Diagnosis Of Peripheral T-cell Lymphoma Research Articles

Update on T-cell lymphoma

Update on T-cell lymphoma

Primary T-cell lymphoma of the thyroid: case report and review of the literature

Here we report a rare case of primary T-cell lymphoma of the thyroid gland. A 32-year-old Chinese man was admitted to our hospital because of marked goiter and subcutaneous nodules. Computed tomography (CT) scan of the neck disclosed diffuse enlargement of the thyroid gland. A diagnosis of peripheral T-cell lymphoma was made according to cytopathological findings of fine-needle aspiration (FNA) of the thyroid gland and skin biopsy. Immunohistochemistry stain showed that the tumor was positive for CD3 and negative for CD20. Clonal T-cell receptor (TCR-gamma) gene rearrangements were demonstrated by polymerase chain reaction. After six cycles of combination chemotherapy (bleomycin, cyclophosphamide, doxorubicin, vincristine, and prednisone), the thyroid retracted to normal size gradually.

Does High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation Have a Role in the Primary Treatment of Peripheral T-Cell Lymphomas?

Abstract A 58-year-old woman presents with a recent diagnosis of peripheral T-cell lymphoma, unspecified. She has read through Google® that the “best treatment” for this disorder is stem cell transplantation—she asks you if you recommend this treatment?

Peripheral T-cell Lymphoma Presenting as Sclerouveitis

To report an unusual case of ocular peripheral T-cell lymphoma presenting as sclerouveitis. A 53-year-old woman presented with painful, unilateral sclerouveitis and was initially treated with antivirals and corticosteroids for what was presumed to be isolated ocular HSV infection with vasculitis. When she failed to improve the conjunctiva was biopsied and characterized by immunohistochemical and molecular methods. The literature regarding conjunctival T-cell lymphomas as well as lymphomas mimicking scleritis is reviewed. Biopsies of a scleral/conjunctival nodule from the right eye were obtained on 2 occasions, the second of which revealed the presence of intermediate to large size lymphocytes that were CD3, T-cell intracellular antigen 1 and Granzyme B positive but CD56 and Epstein Barr virus negative. Polymerase chain reaction showed clonal T-cell receptor gamma rearrangements in DNA samples isolated from biopsy tissue. Another biopsy was obtained from a mucosal lesion in the oropharynx, which was shown to contain an identical T-cell receptor gamma rearrangement. These results led to the diagnosis of peripheral T-cell lymphoma. Conjunctival T-cell lymphomas have been reported in two other patients both of which also had involvement of upper airway structures. Five other reports of lymphoma mimicking scleritis are discussed. Peripheral T-cell lymphoma should be considered in the differential diagnosis of patients who present with sclerouveitis of unknown etiology unresponsive to conventional therapy. If a conjunctival T-cell lymphoma is identified a systemic evaluation for lymphoma with particular attention to the upper airway is justified.

Pulmonary manifestations of peripheral T‐cell lymphoma: case report and review of the literature

Peripheral T-cell lymphomas (PTCL) represent approximately 10% of non-Hodgkin's lymphomas. Pulmonary involvement is an uncommon manifestation of this heterogeneous group of malignancies. Report of a case. This case report describes a 75-year-old man with fever, weight loss, anemia, enlargement of spleen and liver, atypical lymphocytes and pulmonary nodules. Lung biopsy showed lymphocytic infiltration of the lung parenchyma. T-cell receptor gamma gene rearrangement by polymerase chain reaction confirmed the diagnosis of peripheral T-cell lymphoma. Unfortunately, the patient died because of refractory and aggressive disease. Pulmonary and pleural involvement are seen in patients with PTCL and usually carry a poor prognosis. The subject of pulmonary involvement in peripheral T-cell lymphoma is discussed.

Peripheral T‐cell lymphoma with diffuse pulmonary infiltration and an increase in serum KL‐6 level

Peripheral T-cell lymphoma is a subtype of non-Hodgkin's lymphoma. A case of peripheral T-cell lymphoma showing diffuse pulmonary involvement together with a marked increase in the level of serum KL-6 is presented. CXR and CT revealed reticular and ground-glass opacities, which mimicked interstitial pneumonia. Immunopathological findings and an analysis of T-cell receptor gene rearrangements of the lung biopsy specimen led to a definite diagnosis of peripheral T-cell lymphoma. In addition, the extensive proliferation of type II pneumocytes, which stained strongly positive for anti-KL-6 antibody suggested that the pneumocytes were the source of serum KL-6.

The Diagnosis, Management, and Role of Hematopoietic Stem Cell Transplantation in Aggressive Peripheral T-Cell Neoplasms

Peripheral T-cell neoplasms (PTCNs) comprise a group of uncommon and heterogeneous lymphoid malignancies. They are more difficult to diagnose and treat and have a worse prognosis than B-cell lymphomas. Although PTCNs initially show a significant degree of chemosensitivity, the outcome of treatment with conventional dose chemotherapy remains poor. We reviewed the literature on the diagnosis, treatment, and collective transplant reports regarding PTCNs. The correct diagnosis of peripheral T-cell lymphoma requires a combination of clinical presentation, morphology, immunophenotype, and molecular study. While no specific treatment other than conventional dose chemotherapy is currently available for aggressive PTCN, histone acetylase inhibitors and monoclonal antibodies such as anti-CD7 and anti-CD52 are being studied in T-cell malignancies. The role of autologous and allogeneic transplantation is being investigated for high-risk, relapsed, and refractory PTCNs with some promising results. Access to hematopathology expertise in a tertiary care setting may lead to earlier and more accurate diagnoses of these diseases. PTCNs comprise a heterogeneous group of diseases with no widely accepted standard of care, and accurate determination of their histologic subtypes correlates with prognosis. Patients in first complete remission with poor risk features and patients with relapsed and refractory disease should be considered for bone marrow transplant due to the poor outcomes obtained with conventional chemotherapy.

Different Outcome for Angioimmunoblastic T-Cell Lymphoma (AIL) and Peripheral T-Cell Lymphoma Unspecified (PTCL-U) Following Upfront Autologous Stem Cell Transplantation.

Introduction: Peripheral T-cell lymphomas (PTCL) are rare diseases and optimal treatment strategies still remain to be defined. With the exception of the ALK-positive anaplastic large cell lymphoma (ALCL) that shows a favourable outcome following conventional chemotherapy, PTCL are known for their poorer prognosis compared to aggressive B-cell lymphomas. However, the impact of the different PTCL-subtypes on treatment outcome has not been clearly demonstrated in prospective studies. PTCL unspecified (PTCL-U) and angioimmunoblastic T-cell lymphoma (AIL) represent the most common subtypes of PTCL in Western countries, accounting for approximately 70% of PTCL. We therefore analysed the data of our study on myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) in primary diagnosed PTCL with regard to the main histologic subtypes.Material and Methods: From 06/00 to 06/06 92 patients with confirmed diagnosis of PTCL entered the study. Primary cutaneous PTCL and ALK+ ALCL were excluded from the trial. Main subtypes were PTCL-U (n= 37) and AIL (n= 28) accounting for 65 of the 92 patients (71%). 0f these patients 53 (PTCL, n= 31; AIL, n= 22) were evaluable for the analysis (82%).Results: Median age was 50 years in the PTCL-U and 47.5 years in the AIL group, respectively. The International Prognostic Index (IPI) did not differ in both groups. In the PTCL-U and the AIL group a low/intermediate-low risk was found in 35% and 36%, respectively and a high/intermediate-high risk in 65% and 64%, respectively. There were slightly more patients in stage IV in the AIL group compared to the PTCL-U group (64% versus 53%). In addition, more patients in the AIL group complained of B-symptoms and had bone marrow involvement compared to the PTCL-U group (86% versus 66% and 48% versus 39%, respectively). However, in an intent-to treat analysis only 58% in the PTCL-U group compared to 82% in the AIL group underwent ASCT mainly due to a higher rate of patients with progressive disease in the PTCL-U group. The median overall survival (OS) was 11 months in the PTCL-NOS and 20 months in the AIL group. Regarding only patients undergoing ASCT, the median OS was 13.5 months in the PTCL-U and 25.5 months in the AIL group.Conclusion: Our analysis suggests that patients with AIL, although showing a slightly more unfavourable risk profile at diagnosis, benefit more from upfront autotransplantation than patients with PTCL-U in our study.

FDG-PET in Peripheral T-Cell Lymphoma.

The sensitivity and specificity of fluorine-18 fluoro-deoxy-glucose positron emission tomography (PET) in the evaluation of peripheral T cell lymphomas (PTCL) is not well established. In this abstract, we describe our experience utilizing PET in the diagnostic evaluation of PTCL.A retrospective review of 2768 PET examinations conducted at our institutionbetween the years 1999–2006 produced twenty-six examinations among twenty-two patients with a biopsy proven diagnosis of PTCL. All patients underwent staging of their disease using both conventional diagnostic methods and PET. Their therapeutic status was also taken into consideration when interpreting PET examinations. PTCL were classified by World Health Organization (WHO) criteria and included: PTCL-unclassified (PTCL-U), anaplastic lymphoma kinase positive (+) and negative (−) anaplastic large cell lymphoma, gioimmunoblastic (AITL n=1), and natural killer T-cell nasal type (NK/T n=1). PET results for each patient were compared against a standard of reference, and the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PET) of PET were calculated.PET had an overall sensitivity of 55% and specificity of 100% in PTCL-U. PET had an overall sensitivity of 83% and specificity of 100% in ALCL. PET had an overall sensitivity of 13% and specificity of 0% in cutaneous PTCL. Among patients with non-cutaneous PTCL-U, the sensitivity and specificity were 83% and 100% respectively. Among patients with non-cutaneous ALCL, the sensitivity and specificity were 100% respectively. Excluding those patients with cutaneous PTCL, PET correlated with clinical outcome in 87% of PTCL-U 100% of ALCL patients. The average maximum standard uptake value (g/mL) of abnormal foci demonstrated greater intensity in patients with ALCL (13.1) than those with PTCL-U (8.87) (Figure 1). PET had excellent correlation with CT, physical examination and clinical follow-up at both nodal and extra-nodal sites, but poor correlation at cutaneous sites (Figure 2).The PPV and NPV of restaging PET in PTCL-U were 75% and 100% respectively. In ALCL, the PPV and NPV of restaging PET were 66% and 100% respectively.PET is useful for staging and restaging patients with nodal and non-cutaneous extra-nodal involvement in PTCL-U and ALCL. It demonstrates a comparatively low sensitivity in cutaneous PTCL. [Display omitted] [Display omitted]

Peripheral T-cell lymphoma in a five year old

We report a case presenting with persistent pyrexia that led to the diagnosis of peripheral T-cell lymphoma, a rare malignancy in childhood. The case illustrates diagnostic conundrums in a patient who is not responding as expected to treatment.

Peripheral T-Cell Lymphoma and Job's Syndrome: A Rare Association

Job's syndrome or hyper-immunoglobulin E syndrome is a primary immunodeficiency characterized by recurrent staphylococcal abscesses and markedly elevated serum immunoglobulin E concentrations. Here we report a case of a woman with hyper-immunoglobulin E syndrome with a diagnosis of peripheral T-cell lymphoma, and we review the pertinent literature.

CALGB 59901: Results of a Phase II Study of 506U78 in CTCL and PTCL.

T-cell lymphoma comprises approximately 10% to 15% of all lymphomas seen in the Western hemisphere and may be broadly categorized into 2 main groups: the various histologies of peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Overall, PTCL patients (pts) are believed to have a worse prognosis than pts with B-cell lymphoma. Except for the favorable subset of ALK-1-positive anaplastic large cell lymphoma, most PTCL are incurable with standard therapy. Salvage chemotherapy is often ineffective in relapsed PTCL or in pts with advanced CTCL no longer responding to agents that modulate T-cell function (e.g. retinoids, interferons, antibodies). New agents are needed for these pts. 506U78 is a pro-drug of ara-G, a deoxyguanosine analogue. Ara-G itself is difficult to synthesize and poorly water soluble. 506U78 is 10 X more water soluble than ara-G and is rapidly demethoxylated in blood to ara-G, which has been shown to be toxic to T-cells at even micromolar concentrations. Based on positive preliminary data with 506U78 in pediatric pts with recurrent/refractory precursor T-lymphoblastic lymphoma or leukemia (PTLL), we activated CALGB protocol 59901, a Phase II study of 506U78 in pts with systemically untreated CTCL or refractory/relapsed PTCL. Objectives were to determine response rate, remission duration, and safety associated with 506U78 given at 1.5 g/m2/day on Days 1, 3, and 5 as an IV infusion q 21 days for a minimum of 2 cycles and/or to continue for 2 cycles after CR (up to max of 8 cycles). Eligibility included: diagnosis of PTCL or CTCL; measurable disease; no CNS lymphoma; no history of seizure disorder or significant (>grade 1) neurologic dysfunction; age <70; PS 0–2; adequate renal and hepatic function; CTCL pts were originally not permitted to have received systemic chemo, but the protocol was amended on 2/15/02 to allow therapy with one prior course of single-agent chemotherapy in an attempt to increase accrual. Nineteen pts were enrolled between 5-15-00 and 3-15-04: 11 CTCL and 8 PTCL pts. Five of 11 CTCL pts had received no prior therapy and 7 of 7 evaluable PTCL pts had received prior chemo and 2 prior BMT. Adverse event (AE) data are available for 18 pts. Grade 3 or 4 AEs were documented in 50% and 28% of pts, respectively. Thirty-three percent of pts experienced Grade 3 or 4 neurologic toxicities which included: ataxia, vertigo, peripheral neuropathy, confusion, and/or depressed consciousness. There were 2 treatment-related deaths, 1 due to infection and 1 due to CNS hemorrhage (both in pts with CTCL). There were 2 PRs to therapy, one each in the PTCL and CTCL groups, with disease progression at 3m and 5.5m, respectively. The overall response rate is 10.5% (1.3% – 33.1%; 95% CI). Fifteen of 19 pts have died. Median EFS was 1.2m (1.0, 1.6 m; 95% CI) and median OS was 3 months (1.4, 9.8m; 95% CI). Due to lack of efficacy and excessive toxicity the protocol was closed on 3/15/04. In contrast to the favorable results seen in pediatric pts with recurrent PTLL, our data demonstrate that 506U78 has low efficacy, is unacceptably toxic and is not recommended as monotherapy in adult pts with CTCL and PTCL.

Differential Expression of T-bet, a T-box Transcription Factor Required for Th1 T-Cell Development, in Peripheral T-Cell Lymphomas

We studied T-bet expression in 91 cases of peripheral T-cell lymphoma (PTCL) by immunostaining and found expression in 42 cases (46%), including all 5 lymphoepithelioid lymphoma cases and 12 (86%) of 14 angioimmunoblastic lymphoma cases, but only 9 (25%) of 36 anaplastic large cell lymphoma cases. Expression of T-bet in PTCL correlates with expression of other markers of Th1 T-cell differentiation, including CXCR3 ( P < .0001), CD69 ( P = .0013), LEF-1 ( P = .0007), and OX40/CD134 ( P = .005), and absence of expression of markers of Th2 T-cell differentiation, including CD30 ( P = .0001) and CXCR4 ( P = .0144). Of 22 cases of PTCL immunoreactive for all Th1- associated markers previously studied and nonreactive for Th2-associated markers, 20 (91%) were immunoreactive for T-bet. Of 22 PTCL cases immunoreactive for Th2-associated markers studied and nonreactive for all Th1-associated markers studied, 4 (18%) were immunoreactive for T-bet. The remaining 47 PTCL cases (52%) exhibited incomplete or mixed staining for Th1- and Th2-associated markers, with 18 (38%) of 47 immuno-reactive for T-bet. T-bet is a new marker that may contribute to the diagnosis and subtyping of PTCLs. T-bet expression in these neoplasms provides further support for a model of PTCL in which tumor subsets express markers of, and may be derived from, Th1- or Th2-committed T cells.

Differential Expression of T-bet, a T-box Transcription Factor Required for Th1 T-Cell Development, in Peripheral T-Cell Lymphomas

We studied T-bet expression in 91 cases of peripheral T-cell lymphoma (PTCL) by immunostaining and found expression in 42 cases (46%), including all 5 lymphoepithelioid lymphoma cases and 12 (86%) of 14 angioimmunoblastic lymphoma cases, but only 9 (25%) of 36 anaplastic large cell lymphoma cases. Expression of T-bet in PTCL correlates with expression of other markers of Th1 T-cell differentiation, including CXCR3 (P < .0001), CD69 (P = .0013), LEF-1 (P = .0007), and OX40/CD134 (P = .005), and absence of expression of markers of Th2 T-cell differentiation, including CD30 (P = .0001) and CXCR4 (P = .0144). Of 22 cases of PTCL immunoreactive for all Th1- associated markers previously studied and nonreactive for Th2-associated markers, 20 (91%) were immunoreactive for T-bet. Of 22 PTCL cases immunoreactive for Th2-associated markers studied and nonreactive for all Th1-associated markers studied, 4 (18%) were immunoreactive for T-bet. The remaining 47 PTCL cases (52%) exhibited incomplete or mixed staining for Th1- and Th2-associated markers, with 18 (38%) of 47 immuno-reactive for T-bet. T-bet is a new marker that may contribute to the diagnosis and subtyping of PTCLs. T-bet expression in these neoplasms provides further support for a model of PTCL in which tumor subsets express markers of, and may be derived from, Th1- or Th2-committed T cells.

Fine needle aspiration cytology in the diagnosis of uncommon types of lymphoma

Aims: Fine needle aspiration (FNA) cytology is an accepted means of diagnosing and typing common forms of lymphoma, particularly small lymphocytic lymphoma, follicular lymphoma, and large B cell lymphoma. However,...

Primary cerebral lymphoma and membranous nephropathy: A still unreported association

Paraneoplastic nephrotic syndrome (NS) in the setting of membranous nephropathy (MN) is a well-known and often prodromal complication of renal and extrarenal malignancy. Primary cerebral lymphoma is a rare neoplasm uncommonly investigated in the setting of NS. We describe for the first time a case of primary cerebral lymphoma in association with MN. An elderly woman presented for renal biopsy because an NS had been diagnosed previously and treated by steroid therapy. Primary membranous glomerulonephritis was diagnosed and immunosuppressive therapy was started. Twenty days later, she was readmitted because of left hemiplegia. Computed tomography and subsequent nuclear magnetic resonance evaluation of the brain documented an extensive cerebral space-occupying lesion. A cerebral malignant lymphoma was diagnosed at intraoperative histologic evaluation, and subsequent light microscopic and immunohistochemical studies allowed the diagnosis of peripheral T-cell lymphoma. Extensive clinical workup, including bone marrow biopsy, documented the lack of any neoplastic involvement outside the brain. Primary cerebral non-Hodgkin's lymphoma of peripheral T-cell derivation consequently was diagnosed. This case suggests that patients with MN, particularly elderly patients, should undergo complete screening for neoplasms. The absence of specific guidelines on this topic may be due partly to the lack of extensive description of all newly identified cases. All cases should be reported to evaluate whether this association is causal or fortuitous. © 2002 by the National Kidney Foundation, Inc.

A single-centre study of treatment outcomes and survival in 120 patients with peripheral T-cell non-Hodgkin's lymphoma.

We conducted a retrospective study of treatment outcomes and survival in 120 consecutive, unselected patients with peripheral T-cell non-Hodgkin's lymphoma, presenting at a single centre over a 20-year period. Cases met the criteria of the Revised European-American Lymphoma (REAL) Classification and patients with peripheral T-cell lymphoma of the following subtypes were included: anaplastic large T-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILD), peripheral T-cell lymphoma unspecified (PTCLu), and intestinal T-cell lymphoma (ITCL). The study population consisted of 120 patients with a presenting diagnosis of peripheral T-cell lymphoma. Cases that had been previously confirmed as T-cell lymphoma at formal pathology review were identified from the lymphoma database of this institution. Staging investigations, treatment type and outcomes were taken from patient records. For each subtype, clinical characteristics, response to initial treatment, duration of response and any subsequent relapse were recorded. Overall, relapse, and progression-free survival figures were calculated. The ALCL group had the best response rate to first line treatment 19 of 22 (86 percent) while the AILD group had the lowest response 12 of 29 (41 percent). Relapse rates were PTCLu 13 of 35 (37 percent), ITCL 10 of 34 (29 percent), ALCL 6 of 22 (27 percent) and AILD 7 of 29 (24 percent). In terms of median overall survival, a significantly superior survival was demonstrated for the ALCL group (7.05 years) compared to the remaining three groups. The ALCL group had the lowest risk of death while the ITCL group had the highest risk (hazard ratio: 2.82). Five-year survival rates were estimated to be ALCL 60 percent, PTCLu 40 percent, AILD 30 percent and ITCL 25 percent. This single-centre study demonstrated different outcomes for each group with significant differences in overall survival rates. These findings support the clinical utility of the REAL lymphoma classification in respect to the PTCL subgroups included in this study.

T cell and NK cell lymphoproliferative disorders.

This review covers the diagnosis and management of natural killer and peripheral T-cell lymphomas (PTCL). Problems with PTCL include their rarity, representing usually 10-15% of non-Hodgkin's lymphomas in the Western Hemisphere, morphologic heterogeneity, and lack of immunophenotypic markers for clonality. Additionally, their clinical behavior is variable and may not correlate with morphology. Dr. Kinney gives a general overview of the diagnosis of PTCL and NK cell neoplasms. Emphasis will be placed on extranodal T cell and natural killer (NK) cell lymphomas such as hepatosplenic lymphoma, subcutaneous panniculitis-like lymphoma and nasal/nasal type T/NK-cell lymphoma. The use of ALK gene regulation in the classification of anaplastic large cell lymphoma is also reviewed. Dr. Loughran describes current understanding of the pathogenesis of large granular lymphocyte (LGL) leukemia. The discussion focuses on LGL leukemia as an instructive model of dysregulated apoptosis causing both malignant and autoimmune disease. Current management options and mechanisms of therapeutic response are also described. Dr. Greer addresses whether PTCL should be treated differently from the more common diffuse large B cell lymphomas. He discusses the therapeutic options for anaplastic large cell lymphoma (ALCL), from a conservative approach for primary cutaneous ALCL to combination chemotherapy for the highly chemosensitive ALCL expressing anaplastic lymphoma kinase. He reviews therapy options for the extranodal subtypes of PTCL by drawing from series in adults, pediatrics, dermatology, and the Far East.

Ｔ細胞リンパ腫に移行したキャッスルマン病例

A 57-year-old male was admitted with severe fatigue and systemic lymphadenopathy. Surgical biopsy specimens revealed Castleman's disease of hyaline vascular type. After admission, Guillain-Bane syndrome developed and the ptient was treated with predonisolone and plasma pheresis was given. The patient's symptoms and lymphadenopathy responded and disappeared rapidly. Five months later, systemic lymphadenopathy recurred. Surgical biopsy was performed and the histological features were consistent with a diagnosis of peripheral T-cell lymphoma of diffuse mixed type, probably resulting from the progression of the Castleman's disease.

Acute renal failure in a patient with hemophagocytic syndrome

Acute renal failure (ARF) occurred in a 47-year-old man with hemophagocytic syndrome. Histological findings of the kidney revealed diffuse infiltration of interstitium by phagocytosing cells mixed with atypical lymphoid cells of varying size. The cytological features of the lymphoid population in liver and spleen were consistent with a diagnosis of peripheral T-cell lymphoma. We believe that this ARF could have been exacerbated by the interstitial infiltration of phagocytosing cells, reactive lymphoid cells, and T-cell lymphoma cells.