|Year : 2020 | Volume
| Issue : 1 | Page : 94-97
T-cell lymphomas in a tertiary care center of Mangalore
Flora D Lobo, Priya Garg, Radha R Pai, Hema Kini, Krishna Prasad
Departments of Pathology and Oncology, Kasturba Medical College, M.A.H.E., Mangalore, Karnataka, India
|Date of Submission||18-Jan-2017|
|Date of Acceptance||25-Feb-2018|
|Date of Web Publication||26-Oct-2018|
Department of Pathology, Kasturba Medical College, Light House Hill Road, Mangalore . 575 001, Karnataka
Source of Support: None, Conflict of Interest: None
Background: The clinicomorphology and immunohistochemical features of T-cell lymphomas have been documented.
Aim: The aim of the study was to evaluate the spectrum of clincopathological features of T-cell lymphoma with immunohistochemistry correlation in a tertiary care center.
Materials and Methods: The present study was conducted on 19 biopsy specimens received from the Department of Pathology, Kasturba Medical College, from referral hospitals of Mangalore city. Cases of nodal and extranodal T-cell lymphomas diagnosed between January 2012 and December 2015 were selected with evaluation of clinical data, histomorphological features, and immunophenotyping. Appropriate panel of antibodies was chosen after morphological evaluation of the cases.
Results: Of the 19 cases of T-cell lymphomas, 14 were nodal disease and 5 were extranodal disease. Among the nodal lymphomas, five were primary peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), four were cases of lymphoblastic lymphoma, three were cases of angioimmunoblastic T-cell lymphomas, and two were cases of anaplastic large-cell lymphoma anaplastic lymphoma kinase (ALK) negative. In extranodal disease, two were mycosis fungoides of skin, one case each of subcutaneous panniculitis-like T-cell lymphoma, T-cell lymphoblastic lymphoma of tonsil, and T-cell lymphoma of the stomach.
Conclusions: The diagnosis and subclassification of PTCLs is necessary for therapeutic and prognostic purposes.
Keywords: Immunohistochemistry, non-Hodgkin's lymphoma, T-cell lymphomas
|How to cite this article:|
Lobo FD, Garg P, Pai RR, Kini H, Prasad K. T-cell lymphomas in a tertiary care center of Mangalore. J Can Res Ther 2020;16:94-7
| > Introduction|| |
T-cell lymphomas are a generic group of tumors composed of neoplastic lymphocytes. They are heterogeneous in nature manifesting primarily at nodal sites and less commonly at extranodal sites. The phenotypic and genotypic features of these tumor cells are similar to that of T-cells. The T-cell lineage tumors often present with perifollicular, paracortical, and occasionally follicular growth patterns. Non-Hodgkin's lymphomas (NHLs) derived from T-lymphocytes that are mature or natural killer cells are considered as peripheral T-cell lymphomas (PTCLs). It comprises 12%–15% of all NHLs. Those that are derived from precursor T-cells are lymphoblastic T-cell lymphomas. T-cell lymphoma entities lack defining genetic aberrations, and their classification lies on less well-characterized diagnostic criteria. For appropriate treatment, correct diagnosis of each entity is mandatory.
| > Materials and Methods|| |
This is a retrospective and prospective study. This study included T-cell lymphoma cases diagnosed between January 2012 and December 2015 with evaluation of clinical data, histomorphological features, and immunophenotyping. The cases were classified according to the WHO 2008 classification. Immunohistochemical (IHC) markers used were leukocyte common antigen (LCA), CD3, CD5, CD20, CD30, CD5, CD99, and CD23 DAKO. The antibodies used in a given case were determined after morphological evaluation.
| > Results|| |
Of the 19 cases of T-cell lymphomas, 14 (73.7%) involved lymph nodes and five were of extranodal sites (26.3%). Extranodal sites were two cutaneous, one each of subcutaneous fat, tonsil, and stomach. Out of the 14 nodal cases, five were PTCL-not otherwise specified (NOS) (35.7%), four were T-cell lymphoblastic lymphomas (28.6%), three were angioimmunoblastic T-cell lymphomas (AITCLs) (21.4%), and two were anaplastic large-cell lymphoma anaplastic lymphoma kinase negative (ALCL ALK negative) (14.3%).
The mean age of five (35.7%) cases of nodal PTCL-NOS was 60 years, with male: female ratio of 3:2. Hepatosplenomegaly with generalized lymphadenopathy was present in all the cases with absence of B-symptoms. Serum lactate dehydrogenase (LDH) was increased in all the cases. The morphology of PTCL-NOS was heterogeneous comprising of a spectrum of small-to-intermediate cells with dispersed large cells. The proliferating cells showed coarse clumped chromatin with occasional nucleoli. The larger cells had multilobated nuclei. Atypical mitoses were seen [Figure 1]. The three morphological variants observed were three cases of T-zone variant, one each of lymphoepithelioid and follicular variant. IHC showed consistent expression of CD3 in all the cases, two cases expressed CD5. Five cases of T-cell lymphoblastic lymphoma were seen, four involving lymph nodes and one of tonsil. The mean age was 25 years with male: female ratio of 4:1. Bone marrow was involved in all the cases. Two cases presented with B-symptoms and LDH was high in all the cases. The neoplastic cells were monomorphic. The cells had high nuclear-to-cytoplasm ratio, minimal cytoplasm with coarse-to-fine chromatin. CD3 and CD99 were positive in the tumor cells.
|Figure 1: (a) Peripheral T-cell lymphoma-not otherwise specified nodular pattern of neoplastic tumor cells – follicular variant, 40×. (b) Leukocyte common antigen positive. (c) CD3-positive tumor nodules. (d) CD20 negative in the tumor cells|
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Three cases of nodal AITCL were diagnosed, with mean age of 60 years and male:female ratio of 1:2. Hepatosplenomegaly with B-symptoms was present. Generalized lymphadenopathy was seen in one case. The neoplastic cells were arranged in a diffuse pattern which completely replaced the lymph node architecture. There were numerous arborizing blood vessels. The neoplastic cells were variable in number comprising of small- and large-sized cells with vesicular nuclei. They were associated with numerous reactive lymphoplasmacytic cells, histiocytes, and eosinophils [Figure 2]. LCA and CD3 positivity was seen in all the three cases with negative CD30 and CD20. CD23 was positive in the follicular dendritic cells around the blood vessels.
|Figure 2: (a) Angioimmunoblastic T-cell lymphoma. Tumor cells with arborizing blood vessels, 40×. (b) Leukocyte common antigen positive. (c) CD3 positive in tumor cells. (d) CD20 negative in tumor cells. (e) CD23-positive follicular dendritic cells around the blood vessels. (f) CD30 negative|
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Two cases of nodal ALCL were reported in 37- and 62-year-old male patients. There was absence of hepatosplenomegaly and B-symptoms. The neoplastic cells were in cohesive pattern mimicking metastasis from epithelial malignancy, the infiltrate being predominantly sinusoidal. Pleomorphic tumor cells with mitoses were seen. Both cases were CD3 and CD30 positive, while ALK was negative.
Two cases of mycosis fungoides (MF), a 48-year-old male and a 37-year-old female, were seen. Organomegaly was absent and the female patient had B-symptoms. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed in a 42-year-old male with hepatosplenomegaly, B-symptoms, high LDH, and pancytopenia. LCA, CD3, and CD5 were positive in the tumor cells. The single case of gastric T-cell lymphoma diagnosed in a 38-year-male presented with an infiltrative mass in the wall of stomach ulcerating through the mucosa. LCA and CD3 were positive and CD20 was negative.
| > Discussion|| |
T-cell lymphomas are rare diverse neoplasms comprising 10%–15% of all NHLs and have a poor prognosis.,, They are often nodal and do occur at extranodal sites. Among extranodal T-cell lymphomas, cutaneous involvement is the most common.
In the present study, lymph nodes are the most common site of primary presentation (73.7%). Burad has documented an incidence of 42% of nodal T-cell lymphoma. Among the 14 nodal T-cell NHLs studied, PTCL-NOS was the most common subtype (35.7%) followed by lymphoblastic lymphoma (28.6%), angioimmunoblastic lymphoma (21.4%), and ALCL (14.3%). According to the WHO classification, the cases not categorized as any specific entity are then termed as PTCL-NOS., Of the 14 nodal cases, five were (35.7%) PTCL-NOS which is the “diffuse large B-cell” equivalent of T-cell lymphomas. The mean age was 60 years with male: female ratio of 3:2. Organomegaly with raised LDH was seen. In a recent study by Lage et al ., similar observations were seen. Morphologically, a mixture of small and large, pleomorphic, atypical CD3-positive neoplastic cells was seen. CD5 and CD7 expression is frequently lost., In the present study, CD5 was positive in two of the five cases. We have one case of follicular variant of PTCL-NOS which mimicked follicular lymphoma and one of the lymphoepithelioid variants of PTCL-NOS with many histiocytes and noncaseating epithelioid granulomas.
Thirty percentage of PTCL-NOS are CD30-positive tumors, which need to be distinguished from ALCL-ALK-negative NHLs and from classical HLs by morphology and IHC., Jaffe in 2006 described the entity PTCL-NOS that contains pleomorphic or monomorphic tumor cells, mimicking diffuse large B-cell lymphomas. Due to the above-mentioned variations, IHC is absolutely necessary for the diagnosis of PTCL-NOS.
Precursor T-cell lymphoblastic lymphoma refers to a neoplastic proliferation of immature lymphoid cells of T-cell lineage. They comprise 85%–90%, and often present as mediastinal mass. Nodal localization with absence of mediastinal involvement is uncommon. In our study, we have five cases of T-cell lymphoblastic lymphomas, four involving cervical and mediastinal nodes and one of tonsil. Marrow infiltration was seen in all the cases. Patients' mean age was 25 years. Cortelazzo et al . and Ambrosio et al . recorded similar observations. The neoplastic cells consistently expressed CD3 and CD99, and a similar expression of these IHC markers by tumor cells in T-cell lymphoblastic lymphoma has been documented by several studies.,, Lymphoblastic lymphoma is to be distinguished with mantle cell lymphoma-blastoid variant, myeloid leukemic infiltration, and Burkitt's lymphoma by IHC and ancillary tests.
AITCL, a subtype of PTCL, originates from follicular helper T-cells that define its clinical and pathological features., In the present study, AITL of three cases was seen in elderly individuals with a median age of 65 years. Patients presented with generalized lymphadenopathy and hepatosplenomegaly. Similar observations are seen in studies by Savage, Gaulard and de Leval, and Lage et al .,, Raised LDH and erythrocyte sedimentation rate were noted in one case. Neoplastic cells expressed CD3 positivity. CD23 positivity was seen in meshworks of follicular dendritic cells. Similar observations were recorded in our study. Lage et al . described interfollicular areas with CD20- and CD79a-positive immunoblasts. The immunoblasts mimic Reed–Sternberg-like cells infected by Epstein–Barr virus of classical HL.
In our study, two cases of ALCL ALK negative, 37- and 62-year-old males, were diagnosed involving lymph nodes. On IHC, positive expression of LCA and CD30 was noted, while ALK was negatively expressed in both the cases. Seventy-five percentage of ALCL ALK-negative tumors are CD3-negative tumors,, which is focally positive in our present study. CD30 is diffusely expressed in the neoplastic cells. ALCL ALK-negative tumors are epithelial membrane antigen-positive tumors., Sometimes, the malignant cells of ALCL ALK-negative tumors resemble Reed–Sternberg-like cells. They simulate metastatic epithelial malignancies due to the sinusoidal growth of tumor cells.
Cutaneous T-cell lymphomas (CTCLs) are clonal proliferation of mature, malignant skin-infiltrating cells. They represent 65% of primary cutaneous lymphomas, with MF being the most common. MF shows a male preponderance and seen after the fourth decade in life. In our study, two cases of MF were reported: one in a 48-year-old male and the other in a 37-year-old female; both cases had CD3-positive tumor cells consistent with previous reports by Jaffe and Pandey et al .,
SPTCL is a primary cutaneous lymphoma characterized by hypodermal involvement and has a poor prognosis. Clinically and histologically, it mimics panniculitis. We have seen SPTCL in a 42-year-old male patient who presented with multiple indurated lesions in the subcutaneous fat on the lower legs with fever, pancytopenia, and hepatosplenomegaly. Histologically, the atypical lymphocytes were seen rimming the individual adipocytes in a lace-like pattern and nonepidermotropic fashion. The tumor cells were positive for CD45, CD3, and CD5 and negative for CD20. Similar findings were documented in previous Indian studies by Pandey and Kini in 2014., Location of atypical lymphoid cells in SPTCL is subcutaneous, while in other cutaneous lymphomas, dermis is predominantly involved. Nonneoplastic lesions such as lupus panniculitis mimic SPTCL. One of the significant complications of SPTCL is hemophagocytic syndrome.
Primary gastrointestinal tract T-cell lymphomas are very rare and commonly present secondary to nodal disease. In the present study, one case of primary T-cell gastric lymphoma has been reported in a 38-year-old male. On IHC, CD3 and LCA were positive and CD20 was negative.
Treatment of PTCLs is based on Cyclophosphamide, doxorubicin hydrochiorde, oncovin and prednisone (CHOP) therapy. Chemotherapies and target therapies will be more appropriate. Anti-CD30 monoclonal antibodies have shown efficacy in CD30-positive ALCL because of its strong expression in anaplastic lymphomas.
| > Conclusions|| |
T-cell lymphomas are a heterogeneous group of NHLs with rare occurrence. The diagnosis and subclassification of PTCLs is necessary for therapeutic and prognostic purposes, which is reliably achieved by morphology, IHC, and ancillary tests.
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Conflicts of interest
There are no conflicts of interest.
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