diffuse large b cell lymphoma | B-cell lymphoma diffuse large cell 1 review Hematology

B-cell lymphoma diffuse large cell 1 review Hematology 


 Lymphoma diffuse B large cell anaplastic morphology Anaplastic diffuse large B-cell lymphoma Copyright 2017 John Libbey Eurotext. Downloaded by a robot coming from on 03/02/2017. Helen Duval 1 Stanislas Nimubona 2 Céline Pangault 3 Stephan Saïkali 1 Sylvie Caulet-Maugendre 1 1 Department of Anatomy and pathological cytology, CHU Pontchaillou, rue Henri Le Guilloux, Rennes 2 Service d Clinical Hematology, Centre Eugène Marquis,. Rennes 3 Service d biological Haematology, CHU Pontchaillou, Rennes reprints: H. Duval summary. Diffuse B Lymphoma from anaplastic morphology are remarkable entities belonging to the category of B lymphomas diffuse large cell and not that of anaplastic lymphoma. Histological characteristics are those d a tumor cells Pleomorphic, requiring d eliminate different diagnoses as a metastasis melanoma, d d a germ tumor or d a sarcoma. Here we report the case of a 64 year old patient who presented a ganglionic breach aortico-cellar emphasizing the histological features and immunohistochemical of this lymphoma. Key words: B-cell lymphoma large cell anaplastic Lymphoma, ALK Abstract. Anaplastic diffuse large B cells lymphoma are morphological variants of diffuse large B cells lymphoma and they are separate from anaplastic large lymphoma cells. The pleomorphic characteristics of the neoplastic cells need to exclude metastasis of melanoma, germ cells tumor or sarcoma. We report the case of a 64-years-old patient with aortic adenopathy and we underline the histological features and the immunohistochemical profile of such injury Key words: anaplastic large cell lymphoma, ALK Observation the patient, aged 64, without notable medical history, presented the general State tampering associated with lower back pain. In this context, the biological assessment has highlighted an inflammatory syndrome with anaemia microcytic, without other abnormalities of the blood count. Explorations made during his hospitalization have objectified of Lymphadenopathy multiple, located along the axes inter-aorticocave and latero-aortic, as well as to the level of the pancreatic Lodge. There was also a rise in LDH at 1152 U/L (normal: U/L). An exploratory laparotomy was then conducted with resection of two retroperitoneales to diagnostic Lymphadenopathy. The histological review highlighted a d aspect Pleomorphic tumor proliferation that totally destroyed l architecture lymph nodes. By place, there was a significant MS, realizing a compartmentalized architecture. Tumor cells were large, with stomach to chromatin decondensee nuclei and clear cytoplasms, to little visible limits. Many elements were very large, sometimes plurinuclees or lobules, large nuclei. A few sternbergoides cells were also observed as well as a few small residual lymphocytes (figures 1 and 2). 195

2 figure 1. Ganglionic cytology, affixing (nom, original magnification x 1000, immersion). Figure 2. Large, rounded, oval or polygonal tumor cells with nuclei Pleomorphic (HES, original magnification x 400). 196. in this context, the diagnoses of anaplastic Lymphoma, d ganglionic metastasis carcinoma little differentiated, d a melanoma, Sarcoma, d d a Histiocyte malignancy or d a germ tumor could be considered. Immunohistochemistry has therefore been a study on cuts of fabric in a 4% formalin solution and included in paraffin. Ganglionic metastasis diagnosed d a little differentiated carcinoma was eliminated before the lack of expression by the tumor cells of the cytokeratins broad-spectrum CK22, CKKL1, AE1 - AE3 and l ACE. Them

Figure 3 3. Expression of the marker pan B CD79a by tumor cells (IMMUNOHISTOCHEMISTRY, original magnification 400). assumptions d a ganglionic metastasis d a melanoma or d a little differentiated Sarcoma could be overturned by the negativity of the study Immunohistochemistry with antibodies anti-hmb45, anti-ps 100 (markers Nevus) and anti-vimentin antibodies. anti desmine and anti-myogenine (muscle markers). The absence of positivity with antibody anti-cd 68 l was eliminate a Histiocyte malignancy and the hypothesis d a d metastasis tumor of germ was ruled out due to the lack of expression of the HCG, of PLAP (alkaline phosphatase placental) or CD 117. On the other hand, about 30% of the tumor cells had an intense expression of Leukocyte common Antigen (CD 45 - RA) l and a few multinucleated cells expressed l EMA and the 30 CD. The T lymphoid proliferation markers were negative (CD 2, CD 3, CD 5, 7 CD and CD 43) then B markers were positive (CD 79A and CD 20/L26) (figure 3). The marking by l antibodies anti-alk1 was negative. Molecular Biology don't detect NPM - ALK rearrangement. This process lymphomateux of unusual morphology, Pleomorphic and rich in giant cells, could be classified as part of the anaplastic lymphomas of the result of the expression of lymphoid B markers. So the diagnosis after discussion was that of B-cell lymphoma diffuse large cell anaplastic morphology. In addition, profile Immunohistochemistry of this Lymphoma (figure 4), CD 10 - Bcl 6 + MUM 1 + suggested the post-centrogerminatif character, active and there was an expression of Bcl2, but without molecular rearrangement of BCL2-JH. Moreover, more than 90 percent of tumor cells expressing l Antigen Ki67 proliferation marker. The patient received 8 courses of chemotherapy CHPOP + rituxumab, supplemented by abdominal radiation of the fact of partial response and l alteration of the general State not allowing to offer a remedial therapy more heavy. The evolution has unfortunately been unfavorable despite a new chemotherapy and the patient died 12 months after diagnosis. Discussion according to the classification of Kiel-Lennert [1], the term of anaplastic large cell lymphoma consisted of malignant lymphomas of B, T or null phenotype. Further classifications of who [2] and [3] REAL separated phenotype T lymphomas or no lymphomas of anaplastic morphology of phenotype B l d activation CD30 Antigen express and that fall into the category of B lymphomas diffuse to large cells [2-4]. B lymphomas diffuse large cell 30 to 40% of malignant lymphomas not hodgkiniens. They occur at any age, and more frequently after 60 years for men. Their cause is unknown, but they usually occur from novo [2, 4, 5]. Patients most often present a ganglionic breach and in 40% of cases, l reached is only extranodal, including gastric or ileo-caecale [3]. On the microscopic level, the normal lymph node structures are replaced by a diffuse lymphomateux, with sinus infiltration rate. Four variants were 197

4 198 described: centroblastique, immunoblastique, rich in lymphocytes T/histiocytes and anaplastic [2]. The centroblastique Variant can be monomorphic or polymorphic and appear composed of lymphocytes of medium-sized to large, morphology centroblastique, nuclei with an decondensee chromatin stomach and one or two nucleoli NET, often located against the nuclear membrane. The immunoblastique variant is characterized by a predominance of cells of large size, immunoblastiques, whose nuclei contain an decondensee chromatin and a prominent central nucleolus, representing more than 90% of the elements present. In the rich in lymphocytes T, cells type neoplastic B are minority, representing less than 10% of the items, no tumor T and histiocytes lymphocytes predominate. The anaplastic variant has large, rounded, oval or polygonal cells with nuclei Pleomorphic, sometimes evoking Reed-Sternberg cells. The immuno-phenotypic map, these lymphomas express markers pan - b as the CD19, the CD20, the CD22 or the CD79a but way sometimes fickle [6]. The vast majority of the morphology of anaplastic lymphoma cells express the CD30 Antigen d activation also expressed by Reed-Sternberg cells [7]. The study of this marker is thus recommended, associated with CD3, CD20 and CD45. Figure 4. Profile Immunohistochemistry 6 CD - 10 (a) Bcl + (b) MUM 1 + (c) confirming the post-centrogerminatif character, activated (IMMUNOHISTOCHEMISTRY, original magnification 400). B on the histological level, the differential diagnosis is d a d ganglionic metastasis carcinoma little differentiated, d all the more that a few cells can express the EMA. Observed microscopic aspects can also evoke a metastasis ganglionic a melanoma, d d a sarcoma or d a germ tumor. These lymphomas are also a problem of differential diagnosis with classical anaplastic lymphomas of phenotype T / tie that occur rather during the third decade and are biologically distinct, associated with translocation t(2;5) (p23 (; q35), and its variants, and the expression of the ALK protein due to the rearrangement of NPM - ALK [8, 9]. The profile of gene expression of these lymphomas affects the prognosis. Indeed, profile centrogerminatif Lymphoma patients have a better prognosis than those with lymphoma profile postcentrogerminatif or active [10]. In addition, according to a recent study, the good correlation between studies genotypic and phenotypic data in Immunohistochemistry on fixed tissue would d profile IMMUNOHISTOCHEMISTRY, prognostic value [11]. Thus, alongside the IPI clinical score [12], the prognosis can be evaluated by the study Immunohistochemistry of the expression of CD10, l oncoproteine Bcl6 and MUM1 (IRF4, interferon regulating factor 4) which allows to determine the profile centrogerminatif or no [11]. In addition, the expression of Bcl2 C oncoproteine l

5 also seems to be a pejorative additional prognostic factor in not centro-germinative profile lymphomas [11]. Conclusion this observation makes it possible to draw attention to the differential histological diagnosis of lymphoma from anaplastic morphology of ganglionic location: d metastasis carcinoma little differentiated, d a sarcoma or d a melanoma. In addition, it allows to remind that Lymphoma from anaplastic morphology of phenotype B fall into the category of B lymphomas diffuse large cell and not in that of anaplastic lymphomas, which concerns only the lymphomas of T or null phenotype. This observation underscores the interest of immunophenotypiques to sight prognostic studies, achievable in Immunohistochemistry on fixed and included in paraffin tissue. Thanks. Thanks to Mr. Pr Delsol who had the kindness to confirm this observation. REFERENCES 1. Lennert K. Morphology and classification of malignant lymphomas and so called reticuloses. ACTA Neuropathol (Berl) Suppl 1975(suppl 6): gate KC, Warnke RA. Diffuse large B-cell lymphoma. In: Jaffe are, Lee Harris N, H Stein, Vardiman JW, eds. Tumours of haematopoietic and lymphoid tissues. Whorld Health Organization Classification of tumours. Lyon: IARC Press, 2001: Harris NL, Jaffe are, Stein H, et al. A revised European - American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: Delsol G, Al Saati T, Lamant Selves J, Brousset P. Classification histopathological, immunological, cytogenetic and molecular lymphomas. In: Surgical encyclopedia. Paris, Elsevier, 1998: A gate KC, Warnke RA. Diffuse large B-cell lymphoma. In: Jaffe are, Lee Harris N, H Stein, Vardiman JW, eds. Tumours of haematopoietic and lymphoid tissues. WHO classification of tumours. Lyon: IARC Press, 2001: Doggett RS, GS, Horning Wood S, et al. The immunologic characterization of 95 nodal and extranodal diffuse large cell lymphomas in 89 patients. Am J Edition 1984; 115: Piris M, Brown DC, KC, Mason DY gate. CD30 expression in non-hodgkin lymphomas s. Histopathology 1990; 17: Haraalmbieva E, k Pulford, Lamant L, et al. Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma kinase (ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas. BR J Hematol 2000; 109: Delsol G, Lamant L, Al Saati Auvigne, T I, Brousset P. The disease of Hodgkin and anaplastic Lymphoma in Ann Edition 1998; 4: Alizadeh AA, Eisen MB, Davis RE, et al. Separate types of diffuse large B-cell lymphoma identified by expression profiling. Nature 2000; 403: Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Davis J, Ott G, Müller-Hermelink HK. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: A predictive model for aggressive non-Hodgkin's lymphoma s.