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Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 265-267
Follicular variant of peripheral T-cell lymphoma

Department of Histopathology, Apollo Hospitals, Chennai, Tamil Nadu, India

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Date of Web Publication19-Jun-2017


Globally, peripheral T-cell lymphomas (PTCLs) constitute about 12% of all non-Hodgkin lymphomas, of which the unspecified category is the most common subtype (30%). Mostly, the unspecified category shows a diffuse pattern of involvement in the lymph nodes. However, rarely, they may show a follicular/nodular pattern mimicking a follicular lymphoma. We report a case of a follicular variant of PTCL, not otherwise specified. This case displayed a striking nodular/follicular pattern with an admixture of small (centrocyte-like) and large (centroblast-like) cells, thus mimicking a follicular lymphoma. The neoplastic cells were strongly positive for both CD3 and CD20. In addition, they were positive for pan T-cell markers and PD-1. T-cell receptor gene rearrangement studies highlighted a monoclonal T-cell population. Even though this variant of PTCL is very rare, it is important to keep it as a differential for the lymphomas exhibiting nodular pattern.

Keywords: Follicular lymphoma, follicular, follicular-peripheral T-cell lymphoma, peripheral T-cell lymphoma

How to cite this article:
Lakshmanan A, Annapurneswari S, Nair S. Follicular variant of peripheral T-cell lymphoma. Indian J Pathol Microbiol 2017;60:265-7

How to cite this URL:
Lakshmanan A, Annapurneswari S, Nair S. Follicular variant of peripheral T-cell lymphoma. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Jan 20];60:265-7. Available from: https://www.ijpmonline.org/text.asp?2017/60/2/265/208408

   Introduction Top

Peripheral T-cell lymphomas (PTCLs) constitute about 12% of all non-Hodgkin lymphomas (NHL) globally.[1] PTCL, not otherwise specified (NOS), is the most common subtype. It is often nodal in presentation with a diffuse pattern. Recently, a few cases of PTCL, NOS with a follicular or a nodular pattern, have been described.[2],[3],[4],[5] These lymphomas were considered to arise from follicular T-helper cells, a subset of CD4+ T-cells which are normally present within the germinal centers.

We report a case of PTCL with a follicular pattern which morphologically mimicked follicular lymphoma and further compounded by CD20 coexpression.

   Case Report Top

A 72-year-old woman presented with complaints of swelling in the inguinal region, generalized weakness, and significant weight loss. Examination revealed enlarged cervical, axillary, and inguinal lymph nodes. Computed tomography scans of the chest and abdomen revealed enlarged axillary, mediastinal, retroperitoneal, para-aortic, paracaval, and mesenteric lymph nodes. Excisional biopsy of the right inguinal lymph node was done. The lymph node was fixed in formalin, paraffin embedded, sectioned at 4 micron thickness and stained with hematoxylin and eosin. Immunohistochemistry was performed on paraffin-embedded tissue in the automated stainer (Ventana Benchmark XT) using the manufacturer's protocol. Polymerase chain reaction (PCR) was done to assess the clonality of T-cells using the Invivoscribe Identiclone T-cell Receptor Gamma Gene Rearrangement Assay 2.0. This PCR assay employs multiple consensus DNA primers that target conserved genetic regions within the T-cell receptor (TCR) gamma-chain gene. Amplification of the region with fluorescent labeled primers is followed by fractionation by capillary electrophoresis and analysis by instrument software. Upon diagnosis, the patient refused to undergo further investigations and declined to accept treatment. On follow-up of 3 months, the patient's condition deteriorated with loss of weight and increasing lymphadenopathy. Then, the patient was lost to follow-up.

   Results Top

The histopathological examination of the lymph node showed effaced architecture with multiple closely packed nodules of varying sizes. The nodules were composed of predominantly small cells with scant to moderate pale cytoplasm and irregular hyperchromatic nuclei. Amidst these cells were few large cells with moderate cytoplasm, vesicular nuclei with 1-2 prominent membrane based nucleoli. Occasional bilobate and multilobate cells are noted along with rare mummified cells. The paracortical area also showed infiltration by small cells with similar morphology as noted within the follicles. There was extensive perinodal spread [Figure 1].
Figure 1: (a and b) The lymphoma shows a striking follicular/nodular pattern with extensive perinodal spread (H and E, ×4 and ×10). (c) There is admixture of small and large lymphoid cells resembling centrocytes and centroblasts (H and E, ×40). (d) Few bi and multilobate cells and occasional mummified cells are also seen (H and E, ×40)

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The immunostaining results are shown in [Figure 2]. CD3 was strong and diffuse involving both follicles and interfollicular areas, staining both the small and large neoplastic cells. A similar staining pattern was noted with CD2, CD5, CD7, CD4, and PD-1. CD20 was also diffuse but less intense than CD3. CD79a and Pax-5 were negative in the neoplastic cells. CD23 highlighted the dendritic meshwork within the follicles, and there was no expansion or disruption. CD10 was focally positive. Bcl-6 was negative. The proliferation index was low (20%). CD30 and Epstein–Barr virus latent membrane protein 1 were negative.
Figure 2: Immunohistochemistry. The neoplastic cells within the follicles and interfollicular area are highlighted by CD3, CD20, CD4, PD-1, and Bcl-2. The proliferation index (Ki67) is low around 20%. Some of the follicles at the periphery were weakly positive for CD10. CD23 highlights a preserved follicular dendritic meshwork

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The neoplastic nature of the T-cell proliferation was further confirmed by TCR clonality assay which was positive for the detection of clonal TCR gamma-chain gene rearrangement [Figure 3].
Figure 3: T-cell receptor clonality assay. A monoclonal peak is noted in the test, thus confirming a clonal T-cell population

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   Discussion Top

Follicular pattern was initially described only in B-cell NHLs. de Leval et al. described the first case series of T-cell lymphomas with a follicular pattern.[6] Follicular PTCL is a recently described variant of PTCL, NOS in the World Health Organization (WHO) classifications of lymphoid neoplasms 2008.[7] Histologically, this variant shows a nodular or a follicular growth pattern. The neoplastic cells are considered to be of follicular T-helper cell origin. In the reported cases, this variant either showed a follicular or a perifollicular/marginal zone pattern morphologically mimicking follicular lymphoma, nodal marginal zone lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma.[2],[3],[4],[5]

Follicular-peripheral T-cell lymphoma (F-PTCL) shows some overlapping morphological and immunophenotypic features with angioimmunoblastic T-cell lymphoma (AITL). Three histologic patterns of AITL have been described, of which type I shows hyperplastic follicles closely mimicking follicular variant of PTCL.[2],[3],[4] The criteria based on which AITL was excluded in this case were monomorphic appearance with absent characteristic background (eosinophil-rich polymorphic infiltrate), absence of medium-sized cells with clear cytoplasm, absent follicular dendritic cell meshwork expansion, and absent postcapillary venules proliferation. F-PTCL and AITL share similar follicular helper T-cell molecular signature by gene expression profiling, raising the question of possible relationship between these two lymphomas.[8] Whether F-PTCL represents a variant or an early stage of AITL is difficult to discern. In the latest update of the WHO classification, F-PTCL, AITL, and cases of nodal PTCL with TFH phenotype are being unified under a common heading.[9]

The present case posed another diagnostic difficulty as the neoplastic cells also strongly expressed CD20. However, the other B-cell markers such as CD79a and Pax-5 were negative. On reviewing the literature, we found few reports of T-cell lymphomas expressing CD20, most of which were PTCL, NOS.[10],[11] Most often the CD20 expression was weak; however, cases with diffuse and strong positivity similar to our case have also been reported.[11] CD20-positive T-cell lymphomas may pose a diagnostic challenge, especially in cases such as the present case which morphologically mimicked a B-cell lymphoma. Hence, awareness about aberrant expression of CD20 in T-cell lymphomas is necessary to avoid misinterpreting these lymphomas as B-cell lineage.

   Conclusion Top

The rarity of this follicular variant of PTCL raises the concern of misdiagnosing these lesions. Hence, we should consider this variant of PTCL as a differential whenever a lymph node shows a follicular or a nodular pattern. It is important to diagnose this entity since T-cell lymphomas tend to have a worse prognosis. A proper and thorough histopathological examination along with appropriate use of immunostains and molecular studies is necessary to arrive at the correct diagnosis.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin's lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin's Lymphoma Classification Project. Ann Oncol 1998;9:717-20.  Back to cited text no. 1
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. 2
Bacon CM, Paterson JC, Liu H, Payne K, Munson P, Du MQ, et al. Peripheral T-cell lymphoma with a follicular growth pattern: derivation from follicular helper T cells and relationship to angioimmunoblastic T-cell lymphoma. Br J Haematol 2008;143:439-41.  Back to cited text no. 3
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. 4
Jiang L, Jones D, Medeiros LJ, Orduz YR, Bueso-Ramos CE. Peripheral T-cell lymphoma with a “follicular” pattern and the perifollicular sinus phenotype. Am J Clin Pathol 2005;123:448-55.  Back to cited text no. 5
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. 6
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. 7
de Leval L, Rickman DS, Thielen C, Reynies AD, Huang YL, Delsol G, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 2007;109:4952-63.  Back to cited text no. 8
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.  Back to cited text no. 9
Yao X, Teruya-Feldstein J, Raffeld M, Sorbara L, Jaffe ES. Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a diagnostic pitfall. Mod Pathol 2001;14:105-10.  Back to cited text no. 10
Rahemtullah A, Longtine JA, Harris NL, Dorn M, Zembowicz A, Quintanilla-Fend L, et al. CD20+ T-cell lymphoma: clinicopathologic analysis of 9 cases and a review of the literature. Am J Surg Pathol 2008;32:1593-607.  Back to cited text no. 11

Correspondence Address:
Archana Lakshmanan
Department of Histopathology, Apollo Hospitals, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_710_16

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