vivo sentinel lymph node mapping in colorectal cancer using a magnetic nanoparticle tracer to improve staging accuracy: a pilot study.

AIM: Nodal status is the most important prognostic factor in colorectal cancer (CRC). Small occult metastases may remain undetected on conventional histopathological examination, potentially resulting in undertreatment. Ex vivo sentinel lymph node mapping (SLNM) can be used to improve the accuracy of nodal staging, but the currently used tracers suffer from drawbacks, which hamper implementation of the technique in routine clinical practice. Magnetic tracers are the optimal size for sentinel lymph node (SLN) retention and allow objective quantitative selection of SLNs; they therefore have great potential for SLNM in CRC. The study evaluates the feasibility of ex vivo magnetic SLNM and compares the performance of this technique with blue dye SLNM. METHOD: Twenty-eight ex vivo SLNM procedures were performed in 27 histological node-negative patients with CRC using a magnetic tracer and blue dye. A magnetometer was used to select magnetic SLNs after formalin fixation of the CRC specimen. Both magnetic and blue SLNs were subjected to serial sectioning and immunohistochemical staining to reveal occult metastases. RESULTS: At least one SLN was successfully identified in 27/28 (96%) and 25/28 (89%) of the cases with the magnetic technique and blue dye. Isolated tumour cells were detected in 10 patients. This was predicted with 100% sensitivity and accuracy using the magnetic technique, and with 91% sensitivity and 96% accuracy using the blue dye technique. CONCLUSION: This study demonstrates that ex vivo magnetic SLNM is a feasible technique for use in routine clinical practice, improving nodal staging accuracy of CRC patients.

Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy.

BACKGROUND: Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow-up are lacking. OBJECTIVES: To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin. METHODS: Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow-up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed. RESULTS: Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow-up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B-cell lymphoma (one case) and peripheral T-cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH. CONCLUSIONS: The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long-term follow-up are therefore warranted in such patients.

Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study.

OBJECTIVES: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS: We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS: After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS: In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

Microscopic colitis: prevalence and distribution throughout the colon in patients with chronic diarrhoea.

BACKGROUND: Microscopic colitis presents with chronic diarrhoea with or without abdominal pain. Microscopic colitis is an important cause of chronic diarrhoea. It can be distributed throughout the colon, as well as limited to the right colon. Microscopic colitis is associated with coeliac disease. We studied the prevalence and distribution of microscopic colitis in patients with diarrhoea and normal colonoscopy and we studied the association with coeliac disease. METHODS: Colonoscopy was performed. Biopsies were taken from every segment of the colon. Lymphocytic colitis was defined as the presence of more than 20 lymphocytes per 100 epithelial cells and collagenous colitis was defined as thickening of the basal membrane of more than 10 microm. Upper endoscopy was performed if upper intestinal symptoms were present. If this was the case, small bowel biopsies were taken. RESULTS: Microscopic colitis was found in 13 out of 103 patients. The distribution was diffuse throughout the colon in ten and restricted to the right colon in three patients. In seven patients, upper endoscopy was performed. Marsh I/II lesions were found in six out of seven patients. CONCLUSION: Microscopic colitis was limited to the right colon in 23% of patients. Biopsies of macroscopically normal colonic mucosa in patients with diarrhoea is mandatory.

Duodenal versus jejunal biopsies in suspected celiac disease.

BACKGROUND AND STUDY AIMS: In the past, small-bowel biopsies for diagnosis of celiac disease were taken from the jejunum with a suction capsule, but nowadays most physicians take endoscopic biopsies from the distal duodenum. To validate that practice we compared the diagnostic yield of endoscopic duodenal biopsies with that of endoscopic jejunal biopsies. In addition, we describe a method of orienting biopsy specimens optimally. PATIENTS AND METHODS: Upper endoscopy was performed with a colonoscope. Four jejunal and four duodenal biopsies were taken and oriented immediately thereafter. The pathologist rated the orientation as poor, adequate, or good, and histopathological results were expressed according to the Marsh classification. Jejunal and duodenal biopsy results were compared. RESULTS: 146 patients were included. Jejunal biopsies were taken in 142 patients, and Marsh I-II lesions were found in 56 and Marsh III lesions in 15 patients. In three patients duodenal biopsies were normal while jejunal biopsies showed Marsh I-II lesions. No discrepancies were found in patients with Marsh III lesions. Orientation was good in all biopsies. CONCLUSION: Duodenal biopsies are sufficient to diagnose full-blown celiac disease (Marsh III), but Marsh I-II lesions may be missed in some cases.

Change in anatomic distribution and incidence of colorectal carcinoma over a period of 15 years: clinical considerations.

PURPOSE: Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical implications for the use of diagnostic or screening tools for colorectal cancer. This study was designed to investigate the change in incidence and anatomic distribution of colorectal cancer in a population over a period of 15 years. METHODS: The incidence of colorectal cancer in an eastern part of the Netherlands (700,000 inhabitants) was determined for two years, 1981 and 1996. From the regional laboratory of pathology, data including age, gender, subsite location, and Dukes classification were collected. The subsite location of colorectal cancer was divided into two groups: proximal and distal (the latter being within sigmoidoscopy reach). RESULTS: No differences in age and gender distribution were found. In 1981, the diagnosis of colorectal cancer was made in 232 patients in this region, and in 1996, it was made in 410 patients. The population remained almost stable during this time. Therefore, the incidence rose from 33 to 55 per 100,000 inhabitants from 1981 to 1996, respectively. In 1981, 25 percent of the carcinomas were proximal (to the sigmoid colon); this increased to 37 percent in 1996 ( P< 0.05). CONCLUSIONS: The incidence of colorectal cancer has almost doubled from 1981 to 1996 in this Dutch region. The proportion of proximal colorectal cancer has increased from 25 to 37 percent. These findings add to the notion that sigmoidoscopy is not the optimal diagnostic or screening tool for colorectal cancer.

Treatment of the Budd-Chiari syndrome by insertion of a wall-stent in the hepatic vein after percutaneous transluminal angioplasty: the necessity of follow-up.

Budd-Chiari syndrome is a rare disease and, with or without treatment, the prognosis is usually poor. Percutaneous transluminal angioplasty of the hepatic vein in Budd-Chiari syndrome is a safe method, although recurrent stenosis makes it necessary to repeat it several times in most cases. Insertion of a wall-stent in the hepatic vein seems to be a more long-lasting treatment. Monitoring the blood flow through the wall-stent every 6 months is important because of the apparent obliteration of the wall-stent by intimal fibrosis of the hepatic vein. Further follow-up investigations of this method are necessary.

An important role for chromosome 17, band q25, in the histogenesis of alveolar soft part sarcoma.

A cytogenetic study of two cases of alveolar soft part sarcoma showed near-diploid karyotypes with multiple chromosomal rearrangements. An abnormality of the long arm of chromosome 17, involving band q25, is present in both cases and in 2 of 4 cases in the literature. This recurrent structural abnormality probably plays an important role in the histogenesis of this unusual neoplasm and therefore is important for further molecular investigation.

Tophus-like cholesterol nodules in 2 patients with rheumatoid disease.

We describe 2 patients, both with rheumatoid disease, with tophus-like nodules that contained cholesterol crystals. A tophus-like cholesterol nodule had developed in a tendon sheath of the left little finger of one. The other presented with multiple tophus-like nodules on his left elbow and both forefeet. We discuss the etiology and pathogenesis of crystalline deposits of cholesterol. Nodules at sites of local pressure in patients with rheumatoid arthritis may be deposits of cholesterol crystals.

Treatment of localized non-Hodgkin's lymphomas of the head and neck.

BACKGROUND: Localized non-Hodgkin's lymphomas of the head and neck are generally treated with radiotherapy with or without chemotherapy, although the results of treatment of localized non-Hodgkin's lymphomas with of treatment of localized non-Hodgkin's lymphomas with chemotherapy alone appear to be favorable. It is unclear if and when combined modality therapy should be used. METHODS: The authors reviewed the records of 53 patients with Stage I or II non-Hodgkin's lymphoma of the head and neck, who were treated with radiotherapy alone (13 patients), chemotherapy according to the cyclophosphamide, doxorubicin, vincristine, prednisone- (CHOP) regimen (27 patients), or a combination of both treatments (13 patients). RESULTS: A complete remission was achieved in 43 (81%) patients. The 5-year survival for all patients was 78%. A significant difference (P = 0.03) in 5-year relapse-free survival was observed between Stages I and II disease, of 92 and 60%, respectively. Extensive tumor was a significantly poor prognostic factor (P = 0.04) with a 5-year relapse-free survival of 52 versus 84% for patients with nonextensive lymphoma. Eight relapses occurred; in five patients, a local relapse was the first presentation. Although salvage radiotherapy was successful in these five patients, a distant relapse developed in three. No relapses were observed in previously irradiated areas. CONCLUSIONS: Our results suggest that radiotherapy alone is the appropriate treatment for nonextensive Stage I intermediate grade non-Hodgkin's lymphoma of the head and neck. For extensive Stage I or II non-Hodgkin's lymphomas, chemotherapy is preferable. The value of combined modality therapy remains unclear.

In-toto removal of a subretinal Cysticercus cellulosae by pars plana vitrectomy.

A case of subretinal cysticercosis was treated with laser coagulations round the cyst prior to surgery. In-toto removal of the living cysticercus was performed by pars plana vitrectomy. Two weeks after surgery 25/20 vision was regained. Histopathology of the cyst confirmed the clinical diagnosis.

Constrictive pericarditis caused by primary liposarcoma.

A 30 year old man presented with symptoms of constrictive pericarditis. Echocardiography and computed tomography showed a mass extending from the pericardium to surround the heart and penetrating the left ventricular apex. An unresectable pleomorphic liposarcoma arising from the pericardium was found at thoracotomy.

The thymus in acquired immune deficiency syndrome. Comparison with other types of immunodeficiency diseases, and presence of components of human immunodeficiency virus type 1.

The authors studied thymus specimens taken at autopsy from eight acquired immune deficiency syndrome (AIDS) patients and compared these with those taken from four patients with congenital immunodeficiency (unrelated to an intrinsic thymus defect) and seven patients after allogeneic bone marrow transplantation. In all cases, histology showed a severely involuted architecture, compatible with a debilitating disease before death. There were no major differences between thymus tissue in AIDS patients and in the other patients studied. This argues against the claim expressed in the literature that the epithelial microenvironment incurs particular HIV-1-induced injury in AIDS. This conclusion is substantiated by immunohistochemistry for HIV-1 gag and env proteins, and by hybridohistochemistry for gag/pol and env mRNA of HIV-1. Positive cells were observed only in low numbers, both inside the epithelial parenchyma and in the (expanded) perivascular areas. An interesting finding was the labeling of subcapsular/medullary epithelium in normal uninvoluted thymus by a number of antibodies to HIV-1 gag p17 and p24 proteins. Compatible with this labeling was the staining of epithelial stalks in hyperinvoluted thymuses irrespective of disease category. The previously reported cross-reactivity between HIV-1 core protein and thymosin alpha 1 cannot fully explain this observation, because the epithelium in the hyperinvoluted state is negative for thymosin alpha 1. This study confirms and extends previous reports on the endogenous presence of epitopes of retroviral antigens in thymic epithelium.

Fetal limb constriction: a possible complication of CVS.

A case of fetal loss due to infection after first-trimester chorionic villus sampling is described. The fetus was born at 18 3/7 weeks and showed an annular constriction of one of the arms as seen in the amniotic band sequence. Induction of congenital defects might be one of the complications of chorionic villus sampling.

Acute thymus involution during infancy and childhood: immunohistology of the thymus and peripheral lymphoid tissues after acute illness.

We previously reported that the histologic grade of accidental involution of the thymus in infancy and childhood after a short period of acute illness correlates strongly with the duration of illness (Van Baarlen et al., Hum Pathol 1988;19:1155-60). We now extend this finding by reporting the phenotypic expression of thymus lymphoid and stromal cells. The thymic findings were correlated with changes in peripheral lymphoid organs. In the involuted thymus the immature and proliferating lymphoid populations that are present in the normal (uninvoluted) cortex were completely absent but the cortical epithelial network remained essentially intact even with increasing histologic grades of involution. Cells expressing the phenotype of subcapsular and medullary epithelium were found in this cortical stroma. In the subcapsular area, loss of expression of thymosin components alpha 1 and beta 4 was observed, without loss of epithelial cells. In the medulla a loss of cells expressing HLA-DR was observed, probably reflecting a loss of interdigitating cells. There was no correlation between changes in the thymus and peripheral lymphoid organs.

Acute thymus involution in infancy and childhood: a reliable marker for duration of acute illness.

To evaluate the relationship between histologic parameters and clinical data, we studied thymus histology in 234 fetuses and young children who died after a short period of acute illness. Thymus weight and volume percentages of interstitium, cortex, and medulla were significantly related to prenatal or postnatal status and age of the patient. Thymus weight was related to the duration of acute illness only in prenatal patients. The histology, categorized in five grades according to appearance of macrophages (with a starry-sky aspect) in the cortex, increase of interlobular interstitium, and lymphodepletion of the cortex, correlated significantly with the duration of acute illness and not with any other clinical parameter. This finding enables the pathologist to estimate the duration of acute disease before death.

Immunophenotyping of non-Hodgkin's lymphoma. Correlation with relapse-free survival.

In a retrospective analysis the authors studied the relation between the immunologic phenotype of B-cell non-Hodgkin's lymphoma (NHL) and disease-free survival. The phenotype included immunoglobulin isotypes; B-cell maturation/differentiation antigens of clusters of differentiation CD9, CD10, CD19-24, CD37, CD38; T-lymphocyte antigens in CD5-7; HLA-DR; peanut agglutinin binding capacity; terminal deoxynucleotidyl transferase; the activation marker CD25 (interleukin-2 receptor); and the proliferation marker transferrin receptor. The phenotype and clinical data were available for 109 patients. Two patients underwent bone marrow transplantation, and 15 patients (with low or intermediate grade NHL) did not receive treatment intended to achieve complete remission. These 17 cases were excluded from the analysis. For individual markers, CD23 expression was associated with a longer actuarial disease-free survival (50% survival in CD23-positive cases was 40 months; and in CD23-negative cases, 16 months; P = 0.01). Among the total study population of 92 patients, this finding applied in particular to those with a low-grade malignancy according to the Kiel classification (P = 0.03). In high-grade NHL (Kiel classification) the absence of CD38 or presence of CD24 on tumor cells correlated with a higher degree of disease-free survival (P values 0.009 and 0.04, respectively). For a combination of five CD markers associated with stages in physiologic B-lymphocyte maturation/differentiation (CD9, CD10, CD21-23), the lowest measure of disease-free survival was observed where NHLs were at an immature stage, and the greatest extent of survival where NHLs were associated with a resting B-cell stage (P = 0.006). These statistical significances aside, the detailed immunologic phenotyping has relatively little prognostic value when compared with that of the malignancy grade assessed by conventional histopathology.

Multilobated non-Hodgkin's lymphoma. A clinicopathologic entity.

Multilobated non-Hodgkin's lymphomas (NHL) have recently been recognized as an NHL variant. During a period of 10 years we observed 30 individuals with NHL in which more than 30% of the malignant cells had a characteristic multilobation. The immunologic phenotype was determined in 14 of these cases. One was of T-cell lineage, and the others exhibited B-lymphoid markers. Sixty-eight percent of the patients presented with extranodal localizations. In the clinical follow-up a complete remission was observed in 78% of patients with a mean duration of 37 months (range, 5 to 120 months). The actuarial survival after 5 years was 45%. From these data we conclude that multilobated NHL are comparable to diffuse, large cleaved-cell NHL of an intermediate grade malignancy according to the Working Formulation or are comparable to the diffuse centrocytic-centroblastic NHL according to the Kiel classification. The neoplastic cells are to be considered as variants of follicle center cells, but the clinicopathologic correlation indicates that multilobated NHL represent a distinct nosologic entity.

Plasmacellular hyperplasia after allogeneic bone marrow transplantation.

B lymphoid cells with monotypic immunoglobulin (Ig) expression, i.e., a single Ig heavy chain isotype combined with a single light chain type, were observed in five of nine patients after allogeneic bone marrow transplantation. Three patients exhibited plasmacellular hyperplasia of lymph nodes and spleen; in one case the monotypic cells were immunoblasts in a lymph node, and one patient suffered from an immunoblastic lymphoma along the gastrointestinal tract. We present the clinical history and the detailed (immuno) histologic analysis of lymphoid tissue from three patients. In DNA analysis of lymph node using DNA probes specific for the JH-gene segment of Ig heavy chains and for light chains, bands indicative of single Ig gene rearrangements were not observed. Thus, the monotypic B lymphoid elements represent polyclonal B cell expansion.