[Severe diarrhoea with invasive intestinal spirochaetosis]. / Ernstige diarree met invasieve intestinale spirochetose.

A 38-year-old heterosexual male presented with a 6 to 7 week history of severe diarrhoea but no other complaints. In routine faecal cultures and routine parasitological investigations no pathogenic micro-organisms were observed. Colonoscopy revealed a normal mucosa. Multiple biopsies were obtained. The histological diagnosis was invasive intestinal spirochaetosis. The immunostain for Borrelia burgdorferi cross-reacted with the spirochetes of the intestinal spirochaetosis. After two weeks of incubation under strict anaerobic conditions a spirochaete was cultured from a biopsy of the sigmoid mucosa. The 16SrDNA sequence was consistent with Brachyspira aalborgi. The HIV and syphilis results were negative. The patient was treated first with metronidazole and then by clindamycin. The diarrhoea subsided after the second course of treatment and the cause was presumed to have been the invasive intestinal spirochaetosis. Intestinal spirochaetosis is usually found coincidentally at histological examination of colon biopsies. There is no general consensus that intestinal spirochaetosis is the cause of the diarrhoea. There is however an association between the presence of symptoms and the invasivity of spirochaetes, morphological colon epithelial changes and evidence of immune response. The literature reports patients who improve symptomatically without specific treatment. Treatment may be given to patients with severe symptoms.

[Diagnostic image (215). A woman with abdominal pain and hepatosplenomegaly]. / Diagnose in beeld (215). Een vrouw met buikpijn en hepatosplenomegalie.

A 30-year-old woman presented with abdominal pain, cholelithiasis and hepatosplenomegaly, due to Gaucher's disease.

[Diagnostic image (166). Sudden death in a young woman. Cyst of the pineal gland with a prominent cerebellar tonsillar herniation]. / Diagnose in beeld (166). Plotse dood bij een jonge vrouw. Gliale cyste van de glandula pinealis met inklemming van de cerebellaire tonsillen.

A 27 year-old woman died unexpectedly due to a cyst of the pineal gland with a prominent cerebellar tonsillar herniation.

Primary malignant peripheral nerve sheath tumour of the heart.

AIMS: Malignant peripheral nerve sheath tumour (MPNST) is an unusual sarcoma of the heart and should be differentiated from other spindle cell sarcomas. METHODS AND RESULTS: We combined morphological, immunohistochemical and cytogenetic techniques in the differential diagnosis, particularly from monophasic synovial sarcoma. The tumour consisted of dense fascicles, alternating with hypocellular, myxoid zones. There was a marked herniation of tumour cells into the vascular lumen. Immunohistochemically, the tumour cells expressed vimentin and focally S100 protein. There was no expression of cytokeratin or epithelial membrane antigen (EMA). Although we found a complex karyotype, the finding of involvement of 17q11. the loss of chromosome 22, and the absence of a t(X:18)(p11.2:q11.2), which characterizes synovial sarcoma allowed us to the final diagnosis of malignant peripheral nerve sheath tumour. CONCLUSION: MPNST of the heart can be diagnosed by combining morphological and immunohistochemical data. Cytogenetics can be useful in reaching a correct diagnosis, also by helping to rule out monophasic synovial sarcoma.

Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

Conflicting prognostic results with regard to DNA flow cytometric cell cycle variables have been reported for breast cancer patients. An important reason for this may be related to differences in the interpretation of DNA histograms. Several computer programs based on different cell cycle fitting models are available resulting in significant variations in percent S-phase and other cell cycle variables. Our present study evaluated the prognostic value of percent S-phase cells obtained using 5 different cell cycle analysis models. Flow cytometric DNA histograms obtained from 1,301 fresh frozen breast cancer samples were interpreted with 5 different cell cycle analysis models using a commercially available computer program. Model 1 used the zero order S-phase calculation and "sliced nuclei" debris correction, model 2 added fixed G2/M- to G0/G1-phase ratio, and model 3 added correction for aggregates. Model 4 applied the first-order S-phase calculation and sliced debris correction. Model 5 fixed the coefficients of variation CVs of the G0/G1- and G2/M-phases in addition to applying the sliced nuclei debris correction and zero order S-phase calculation. The different models yielded clearly different prognostic results. The average percent S-phase cells of the aggregate correction model (model 3) provided the best prognostic value in all cases for overall survival (OS) as well as disease-free survival (DFS) (OS: p < 0.0001; DFS: p < 0.0001), in lymph node-positive cases (OS: p < 0.0001; DFS: p = 0.004) and in DNA-diploid subgroups (OS: p = 0.004; DFS: p = 0.001). For the lymph node negative and DNA-non-diploid subgroups, the percent S-phase of the second cell cycle reached slightly better prognostic significance than the average percent S-phase cells. In multivariate analysis, the average percent S-phase of the aggregate correction model had the best additional prognostic value to tumor size and lymph node status. In conclusion, different cell cycle analysis models yield clearly different prognostic results for invasive breast cancer patients. The most important prognostic percent S-phase variable was the average percent S-phase cells when aggregate correction was included in cell cycle analysis.

[Ascites, hydrothorax and ovarian tumor: Meigs' syndrome in a patient with small ovaries and increased CA 125 level]. / Ascites, hydrothorax en ovariumtumor: syndroom van Meigs, bij een patiënte met kleine ovaria en gestegen CA 125-waarde.

In a 51-year-old woman with bilateral Brenner tumours of the ovaries and with intermittent hydrothorax and ascites, Meigs' syndrome was diagnosed. The serum CA 125 level was 620 U/ml (normal: 5-35). Bilateral ovariectomy, hysterectomy and omentectomy were carried out. The ovaries were not enlarged. Postoperatively, the pleural effusion and ascites resolved and the CA 125 level decreased to 8.4 U/ml. The pathogenesis of hydrothorax probably involves passage through the diaphragm, and the CA 125 may be produced by the peritoneal lining or by the Brenner tumours.

Efforts to improve interobserver agreement in histopathological grading.

The present study aimed to assess the interobserver variation in histopathological grading of 88 slides by four experienced pathologists who, before the start of the study, reached consensus about the method of grading through a joint session behind a discussion microscope. The results were compared with two previous studies, the first assessing the observer variation under normal conditions, the second doing the same after theoretical agreement about which morphological characteristics were relevant for grading. In the present study the pathologists first made a provisional diagnosis on low power view, followed by a final diagnosis on high power view, scoring various morphological characteristics as in the second study. The unweighted and weighted group kappa values for the final diagnosis were 0.41 and 0.71 respectively in the present study (after the consensus meeting), compared to 0.33 and 0.70 respectively in the second study (after only theoretical consensus), and 0.28 and 0.55 in the first study (without consensus). We conclude that a consensus meeting appears to be useful to improve the interobserver agreement.

Gastric epithelial atypia complicating hepatic arterial infusion chemotherapy.

Severe gastric lesions developed in five patients during hepatic arterial infusion chemotherapy employing 5-fluorouracil plus either leucovorin or mitomycin C. Ulceration with marked epithelial atypia was observed with striking structural distortion and cellular pleomorphism of the affected gastric mucosa. These features should be considered to be a complication of such treatment and should not be misinterpreted as malignancy.

Sources of interobserver variation in histopathological grading of cervical dysplasia.

The present study aimed to assess where the interobserver variation in grading cervical dysplasia stems from. Four experienced pathologists examined 93 histological slides, after they agreed on which morphological characteristics should be considered relevant for grading. They scored 6 morphological characteristics for each slide and assigned it to a degree of dysplasia. Compared to a previous study, the interobserver variation showed a statistically significant improvement: the weighted group kappa value increased from 0.55 to 0.69. For the scores of the individual characteristics considerable interobserver variation was observed: weighted group kappa values ranged from 0.28 to 0.49. The pathologists slightly differed in which characteristics they considered most important for their grading. The agreement on the degree of dysplasia turned out to be better than the agreement on the morphological characteristics on which this diagnosis is based. In the discussion, a few explanations for this paradoxical finding are put forward.

Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project.

The Multicenter Morphometric Mammary Carcinoma Project is a prospective study on the reproducibility and prognostic value of routine quantitative assessments, especially the mitotic activity index (MAI), the multivariate prognostic index (MPI; a combination of MAI, tumor size, and lymph node status), the mean nuclear area, and DNA ploidy assessments in patients with invasive breast cancer. Fourteen pathology laboratories providing routine services to 35 hospitals throughout The Netherlands are participating in this project. In this article, the reproducibility of MAI and MPI assessments is described. Assessment of the MAI was, according to a strict protocol, first performed in the participating laboratories; thereafter, slides were transferred to the coordination center in Amsterdam for quality control. Analysis of the reproducibility of the assessments in 2,469 patients showed correlation coefficients between 0.81 and 0.96 (mean, 0.91) for the MAI and between 0.91 and 0.97 (mean, 0.96) for the MPI. The reproducibility was fairly constant in time, although it showed a slight drop in the middle of the 2-year intake period. A prognostically relevant discrepancy in MPI (caused by differences in MAI) between the original and quality control assessments was found in only 7.2% of the cases. When analyzing the reasons for these discrepancies, a plausible explanation could be found in all cases: bad tissue processing and ignorance of or negligence in following the protocol guidelines for selection of the counting area or in the process of counting were the most important flaws. Since these errors are largely controllable, an even lower discrepancy rate is theoretically achievable. In conclusion, in a routine setting it can be learned, within a reasonable time, to perform mitosis counting in a highly reproducible way if a strict protocol is carefully followed. This opens the way for a wider application of the MAI and MPI in breast cancer patients. Motivation is, however, an important factor to obtain reproducible results, and ongoing quality control is essential to guarantee the reproducibility of the assessments.

[3 children with a melanoma of the skin]. / Drie kinderen met een melanoom van de huid.

Melanoma rarely occurs in children not over 14 years of age. We report on the clinical and pathological features of three patients (two girls and one boy aged 6, 12 and 11 years respectively) from the St Laurentius hospital (Roermond, Netherlands) with melanoma of the skin, in whom the lesions histologically resembled the more frequently occurring spindle and epithelioid cell naevus (SE naevus). In all three cases, metastases were found in the regional lymph nodes. Further metastases were found in the last patient only, after follow-up periods of 29, 8 and 3 years respectively. The problems in distinguishing between melanoma and SE naevus are discussed, on the basis of a literature study and a retrospective analysis of 40 cases retrieved from PALGA (the nationwide computerized pathological archive in the Netherlands) up to and including 1990. As the diagnosis in such cases has important therapeutic consequences, we advise to submit the slides to experienced pathologists in the field, such as the Pathology Panel of the Dutch Melanoma Committee (Nederlandse Melanoom Werkgroep).

Interobserver variation in histopathological grading of cervical dysplasia.

In order to assess the variability among histopathologists in grading cervical dysplasia, four experienced histopathologists examined the same set of 106 biopsy specimens and assigned them to one of five diagnostic categories. These were: no dysplasia, mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ. The histopathologists did not discuss the grading criteria beforehand. There was considerable disagreement among the pathologists: unweighted group kappa 0.28, weighted group kappa 0.56. It appeared that all grades of dysplasia were equally difficult to distinguish from adjacent categories. Various explanations for this interobserver variation are put forward.

[Detection of Mycobacteria in tissue sections]. / Opsporing van mycobacteriën in weefselcoupes.

A study of 31 patients with Mycobacterium infection was performed. The results of Ziehl-Neelsen(ZN) and auramine-rhodamine(AR) staining techniques were compared with the results of cultures. This study demonstrates that the AR method is more sensitive than the ZN method, but they complement each other and when used in combination allow fast and reliable screening for organisms. The culture is important for classification of Mycobacterium species and drug susceptibility testing.

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP). A nationwide prospective study on reproducibility and prognostic power of routine quantitative assessments in The Netherlands.

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP) has been set up to investigate prospectively the prognostic value and reproducibility of routine assessments of the morphometric Multivariate Prognostic Index (MPI) and other quantitative parameters in comparison with classical prognosticators and steroid receptors in breast cancer patients. In this project, 34 hospitals participate, divided over six geographically different regions. Of each patient entering in the study, multiple clinical and classical pathological parameters (including tumor size and lymph node status) as well as several quantitative parameters such as mean nuclear area, DNA index and mitotic activity index will be evaluated. Of all patients, the MPI will be assessed with tumour size, lymph node status and mitotic activity index. The quantitative assessments are performed in all consecutive breast cancers which enter the participating pathology laboratories, and all measurements are controlled in Amsterdam. The patient intake time will be from January 1, 1988 until January 1, 1990. It is expected that 3000 patients will enter in this study. Follow up data will be gathered up to 10 years. However, two to five years after the initiation of the Project, a first evaluation of the reproducibility and prognostic significance of routine MPI and other assessments in breast cancer patients will be possible. A detailed description of this project is given.

Malignant lymphoma, immunoblastic with plasmacytic differentiation, complicating Crohn's disease.

A case of malignant lymphoma (immunoblastic with plasmacytic differentiation) of the colon complicating Crohn's disease is reported. The rarity of this complication in inflammatory granulomatous disease of the intestine is stressed. The possible relationship between intestinal lymphoma and Crohn's disease is discussed.