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Follicular T-cell lymphoma

1 Department of Pathology, AIIMS, Deoghar, Jharkhand, India
2 Mahavir Cancer Sansthan, Patna, Bihar, India

Date of Submission11-Jul-2019
Date of Decision04-Sep-2019
Date of Acceptance01-Dec-2019
Date of Web Publication07-Nov-2020

Correspondence Address:
Mona Lisa,
302 B Ramdeokunj Anandpuri, Patna - 800 001, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_486_19

 > Abstract 

Follicular T-cell lymphoma is a recently described, rare neoplasm with the true incidence still unknown. It is a lymph node-based tumor in which the node shows a follicular pattern of growth. Immunohistochemistry confirms the cells of origin to be follicular helper T-cells and thus plays an important role in the diagnosis of the tumor. We report a case of follicular variant of peripheral T-cell lymphoma, which was erroneously reported as Hodgkin lymphoma on fine-needle aspiration, and follicular lymphoma on hematoxylin and eosin.

Keywords: Follicular, helper T-cell, lymphoma

How to cite this URL:
Lisa M, Verma PK, Nishi, Shuchismita, Hussain MA. Follicular T-cell lymphoma. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=330266

 > Introduction Top

A 60-year-old male presented with bilateral inguinal lymphadenopathy and pain in the abdomen for 2 months. Blood chemistry was within the normal limits. Fine-needle aspiration cytology (FNAC) from the inguinal node was reported as Hodgkin lymphoma classical type. On inguinal node biopsy, we found the node involved by an atypical follicular proliferation. The interfollicular space showed some immunoblasts and high endothelial venule proliferation. The lesional lymphoid cells expressed CD3, CD5, CD2, CD4, and PD1 and were immunonegative for CD20, CD10, CD23, CD30, and CD8 and bcl6. The bystander immunoblasts were CD30 and Epstein–Barr virus-encoded RNA in situ hybridization (EBER-ISH) positive. The tumor was thus reported as non-Hodgkin lymphoma of follicular T-cell type.

 > Case Report Top

A 60-year-old male presented to the department of medical oncology with a chief complaint of pain in the abdomen, loss of appetite, and left inguinal swelling. There was no significant hepatosplenomegaly, and bilateral, multiple inguinal nodes were enlarged on clinical examination with largest on the left side measuring approximately 5 cm in diameter. The patient was hepatitis B surface antigen positive, detected by chemiluminescent immunoassay. Routine blood investigation was within the normal limits. Positron emission tomography scan [Figure 1]a for initial staging revealed multiple enlarged cervical (largest 2 cm, standard uptake value [SUV]: 8), axillary (largest 3 cm, SUV: 10.7), and abdominopelvic nodes (largest external iliac 4 cm, SUV: 12.2). The radiological differential diagnosis was lymphoma. FNAC from the inguinal node showed scattered Reed–Sternberg (RS)-like cells in a background of lymphocytes, along with a few scattered eosinophils and plasma cells [Figure 1]b. It was thus reported as Hodgkin lymphoma.
Figure 1: (a) Positron emission tomography scan image showing enlarged abdominopelvic lymph nodes. (b) Fine-needle aspiration – Reed–Sternberg-like cells (black arrow) in a background of mixed inflammatory infiltrate (×40). (c) Effacement of lymph node architecture with a diffuse follicular pattern (×4). (d and e) Interfollicular area with high endothelial venule proliferation, scattered immunoblasts in a mixed inflammatory background (×40, ×100)

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One of the left inguinal lymph nodes was excised for histopathological examination. The lymph node was measured 2 cm × 2 cm × 1.8 cm and was well encapsulated, solid grayish white on cut. Formalin-fixed paraffin-embedded lymph node was sectioned and stained with hematoxylin and eosin. Microscopy showed effacement of lymph node architecture and a definite follicular pattern of proliferation [Figure 1]c. These follicles were composed of medium-sized lymphoid cells with clear cytoplasm, round hyperchromatic nuclei, and inconspicuous nucleoli. There was a paucity of tingible body macrophages in the follicles. The interfollicular area showed a few immunoblasts and high endothelial venule proliferation along with scattered eosinophils and plasma cells [Figure 1]d and [Figure 1]e. It was reported as non-Hodgkin lymphoma with a possibility of follicular lymphoma, Grade 1 as a differential on hematoxylin and eosin, and immunohistochemistry was advised. Immunohistochemistry was performed on paraffin-embedded tissue in the semi-automated stainer (BioGenex) as per the manufacturer's protocol, using a pressure cooker for antigen retrieval. The lesional lymphoid cells expressed CD3, CD5, CD2, CD4, and PD1. The tumor cells were immunonegative for CD7, CD20, CD10, CD23, CD30, and CD8 [Figure 2] and [Figure 3]. Ki67 proliferation index was 30%. The expression of T-cell markers in the follicles as well as immunonegativity for the B-cell markers confirms it to be a T-cell lymphoma. The expression of PD1 and CD4 in the same follicular lymphocytes shows that the tumor originates from follicular helper T-cells. The follicular dendritic cell meshwork expansion (as observed by CD23-positive cells) commonly found in angioimmunoblastic T-cell lymphoma (AITL) was absent in our case [Figure 4]. The bystander immunoblasts were CD30 and EBER-ISH positive, and these cells might have given a false impression of Hodgkin lymphoma on FNAC. The tumor was thus reported as non-Hodgkin lymphoma of follicular T-cell type. The patient is on oral alkylating agent monotherapy and is keeping well.
Figure 2: (a and b) Strong membranous expression of CD3 in the follicles (×10, ×40). (c) PD1 expression in the similar fashion (×10). (d) Remnant follicular B-cells expressing CD20 (×10)

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Figure 3: (a-c) CD2, CD4, and CD5 expression respectively in the follicular T-cells, in a similar fashion as CD3 (×10)

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Figure 4: (a and b) CD23-positive follicular dendritic cells. As obvious, the follicular dendritic meshwork is not considerably expanded (×4, ×40). (c) CD30-positive bystander immunoblasts. (d) Ki67 proliferation index was 30%

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 > Discussion Top

Follicular pattern of growth was thought to be restricted to B-cell lymphomas. In 2001, de Leval et al. described the first case series of T-cell lymphomas morphologically having a follicular growth pattern.[1] Follicular peripheral T-cell lymphoma (FPTCL) was included as a variant of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in the WHO classifications of lymphoid neoplasms in 2008.[2] Most of the PTCL-NOS arise from the memory T-cells, but the FPTCL is known to arise from the follicular helper T-cells expressing PD-1, CXCL13, and ICOS3.[2],[3] Lymphomas arising from follicular helper T-cells are now a group separate from PTCL-NOS in the recent WHO classification.[4]

Ikonomou et al. have described two variants of PTCL with nodular architecture: one localizing to the marginal or the perifollicular region and the other localizing to the germinal center.[5] Our case represents the former variant with medium-sized, CD3, and PD1-positive T-cells having clear cytoplasm and distinct cell membrane, expanding the perifollicular region, whereas the remnant germinal centers show CD20-positive B-cells. The interfollicular region also showed scattered CD3- and PD1-positive T-cells along with some high endothelial venules and bystander immunoblasts.

FPTCL shows some overlapping morphological and immunophenotypic features with AITL. The initial phase of AITL also shows hyperplastic follicles which can mimic FPTCL; however, clinical features such as hypergammaglobulinemia, skin rash, and other autoimmune manifestations are not seen in the former. Some studies, however, have suggested that FPTCL could be a peculiar stage of AITL.[6],[7] A study by Miyoshi et al. states that systemic symptoms were noted in as high as 50% of cases of FPTCL.[7] The same study also points out that expression of Bcl6 may be associated with systemic symptoms in patients of FPTCL and that Bcl6 may have a role to play in the transition of FPTCL to AITL. Whether FPTCL and AITL are two ends of a common spectrum is a matter that needs further investigation. Our case was also Bcl6 negative and did not show any of the systemic manifestations. In the recent 2017 edition of the WHO classification, FPTCL, AITL, and cases of nodal PTCL with TFH phenotype have been unified under a common heading.[4]

Hodgkin/RS-like large cells may be present in the interfollicular region, surrounded by neoplastic T-cells, which can lead to a mistaken diagnosis of Hodgkin lymphoma.[8],[9] In our case also, there were some scattered bystander immunoblasts that were CD30 and EBER-ISH positive. There was also some vascular proliferation with high endothelial venules and scattered inflammatory cells including eosinophils and plasma cells. This might have been the reason that the FNA aspirate gave a picture similar to Hodgkin lymphoma, mixed cellularity type.

 > Conclusion Top

Peripheral T-cell lymphomas having a follicular architecture are rare, but they must be kept as a differential for such lesions. These lesions can also have RS-like cells and one should be cautious before diagnosing it as a Hodgkin lymphoma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

de Leval L, Savilo E, Longtine J, Ferry JA, Harris NL. Peripheral T-cell lymphoma with follicular involvement and a CD4+/bcl-6+phenotype. Am J Surg Pathol 2001;25:395-400.  Back to cited text no. 1
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues. Lyon: International Agency of Research on Cancer (IARC); 2008.  Back to cited text no. 2
Agostinelli C, Hartmann S, Klapper W, Korkolopoulou P, Righi S, Marafioti T, et al. Peripheral T cell lymphomas with follicular T helper phenotype: A new basket or a distinct entity? Revising Karl Lennert's personal archive. Histopathology 2011;59:679-91.  Back to cited text no. 3
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri. editors. WHO Classification of Tumors of Haematopoetic and Lymphoid Tissues. Revised. 4th ed. Lyon: International Agency for Research on Cancer; 2017.  Back to cited text no. 4
Ikonomou IM, Tierens A, Troen G, Aamot HV, Heim S, Lauritzsen GF, et al. Peripheral T-cell lymphoma with involvement of the expanded mantle zone. Virchows Arch 2006;449:78-87.  Back to cited text no. 5
Huang Y, Moreau A, Dupuis J, Streubel B, Petit B, Le Gouill S, et al. Peripheral T-cell lymphomas with a follicular growth pattern are derived from follicular helper T cells (TFH) and may show overlapping features with angioimmunoblastic T-cell lymphomas. Am J Surg Pathol 2009;33:682-90.  Back to cited text no. 6
Miyoshi H, Sato K, Niino D, Arakawa F, Kimura Y, Kiyasu J, et al. Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders. Am J Clin Pathol 2012;137:879-89.  Back to cited text no. 7
Quintanilla-Martinez L, Fend F, Moguel LR, Spilove L, Beaty MW, Kingma DW, et al. Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection. Am J Surg Pathol 1999;23:1233-40.  Back to cited text no. 8
Nicolae A, Pittaluga S, Venkataraman G, Vijnovich-Baron A, Xi L, Raffeld M, et al. Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: Both EBV-positive and EBV-negative variants exist. Am J Surg Pathol 2013;37:816-26.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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