C. De Wolf-Peeters

Tumours of histiocytes and accessory dendritic cells: An immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Prognostic factors in the myelodysplastic syndromes: importance of initial data on peripheral blood counts, bone marrow cytology, trephine biopsy and chromosomal analysis

An analysis of clinical, haematological, histological and cytogenetic data was performed in 85 consecutive patients with myelodysplastic syndromes (MDS). The criteria for diagnosis of refractory anaemia (RA), acquired idiopathic sideroblas‐tic anaemia (AISA) and chronic myelomonocytic leukaemia (CMML) were clearly defined, since the inclusion criteria provided by the FAB co‐operative group are imprecise. None of these patients has received chemotherapy during the follow‐up period. The median survival of the whole group was only 15 months, with less than 10% of the patients surviving after 5 years. Fifteen patients (17.6%) were still alive at time of analysis, 31 (36.5%) have developed acute myeloid leukaemia (AML) and only one of them is still alive; 30 (35.3%) died of infectious and/or haemorrhagic complications. Patients who developed AML had a shorter survival (median survival time 9.5 versus 15 months) but this difference was not significant (P = 0.10). Factors with prognostic value are in order of significance: abnormal localized immature myeloid precursors (= ALIP) in the trephine biopsy. circulating myeloblasts, excess of blasts in the bone marrow smears, age, FAB classification and granulocyte count. In comparison to refractory anaemia with excess of blasts (RAEB), CMML and RAEB in transformation (RAEBt), patients with RA and AISA had a lower incidence of evolution to AML (11% versus 56%), but a higher mortality rate from infections and/or bleeding (59.2% versus 29%). ALIP negative cases were only found among patients with RA and AISA, whereas ALIP positivity was observed in all cases of RAEB and RAEBt. in 10/11 patients with CMML and in almost half the cases of RA and AISA. In RA and AISA patients survival was significantly different between

Bone marrow histology in myelodysplastic syndromes. II. Prognostic value of abnormal localization of immature precursors in MDS.

A study has been performed of 40 bone marrow trephine biopsies from patients with myelodysplastic syndromes (MDS). Histology, more specifically the abnormal localization of immature precursors (ALIP), cytology and karyotype analysis were correlated with survival time and the prognostic value of these factors was determined. The presence or absence of ALIP proved to be highly significant in predicting the duration of survival (P = 0.007): the presence of ALIP predisposes patients to early death with high probability of developing acute myeloid leukaemia (AML), whereas the absence of ALIP carries a better prognosis with more long-term survivors and low probability of transformation to AML. The presence or absence of ALIP was not correlated with increased mortality from infection and/or bleeding. In contrast with ALIP, the main histological parameter, we were not able to obtain statistically significant prognostic information for cytology (FAB classification) or karyotype analysis (normal or abnormal chromosomes). We conclude that bone marrow biopsy provides useful information for the prognosis of MDS and that the presence of ALIP has greater predictive value than the more commonly used parameters deduced from cytology and karyotype.

The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations

Summary Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty‐one patients (45.5%) progressed to AML (> 30% blasts in bone marrow smears).

A cutaneous apudoma or merkel cell tumor? A morphologically recognizable tumor with a biological and histological malignant aspect in contrast with its clinical behavior

Clinical, microscopic, ultrastructural, and histochemical characteristics of a primary cutaneous tumor, identified as an APUDoma possibly arising from Merkel cells, are presented. The tumor can be diagnosed by means of routine histology. In some cases the argyrophylic staining technique can be helpful. The dermatological and histological aspects of this tumor suggest a highly malignant undifferentiated process. The biological behavior of this tumor, however, seems to be of a low‐grade malignancy. It is therefore important to recognize it from undifferentiated, highly malignant, mostly metastatic processes in the skin. There is also a summary of the clinical history and microscopic findings of identical tumors in 4 other patients.

FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( × 1), gastric MALT lymphoma ( × 1) and B-cell non-Hodgkins lymphoma, not otherwise specified ( × 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.

Histiocyte-rich B-cell lymphoma. A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodgkin's disease, paragranuloma subtype

This study reports six non-Hodgkins lymphoma cases that we called histiocyte-rich B-cell lymphoma (BCL) because of the prominent reactive histiocytic infiltrate obscuring the malignant B-cell population. The involved lymph nodes are characterized by a mixed nodular and diffuse infiltrate and occasionally feature prominent sinuses. The infiltrate is composed of reactive lymphocytes and numerous histiocytes obscuring a tumor population composed of variably sized scattered cells with irregular or multilobar vesicular nuclei. Immunostaining of paraffin sections for the B-cell marker recognized by L26 helps in the identification of these neoplastic cells. The clonal nature and further evidence of the B-cell lineage of this condition is shown by immunoglobulin gene rearrangements detected in three cases. The six cases of histiocyte-rich BCL are remarkably similar clinically: all presented with stage IVB disease with splenomegaly and follow an aggressive clinical course. Except for these features, our series show striking similarities to paragranuloma lymphocyte-predominant Hodgkins disease, including male preponderance (all patients are male), age distribution (mean age, 41 years), propensity to progress to a diffuse, large B-cell lymphoma (two cases), as well as morphology of the neoplastic B-cell population and expression of Hodgkins cell markers (Leu-M1 positivity after neuraminidase digestion in three cases, Leu-M1 positivity without neuraminidase digestion in one case, and additional epithelial membrane antigen [EMA] positivity in two cases). Both morphologically and clinically, the present series can be differentiated from other types of infiltrate-rich BCL, such as T-cell-rich BCL. Although additional cases will have to be recognized, histiocyte-rich B-cell lymphoma most likely represents a distinct clinicopathological entity. We speculate that it develops from a subset of B cells that also gives rise to the lymphocytic-histocytic (L/H) cell, the Hodgkins cell variant of lymphocyte-predominant Hodgkins disease, paragranuloma subtype.

Characteristic pattern of chromosomal gains and losses in marginal zone B cell lymphoma detected by comparative genomic hybridization

Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non-Hodgkin’s lymphoma, which has been recently recognized and defined as a disease entity. We investigated 25 cases (18 at primary diagnosis and seven during the course of disease) of MZBCL by comparative genomic hybridization (CGH) and compared these results with cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data. Twenty of the 25 cases (80%) showed gains (total 49) or losses (total 15) of genetic material. In extranodal, nodal, and splenic MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (16%) was most frequently gained, whereas losses predominantly involved chromosomes 17 (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and 18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and 8q and losses of chromosome 17 or 17p occurred more frequently in relapsed or progressive lymphomas. For all of the frequently affected chromosomes, CGH allowed narrowing of the relevant subregions including 3q21-23, 3q25-29 and 18q21-23. By Southern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were found to be a part of the over-represented regions in two cases, one case, and two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH revealed chromosomal imbalances which were not detected by cytogenetic analysis but could be confirmed by FISH or Southern blot analysis in all cases investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and deletion 7q in three cases with a low proportion of tumor cells bearing these abnormalities, as shown by interphase FISH. The characteristic pattern of chromosomal gains and losses detected in this study confirms the distinct nature of MZBCL and may point to chromosomal regions involved in the pathogenesis of these neoplasms.

The human placental bed: Electron microscopic study of trophoblastic invasion of spiral arteries

During normal human pregnancy the spiral arteries of the placental bed became so greatly distended that they are capable of delivering a tenfold increase in the supply of blood required by the fetoplacental unit in the third trimester. Studies performed with the use of light and electron microscopes have shown remarkable structural alterations in the walls of these arteries at the end of normal human pregnancy. In order to evaluate the various hypotheses of the histogenesis of these vascular physiologic changes, the present study with light and electron microscopes was carried out on the spiral arteries during the second trimester of normal human pregnancy. Special attention was given to the intravascular migration of trophoblast, as well as to the consequent interaction between fetal and maternal tissues.

Ultrastructure of the spiral arteries in the human placental bed at the end of normal pregnancy

Abstract An electron microscopic investigation has been carried out on spiral arteries in placental bed biopsies at the end of normal human pregnancy. The musculoelastic tissue is replaced to a greater or lesser extent by a fibrillar and granular material in which giant cells are found. These cells, by morphologic criteria, are identical to trophoblastic cells while part of the granular and fibrillar material shows the characteristics of fibrin. Furthermore, it is suggested that another part of this fibrinoid material is derived from the degeneration of trophoblastic cells in the spiral artery wall. These structural modifications to the arterial wall are probably the direct consequence of invasion of the wall by trophoblastic cells; they are more pronounced in the decidual than in the myometrial portions of the spiral arteries, but the mechanism of their production is presumably the same for both segments.