Pt.1 K.Gu.- Clinical presentation K.G. was a 59 y.o. female in 1990 when she noted the development of enlarged lymph nodes.
Download ReportTranscript Pt.1 K.Gu.- Clinical presentation K.G. was a 59 y.o. female in 1990 when she noted the development of enlarged lymph nodes.
Pt.1 K.Gu.- Clinical presentation K.G. was a 59 y.o. female in 1990 when she noted the development of enlarged lymph nodes in her left inguinal region. A lymph node biopsy yielded a diagnosis of lymphoma, and subsequent staging yielded evidence of periaortic, bilateral inguinal, and bilateral axillary lymph node involvement, and bone marrow infiltration. In 1994, the patient noted enlargement of a right inguinal lymph node, and another lymph node biopsy was performed. K.G.- 1990 biopsy K. G. - 1990 biopsy 50x Pt.1 K.G.- Flow analysis Lymphoid T Lymphoid B ‘90 Natural killer/myeloid ‘90 CD2 21 C D19 50 CD3 20 Kappa 73 CD4 17 C D5 Myeloid ‘90 CD56 Other ‘90 ‘90 CD13 C D10 66 CD14 CD34 Lambda 2 CD15 CD41 21 C D19/ C D10 66 CD33 CD45 96 CD7 21 C D20 70 HLADR 78 CD8 2 C D20/ C D5 <1 GP -A K.G.-Bcl2 immunohistochemistry Pt. 1 K.G. Diagnosis: 1990: Follicular lymphoma, Grade I Frequency of lymphomas Indolent versus aggressive Indolent Small lymphocytic lymphoma/CLL Follicular lymphoma, Grades 1/2 Extranodal Marginal zone lymphoma of MALT type Nodal marginal zone lymphoma Splenic marginal zone lymphoma Hairy cell leukemia Lymphoplasmacytic lymphoma Plasma cell myeloma Plasmacytoma Cutaneous T cell lymphoma Cutaneous CD30+ anaplastic large cell lymphoma Aggressive Prolymphocytic leukemia Large B cell lymphoma Burkitt lymphoma Mantle cell lymphoma Anaplastic large cell lymphoma All peripheral T cell lymphomas Divides B and T Pt K.G. Diagnosis: 1990: Follicular lymphoma, Grade I Therapy 1990 Prognosis 1990 Table X: Indolent B cell lymphomas Frequency (% all ly mphomas Age of onset median Stage at Presentation Response to Therapy 5 yr survival Predominant site presentation Pattern of nodal Infiltration Benign cell Equivalent Dominant cell type Im munopheno -type Molecular Pathogenesis Follicular Lymphoma (Grade I) 22% Marginal zone Lymphoma Small lymphocytic lymphoma/CLL 8 7 59 61 65 Stage III/I V Diss eminated Good to most treatments, but incurable short of transplant 72% Stage I Stage IV Frequently curable Similar to Follicular lymphoma 74% 51% Nodal Ex tranodal Marrow/nodal Follicular Dif f use Dif f use Germinal center small cleaved cell Small cleaved cell i n most cases, but can be large cell Positive: CD19 CD10, Bcl2+ Negative: CD5- Marginal zone Lymphocyte Virgin B cell Mix of small lymphocytes, plasma cells t(14;18) Bcl2/JH t(11;18), Trisomy 3 Small lymphocytes w ith round nucleus Positive: CD19, CD5 CD23 Negative: CD10 Trisomy 12 Positive: CD19, Bcl2 Negative: CD10, CD5 K. G. - 1994 biopsy K. G. Biopsy 1994 - 50x Pt. K.G.- Flow analysis Lymphoid T Lymphoid B ‘90 ‘94 CD2 21 CD3 20 CD4 ‘90 ‘94 C D19 50 90 10 Kappa 73 17 8 C D5 21 10 CD7 21 CD8 2 7 NK associated Myeloid ‘90 ‘94 CD56 Other ‘90 ‘94 ‘90 ‘94 CD13 C D10 66 63 88 CD14 CD34 Lambda 2 4 CD15 CD41 C D19/ C D10 66 63 CD33 CD45 96 99 C D20 70 95 HLADR 78 40 C D20/ C D5 <1 <1 GP -A Pt. K.G. Diagnosis: 1990:Follicular lymphoma, Grade I 1994: Progression to diffuse large cell lymphoma Therapy 1994 Prognosis1994 Clinical follow-up K G. lessons Follicular lymphomas are the second most common type of lymphoma seen in Western countries Most are disseminated at diagnosis, Stage III or IV In the most common forms, Grades 1 and 2, they are indolent lymphomas Mean survival >7 years Pathogenesis due to failure of apoptosis, programmed cell death Caused by translocation, t(14;18)(q32;q21) Produces constitutive expression of Bcl2, an anti-apoptotic protein, so cell immortalized, but small replicating fraction and slow growth of tumor Therapy during indolent phase based on age, stage, symptoms Until recently, felt to be incurable, but controllable Watch and wait vs limited chemotherapy vs transplant Can progress to large cell lymphoma More aggressive disease due to activation of cell cycle mechanism Now increased growth fraction plus defective cell death Requires more aggressive multiagent chemotherapy vs transplant K. G. Lessons 2 Large B cell lymphoma can present de novo Most common type of lymphoma in Western countries Classic type of aggressive lymphoma, a disease of excessive cell growth and replication Morphologic manifestation is large cell with “vesicular” chromatin pattern and prominent nucleoli, and increased mitoses Median survival in absence of effective therapy less than 2 years Most will respond to aggressive, multiagent therapy Overall, 60% will relapse, 40% can be cured K G-lessons Prognostic factors in diffuse large cell lymphoma: International Prognostic Index factors • • • • • Age Stage LDH level Number of extranodal sites Performance score K G.-lessons Prognostic factors in diffuse large cell lymphoma: International Prognostic Index factors • • • • • Age Stage LDH level Number of extranodal sites Performance score Biologic predictors • Cytogenetics • Upregulated proteins • Microarray pattern – Follicular center cell phenotype – Activated B cell phenotype Pt.2 S.N.- Clinical presentation S.N. was a 56 y.o. male in May, 1996 when he noted the onset of fever, night sweats, and weight loss. Physical examination revealed splenomegaly and a right upper quadrant mass. Radiologic study and MRI revealed mediastinal lymph nodes and jejunal thickening. A CBC revealed a WBC of 12,000, with 50% atypical lymphocytes. A laparotomy was performed at an outside hospital, with lymph node and liver biopsies. A bone marrow study was subsequently performed at DHMC. Pt.2 S.N.- Lymph node Pt.2 S.N.- Lymph node CD3 Pt.2 S.N.- Lymph node CD3 Pt.2 S.N.- Liver biopsy Pt.2 S.N.- Peripheral blood Pt.2 S.N.- Peripheral blood Pt.2 S.N.- Bone marrow Pt.2 S.N.- Bone marrow Pt.2 S.N.- Flow cytometry Lymphoid T LN CD3 19 CD4 19 CD5/ CD20- 1 CD8 1 Lymphoid B PB <1 <1 LN PB C D19 89 94 Kappa 86 Lambda NK associated LN CD56 Myeloid PB LN Other PB CD13 C D10 97 CD14 CD34 7 1 CD15 CD41 C D20/ C D5+ 97 99 CD33 CD45 C D20/ C D23+ <1 <1 FMC 7 58 98 CD22 34 12 HLADR GP -A LN PB <1 <1 Pt.2 S.N.- CD5 Pt. S.N.- Cyclin D1 Pt. SN- Diagnosis: mantle cell lymphoma Therapy 1996 Current therapy approach Prognosis 1996 Clinical follow-up Lessons-the indolent lymphoma imitator Table X: Indolent B cell lymphomas Follicular Lymphoma (Grade I) 22% Marginal zone Lymphoma Small lymphocytic Mantle cell lymphoma/CLL Lymphoma 8 7 6 59 61 65 63 Stage III/I V Diss eminated Good to most treatments, but incurable short of transplant 72% Stage I Stage IV Stage III/IV Frequently curable Similar to Follicular lymphoma Poor response to all therapies to date 74% 51% 27% Predominant site presentation Pattern of nodal Infiltration Nodal Ex tranodal Marrow/nodal Nodal Follicular Dif f use Dif f use Benign cell Equivalent Germinal center small cleaved cell Small cleaved cell i n most cases, but can be large cell Marginal zone Lymphocyte Virgin B cell Diffuse, nodular or Òmantle zoneÓ Mantle cell Mix of small lymphocytes, plasma cells Small lymphocytes w ti h round nucleus Frequency (% all ly mphomas Age of onset median Stage at Presentation Response to Therapy 5 yr s urvival Dominant cell type Im munopheno -type Positive: CD19 Positive: CD10, Bcl2+ CD19, Bcl2 Negative: CD5- Negative: CD10, CD5 Molecular Pathogenesis t(14;18) Bcl2/JH Trisomy 3 Positive: CD19, CD5 CD23 Negative: CD10 Trisomy 12 Small cell with irregular nucleus, similar to cleaved Positive: CD19, CD5, Bcl2 Negative: CD10 t(11;14) Bcl1/JH >70% 5 yr. surv 30-49% 5 yr. surv 50-70% 5 yr. surv <30% 5 yr. surv Patient JC JC is a 22 yo male who presented to his local MD in March, 2001 with severe back spasms, initially treated with NSAIDS. He then developed increasing abdominal and left shoulder pain, fatigue, and 15 lb weight loss over the next six weeks, followed by night sweats seven days before admission to DHMC. Initial chest and abdominal X-rays at an outside hospital were negative, but a subsequent abdominal CT scan detected a retroperitoneal mass estimated at 18x11x8.5cms and a smaller soft tissue mass in the right anterior abdomen. Chest CT revealed bilateral axillary adenopathy. The abdominal wall mass was biopsied. The patient was transferred to DHMC. Physical examination here detected additional adenopathy at the angle of the jaw. Labs WBC 9300, Hgb 12.7gr., Platelets 288K, BUN 10, LDH 664, other LFT’s normal. J.C. - Abdominal wall mass biopsy J.C. abdominal wall mass-50x J.C.- Flow cytometric analysis Lymphoid T CD2 Lymphoid B C D19 95 NK associated CD56 25 Myeloid Other CD13 C D10 CD3 18 C D19/ C D10 95 CD14 CD34 CD4 <1 Kappa 15 CD15 CD41 CD5 <1 Lam bda 80 CD33 CD45 CD7 CD8 8 C D20 99 HLADR CD23 39 GP -A 98 J.C. Diagnosis: Burkitt Lymphoma Bone marrow negative for lymphoma CSF positive for Burkitt lymphoma Treatment Prognosis Current status Burkitt lymphoma-lessons 2% of all lymphomas in adults 1/3 of all lymphomas in children Increased incidence in HIV disease Very aggressive B cell lymphoma Can present as acute leukemia or with leukemic component Pathogenesis: Translocations bringing the myc cell cycle control gene/oncogene normally on chromosome 8 to sites of constitutively expressed B cell antigen receptor genes/ promoters Results in excessive myc production and constant replication T(8;14) Ig heavy chain gene T(2;8) Ig kappa light chain gene T(8;22) Ig lambda light chain gene Burkitt lymphoma In Africa, associated with Epstein-Barr virus (endemic Burkitt’s) Not so in US (non-endemic Burkitt) In US, usually presents in abdomen, often with acute abdomen/bowel obstruction Until 10 years ago, rapid fatal, with median survival <1year Now cure rates >80% in children, 40-50% in adults (less in HIV setting) Requires very aggressive, multiagent therapy Pt. O.I.- Clinical presentation O.I. was a 61 y.o. male in April, 1997 when he noted the onset of discomfort in his right groin and testicle with walking, accompanied by a small nodule in his right groin. A CT scan of the abdomen and pelvis revealed a right retroperitoneal mass extending into the pelvis. A needle biopsy of the retroperitoneal mass was performed at an outside hospital, which led to a diagnosis of undifferentiated neoplasm suspicious for large cell lymphoma. A week later, the patient was transferred to DHMC for further evaluation and treatment. In the interim period, the mass demonstrated rapid enlargement, with an LDH level rising from 1200 to 7000U. A repeat needle biopsy and aspirate were performed at DHMC for further characterization of the tumor. Sufficient cells were obtained to perform flow cytometric analysis. Material for cytogenetics was also submitted. Pt. O.I.- Needle biopsy 1 Pt. O.I.- Needle biopsy 1 Pt. O.I.- Needle bx 1 Pt. O.I.- Needle bx 1- CD20 Pt. O.I.- Needle biopsy 1- CD3 Pt. O.I.- Needle biopsy 2 Pt. O.I.- Biopsy 2-Touch imprint Pt. O.I.- Flow analysis Lymphoid T CD2 Lymphoid B C D19 95 NK associated CD56 25 Myeloid Other CD13 C D10 CD3 18 C D19/ C D10 95 CD14 CD34 CD4 <1 Kappa 15 CD15 CD41 CD5 <1 Lam bda 95 CD33 CD45 CD7 CD8 8 C D20 99 HLADR CD23 39 GP -A 98 Pt. O.I. Diagnosis: Small noncleaved lymphoma, non-Burkitt type (Burkitt lymphoma, variant type, by WHO) Therapy Prognosis Clinical outcome Pt. J.L.I. JLI was a 74 y.o. male in spring 2001 when he noted a decrease in appetite and intermittent nausea which progressed to epigastric pain. Upper GI series with small bowel followthrough and abdominal CT were non-diagnostic. Endoscopic examination was abnormal and urease breath test was positive for helicobacter pylori. Helicobacter antibacterial therapy was initiated. The patient was then referred to DHMC for follow-up endoscopy and biopsies. JLI-gastric endoscopic biopsy JLI gastric biopsy JLI-gastric biopsy JLI-gastric biopsy Kappa light chain Diagnosis: Extranodal Marginal zone lymphoma of mucosal associated lymphoid tissue (MALT) Staging Therapy Prognosis Table X: Indolent B cell lymphomas Frequency (% all ly mphomas Age of onset median Stage at Presentation Response to Therapy 5 yr survival Predominant site presentation Pattern of nodal Infiltration Benign cell Equivalent Dominant cell type Im munopheno -type Molecular Pathogenesis Follicular Lymphoma (Grade I) 22% Marginal zone Lymphoma Small lymphocytic lymphoma/CLL 8 7 59 61 65 Stage III/I V Diss eminated Good to most treatments, but incurable short of transplant 72% Stage I Stage IV Frequently curable Similar to Follicular lymphoma 74% 51% Nodal Ex tranodal Marrow/nodal Follicular Dif f use Dif f use Germinal center small cleaved cell Small cleaved cell i n most cases, but can be large cell Positive: CD19 CD10, Bcl2+ Negative: CD5- Marginal zone Lymphocyte Virgin B cell Mix of small lymphocytes, plasma cells t(14;18) Bcl2/JH t(11;18), Trisomy 3 Small lymphocytes w ith round nucleus Positive: CD19, CD5 CD23 Negative: CD10 Trisomy 12 Positive: CD19, Bcl2 Negative: CD10, CD5 JLI-followup Gastric ultrasound was performed to assess the depth of infiltration and status of perigastric lymph nodes Completion of helicobacter antibiosis led to recurrent pain A second course of antibiotic therapy was added Treatment plan: Repeat biopsies and helicobacter studies were performed q3mos for next year Patient improved with disappearance of pain and increased appetite/weight gain Biopsies continued to show foci of persistent clonal disease for next few months, then negative Extranodal lymphomas of MALT type Lymphomas of the Mucosal Associated immune system-extranodal Indolent lymphomas that break all the rules Mix of cell types Benign germinal centers can be seen intermixed with malignant marginal cells Location associated therapy Excellent long term survival, though can have very late recurrences Can however undergo further mutations, with a small subset progressing to large cell lymphoma Intriguing interaction with helicobacter infection in gastric lymphoma MALT Lymphoma-pathogenetic pathways >70% 5 yr. surv 30-49% 5 yr. surv 50-70% 5 yr. surv <30% 5 yr. surv The End !