Sophie Camilleri-Broët

Myeloid Sarcoma: Clinical and Morphologic Criteria Useful for Diagnosis

Extramedullary accumulation of myeloblasts or immature myeloid cells form tumors called myeloid sarcoma in the WHO classification. Such tumors develop in lymphoid organs, bone (skull, orbit, etc.), skin, soft tissue, various mucosae and organs, and the CNS. They may precede or occur concurrently with acute myeloid leukemia, or reveal blastic transformation of chronic myeloproliferative disorders or myelodysplastic syndromes. They may also reveal relapses in treated patients. They are constituted by a diffuse infiltrate made up of medium-to-large cells. The cells are difficult to identify. Imprints are very useful. Immunohistochemistry can help diagnose and distinguish four variants: granulocytic myeloperoxidase (MPO+, CD 68+ [KP1, PGM1-] lysozyme+, CD 34), monoblastic (MPO-, CD 68+, [KPI+, PGMI+] lysozyme+, CD 34-), myelomonoblastic (MPO-, CD 68+, [KPI+, PGM1+] lysozyme+, CD 34-), or megakaryoblastic (positivity for factor VIII, CD 61, CD 31). Immunohistochemistry sometimes demonstrates expression of CD 43, CD 7, CD 79a, and CD 56 (particularly the monoblastic variant with t[8;2 1]). Recently the demonstration of CD 99 and CD 1 7, which can now be done on paraffin sections, may be useful to identify blasts of granulocytic origin. The diagnosis is missed in about 50% of cases when immunohistochemistry is not used. Patients with myeloid sarcomas should be treated in the same way as patients with acute myeloblastic leukemia. Disease progression and prognosis are similar for the two conditions.

Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group)

Epidermal growth factor receptor 1 (EGFR-1) overexpression is usually described as linked with a worse prognosis in a variety of tumours of epithelial origin. However, its role in ovarian cancer is still controversial. The aim of the present study was to analyse the prognostic impact of EGFR-1 in a retrospective series of 93 stage III–IV primary ovarian epithelial tumours. All patients, enrolled in a multicentre GINECO prospective clinical trial, were treated with the same platinum-based combination chemotherapy, and were followed up with a median of 69 months. Epidermal growth factor receptor 1 plasma membrane expression, assessed by immunohistochemistry on paraffin-embedded tissues, was correlated with clinical parameters as well as immunohistochemical expression results of HER-2 (c-erbB-2), BAX, BCL-2, p53 and anti-Ki-67, previously studied in the same series of patients. Positive immunostaining for EGFR-1 was seen in 31 of the 93 analysed cases (33%). No correlation was found between EGFR-1 expression and clinical parameters. No correlation was found between EGFR-1 expression and other biological markers, except for HER-2, which was limit for significance. Indeed, among the EGFR-1-negative cases, 10.3% expressed HER-2, whereas the HER-2-expressing tumours accounted for 27.6% of EGFR-1-positive cases (P=0.06). Epidermal growth factor receptor 1 overexpression had no prognostic impact on both overall and progression-free survival through univariate and multivariate analyses. The potential effect of EGFR-1 and HER-2 co-expression on targeted therapy against EGFR-1 and/or HER-2 molecules has to be further analysed.

Bone marrow manifestations of infections and systemic diseases observed in bone marrow trephine biopsy

Bone marrow modifications resulting from infections and systemic diseases can be studied by analysis of morphology and aetiology. Two types of lesions or modifications can be observed, those occurring in the connective tissue comprising inflammatory processes, acute and chronic, as well as immune reactions, and those involving the normal haematopoietic cell lines, with possible hyperplastic or aplastic changes in one or more cell lines. The main lesions are described (oedema, haemorrhage, necrosis, suppuration, granulomas, lymphoid nodules and hyperplasia, immunoblastic or plasmacytic hyperplasia), as well as the main aetiologies. In association, the three main haematopoietic cell lines show hyperplasia, hypoplasia, aplasia of one or all of the cell lines, sometimes with dysmyelopoiesis. The stroma and vessel reactions comprise myelofibrosis, gelatinous transformation or amyloid deposits.

FcγRIIB is differentially expressed during B cell maturation and in B‐cell lymphomas

FcγRIIB, a low affinity receptor for the Fc portion of immunoglobulin G (IgG), is thought to drive negative selection of B cells in germinal centers (GC) by inducing apoptosis upon interaction with immune complexes. Its expression was investigated by immunohistochemistry in 22 reactive lymphoid tissues and 112 B‐cell lymphomas. Pre‐GC mantle cells, marginal zone cells and their neoplastic counterparts expressed FcγRIIB. The B chronic lymphocytic leukaemia (B‐CLL)/small lymphocytic lymphomas were also positive. Not detected in GC, FcγRIIB was expressed in 52% of follicular lymphomas and in 20% of diffuse large B cell lymphomas (DLBCL). In DLBCL, FcγRIIB expression was linked to transformation (P < 0·001). Re‐analysis of a gene profile data set from the Lymphochip microarrays showed that FcγRIIB expression in the activated B‐like DLBCL subgroup was higher than in the GC‐like one (P < 0·04), and was associated with an adverse prognostic both in univariate (P < 0·003) and in multivariate analysis including the International Prognostic Indicator (IPI) (P < 0·01). Thus these results challenge the potential role of FcγRIIB during B‐cell selection in GC, and suggest a prognostic value of FcγRIIB expression in DLBCL.

Morphological variability of tumour cells in T-cell-rich B-cell lymphoma

T-cell-rich B-cell lymphoma (TCRBCL) is an unusual lymphoma which is difficult to diagnose. A majority of reactive T-cells and numerous histiocytes mask the few large neoplastic B-cells. Fourteen cases of TCRBCL were studied in order to identify the main histological and cytological features useful for this diagnosis. Neoplastic cells are atypical and sometimes difficult to classify. Several types are seen; they are mostly centroblasts, which represent more than 50% of the tumour cells but are sometimes multilobated, immunoblasts- or Reed-Sternberg-like cells. Interestingly, at least two, and often three, types of tumour cell are present in all the cases. Epithelioid cells and histiocytes are always found and are often numerous. Hypervascularization and fibrosis are present in the majority of cases, but without annular bands. Necrosis is absent. All tumour cells express CD20 but EMA is expressed in less than half the cases. In two cases, the association of a diffuse large B-cell lymphoma in one site and a TCRBCL in another suggests that TCRBCL may be considered as a peculiar pattern of a diffuse large B-cell lymphoma with a strong stroma reaction. TCRBCL may not represent a clinicopathological entity.

Fc gamma receptors and cancer

FcγRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcγR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcγR are involved in the therapeutic activity of monoclonal IgG antibodies by activating the cytotoxic activity of FcγR-positive cells such as NK cells, monocytes, macrophages and neutrophils and by increasing antigen presentation by dendritic cells. Since many cell types co-express activating and inhibitory FcγR, the FcγR-dependent effector functions of IgG anti-tumor antibodies are counterbalanced by the inhibitory FcγRIIB. In addition, some tumor cells express FcγR either constitutively, such as B cell lymphomas or ectopically, such as 40% of human metastatic melanoma. The tumor FcγR isoform is preferentially FcγRIIB, which is functional at least in human metastatic melanoma. This review summarizes these data and discusses how FcγRIIB expression may influence the anti-tumor immune reaction and how beneficial or deleterious this expression could be for the efficiency of therapeutics based on monoclonal anti-tumor antibodies.