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1.
Mol Brain ; 14(1): 154, 2021 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-34615523

RESUMEN

Studies on the development of central nervous system (CNS) primarily rely on the use of specific molecular markers for different types of neural cells. S100B is widely being used as a specific marker for astrocytes in the CNS. However, the specificity of its expression in astrocyte lineage has not been systematically investigated and thus has remained a lingering issue. In this study, we provide several lines of molecular and genetic evidences that S100B is expressed in both protoplasmic astrocytes and myelinating oligodendrocytes. In the developing spinal cord, S100B is first expressed in the ventral neuroepithelial cells, and later in ALDH1L1+/GS+ astrocytes in the gray matter. Meanwhile, nearly all the S100B+ cells in the white matter are SOX10+/MYRF+ oligodendrocytes. Consistent with this observation, S100B expression is selectively lost in the white matter in Olig2-null mutants in which oligodendrocyte progenitor cells (OPCs) are not produced, and dramatically reduced in Myrf-conditional knockout mutants in which OPCs fail to differentiate. Similar expression patterns of S100B are observed in the developing forebrain. Based on these molecular and genetic studies, we conclude that S100B is not a specific marker for astrocyte lineage; instead, it marks protoplasmic astrocytes in the gray matter and differentiating oligodendrocytes.


Asunto(s)
Astrocitos/metabolismo , Sustancia Gris/citología , Oligodendroglía/metabolismo , Prosencéfalo/crecimiento & desarrollo , Subunidad beta de la Proteína de Unión al Calcio S100/biosíntesis , Médula Espinal/crecimiento & desarrollo , Animales , Biomarcadores , Encéfalo/crecimiento & desarrollo , Linaje de la Célula , Citoplasma/metabolismo , Proteína Ácida Fibrilar de la Glía/análisis , Glutamato-Amoníaco Ligasa/análisis , Ratones , Vaina de Mielina/fisiología , Neuronas/metabolismo , Especificidad de Órganos , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/análisis , Prosencéfalo/citología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Subunidad beta de la Proteína de Unión al Calcio S100/genética , Factores de Transcripción SOXE/análisis , Médula Espinal/citología
2.
Science ; 372(6547)2021 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-34112666

RESUMEN

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti-programmed cell death-1 (PD-1)-based therapy, including CD163+PD-L1- myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti-PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/análisis , Técnica del Anticuerpo Fluorescente , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Antígeno B7-H1/análisis , Antígenos CD8/análisis , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Proteínas de Punto de Control Inmunitario/análisis , Macrófagos/química , Masculino , Melanoma/química , Melanoma/inmunología , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Receptor de Muerte Celular Programada 1/análisis , Supervivencia sin Progresión , Receptores de Superficie Celular/análisis , Factores de Transcripción SOXE/análisis , Análisis de la Célula Individual , Subgrupos de Linfocitos T/química , Subgrupos de Linfocitos T/inmunología , Resultado del Tratamiento , Microambiente Tumoral
3.
Am J Otolaryngol ; 42(6): 103139, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34174671

RESUMEN

The cellular blue nevus tumor is a type of dendritic melanocytic nevus that is typically benign and exceedingly rare. The incidence of all blue nevi is about 1%, usually affecting the adult population and appearing on the extremities, sacrococcygeal or gluteal regions. There have only been a handful of case reports cited in the literature where cellular blue nevi present in the head and neck region, usually affecting the scalp and young adult population (7, 8). As such, it is exceedingly rare to encounter a cellular blue nevus tumor in the neck or infiltrating into neck lymph nodes. Here we report a rare case of a cellular blue nevus tumor presenting as a right neck mass in a pediatric 16-year-old patient, shown to invade into the submandibular lymph node and surrounding soft tissue. It is important to be aware of the cellular blue nevus tumor as a differential diagnosis in pediatric neck masses. Histological evaluation is necessary to determine tumor aggression and malignant potential which can guide further treatment in pediatric patients.


Asunto(s)
Ganglios Linfáticos/patología , Mandíbula , Nevo Azul/patología , Neoplasias Cutáneas/patología , Adolescente , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Femenino , Humanos , Ganglios Linfáticos/cirugía , Antígeno MART-1/análisis , Nevo Azul/diagnóstico , Nevo Azul/cirugía , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Antígeno gp100 del Melanoma/análisis
4.
Med Mol Morphol ; 54(3): 281-288, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34009452

RESUMEN

Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.


Asunto(s)
Carcinoma Intraductal no Infiltrante/diagnóstico , Neoplasias de los Labios/diagnóstico , Pueblo Asiatico , Biomarcadores de Tumor/análisis , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/cirugía , Receptores ErbB/análisis , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Japón , Queratina-19/análisis , Queratina-19/genética , Queratina-5/análisis , Queratina-5/genética , Queratina-6/análisis , Queratina-6/genética , Labio/cirugía , Neoplasias de los Labios/metabolismo , Neoplasias de los Labios/cirugía , Persona de Mediana Edad , Receptores Androgénicos/análisis , Receptores Androgénicos/genética , Factores de Transcripción SOXE/análisis , Factores de Transcripción SOXE/genética
5.
Surg Pathol Clin ; 14(1): 43-51, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33526222

RESUMEN

Sialadenoma papilliferum (SP) is a rare, benign salivary gland neoplasm sharing similar histopathologic features and harboring the same genetic alterations, BRAF V600E or HRAS mutations, with syringocystadenoma papilliferum. SP most commonly occurs in the hard palate and in older adults. Clinically, SP is most likely to be diagnosed as a squamous papilloma. Microscopically, SP shows an exophytic papillary epithelial proliferation and a contiguously endophytic ductal proliferation. Two distinct subtypes are identified: classic SP and oncocytic SP. Conservative surgical treatment seems to be adequate with a low recurrence. SOX10 immunohistochemistry and BRAF analysis may be useful in differential diagnosis.


Asunto(s)
Adenoma/patología , Neoplasias de las Glándulas Salivales/patología , Adenoma/clasificación , Adenoma/diagnóstico , Adenoma/cirugía , Proliferación Celular , Diagnóstico Diferencial , Células Epiteliales/patología , Humanos , Inmunohistoquímica , Mutación , Paladar Duro/patología , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Factores de Transcripción SOXE/análisis , Neoplasias de las Glándulas Salivales/clasificación , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/cirugía , Glándulas Salivales Menores/patología
6.
Int J Surg Pathol ; 29(5): 470-474, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33543662

RESUMEN

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/diagnóstico , Factores de Transcripción SOXE/análisis , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/secundario , Estudios de Casos y Controles , Estudios de Factibilidad , Femenino , Factor de Transcripción GATA3/análisis , Factor de Transcripción GATA3/metabolismo , Humanos , Queratina-7/análisis , Queratina-7/metabolismo , Persona de Mediana Edad , Factores de Transcripción SOXE/metabolismo , Sensibilidad y Especificidad , Análisis de Matrices Tisulares , Adulto Joven
7.
Dermatol Online J ; 27(10)2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35130387

RESUMEN

Report _Case Presentation _Photo Vignette _Letter Authors declare that the contents of this article are their own original unpublished findings. Title: Primary cutaneous perivascular epithelioid cell tumors: two cases and a review of the literature Authors: Jennifer Wong1 DO, Jason Mammino2 DO, Jennifer Seyffert3 DO, Kristen Schmits4 MD, Etan Marks4 MD, Daniel Rivlin3 MD Affiliations: 1Department of Dermatology, LECOM- Larkin Community Hospital, Miami, Florida, USA, 2Department of Dermatology, KCUMB - Advanced Dermatology and Cosmetic Surgery, Orlando, Florida, USA, 3Department of Dermatology, LECOM- Skin and Cancer Associates, Miami Beach, Florida, USA, 4Department of Dermatopathology Advanced Dermatology and Cosmetic Surgery Pathology Laboratory, Delray Beach, Florida, USA Corresponding Author: Jennifer Seyffert DO, 4308 Alton Road, Suite 510, Miami Beach, FL 33140, Tel: 305-674-8865, Fax: 305-674-1459, Email: jseyf12@gmail.com Abstract: Perivascular epithelioid cell tumors, also known as PEComas, are mesenchymal neoplasms which uncommonly originate within the skin, with only 23 cases documented within the literature. These rare neoplasms classically display epithelioid cells composed of granular or clear cytoplasm arranged in sheets, nests, or cords. Their immunoreactivity for melanocytic and smooth muscle markers makes these tumors distinct and unique.[1] We herein present two cases of primary cutaneous PEComas that clinically mimic other common cutaneous neoplasms and illustrate the necessity for clinical-pathologic correlation. A literature review is also presented to compare the different clinical and histological presentations of cutaneous PEComas.


Asunto(s)
Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias Cutáneas/patología , Anciano , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Femenino , Humanos , Factor de Transcripción Asociado a Microftalmía/análisis , Persona de Mediana Edad , Neoplasias de Células Epitelioides Perivasculares/inmunología , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/inmunología , Antígeno gp100 del Melanoma/análisis
8.
Histopathology ; 78(5): 717-726, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33065755

RESUMEN

AIMS: Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. METHODS AND RESULTS: Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. CONCLUSIONS: To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.


Asunto(s)
Melanoma , Enfermedades de la Uña , Neoplasias Cutáneas , Adulto , Biomarcadores de Tumor/análisis , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Antígeno MART-1/análisis , Masculino , Melanocitos/patología , Melanoma/diagnóstico , Melanoma/patología , Persona de Mediana Edad , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/patología , Estudios Retrospectivos , Proteínas S100/análisis , Factores de Transcripción SOXE/análisis , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología
9.
Am J Dermatopathol ; 43(4): 273-277, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32675472

RESUMEN

ABSTRACT: Lentigo maligna (LM) represents an overgrowth of atypical melanocytes at the dermal-epidermal junction of chronically sun-damaged skin. The presence of LM on sun-damaged skin poses a diagnostic challenge because the solar-induced melanocytic hyperplasia makes it difficult to assess the LM margins. Melanocytic density can be used to discriminate sun-damaged skin from LM. The aim of this study was to quantify the melanocytic density at the surgical margins of scanned whole-slide images of LM comparing sections stained with H&E and SOX10. Twenty-six surgically excised LM diagnosed at the Department of Pathology at Sahlgrenska University Hospital were collected. The slides that contained the closest surgical margin or harbored the highest density of melanocytes at the margin were selected for serial sectioning using H&E and SOX10. Whole-slide imaging at ×40 magnification was used, and a circular field with a diameter of 0.5 mm at the surgical margin was superimposed on the image. Five blinded pathologists reviewed the slides in a randomized order. In the majority of the cases (24/26), the pathologists identified more melanocytes on the SOX10 slides than those on the H&E slides. On average, 2.5 times more melanocytes were counted using SOX10 compared with H&E (P < 0.05). Furthermore, the average group SD on the H&E slides was 4.12 compared with 2.83 on the SOX10 slides (P = 0.004). Thus, the use of SOX10 staining leads to higher melanocytic density counts compared with H&E staining when assessing the surgical margins of LM. The use of SOX10 staining also significantly decreased the interobserver variability between pathologists.


Asunto(s)
Biomarcadores de Tumor/análisis , Proliferación Celular , Peca Melanótica de Hutchinson/química , Inmunohistoquímica , Melanocitos/química , Microscopía , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/química , Coloración y Etiquetado , Colorantes , Eosina Amarillenta-(YS) , Hematoxilina , Humanos , Peca Melanótica de Hutchinson/patología , Interpretación de Imagen Asistida por Computador , Melanocitos/patología , Variaciones Dependientes del Observador , Patólogos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Neoplasias Cutáneas/patología
10.
Mod Pathol ; 34(Suppl 1): 62-77, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33110239

RESUMEN

Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation criteria and potential pitfalls. Immunohistochemistry assists in supporting breast origin for primary or metastatic carcinomas and identifying non-mammary metastases to the breast; however, no single immunostain is perfectly sensitive nor specific. GATA3 and Sox10 are particularly useful immunostains to identify triple negative breast carcinoma, which are often negative for other markers of mammary differentiation. Sox10 labeling is a major potential diagnostic pitfall, as Sox10 and S-100 label both triple negative breast carcinoma and metastatic melanoma; a pan-cytokeratin immunostain should always be included for this differential diagnosis. Novel immunohistochemistry serves as surrogates for the molecular alterations unique to several of special-type breast carcinomas, including the use of MYB in adenoid cystic carcinoma, pan-TRK in secretory carcinoma, and mutant IDH2 in tall cell carcinoma with reversed polarity (TCCRP). In addition, PD-L1 immunohistochemistry is an emerging, albeit imperfect, biomarker for breast cancer immunotherapy, with different assay parameters and scoring criteria in breast carcinoma compared to other tumor types. The expanding repertoire of novel immunohistochemistry provides additional diagnostic tools and biomarkers that improve diagnostic breast pathology and patient care.


Asunto(s)
Neoplasias de la Mama , Inmunohistoquímica/métodos , Antígeno B7-H1 , Biomarcadores de Tumor/análisis , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/patología , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patología , Diagnóstico Diferencial , Femenino , Factor de Transcripción GATA3/análisis , Humanos , Factores de Transcripción SOXE/análisis , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/patología
11.
Hum Pathol ; 103: 52-62, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32673681

RESUMEN

Oncocytomas (OCs) in salivary glands are rare benign tumors composed of mitochondria-rich epithelial cells (oncocytes), mostly localized in the parotid gland. The treatment of choice is simple excision. Extensive oncocytic metaplasia of pleomorphic adenoma (PA) and myoepithelioma (ME) can be diagnostically challenging and may camouflage the correct diagnosis. These tumors should be treated more carefully compared with OC, given the risk of frequent recurrences and the possibility of malignant transformation. We have investigated 89 oncocytic lesions from our files, including OC (n = 74) and metaplastic oncocytic variant of PA/ME (n = 15). All OCs were stained for S100 protein and SOX10. The tumors with immunohistochemical expression of one or both markers were tested by next-generation sequencing (NGS). The NGS results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH). Ten cases originally diagnosed as OC, and 1 low-grade uncertain oncocytic tumor (11/74) revealed nuclear-cytoplasmic and/or nuclear positivity for S100 protein and/or SOX10, respectively. Fusion transcripts CHCHD7-PLAG1 and GEM-PLAG1 were found in 2 cases (1 fusion in each), and these were confirmed by RT-PCR and PLAG1 break-apart FISH probe, respectively. Another 5 cases were positive for PLAG1 rearrangement by FISH. In the control group of 15 oncocytic PA/ME, 4/15 tested tumors harbored gene fusions including NFT3-PLAG1, CHCHD7-PLAG1, FBXO32-PLAG1, and C1orf116-PLAG1 (1 fusion in each case) as detected by NGS. Two fusions were confirmed by RT-PCR, 1 case by FISH, and 1 case was not analyzable by FISH. We additionally tested 24 OCs negative for S100 protein and SOX10 by immunohistochemistry (IHC) and by FISH for rearrangement of PLAG1 gene, but none of them were positive. SOX10 and/or S100 protein immunopositivity in conjunction with rearrangement of the PLAG1 gene assisted in reclassification of a subset of oncocytomas as oncocytic variants of PA and ME. Therefore, we recommend to include S100 protein and SOX10 IHC when diagnosing tumors with predominantly oncocytoma-like differentiation. In addition, by NGS, 3 new gene fusions were detected in oncocytic ME, including NTF3-PLAG1, FBXO32-PLAG1, and GEM-PLAG1, and a new fusion C1orf116-PLAG1 was detected in oncocytic PA.


Asunto(s)
Adenoma Oxifílico/diagnóstico , Adenoma Pleomórfico/diagnóstico , Biomarcadores de Tumor/análisis , Mioepitelioma/diagnóstico , Neoplasias de las Glándulas Salivales/diagnóstico , Adenoma Oxifílico/genética , Adenoma Pleomórfico/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mioepitelioma/genética , Fusión de Oncogenes , Estudios Retrospectivos , Proteínas S100/análisis , Proteínas S100/biosíntesis , Factores de Transcripción SOXE/análisis , Factores de Transcripción SOXE/biosíntesis , Neoplasias de las Glándulas Salivales/genética
12.
Hum Pathol ; 103: 107-119, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32707054

RESUMEN

The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4-457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2-77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Conjuntiva/diagnóstico , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Antígenos Específicos del Melanoma/análisis , Persona de Mediana Edad , Factores de Transcripción SOXE/análisis , Adulto Joven , Antígeno gp100 del Melanoma
13.
Neuropathology ; 40(4): 373-378, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32301179

RESUMEN

We herein report a patient who was diagnosed as having olfactory groove schwannoma (OGS) which was negative for CD57 (Leu7) but positive for Schwann/2E and Sox10. A 13-year-old female with a chief complaint of headache was referred to our department due to a tumor lesion in the anterior skull base identified by magnetic resonance imaging (MRI). At the first visit, she did not exhibit altered consciousness, motor palsy, anosmia, seizures, or café au lait spots. On contrast-enhanced computed tomography (CT), a heterogeneously enhanced tumor, 50 × 45 × 50 mm in size, was observed at the anterior skull base. The left cribriform plate was thinner on bone window CT. The tumor exhibited strong, heterogeneous gadolinium enhancement on MRI as well. Slight tumor staining was observed by angiography of the left internal carotid artery but not the left external carotid artery. The patient was preoperatively diagnosed as having meningioma and underwent gross tumor resection via the basal interhemispheric approach. The tumor was strongly positive for S-100 protein and negative for epithelial membrane antigen and CD57 by immunostaining. The tumor was positive for both Schwann/2E and Sox10, which aided in the differential diagnosis between OGSs and olfactory ensheathing cell (OEC) tumors, and the definitive diagnosis was OGS. The assessment of immunoreactivities for Schwann/2E and Sox10 might be necessary to differentiate CD57-negative Schwannomas from OEC tumors.


Asunto(s)
Biomarcadores de Tumor/análisis , Fosa Craneal Anterior/patología , Neoplasias de la Vaina del Nervio/diagnóstico , Neurilemoma/diagnóstico , Neoplasias de la Base del Cráneo/diagnóstico , Adolescente , Diagnóstico Diferencial , Femenino , Humanos , Factores de Transcripción SOXE/análisis
14.
Histopathology ; 77(6): 936-948, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32304249

RESUMEN

AIMS: Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). METHODS AND RESULTS: We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort. CONCLUSION: SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.


Asunto(s)
Biomarcadores de Tumor , Factores de Transcripción SOXE , Neoplasias de la Mama Triple Negativas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Femenino , Factor de Transcripción GATA3/análisis , Factor de Transcripción GATA3/metabolismo , Humanos , Mamoglobina A/análisis , Mamoglobina A/metabolismo , Persona de Mediana Edad , Factores de Transcripción SOXE/análisis , Factores de Transcripción SOXE/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Adulto Joven
15.
Am J Dermatopathol ; 42(9): 697-699, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32149837

RESUMEN

An 83-year-old man presented with a tumor of the neck, clinically consistent with an epidermal inclusion cyst. Excisional biopsy revealed a deeply infiltrating spindled cell tumor. Immunohistochemical markers for S100, SOX-10, Melan-A, HMB-45, and NK1/C3 were negative. Based on the presence of an area of lentigo maligna and the histologic pattern of the spindle cell component, a diagnosis of desmoplastic melanoma was made despite the absence of immunophenotypic evidence for melanocytic differentiation. To the best of our knowledge, the complete lack of both S100 and SOX-10 makes this tumor an unprecedented case. To avoid ruling out the diagnosis of desmoplastic melanoma prematurely, physicians should be made aware of this possible immunohistochemical profile.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de Cabeza y Cuello/química , Melanoma/química , Proteínas S100/análisis , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/química , Anciano de 80 o más Años , Biopsia , Diagnóstico Diferencial , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Inmunohistoquímica , Masculino , Melanoma/patología , Melanoma/cirugía , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía
16.
Am J Surg Pathol ; 44(5): 665-672, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31895100

RESUMEN

Odontogenic tumors show considerable morphologic heterogeneity and at times the diagnosis can be challenging. Ameloblastoma, the most common odontogenic tumor, can have morphologic similarity to some salivary gland tumors and therefore we sought to identify biomarkers that might aid in the diagnosis by performing transcriptome wide gene expression profiling of 80 odontogenic and salivary gland neoplasms. These data identified the FOXP1/SOX10 expression profile as characteristic of many odontogenic tumors including ameloblastoma but largely absent in salivary gland tumors. We then assessed 173 salivary gland tumors and 108 odontogenic tumors by immunohistochemistry for FOXP1 and SOX10 expression and found that 34/35 (97%) cases of ameloblastomas were diffusely positive for FOXP1 but completely negative for SOX10. None of the basaloid salivary neoplasms (basal cell adenoma, adenoid cystic carcinoma, polymorphous adenocarcinoma, and myoepitheloma) demonstrated FOXP1/SOX10 expression pattern. Taken together, the results of this study suggest that the FOXP1/SOX10 immunophenotype is common in odontogenic tumors including ameloblastoma and might be useful distinguishing these from similar appearing basaloid salivary gland tumors.


Asunto(s)
Ameloblastoma/genética , Biomarcadores de Tumor/genética , Carcinoma/genética , Factores de Transcripción Forkhead/genética , Perfilación de la Expresión Génica , Proteínas Represoras/genética , Factores de Transcripción SOXE/genética , Neoplasias de las Glándulas Salivales/genética , Ameloblastoma/química , Ameloblastoma/patología , Biomarcadores de Tumor/análisis , Colombia Británica , Carcinoma/química , Carcinoma/patología , Diagnóstico Diferencial , Factores de Transcripción Forkhead/análisis , Humanos , Inmunohistoquímica , Valor Predictivo de las Pruebas , Proteínas Represoras/análisis , Factores de Transcripción SOXE/análisis , Neoplasias de las Glándulas Salivales/química , Neoplasias de las Glándulas Salivales/patología , San Francisco , Transcriptoma
17.
Sex Med Rev ; 8(4): 615-621, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31926907

RESUMEN

INTRODUCTION: Patients with penile schwannoma are rare and usually with variant presentations. No evidence-based clinical guideline exists for diagnosis or treatment. To put schwannoma into differential diagnoses of benign soft tissue lesions in the penis is important. AIM: To analyze and categorize clinical, histopathological, and radiological presentations and apply possible explanation on several fields of penile schwannoma. METHODS: We collected the English literature through the PubMed database of the National Library of Medicine up to October 2019. A newly diagnosed case in Chang Gung Memorial Hospital, Taiwan, was also included. This study categorized lesion locations into the penile body or shaft, glans, or penile root, dorsal or ventral. MAIN OUTCOME MEASURE: The main outcome measure was to demonstrate clinical, pathological, ultrasonography, and MRI manifestations of penile schwannoma and perform immunohistochemistry staining that has not been performed among penile schwannomas. RESULTS: We collected 40 cases. Data were arranged in tables. Clear descriptions were added on several fields of penile schwannoma in detail in Discussion. CONCLUSION: Penile schwannomas are mostly located at the penile shaft and dorsum of the penis. Dyspareunia is the most reported complaint for sexual dysfunction. This study is the first study in the world to document the expressions of calretinin, SOX10, glial fibrillary acid protein, D2-40 (podoplanin), and cytokeratin AE1/AE3 in penile schwannoma and claims magnetic resonance imaging and pathologic presentations of penile schwannomas are synonymous with schwannomas from head to toe. The current patient may be the first to present with penile schwannoma with schwannomatosis. Huang LC, Wang HZ, Chu YC, et al. Clinicopathological Presentation and Management of Penile Schwannoma. Sex Med Rev 2020;8:615-621.


Asunto(s)
Neurilemoma/diagnóstico , Neurilemoma/patología , Neurilemoma/terapia , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/patología , Neoplasias del Pene/terapia , Calbindina 2/análisis , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Inmunohistoquímica , Masculino , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Neurilemoma/complicaciones , Neurilemoma/diagnóstico por imagen , Neurofibromatosis/complicaciones , Neoplasias del Pene/diagnóstico por imagen , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/complicaciones
18.
Head Neck Pathol ; 14(2): 406-411, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31222589

RESUMEN

Differentiating between adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAC) can be difficult on small biopsies and cytologic specimens. As such, further characterization of their immunophenotype may aid in distinction. Previous studies have found AdCC to be SOX10+/GATA3 variable and PAC to be GATA3 negative. SOX10 expression in PAC has, as yet, not been established. We performed GATA3 and SOX10 immunohistochemistry on whole sections of 25 cases each of AdCC and PAC (including both classic PAC and the cribriform variant) to assess whether these markers are of diagnostic utility in distinguishing between these entities. SOX10 was found to be positive in 100% of PAC and AdCC whereas GATA 3 was immunoreactive in 45% of AdCCs and 20% of PAC. While this is the first series to compare SOX10 and GATA3 staining in these two tumor types, their frequent expression and similar staining patterns render them of limited value in discriminating between these neoplasms.


Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/análisis , Carcinoma Adenoide Quístico/diagnóstico , Factor de Transcripción GATA3/biosíntesis , Factores de Transcripción SOXE/biosíntesis , Neoplasias de las Glándulas Salivales/diagnóstico , Diagnóstico Diferencial , Factor de Transcripción GATA3/análisis , Humanos , Factores de Transcripción SOXE/análisis
19.
Ann Dermatol Venereol ; 146(5): 372-376, 2019 May.
Artículo en Francés | MEDLINE | ID: mdl-30910333

RESUMEN

BACKGROUND: Myxoid melanoma is a rare variant of melanoma that must be recognised. Herein we describe a new metastatic case. PATIENTS AND METHODS: A 78-year-old woman consulted for a firm, pinkish nodule measuring 25mm and present for six months on her left leg. Analysis of the biopsy revealed achromic fusiform tumour cells separated by large myxoid plaques. Labeling of SOX10, HMB45 and PS100 was diffuse and of moderate to strong intensity. A diagnosis of myxoid melanoma was considered, with Breslow thickness of 9mm. Surgery was carried out with a 2-cm margin and confirmed the diagnosis. Dermatological follow-up at one year revealed metastatic spread to the ganglia, pleura, liver and bone. DISCUSSION: Few cases of primary myxoid melanoma have been described, and the condition is probably underdiagnosed. The classic clinical presentation of this condition consists of a solitary achromic nodule found chiefly on the limbs. The microscopic appearance is relatively non-specific. Immunohistochemical analysis may indicate melanocytic involvement: cells exhibit expression of SOX10, diffuse expression of protein S100, and less consistent and more variable expression of HMB45. The increasingly common use of anti-SOX10 is of value since it is expressed in the nucleus of melanocytes. Mastocytes and TGF-ß secretion appear to be involved in myxoid stroma production. In the absence of specific codification, management of myxoid melanoma is comparable to that of other types of melanoma. There is uncertainty about the prognosis, with the involvement of TGF-ß possibly indicating the aggressive potential of this type of tumour.


Asunto(s)
Pierna , Melanoma/patología , Neoplasias Cutáneas/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Femenino , Humanos , Melanocitos/química , Melanoma/química , Antígenos Específicos del Melanoma/análisis , Proteínas S100/análisis , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/química , Antígeno gp100 del Melanoma
20.
J Drugs Dermatol ; 18(3): 262-264, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30909330

RESUMEN

Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs. J Drugs Dermatol. 2019;18(3):262-264.


Asunto(s)
Queratinas/análisis , Cirugía de Mohs/métodos , Nervios Periféricos/patología , Factores de Transcripción SOXE/análisis , Neoplasias Cutáneas/patología , Carcinoma Basocelular/patología , Carcinoma Basocelular/prevención & control , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/prevención & control , Secciones por Congelación , Humanos , Inmunohistoquímica , Invasividad Neoplásica/patología , Piel/inervación , Piel/patología , Neoplasias Cutáneas/cirugía
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