Primary Cutaneous Gamma-delta T-cell Research Articles

Primary Cutaneous Gamma Delta T Cell Lymphoma: A Clinicopathological Analysis

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.

NK/T-cell lymphoma, nasal type, γδ T-cell lymphoma, and CD8-positive epidermotropic T-cell lymphoma-clinical and histopathologic features, differential diagnosis, and treatment.

The cytotoxic lymphomas of the skin constitute a heterogeneous group of rare lymphoproliferative diseases that are derived from mature T cells and natural killer (NK) cells that express cytotoxic molecules (T-cell intracellular antigen- 1, granzyme A/B, and perforin). Although frequently characterized by an aggressive course and poor prognosis, these diseases can have variable clinical behavior. This review delivers up-to-date information about the clinical presentation, histopathologic features, differential diagnosis, and therapy of extranodal NK/T-cell lymphoma, nasal type, primary cutaneous gamma delta T-cell lymphoma, and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma.

Primary Cutaneous T-Cell Lymphomas Showing Gamma-Delta (γδ) Phenotype and Predominantly Epidermotropic Pattern are Clinicopathologically Distinct From Classic Primary Cutaneous γδ T-Cell Lymphomas.

Primary cutaneous gamma-delta (γδ) T-cell lymphoma is a rare disease that typically involves the dermis and subcutis. Cases of primary cutaneous T-cell lymphomas showing γδ phenotype and predominantly epidermotropic pattern (EγδTCL) are not well defined. In this series, cases of primary cutaneous T-cell lymphomas showing γδ phenotype were reviewed and classified as predominantly epidermotropic (EγδTCL) when >75% of lymphoma cells resided in the epidermis or predominantly dermal and/or subcutaneous (DSγδTCL). Clinical, pathologic, and immunophenotypic features were compared in 27 biopsies from 13 patients of EγδTCL and 13 biopsies from 7 patients of DSγδTCL. The lymphoma cells were diffusely positive for CD3 and T-cell receptor (TCR)γ, mostly positive for granzyme B and TIA-1, variably positive for CD8, CD7, and CD30, and negative for CD4 and TCRβ. Two patients with EγδTCL had dissemination to lymph nodes and 1 to the lung; 1 patient with DSγδTCL had gastrointestinal involvement. The median survival of patients with EγδTCL was not reached, and with a median follow-up of 19.2 months, 3/13 died. In contrast, the median survival of patients with DSγδTCL was 10 months, and after a median follow-up of 15.6 months, 5/5 died (P<0.01). EγδTCL is a rare presentation of cutaneous T-cell lymphoma that can be distinguished from DSγδTCL based on the extent of epidermotropism and has a better prognosis and longer median survival than DSγδTCL. However, although EγδTCL resembles mycosis fungoides clinically and histologically, a subset of EγδTCL is more likely to behave more aggressively than typical mycosis fungoides.

Outcome of Patients with Peripheral T-Cell Lymphoma Undergoing Allogeneic Stem Cell in British Columbia

Background:Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) that accounts for approximately 10% of all aggressive NHLs in Western countries. The optimal management remains unclear, however, given the poor outcome, allogeneic transplant (allo-SCT) has been integrated into the front-line treatment for some rare extranodal subtypes as well in relapsed/refractory setting. We report our provincial experience of the outcome of patients with PTCL who have undergone allo-SCT at the British Columbia Cancer Agency (BCCA).Methods:The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with PTCL who have undergone allo-SCT between November 1990 and January 2016. Overall survival and relapse free survival were estimated using the Kaplan-Meier method.Results:We identified 36 cases of PTCL patients who have undergone allogeneic transplant from a median time of 11 months from primary diagnosis (range 4-64) with the following clinical features: median age at transplant was 45 years (range 16-58 years); 24 (67%) were male; 32 (89%) patients had advanced stage disease; 22 (61%) had B-symptoms at diagnosis. Bone marrow involvement detected in 13/34 (38%) patients. Histological diagnosis based on the WHO 2008 classification were: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) n=15 (42%); anaplastic large cell lymphoma (ALCL) n=7 (19%) out of which three were ALK positive, angioimmunoblastic T-cell lymphoma (AITL) n=6 (17%), hepatosplenic T-cell lymphoma n=5 (14%), enteropathy associated T-cell lymphoma type I n=1, advanced primary cutaneous gamma-delta T-cell lymphoma n=1 and Sezary syndrome n=1. Ten patients (28%) underwent allo-SCT as part of planned primary therapy after achieving their first remission [6 were in complete remission 1 (CR1) and 4 were in partial remission 1 (PR1)], whereas 26 patients (72%) underwent allo-SCT for relapsed/refractory disease. CHOP was administered in 19 patients (53%) as the primary therapy. 17 (47%) patients received alternative chemotherapy regimen due to patient and/or physician preference. The clinical status at the time of transplantation was CR in 12 patients (33%), relapsed sensitive disease n=10 (28%), relapsed untreated n=5 (14%), partial remission (PR) in 5 (14%), primary progressive disease n=3 (8%) and relapsed resistant disease n=1 (3%).Thirty two patients (89%) underwent myeloablative conditioning, 4 (11%) underwent reduced intensity conditioning (RIC). The conditioning regimens included: cyclophosphamide/TBI n=24 (67%), busulfan/cyclophosphamide n=5 (14%), fludarabine containing reduced intensity n=4 (11%), and other regimens n= 3 (8%). With a median follow-up of alive patients from the time of allo-SCT of 69 months (range 1-186 months). At last follow-up, 17 (47%) patients have died, 6 from disease relapse, 5 from graft vs host disease (GVHD), 2 from regimen related toxicity and 4 from other causes. Nineteen patients (53%) still alive at last follow up post-transplant of which 14 (39%) still in remission. The 5-year event free survival (EFS) and overall survival (OS) from the time of allo-SCT of all patients were 43% and 63%, respectively. For PTCL-NOS the 5-year EFS and OS were 52% and 69%, respectively. Table 1 summarizes the patients' characteristics. Figures 1 and 2 shows the Kaplan-Meier curves for OS and EFS respectively.Conclusion:Allo-SCT can be effective strategy in select patients with relapsed/refractory PTCL and those with high risk histologies in the upfront setting PTCL with an acceptable toxicity. [Display omitted] [Display omitted] [Display omitted] DisclosuresToze:Roche Canada: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Scott:NanoString Technologies: Patents & Royalties: named inventor on a patent for molecular subtyping of DLBCL that has been licensed to NanoString Technologies. Villa:Lundbeck: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria. Connors:NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding; Seattle Genetics: Research Funding; Millennium Takeda: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding.

Primary cutaneous gamma delta T-cell lymphoma with a predominantly epidermotropic pattern

Primary cutaneous gamma delta T-cell lymphoma with a predominantly epidermotropic pattern

Rare but deadly: A case of primary cutaneous gamma-delta T-cell lymphoma

Rare but deadly: A case of primary cutaneous gamma-delta T-cell lymphoma

Gamma-delta t-cell lymphomas.

Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, which naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies.

Cytotoxic and Gamma-Delta Subtypes Of Peripheral T-Cell Lymphoma: A Single Center Experience

BackgroundPeripheral T-cell lymphomas (TCLs) are uncommon neoplasms. TCLs in which gamma-delta T-cell receptors are expressed are extremely aggressive and rare, accounting for less than 1% of lymphoid neoplasms. The two main types of CTLs recognized in the 2008 WHO classification of lymphoid neoplasms are hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL). Although rare, these diseases are associated with an aggressive clinical course, refractoriness to conventional therapies, and poor prognosis. MethodsPatients with newly diagnosed cytotoxic or gamma-delta TCLs treated from 2005-2012 were retrospectively identified. Analyses included patient characteristics, clinical presentation, pathology, treatment and outcome. ResultsTwenty-two patients (11 cutaneous gamma-delta TCL, 5 primary cutaneous aggressive epidermotropic CD8+TCL, 4 hepatosplenic gamma-delta TCL, 2 cytotoxic TCL involving the intestine) were identified. Median age was 48 (range: 18-70), 12% (12/22) were male, and 54.5% (12) presented with B symptoms. Initial therapy included CHOP based chemotherapy in 6, denileukin difititox with CHOP in 5, and single agent denileukin diftitox in 4. One patient died with hemophagocytosis prior to initiation of chemotherapy. Fifteen of 21 pts responded to initial therapy but 10 of 15 required more than one regimen containing either etoposide or gemcitabine to achieve remission. The median number of regimens was 2 (range 0-4). In the salvage setting, two patients had partial responses with romidepsin, one had a PR with pralatrexate and one had a CR after pralatrexate salvage therapy. Thirteen patients underwent stem cell transplantation in first remission: autologous in 5 pts who had no donor, and allogeneic in 8 pts. At a median follow up of 3 years, 60% relapsed, and 14 (63%) are still alive. Of the patients who underwent transplant, one auto pt died from hemophagocytosis, 2 alloBMT patients died from acute GVHD, and 2 alloBMT pts died from disease progression. One alloBMT patient with cutaneous gamma delta TCL relapsed and responded to salvage therapy. ConclusionsCytotoxic and gamma-delta TCLs are rare diseases that have traditionally responded poorly to treatment. In our experience, many patients have a suboptimal response to CHOP alone and require additional therapy to achieve remission. We report a favorable outcome after stem cell transplantation and with implementation of novel agents. Advances in understanding biology and international collaborative efforts are required to improve outcome in these rare entities. Disclosures:Off Label Use:sorafenib in t cell nhl. Foss:merck: Research Funding; spectrum: Research Funding; eisai: Membership on an entity's Board of Directors or advisory committees; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Honoraria, Research Funding; seattle genetics: Research Funding.

Primary Cutaneous Gamma-Delta T-Cell Lymphoma With Marked Pagetoid Epidermotropism Shortly After Allogeneic Stem Cell Transplantation

Primary Cutaneous Gamma-Delta T-Cell Lymphoma With Marked Pagetoid Epidermotropism Shortly After Allogeneic Stem Cell Transplantation

Primary Cutaneous Gamma Delta T-Cell Lymphoma With Brain Involvement and Hemophagocytic Syndrome

Primary cutaneous gamma delta T-cell lymphoma is a rare diagnosis with only 40 reported cases. We describe a case of cutaneous gamma delta T-cell lymphoma with hemophagocytic syndrome and brain involvement that was not apparent morphologically on skin biopsy and was diagnosed as perifolliculitis and lobular panniculitis. The biopsy was sent later for molecular studies to the University of Washington, which demonstrated a T-cell clone. This case demonstrates that a T-cell clone may be present in a skin biopsy without morphologic or immunophenotypic evidence of lymphoma.

Comprehensive cytogenetic study of primary cutaneous gamma-delta T-cell lymphoma by means of spectral karyotyping and genome-wide single nucleotide polymorphism array

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL), which originates from activated mature gamma-delta T cells with a cytotoxic phenotype is a rare T-cell lymphoproliferative disease. The prognosis of PCGD-TCL has been rather unfavorable due to poor response to conventional chemotherapy, and its molecular features and pathophysiology underlying disease development remain unknown. We report here a case with primarily treatment-resistant PCGD-TCL featuring highly complex cytogenetic and genetic aberrations detected by spectral karyotyping and genome-wide single nucleotide polymorphism (SNP) array. Chromosomal aberrations included several chromosomal translocations involving breakpoints at 9p21, 14q11.2, 14q32.1, or 16q23.1, suggesting the involvement of WWOX, TCL gene cluster, and BCL11B, which are crucial for tumorigenesis in T-cell lymphomas. SNP analysis also identified genome copy number gains and losses in various regions, which can potently deregulate expression of various pro- and anti-oncogenic genes involved in RAS-related protein pathways, PI3K/AKT/MTOR-related pathways, MYC-related signaling, or TP53-related signaling. Thus, this case report may shed some light on the complex molecular abnormalities involved in the development of PCGD-TCL and on information that can aid the search for druggable target molecules in this disease.

Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia

Mature T/NK cell lymphomas (MTNKL) presenting as leukemia are rare and show considerable overlapping of clinical, morphological and immunophenotypic features. Critical analysis of the morphology and immunophenotypic profile of MTNKL. We reviewed 380 consecutive cases of mature lymphoid neoplasm that presented as leukemia and were diagnosed on morphology and immunophenotyping of bone marrow and/or peripheral blood samples. Peripheral blood and bone marrow involvement was seen in all cases. MTNKL constituted 4% (nine cases) of all mature lymphoid neoplasms presenting as leukemia. It included four cases of T-large granular leukemia (T-LGL), two of T-cell prolymphocytic leukemia small cell variant (T-PLL), two of adult T-cell leukemia/lymphoma (ATLL) and one of primary cutaneous gamma delta T-cell lymphoma (PCGDTCL). T-LGL revealed CD4-/CD8+ phenotype in three, and CD4+/CD8+ phenotype in one case. CD56 was absent in all the cases of T-LGL. One case of T- PLL small cell variant showed CD4+/CD8- phenotype, while the other revealed CD4-/CD8+ phenotype. Both cases of ATLL showed CD4+/CD8+/CD25+ phenotype. The single case of PCGDTCL showed CD4-/CD8- phenotype pattern. CD3 and CD5 were expressed in all MTNKL. CD7 was absent in three cases of T-LGL. TCRalpha/beta was performed in three cases of T-LGL and was positive in all. TCRalpha/beta was also seen in both the cases of T-PLL small variant. However, TCRalpha/beta was seen in the single case of PCGDTCL. Mature nodal T/NK cell neoplasms are rare and MTNKL presenting as leukemia are even rarer. There is an overlap between the immunophenotypic profiles of different MTNKL subtypes and elaborate T/NK cell panels are required for their evaluation.

Gamma-delta T-cell lymphomas

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which gammadelta T-cell receptors are expressed (gammadelta TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). gammadelta TCLs originate from gammadelta T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity. Two distinct gammadelta TCL entities are recognized: hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous gammadelta T-cell lymphoma (PCGD-TCL). HSTL is a well-characterized extranodal lymphoma that has a disguised onset, secondary to intrasinusoidal infiltration of the spleen, liver and bone marrow, has a rapidly progressive course that is poorly responsive to chemotherapy, and often ensues in the setting of immune system suppression. PCGD-TCL can present with prominent epidermal involvement or with a panniculitis-like clinical picture that can be complicated by a concurrent hemophagocytic syndrome; the disease shows biological and phenotypic overlap with other extranodal gammadelta TCLs that involve the respiratory or gastrointestinal tract mucosa. The regular application of phenotypic and molecular techniques is crucial for the diagnosis of gammadelta TCLs. In this Review, we discuss the clinical and biological features, the diagnostic challenges and the therapeutic perspectives of HSTL and PCGD-TCL.