Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of ...GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy.
•Ten cases of an indolent T-cell lymphoproliferative disease of the gastrointestinal tract are reported.•It is important to recognize this condition because it can be mistaken for aggressive T-cell lymphoma, which may lead to unnecessary therapy.
Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular ...classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL–not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK+ ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1–induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.
We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with breast implants. Patient age ranged from 39 to 68 years, and the interval from implant to ALCL was 4 to 29 years. All ...tumors were composed of large, pleomorphic cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell receptor γ-chain rearrangements. Two patient subgroups were identified. Ten patients presented with effusion surrounded by fibrous capsule without a grossly identifiable tumor mass. Nine patients had stage I and 1 had stage II disease. Eight patients underwent implant removal and capsulectomy. Four patients received chemotherapy and 4 radiation therapy. All patients were alive without disease at last follow-up. A second subgroup of 3 patients had effusion and a distinct mass adjacent to the implant. One patient had stage I and 2 stage II disease. One patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1-year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis of ALCL associated with breast implant. Two patients received chemotherapy and 1 radiation therapy. Two patients died 2 and 12 years after diagnosis, respectively. We conclude that the clinical behavior of ALCL associated with breast implants is heterogeneous. Patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30 lymphoproliferative disorder of skin. In contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis.
Assessment of T-cell receptor γ gene (TRG) rearrangements is an importants consideration in the diagnostic workup of lymphoproliferative diseases. Although fragment analysis by PCR and capillary ...electrophoresis (CE) is the current standard of such assessment in clinical molecular diagnostic laboratories, it does not provide sequence information and is only semi-quantitative. Next-generation sequencing (NGS)-based assays are an attractive alternative to the conventional fragment size-based methods, given that they generate results with specific clonotype sequence information and allow for more accurate quantitation. The present study evaluated various test parameters and performance characteristics of a commercially available NGS-based TRG gene-rearrangement assay by testing 101 clinical samples previously characterized by fragment analysis. The NGS TRG assay showed an overall accuracy of 83% and an analytical specificity of 100%. The concordance rates were 88% to 95% in the V
1-8, V
10, and V
11 gene families, but lower in the V
9 gene family. This difference was mostly attributed to the incomplete polyclonal symmetry resulting from the two-tube CE assay versus the one-tube design of the NGS assay. The NGS assay also demonstrated strengths in distinguishing clonotypes of the same fragment size. This clinical validation demonstrated robust performance of the NGS-based TRG assay and identified potential pitfalls associated with CE assay design that are important for understanding the observed discrepancies with the CE-based assay.
Chronic active Epstein-Barr virus (EBV) infection of T-cell and NK-cell type, systemic form (CAEBV-T/NK-S) is characterized by EBV T-cell and/or NK-cell proliferation with no changes suggesting ...malignancy. Therefore, when Hodgkin/Reed-Sternberg (HRS)-like cells are scattered in CAEBV-T/NK-S, it is more likely to be misdiagnosed as classic Hodgkin lymphoma. We encountered a case wherein the patient showed HRS-like cells with typical NK phenotype. Therefore, we further investigated 8 similar cases to provide clinicopathologic and genetic features and discuss their distinction from other related diseases. Clinically, all cases met the diagnostic criteria of CAEBV. Moreover, 4/8 patients had hemophagocytic lymphohistiocytosis. The median survival was 16 months (range, 5 to 35 mo). Pathologically, all lymph node samples had a remarkably similar morphology with scattered HRS-like cells surrounded by a mixture of small-sized lymphocytes, plasma cells, and macrophages that masqueraded classic Hodgkin lymphoma. Besides, erythrophagocytosis was detected in 4/11 samples. The HRS-like cells were positive for CD2, CD3p, CD30, CD56, GrB, and EBER-ISH, but negative for CD20, CD5, PAX-5, and LMP-1. The surrounding lymphocytes were mainly CD8 cytotoxic T cells, without obvious aberrant expression. In addition, all patients were polyclonal in the T-cell receptor γ rearrangement test. The harbored mutations were mainly in epigenetic modifiers, JAK-STAT signaling pathway, and apoptosis/cell cycle pathway, including SOCS1, DDX3X, and KMT2D, similar to other EBV-associated T/NK-cell lymphoproliferative disorders. Therefore, the evidence indicates that "HRS-like cells of NK phenotype" is a variant of CAEBV-T/NK-S. This study may raise awareness of such confounding CAEBV-T/N-S cases in clinical practice to avoid misdiagnosis and treatment delay.
Summary
Background
Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports.
Aim
To further describe the clinical ...and histological features of LyP D and E based on a retrospective multicentre study.
Methods
The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms.
Results
After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow‐up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self‐regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar‐like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma.
Conclusion
LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.
1 Departament of Haematology and Bone Marrow Transplantation, Silesian Medical University, Katowice
2 Institute of Haematology and Transfusion Medicine, Medical University, Warsaw, Poland
...Correspondence: Grzegorz Helbig MD, PhD, Department of Haematology and Bone Marrow Transplantation, Silesian Medical University, Dabrowski Street 25, 40-032 Katowice, Poland., E-mail: ghelbig{at}o2.pl
Background: A T-cell clone, thought to be the source of eosinophilopoietic cytokines, identified by clonal rearrangement of the T-cell receptor and by the presence of aberrant T-cell immunophenotype in peripheral blood defines lymphocytic variant of hypereosinophilic syndrome (L-HES).
Design and Methods: Peripheral blood samples from 42 patients who satisfied the diagnostic criteria for HES were studied for T-cell receptor clonal rearrangement by polymerase chain reaction according to BIOMED-2. The T-cell immunophenotype population was assessed in peripheral blood by flow cytometry. The FIP1L1-PDGFRA fusion gene was detected by nested polymerase chain reaction.
Results: Forty-two HES patients (18 males and 24 females) with a median age at diagnosis of 56 years (range 17–84) were examined in this study. Their median white blood cell count was 12.9 x 10 9 /L (range 5.3–121), with an absolute eosinophil count of 4.5 x 10 9 /L (range 1.5–99) and a median eosinophilic bone marrow infiltration of 30% (range 11–64). Among the 42 patients, clonal T-cell receptor rearrangements were detected in 18 patients (42.8%). Patients with T-cell receptor clonality included: T-cell receptor β in 15 patients (35%), T-cell receptor in 9 (21%) and T-cell receptor in 9 (21%) patients, respectively. Clonality was detected in all three T-cell receptor loci in 4 cases, in two loci in 7 patients and in one T-cell receptor locus in the remaining 7 patients. The FIP1L1-PDGFRA fusion transcript was absent in all but 2 patients with T-cell receptor clonality. Three patients out of 42 revealed an aberrant T-cell immunophenotype. In some patients, an abnormal CD4:CD8 ratio was demonstrated.
Conclusions: T-cell abnormalities are present at high frequencies in patients with HES.
Key words: T cells, T-cell receptor, hypereosinophilic syndrome, FIP1L1-PDGFRA .
Related Article
Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations
Florence Roufosse
Haematologica 2009 94: 1188-1193.
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The prognostic value of skin and blood T-cell receptor clonality in mycosis fungoides is a matter of debate. Our aim was to ascertain the relation between the presence of a monoclonal T-cell ...population in the blood and in the skin with response to treatment in patients with mycosis fungoides.
Clinical features and follow-up data were retrospectively collected and analyzed in 94 patients with mycosis fungoides seen at a cutaneous lymphoma clinic in a single tertiary center. All patients had results of polymerase chain reaction analysis of T-cell receptor gamma gene rearrangement in lesional skin and in peripheral blood at time of diagnosis. Association of response to treatment with clonality in the tissue and in the blood was assessed.
T-cell monoclonality was detected in the skin in 30 of 94 patients, in the blood in 12 of 94 cases and the same clone was found in both tissues in 6 of 94 patients. The presence of a polyclonal T-cell population in the circulation was associated with complete response (P = .006). Lack of response to treatment (stable disease or progression of disease) was associated with T-cell clonality in skin (P = .009), in blood (P = .002) and in both tissues (P < .001). A multivariate analysis showed that T-cell monoclonality in the skin is independently associated with lack of response of mycosis fungoides to therapy.
Blood and skin should be studied for T-cell clonality as part of the routine initial workup, even in patients with early-stage disease.
γδ T cells represent a minor T-cell subset that is mainly distributed in mucosal surfaces. Two distinct lymphomas derived from these cells have been recognized: hepatosplenic γδ T-cell lymphoma ...(HSTL) and primary cutaneous γδ T-cell lymphoma (PCGD-TCL). However, whether other anatomic sites may also be involved and whether they represent a spectrum of the same disease are not well studied. The lack of T-cell receptor (TCR)β expression has been used to infer a γδ origin when other methods are not available. We studied 35 T-cell tumors suspected to be γδ TCL using monoclonal antibodies reactive with TCR δ or γ in paraffin sections. We were able to confirm γδ chain expression in 22 of 35 cases. We identified 8 PCGD-TCLs, 6 HSTLs, and 8 γδ TCLs without hepatosplenic or cutaneous involvement involving mainly extranodal sites. Two such cases were classified as enteropathy-associated T-cell lymphoma, type II. The other γδ TCL presented in the intestine, lung, tongue, orbit, and lymph node. In addition, we observed 13 cases with mainly extranodal involvement that lacked any TCR expression ("TCR silent"). In all cases, a natural killer cell origin was excluded. In conclusion, the lack of TCRβ expression does not always predict γδ-T-cell derivation, as TCR silent cases may be found. The recognition of γδ TCL presenting in extranodal sites other than skin and liver/spleen expands the clinical spectrum of these tumors. However, non-HSTL γδ TCL do not seem to represent a single entity. The relationship of these tumors with either HSTL or PCGD-TCL requires further study.
Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this ...study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ(+) cases showed EBV subtype A. Two TCR-γ(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.
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