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Follicular lymphoma: updates for pathologists
Mahsa Khanlari, Jennifer R. Chapman
J Pathol Transl Med. 2022;56(1):1-15.   Published online December 27, 2021
DOI: https://doi.org/10.4132/jptm.2021.09.29
  • 15,899 View
  • 844 Download
  • 15 Web of Science
  • 13 Crossref
AbstractAbstract PDF
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

Citations

Citations to this article as recorded by  
  • Relapsed/Refractory Follicular Lymphoma: Current Advances and Emerging Perspectives
    Giulio Caridà, Enrica Antonia Martino, Antonella Bruzzese, Daniele Caracciolo, Caterina Labanca, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Teresa Rossi, Antonino Neri, Ernesto Vigna, Pierfrancesco Tassone, Pierosandro Tagliaferri, Fortunato Mo
    European Journal of Haematology.2025; 114(5): 775.     CrossRef
  • Transformation of low-grade follicular lymphoma to a high-grade follicular lymphoma with the histopathological diagnosis from oral biopsy: a case report
    Gabriela Silveira de Araujo, Leandro Dorigan de Macedo, Alfredo Ribeiro-Silva, Hilton Marcos Alves Ricz, Lara Maria Alencar Ramos Innocentini
    Hematology, Transfusion and Cell Therapy.2024; 46: S380.     CrossRef
  • The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
    Andrea J. Radtke, Mark Roschewski
    Blood.2024; 143(12): 1069.     CrossRef
  • Chronic pancreatitis for the clinician: complications and special forms of the disease. Interdisciplinary position paper of the Catalan Society of Digestology (SCD) and the Catalan Pancreatic Society (SCPanc)
    Xavier MOLERO, Juan R. AYUSO, Joaquim BALSELLS, Jaume BOADAS, Juli BUSQUETS, Anna CASTERÀS, Mar CONCEPCIÓN, Míriam CUATRECASAS, Gloria FERNÀNDEZ ESPARRACH, Esther FORT, Francisco GARCIA BOROBIA, Àngels GINÈS, Lucas ILZARBE, Carme LORAS, Miquel MASACHS, Xa
    Minerva Gastroenterology.2024;[Epub]     CrossRef
  • Concurrent identification of follicular lymphoma and papillary thyroid carcinoma
    Lama A. Alzelfawi, Norah ALhumaidan, Abrar H. Alageel, Buthaina J. Yahya, Saud D. Alrasheedi, Adel S. Alqahtani
    International Journal of Surgery Case Reports.2024; 122: 110009.     CrossRef
  • Impact of Primary Disease Site of Involvement by Early-Stage Follicular Lymphoma on Patient Outcomes
    Olivia Davis, Carmen Lessani, Rana Kasht, Andrew Cohoon, Sami Ibrahimi, Adam Asch, Silas Day, Taha Al-Juhaishi
    Clinical Lymphoma Myeloma and Leukemia.2024; 24(12): 837.     CrossRef
  • Recent developments in CD19-targeted therapies for follicular lymphoma
    Aditi Saha, Julio C. Chavez
    Expert Opinion on Biological Therapy.2024; 24(10): 1049.     CrossRef
  • Unraveling the complexity of follicular lymphoma: insights and innovations
    Xijing Li
    American Journal of Cancer Research.2024; 14(12): 5573.     CrossRef
  • Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis
    Hao Wu, Hui-Cong Sun, Gui-Fang Ouyang
    World Journal of Clinical Cases.2023; 11(14): 3176.     CrossRef
  • A rare case of follicular lymphoma of the bladder
    Matthew DeSanto, Robert Strait, Jared Zopp, Kevin Brown, Samuel Deem
    Urology Case Reports.2023; 51: 102542.     CrossRef
  • Analysis of immunophenotypic features in hyaline vascular type Castleman disease
    Yu Chang, Yu Ma, Chen Chang, Wensheng Li
    Diagnostic Pathology.2023;[Epub]     CrossRef
  • Leg Edema Unveiled: The Uncommon Culprit of Follicular Lymphoma
    Syed Muhammad IbnE Ali Jaffari, Samaha Nisar, Narjis Malik, Syed Muhammad Aun Ali Jaffari, Omar Nisar
    Journal of Shalamar Medical & Dental College - JSHMDC.2023; 4(2): 125.     CrossRef
  • A Review of the Totality of Evidence in the Development of ABP 798, A Rituximab Biosimilar
    Patrick Cobb, Dietger Niederwieser, Stanley Cohen, Caroline Hamm, Gerd Burmester, Neungseon Seo, Sonya G Lehto, Vladimir Hanes
    Immunotherapy.2022; 14(9): 727.     CrossRef
Case Study
Article image
Composite follicular lymphoma and classic Hodgkin lymphoma
Han-Na Kim, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul-Won Choi, Young Hyeh Ko
J Pathol Transl Med. 2022;56(1):57-60.   Published online November 16, 2021
DOI: https://doi.org/10.4132/jptm.2021.10.09
  • 5,296 View
  • 230 Download
  • 6 Web of Science
  • 5 Crossref
AbstractAbstract PDF
Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

Citations

Citations to this article as recorded by  
  • Composite Lymphoma: A Rare Case of Vomiting
    Changqin Liu, Dongyan Han, Xiaomin Sun
    United European Gastroenterology Journal.2025;[Epub]     CrossRef
  • T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy
    Guido Ghilardi, Joseph A. Fraietta, James N. Gerson, Vivianna M. Van Deerlin, Jennifer J. D. Morrissette, Gabriel C. Caponetti, Luca Paruzzo, Jaryse C. Harris, Elise A. Chong, Sandra P. Susanibar Adaniya, Jakub Svoboda, Sunita D. Nasta, Ositadimma H. Ugwu
    Nature Medicine.2024; 30(4): 984.     CrossRef
  • Double trouble: insights from a rare case of extranodal composite lymphoma in an elderly man, with comprehensive literature review
    Aadya Kerkar
    American Journal of Translational Research.2024; 16(6): 2599.     CrossRef
  • Composite Lymphoma with Follicular Lymphoma Transformation to Clonally Related Epstein–Barr Virus (EBV) Positive Diffuse Large B-Cell Lymphoma and EBV-PositiveClassic Hodgkin Lymphoma
    Christopher B. Ryder, Hayder Saeed, Mohammad Hussaini, Pier Paolo Piccaluga
    Case Reports in Hematology.2023; 2023: 1.     CrossRef
  • Plasticity in Classical Hodgkin Composite Lymphomas: A Systematic Review
    Alexis Trecourt, Marie Donzel, Juliette Fontaine, Hervé Ghesquières, Laurent Jallade, Gabriel Antherieu, Camille Laurent, Claire Mauduit, Alexsandra Traverse-Glehen
    Cancers.2022; 14(22): 5695.     CrossRef
Original Article
Article image
Upward trend in follicular lymphoma among the Korean population: 10-year experience at a large tertiary institution
Meejeong Kim, Hee Sang Hwang, Hyungwoo Cho, Dok Hyun Yoon, Cheolwon Suh, Chan Sik Park, Heounjeong Go, Jooryung Huh
J Pathol Transl Med. 2021;55(5):330-337.   Published online September 2, 2021
DOI: https://doi.org/10.4132/jptm.2021.07.25
  • 4,321 View
  • 112 Download
  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary Material
Background
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases.
Methods
We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes.
Results
The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066).
Conclusions
We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.

Citations

Citations to this article as recorded by  
  • Incidence Trend of Follicular Lymphoma in Taiwan Compared to Japan and Korea, 2001–2019
    Liang-Chun Chiu, Chih-Wen Lin, Hung-Ju Li, Jian-Han Chen, Fu-Cheng Chuang, Sheng-Fung Lin, Yu Chang, Yu-Chieh Su
    Journal of Clinical Medicine.2023; 12(4): 1417.     CrossRef
  • A Case Report on the Complete Response of a Patient with Recurrent Follicular Lymphoma Treated with Integrative Medicine
    Kyung-dug Park, Jisoo Kim, Yoona Oh, Beom-Jin Jeong, Yu-jin Jung, Sunhwi Bang
    The Journal of Internal Korean Medicine.2023; 44(3): 585.     CrossRef
  • Recent Updates on Diagnosis and Treatment of Follicular Lymphoma
    Ga-Young Song, Deok-Hwan Yang
    The Korean Journal of Medicine.2023; 98(5): 231.     CrossRef
  • Classical Hodgkin lymphoma following follicular lymphoma: a case report
    Bomi Kim
    Journal of Yeungnam Medical Science.2023; 40(Suppl): S113.     CrossRef
  • Incidence, clinicopathological features and genetics of in‐situ follicular neoplasia: a comprehensive screening study in a Japanese cohort
    Naoki Oishi, Takahiro Segawa, Kunio Miyake, Kunio Mochizuki, Tetsuo Kondo
    Histopathology.2022; 80(5): 820.     CrossRef
Case Study
Article image
Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease
Jiwon Koh, Yoon Kyung Jeon
J Pathol Transl Med. 2020;54(3):253-257.   Published online February 5, 2020
DOI: https://doi.org/10.4132/jptm.2019.12.17
  • 6,437 View
  • 228 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDF
Follicular lymphoma (FL) with hyaline-vascular Castleman disease (FL-HVCD)-like features is a rare morphologic variant, with fewer than 20 cases in the literature. Herein, we report a case of FL-HVCD in a 37-year-old female who presented with isolated neck lymph node enlargement. The excised lymph node showed features reminiscent of HVCD, including regressed germinal centers (GCs) surrounded by onion skin-like mantle zones, lollipop lesions composed of hyalinized blood vessels penetrating into regressed GCs, and hyalinized interfollicular stroma. In addition, focal areas of abnormally conglomerated GCs composed of homogeneous, small centrocytes with strong BCL2, CD10, and BCL6 expression were observed, indicating partial involvement of the FL. Several other lymphoid follicles showed features of in situ follicular neoplasia. Based on the observations, a diagnosis of FL-HVCD was made. Although FLHVCD is very rare, the possibility of this variant should be considered in cases resembling CD. Identification of abnormal, neoplastic follicles and ancillary immunostaining are helpful for proper diagnosis.

Citations

Citations to this article as recorded by  
  • Unicentric Castleman Disease: Illustration of Its Morphologic Spectrum and Review of the Differential Diagnosis
    Siba El Hussein, Andrew G. Evans, Hong Fang, Wei Wang, L. Jeffrey Medeiros
    Archives of Pathology & Laboratory Medicine.2024; 148(1): 99.     CrossRef
  • Finding a Needle in the Haystack
    Hung-Yu Lin, Yi-Jen Peng, Yi-Ying Wu, Ping-Ying Chang
    Journal of Medical Sciences.2023; 43(6): 292.     CrossRef
  • Analysis of immunophenotypic features in hyaline vascular type Castleman disease
    Yu Chang, Yu Ma, Chen Chang, Wensheng Li
    Diagnostic Pathology.2023;[Epub]     CrossRef
  • In‐situ follicular neoplasia: a clinicopathological spectrum
    Gurdip S Tamber, Myriam Chévarie‐Davis, Margaret Warner, Chantal Séguin, Carole Caron, René P Michel
    Histopathology.2021; 79(6): 1072.     CrossRef
Original Article
Fine Needle Aspiration Cytologic Features of Follicular Lymphoma.
Jin Haeng Chung, Hwa Jeong Ha, Sun Hoo Park, Jae Soo Koh, Min Suk Kim, Seung Sook Lee, Kyung Ja Cho
Korean J Cytopathol. 2002;13(2):60-65.
  • 3,260 View
  • 119 Download
AbstractAbstract PDF
The accuracy of fine needle aspiration cytology(FNAC) for the diagnosis of follicular lymphoma was investigated by a review of 13 FNAC specimens from 10 patients. All patients included in this study were confirmed by surgical biopsy preceded by FNAC. Three aspirates were unsatisfactory because of scanty cellularity. Among the remaining 10 cases, 5(50%) were diagnosed as lymphoma, 3(30%) as reactive hyperplasia, one(10%) as metastatic small cell carcinoma, and one(10%) as granulomatous inflammation. Cytologic distinction between follicular lymphoma and reactive hyperplasia is very difficult with cytomorphology alone. Compared to reactive hyperplasia, the characteristic cytologic features such as relatively homogeneous cellular constituent, paucity of tingible body macrophages and lymphohistiocytic aggregates, and less mitotic activity in follicular lymphoma are important findings to prevent false negative diagnosis. In addition, lymphoglandular bodies are useful in distinguishing malignant epithelial tumor from lymphoid lesion.

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