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1.
Immunooncol Technol ; 24: 100714, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39045171

RESUMO

Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs. Patients and methods: We retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands. TILs were scored on representative hematoxylin and eosin (H&E) stains of the primary melanoma and pretreatment melanoma metastasis as 'absent', 'nonbrisk', or 'brisk'. A univariable logistic regression analysis was carried out to assess the association between the TIL scores and the development of severe irAEs. Fine and Gray subdistribution hazard models were used to estimate the cumulative incidence of severe irAEs. Results: Of the 1346 eligible patients, 536 patients had primary melanoma specimens available, and 613 patients had metastasis specimens available. Severe irAEs occurred in 15% of anti-PD-1-treated patients and 49% of anti-PD-1 + anti-CTLA-4-treated patients. The presence of TILs was not associated with the occurrence of grade ≥3 irAEs in primary melanoma specimens (P = 0.70) nor pretreatment metastasis specimens (P = 0.91). In the univariable analysis, patients with brisk TILs did not have a higher chance of developing severe irAEs compared with patients with absent TILs, for both primary specimen (odds ratio 1.15, 95% confidence interval 0.60-2.18) and metastasis specimen (odds ratio 0.77, 95% confidence interval 0.37-1.59). There was also no significant difference in the lifetime risk or timing of the development of severe irAEs in patients with TILs present compared with patients with TILs absent. Conclusion: There was no association between the TIL scores on H&E-stained slides from the primary melanoma or pretreatment metastasis and the development of grade 3 or higher irAEs. Additionally, no correlation was found between the presence of TILs and the timing of irAEs.

2.
Virchows Arch ; 480(3): 693-697, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34142226

RESUMO

Mucosal melanomas are rare and only a small portion bear BRAF mutations while cutaneous melanomas have a much higher prevalence and often harbor BRAF mutations. We present two cases in which, after a malignant melanocytic mucosal lesion with a BRAF mutation was found, the primary cutaneous source was identified and clonality confirmed between the lesions. In both cases, primary lesions occurred on the scalp, an often-overlooked site. Both lesions showed signs of regression implying that in due time these lesions could have been fully regressed and might never have been detected. In that case, the metastatic mucosal lesion would erroneously be identified as a BRAF-mutated mucosal melanoma. These cases give warrant; a careful dermatological inspection should be instigated when confronted with a BRAF-mutated mucosal melanoma. We hypothesize that some BRAF-mutated mucosal melanomas might actually represent metastases of regressed cutaneous melanomas.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/patologia , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Couro Cabeludo/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
3.
Br J Dermatol ; 175(2): 382-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26931394

RESUMO

BACKGROUND: TOX (thymocyte selection-associated high-mobility group box) was shown to be aberrantly expressed in mycosis fungoides (MF) and Sézary syndrome (SS) and is suggested to have additional diagnostic value. However, data on expression in other types of cutaneous T-cell lymphoma (CTCL) are scarce and it is unknown whether TOX is expressed only by MF with a CD4(+)  CD8(-) phenotype. OBJECTIVES: To investigate TOX expression in various types of CTCL with different T-cell phenotypes. METHODS: Immunohistochemical expression of TOX was evaluated on 153 skin biopsies of 132 patients with CTCL and 60 patients with benign inflammatory dermatoses (BIDs). RESULTS: TOX was expressed by > 50% of the neoplastic T cells in 49 of 59 patients (83%) with MF and in 19 of 22 patients (86%) with SS. The TOX(+) cases of MF included 34 of 35 cases (97%) with a CD4(+)  CD8(-) phenotype, but also five of eight cases (63%) with a CD4(-)  CD8(+) phenotype and 10 of 16 cases (63%) with a CD4(-)  CD8(-) phenotype. TOX expression in other types of CTCL was common but showed variable intensity. Although only one of 60 patients (2%) with a BID expressed TOX in > 50% of the skin-infiltrating T cells, some caution is warranted, as the majority of BIDs had TOX(+) T cells varying between 11% and 50%. CONCLUSIONS: TOX expression is not tumour specific, is not restricted to CTCL with a CD4(+)  CD8(-) phenotype, and, on its own, is insufficient for diagnosis of CTCL. However, it may have an adjunctive diagnostic role in conjunction with other clinical and histological data.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Linfoma Cutâneo de Células T/diagnóstico , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Diagnóstico Diferencial , Humanos , Micose Fungoide/diagnóstico , Fenótipo , Síndrome de Sézary/diagnóstico
4.
Ned Tijdschr Geneeskd ; 155(33): A5130, 2012.
Artigo em Holandês | MEDLINE | ID: mdl-22894801

RESUMO

BACKGROUND: Due to a great diversity of clinical presentations secondary syphilis can mimic various skin diseases, which means that the diagnosis of this sexually transmitted condition can be missed. Occurrence of a granulomatous inflammatory reaction in secondary syphilis is rare and may be confused with other granulomatous dermatoses. CASE DESCRIPTION: We present a 37-year-old homosexual male with a granulomatous dermatitis due to secondary syphilis. The differential diagnosis based on clinical and histopathological findings was lengthy and the initial syphilitic serology results were negative, resulting in delayed diagnosis. After revision of the histopathology and repeated serological testing secondary syphilis could be diagnosed. CONCLUSION: Not only the clinical, but also the histopathological presentation of secondary syphilis is variable. To prevent transmission, treatment delay and complications, we recommend repeating syphilitic serology following negative results if there is clinical or histopathological suspicion of this disease, especially in patients displaying high-risk behaviour. Syphilis should be also excluded in granulomatous dermatoses with plasma cells.


Assuntos
Dermatite/diagnóstico , Granuloma/diagnóstico , Sífilis/diagnóstico , Adulto , Dermatite/patologia , Diagnóstico Diferencial , Granuloma/patologia , Humanos , Masculino , Sífilis/patologia
5.
Am J Physiol Cell Physiol ; 279(2): C286-94, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10912994

RESUMO

Ligation of the main excretory duct of the rat submandibular gland (SMG) produces a pronounced atrophy that is reversed upon ligature removal. Based on previous studies by our group and others suggesting that P2Y(2) nucleotide receptors are upregulated in response to tissue damage, we hypothesized that P2Y(2) receptor activity and mRNA levels would increase after duct ligation and return to control levels after ligature removal. Our results support this hypothesis. Intracellular Ca(2+) mobilization in response to the P2Y(2) receptor agonist UTP in SMG cells was increased significantly after ligation periods of 1.5 to 7 days, whereas no significant response was observed in the contralateral, nonligated gland. P2Y(2) receptor mRNA, as measured by semiquantitative RT-PCR, increased about 15-fold after 3 days of ligation. These increases reverted to control levels by 14 days after ligature removal. In situ hybridization revealed that the changes in P2Y(2) receptor mRNA abundance occurred mostly in acinar cells, which also were more adversely affected by ligation, including an increase in the appearance of apoptotic bodies. These findings support the idea that P2Y(2) receptor upregulation may be an important component of the response to injury in SMG and that recovery of normal physiological function may signal a decreased requirement for P2Y(2) receptors.


Assuntos
Cálcio/metabolismo , Receptores Purinérgicos P2/metabolismo , Glândula Submandibular/metabolismo , Animais , Feminino , Ligadura , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2Y2 , Glândula Submandibular/ultraestrutura
6.
J Homosex ; 37(1): 3-24, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10203067

RESUMO

This study examines and evaluates the contents of the first 24 volumes of Journal of Homosexuality (JH), from 1974 to 1993. Data from each issue of JH, in terms of source articles and contributing authors, were collected and analyzed. JH is shown to be a scholarly journal, with high rates of citations per article, high levels of author education, a prevalence of scholarly methodological approaches, and a low rate of self-citation. Articles that disseminated the findings of empirical research noticeably decreased over time, while articles focusing on historical analysis noticeably increased. This trend was consonant with the change over time of JH's mission statement and editorial policy.


Assuntos
Bibliometria , Homossexualidade , Humanos , Publicações Periódicas como Assunto , Fatores de Tempo
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