Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide.

The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The DNA of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.     

T-cell chronic lymphocytic leukemia. Unusual morphologic, phenotypic, and karyotypic features in association with light chain amyloidosis.

BACKGROUND. Lymphocytes that display a phenotype of mature B-cells, T-cells, natural killer (NK) cells, or a combination of T-cells and NK cells can be found in patients with lymphoproliferations that manifest as expansions of peripheral blood lymphocytes (PBL). If these PBL expansions exhibit clonality, they can be classified as chronic lymphocytic leukemia (CLL). METHODS/RESULTS. A patient who had two simultaneous, clonal lymphoproliferative disorders manifested as an unusual T-cell CLL in conjunction with systemic light chain amyloidosis is described. Gene rearrangement studies of the PBL of the patient showed clonal rearrangements of both the T-cell receptor beta (T beta) chain and the immunoglobulin genes. Additional immunologic and microscopic studies of the T-cells of the patient showed that they were large, agranular, CD4+ T-cells that also expressed the NK cell marker CD57. Cytogenetics disclosed an unusual karyotype in the PBL. CONCLUSIONS. The pathogenesis of this T-cell CLL and whether it truly represents a malignant disorder, as well as its relation to amyloidosis, is discussed.     

Nasal T/natural killer (NK)-cell lymphomas are derived from Epstein-Barr virus–infected cytotoxic lymphocytes of both NK- and T-cell lineage

The cellular nature of nasal T/natural killer (NK)-cell lymphomas (NLs) remains controversial. It is still debatable whether these represent T-cell lymphomas with extensive loss of surface antigens or are, in fact, true NK-cell lymphomas. They are associated closely with Epstein-Barr virus (EBV), to the extent that EBV-encoded small non-polyadenylated RNAs (EBER) expression can be used as a marker for the neoplastic cells. The cell lineage of this group of lymphomas was examined further by correlating immunophenotype, genotype and EBV status with the expression of cytotoxic granule-associated proteins, perforin and T-cell intracellular antigen-1 (TIA-1) in 13 cases of NL. Combined immunophenotypic and gene rearrangement analyses demonstrated that NLs can be identified clearly as either NK-cell or T-cell tumours. Nasal NK-cell lymphomas lacked clonal rearrangement of both T-cell receptor (TCR) γ and immunogloulin heavy chain (IgH) genes and were either CD3(Leu4)⁻CD56⁺ (8 cases) or CD3(Leu4)⁺CD56⁺ (2 cases), whereas nasal T-cell lymphomas had rearranged TCRγ and germ-line IgH genes and were either CD3(Leu4)⁺CD56⁺ (2 cases) or CD3(Leu4)⁺CD56⁻ (1 case). Immunohistochemical (IH) studies showed that both perforin and TIA-1 were expressed universally in NL, irrespective of NK- or T-cell lineage. Dual labelling of TIA-1 by IH and EBER by in situ hybridisation demonstrated that the granule proteins were expressed predominantly by the EBER⁺ tumour cells. Our results indicate that NLs are derived from EBV-infected cytotoxic lymphocytes of both NK- and T-cell lineage. We postulate that cytotoxic lymphocytes generated during the cellular immune response to EBV infection or re-activation at the nasal region themselves may become targets for EBV infection and subsequent transformation. Int. J. Cancer 73:332–338, 1997. © 1997 Wiley-Liss, Inc.     

Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosis morphology.

Nasal lymphoma with polymorphic reticulosis (PR) morphology is now categorized as T/natural killer (T/NK) cell lymphoma. In this study, immunophenotypes and genotypes of proliferating cells in 21 cases with PR were examined. The patients included 13 men and 8 women ranging in age from 20 to 74 (median 37) years. All patients presented with lesions in the upper respiratory tract, mostly in the nasal cavity. Histological specimens obtained from the primary lesions (19 cases) and metastatic cervical lymph nodes (2 cases) were used for analyses. Histologically, polymorphous proliferation was found in 20 cases, and these were thus diagnosed as PR. A monomorphous pattern was found in the remaining last case. Immunohistochemical analysis revealed that the proliferating cells were CD56 (123C3)+ and/or CD16 (2H7)+, TIA-1+ and frequently stained CD3 epsilon+. Tumor cells were frequently stained positively with monoclonal antibodies (mAbs) for T lymphocytes, but were negative for T-cell receptor (TCR) beta and delta chain expression. In situ hybridization analysis using an Epstein-Barr virus-encoded early RNA 1 (EBER-1) probe revealed positive signals in 13 of the 15 cases examined. Southern blotting analysis for clonality of the Epstein-Barr virus (EBV) genome in 12 positive cases confirmed the presence of monoclonal proliferation in 7 cases. The pattern of TCR gamma chain gene rearrangement was examined by PCR analysis of DNA from tumor tissues by the denaturing gradient gel electrophoresis method. The results demonstrated no clonal rearrangement in any of the 21 cases examined, including 7 cases with proven clonal proliferation of EBV-infected cells, indicating the absence of T-cell clones. Our findings strongly suggested that nasal T-cell lymphoma is in fact a NK cell lymphoma.     

T-large granular lymphocyte leukemia accompanied by an increase of natural killer cells (CD3-) and associated with ulcerative colitis and autoimmune hepatitis

Clonal expansion of large granular lymphocyte(LGL) have been classified into T-LGL and NK-LGL leukemia. T-LGL leukemia cells have a CD3+ phenotype and show clonal T-cell receptor(TCR) gene rearrangement. NK-LGL leukemia cells have a CD3- phenotype and no TCR gene rearrangement. We report a case of T-LGL leukemia accompanied by NK LGL expansions in a 65-year-old man who was observed 3 years earlier to have a LGL lymphocytosis in association with ulcerative colitis(UC) and autoimmune hepatitis (AIH). Phenotypic analysis of peripheral blood by flow cytometry disclosed an increase of both T-LGL(CD3+,CD56-,CD57+,and TCRalphabeta+) and NK-LGL (CD3-,CD16+,CD56+, and CD57+). Clonal rearrangement of the TCR beta gene was detected. A diagnosis of UC and AIH was made on the basis of the X-ray and mucosal biopsy findings of the large intestine, and on the scoring system for diagnosis of AIH, respectively. The disease was nonprogressive, and mesalazine and prednisolone were successful for treatment of UC and AIH. Previously reported cases of T-LGL, NK-LGL leukemia, or NK cell lymphocytosis had no association with UC or AIH, and there have been no reports having both T-LGL leukemia with T-cell receptor gene rearrangement and chronic NK cell lymphocytosis co-existing in a single patient.     

An autopsy case of lethal midline granuloma that terminated in an intracranial hemorrhage

Reported is an autopsy case of a lethal midline granuloma (LMG) that originally had been manifested as chronic sinusitis and that terminated in intracranial hemorrhage. A 30-year-old woman developed a necrosis of the nasal cavity while being treated for chronic sinusitis for approximately four months. She subsequently died of an intracranial hemorrhage, and an autopsy revealed a necrosis that had progressed from the nasal cavity to the frontal base of the brain, and an infiltration of atypical cells that had an immunoreactivity to the T-cell antigens was observed. Recent studies have strongly suggested the possibility that some cases of an LMG, if not all, may be identical to a T-cell lymphoma. Our case is described and this disease is discussed.     

Diagnostic significance of TCR gene clonal rearrangement analysis in early mycosis fungoides

Mycosis fungoides(MF),the most common type of cutaneous T-cell lymphoma,has various unspecific clinical and histological characteristics.Its early diagnosis is challenging.The application of T-cell receptor(TCR) gene clonal rearrangement to the diagnosis of MF has been widely studied.In this study,we used polymerase chain reaction(PCR) to investigate the diagnostic significance of detecting TCR-γ and-β gene clonal rearrangement in the early diagnosis of mycosis fungoides.PCR for TCR-γ and TCR-β gene rearran...     

Diagnostic and prognostic importance of T-cell receptor gene analysis in patients with Sézary syndrome.

BACKGROUND: Sézary syndrome (SS) is characterized by erythroderma, peripheral lymphadenopathy, and circulating Sézary cells and is clinically heterogeneous. METHODS: T-cell receptor (TCR) gene analysis was performed using DNA extracted from peripheral blood mononuclear cells from 74 patients, and the results were correlated with a variety of other diagnostic parameters and patient outcomes. RESULTS: Two groups were identified: 66 patients with clonal TCR gene rearrangement (clonal patients) detected with Southern blot analysis and/or polymerase chain reaction/single-strand conformational polymorphism analysis and 8 patients with no clonal rearrangement detected (nonclonal patients) using either technique. Clonal patients were compared with nonclonal patients. The following median blood parameters were significantly greater in the clonal group: total white cell count (13.7 10(9)/L vs. 9.6 10(9)/L), lymphocyte count (4.9 10(9)/L vs. 2.2 10(9)/L), absolute Sézary count (3.22 10(9)/L vs. 0.99 10(9)/L), CD4 count (3.17 10(9)/L vs. 1.36 10(9)/L), and CD4:CD8 ratio (15.86 vs. 3.21). An expanded population of T-cells of a specific TCR variable beta subset was detected in 7 of 36 clonal patients and in 1 of 4 nonclonal patients. Cytogenetic analysis of peripheral blood from 1 nonclonal patient and 6 clonal patients was normal. The median survival from the time of diagnosis was 45 months in the clonal group, and 40 of 49 deaths were cutaneous T-cell lymphoma (CTCL)-related, whereas 3 deaths in the nonclonal group were unrelated to CTCL (P < 0.01; log-rank test). Multivariate proportional hazards analysis showed that the absolute Sézary count and lymph node status were independent prognostic variables (P = 0.016 and P = 0.036, respectively). CONCLUSIONS: TCR gene analysis defines a distinct clinicopathologic group of patients with SS. Clonal patients have a poor prognosis and are likely to die from leukemia/lymphoma, whereas nonclonal patients may have a reactive, inflammatory T-cell disorder. The authors suggest that the definitive diagnostic criteria for patients with SS should include the presence of a clonal TCR gene rearrangement.     

Clinicopathologic and therapeutic aspects of angioimmunoblastic lymphadenopathy-related lesions.

The clinicopathologic features of 14 patients with angioimmunoblastic lymphadenopathy (AIL)-related lesions were analyzed. Lymph node biopsy specimens from all the patients showed a diffuse obliteration of lymph node architecture, prominent vascular proliferation, a polymorphous cellular infiltrate, including immunoblasts, and varying degrees of clear cell proliferation. The patients were eight males and six females, with a median age of 58.5 years. All but one were in an advanced stage at the time of diagnosis. Bone marrow involvement was observed in eight patients. Thirteen patients had a negative serologic reaction for antibody to human T-cell leukemia virus type I (HTLV-I), and one patient was considered to be a HTLV-I carrier. Polyclonal hypergamma-globulinemia was observed in 6 patients, and 6 of the 12 patients showed elevated IgE levels. Immunophenotyping of the involved lymph nodes revealed a preponderance of T-cells in all the patients. Eleven of these patients showed a predominance of CD4+ over CD8+ T-cells, and only one patient showed a predominance of CD8+ over CD4+ T-cells. Two of five patients whose gene analysis was carried out showed clonal rearrangement of the T-cell receptor beta chain gene without rearrangement of the immunoglobulin heavy chain genes. Twelve patients received doxorubicin-containing combination chemotherapy; of these, 7 patients achieved complete response, and the other 5 had partial response. Nine patients are still alive with a median follow-up period of 21 months, and five patients died during the follow-up period. Progression to high-grade T-cell lymphoma with systemic infiltration was ascertained in two of three cases for which autopsy was performed. From our experience, we recommend doxorubicin-containing combination chemotherapy as initial therapy for AIL-related lesions.     

Expression of myeloid cell phenotypes by a novel adult T-cell leukemia/lymphoma cell line.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) can infect a number of cells of different lineages in vitro, yet the immunophenotypes of most adult T-cell leukemia/lymphomas (ATLs) are restricted to CD4+. The apparent discrepancy between these findings is still largely unknown. PURPOSE: We report on a unique case of ATL in which the leukemia cells were positive for both T-cell and myeloid cell antigens. To characterize these cells, we isolated cell lines from this patient with ATL. METHODS: The fresh leukemia cells were cultured without the addition of interleukin-2. Cell cloning was carried out by limiting dilution. RESULTS: A cell line (MU) and its clonal sublines were established. MU cells showed the same chromosomal abnormalities and T-cell receptor beta-chain gene rearrangement pattern as those of fresh leukemia cells. MU cells were exclusively positive for a myeloid cell marker (CD13) but not for T-cell markers, despite the presence of T-cell receptor gene rearrangement. CONCLUSION: The established ATL cell line showed both T-cell and myeloid cell characteristics, which seems to be the first evidence for the close association of ATL cells with both lymphoid and myeloid features. The cell line may provide a new insight for the targets of HTLV-1 infection and transformation in vivo.     

A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.     

Primary cutaneous follicle center lymphoma associated with alopecia areata

We report a patient who presented simultaneously with primary cutaneous follicle center lymphoma (PCFCL) of the face and scalp and alopecia areata of the scalp and beard bearing a clonal T-cell receptor gene rearrangement. To our knowledge, alopecia areata has not been previously reported in association with PCFCL. Both lesions regressed with topical imiquimod and systemic steroids, which suggests an inter-relationship in this case between the clonal B-cell and T-cell populations in driving outgrowth of these lesions.     

Natural killer cell lymphoma in the duodenum

We present a case of duodenal non-Hodgkin lymphoma in a 71-year-old woman. Immunohistochemistry characterized the lymphoma cells as CD2(+); surface CD3(-) but cytoplasmic CD3(+); CD7(+); and CD56(+) without a rearrangement of the T-cell receptor gene. Cells had a high N/C ratio and irregular nuclear outlines and lacked azurophilic granules and these features indicated that the lymphoma cells arose from natural killer (NK) cells. She was treated with intensive chemotherapy including pirarubicin, cyclophosphamide, vincristine, and prednisolone, but died three weeks after diagnosis. CD56(+) lymphomas originate from NK or cytotoxic T cells and are designated "extranodal NK/T-cell lymphoma, nasal type" in the WHO classification. Nasal NK cell lymphoma is most common in East Asians and CD56(+) lymphomas usually occur in the nasal area. Extranasal forms such as gastrointestinal lymphomas are very rare and usually carry a poor prognosis. Extranodal NK/T-cell lymphoma, nasal type, is characterized by a broad morphologic spectrum and have variable prognosis. These lymphomas constitute an heterogeneous group, and their subclassification has not yet been established.     

Detection of clonal Epstein-Barr virus in malignant proliferation of peripheral blood CD3+ CD8+ T cells.

Epstein Barr virus (EBV) DNA was detected in a monoclonal proliferation of T cells in a three-year-old girl who presented with a history of fever, hepatosplenomegaly, and generalised lymphadenopathy. The disease ran a rapid, fulminant course and the patient died 11 days after presentation. Examination of the blood showed a lymphocytosis of 50 x 10(9)/l with all the cells showing the morphology of large granular lymphocytes. These cells were CD2+3+8+25+. Cytogenetic studies showed the presence of a 6q- clone. Southern blotting and hybridisation with a constant region probe for the T-cell receptor (TCR) beta chain gene showed clonal rearrangement of the TCR beta gene. Hybridisation of the Southern blot to the EBV XhoI probe revealed a clonal pattern of episomal EBV DNA. Our results establish the association between clonal EBV infection to a malignant proliferation of peripheral blood CD8+ T cells.     

Presence of Epstein-Barr virus DNA in nasal lymphomas of B and 'T' cell type

We studied 12 tumours from 11 Chinese patients with primary nasal lymphoma for presence of Epstein-Barr Virus (EBV) DNA, using Southern-blot analysis. These results were correlated with immunophenotype and T-cell receptor (TcR) or immunoglobulin gene rearrangement patterns. EBV DNA was detected in all nine tumours with a 'T' phenotype, in both primary and secondary sites. When the structure of the viral genomic termini was studied using the EcoRI-Dhet probe, a single clonal episomal band was demonstrated in five tumour samples, with one other case showing a biclonal pattern. However, none of these cases showed clonal rearrangement of TcR beta chain gene, and TcR gamma rearrangement was found only in one. The lineage of these phenotypic 'T' lymphomas therefore require further studies for confirmation. Two out of three B-lymphomas were also EBV DNA+; clonal EBV DNA was found in one. Their B-lineage was confirmed by detection of clonal immunoglobulin gene rearrangements. The association of EBV with an increasing number of lymphomas of different types highlights the need for continued study into its role in oncogenesis.     

Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias,rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin

We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.     

Epstein-Barr virus-associated peripheral T-cell lymphoma of activated CD8 phenotype

Two childhood cases are reported of peripheral T-cell lymphoma; the neoplastic cells expressed activated CD8 (T8) phenotype and contained Epstein-Barr viral (EBV) DNA. Both patients had an aggressive and rapid clinical course despite chemotherapy. Elevated titers of antibodies to EBV-viral capsid antigen (greater than 640) and early antigen (greater than 10) were found in both patients. Histology revealed pleomorphic immunoblastic lymphoma with extensive necrosis in one case and an angioimmunoblastic lymphadenopathy-like pattern containing Reed-Sternberg-like giant cells in the other. Southern blot hybridization studies showed clonal rearrangement of the T-cell-receptor beta gene in both cases, and a cytogenetic study on one case revealed clonal structure abnormality involving chromosomes 1, 6, 7, 10, and 19. Analysis of the tumor DNA showed a high copy number of EBV genome per cell compared with that of Raji and Marmoset B 95.8 lines; the study for human T-cell leukemia virus type I was negative. The EBV genome was found by in situ hybridization in the tumor nuclei in both cases. In addition to Burkitt's lymphoma, T-cell lymphoma of the helper phenotype, and Hodgkin's disease, EBV can contribute to the development of CD8-positive aggressive T-cell lymphoma.     

Establishment of a novel cell line with T-lineage phenotype (HPB-MLp-W) from a non-Hodgkin's lymphoma patient

We report the characterization of a novel human T-cell line, HPB-MLp-W, which was established from blastic cells of a lymph node specimen from a patient with non-Hodgkin's lymphoma. They demonstrated the T-cell association antigens, CD2 and CD4, but no CD3, CD8, CD1, CD5, CD7 nor T-cell antigen receptor on their cell surfaces. They were also positive for Ia and Ki-1 antigen, and negative for CD25 (Tac-1). The cell line HPB-MLp-W had the same pattern of antigen expression as the patient's cells. Southern-blot analysis of DNA showed a rearrangement of the T-cell receptor-alpha and beta genes. To our knowledge, this is a novel cell line with unique T-lineage marker, to be established from a case of non-Hodgkin's lymphoma.     

Primary central nervous system extranodal NK/T-cell lymphoma,nasal type: case report and review of the literature

Primary central nervous system (CNS) extranodal NK/T-cell lymphoma, nasal type (NKTCL), is an extremely rare tumor. To the best of our knowledge, only four cases have been described previously. Here, we report a case of primary CNS NKTCL in a 25-year-old immunocompetent Chinese male. The patient presented with worsening dizziness, headaches, and vomiting for approximately 2 weeks. Magnetic resonance imaging demonstrated three masses with solid components entirely in the parenchyma of the right hemisphere, and no sinonasal/nasopharyngeal lesions were found. The patient underwent a partial resection of the right temporal mass. Histological examination revealed that intermediate-sized, pleomorphic lymphocytes were arranged in an angiocentric distribution with large geographic necroses. The tumor cells expressed CD3ε, CD56, TIA-1, granzyme B, and Epstein−Barr virus-encoded RNAs. A rearrangement study showed T-cell receptor γ-chain gene rearrangement with monoclonal appearance. Postoperative chemotherapy and radiotherapy were also given, but the lymphoma failed to respond to therapy and the patient died 18 months later. Our observation and the four others found in the literature indicate that primary CNS NKTCL occurs predominantly in adult males. This is the youngest patient with primary CNS NKTCL reported.     

Follicular T-cell lymphoma mimicking lymphocyte-rich classic Hodgkin lymphoma: a case report of a diagnostic pitfall

Follicular T-cell lymphoma (FTCL), one of the nodal T-cell lymphomas with T follicular helper (T_^FH) phenotype, is an uncommon disease. The diagnosis of FTCL is challenging on the distinction from the morphological mimics mostly exemplified by follicular lymphoma. Here, we described a case of FTCL that mimicked lymphocyte-rich classic Hodgkin lymphoma (LRCHL). A 47-year-old male presented with cervical lymphadenopathy. The biopsy specimen demonstrated nodular lymphoid proliferation, which included scattered CD30+ CD15- CD20- PAX5 weakly+ Hodgkin and Reed-Sternberg (HRS)-like cells and a rich distribution of CD3+ CD4+ PD1+ T-cells. Epstein Barr virus was not detected in HRS-like cells, but it was detected in a small proportion of the scattered lymphocytes. The large cells were also negative for programmed cell death ligand 1, which appeared to be coincidental as described in our previous report of LRCHL. However, flow cytometry showed a CD3- CD4+ T-cell population that constituted 37.4% of all gated lymphocytes. A PCR analysis showed a clonal T-cell receptor-gamma gene rearrangement, but not a clonal immunoglobulin heavy chain gene rearrangement, and showed RHOA G17V mutation. The constellation of these findings led us to revise the diagnosis to FTCL. This result indicated that our case belonged to a relatively indolent subgroup of nodal peripheral T-cell lymphoma of T_^FH phenotype, which affects patients ≤60 years old, recently proposed by our group. This case report expands our understanding of the morphologic spectrum of FTCL and its clinicopathologic significance.