Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

(PowerPoint)

585 views

Published on

  • Be the first to comment

(PowerPoint)

  1. 1. Primary Mediastinal B-cell Lymphoma Grand Rounds 9/24/2004 Caron Rigden, M.D.
  2. 2. Case Presentation • 34 y/o male presented with a 3 week history of sob, chest pain, and increased facial swelling • He also reported intermittent fevers, no chills, increased fatigue, decreased appetite, and a 10 pound weight loss over the previous month
  3. 3. • PMH- none • NKDA • Medications- none • Social- single, lives alone, 1 ppd tobacco, 6 beers/week, +marijauna • FHx- father MI at 40, mother “thyroid problems”, brother surgery for “aortic problems”, sister Graves disease
  4. 4. Exam: 96.4 77 147/95 18 100% r.a. Gen: sitting comfortably, well-nourished Heent: sclera anicteric, mmm, no LAD, neck supple, no thyromegally, trachea midline, + R supraclavicular fullness Lungs: cta b Cvs: RRR with distant heart sounds Abd: +bs, soft, nt/nd, no HSM appreciated Ext: no c/c/e Skin: no rashes Neuro: non-focal
  5. 5. Laboratory Data: • BMP wnl • Wbc 8 with normal differential • Hgb 14 • Plt 368 • Ca 8.5 • Alb 4.1 • Alk phos 73 • Ast/Alt 20/14 • U/A wnl • LDH 321 • Uric acid 4.2
  6. 6. Imaging: • CXR: widened mediastinum • CT thorax: anterior mediastinal mass 10x8x8 cm extending up to the thoracic inlet. Marked encasement and extrinsic compression of the adjacent great vessels. Distal narrowing of the trachea. No pulmonary masses. • CT abd/pelvis: mild hepatomegally, no lad
  7. 7. Ddx: • Lymphoblastic lymphoma • Primary mediastinal b-cell lymphoma • Hodgkin’s disease • Anaplastic large-cell lymphoma • Germ cell tumor • Thymoma
  8. 8. Tissue dx: Primary Mediastinal B- Cell Lymphoma +CD 20, vimentin - CD 30, keratin, cea, and S-100 • BMbx: normocellular, negative for lymphoma involvement
  9. 9. Background • First described in 1980 by Lichtenstein et al • 1980’s cell of origin (resident B-cells of the thymus) was determined • 1994 REAL classification described PMBCL as a distinct subtype of DLBCL • 2.4 % of all NHL
  10. 10. Clinical Features • Median age 30 • Female>male 2:1 • Symptoms are related to the rapidly growing mediastinal mass: SVC most common complication at dx 30% phrenic nerve palsy hoarseness chest pain sob breast swelling 1/6 have fever/weight loss pruritis is rare
  11. 11. • Staging: Ann Arbor CXR, CT C/A/P, B BMbx, serum LDH, B-2 microglobulin • 5/6 of patients are stage IE or IIE at the time of dx • Extranodal disease • At dx 70% are locally advanced usually involving the lungs, pleura, pericardium, and chest wall • Involvement of the bone marrow or extrathoracic structures is rare at dx • With recurrence, 90% of cases involve the CNS, kidneys, ovaries, adrenals, and pancreas
  12. 12. • Diffuse proliferation of medium-large cells of heterogeneous morphology • Strands of fibers and/or sclerosis present in varying degrees in 50% of cases • Clear cells • No pathognomonic morphologic feature that reliably distinguishes PMBCL from DLBCL Histopathology
  13. 13. Pileri et al, Histopathology 2002, 41: 482-509
  14. 14. B Barth et al, The Lancet Oncology 2002, 3: 229-234
  15. 15. Immunophenotype: • B-cell origin with positivity for: CD45, CD20, CD19, CD22 • Surface IG negative • CD 21 negative • MHC I negative • CD 30 may be positive, but stain with less intensity than Hodgkin/Anaplastic Large Cell • CD 3 and other T-cell markers negative Cytogenetics: • Gains in segments of 9q, 12,q, and Xq have been observed
  16. 16. Barth et al, Lancet Oncology 2002, 3: 229-234
  17. 17. Proportion of Cases That Overexpress or Have Mutations in Certain Oncogenes in PMBCL vs DLBCL PMBCL DLBCL Bcl-2 rearrangement none 20% Bcl-2 overexpression 20-30% 20-30% Bcl-6 mutation none 50% Mal overexpression yes no van Besien et al, JCO 2001, 19: 1855-1864
  18. 18. Reported Studies on Management and Outcome of Patients with PMBCL van Besien et al, JCO 2001, 19: 1855-1864
  19. 19. Multicenter Italian retrospective study of 138 patients from 1982-1999 treated with CHOP vs. M MACOP-B/VACOP-B + IF-RT as consolidation. • 70% stage I-II • IPI 59.4% low-intermediate, 16.6 % high-intermediate, 5.7% high risk • Median f/u 66 months • Overall CR was 70% and EFS 64.4% • IF-RT given only to patients in CR
  20. 20. Todeschini et al, BJC 2004, 90: 372-376
  21. 21. Todeschini et al, BJC 2004, 90: 372-376
  22. 22. Tedeschini et al, BJC 2004, 90: 372-376
  23. 23. van Besien et al, JCO 2001: 1855-1864
  24. 24. Retrospective analysis of 35 patients with PMBCL treated with high-dose CBV plus autologous transplant to determine outcome and prognostic features for progression-free survival. • Estimated survival varied significantly depending upon disease status at transplantation: -first response had an estimated 5-yr. PFS of 83%. -refractory had an estimated 5-yr PFS of 58% -relapsed had an estimated 5-yr PFS of 27% • Strongest predictor of PFS was chemotherapy responsiveness immediately before transplantation. • Even chemotherapy non-responsive had an estimated 5-yr PFS of 33% Sehn et al, Blood 1998, 91: 717-723
  25. 25. Sehn et al, Blood 91: 717-723
  26. 26. Sehn et al, Blood 91: 717-723
  27. 27. • Overall standard of care is anthracycline based regimen +/- IF-RT. • Upon re-imaging if residual mass about 20% of original volume then risk of recurrence is high requiring consolidation with radiation or high dose chemotherapy and transplant • No prospective trials comparing transplantation and conventional chemotherapy • Patients receiving a response lasting longer than 18 months are likely to be cured • Treatment failure usually occurs during initial treatment or within 6-12 months of completion of therapy
  28. 28. So where is our patient? Completed 12 weeks of VACOP-B with a good partial response. Subsequently completed 20 days of radiation. Currently awaiting restaging.
  29. 29. References: Aisenberg A, Primary Large Cell Lymphoma of the Mediastinum. Seminars in Oncology 26: 251-258, 1999 Barth T, Leithauser F, Joos S, Bentz M, Moller P: Mediastinal (Thymic) Large B-Cell Lymphoma: Where Do We Stand? Lancet Oncology 3: 229-234, 2002 Sehn H. L, Antin J, Shulman L, Mauch P, Elias A, Kadin M, Wheeler C: Primary Diffuse Large B-Cell Lymphoma of the Mediastinum: Outcome Following High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantion. Blood 91: 717-723, 1998 Piler SA, Dirnhofer S, Went P, Ascani S, Sabattini E, Marafioti T, Tzankov A, Leoncini L, Falini B, Zinzani PL: Diffuse Large B-Cell Lymphoma: One or More Entities? Presents Controversies and Possible Tools for its Subclassification. Histopathology 41: 482-509, 2002 Todeschini g, Secchi S, Morra E, Vitolo U, Orland E, Pasini F, Gallo E, Ambrosetti A, Tecchio C, Tarella C, Gabbas A, Gallamini A, Gargantini L Pizzuti M, Fioritoni G, Gottin L, Rossi G, Lazzarino M, Menestrina F, Paulli M Palestro M, Cabras M, Di Vito F, Pizzolo G: Primary Mediastinal Large B- Cell Lymphoma: Long-term Results from a Retrospective Multicentre Italian Experience in 138 Patients Treated With CHOP or MACOP-B/VACOP-B. BJC 90: 372-376, 2004 Van Besien K, Kelta M, Bahagunu P: Primary Mediastinal B-Cell Lymphoma: A Review of Pathology and Management. JCO 19: 1855-1864, 2001

×