Cd79a, cd3, cd 56, cd10, ki67, hhv8, alk1, and cyclin d1. Section of plasmablastic lymphoma g wrightgiemsa, original magnification. Epidemiological studies have consistently shown that increased exposure to female sex hormones is associated with a lower risk of crc in women, and cyclin d1, an important downstream. N2 this report describes an unusual case of cyclin d1 expression by an otherwise typical follicular lymphoma, of low histological grade. Optimal minimal panels of immunohistochemistry for. Plasmablastic lymphoma pbl is a unique lymphoma, first described by delecluse and associates as a rare variant of diffuse large bcell lymphoma dlbcl involving the oral cavity. Although increasingly recognized in other lymphoproliferative disorders, cyclin d1 expression and ccnd1 gene abnormalities have not been well studied in nodular lymphocytepredominant hodgkin lymphoma nlphl. Cyclin d1 is a regulatory subunit of cyclin dependent kinases cdk4 and cdk6. A novel vaccine for mantle cell lymphoma based on targeting. Pbl is considered as a special morphological variation in diffuse large b cell lymphoma 1, 2. Fluorescence in situ hybridization fish analysis demonstrated a loss of tp53 and no myc or igm disruption. Jan 12, 2018 cd3positive plasmablastic bcell neoplasms. Diagnosis and treatment of cd20 negative b cell lymphomas. New therapeutic approaches based on boosting antitumor immunity are needed.
Lca, cyclin d1, cd20, cd3, alk, cd21, cd23 and ck56. Cytologic features of plasmablastic lymphoma lin 2005. Cyclin d1 positive plasma cell myeloma to the editor. The gene is overexpressed in mantle cell lymphomas due. We report the unique finding of cyclin d1 expression in an otherwise typical follicular lymphoma, grade 1, found at second relapse in a 51yearold female patient with an original diagnosis of diffuse large b cell lymphoma made 8 years earlier. Cyclin d1 positive follicular lymphoma journal of clinical. Based on the morphological features and immunohistochemical profile, the diagnosis of plasmablastic lymphoma was made. The second case case 230 was more challenging in that it was negative for cyclin d1 and the appropriate diagnosis was indicated only by the lack of immunoglobulin heavy chain expression by the neoplastic pcs and the subsequent clinical course with. The chart showing pdf series, word series, html series, scan qr codes. In addition, stains for cd56 and cyclin d1 can be useful because these markers may be positive in plasma cell myelomas and extramedullary plasmacytomas but are negative in pbls. Plasmablastic lymphoma pbl is an unusual entity of. Plasmablastic lymphoma pbl is a very aggressive lymphoma with a diffuse proliferation of large neoplastic cells, most of which resemble b immunoblasts or plasmablasts, that have a cd20negative plasmacytic phenotype. Clinicopathologic features of plasmablastic lymphoma. Plasmablastic lymphoma pbl, initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in hivinfected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states.
Signs and symptoms of adult nonhodgkin lymphoma include swollen lymph nodes. Cyclin d1 expression in mzls has been reported but is rare 27. Cd20 negative nhl is frequently associated with extranodal involvement, atypical morphology, aggressive clinical behaviour, resistance to standard chemotherapy and poor prognosis. According to the 2008 monograph on the who classification of hematolymphoid tumors, lpl is a neoplasm of small b lymphocytes, plasmacytoid lymphocytes, and plasma cells, usually involving bone marrow bm, sometimes lymph nodes and spleen, which does not fulfill the criteria for any of the other small b cell lymphoid. Braf v600e mutation and clonal evolution in a patient with.
Clinicopathologic features have been largely derived from cases reports and small series with limited outcome analyses. Together with its binding partners cyclin dependent kinase 4 and 6 cdk4 and cdk6, cyclin d1 forms active complexes that promote cell cycle progression by phosphorylating and inactivating the retinoblastoma protein rb. Cyclin d1 expression in bcell lymphomas sciencedirect. Although colorectal cancer crc is generally not considered to be a hormonedependent malignancy, several sexrelated differences in incidence, molecular characteristics and survival have been reported. Mantle cell lymphoma mcl is a distinct clinical pathologic subtype of b cell nonhodgkins lymphoma often associated with poor prognosis. Diffuse aggressive bcell lymphomas clinical features dlbcl 30% burkitt 3% and b. Bcl1 gene, which leads to the overexpression of cyclin d1. Plasmablastic lymphoma pbl is a rare subtype of nonhodgkins lymphoma. Marginal zone b cell lymphomas with extensive plasmacytic. Cd20 negative b cell nonhodgkin lymphoma nhl is rare and accounts for approximately 12% of b cell lymphomas. A, the bone marrow aspirate contained numerous lymphoplasmacytic forms. Expression of the protein may occasionally be observed in eps 12,28.
The cyclin d1 protooncogene is an important regulator of g1 to s phase progression in many different cell types. A practical approach to diagnosis of bcell lymphomas with. Peripheral tcell lymphoma with cyclin d1 overexpression. Dlbcl, cyclin d1 expression should be assessed by ihc in. Characterized by its aggressive nature and plasmacytic differentiation, pbl remains a therapeutic and diagnostic challenge. However, it can be oversexpressed in other hematological malignans cies such as plasma cell myeloma. Bcl2igh and ccnd1igh fusions were identified by interphase. Biopsy of the neck mass revealed large atypical cells expressing cd4, cd15, cd30, cd38, cd45, cd79a, cd8, and mum1, with focal reactivity for cd3, cd7, and cyclin d1, findings that were consistent with plasmablastic lymphoma pbl arising from a background of chronic lymphocytic leukemia.
Furthermore, a recombinant vaccine based on targeting cyclin d1 antigen to human dcs via an anticd40 mab was. Diagnostic algorithm of common mature bcell lymphomas. Cyclin d1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Plasma cell myeloma and related neoplasms american journal. Eps are infrequently encountered in the salivary gland. The biopsy showed a diffuse infiltrate of similarappearing lymphoid cells b. Aberrant cd3 expression in a relapsed plasma cell neoplasm. The many faces of small b cell lymphomas with plasmacytic. Plasmablastic lymphoma, stomach, nonhodgkin lymphomas introduction plasmablastic lymphoma pbl is a rare entity. The immunohistochemical findings of ten cases are almost consistent with.
Case of plasmablastic lymphoma of the sigmoid colon and literature. For western blots, incubate membrane with diluted primary. Immunecheckpoint expression in epsteinbarr virus positive and. Cyclin d1 prad1, bcl1, ccnd1 this gene was first identified from parathyroid adenomas and designated prad1 parathyroid adenomatosis 16,17. Brentuximab vedotin demonstrates activity in a patient with. Pitfalls in immunohistochemistry in hematopathology. Barr encoding region eber, hhv8, cyclin d1, cd56, iga, and igm. Cyclin d1 ams plification is known to be associs ated with mantle cell lymphoma. Relevance of cyclin d1b expression and ccnd1 polymorphism.
Cyclin d1specific t cells secrete ifng and type 2 cytokines including il5 and il. Lymphoma is a group of blood cancers that develop from lymphocytes a type of white blood cell. The proliferative rate with ki67 ranged from 60% in the tumors that showed a greater number of more mature plasma cells, to. Oral and extraoral plasmablastic lymphoma american journal. The 2008 world health organization who classification of hematopoietic and lymphoid tumors and the associated monograph represent the established guidelines for the diagnosis of malignant lymphomas. Cyclin d protein is anywhere from 155 in zebra mussel to 477 in drosophila amino acids in length once cells reach a critical cell size and if no mating partner is present in yeast and if growth.
Plasmablastic lymphoma is a rare and aggressive diffuse large bcell lymphoma. Sox11 is useful in differentiating cyclin d1positive diffuse large b. The 2016 revision of the world health organization. The name often refers to just the cancerous versions rather than all such tumors. Western blot analysis of extracts from c6 and l929 cells, using cyclin d1 antibody. Table 1 immunohistochemistry panels in phase 1 histology panel suspected cllsll cd20, cd5, cd23, cd10, and cyclin d1 suspected fla cd20, cd21, cd10, bcl2, and. Cd56 andor cyclin d1 expression by plasma cells was helpful for making a correct diagnosis.
Targeting cyclin d1 for mantle cell lymphoma journal for. Cyclin d protein is anywhere from 155 in zebra mussel to 477 in drosophila amino acids in length. Relevance of cyclin d1b expression and ccnd1 polymorphism in. Mcl is associated with overexpression of cyclin d1 thus rendering this molecule an interesting target for immunotherapy. Notice the irregular nuclear contours of the mediumsized lymphoma cells and the presence of a pink histiocyte. Cyclin d1 is a regulatory subunit of cyclindependent kinases cdk4 and cdk6. Jun, 2005 in addition, stains for cd56 and cyclin d1 can be useful because these markers may be positive in plasma cell myelomas and extramedullary plasmacytomas but are negative in pbls. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired.
The expression of cyclin d1 in bcells in which the protein is physiologically absent, is supposed to be causal in the transformation process. The proliferation index ki67 was approximately 80%. Plasmablastic lymphoma pbl is a rare form of nonhodgkins lymphoma. Notably, the tumor cells had strong expression of cd20 and cyclin d1, closely resembling blastoid mantle cell lymphoma. An unusual case of plasmablastic lymphoma presenting as. Cyclin d1 gene abnormality has also described in cutaneous lymphoma where the cyclin d1 gene copy gain is an infrequent event and it seems associated to malignant phenotype. Request pdf sox11 is useful in differentiating cyclin d1positive diffuse large b cell lymphoma from mantle cell lymphoma hsiao sc, cortada i r, colomo l. Cyclin d1positive diffuse large bcell lymphoma request pdf. Cyclin d1 expression in peripheral tcell lymphomas. Using a double stain for cd20cyclin d1, we quantified cyclin d1 expression in 10 cases.
Lymphoplasmacytic lymphoma and the impact of myd88 l265p mutations. Conflicting data are reported on the clinical significance of cyclin d1. Cyclin d1 is a protein required for progression through the g1 phase of the cell cycle. Mar 18, 20 the patients lactate dehydrogenase level was 208 ul. Optimal minimal panels of immunohistochemistry for diagnosis.
Cyclin d1 specific t cells secrete ifng and type 2 cytokines including il5 and il. Request pdf on jul 1, 2008, rodriguezjusto m and others published cyclin d1positive diffuse large bcell lymphoma find, read and cite all the research you need on researchgate. The most common types of these include plasmablastic lymphoma, primary. The demographic, clinicopathologic features, and clinical outcomes of a cohort of 61. Diagnostic algorithm of common mature bcell lymphomas by. The neoplastic cells strongly and uniformly expressed pax5 c, cd20 d, and cyclin d1 e. Nonhodgkin lymphoma is a disease in which malignant cancer cells form in the lymph system. Plasmablastic lymphoma pbl is a rare aggressive neoplasm with lymphoid and plasmacytic differentiation that is commonly associated with immunodeficiency and an unfavorable prognosis. Mantle cell lymphoma is usually, but not always, negative for bcl6, cd10 see below, and cd23. Plasmablastic lymphoma pbl is a rare highgrade large bcell lymphoma with. Rare concurrent indolent bcell lymphoma and plasmablastic.
The synthesis of cyclin d is initiated during g1 and drives the g1s phase transition. Plasma cell myeloma and related neoplasms american. Cyclin d is a member of the cyclin protein family that is involved in regulating cell cycle progression. Oral and extraoral plasmablastic lymphoma american. Cyclin d1 is also expressed in lymphoid tumors such as mantle cell lymphoma mcl and multiple myeloma mm. Mcl is easily diagnosed, regardless of cd5 immunoreactivity. Plasma cell myeloma with small lymphocytelike morphologic features, t11. Median values of normalized cyclin d1 expression determined by realtime quantitative polymerase chain reaction were 1.
In mcl, ccnd1 encoding cyclin d1 is activated by the t11. Immunohistological recognition of cyclin d1 expression by nona. Mar 26, 2010 plasmablastic lymphoma with myc translocation. The most common types of these include plasmablastic lymphoma, primary effusion lymphoma, large bcell. During the g1 phase, it is synthesized rapidly and accumulates in the nucleus, and is degraded as the cell enters the s phase.
Here we report a case of peripheral tcell lymphomas not otherwise specified with cyclin d1 gene copy gain associated with protein overexpression. The cytomorphology, cd20 expression and cyclin d1 expression, together. Cyclin d1 positive follicular lymphoma mayo clinic. Only one case was positive for cmyc gene by ihc fig. Cyclin d1 expression was subsequently demonstrated in the diffuse large b cell lymphoma, and in. Nasopharyngeal tumor composed of oval and round shaped cells with eccentric nuclei and abundant eosinophilic cytoplasm, in a diffuse sheetlike and cohesive growth pattern. Cyclin d1 expression in colorectal cancer is a favorable. The tumor cells were also positive for eber ish fig. The patients lactate dehydrogenase level was 208 ul. Brentuximab vedotin demonstrates activity in a patient. Older age, being male, and having a weakened immune system can increase the risk of adult nonhodgkin lymphoma. Nccn clinical practice guidelines in oncology nccn. We show here a novel strategy for the development of.
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