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% December 2018 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions December 2018 Case Authors Michelle Don, MD (Hematopathology fellow), Jean Lopategui, MD (Attending) and Sumire Kitahara, MD (Attending) Subject Hematopathology Clinical History This case is that of a 78 year old male with a history of angioimmunoblastic T-cell lymphoma (AITL) diagnosed on lymph node biopsy, status 5 years post chemotherapy. He had disease recurrences at 4 years and 5 years after diagnosis.
Elijah Patel Member
access_time 4 minutes ago
% December 2018 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions December 2018 Case Authors Michelle Don, MD (Hematopathology fellow), Jean Lopategui, MD (Attending) and Sumire Kitahara, MD (Attending) Subject Hematopathology Clinical History This case is that of a 78 year old male with a history of angioimmunoblastic T-cell lymphoma (AITL) diagnosed on lymph node biopsy, status 5 years post chemotherapy. He had disease recurrences at 4 years and 5 years after diagnosis.
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Madison Singh 4 minutes ago
Past medical history was also significant for history of treated tuberculosis several decades ago. H...
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Past medical history was also significant for history of treated tuberculosis several decades ago. He presented again, in the fifth year after diagnosis, with recurrent fevers and pulmonary effusions and was admitted to the hospital. Upon admission, he was noted to have pancytopenia and a bone marrow examination was performed.
Madison Singh Member
access_time 6 minutes ago
Past medical history was also significant for history of treated tuberculosis several decades ago. He presented again, in the fifth year after diagnosis, with recurrent fevers and pulmonary effusions and was admitted to the hospital. Upon admission, he was noted to have pancytopenia and a bone marrow examination was performed.
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Alexander Wang 2 minutes ago
Immunohistochemistry And Special Studies Study Test Result CD3 Highlights T-cells in granuloma...
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Immunohistochemistry And Special Studies Study Test Result CD3 Highlights T-cells in granulomas CD20 Negative CD10 Negative in granulomas CD4 Highlights T-cells and monocytes PD1 Minimal immunoreactivity in granulomas CXCL13 Nonspecific staining EBER-ISH Negative AFB No acid fast bacilli identified GMS No fungal forms identified Auramine O/Rhodamine Negative Molecular Studies PCR for mycobacterium (aspirate clot and core biopsy; performed at the Centers for Disease Control, Atlanta, GA): Negative Next generation sequencing (NGS) DNMT3A p.PHE608Serfs*43, VAF 6.77% Diagnosis Consistent with persistent/recurrent angioimmunoblastic T-cell lymphoma Discussion This case demonstrates the utility of abnormalities found by next generation sequencing (NGS) in making a diagnosis of angioimmunoblastic T-cell lymphoma (AITL) presenting as bone marrow granulomas in a patient with remote history of tuberculosis (TB). Patients with AITL are immunodeficient due to immune dysregulation caused by the lymphoma's interaction with its microenvironment. This case posed a diagnostic dilemma in determining whether the bone marrow granulomas were secondary to TB recurrence or a granulomatous manifestation of persistent/recurrent lymphoma.
Joseph Kim Member
access_time 12 minutes ago
Immunohistochemistry And Special Studies Study Test Result CD3 Highlights T-cells in granulomas CD20 Negative CD10 Negative in granulomas CD4 Highlights T-cells and monocytes PD1 Minimal immunoreactivity in granulomas CXCL13 Nonspecific staining EBER-ISH Negative AFB No acid fast bacilli identified GMS No fungal forms identified Auramine O/Rhodamine Negative Molecular Studies PCR for mycobacterium (aspirate clot and core biopsy; performed at the Centers for Disease Control, Atlanta, GA): Negative Next generation sequencing (NGS) DNMT3A p.PHE608Serfs*43, VAF 6.77% Diagnosis Consistent with persistent/recurrent angioimmunoblastic T-cell lymphoma Discussion This case demonstrates the utility of abnormalities found by next generation sequencing (NGS) in making a diagnosis of angioimmunoblastic T-cell lymphoma (AITL) presenting as bone marrow granulomas in a patient with remote history of tuberculosis (TB). Patients with AITL are immunodeficient due to immune dysregulation caused by the lymphoma's interaction with its microenvironment. This case posed a diagnostic dilemma in determining whether the bone marrow granulomas were secondary to TB recurrence or a granulomatous manifestation of persistent/recurrent lymphoma.
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Luna Park 7 minutes ago
We briefly discuss below lymphoma pathogenesis, clinical and histologic features, and the diagnostic...
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Isabella Johnson 12 minutes ago
It is a neoplasm of follicular helper T (TFH) cells which release factors (such as CXCL13, IL21, IL1...
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We briefly discuss below lymphoma pathogenesis, clinical and histologic features, and the diagnostic approach taken in this case. AITL is a rare subtype of peripheral T-cell lymphoma, accounting for 1-2% of all non-Hodgkin lymphoma, with an overall poor prognosis and a median survival of less than 3 years.
Andrew Wilson Member
access_time 20 minutes ago
We briefly discuss below lymphoma pathogenesis, clinical and histologic features, and the diagnostic approach taken in this case. AITL is a rare subtype of peripheral T-cell lymphoma, accounting for 1-2% of all non-Hodgkin lymphoma, with an overall poor prognosis and a median survival of less than 3 years.
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Alexander Wang 19 minutes ago
It is a neoplasm of follicular helper T (TFH) cells which release factors (such as CXCL13, IL21, IL1...
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Liam Wilson 11 minutes ago
Immunodeficiency occurs secondary to the neoplastic process. Reactivation of EBV frequently occurs (...
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It is a neoplasm of follicular helper T (TFH) cells which release factors (such as CXCL13, IL21, IL10, TGF-beta, VEGF) that contribute to expansion of TFH cells, B-cells, production of IL-6, follicular dendritic cells and vascular proliferation (figure 1). As a consequence, patients present with any combination of symptoms including generalized lymphadenopathy, hepatosplenomegaly, B-symptoms (fever, weight loss, night sweats), polyclonal hypergammaglobulinemia, skin rash, pruritus, pleural effusion, arthritis, ascites, hemolytic anemia, circulating immune complexes and cold agglutinins.
Harper Kim Member
access_time 15 minutes ago
It is a neoplasm of follicular helper T (TFH) cells which release factors (such as CXCL13, IL21, IL10, TGF-beta, VEGF) that contribute to expansion of TFH cells, B-cells, production of IL-6, follicular dendritic cells and vascular proliferation (figure 1). As a consequence, patients present with any combination of symptoms including generalized lymphadenopathy, hepatosplenomegaly, B-symptoms (fever, weight loss, night sweats), polyclonal hypergammaglobulinemia, skin rash, pruritus, pleural effusion, arthritis, ascites, hemolytic anemia, circulating immune complexes and cold agglutinins.
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Immunodeficiency occurs secondary to the neoplastic process. Reactivation of EBV frequently occurs (75%) in the context of a dysregulated immune system. Microscopically, AITL can cause partial or total effacement of the lymph node architecture with a neoplastic proliferation of TFH cells within a mixed inflammatory background (reactive lymphocytes, histiocytes, plasma cells and eosinophils), proliferation of high endothelial vessels, and expanded follicular dendritic meshworks.
Thomas Anderson Member
access_time 12 minutes ago
Immunodeficiency occurs secondary to the neoplastic process. Reactivation of EBV frequently occurs (75%) in the context of a dysregulated immune system. Microscopically, AITL can cause partial or total effacement of the lymph node architecture with a neoplastic proliferation of TFH cells within a mixed inflammatory background (reactive lymphocytes, histiocytes, plasma cells and eosinophils), proliferation of high endothelial vessels, and expanded follicular dendritic meshworks.
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Isabella Johnson 1 minutes ago
The lymphoma cells are small to medium in size with clear to pale cytoplasm, distinct cell membranes...
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Mason Rodriguez 7 minutes ago
Pan-T-cell antigen expression is usually maintained. They are often arranged in clusters, surrounded...
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The lymphoma cells are small to medium in size with clear to pale cytoplasm, distinct cell membranes, and without cytological atypia. Some cases may exhibit an infiltrate of reactive epithelioid histiocytes which can mimic a granulomatous reaction. The lymphoma cells demonstrate an immunophenotype of TFH cells, expressing CD4, CD10, CXCL13, ICOS, BCL6 and PD1.
James Smith Moderator
access_time 7 minutes ago
The lymphoma cells are small to medium in size with clear to pale cytoplasm, distinct cell membranes, and without cytological atypia. Some cases may exhibit an infiltrate of reactive epithelioid histiocytes which can mimic a granulomatous reaction. The lymphoma cells demonstrate an immunophenotype of TFH cells, expressing CD4, CD10, CXCL13, ICOS, BCL6 and PD1.
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Mason Rodriguez 6 minutes ago
Pan-T-cell antigen expression is usually maintained. They are often arranged in clusters, surrounded...
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Pan-T-cell antigen expression is usually maintained. They are often arranged in clusters, surrounded by dendritic processes highlighted by CD21 stain.
Liam Wilson Member
access_time 32 minutes ago
Pan-T-cell antigen expression is usually maintained. They are often arranged in clusters, surrounded by dendritic processes highlighted by CD21 stain.
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Liam Wilson 5 minutes ago
Most cases are associated with EBV-infected B-cells. Positive T-cell receptor gene rearrangement stu...
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Oliver Taylor 2 minutes ago
Recent studies utilizing next generation sequencing have identified recurrent mutations that help to...
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Most cases are associated with EBV-infected B-cells. Positive T-cell receptor gene rearrangement studies are seen in 75-90% of cases of AITL.
Alexander Wang Member
access_time 27 minutes ago
Most cases are associated with EBV-infected B-cells. Positive T-cell receptor gene rearrangement studies are seen in 75-90% of cases of AITL.
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Recent studies utilizing next generation sequencing have identified recurrent mutations that help to unify AITL and other follicular T-cell lymphomas. Common mutations seen in AITL include RHOA (60-70%), TET2 (50- 80%), IDH2 (20-30%), and DNMT3A (20-30%).
Natalie Lopez Member
access_time 30 minutes ago
Recent studies utilizing next generation sequencing have identified recurrent mutations that help to unify AITL and other follicular T-cell lymphomas. Common mutations seen in AITL include RHOA (60-70%), TET2 (50- 80%), IDH2 (20-30%), and DNMT3A (20-30%).
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Lucas Martinez 10 minutes ago
Frequent mutations in epigenetic modifiers (TET2, IDH2, DNMT3A) suggest that aberrant DNA methylatio...
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Charlotte Lee 8 minutes ago
There is speculation as to whether AITL arises from a common progenitor as myeloid malignancies. In ...
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Frequent mutations in epigenetic modifiers (TET2, IDH2, DNMT3A) suggest that aberrant DNA methylation contributes to AITL pathogenesis. Additionally, since both IDH2 and TET2 are associated with promoter hypermethylation, there is strong consideration for utilizing hypomehtylating agents as well as IDH2 inhibitors as targeted therapy of AITL to improve outcome.
Sophie Martin Member
access_time 11 minutes ago
Frequent mutations in epigenetic modifiers (TET2, IDH2, DNMT3A) suggest that aberrant DNA methylation contributes to AITL pathogenesis. Additionally, since both IDH2 and TET2 are associated with promoter hypermethylation, there is strong consideration for utilizing hypomehtylating agents as well as IDH2 inhibitors as targeted therapy of AITL to improve outcome.
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There is speculation as to whether AITL arises from a common progenitor as myeloid malignancies. In this case presenting a diagnostic dilemma due to bone marrow presentation of granulomatous infiltrates in a patient with history of recurrent AITL and TB, we utilized various ancillary tests to exclude TB and rule in AITL.
Madison Singh Member
access_time 48 minutes ago
There is speculation as to whether AITL arises from a common progenitor as myeloid malignancies. In this case presenting a diagnostic dilemma due to bone marrow presentation of granulomatous infiltrates in a patient with history of recurrent AITL and TB, we utilized various ancillary tests to exclude TB and rule in AITL.
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Julia Zhang 43 minutes ago
AFB stains were negative for acid fast bacilli; Auramine O/Rhodamine B fluorescent stains were incon...
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AFB stains were negative for acid fast bacilli; Auramine O/Rhodamine B fluorescent stains were inconclusive; and polymerase chain reaction testing for mycobacterium was negative. Immunohistochemistry was non-contributory in establishing a diagnosis of AITL due to lack of significant staining for PD1 and CXCL13.
Luna Park Member
access_time 13 minutes ago
AFB stains were negative for acid fast bacilli; Auramine O/Rhodamine B fluorescent stains were inconclusive; and polymerase chain reaction testing for mycobacterium was negative. Immunohistochemistry was non-contributory in establishing a diagnosis of AITL due to lack of significant staining for PD1 and CXCL13.
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T-cell receptor gene rearrangement studies were negative, though the aspirate was scanty and likely unrepresentative. NGS testing showed a DNMT3A mutation (frameshift mutation; p.PHE608Serfs*43). DNMT3A mutations are not specific, commonly seen in myeloid malignancies, and notably in age-related clonal hematopoiesis.
Scarlett Brown Member
access_time 28 minutes ago
T-cell receptor gene rearrangement studies were negative, though the aspirate was scanty and likely unrepresentative. NGS testing showed a DNMT3A mutation (frameshift mutation; p.PHE608Serfs*43). DNMT3A mutations are not specific, commonly seen in myeloid malignancies, and notably in age-related clonal hematopoiesis.
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Charlotte Lee 18 minutes ago
Additionally, in the setting of AITL, it has been shown that DNMT3A mutations occur concurrently wit...
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Victoria Lopez 4 minutes ago
References 1. Lunning M.A., Vose J.L. Angioimmunoblastic T-cell lymphoma: The many-faced lymphoma....
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Additionally, in the setting of AITL, it has been shown that DNMT3A mutations occur concurrently with TET2 mutations. Despite limitations in sensitivities and specificities of the testing which we performed, in the current setting with a relatively high pretest probability of recurrent AITL, this positive NGS result with a negative mycobacterium workup supported the clinical suspicion of involvement by AITL in the bone marrow. In fact, subsequent bone marrow biopsies were additionally performed, demonstrating more overt morphologic involvement by lymphoma (Image 3) with positive T-cell receptor gene rearrangement studies.
Zoe Mueller Member
access_time 75 minutes ago
Additionally, in the setting of AITL, it has been shown that DNMT3A mutations occur concurrently with TET2 mutations. Despite limitations in sensitivities and specificities of the testing which we performed, in the current setting with a relatively high pretest probability of recurrent AITL, this positive NGS result with a negative mycobacterium workup supported the clinical suspicion of involvement by AITL in the bone marrow. In fact, subsequent bone marrow biopsies were additionally performed, demonstrating more overt morphologic involvement by lymphoma (Image 3) with positive T-cell receptor gene rearrangement studies.
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Nathan Chen 43 minutes ago
References 1. Lunning M.A., Vose J.L. Angioimmunoblastic T-cell lymphoma: The many-faced lymphoma....
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References 1. Lunning M.A., Vose J.L. Angioimmunoblastic T-cell lymphoma: The many-faced lymphoma.
Brandon Kumar Member
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References 1. Lunning M.A., Vose J.L. Angioimmunoblastic T-cell lymphoma: The many-faced lymphoma.
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Blood. 2017,129: 1095-1102. 2....
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Swerdlow SH, Campo E, Harris NL, Jaffee ES, Pileri SA, Stein H, Thiele J (Eds): WHO classification o...
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Blood. 2017,129: 1095-1102. 2.
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Blood. 2017,129: 1095-1102. 2.
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Swerdlow SH, Campo E, Harris NL, Jaffee ES, Pileri SA, Stein H, Thiele J (Eds): WHO classification o...
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Swerdlow SH, Campo E, Harris NL, Jaffee ES, Pileri SA, Stein H, Thiele J (Eds): WHO classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition) IARC: Lyon 2017. 3. Odejide O, Weigert O, Lane A.A, Toscano D, Lunning MA, Kopp N, Kim S, van Bodegom D, Bolla S, Schatz JH, Teruya-Feldstein J, Hochberg E, Louissaint A, Dorfman D, Stevenson K, Rodig SJ, Piccaluga PP, Jacobsen E, Pileri SA, Harris NL, Ferrero S, Inghirami G, Horwitz SM, and Weinstock DM.
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A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood.
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Dunleavy D, Wilson WH, Jaffee E. Angioimmunoblastic T-cell lymphoma: pathological insights and clinical implications.
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IDH2 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood. 2015,126:1741-1752.
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IDH2 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood. 2015,126:1741-1752.
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Have Questions or Need Help If you have questions or would like to learn more about the Anatomic and Clinical Pathology Residency Program at Cedars-Sinai, please call or send a message to Academic Program Coordinator, LeeTanya Marion-Murray. Department of Pathology and Laboratory Medicine 8700 Beverly Blvd., Room 8709 Los Angeles, CA 90048-1804 310-423-6941 send a message Please ensure Javascript is enabled for purposes of website accessibility
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Have Questions or Need Help If you have questions or would like to learn more about the Anatomic and Clinical Pathology Residency Program at Cedars-Sinai, please call or send a message to Academic Program Coordinator, LeeTanya Marion-Murray. Department of Pathology and Laboratory Medicine 8700 Beverly Blvd., Room 8709 Los Angeles, CA 90048-1804 310-423-6941 send a message Please ensure Javascript is enabled for purposes of website accessibility
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Brandon Kumar 85 minutes ago
Past medical history was also significant for history of treated tuberculosis several decades ago. H...

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