Journal of Pathology and Translational Medicine

Volume 56(1); January 2022

Review

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

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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

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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

Original Articles

Clinicopathological differences in radiation-induced organizing hematomas of the brain based on type of radiation treatment and primary lesions: Myung Sun Kim, Se Hoon Kim, Jong-Hee Chang, Mina Park, Yoon Jin Cha; J Pathol Transl Med. 2022;56(1):16-21. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.30

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Abstract PDF

Background
Radiation-induced organizing hematoma (RIOH) is a sporadic form of cavernous hemangioma (CH) that occurs after cerebral radiation. RIOH lesions are distinct histologically from de novo CH; however, detailed research on this subject is lacking. In the present study, the clinical and histological features of RIOHs were evaluated based on causative lesions.
Methods
The present study included 37 RIOHs confirmed by surgical excision from January 2009, to May 2020, in Yonsei Severance Hospital. All cases were divided into subgroups based on type of radiation treatment (gamma knife surgery [GKS], n = 24 vs. conventional radiation therapy [RT], n = 13) and pathology of the original lesion (arteriovenous malformation, n = 14; glioma, n = 12; metastasis, n = 4; other tumors, n = 7). The clinicopathological results were compared between the groups.
Results
Clinical data of multiplicity, latency, and size and wall thickness of the original tumors and RIOHs were analyzed. The GKS group showed shorter latency (5.85 ± 4.06 years vs. 11.15 ± 8.27 years, p = .046) and thicker tumor wall (693.7 ± 565.7 μm vs. 406.9 ± 519.7 μm, p = .049) than the conventional RT group. Significant difference was not found based on original pathology.
Conclusions
RIOH is more likely to occur earlier with thick tumor wall in subjects who underwent GKS than in patients who underwent conventional RT. These results indicate the clinical course of RIOH differs based on type of treatment and might help determine the duration of follow-up.

Citations

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End-stage ADPKD with a low-frequency PKD1 mosaic variant accelerated by chemoradiotherapy
Hiroaki Hanafusa, Hiroshi Yamaguchi, Naoya Morisada, Ming Juan YE, Riki Matsumoto, Hiroaki Nagase, Kandai Nozu
Human Genome Variation.2024;[Epub] CrossRef
Recapitulating the Key Advances in the Diagnosis and Prognosis of High-Grade Gliomas: Second Half of 2021 Update
Guido Frosina
International Journal of Molecular Sciences.2023; 24(7): 6375. CrossRef
Earlier Age at Surgery for Brain Cavernous Angioma-Related Epilepsy May Achieve Complete Seizure Freedom without Aid of Anti-Seizure Medication
Ayataka Fujimoto, Hideo Enoki, Keisuke Hatano, Keishiro Sato, Tohru Okanishi
Brain Sciences.2022; 12(3): 403. CrossRef

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas: Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim; J Pathol Transl Med. 2022;56(1):22-31. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.31

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Abstract PDF

Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Citations

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High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation
Takuro Hakata, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Nobuya Inagaki
Endocrinology.2024;[Epub] CrossRef
Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification
Lorenzo Ugga, Raduan Ahmed Franca, Alessandra Scaravilli, Domenico Solari, Sirio Cocozza, Fabio Tortora, Luigi Maria Cavallo, Marialaura Del Basso De Caro, Andrea Elefante
Neuroradiology.2023; 65(4): 675. CrossRef
A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izat
Clinical Epigenetics.2023;[Epub] CrossRef
Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
Hongyan Liu, Saichun Zhang, Ting Wu, Zhaohui Lv, Jianming Ba, Weijun Gu, Yiming Mu
Frontiers in Oncology.2022;[Epub] CrossRef

Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma: Ki Rim Lee, Jiwon Koh, Yoon Kyung Jeon, Hyun Jung Kwon, Jeong-Ok Lee, Jin Ho Paik; J Pathol Transl Med. 2022;56(1):32-39. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.05

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Abstract PDF: Background
Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications.
Methods
We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90).
Results
PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012).
Conclusions
PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer: Hyunseung Oh, Soon Gu Kim, Sung Uk Bae, Sang Jun Byun, Shin Kim, Jae-Ho Lee, Ilseon Hwang, Sun Young Kwon, Hye Won Lee; J Pathol Transl Med. 2022;56(1):40-47. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.07

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Abstract PDF Supplementary Material: Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Case Studies

Chronic lymphocytic leukemia and concurrent seminoma in the same testis: Kosuke Miyai, Fumihisa Kumazawa, Kimiya Sato, Hitoshi Tsuda; J Pathol Transl Med. 2022;56(1):48-52. Published online October 22, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.10

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Abstract PDF: A 59-year-old man presented with a painless testicular mass and underwent a radical orchiectomy. The resected specimen showed a 5-cm-sized, white-yellow and homogenous solid mass in the testicular parenchyma. Histologically, the central part of the tumor exhibited typical features of seminoma. The peripheral part of the tumor exhibited diffuse infiltration of small, monotonous lymphoid cells involving the tunica albuginea. The monotonous lymphoid cells were immunoreactive for CD20, CD79a, CD5, and CD23, and negative for CD3, CD10, and cyclin D1. Kappa light chain restriction was detected on flow cytometry using the resected specimen. Considering the circulating lymphoid cell count of >5.0×10³/µL, we diagnosed the peripheral component of the tumor as an infiltration of chronic lymphocytic leukemia. This extremely rare combination of seminoma and lymphoid neoplasm should be considered in the differential diagnosis of classic seminoma with extensive lymphoid reaction in tumors arising in elderly patients.

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma: Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta; J Pathol Transl Med. 2022;56(1):53-56. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.16

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Abstract PDF

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

Citations

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SMARCA4-deficient Non–small Cell Lung Cancer on 18F-FDG PET/CT
Tao Liu, Hengshan Ji, Siyuan Jiang, Rongxin Qi, Xiaodie Zhou, Jingjing Sun, Jiang Wu
Clinical Nuclear Medicine Open.2025;[Epub] CrossRef
One Case of Non-Small Cell Lung Cancer with SMARCA4 Deletion Was Reported
允龙宋
Medical Diagnosis.2024; 14(01): 137. CrossRef
Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
World Journal of Clinical Cases.2022; 10(29): 10501. CrossRef
Novel germline SMARCA4 mutation in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Anurag Mehta, Himanshi Diwan, Diksha Karki, Divya Bansal, Meenakshi Kamboj, Anila Sharma, Shrinidhi Nathany, Sakshi Mattoo, Dushyant Kumar
Current Problems in Cancer: Case Reports.2022; 8: 100205. CrossRef

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

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Abstract 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.

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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
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Double trouble: insights from a rare case of extranodal composite lymphoma in an elderly man, with comprehensive literature review
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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

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