Josée Audouin

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin.

Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastras antibody and 56 cases (65%) with Dakos. Significant discordance was observed (P< 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibodys clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas.

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.

Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes

Summary. We studied 86 bone marrow biopsies (BMB) from 58 patients presenting with primary splenic marginal zone lymphoma (PSMZL). In 42 patients, a splenectomy was performed which enabled a histopathological diagnosis. In these patients, 44 biopsies were carried out before, and 25 after, splenectomy. In 16 recently observed patients, 17 BMB led to PSMZL diagnosis, and these patients were treated without splenectomy. Seven different patterns of infiltrates were recognized: intravascular, interstitial, nodular, massive, plasmacytic mimicking myeloma and transformation into large B‐cell lymphoma (DLBCL). The association of an intravascular infiltrate and nodules with a germinal centre and/or a marginal zone favoured a diagnosis of MZL. Immunohistochemistry demonstrated the expression of B cell‐associated antigens and, in 40% of the patients, a monotypic lymphoplasmacytic cell component. These patients often presented a serum M component and autoimmune disorders. In the past, such cases have been diagnosed as lymphoplasmacytic lymphoma. BM involvement was present in all patients. Successive biopsies showed progression and, after chemotherapy, a slight decrease in infiltrates. Transformation into DLBCL occurred in 11 of 34 patients. The patterns described are not specific for PSMZL and occur also in primary nodal MZL and, more rarely, in MALT‐type lymphoma.

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.

LAV-like viral particles in lymph node germinal centers in patients with the persstent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex: An ultrastructural study of 30 cases

The detection of LAV- or HTLV III-type viral particles in lymph node germinal centers from patients with the persistent lymphadenopathy syndrome (LAS) or the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) is an important diagnostic factor in the prodromal stages of AIDS. These particles, the morphology of which is defined, are situated solely in the extracellular spaces delimited by cytoplasmic extensions of the dendritic reticular cells. Often few in number, they were found in 26 of the 30 lymph nodes studied, selected uniquely on the basis of light microscopic criteria (predominantly follicular lymphoid hyperplasia). The four negative nodes contained no, or fewer than two, germinal centers in the samples taken for ultrastructural study. The diagnosis of the LAS or the ARC was always confirmed clinically and biologically. Thus, lymph node biopsy and the corresponding ultrastructural study are important steps in the diagnosis of AIDS.

Primary Lymphoplasmacytic Lymphoma of the Larynx: A Rare Localization of Malt-Type Lymphoma

Laryngoscopy carried out in a 46-year-old man revealed a left paralaryngeal tumor. The mass was entirely removed by left pharyngolaryngotomy. Microscopic study showed a diffuse malignant lymphoma of low-grade malignancy, exhibiting all the criteria of the MALT-type lymphoma: The proliferation of centrocyte-like and lymphoplasmacytic cells, lymphoepithelial lesions, and the presence of germinal centers. Primary lymphoma of the larynx is a rare condition. Most of the reported low-grade lymphomas and the pseudolymphomas probably belong to the category of MALT-type lymphoma. Remission can be obtained by surgery, radiotherapy, and polychemotherapy.

Analysis of African Burkitt's and high-grade B cell non-Burkitt's lymphoma for Epstein-Barr virus genomes using in situ hybridization.

Summary. We investigated the association of Epstein‐Barr virus (EBV) with African cases of Burkitts lymphoma (BL) and high grade B cell non‐Burkitts lymphoma (non‐BL) occurring in areas where BL is endemic. The presence of EBV genomes was analysed in 24 cases using in situ hybridization with a 15S‐labeiled EBV probe applied to paraffin sections. EBV DNA was detected in each of 10 cases of BL in which technically satisfactory results were obtained, the virus being homogenously distributed in all identifiable tumour cells. Two other cases of BL could not be evaluated because of technical problems. In contrast, EBV DNA was not detected in any case of high‐grade non‐BL (10 centroblastic and two immunoblastic lymphomas). These results confirm previous reports of the strong association of EBV with endemic BL, but suggest that the virus is not important in the pathogenesis of other types of African high‐grade B cell lymphoma from regions where BL is endemic.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources : a clinicopathologic study of seven cases

Bone marrow examination revealed a lipid‐laden histiocytosis in seven patients undergoing long‐term total parenteral nutrition necessitated by extensive short‐bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months.  The most striking change within the bone marrow was the presence of many pigment‐laden histiocytes which had the typical morphology of sea‐blue histiocytes seen in the so‐called idiopathic sea‐blue histiocyte syndrome. The occurrence of sea‐blue histiocytosis in the bone marrow in association with long‐term parenteral nutrition for short‐bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea‐blue histiocytosis.

Herpes simplex virus lymphadenitis mimicking tumoral relapse in a patient with Hodgkin's disease in remission

A patient treated for Hodgkins disease and presenting 12 years later with a left inguinal lymphadenopathy mimicking a relapse is reported. Histopathological study disclosed large histiocytic granulomas in the sinuses. Some of these granulomas showed necrotic areas with numerous neutrophils. At the edge of the necrotic zones, cells of undetermined origin exhibited intra-nuclear inclusions typical of Herpes simplex virus. The diagnosis was confirmed by immunolabelling, revealing Herpes simplex viral antigens in frozen and paraffin sections, and by ultrastructural studies. The diagnostic value of the histological methodology and pathological changes and the significance of the disease, appearing in a patient treated for Hodgkins disease are discussed.