Karine Montagne

Immunohistochemical markers to distinguish between hemangioblastoma and metastatic clear-cell renal cell carcinoma in the brain: utility of aquaporin1 combined with cytokeratin AE1/AE3 immunostaining.

Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-α and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-α, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-α (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-α for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.

Les conséquences moléculaires de la fixation et de l’inclusion: exemple des acides nucléiques et des protéines

Resume L’utilite scientifique des donnees moleculaires obtenues a partir d’echantillons tissulaires depend directement de la qualite de ces derniers. L’echantillon ideal est une representation complete et non modifiee de la realite tissulaire in vivo . Le but de cette revue est de resumer les effets de la fixation et de l’inclusion sur le contenu et l’integrite des acides nucleiques et des proteines.

Platelet satellitism and lympho‐agglutination as presenting finding in marginal zone B‐cell lymphoma

A 48-year-old man presented with non-documented chronic infection. Blood cell count analysis showed a WBC count of 16.8 G ⁄L with lymphocytosis (13.7 G ⁄L), haemoglobin level to 12.2 g ⁄dL and a platelet count to 102 G ⁄L. EDTA peripheral blood smears showed atypical lymphocytes (small to medium-sized with more dispersed chromatin and abundant pale cytoplasm). Moreover, atypical lymphocytes were engaged via platelet satellitism phenomenon (Fig. 1) with image of lympho-agglutination (Fig. 2). The remaining leucocytes, including normal lymphocytes were not involved in platelet satellitism. The disruption of platelet-lymphoma cells agglutination followed blood incubation 30 min at 37 C. This phenomenon did not occur if the blood was not anticoagulated as in bone marrow aspirate or anticoaguled by heparin, citrate. Platelet satellitism was not reproduced by incubating patient EDTA plasma with EDTA-anticoagulated blood from normal subjects which contains normal lymphocytes. Platelet antibodies were not detected and the abnormality was still present a month later. Flow cytometry immunophenotype on peripheral blood sample revealed a monoclonal population of B cells (kappa) that was negative for CD5 and positive for CD19, CD20, CD22, CD23, CD79a and FMC7 with a Matutes score to 2. Histology study showed intravascular and interstitial infiltration by CD20+ centroblast, which is suggestive of marginal zone-B cell lymphoma. This diagnosis was concordant with morphology features. Platelet satellitism is virtually always an in vitro phenomenon involving polymorphonuclear neutrophils in EDTA-anticoaguled blood at room temperature. It can be an important cause of spurious thrombocytopenia The proposed mechanisms include imuunological bounding through EDTA-dependent antiplatelet and antineutrophil IgG autoantibodies directed against the platelet glycoprotein IIb ⁄ IIIa complex and the neutrophil FccRIIIb (CD16) receptor, or non-immunological adherence mediated by thrombospondin or some other cytoadhesive platelet a-granule protein. This phenomenon has also been found around monocytes and natural killer cells (Espanol I, 2000) which have FccRIIIa receptors. Our finding is, to the best of our knowledge, the first description of platelet satellitism described in marginal zone-B cell lymphoma. It has been reported around lymphoma cells in mantle cell lymphoma (Cesca, 2001). In

Glioblastome avec métastases systémiques d'emblée

Resume Les gliomes metastatiques sont une entite rare. Nous rapportons le cas d’un glioblastome cerebral diagnostique au stade de metastases revelees par une bicytopenie secondaire a une infiltration tumorale medullaire. Lors de l’autopsie, d’autres localisations secondaires ont ete retrouvees : pulmonaires, ganglionnaires mediastinales, et sous forme d’emboles vasculaires spleniques.

Le glyoxal: un possible substitut polyvalent du formaldéhyde en anatomie pathologique ?

The quest for formaldehyde substitutes is motivated by two fundamental developments: the OSHA regulation standard declaring it hazardous and advocating its substitution with less dangerous chemicals and the fact that formalin is a poor preserver of nucleic acids. Among the non-alcoholic formalin substitute, glyoxal has been hailed as the best alternative. In this work, we showed that glyoxal-containing fixatives are not plausible polyvalent substitution options.

Sarcome à cellules claires primitif de l’iléon

Resume Le sarcome a cellules claires ou melanome des parties molles est un sarcome de haut grade avec differenciation melanocytaire, developpe principalement au niveau des tendons et aponevroses des extremites chez l’adulte jeune. Les localisations viscerales sont exceptionnelles et seulement huit cas interessant le tractus gastro-intestinal sont rapportes dans la litterature. Nous presentons ici l’observation d’un sarcome a cellules claires de siege ileal, survenant chez une femme de 26 ans. A travers cette observation, nous abordons les problemes de diagnostic de ce type rare de sarcome, caracterise par la translocation specifique t(12;22)(q13;q12).

Léiomyosarcome de l’épididyme : à propos d’un cas avec revue de la littérature

Primary epididymal leiomyosarcoma is uncommon: only 16 cases has been reported in the literature. We present an additionnal case in a 78-year-old man, treated for a prostatic adenocarcinoma by gonadorelin (LH-RH) analogue, who had an epididymal tumor. A right orchidectomy with high ligation of the spermatic cord was performed. The diagnostic of primary leiomyosarcoma of the epididymis was made. The patient is dead 2 years later with no recurrence of disease. A review of reported cases is made.

Clear cell adenocarcinoma: a rare variant of primary colonic tumour

Dear Editor: Since the first report of primary clear cell adenocarcinoma of the large intestine published in 1964, only seven cases have been reported in literature. In this paper, we describe the eighth case of this rare oncological entity. Immunohistochemical study is indispensable in establishing the primary colonic origin of the lesion. A previously healthy 84-year-old woman was admitted in our hospital because of ferriprive anaemia, necessitating a blood transfusion. Her past medical history included high blood pressure, arthritis and appendicectomy. On admission, the patient presented no complaint. On physical examination, the patient was found to be completely oriented, with no abnormal signs. Colonoscopy revealed an ulcerated, stenotic and infiltrated tumour developed in the left colon at 40 cm from anal margin. Biopsy specimen of the tumour showed an adenocarcinoma. Abdominal echography and computed tomographic scan found no metastatic extension and no abnormal findings from liver, kidneys, genital tractus and ovaries. A left segmental resection was performed with an end-to-end anastomosis. No complementary treatment was performed. The patient was discharged in good health and free of disease 9 months after surgery. Gross examination of the surgical specimen revealed a 30 cm length of colon. An ulcerated tumour involved the mucosa and infiltrated through the full thickness of the colonic wall. It measured 3.5×1.5 cm. Twenty-one lymph nodes were found. Histology of the tumour showed an ulcerated surface. The tumour was entirely composed of cells with microvacuoled cytoplasm and a centrally located nucleus. However, most of the tumour had a pronounced glandular pattern, cribriform areas were also identified. There was moderate nuclear pleomorphism, and numerous foci of necrosis were observed. The adjacent colonic mucosa was devoid of dysplasic features. Histochemical examination of the cytoplasm of the clear cells showed no periodic acid-Schiff (PAS) and alcian blue pH 2.5 staining. Red oil staining failed to detect lipid, and ultra structural examination found no glycogen and no lipid. Immunohistochemical staining showed diffuse strong positive membrane staining of tumour cells with CEA (ZYMED, San Francisco, USA). There were also diffuse cytoplasmic strong positivity for cytokeratin 20 (Dakocytomation, Trappes, France), but no staining for cytokeratin 7 (Dakocytomation), CD 10 (Novocastra, Newcastle Upon Tine, UK) and vimentin (Dakocytomation). Overexpression of p53 (Dakocytomation) was not observed. Ki-67 MIB-1 (Dakocytomation) labeling index was calculated by counting the positive nuclei per 1,000 cells; 44% of tumoural cells show a positive staining. Apoptotic index was calculated by counting positive tumoural cells staining with anti-activated caspase-3 (BD Biosciences, Franklin Lakes, USA) per 1,000 cells; 10% of tumoural cells showed a positive staining. Expression of MLH1, MSH2 and MSH6 (Diagnostic BioSystems, Pleasanton, USA) was preserved. Upon the bases of these findings, the diagnostic of primary clear cell adenocarcinoma of the colon was made. The tumour infiltrated through the full thickness of the colonic wall into surrounding fat and serosa. All lymph nodes were regular. Tumour stage was T4b N0 M0. Primary clear cell colonic adenocarcinoma is a very rare entity, with only seven cases described in the Englishlanguage literature. Most reported patients are men, and all Int J Colorectal Dis (2008) 23:137–138 DOI 10.1007/s00384-007-0291-1