Quality assessment of HER2 testing by monitoring of positivity rates.

Interlaboratory variation in human epidermal growth factor receptor 2 (HER2) testing provides a challenge for targeted therapy in breast and gastric cancer. Assessment of positivity rates among laboratories could help monitor their performance and define reference values for positivity rates to be expected in a geographic region. Pathologists regularly determined the number of HER2-positive cases (HER2 3+, HER2 2+/amplified or amplified) in their laboratory, and figures were continuously entered into a central website.

Analysis of risk factors of the evolution of myelofibrosis in pre-fibrotic chronic idiopathic myelofibrosis: a retrospective study based on follow up biopsies of 70 patients by using the RECPAM method.

The advanced, fibrotic phase of chronic idiopathic myelofibrosis (CIMF) is preceded by a pre-fibrotic stage. However, the factors which may influence or predict the development of myelofibrosis are not well established. Thus we investigated follow up biopsies of 70 patients with CIMF, diagnosed in stages of no or only scant fiber increase, for the development of myelofibrosis.

Chronic idiopathic myelofibrosis: prognostic impact of myelofibrosis and clinical parameters on event-free survival in 122 patients who presented in prefibrotic and fibrotic stages. A retrospective study identifying subgroups of different prognoses by using the RECPAM method.

In chronic idiopathic myelofibrosis (CIMF) the factors predicting survival in patients who were already in the fibrotic stage have been well documented by numerous studies. Prefibrotic stages were only rarely evaluated so that the prognostic impact of myelofibrosis is currently not well known. Also predictive factors for disease-related events were not included in those studies.

Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens.

Although the new World Health Organization (WHO) classification acknowledges "prefibrotic" phases, progression of myelofibrosis in chronic idiopathic myelofibrosis (cIMF) is controversial because there are only a few studies about sequential biopsy specimens, and they yield conflicting results. The conflicting results might be due to a mixture of different degrees of myelofibrosis and therapy regimens within the respective groups studied. To prove this hypothesis, we studied sequential bone marrow biopsy specimens from patients with cIMF and compared 3 groups with different degrees of myelofibrosis at initial diagnosis with a group of patients with primarily unfibrosed disease who met the WHO criteria for prefibrotic cIMF.

[The development of myelofibrosis in prefibrotic cIMF. An investigation of the progression by sequential bone marrow biopsies in 38 patients].

Overt myelofibrosis in bone marrow biopsies as a diagnostic postulate in cIMF has been discarded only recently by the WHO. Therefore, only a few studies have been performed on the evolution of myelofibrosis in "prefibrotic" cIMF by means of sequential bone marrow biopsies. We carried out this study on 38 patients, split up into two groups, A and B according to treatment modalities, to evaluate the dynamics and frequency of myelofibrosis in both groups.

Fibre content and cellularity of the bone marrow of the iliac crest, vertebral column and sternum in chronic myeloproliferative disorders.

Heterogeneous content of fibres and haematopoesis within the bone marrow may affect diagnosis and staging in chronic myeloproliferative disorders (CMPDs). To evaluate their distribution, we conducted a post mortem histomorphometric study of 22 patients with CMPD in chronic phases. In bone marrow specimens from the anterior and posterior iliac crest (right and left of each), the sternum, the 7th thoracic and the 3rd lumbar vertebra, the argyrophil fibres were counted using the line intersection method and the cellular and fatty bone marrow using the point count method.

Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies.

The present study illustrates characteristic features of histopathology in the 3 non-leukemic, Ph-negative groups of chronic myeloproliferative diseases (CMPD). Attention is paid to the final outcome of CMPD, especially its transformation into acute leukemias and the occurrence of myelofibrosis from bone marrow biopsies (BMB) in a total of 1,716 CMPD patients. Essential thrombocythemia (ET), polycythemia vera (P.

Comparison of scoring systems in primary myelodysplastic syndromes.

To compare the prognostic value of scoring systems in primary myelodysplastic syndromes (pMDS), four clinicohematological systems (Rennes, Bournemouth, Düsseldorf, Pavia) and the histopathological Hannover Scoring System were applied to 415 MDS patients from the Bone Marrow Registry of Hannover Medical School. According to the FAB classification, 180 patients (43%) were diagnosed as RA, 33 (8%) as RARS, 99 (24%) as RAEB, 36 (9%) as RAEBt, and 48 (12%) as CMMOL; 19 patients (4%) were not further classified (MDS.UC).

[Histopathology of Ph1-negative chronic myeloproliferative diseases].

The Ph1-negative groups of chronic myeloproliferative diseases (CMPD) are described, and histopathological criteria that distinguish them from each other are given. These are based upon observations in primary biopsies from 2,331 patients with CMPDs among a total of 34,160 patients referred between 1 January 1989 and 30 June 1994 to the Bone Marrow Registry. These cases of CMPD break down into the main groups as follows: CML 23.

[Morphometry of megakaryocytes for supporting the histologic diagnosis of chronic myeloproliferative diseases].

Morphometric analysis of sections of biopsy specimens from patients with chronic myeloproliferative disorders (CMPD) can complement the individual histological diagnosis and help to distinguish the four groups of CMPD. A total of 130 diagnostic biopsies from 29 cases of chronic myelocytic leukemia (CML.CT), 26 cases of (CML.

Life expectancy in primary myelodysplastic syndromes: a prognostic score based upon histopathology from bone marrow biopsies of 569 patients.

The retrospective evaluation of bone marrow biopsies of 569 patients with primary myelodysplastic syndrome--pMDS--revealed 256 refractory anemias--RA--, 52 refractory anemias with ringed sideroblasts--RARS--, 133 refractory anemias with excess of blasts--RAEB--, 52 refractory anemias with excess of blasts in transformation--RAEB-t--, and 53 chronic myelo-monocytic leukemias--CMMOL--according to FAB-criteria, 23 patients were not otherwise specified (myelodysplastic syndrome: not otherwise specified--MDS.NOS--). RARS-patients had the best prognosis (median survival 41.

[Cytogenetics in addition to histopathology exemplified by myelodysplastic syndrome].

The value of cytogenetics performed simultaneously with histopathology was evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype changes of the bone marrow cells supporting the histological diagnosis were found in 38/69 cases (55%). The chromosome aberrations, especially complex changes, were significantly correlated to distinct histopathological findings such as atypias of the haematopoietic cell lines and myelosclerosis.

Comparison of bone marrow and hematologic findings in patients with human immunodeficiency virus infection and those with myelodysplastic syndromes and infectious diseases.

The histologic, hematologic, and morphometric findings of 40 patients positive for the human immunodeficiency virus (HIV) were compared statistically with those of 40 patients with primary myelodysplastic syndromes (MDS) and those of 32 HIV-negative patients with infectious diseases. The severity of anemia and the abnormalities of erythropoiesis in the group of HIV patients were less pronounced than in the group with MDS; megakaryopoiesis showed similarities only with the group of patients with infectious diseases, and characteristics of dysplasia were not observed. Granulopoiesis in MDS showed an increase of blasts in several cases; this was not found in any biopsy specimen from the HIV group.

Hypoplastic myelodysplastic syndrome: incidence, morphology, cytogenetics, and prognosis.

The present study, based upon the retrospective evaluation of 352 patients with primary myelodysplastic syndrome (pMDS), revealed hypoplastic MDS in 42 patients (11.9%). Median age is similar in hypo- and normo-/hypercellular MDS (72.

Myelofibrosis in chronic myeloproliferative disorders. Incidence among subtypes according to the Hannover Classification.

The distribution and the development of fibrosis were evaluated from bone marrow biopsies of patients with chronic myeloproliferative disorders (CMPD), regarding two groups of patients: (1) 564 with follow-up biopsies over a period of up to twelve years observation time, and (2) 1.787 diagnostic bone marrow biopsies from CMPD patients. Fibrosis was divided into three grades of fiber increase: early myelosclerosis, myelofibrosis, and advanced myelofibrosis.

Histomorphometry in paraffin sections of thyroid tumors.

Planimetric features of cell nuclei in paraffin-embedded histological sections of benign and malignant thyroid tumors, as well as normal thyroid tissue as control, were determined by means of a semiautomatic system. The main aim was to objectify possible quantitative differences between adenomas and carcinomas of the thyroid gland, which had recently been reported by several authors. For each nuclear profile, the area, the maximum diameter as well as two form factors were calculated.

Elliptic Fourier analysis of megakaryocyte nuclei in chronic myeloproliferative disorders.

Elliptic Fourier analysis was applied to megakaryocyte nuclei in bone marrow biopsies from 15 patients with chronic myelocytic leukemia with megakaryocyte predominance and from 15 patients with chronic megakaryocytic granulocytic myelosis. To assess the reliability of this procedure, the biopsies were evaluated also by the semiautomatic measurement of nuclear area and form factor, and both methods were compared with respect to the degree of morphologic differences obtained between these two types of chronic myeloproliferative disorders (CMPDs). Discriminant analysis revealed correct reclassification of all cases both for elliptic Fourier analysis and for semiautomatic planimetry, whereas discriminant scores were much higher for Fourier analysis.

Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients.

In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61).

Introduction of a neuronal network as a tool for diagnostic analysis and classification based on experimental pathologic data.

A neuronal network, as well as uni- and multivariate statistics and a discriminant analysis were applied to a morphometric database of 58 cases with thyroid neoplasms and normal thyroid tissue. The ability to classify cases correctly according to their diagnosis was compared between the neuronal network and discriminant analysis. For all pairwise comparisons, classification by neuronal network was as least as good as classification by discriminant analysis.

Chromosome analyses in patients with myelodysplastic syndromes: correlation with bone marrow histopathology and prognostic significance.

Chromosome analyses of bone marrow and peripheral blood cells were performed in a total of 51 patients with myelodysplastic syndromes (MDS) simultaneously with histopathological examination of resin-embedded bone marrow biopsies. Diagnosis of MDS was established by histopathology according to the French-American-British (FAB) classification, and reassessed by haematological data and clinical course. Clonal karyotypic changes were found in 30 of the 51 patients (59%): in 15 of 19 (79%) patients with refractory anaemia, 7 of 11 (64%) with refractory anaemia and excess of blasts (RAEB), 6 of 10 (60%) with RAEB in transformation, and 2 of 11 (18%) with chronic myelomonocytic leukaemia.

The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia.

A histological study on sequential bone marrow biopsies in patients with chronic myeloid leukaemia (CML) was performed. We wished to answer the question as to whether a different content of megakaryopoiesis in the bone marrow of CML patients has a prognostic significance for the development of myelofibrosis during the course of disease. In addition, the significance of possible changes in the quantity of megakaryopoiesis in this process was assessed.

[Histopathology and morphometry of hematopoiesis in bone marrow of AIDS patients in comparison with patients with myelodysplastic syndrome].

Hematological data and histopathological bone marrow findings were compared in 60 patients with acquired immune deficiency syndrome (AIDS), 40 patients with myelodysplastic syndrome (MDS) and concurrent inflammation, and 39 HIV-negative patients with severe inflammation. Results show that the hematologic, histologic, and morphometric findings in patients with AIDS have a closer resemblance to the findings in patients with severe inflammation than to those in patients with MDS. It is concluded, that the peripheral cytopenia frequently observed in AIDS-patients is rather a consequence of severe inflammation, than of ineffective hematopoiesis.

Planimetric analysis of megakaryocytes in the four main groups of chronic myeloproliferative disorders.

Planimetry of megakaryocytes (MK) was performed in bone marrow biopsies (BMBs) from patients with chronic myeloproliferative disorders (CMPD) to substantiate cytomorphologic differences in this cell lineage between the four main groups of CMPD. The biopsy specimens were classified histologically prior to morphometry, according to the Hannover Classification of CMPD. Five histological groups were investigated, evaluating between 21 and 30 biopsies in each group.