Cutaneous Lymphoma Lesions Research Articles

Pathological landscape of tumor flare reaction to epcoritamab treatment.

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed "tumor pseudoprogression." The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12mg/day. The third injection, scheduled for day 15, was delayed by 1week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20+ large atypical lymphocytes forming residual nodules, encircled by CD4+ and CD8+ lymphocytes, with a predominance of CD8+ T cells over CD4+ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.

Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma.

Mycosis fungoides is one of the most common types of extranodal T-cell lymphomas, considered to be caused by malignant transformation of the mature T cells residing in the skin. However, some clinical observations such as the multifocal distribution of mycosis fungoides lesions or patterns of relapse after radiotherapy are not readily explainable by the mature T-cell origin theory. We have performed a detailed analysis of T-cell receptor (TCR) rearrangements in single malignant cells and in biopsies from mycosis fungoides tumors composed of >80% of malignant cells using next-generation sequencing (NGS) to pinpoint the relationship between neoplastic cells in mycosis fungoides. We have also aimed to detect malignant, circulating T-cell by whole blood TCR sequencing. We found a substantial clonal heterogeneity in the mycosis fungoides samples with regards to TCR, and we demonstrated that lymphoma cells harboring identical TCRγ sequences may harbor different TCRα and β sequences. Lack of absolute TCRα, -β, -γ monoclonality was further confirmed by TCR amplification and sequencing from microdissected lymphoma cells. We have also found the TCR rearrangements characteristic for lymphoma cells in patients' peripheral blood despite the lack of leukemic blood involvement; however, the circulating TCRγ clonotype did not always represent the dominant cutaneous clonotype. These findings can be explained by a model where malignant transformation takes place during early T-cell development giving rise to circulating premalignant clones, which home to the skin producing clinically apparent lesions of cutaneous lymphoma. Therapeutic strategies in T-cell lymphoma should therefore target those early lymphoma precursor cells.

Dose Fidelity and Conformality for High-Dose-Rate Surface Applicator Brachytherapy for Cutaneous Lymphoma Lesions of the Hands and Feet

Dose Fidelity and Conformality for High-Dose-Rate Surface Applicator Brachytherapy for Cutaneous Lymphoma Lesions of the Hands and Feet

Significance of Marek's disease virus serotype 1‐specific phosphorylated proteins in Marek's disease skin lesions

Summary Skin tissues were obtained from 12 chickens showing Marek's disease (MD) skin tumour induced by a very virulent MD/5 strain of Marek's disease virus serotype 1 (MDVl) and taken from 24 field broiler chickens (8 to 9‐weeks‐old) manifesting MD skin tumour. They were examined by the immunohistochemical method in order to examine the topographic expression of MDV1‐specific phosphorylated proteins (PP) and by the reverse‐transcription polymerase chain reaction following Southern hybridization to analyse their gene transcriptional activity. PP were massively detected and their gene transcripts were abundantly expressed only in the necrotic areas of some experimentally‐induced MD cutaneous lymphoma lesions. Strong PP‐positive cells were degenerate or necrotic lymphoblasts. The other field or experimentally‐induced MD cutaneous lymphoma lesions, even those consisting almost completely of tumorous lymphoblasts, had only a few PP‐positive lymphoid cells and few gene transcripts. Necrotic areas of feather pulp MD lymphoma lesions consisting mainly of degenerate or necrotic lymphoblasts and cytolytic feather follicle epithelium (FFE) were also strongly positive for PP. PPs and their gene transcripts were detectable only in the cytolytically infected cells such as FFE and tumorous lymphoblasts converting to the abortic state.

Acquired cutis laxa associated with cutaneous angiocentric T‐cell lymphoma

A 64‐year‐old man presenting with adenomegaly was diagnosed with stage IV A angiocentric cutaneous T‐cell lymphoma in 1988. Since he showed a poor response to psoralen plus UVA (PUVA) after 1 year of therapy, he was switched to systemic chemotherapy (COP), and was considered to be in remission after completion of 5 months of this regimen. In December 1989, the patient noted an asymptomatic lesion at the superior and internal aspect of his right thigh; on examination, there was a poorly circumscribed, noninflammatory, whitish, atrophic macula near the inguinal fold and a palpable adenopathy; its surface was irregular, showing small wrinkling, and could be depressed on palpation. There were no preceding inflammatory lesions and no cutaneous lymphoma lesions at this site. Slowly, the initial macule extended, and new similar lesions insidiously appeared symmetrically on the left thigh. In October 1990, the patient received electron beam therapy for a relapse that presented as troncular nodules and responded well to this therapy. In the months that followed, the skin of his whole body became progressively sagging and pendulous, without recoil. This was not preceded by an inflammatory phase or eruption. There was no family history of elastolytic disorder, and the patient was not taking any medication other than that described above. On questioning, there were no symptoms suggesting systemic involvement of this elastolytic disorder. On physical examination, the patient's whole body skin seemed redundant, nonresllient, and wrinkled, this being most obvious in the axillae, inguinal region, antecubital fossa, neck, and trunk, where loose and pendulous skin folds could be seen (Fig. 1). Also, the patient's face was excessively wrinkled and sagging and he had bilateral ectropion. At the superior and internal aspect of both thighs, large, poorly circumsoribed, but distinct, round patches of 1‐5 cm in diameter were observed; they were atrophic and whitish, with an uneven surface, and could be depressed on palpation. Apart from 1 cm, mobile, but firm, axillary and inguinal adenopathy and three subcutaneous nodules on the arm and trunk, the rest of the physical examination was unremarkable.Routine blood tests were normal, as was a chest X‐ray. Sezary cells were absent on blood smear, and borrelia and syphilis serology were negative. Thyroid function tests, angiotensin converting enzyme, and immunoelectrophoresis were within normal limits, and antinuclear antigen was negative. Two cutaneous biopsies were performed: one in an atrophic herniating lesion of the right thigh and the one on the abdomen. Both showed, on hematoxylin‐phloxin‐safran staining, a mild dermal perivascular inflammatory infiltrate with a predominance of mononuclear cells. On Weigert staining, both were marked by a net reduction in elastic fibers throughout the dermis.

Identification and possible significance of HNK-1+ human lymphocytes, macrophages, and non-neoplastic T-cells in cutaneous lymphoma.

Experimental work on animal models suggests that various lymphoid subpopulations (K/NK, lymphocytes, macrophages, T-cells) may play a role in immunity against neoplasia, including lymphomas. The incidence and possible role of these cells in spontaneously occurring human tumors is less clear. The prevalence of these lymphoid subpopulations was studied in 60 cutaneous biopsy specimens using in situ immunocytochemistry. Monoclonal HNK-1 (Leu 7), which detects human granular lymphocytes with K/NK function, was used to detect K/NK lymphocytes; macrophages were identified by diffuse cytoplasmic esterase activity; T-cells were identified using monoclonal antibodies OKT3 and Leu 1. HNK-1+ lymphocytes, esterase-positive macrophages, and infiltrating T-cells were identified in varying numbers in the cases studied. The demonstration of HNK-1+ lymphocytes, macrophages, and T-lymphocytes in cutaneous lymphoma lesions is of potential therapeutic application. Whatever the naturally occurring role of these immune cells, it is possible that they may be manipulated pharmacologically for the benefit of the patient.

Necrotizing vasculitis within cutaneous lesions of mycosis fungoides

Mycosis fungoides is a T cell lymphoma with a predilection for cutaneous involvement. This paper describes the clinical manifestations and histopathologic features of a case of mycosis fungoides with necrotizing vasculitis localized to the lesions of cutaneous lymphoma. Elevated levels of circulating immune complexes were found in this patient. The large numbers of perivascular malignant helper T lymphocytes may have induced immunoglobulin synthesis, resulting in the formation of these complexes followed by deposition in vessel walls and subsequent necrotizing vasculitis. Possible alternative mechanisms include the presence of anti-T cell antibodies, or cytotoxic effector cells.

Alterations of lesions of mycosis fungoides lymphoma by direct imposition of delayed hypersensitivity reactions.

Plaque lesions of mycosis fungoides lymphoma in six patients sensitized to both 2-4 dinitrochlorobenzene (DNCB) and S, 2-aminoethylisothiuronium (AET) were treated topically with varying doses of the chemicals to evoke delayed hypersensitivity reactions. Complete or partial clearing of lesions, lasting several months, was observed in 22 of 31 plaques treated. No clinical benefit was observed following applications of a cutaneous irritant, sodium lauryl sulfate, nor with four chemical congeners of DNCB not cross-antigenic with DNCB. Cutaneous lymphoma lesions of one patient anergic to DNCB did not regress following large topical doses of the chemical. This evidence indicates that lesions of the lymphoma mycosis fungoides may be altered significantly by delayed hypersitivity responses, an event of seeming importance to understanding the pathogenesis of this disease.