Future Directions in ALK Negative Anaplastic Large Cell Lymphoma
Andrs Quesada Fellow, Hematopathology, MDACC Updates in Hematopathology: 3rd Annual Meeting for Alumni and Friends of the Department of Hematopathology Clinical History 33 year old man
Right cervical and axillary lymphadenopathy Night sweats and fever Duration: Several months PMH: Sleep apnea Family history: No significant family history Right axillary lymph node excisional biopsy 100x 100x 400x 400x 400x 1000x 1000x CD3 CD4 CD43 CD15 CD30 ALK1 Ki67 CD 43 20x CD43 Positive Negative CD15 (subset) CD1a ALK CD30 (diffuse, strong) CD3 BCL2 CD43 CD4 BCL6 Ki67 (~90%) CD5 PAX5 CD7 Granzyme B CD10 EMA CD20 S100 CD45 CAM5.2 CD68 Final Diagnosis Right axillary lymph node, excisional biopsy:
ALK NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA 1. Right axillary lymph node (NAC , 8/25/2015): The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 2. Right axillary lymph node and upper limb (SAC , 9/25/2015): Per submitted surgical pathology report, sections of the lymph node reportedly showed sheets of large neoplastic lymphocytes with areas of geographic necrosis.Lymph node architecture was not appreciated.The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm.Hallmark cells were seen focally. Mitotic figures were conspicuous. We also reviewed immunohistochemical stains performed elsewhere: CD1a:Negative CD3:Negative in large cells CD4:Negative in large cells CD5:Negative in large cells CD7:Negative in large cells CD10:Negative in large cells CD15:Positive in subset of large cells CD20:Negative in large cells CD30:Positive, diffuse, strong in most cells in the infiltrate CD43:Positive in ~50% of large cells CD45:Negative in large cells CD68:Negative in large cells ALK:Negative in large cells BCL2:Negative in large cells BCL6:Negative in large cells PAX5:Negative in large cells Ki67:~90% of cells in the infiltrate are positive Granzyme B:Negative in large cells; scattered small cells are positive EMA:Rare large cells are faintly positive S100: Loose clusters of dendritic cells are positive CAM5.2:Negative According to outside pathology report, additional studies were performed at UCLAand reportedly showed the lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few); negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) performed at Neogenomics showed the presence of monoclonal T-cell receptor gene rearrangements. It was negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. The findings were reported to be diagnostic of ALK negative anaplastic large cell lymphoma. Please note that specimen SAC is not received for review. 3. Bone marrow, (FAC , 10/15/2015): A complete blood count and peripheral blood smear shows white blood cell count 9.7, hemoglobin 10.7, and platelets The red blood cells are normocytic and normochromic with slight polychromasia.The white blood cells are adequate in number and morphology.There is no left-shift, dysplasia, circulating blasts or lymphoma cells seen. The platelets are normal in number with unremarkable morphology. The bone marrow aspirate smear demonstrates trilineage hematopoiesis. There is a sequential maturation in the erythroid and granulocytic lineages. The erythrocytes show some dysplastic features including nuclear budding and nuclear to cytoplasmic asynchrony. There is no increase in blasts.No obvious lymphoma cells are seen.Megakaryocytes are present and slightly increased in number.An iron stain shows decreased iron storage.No ring sideroblasts are seen. The bone marrow bone marrow and clot demonstrate 70% cellular marrow.Trilineage hematopoiesis is evident.Megakaryocytes are present and slightly increased in number (up to 9 per high-power field).Occasional hypolobated forms are seen.No lymphoid aggregates or sheets of lymphoid cells are seen. On submitted immunohistochemical stains performed on the bone marrow biopsy, CD3 and CD20 highlight scattered small and mature appearing T and B lymphocytes, respectively.The CD3-positive lymphocytes outnumber the CD20-positive lymphocytes. CD30 fails to demonstrate the presence of large cells. Per report, flow cytometric analysis of the bone marrow showed no evidence of a monoclonal B-cell population, but showed a mildly inverted CD4/CD8 ratio (0.8). Per report, cytogenetics performed at Neogenomics, showed a normal male karyotype (46,XY[20]). Per report, PCR performed on the bone marrow was positive for a monoclonal T-cell receptor gene rearrangement. In summary, we agree with the diagnosis of ALK negative anaplastic large cell lymphoma rendered on the right axillary lymph node. The bone marrow is not involved morphologically, but there is a T-cell gene rearrangement reportedly present by PCR. Although this is may be suggestive of involvement by ALCL, it is alone inconclusive to render a diagnosis of bone marrow involvement especially in the complete absence of CD30 positive large cells. RM:AQ/kma 12/3/2015 4:18 PM Comment UCLA additional studies: Polymerase chain reaction (PCR)
Lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few) Negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) Monoclonal T-cell receptor gene rearrangements. Negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. 1. Right axillary lymph node (NAC , 8/25/2015): The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 2. Right axillary lymph node and upper limb (SAC , 9/25/2015): Per submitted surgical pathology report, sections of the lymph node reportedly showed sheets of large neoplastic lymphocytes with areas of geographic necrosis.Lymph node architecture was not appreciated.The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm.Hallmark cells were seen focally. Mitotic figures were conspicuous. We also reviewed immunohistochemical stains performed elsewhere: CD1a:Negative CD3:Negative in large cells CD4:Negative in large cells CD5:Negative in large cells CD7:Negative in large cells CD10:Negative in large cells CD15:Positive in subset of large cells CD20:Negative in large cells CD30:Positive, diffuse, strong in most cells in the infiltrate CD43:Positive in ~50% of large cells CD45:Negative in large cells CD68:Negative in large cells ALK:Negative in large cells BCL2:Negative in large cells BCL6:Negative in large cells PAX5:Negative in large cells Ki67:~90% of cells in the infiltrate are positive Granzyme B:Negative in large cells; scattered small cells are positive EMA:Rare large cells are faintly positive S100: Loose clusters of dendritic cells are positive CAM5.2:Negative According to outside pathology report, additional studies were performed at UCLAand reportedly showed the lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few); negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) performed at Neogenomics showed the presence of monoclonal T-cell receptor gene rearrangements. It was negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. The findings were reported to be diagnostic of ALK negative anaplastic large cell lymphoma. Please note that specimen SAC is not received for review. 3. Bone marrow, (FAC , 10/15/2015): A complete blood count and peripheral blood smear shows white blood cell count 9.7, hemoglobin 10.7, and platelets The red blood cells are normocytic and normochromic with slight polychromasia.The white blood cells are adequate in number and morphology.There is no left-shift, dysplasia, circulating blasts or lymphoma cells seen. The platelets are normal in number with unremarkable morphology. The bone marrow aspirate smear demonstrates trilineage hematopoiesis. There is a sequential maturation in the erythroid and granulocytic lineages. The erythrocytes show some dysplastic features including nuclear budding and nuclear to cytoplasmic asynchrony. There is no increase in blasts.No obvious lymphoma cells are seen.Megakaryocytes are present and slightly increased in number.An iron stain shows decreased iron storage.No ring sideroblasts are seen. The bone marrow bone marrow and clot demonstrate 70% cellular marrow.Trilineage hematopoiesis is evident.Megakaryocytes are present and slightly increased in number (up to 9 per high-power field).Occasional hypolobated forms are seen.No lymphoid aggregates or sheets of lymphoid cells are seen. On submitted immunohistochemical stains performed on the bone marrow biopsy, CD3 and CD20 highlight scattered small and mature appearing T and B lymphocytes, respectively.The CD3-positive lymphocytes outnumber the CD20-positive lymphocytes. CD30 fails to demonstrate the presence of large cells. Per report, flow cytometric analysis of the bone marrow showed no evidence of a monoclonal B-cell population, but showed a mildly inverted CD4/CD8 ratio (0.8). Per report, cytogenetics performed at Neogenomics, showed a normal male karyotype (46,XY[20]). Per report, PCR performed on the bone marrow was positive for a monoclonal T-cell receptor gene rearrangement. In summary, we agree with the diagnosis of ALK negative anaplastic large cell lymphoma rendered on the right axillary lymph node. The bone marrow is not involved morphologically, but there is a T-cell gene rearrangement reportedly present by PCR. Although this is may be suggestive of involvement by ALCL, it is alone inconclusive to render a diagnosis of bone marrow involvement especially in the complete absence of CD30 positive large cells. RM:AQ/kma 12/3/2015 4:18 PM Comment Sheets of large neoplastic lymphocytes with areas of geographic necrosis. Lymph node architecture was not appreciated. The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm. Hallmark cells were seen focally. Mitotic figures were conspicuous. 1. Right axillary lymph node (NAC , 8/25/2015): The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 2. Right axillary lymph node and upper limb (SAC , 9/25/2015): Per submitted surgical pathology report, sections of the lymph node reportedly showed sheets of large neoplastic lymphocytes with areas of geographic necrosis.Lymph node architecture was not appreciated.The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm.Hallmark cells were seen focally. Mitotic figures were conspicuous. We also reviewed immunohistochemical stains performed elsewhere: CD1a:Negative CD3:Negative in large cells CD4:Negative in large cells CD5:Negative in large cells CD7:Negative in large cells CD10:Negative in large cells CD15:Positive in subset of large cells CD20:Negative in large cells CD30:Positive, diffuse, strong in most cells in the infiltrate CD43:Positive in ~50% of large cells CD45:Negative in large cells CD68:Negative in large cells ALK:Negative in large cells BCL2:Negative in large cells BCL6:Negative in large cells PAX5:Negative in large cells Ki67:~90% of cells in the infiltrate are positive Granzyme B:Negative in large cells; scattered small cells are positive EMA:Rare large cells are faintly positive S100: Loose clusters of dendritic cells are positive CAM5.2:Negative According to outside pathology report, additional studies were performed at UCLAand reportedly showed the lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few); negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) performed at Neogenomics showed the presence of monoclonal T-cell receptor gene rearrangements. It was negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. The findings were reported to be diagnostic of ALK negative anaplastic large cell lymphoma. Please note that specimen SAC is not received for review. 3. Bone marrow, (FAC , 10/15/2015): A complete blood count and peripheral blood smear shows white blood cell count 9.7, hemoglobin 10.7, and platelets The red blood cells are normocytic and normochromic with slight polychromasia.The white blood cells are adequate in number and morphology.There is no left-shift, dysplasia, circulating blasts or lymphoma cells seen. The platelets are normal in number with unremarkable morphology. The bone marrow aspirate smear demonstrates trilineage hematopoiesis. There is a sequential maturation in the erythroid and granulocytic lineages. The erythrocytes show some dysplastic features including nuclear budding and nuclear to cytoplasmic asynchrony. There is no increase in blasts.No obvious lymphoma cells are seen.Megakaryocytes are present and slightly increased in number.An iron stain shows decreased iron storage.No ring sideroblasts are seen. The bone marrow bone marrow and clot demonstrate 70% cellular marrow.Trilineage hematopoiesis is evident.Megakaryocytes are present and slightly increased in number (up to 9 per high-power field).Occasional hypolobated forms are seen.No lymphoid aggregates or sheets of lymphoid cells are seen. On submitted immunohistochemical stains performed on the bone marrow biopsy, CD3 and CD20 highlight scattered small and mature appearing T and B lymphocytes, respectively.The CD3-positive lymphocytes outnumber the CD20-positive lymphocytes. CD30 fails to demonstrate the presence of large cells. Per report, flow cytometric analysis of the bone marrow showed no evidence of a monoclonal B-cell population, but showed a mildly inverted CD4/CD8 ratio (0.8). Per report, cytogenetics performed at Neogenomics, showed a normal male karyotype (46,XY[20]). Per report, PCR performed on the bone marrow was positive for a monoclonal T-cell receptor gene rearrangement. In summary, we agree with the diagnosis of ALK negative anaplastic large cell lymphoma rendered on the right axillary lymph node. The bone marrow is not involved morphologically, but there is a T-cell gene rearrangement reportedly present by PCR. Although this is may be suggestive of involvement by ALCL, it is alone inconclusive to render a diagnosis of bone marrow involvement especially in the complete absence of CD30 positive large cells. RM:AQ/kma 12/3/2015 4:18 PM Comment 1. Right axillary lymph node (NAC15-7058, 8/25/2015):
The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 1. Right axillary lymph node (NAC , 8/25/2015): The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 2. Right axillary lymph node and upper limb (SAC , 9/25/2015): Per submitted surgical pathology report, sections of the lymph node reportedly showed sheets of large neoplastic lymphocytes with areas of geographic necrosis.Lymph node architecture was not appreciated.The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm.Hallmark cells were seen focally. Mitotic figures were conspicuous. We also reviewed immunohistochemical stains performed elsewhere: CD1a:Negative CD3:Negative in large cells CD4:Negative in large cells CD5:Negative in large cells CD7:Negative in large cells CD10:Negative in large cells CD15:Positive in subset of large cells CD20:Negative in large cells CD30:Positive, diffuse, strong in most cells in the infiltrate CD43:Positive in ~50% of large cells CD45:Negative in large cells CD68:Negative in large cells ALK:Negative in large cells BCL2:Negative in large cells BCL6:Negative in large cells PAX5:Negative in large cells Ki67:~90% of cells in the infiltrate are positive Granzyme B:Negative in large cells; scattered small cells are positive EMA:Rare large cells are faintly positive S100: Loose clusters of dendritic cells are positive CAM5.2:Negative According to outside pathology report, additional studies were performed at UCLAand reportedly showed the lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few); negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) performed at Neogenomics showed the presence of monoclonal T-cell receptor gene rearrangements. It was negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. The findings were reported to be diagnostic of ALK negative anaplastic large cell lymphoma. Please note that specimen SAC is not received for review. 3. Bone marrow, (FAC , 10/15/2015): A complete blood count and peripheral blood smear shows white blood cell count 9.7, hemoglobin 10.7, and platelets The red blood cells are normocytic and normochromic with slight polychromasia.The white blood cells are adequate in number and morphology.There is no left-shift, dysplasia, circulating blasts or lymphoma cells seen. The platelets are normal in number with unremarkable morphology. The bone marrow aspirate smear demonstrates trilineage hematopoiesis. There is a sequential maturation in the erythroid and granulocytic lineages. The erythrocytes show some dysplastic features including nuclear budding and nuclear to cytoplasmic asynchrony. There is no increase in blasts.No obvious lymphoma cells are seen.Megakaryocytes are present and slightly increased in number.An iron stain shows decreased iron storage.No ring sideroblasts are seen. The bone marrow bone marrow and clot demonstrate 70% cellular marrow.Trilineage hematopoiesis is evident.Megakaryocytes are present and slightly increased in number (up to 9 per high-power field).Occasional hypolobated forms are seen.No lymphoid aggregates or sheets of lymphoid cells are seen. On submitted immunohistochemical stains performed on the bone marrow biopsy, CD3 and CD20 highlight scattered small and mature appearing T and B lymphocytes, respectively.The CD3-positive lymphocytes outnumber the CD20-positive lymphocytes. CD30 fails to demonstrate the presence of large cells. Per report, flow cytometric analysis of the bone marrow showed no evidence of a monoclonal B-cell population, but showed a mildly inverted CD4/CD8 ratio (0.8). Per report, cytogenetics performed at Neogenomics, showed a normal male karyotype (46,XY[20]). Per report, PCR performed on the bone marrow was positive for a monoclonal T-cell receptor gene rearrangement. In summary, we agree with the diagnosis of ALK negative anaplastic large cell lymphoma rendered on the right axillary lymph node. The bone marrow is not involved morphologically, but there is a T-cell gene rearrangement reportedly present by PCR. Although this is may be suggestive of involvement by ALCL, it is alone inconclusive to render a diagnosis of bone marrow involvement especially in the complete absence of CD30 positive large cells. RM:AQ/kma 12/3/2015 4:18 PM Diagnosis Bone marrow, left iliac, biopsy, clot sections, aspiration and peripheral blood: Normocellular bone marrow with trilineage hematopoiesis and sequential maturation No morphologic support for involvement by lymphoma 1. Right axillary lymph node (NAC , 8/25/2015): The cell block shows blood clot with admixed lymphoid tissue. Within the lymphoid tissue are occasional large atypical cells. Direct smears show lymphoid tissue with scattered large highly atypical cells. On submitted immunohistochemical stains, CD3 shows scattered predominantly mature appearing T lymphocytes. Pancytokeratin and CAM 5.2 are negative. 2. Right axillary lymph node and upper limb (SAC , 9/25/2015): Per submitted surgical pathology report, sections of the lymph node reportedly showed sheets of large neoplastic lymphocytes with areas of geographic necrosis.Lymph node architecture was not appreciated.The neoplastic lymphocytes displayed large pleomorphic nuclei, finely dispersed chromatin, prominent nucleoli and moderate amount of cytoplasm.Hallmark cells were seen focally. Mitotic figures were conspicuous. We also reviewed immunohistochemical stains performed elsewhere: CD1a:Negative CD3:Negative in large cells CD4:Negative in large cells CD5:Negative in large cells CD7:Negative in large cells CD10:Negative in large cells CD15:Positive in subset of large cells CD20:Negative in large cells CD30:Positive, diffuse, strong in most cells in the infiltrate CD43:Positive in ~50% of large cells CD45:Negative in large cells CD68:Negative in large cells ALK:Negative in large cells BCL2:Negative in large cells BCL6:Negative in large cells PAX5:Negative in large cells Ki67:~90% of cells in the infiltrate are positive Granzyme B:Negative in large cells; scattered small cells are positive EMA:Rare large cells are faintly positive S100: Loose clusters of dendritic cells are positive CAM5.2:Negative According to outside pathology report, additional studies were performed at UCLAand reportedly showed the lymphoma cells positive for CD2 (occasional low), and TIA-1 (occasional few); negative for CD8, TCR gamma/delta, TCR F1, TdT, PD1, and EBER (extremely rare positive small cells). Polymerase chain reaction (PCR) performed at Neogenomics showed the presence of monoclonal T-cell receptor gene rearrangements. It was negative for B-cell gene rearrangements. Per submitted pathology report, flow cytometric analysis of the right axillary lymph node showed no evidence of a lymphoproliferative disorder. The findings were reported to be diagnostic of ALK negative anaplastic large cell lymphoma. Please note that specimen SAC is not received for review. 3. Bone marrow, (FAC , 10/15/2015): A complete blood count and peripheral blood smear shows white blood cell count 9.7, hemoglobin 10.7, and platelets The red blood cells are normocytic and normochromic with slight polychromasia.The white blood cells are adequate in number and morphology.There is no left-shift, dysplasia, circulating blasts or lymphoma cells seen. The platelets are normal in number with unremarkable morphology. The bone marrow aspirate smear demonstrates trilineage hematopoiesis. There is a sequential maturation in the erythroid and granulocytic lineages. The erythrocytes show some dysplastic features including nuclear budding and nuclear to cytoplasmic asynchrony. There is no increase in blasts.No obvious lymphoma cells are seen.Megakaryocytes are present and slightly increased in number.An iron stain shows decreased iron storage.No ring sideroblasts are seen. The bone marrow bone marrow and clot demonstrate 70% cellular marrow.Trilineage hematopoiesis is evident.Megakaryocytes are present and slightly increased in number (up to 9 per high-power field).Occasional hypolobated forms are seen.No lymphoid aggregates or sheets of lymphoid cells are seen. On submitted immunohistochemical stains performed on the bone marrow biopsy, CD3 and CD20 highlight scattered small and mature appearing T and B lymphocytes, respectively.The CD3-positive lymphocytes outnumber the CD20-positive lymphocytes. CD30 fails to demonstrate the presence of large cells. Per report, flow cytometric analysis of the bone marrow showed no evidence of a monoclonal B-cell population, but showed a mildly inverted CD4/CD8 ratio (0.8). Per report, cytogenetics performed at Neogenomics, showed a normal male karyotype (46,XY[20]). Per report, PCR performed on the bone marrow was positive for a monoclonal T-cell receptor gene rearrangement. In summary, we agree with the diagnosis of ALK negative anaplastic large cell lymphoma rendered on the right axillary lymph node. The bone marrow is not involved morphologically, but there is a T-cell gene rearrangement reportedly present by PCR. Although this is may be suggestive of involvement by ALCL, it is alone inconclusive to render a diagnosis of bone marrow involvement especially in the complete absence of CD30 positive large cells. RM:AQ/kma 12/3/2015 4:18 PM PET Imaging Multiple sites of disease above and below the diaphragm
Diffuse hypermetabolic activity in the axial skeleton, pelvis and humerus Treatment CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) x 3 cycles with good response Plan: CHOP plus Etoposide x 3 additional cycles followed by autologous stem cell transplant WHO Definition 2008 WHO provisional entity CD30+ T-cell neoplasm
Not reproducibly distinguishable on morphologic grounds from ALK+ ALCL Lacks ALK protein Blood 1999 Apr 15;93(8): Immunohistochemistry and FISH
73 ALK- ALCL 32 ALK+ ALCL ALK- ALCL (n=73) 22 (30%) had DUSP22 rearrangements 6 (8%) had TP63 rearrangements Events were mutually exclusive Not seen in any ALK+ ALCL 45 (62%) lacked both, termed triple negative Survival Analysis by ALK Status
ALK+ ALCL N=29 5 yr OS: 85% ALK- ALCL N=67 5 yr OS: 52% Figure 1. Outcomes in patients with ALCL based on genetic subtype. (A) OS rates in patients with ALCL, stratified by ALK status only (ALK positive, N = 29; ALK negative, N = 67). Survival Analysis ALK- ALCL by Genetic Subtype
5 yr OS: 85% DUSP22 rearranged N=21 5 yr OS: 90% TP63 rearranged N=6 5 yr OS: 17% Triple Negative ALCL N=40 5 yr OS: 42% Figure 1. Outcomes in patients with ALCL based on genetic subtype (B) OS rates in patients with ALCL, stratified by rearrangements of ALK (N = 29), DUSP22 (N = 21), and TP63 (N = 6). -/-/-, triple-negative cases lacking all 3 rearrangements (N = 40). Survival Analysis Only non-transplanted cases DUSP22 rearranged
ALK+, N=21 DUSP22, N=15 TP63, N=5 -/-/-, N=34 DUSP22 rearranged 5 yr OS: 87% Figure 1. Outcomes in patients with ALCL based on genetic subtype. (C) OS rates in patients with ALCL who did not undergo transplantation, stratified by rearrangements of ALK (N = 21), DUSP22 (N = 15), and TP63 (N = 5). -/-/-, N = 34. Author Recommendations
All ALK negative ALCL undergo FISH testing for rearrangements involving DUSP22 and TP63 Include in the pathology report if present Mention prognostic implication IHC for p63 and cytotoxic markers are not specific and cant substitute for FISH DUSP22rearrangements in pcALCL have an overall frequency of approximately 30% Take Home Points ALK(-) ALCL
No longer a provisional entity More heterogeneous than once thought Future risk stratification may include studies to determine DUSP22 and TP63 status Will ALK(-) ALCL be further sub-classified by mutational status? Thank You! Thank You!