Workshop Case # 8 (H 4205/07)

Transcription

1 Workshop Case # 8 (H 4205/07) 53 y old male patient had a history of gastrectomy 15 years earlier for gastric carcinoma.on routine sonographic and CT control an enlarged lymph node was detected in the hepatoduodenal ligament. Biopsy taken suspecting a late recurrence or metastasis.sent as consultation case because of concern of the patient. A reactive lymphofollicular hyperplasia?

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9 CD 20 CD 3

10 Ki 67

11 Cyclin D1

12 In situ MCL vs. clonal hyperplasia of CCND1+ mantle lymphocytes Kanehira K, Braylan R C, Lauwers GY. Early phase of intestinal mantle cell lymphoma: a report of two cases associated with advanced colonic adenocarcinoma. Mod Pathol. 2001; 14: Espinet B, Solé F, Pedro C, García M, Bellosillo B, Salido M, Florensa L, Camacho FI, Serrano S. Clonal hyperplasia of cyclin D1+ mantle lymphocytes in an asymptomatic patient: a new entity or an early stage event in the development of a mantle cell lymphoma? Hematol. Citocinas Inmunoter. Ter. Cel Terauchi, 2001; Hurlstone DP, 2002; Anagnostopoulos I, Foss HD, Hummel M, Trenn G, Stein H. Histopathology. 2001;39: Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma. Nodit L, Bahler DW, Jacobs SA, et. al: Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes. Hum Pathol 2003; 104:

13 Diagnosis Mantle Cell Lymphoma in situ E.Campo,EAHP (2006), Wien

14 In situ ( early ) and indolent Mantle cell lymphoma? In situ mantle cell lymphoma may not require teatment( Nodit et al. Hum. Pathol. (2003);Richard et al. J.Clin.Pathol.(2006)) May be limited involvement in common and progressive MCL Indolent MCL :Blood, BM and Spleen Involvement without lymphadenopathy SOX11, a new marker of mantle cell lymphoma, is usually negative in indolent and in situ mantle cell lymphoma

15 Ø MCLIS is a very rare phenomenon in patients without known MCL, in good relationship to the very rare t(11;14)+ B cells in healthy people Ø However, MCL patients show in up to 27% preclinical Infiltration of Cyclin D1+ Cells, only detectable by immunohistochemistry ØIn contrast, 2,3% of unselected lymph node biopsies in 3/133 patients may show in situ FL by immune histochemical analysis and FISH Patrick Adam et al. ( 2012) in press and Henopp T, Quintanilla-Martı nez L, Fend F & Adam P (2011) Histopathology 59,

16 Commentary Terminology similar to FL in situ (Cong et al Blood (2002) having a similar overall appearance May behave differently, few published follow-up, In situ and early stages may differ in SOCS 11 reactivity Most cases represent early involvement by MCL Interesting and controversial concept: Pre- vs. Early stage MCL biologically important

17 BCL-2

18 H11514/06 FL in situ

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21 H1299/06 partial involvement Of l.n. by FL

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24 Partial Infiltration in Follicular Lymphoma BCL-2 Ki-67 BCL-2 Adam et al. 2005

25 Partial infiltration and persistence of reactive follicles is associated with a localized tumor stage ( stage I/II) Control group (Complete infiltratio) (n=49) Study group (Partial infiltration) (n=53) Cases with at least one tumor-free follicle (n=40) Validation group: all cases with partial infiltration in the year 2001 (n=34) Validation group: cases with at least one tumor-free follicle (n=16) Stage I Stage II 3 (6 %) 7 (14 %) 33 (62 %) 11 (21 %) 32 (80 %) 6 (15 %) 15 (44%) 11 (32%) 10 (63%) 6 (37%) Stage I / II Stage III Stage IV 10 (20 %) 16 (33 %) 23 (47 %) 44 (83 %) 6 (11 %) 3 (6 %) 38 (95 %) 0 (0%) 2 (5 %) 26 (76%) 5 (15%) 3 (9%) 16 (100%) 0 (0%) 0 (0%) Stage III / IV 39 (80 %) 9 (17 %) P< (5 %) P< (24%) P< (0%) P<0.001 Adam et al. AJSP 2005

26 Size of B-cell clones B-cell clones Cases

27 Size of B-cell clones B-cell clones LYMPHOMAS REQUIRING TREATMENT Cases

28 Size of B-cell clones B-cell clones CASES DENOMINATED AS LYMPHOMA (require now or may require future treatment) In situ FL, In situ MCL, MZL-MALT Cases

29 Size of B-cell clones B-cell clones MONOCLONAL REARRANGEMENT NOT ALL WILL PROGRESS TO LYMPHOMA Cases

30 Open issues in situ early indolent smoldering intrafollicular?

31 Take home Message In situ stages of FL and MCL may not been seen in H&E stained sections and hidden in a lymphofollicular hyperplasia May be a preneoplastic stage ( and hyperplasia) of t( 14;18)+ cells in healthy individuals in FL Has to be differentiated from partial involvement of lymph nodes by FL In MCL in situ stage may already been an early involvement.speed of clonal evolution and tumor progression dependent of biological features of tumor cells These preclinical stages need exact staging, but otherwise may be followed without needing treatment