OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.
Female ; Humans ; Male ; Collagen Type I, alpha 1 Chain ; Dermatofibrosarcoma/pathology* ; In Situ Hybridization, Fluorescence ; Oncogene Proteins, Fusion/genetics* ; Proto-Oncogene Proteins c-sis/genetics* ; Skin Neoplasms/pathology* ; Adult

Humans ; Ependymoma/secondary* ; Brain Neoplasms/pathology* ; Skin Neoplasms ; Melanoma ; Spinal Cord Neoplasms/pathology*

OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively. RESULTS: 4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine. CONCLUSION The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.
Humans ; Dendritic Cells ; Retrospective Studies ; Skin Neoplasms/pathology* ; Antineoplastic Agents/therapeutic use* ; Bone Marrow/pathology* ; Myeloproliferative Disorders ; Hematologic Neoplasms/drug therapy*

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals ; Mice ; Dinitrochlorobenzene/metabolism* ; Skin/metabolism* ; Cytokines/metabolism* ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dermatitis, Allergic Contact/pathology* ; Dermatitis, Atopic/chemically induced* ; Signal Transduction ; RNA, Messenger/metabolism* ; Mice, Inbred BALB C

OBJECTIVE: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed. RESULTS: Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months. CONCLUSION BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Leukemia/pathology* ; Hematopoietic Stem Cell Transplantation ; Prognosis ; Myeloproliferative Disorders ; Skin Neoplasms/pathology* ; Acute Disease ; Dendritic Cells

Humans ; Ulcer/pathology* ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Skin Diseases

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.
Humans ; Melanosis/pathology* ; Pigmentation ; Skin/pathology*

OBJECTIVE: To investigate the clinicopathological features of blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS: A total of 13 cases of BPDCN diagnosed in Peking University First Hospital from January 2013 to March 2022 were collected. The clinical features, histopathological characteristics, immunophenotypes and prognosis of the patients were analyzed retrospectively, and the related literatures was reviewed as well. RESULTS: Among the 13 patients, 11 were male and 2 were female, with a median age of 62 years (ranging from 5 to 78 years). Among them, single organ involvement occurred in 5 cases, all of which presented with skin lesions. Two or more organs were involved in other 8 cases (single organ with bone marrow involved in 3 cases; skin, bone marrow and lymph node involved simultaneously in 3 cases; skin, bone marrow, lymph node and spleen involved simultaneously in 2 cases). Histopathologically, it was characterized by the proliferation of medium to large atypical blastic cells, which infiltrated the whole thickness of dermis. When involved, the bone marrow lesions mainly appeared in a diffuse pattern, while the lymph node structure was usually destroyed, and the red pulp of the affected spleen was diffusely invaded. Immunohistochemical staining showed that all the 13 cases were positive for CD4, CD56, and CD123 (13/13) in varying degrees. All the 9 cases expressed TCL1 (9/9). Variable expression of CD68 (KP1) (8/13), TdT (7/12), CD117 (2/6), and high Ki-67 proliferation index (40%~80%) were showed. The neoplastic cells lacked expressions of CD20, CD3, MPO, CD34, or CD30; EBER in situ hybridization were negative (0/9). After definite diagnosis, 6 cases received chemotherapy, among which 1 received adjuvant radiotherapy, and 2 received subsequent bone marrow transplantation. Another 2 cases only received maintenance treatment. The median follow-up time was 14 months (ranging from 6 to 36 months), 5 patients died of the disease (6 to 18 months), 3 patients survived (7 to 36 months up to now), and the remaining 5 patients lost follow-up. CONCLUSION BPDCN is a rare type of malignant lymphohematopoietic tumor with aggressive behavior and poor prognosis. The diagnosis should be made combining clinical features, histopathology, and immunohistochemical phenotype. Attention should be paid to differentiating BPDCN from other neoplasms with blastoid morphology or CD4+CD56+ tumors.
Male ; Female ; Humans ; Hematologic Neoplasms ; Retrospective Studies ; Dendritic Cells ; Skin Neoplasms/pathology* ; Skin/pathology*

Humans ; Leg/pathology* ; Skin Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*