Lesions Of T-cell Lymphoma Research Articles

ИСПОЛЬЗОВАНИЕ ВОДНОГО БОЛЮСА ПРИ ЛУЧЕВОЙ ТЕРАПИИ ПАЦИЕНТОВ С ИЗОЛИРОВАННЫМИ ПОВЕРХНОСТНЫМИ ПРОЯВЛЕНИЯМИ Т-КЛЕТОЧНОЙ ЛИМФОМЫ КОЖИ

Purpose: To demonstrate the effectiveness of water bolus, combined with individual immobilization for the treatment of lesions in the pedal region of the foot on a patient with isolated cutaneous T-cell lymphoma lesions. Material and methods: Construction of individual immobilization devices, simultaneously functioning as a bolus, in two clinical cases of T-cell cutaneous lymphoma radiation therapy in the pedal region of the foot, along with 3D-CRT and VMAT treatment planning, accompanied by retrospective evaluation of interfractional motion. Results: The proposed methodology demonstrates the effectiveness of the individual immobilization devices in minimizing interfractional motion, as well as the benefit of the bolus effect of the device in achieving optimal dose distribution in the treatment of superficial T-cell lymphoma lesions.

1126 A pilot of a microdevice for in situ candidate drug screening in cutaneous lesions of T-cell lymphoma

1126 A pilot of a microdevice for in situ candidate drug screening in cutaneous lesions of T-cell lymphoma

Malignant T Cell Activation by a Bacillus Species Isolated from Cutaneous T-Cell Lymphoma Lesions

Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells. By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.

Determining the immune environment of cutaneous T-cell lymphoma lesions through the assessment of lesional blood drops

Detailed analysis of the cells that infiltrate lesional skin cannot be performed in skin biopsy specimens using immunohistochemistry or cell separation techniques because enzyme treatments applied during the isolation step can destroy small amounts of protein and minor cell populations in the biopsy specimen. Here, we describe a method for isolating T cells from drops of whole blood obtained from lesions during skin biopsy in patients with cutaneous T-cell lymphoma. Lesional blood is assumed to contain lesional resident cells, cells from capillary vessels, and blood overflowing from capillary vessels into the lesion area. The lesional blood showed substantial increases in distinct cell populations, chemokines, and the expression of various genes. The proportion of CD8+CD45RO+ T cells in the lesional blood negatively correlated with the modified severity-weighted assessment tool scores. CD4+CD45RO+ T cells in the lesional blood expressed genes associated with the development of cancer and progression of cutaneous T-cell lymphoma. In addition, CD8+CD45RO+ T cells in lesional blood had unique T-cell receptor repertoires in lesions of each stage. Assessment of lesional blood drops might provide new insight into the pathogenesis of mycosis fungoides and facilitate evaluation of the treatment efficacy for mycosis fungoides as well as other skin inflammatory diseases.

257 Skin liquid biopsy method for assessing the immune environment of cutaneous T-cell lymphoma lesions

Detailed analysis of cells infiltrating lesional skin cannot be performed in skin biopsy specimens by immunohistochemistry or cell separation techniques due to the potential destruction of minor cell populations by enzyme treatment in the isolation step. We hypothesized that cells could be identified in a small amount of blood obtained from the infiltrating lesional skin during diagnostic skin biopsies. We collected small amounts (∼300 μl) of lesional blood and successfully isolated infiltrating cells using a cell sorter.

Quantitative imaging biomarkers of CNS lymphoma and its correlation with genotypic markers.

e14520 Background: Central nervous system (CNS) lymphoma can be divided into primary CNS lymphoma (PCNS) versus secondary involvement of the CNS in systemic lymphoma. Traditionally radiology-pathology correlation is needed to accurately stage these entities, but the invasive nature of intracranial biopsies can add to patient morbidity. As such, there is an unmet need for noninvasive imaging biomarkers of CNS lymphoma. We aim to assess whether quantitative imaging analysis can characterize improve diagnostic specific and identify underlying genomic alterations in CNS lymphoma. Methods: 42 cases of CNS lymphoma (26 males, 16 females) were reviewed. Inclusion criteria required MRI (1.5Tesla or 3.0Tesla) of the brain and time-concordant histopathologic evaluation (i.e. MRI obtained within 72 hours of histologic evaluation) confirming diagnosis of CNS lymphoma. 19 patients met the inclusion criteria: 16 patients with large B-cell and 3 patients with T-cell lymphoma. All diagnoses were confirmed by evaluating biopsies through morphological and immunohistochemical analysis. MRI studies included T1-weighted pre- and post-contrast images, T2-weighted images and diffusion weighted images. Quantitative analysis included 3D-volumetric and textural analysis. Results: In B-cell lymphoma, mean patient age was 57 (22-91) while in T-cell lymphoma mean age of diagnosis was 43 (20-59). On MRI, all cases of CNS lymphoma (B- and T-cell) demonstrated enhancement. All T-cell lymphoma lesions were intra-axial and demonstrated homogeneous enhancement. Meanwhile, B-cell lymphomas demonstrated variable pattern of enhancement (homogenous; reticulonodular; subcortical U-fiber; peripheral). 80% (4/5) patients tested for MYC alterations demonstrated peripheral enhancement. 70% (7/10) tested for BCL2 expression demonstrated homogenous enhancement; while BCL2 & MYC dual-expression was noted in the remaining 30% (3/10) with MRI showing peripheral enhancement. All CNS lymphomas demonstrated restricted diffusion with variable ADC range: 292-980. 84.2% (16/19) of the cases were intra-axial while 15.2 (3/19) were extra-axial (all of which were B-cell lymphoma). Conclusions: Our study shows all lymphomas enhance and demonstrate variable degree of restricted diffusion. Patients with Myc-alterations or dual-expression of BCL2-MYC showed peripheral enhancement, while isolated BCL2 expressed tumors showed homogeneous enhancement.

A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

Intertriginous Mycosis Fungoides

Follicular helper T cells are a subset of helper T cells that facilitate B-cell recruitment and maturation. Rare cases of cutaneous T-cell lymphoma manifesting as de novo tumor lesions in intertriginous skin contain an infiltrate rich in B cells. These cases may represent malignant counterparts of skin-homing follicular helper T cells. Two men and 1 woman (age range, 35-58 years) were seen with predominantly intertriginous tumor-stage cutaneous T-cell lymphoma lesions characterized by the absence of epidermotropism and the presence of a mixed infiltrate rich in B cells. Two of the patients died of the disease less than 3 years from the initial diagnosis. The surviving patient has aggressive disease and underwent hematopoietic stem cell transplantation. Two of the patients had a prominent CXCL13+, Bcl6/CD3+, and programmed death protein 1-positive follicular helper T-cell population. The intertriginous tumor variant of cutaneous T-cell lymphoma is heterogeneous but may be associated in some cases with a follicular helper T-cell immunophenotype. These patients may follow an aggressive clinical course. Tumor progression in sanctuary sites on patients receiving phototherapy may manifest as a similar clinical phenotype. Further characterization of the disease process is needed to confirm this observation.

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70

Malignant T cells in primary cutaneous T-cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis-inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses. Normal (n=10), CTCL (n=9) and benign dermatoses (n=13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n=6). Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T-cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement. Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis-inducing treatment modalities in the setting of intrinsic resistance to apoptosis.

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

Photodynamic therapy utilising topical delta-aminolevulinic acid in non-melanoma skin malignancies of the eyelid and the periocular skin.

Photodynamic therapy utilising delta-aminolevulinic acid-induced protoporphyrin IX photosensitisation, was evaluated as a treatment modality for nonmelanoma skin malignancies of the eyelids and the periocular skin. Photodynamic therapy with laser light at 635 nm was performed in 13 patients with 19 basal cell carcinomas and one patient with 3 cutaneous T-cell lymphoma lesions. A topical application regimen was used and in median 3 treatment sessions were given to each lesion. A visually judged complete response was achieved in 42% (8/19) of the basal cell carcinomas and in 100% of the T-cell lymphoma lesions (3/3). Partial tumour response was seen in 42% (8/19) and no response in 16% (3/19) of the basal cell carcinomas. The median follow-up time was 12 months. No, or very little scarring and loss of cilia were induced by the treatment. Photodynamic therapy with delta-aminolevulinic acid can eradicate eye-close non-melanoma skin malignancies without compromising the function of the eyelids. Further development of the method is needed to reach the same cure rates as those of the conventional treatment modalities.

Photodynamic therapy of non-melanoma malignant tumours of the skin using topical δ-amino levulinic acid sensitization and laser irradiation

Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Genotypic Analysis of T-Cell Clones Derived from Cutaneous T-Cell Lymphoma Lesions Demonstrates Selective Growth of Tumor-Infiltrating Lymphocytes

The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) beta- and gamma-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy.

Cutaneous lymphomas: correlation of histochemical and immunohistochemical characteristics and clinicopathologic features.

Twenty-four cases of cutaneous lymphomas were classified as T-cell (18 cases), B-cell (three cases), and true histiocytic (three cases), on the basis of the histochemical and immunohistochemical characteristics. Important differences in clinical and histopathologic features exist among these three types: skin lesions of T-cell lymphoma are usually chronic, pruritic, and sometimes ulcerative; those of B-cell lymphoma are nonpruritic and nonulcerative; lesions of true histiocytic lymphoma are often pruritic and ulcerative. All three patients with true histiocytic lymphoma died within six months of diagnosis. Two of the three patients with B-cell lymphoma died within two years of diagnosis. Only two of the 18 patients with T-cell lymphoma died, one after 12 years and the other after six years. Histologically, B-cell lymphoma shows a grenz zone in the upper dermis and absence of epidermal involvement; both T-cell and true histiocytic lymphomas show epidermal infiltration and absence of a grenz zone. True histiocytic lymphoma can appear similar to T-cell lymphoma clinically and histologically by routine examination, but histiocytic lymphoma has a much worse prognosis. Histochemical and immunohistochemical studies are very helpful in the differential diagnosis.