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1.
Mol Carcinog ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233490

RESUMEN

Diagnosis and treatment of thyroid disease are affected by the wide range of thyroid cancer subtypes and their varying degrees of aggressiveness. To better describe the indolent nature of thyroid neoplasms previously classified as noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC), the Endocrine Pathology Society working group has recently coined the term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). The purpose of this nomenclature change is to avoid patients the distress of cancer diagnosis and to decrease the overtreatment of thyroid nodules with a RAS-LIKE molecular profile similar to follicular adenoma. Consequently, the reclassification has a significant impact on thyroid nodule clinical care as well as histopathologic and cytopathologic diagnosis. This paper will focus on a unique case of Bilateral NIFTP harboring concomitant HRAS and KRAS mutation; we will also review the background, molecular features, and clinical implications of NIFTP as well as the factors behind the nomenclature update. It also seemed helpful to emphasize the impact of NIFTP on clinical practice to avoid overtreating nodules that could be safely managed with lobectomy alone. Actually, despite the diagnosis is postsurgery, a comprehensive preoperative evaluation may raise a suspicion of NIFTP and suggest a more careful plan for treatment. Here, we present a unique case of bilateral NIFTP after total thyroidectomy; subsequent molecular analysis revealed that the patient's right nodule harbored an isolated p.(Q61K) HRAS mutation, while the left a p.(Q61K) KRAS mutation. To the best of our knowledge, this is the first case report of this nature. The existence of simultaneous mutations highlights the occurrence of intratumoral heterogeneity (ITH) also in the context of FVPTC, which requires comprehensive investigation. The available information shows that NIFTP, identified in accordance with stringent inclusion and exclusion criteria, exhibits a very latent clinical behavior even in the face of conservative lobectomy, lacking of radioactive iodine therapy. However, it cannot be regarded as a benign lesion because there is a small but significant incidence of adverse events, such as lymph nodes and distant metastases. Currently, NIFTP can only be suspected before surgery: several efforts could be explored to identify key molecular, cytological, and ultrasonographic traits that may be helpful in raising the possibility of NIFTP in the preoperative context. Additionally, our discovery of simultaneous mutations within the same lesion strengthens the evidence of ITH even in FVPTC. Although the extent and biological impact of this phenomenon in NIFTP are still debated, a deeper understanding is essential to ensure appropriate clinical management.

2.
J Transl Med ; 22(1): 521, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816839

RESUMEN

BACKGROUND: Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types. METHODS: Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts. RESULTS: Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS. CONCLUSIONS: Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.


Asunto(s)
Neoplasias Encefálicas , Inflamación , Humanos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Masculino , Inflamación/patología , Inflamación/inmunología , Inflamación/genética , Femenino , Persona de Mediana Edad , Anciano , Regulación Neoplásica de la Expresión Génica , Adulto , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Microambiente Tumoral/inmunología , Inmunohistoquímica , Estudios de Cohortes , Análisis de Supervivencia
3.
J Transl Med ; 22(1): 676, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39044184

RESUMEN

BACKGROUND: Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear. METHODS: In this study, we elucidate the connection between FASN and LDHA, pivotal metabolic genes, and their correlation with tumor grade and therapy response using datasets from public repositories. Subsequently, we evaluated the metabolic and proliferative functions upon FASN and LDHA inhibition in breast cancer models. Lastly, we integrated metabolomic and lipidomic analysis to define the contributions of metabolites, lipids, and precursors to the metabolic phenotypes. RESULTS: Collectively, our findings indicate metabolic shifts during breast cancer progression, unvealling two distinct functional energy phenotypes associated with aggressiveness and therapy response. Specifically, FASN exhibits reduced expression in advance-grade tumors and therapy-resistant forms, whereas LDHA demonstrates higher expression. Additionally, the biological and metabolic impact of blocking the enzymatic activity of FASN and LDHA was correlated with resistant conditions. CONCLUSIONS: These observations emphasize the intrinsic metabolic heterogeneity within breast cancer, thereby highlighting the relevance of metabolic interventions in the field of precision medicine.


Asunto(s)
Neoplasias de la Mama , Acido Graso Sintasa Tipo I , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/enzimología , Femenino , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Lipidómica , Metabolómica , L-Lactato Deshidrogenasa
4.
Artículo en Inglés | MEDLINE | ID: mdl-38733254

RESUMEN

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

5.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38732067

RESUMEN

Plexiform fibromyxoma (PF), also referred to as plexiform angiomyxoid myofibroblast tumor, is an exceedingly rare mesenchymal neoplasm primarily affecting the stomach. Herein, we present a case of PF diagnosed in a 71-year-old male with a history of lung cancer, initially suspected to have a gastrointestinal stromal tumor (GIST) of the stomach, who subsequently underwent subtotal gastrectomy. The histopathological and molecular features of the tumor, including mutations in ABL1, CCND1, CSF1R, FGFR4, KDR, and MALAT1-GLI1 fusion, are elucidated and discussed in the context of diagnostic, prognostic, and therapeutic considerations.


Asunto(s)
Fibroma , Neoplasias Gástricas , Humanos , Masculino , Anciano , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/metabolismo , Fibroma/genética , Fibroma/patología , Fibroma/metabolismo , Inmunohistoquímica , Mutación , Biomarcadores de Tumor/genética , Gastrectomía
6.
Int J Mol Sci ; 25(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39273294

RESUMEN

Resistance biomarkers are needed to identify patients with advanced melanoma obtaining a response to ICI treatment and developing resistance later. We searched a combination of molecular signatures of response to ICIs in patients with metastatic melanoma. In a retrospective study on patients with metastatic melanoma treated with an anti-PD-1 agent carried out at Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Naples, Italy. We integrated a whole proteome profiling of metastatic tissue with targeted transcriptomics. To assess the prognosis of patients according to groups of low and high risk, we used PFS and OS as outcomes. To identify the proteins and mRNAs gene signatures associated with the patient's response groups, the discriminant analysis for sparse data performed via partial least squares procedure was performed. Tissue samples from 22 patients were analyzed. A combined protein and gene signature associated with poorer response to ICI immunotherapy in terms of PFS and OS was identified. The PFS and OS Kaplan-Meier curves were significantly better for patients with high expression of the protein signature compared to patients with low expression of the protein signature and who were high-risk (Protein: HR = 0.023, 95% CI: 0.003-0.213; p < 0.0001. Gene: HR = 0.053, 95% CI: 0.011-0.260; p < 0.0001). The Kaplan-Meier curves showed that patients with low-risk gene signatures had better PFS (HR = 0 0.221, 95% CI: 0.071-0.68; p = 0.007) and OS (HR = 0.186, 95% CI: 0.05-0.695; p = 0.005). The proteomic and transcriptomic combined analysis was significantly associated with the outcomes of the anti-PD-1 treatment with a better predictive value compared to a single signature. All the patients with low expression of protein and gene signatures had progression within 6 months of treatment (median PFS = 3 months, 95% CI: 2-3), with a significant difference vs. the low-risk group (median PFS = not reached; p < 0.0001), and significantly poorer survival (OS = 9 months, 95% CI: 5-9) compared to patients with high expression of protein and gene signatures (median OS = not reached; p < 0.0001). We propose a combined proteomic and transcriptomic signature, including genes involved in pro-tumorigenic pathways, thereby identifying patients with reduced probability of response to immunotherapy with ICIs for metastatic melanoma.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Proteómica , Transcriptoma , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Melanoma/mortalidad , Femenino , Masculino , Estudios Retrospectivos , Proteómica/métodos , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Anciano , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Biomarcadores de Tumor/genética , Adulto , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteoma/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/metabolismo , Metástasis de la Neoplasia
7.
J Transl Med ; 21(1): 140, 2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36823670

RESUMEN

BACKGROUND: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment. METHODS: Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study. RESULTS: Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy. CONCLUSIONS: Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Interleucina-6 , Pronóstico , Estudios Retrospectivos
8.
BMC Cancer ; 23(1): 1010, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37858132

RESUMEN

BACKGROUND: Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. METHODS: The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. DISCUSSION: Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05806151.


Asunto(s)
Neoplasias Gastrointestinales , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gastrointestinales/genética , Microambiente Tumoral
9.
Am J Dermatopathol ; 45(3): 153-162, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36730758

RESUMEN

ABSTRACT: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma.


Asunto(s)
Hiperpigmentación , Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Quemadura Solar , Adulto Joven , Humanos , Neoplasias Cutáneas/patología , Dermoscopía , Nevo/patología , Nevo Pigmentado/patología , Melanoma/diagnóstico , Melanoma/patología
10.
Am J Dermatopathol ; 44(5): 355-359, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35170478

RESUMEN

ABSTRACT: Spitz tumors are notoriously characterized by a high propensity to nodal involvement with a morphologically malignant (intraparenchymal) pattern but with little or no tendency toward further spread. We describe a case of spindle cell Spitz neoplasm removed from the thigh in a 34-year-old woman and initially diagnosed as "Spitzoid melanoma;" the sentinel node was characterized by a morphologically benign pattern of nodal involvement, with prevailingly capsular and septal aggregated of melanocytes showing the same cytomorphological features as the cutaneous tumor. Both the cutaneous and the nodal tumor were strongly ROS1-positive on immunohistochemistry; rearrangement of the ROS1 gene was confirmed with fluorescence in situ hybridization on the cutaneous tumor. The clonal relationship between the cutaneous and the nodal capsular/trabecular tumor, as established by their morphological and immunophenotypical resemblance, underlines the existence of a morphologically benign pattern of spread of Spitz neoplasms, as also suggested by the occurrence of eruptive Spitz nevi.


Asunto(s)
Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hibridación Fluorescente in Situ , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugía
11.
Biochim Biophys Acta Rev Cancer ; 1869(1): 78-84, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29126881

RESUMEN

Triple-negative breast cancer (TNBC) is associated with a poor prognosis, due to its aggressive behaviour and lack of effective targeted therapies. Immunocheckpoint inhibitors, such as anti-programmed cell death 1 (PD-1) and anti-PD-ligand(L)1 agents, are in course of investigation in TNBC, used alone or in combination with other systemic or local approaches. However, the high cost of these drugs and the lack of validated predictive biomarkers support the development of strategies aimed to overcome resistance and optimize the efficacy of these approaches. Tumor-Associated Macrophages (TAMs) derive from peripheral blood monocytes recruited into the TNBC microenvironment and, in response to several stimuli, undergo M1 (classical) or M2 (alternative) activation. In TNBC, TAMs promote tumor growth and progression by several mechanisms that include the secretion of inhibitory cytokines, the reduction of effector functions of Tumor Infiltrating Lymphocytes (TILs) and the promotion of Regulatory T cell (Treg). Interestingly, TAMs have been shown to directly and indirectly modulate PD-1/PD-L1 expression in tumor environment. On this scenario, several TAM-centered strategies have been proposed, such as the suppression of TAM recruitment, the depletion of their number, the switch of M2 TAMs into antitumor M1 phenotype and the inhibition of TAM-associated molecules. In this review, we will illustrate the activity of TAMs and associated molecules in TNBC, focusing on their role in modulating the expression of PD-1/PD-L1 and on the emerging TAM-tailored strategies for TNBC patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Linfocitos Infiltrantes de Tumor/fisiología , Macrófagos/fisiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias de la Mama Triple Negativas/terapia , Animales , Resistencia a Antineoplásicos/inmunología , Femenino , Humanos , Inmunomodulación , Pronóstico , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiología
12.
Int J Legal Med ; 135(1): 355-357, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32504148

RESUMEN

Amniotic fluid embolism (AFE) is a rare cause of unexpected late maternal gestational death. The forensic post-mortem diagnosis is rendered upon the histological recognition of fetal "foreign" material inside maternal lung vasculature. The authors propose a double immunohistochemical (anti-CD31 plus anti-cytokeratin AE1/AE3) stain in order to assess accurate amniotic fluid pulmonary embolic burden in a highly reproducible fashion based on the fact that such technique allows to detect an impressive amount of scales within lung vasculature, thereby offering further evidence that pulmonary embolic obstructive microangiopathy, rather than anaphylactoid reaction, is major determinant in AFE-related death.


Asunto(s)
Embolia de Líquido Amniótico/diagnóstico , Células Endoteliales/patología , Patologia Forense/métodos , Pulmón/patología , Adulto , Femenino , Humanos , Inmunohistoquímica , Queratinas/análisis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Embarazo , Coloración y Etiquetado/métodos
13.
Australas J Dermatol ; 62(1): e88-e91, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33107024

RESUMEN

We describe a case of BRCA1-associated protein (BAP1)-inactivated melanocytic tumour (BIMT) in a 22-year-old woman, documenting for the first time with dermoscopy its sudden development with the onset of an atypical vascular pattern within a Miescher naevus. The tumour was histopathologically atypical because of the presence of confluent pleomorphism, solid sheets of cells and grouped mitotic figures: these features were consistent with a melanocytic neoplasm with intermediate morphology ('BAP1-inactivated melanocytoma'; BIM) between a BAP1-inactivated melanocytic naevus and a BAP1-inactivated melanoma. The atypical histopathological features of the present case were different from the criteria quoted for BIM in the World Health Organization 2018 classification of skin tumours.


Asunto(s)
Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Dermoscopía , Femenino , Humanos , Melanocitos/patología , Adulto Joven
14.
Dermatol Online J ; 27(12)2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-35499444

RESUMEN

Laugier-Hunziker syndrome (LHS) is a sporadic, acquired, and infrequent condition characterized by the onset of brown macules on the lips, the oral mucosa, and the acral glabrous skin (mainly fingers and toes) in middle-aged patients. In several cases melanonychia of fingernails and toenails coexists. No other systemic involvement is observed. A case of LHS in a 50-year-old woman is described, with particular attention to dermoscopic features. No dermoscopic specific findings of mucosal/cutaneous maculae have been to date described in the literature. Accumulation of dermoscopic observations of pigmented lesions in LHS is needed and if found to be distinct, it may contribute to a more accurate diagnosis in the future.


Asunto(s)
Hiperpigmentación , Enfermedades de los Labios , Enfermedades de la Uña , Úlceras Bucales , Femenino , Humanos , Hiperpigmentación/diagnóstico , Hiperpigmentación/patología , Enfermedades de los Labios/diagnóstico , Enfermedades de los Labios/patología , Persona de Mediana Edad , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/patología , Síndrome
15.
J Cutan Pathol ; 47(7): 649-653, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32109330

RESUMEN

Discrete junctional cellular aggregates ("nests"), partially staining with melanocytic markers, are described in lichenoid tissue reaction, mainly from chronically sun-exposed skin. The concomitant epidermal flattening and papillary dermal fibrosis with melanophages, may raise the differential diagnosis to that of a regressing melanoma. We describe three cases of interface dermatitis of the head/neck area with clinicopathological features of melanotic discoid lupus erythematosus. These cases showed junctional aggregates, a few composed of inflammatory cells and colloid bodies ("pseudomelanocytic nests"), while others composed of S100- but MART-1+, MITF+, and SOX-10+ cells ("true melanocytic nests"); negativity of the melanocytic component for PRAME was a clue to benignity. True junctional melanocytic nesting may be induced by lichenoid dermatoses on chronically sun-damaged skin. The presence of colloid bodies and of the double negativity for S100 (within nests) and PRAME (both within nests and single melanocytes), together with clinicopathological correlation, avoids misdiagnosis.


Asunto(s)
Dermatitis/diagnóstico , Erupciones Liquenoides/diagnóstico , Piel/patología , Adulto , Anciano , Dermatitis/etiología , Dermatitis/patología , Diagnóstico Diferencial , Femenino , Cabeza/patología , Humanos , Erupciones Liquenoides/patología , Masculino , Melanocitos/patología , Melanoma/diagnóstico , Cuello/patología , Luz Solar/efectos adversos
16.
Australas J Dermatol ; 61(4): e403-e405, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32383170

RESUMEN

A case of pseudoglucagonoma syndrome, that is necrolytic migratory erythema, in a patient with no coexistent glucagonoma, is described. The patient was a 59-year-old man with waxing and waning dermatitis of the buttocks, characterised by arciform erythematous papulo-squamous lesions with micro-pustulation. Histopathology was characteristic for necrolytic migratory erythema, but no other underlying disease was detected. Other cases of pseudoglucagonoma syndrome described in literature are briefly reviewed.


Asunto(s)
Eritema Necrolítico Migratorio/patología , Nalgas , Diabetes Mellitus , Glucagón/sangre , Humanos , Masculino , Persona de Mediana Edad
17.
J Am Acad Dermatol ; 80(6): 1585-1593, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30244062

RESUMEN

BACKGROUND: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. OBJECTIVES: We sought to describe the clinical and dermoscopic features of BIMTs. METHODS: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. RESULTS: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively). LIMITATIONS: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. CONCLUSIONS: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.


Asunto(s)
Melanoma/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adolescente , Adulto , Anciano , Biopsia , Estudios de Casos y Controles , Niño , Bases de Datos Factuales , Dermoscopía , Femenino , Mutación de Línea Germinal , Humanos , Masculino , Melanoma/genética , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Síndromes Neoplásicos Hereditarios/genética , Nevo de Células Epitelioides y Fusiformes/genética , Nevo de Células Epitelioides y Fusiformes/patología , Nevo Pigmentado/genética , Variaciones Dependientes del Observador , Estudios Retrospectivos , Tamaño de la Muestra , Método Simple Ciego , Neoplasias Cutáneas/genética , Adulto Joven
18.
Am J Dermatopathol ; 40(4): 247-253, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28654469

RESUMEN

The occurrence of pseudolymphomatous infiltrates in cutaneous lupus erythematosus (cLE) is described mainly in lupus panniculitis and lupus tumidus/lymphocytic infiltration of the skin (Jessner-Kanof). We collected 15 cases of pseudolymphomatous cLE other than lupus panniculitis and lupus tumidus (M:F = 4:11; age range: 23-79 years; mean age: 50.9 years; median age: 57 years). Of the 15 cases, 9 (60%) were characterized by dense nodular infiltrates. Three cases (20%) showed an angiocentric pattern with cytological atypia of lymphoid cells; 2 cases (13.3%) showed a band-like infiltrate mimicking mycosis fungoides, and 1 case had mixed features of the band-like and angiocentric patterns. Clues to the histopathological diagnosis of cLE were presence of interface dermatitis, clusters of plasmacytoid dendritic cells, and dermal mucin deposition. Our study shows that the spectrum of pseudolymphomatous presentations of cLE is broader than previously described, including band-like cases that may be misconstrued as mycosis fungoides, and angiocentric cases that may be misinterpreted as an aggressive lymphoma. Recognition of such cases is possible only on careful clinicopathologic correlation and requires a high level of histopathological suspicion to allow a correct diagnosis and the proper management of the patients.


Asunto(s)
Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/patología , Seudolinfoma/patología , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Trastornos Linfoproliferativos/diagnóstico , Masculino , Persona de Mediana Edad , Seudolinfoma/diagnóstico , Adulto Joven
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