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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 61  |  Issue : 2  |  Page : 204-208
Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India


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

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Date of Web Publication20-Apr-2018
 

   Abstract 


Aims: In world literature, Peripheral T-cell lymphomas (PTCLs) constituted about 12% of non-Hodgkin's lymphomas (NHL) of which PTCL not otherwise specified (NOS) was the most common subtype. This study was undertaken to ascertain the frequency and to assess the morphologic and immunophenotypic characteristics of PTCL, NOS over a period of 5 years in a tertiary care referral center in Southern India. Materials and Methods: Slides and blocks of all PTCL, NOS were retrieved, and a detailed morphologic and immunophenotypic study using a wide panel of antibodies was done. Results: During this study, NHL constitutes 77.61% of all lymphomas. PTCL formed about 12.55% (251 cases) of all NHL. PTCL NOS was the most common subtype (30.68%). The most common site of involvement was lymph nodes (75%) followed by extranodal sites such as soft tissue (8.33%), gastrointestinal tract including oral cavity (6.67%), nasal cavity (5%), central nervous system (1.67%), lung (1.67%), and spleen (1.67%). PTCL, NOS showed a broad morphologic spectrum and had varied morphologic patterns with some mimicking reactive hyperplasia and some mimicking known type of T-cell lymphomas, B-cell lymphomas, and Hodgkin's lymphoma. Conclusions: PTCL, NOS constituted about 30.68% of all PTCLs in our institution during a 5-year period and was the second most common type of PTCL. Immunophenotyping using a wide panel of T-cell antibodies is necessary to distinguish PTCL, NOS from other lymphomas which they mimic, as they are known to carry a worse prognosis.

Keywords: Non-Hodgkin's lymphomas, peripheral T-cell lymphomas, Peripheral T-cell lymphomas Not Otherwise Specified, T-cell lymphoma

How to cite this article:
Lakshmanan A, Sikri D, Patil S, Kurian A, Annapurneswari S, Nair S. Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India. Indian J Pathol Microbiol 2018;61:204-8

How to cite this URL:
Lakshmanan A, Sikri D, Patil S, Kurian A, Annapurneswari S, Nair S. Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Feb 21];61:204-8. Available from: http://www.ijpmonline.org/text.asp?2018/61/2/204/230549





   Introduction Top


Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non-Hodgkin's lymphomas (NHL) with an aggressive behavior and poor clinical outcome. These neoplasms are rare accounting for <15% of all NHLs in the West, with variations in different geographic regions.[1],[2],[3] PTCL, not otherwise specified (NOS) is the most common subtype in Western literature and other Indian studies.[1],[2],[4],[5] It has marked morphologic and immunophenotypic heterogeneity. PTCL NOS does not correspond to any of the specifically defined T-cell lymphomas in the World Health Organization and hence is a diagnosis of exclusion.[6],[7],[8],[9]

This study was undertaken as a retrospective study to analyze the frequency, distribution of PTCLs and to better understand the immunomorphologic features of PTCL, NOS in a tertiary care center in Southern India.


   Materials and Methods Top


This retrospective study was done in the Department of Histopathology, Apollo Specialty Hospitals, Chennai for 5 years (from January 2010 to December 2014). Cases with histologically and immunophenotypically confirmed the diagnosis of PTCL, NOS according to the WHO 2008 criteria were included in the study, and other distinct entities of PTCL were excluded. The study included both in-house samples as well as referral tissue from outside hospitals. Approval for the study has been obtained from Institutional Review Board at Apollo Hospitals.

A total of 2000 cases of NHLs had been diagnosed during this study of which 251 cases of PTCLs were identified. Of all the PTCLs, PTCL NOS was the most common subtype (77 cases, 30.68%). The frequencies of different subtypes of PTCLs are as shown in [Figure 1]. A detailed immunomorphologic analysis of 60 cases of PTCL NOS was done and the remaining 17 cases were unsuitable due to insufficient material. In all 60 cases, a basic panel of antibodies including CD3, CD2, CD5, CD7, CD4, CD8, Ki67, CD30, CD20, Epstein–Barr virus-latent membrane protein 1 (EBV-LMP1) were performed and additional immunostains such as CD56, Granzyme B, Alk-1, follicular helper T-cell marker PD1 were performed as necessary. Immunohistochemistry testing was performed on the Ventana automated immunostainer using the manufacturer's protocol. The clone and source of antibodies are as mentioned in [Table 1].
Figure 1: Frequency of types of peripheral T-cell lymphomas in this study

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Table 1: List of antibodies with the clones and sources

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   Results Top


Clinical characteristics

The mean age of presentation of PTCL NOS cases was 53 years (range, 24–88 years). There was a male preponderance with a male to female ratio of 2:1. It was predominantly nodal (75%) in the presentation. The rest were extranodal (25%) and included soft tissue (5 cases, 8.33%) followed by gastrointestinal tract including oral cavity (4 cases, 6.67%), nasal cavity (3 cases, 5%), central nervous system (1 case, 1.67%), lung (1 case, 1.67%), and spleen (1 case, 1.67%).

Immunomorphologic characteristics

Of the 45 nodal PTCL NOS, there was diffuse architectural effacement in all the cases; with few preserved follicles noted in 20 cases (23.33%). The cells were predominantly monomorphic in about 45% and the rest showed a polymorphous infiltrate with varied proportions of lymphocytes, plasma cells, histiocytes, neutrophils, and eosinophils. Postcapillary venules were prominent in most of the cases (87.77%) which varied from mild to markedly prominent. Reed–Sternberg (RS) like cells was seen in significant number of cases (55%). Neoplastic cells in 19 cases were predominantly large (31.67%), medium-to-large in 18 cases (30%), medium in 17 cases (28.33%), and small in 6 cases (10%).

On immunohistochemical analysis, all the cases were diffusely positive for CD3. Residual follicles were highlighted by CD20. Thirteen cases (21.67%) showed few scattered large atypical transformed B cells which were CD20+. Most of the cases were predominantly CD4 positive (25 cases, 47.17%), followed by CD8 predominant cases (15 cases, 28.30%), dual positive (9 cases, 16.98%), and few dual negative cases (4 cases, 7.55%). The dual negative cases did not show blastic morphology. Loss of T-cell markers were observed in about 53.33% of cases, with CD7 being the most common marker lost (35%). CD30-positive cells were seen in 33 cases (55%), of which 5 cases had a significant proportion of CD30-positive cells (30%–40%). CD15 is noted in rare large cells in 5 cases with RS like morphology; however, they were positive for CD3.

There was one case of lymphoepithelioid variant with predominant population of cytotoxic T cells admixed with many singly scattered and aggregates of epithelioid histiocytes [Figure 2]. Other WHO defined variants were not observed in this study.
Figure 2: (a and b) Lymphohistiocytic variant with a close admixture of neoplastic cells and histiocytes (a: H and E, ×100 and b: H and E, ×400). (c) Neoplastic cells are diffusely positive for CD8 (CD8-×400). (d) Histiocytes are highlighted by CD68 (CD68-×400)

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Morphologic mimics

The cases in our study showed a broad morphologic spectrum [Figure 3], [Figure 4], [Figure 5], with several cases mimicking other lymphomas.
Figure 3: Hodgkin's lymphoma-like morphology (H and E, ×400) (a). Reed–Sternberg like cells in a polymorphous background (CD3-×400) (b), (c and d) Reed–Sternberg like cells are positive for CD3 and negative for CD15 and CD30 (c: CD15-×400 and d: CD30-×400)

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Figure 4: Angioimmunoblastic lymphoma-like morphology (H and E, ×400) (a) neoplastic cells with clear cytoplasm with prominent postcapillary venules (CD3-×400) (b), (c and d) Neoplastic cells are positive for CD3 and negative for PD 1 and CD23 (c: PD 1-×400) and d: CD23-×400)

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Figure 5: Anaplastic large cell lymphoma-like morphology (H and E, ×400) (a). Sheets of Anaplastic large cells with some resembling Hallmark cells (CD3-×400) (b). The neoplastic cells were diffusely positive for CD3. (c and d) Cells were negative for CD30 and Alk 1 (c: CD30-×400 and d: ALK 1-×400)

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Hodgkin's lymphoma-like

In this study, RS-like cells were noted in 33 cases, of which 25 cases had a polymorphous infiltrate [Figure 3]. The RS-like cells were very few in most of the cases except in 2 cases which had a significant proportion of Hodgkin-like and RS-like cells morphologically mimicking Hodgkin's lymphoma. A few of the large cells were positive for CD30. A PTCL NOS diagnosis was rendered because in all cases; these large cells were positive for CD45, CD3and negative for CD15.

Angioimmunoblastic T-cell lymphoma- like

Twenty cases in our study illustrated angioimmunoblastic T-cell lymphoma (AITL)-like morphology with predominantly medium-sized cells having clear cytoplasm in a background of polymorphous infiltrate rich in eosinophils and with markedly prominent postcapillary venules [Figure 4]. The neoplastic cells were CD4 predominant in 16 cases, CD8 predominant in 2 cases, and showed dual positivity in 2 cases. PD1 was significantly positive in 1 case and was negative in rest of the cases. A diagnosis of PTCL, NOS was made since none of the cases showed expansion of CD21/CD23-positive follicular dendritic meshwork. EBV-LMP1 is negative in all the cases.

Diffuse large B-cell lymphoma-like

Five cases showed diffuse sheets of predominantly monomorphic large cells with plasmablastic or immunoblastic morphology, morphologically resembling a diffuse large cell lymphoma. The large cells were diffusely and strongly positive for CD3 and negative for CD20.

Anaplastic large cell lymphoma (ALCL)-like

Four cases morphologically resembled anaplastic large cell lymphoma (ALCL) with sheets of large cells with markedly pleomorphic nuclei [Figure 5]. There were many multilobate bizarre cells resembling “hallmark cells” of ALCL. However, CD30 and ALK-1 were negative in all the four cases.

Small cell lymphoma-like

Two cases showed predominant or exclusive small cell morphology. Postcapillary venules were markedly prominent in both the cases which were a diagnostic clue toward T-cell lymphoma. The proliferation index was low in both the cases (5% and 30%) which were unusual for T-cell lymphoma. This together with the expression of CD5 did mimic low-grade B-cell lymphomas such as chronic lymphocytic leukemia/Small lymphocytic lymphoma and mantle cell lymphoma. The small cells in all our cases were diffusely positive for CD3 and negative for Pan B-cell markers CD20, CD79a, and Pax-5. They were also negative for CD23 and Cyclin D1differentiating them from small lymphocytic lymphoma and mantle cell lymphoma, respectively.


   Discussion Top


PTCLs are an uncommon and heterogeneous group of neoplasm with frequencies ranging from 1.5% to 25.0%.[3],[10],[11],[12],[13],[14],[15] In this study, PTCL constitutes about 12.6% of all NHLs during the 5-year study. This is similar to that reported in other Indian studies.[4],[5] However, a few studies from Southern India reported a slightly higher frequency.[16],[17]

The differential diagnosis of PTCL, NOS is broad because this category encompasses cases that do not meet any criteria of any specific subtype. PTCL, NOS exhibit a broad morphologic spectrum that overlaps considerably with reactive hyperplasia and other T-cell lymphomas, B-cell lymphomas, and Hodgkin's lymphomas. PTCLs exhibit varied morphologic heterogeneity as compared to B-cell lymphomas and the cytologic features are less predictive of clinical aggressiveness in PTCLs.[18],[19],[20],[21],[22],[23],[24]

PTCL, NOS has considerable morphologic overlap with other known T-cell lymphomas such as AITL and ALCL, as noted in our study.[25],[26],[27],[28],[29] Cases resembling these specific entities but without necessary, sufficient features for definitive diagnosis as such should still be considered as PTCL, NOS. PTCL, NOS can show follicular T helper cell (T-FH) phenotype, as noted in a case in our study with significant PD1 staining. Genetic studies have shown similar recurrent mutations in AITL and PTCL, NOS with T-FH signature. Hence, these entities are unified under a common heading “Nodal PTCL with T-FH phenotype” in the recent 2016 update of the WHO classification.[27] Gene expression profiling data show significant overlap between the signatures of CD30+ PTCL, NOS, and ALK-negative ALCL.[28] In addition, a study by ten Berge et al. found that the prognosis of ALK-negative ALCL is similar to that of PTCL, NOS.[29] The borders between PTCL NOS and these specific entities are still imprecise and are likely to change significantly with upcoming genetic data with high throughput molecular profiling studies.

B-cell lymphoma is a significant mimicker of PTCL, NOS. B-cell lymphomas are known to aberrantly express T-cell markers.[30],[31] The common expression of CD5 in B-cell lymphomas such as Chronic lymphocytic leukemia/Small lymphocytic lymphoma and Mantle cell lymphoma is a rare diagnostic dilemma, especially when the PTCLs show predominant small cell morphology as noted in our study. This is to underline the fact that CD5 is not lineage specific and hence the usage of comprehensive antibody panels with more lineage-specific markers is suggested.

PTCL, NOS with RS-like cells can mimic Hodgkin's lymphoma.[32],[33],[34] These cells are either part of neoplastic clone or may represent bystander B cells. They most often express CD30 and rarely CD15 as well. Negativity for CD43 and weak staining for Pax-5 are most consistent features of Classical Hodgkin's lymphoma and will aid in differentiating from PTCL, NOS.

Since the morphologic mimics are broad, differentiating them from other lymphomas is challenging, particularly with the given overall infrequency with which these neoplasms are encountered in the clinical practice. However, it is important to diagnose these entities as these carry a relatively worse behavior.

To the best of our knowledge, this is the only study on the frequency and morphology of this group of lymphomas from our country. It is important to document that these tumors are not uncommon in our country and mimic other specific and more common types of lymphomas.


   Conclusions Top


  1. PTCL NOS was the most common type of PTCL in our study similar to other Western and Indian studies
  2. There are several morphologic mimics of PTCL NOS including other PTCLs like angioimmunoblastic T-cell lymphomas, ALCLs, as well as B-cell lymphomas and Hodgkin's lymphomas. Hence, a wide panel of immunostains are necessary to differentiate from these
  3. Differentiation from other PTCLs is important since the prognosis of this group of tumors is worse according to the literature.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



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


DOI: 10.4103/IJPM.IJPM_405_17

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