RESUMO
An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.
Assuntos
Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Feminino , Melanoma/diagnóstico , Melanoma/patologia , Criança , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Nevo Pigmentado/patologia , Nevo Pigmentado/diagnóstico , Diagnóstico Diferencial , Melanócitos/patologiaRESUMO
"Inflammatory rhabdomyoblastic tumor" (IRMT) is a recently coined name for a distinctive soft tissue neoplasm characterized by slow growth, a dense histiocytic infiltrate, scattered, bizarre-appearing tumor cells with morphologic and immunohistochemical evidence of skeletal muscle differentiation, a near-haploid karyotype with retained biparental disomy of chromosomes 5 and 22, and usually indolent behavior. There are 2 reports of rhabdomyosarcoma (RMS) arising in IRMT. We studied the clinicopathologic and cytogenomic features of 6 cases of IRMT with progression to RMS. Tumors occurred in the extremities of 5 men and 1 woman (median patient age, 50 years; median tumor size, 6.5 cm). Clinical follow-up (6 patients: median, 11 months; range 4-163 months) documented local recurrence and distant metastases in 1 and 5 of 6 patients, respectively. Therapy included complete surgical resection (4 patients) and adjuvant/neoadjuvant chemo/radiotherapy (6 patients). One patient died of disease, 4 were alive with metastatic disease, and one was without evidence of disease. All primary tumors contained conventional IRMT. Progression to RMS appeared as follows: (1) overgrowth of monomorphic rhabdomyoblasts with diminished histiocytes, (2) monomorphic spindle cell morphology with variably pleomorphic rhabdomyoblasts and low mitotic activity, or (3) morphologically undifferentiated spindle cell and epithelioid sarcoma. All but one were diffusely desmin-positive, with more limited MyoD1/myogenin expression. All RMS arising in IRMT, either primary or metastatic, demonstrated widespread loss of heterozygosity with retained heterozygosity of chromosomes 5 and 20, and all but one displayed additional gains and losses involving loci containing oncogenes/ tumor suppressor genes, most often CDKN2A and CDKN2B. RMS arising in IRMT have unique clinicopathologic and cytogenomic features, warranting classification as a distinct, potentially aggressive RMS subtype. It should be distinguished from other RMSs, particularly fusion-driven spindle cell RMS and pleomorphic RMS.
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Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Neoplasias de Tecidos Moles , Masculino , Feminino , Adulto , Humanos , Criança , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Diferenciação CelularRESUMO
Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures.
Assuntos
Carcinoma Secretor Análogo ao Mamário , Exposição à Radiação , Neoplasias das Glândulas Salivares , Adulto , Biomarcadores Tumorais/genética , Humanos , Masculino , Carcinoma Secretor Análogo ao Mamário/genética , Carcinoma Secretor Análogo ao Mamário/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologiaRESUMO
Primary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full-length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell-rich primary bone tumors. In this report, we present a case of a 16-year-old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X-USP6 promoter swap fusion. This result was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin-specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate-specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.
Assuntos
Cistos Ósseos Aneurismáticos/diagnóstico , Cistos Ósseos Aneurismáticos/genética , Predisposição Genética para Doença , Proteínas de Fusão Oncogênica/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Ubiquitina Tiolesterase/genética , Adolescente , Biomarcadores Tumorais , Biópsia , Bandeamento Cromossômico , Biologia Computacional/métodos , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Acute myeloid leukemia (AML) can be subtyped based on recurrent cytogenetic and molecular genetic abnormalities with diagnostic and prognostic significance. Although cytogenetic characterization classically involves conventional chromosome and/or fluorescence in situ hybridization (FISH) assays, limitations of these techniques include poor resolution and the inability to precisely identify breakpoints. METHOD: We evaluated whether an NGS-based methodology that detects structural abnormalities and copy number changes using mate pair sequencing (MPseq) can enhance the diagnostic yield for patients with AML. RESULTS: Using 68 known abnormal and 20 karyotypically normal AML samples, each recurrent primary AML-specific abnormality previously identified in the abnormal samples was confirmed using MPseq. Importantly, in eight cases with abnormalities that could not be resolved by conventional cytogenetic studies, MPseq was utilized to molecularly define eight recurrent AML-fusion events. In addition, MPseq uncovered two cryptic abnormalities that were missed by conventional cytogenetic studies. Thus, MPseq improved the diagnostic yield in the detection of AML-specific structural rearrangements in 10/88 (11%) of cases analyzed. CONCLUSION: Utilization of MPseq represents a precise, molecular-based technique that can be used as an alternative to conventional cytogenetic studies for newly diagnosed AML patients with the potential to revolutionize the diagnosis of hematologic malignancies.
Assuntos
Aberrações Cromossômicas , Genômica , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Análise de Sequência de DNA , Idoso , Biologia Computacional/métodos , Feminino , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Proteínas de Fusão Oncogênica/genéticaRESUMO
BACKGROUND: HER2 positive (HER2+) breast cancers involve chromosomal structural alterations that act as oncogenic driver events. METHODS: We interrogated the genomic structure of 18 clinically-defined HER2+ breast tumors through integrated analysis of whole genome and transcriptome sequencing, coupled with clinical information. RESULTS: ERBB2 overexpression in 15 of these tumors was associated with ERBB2 amplification due to chromoanasynthesis with six of them containing single events and the other nine exhibiting multiple events. Two of the more complex cases had adverse clinical outcomes. Chromosomes 8 was commonly involved in the same chromoanasynthesis with 17. In ten cases where chromosome 8 was involved we observed NRG1 fusions (two cases), NRG1 amplification (one case), FGFR1 amplification and ADAM32 or ADAM5 fusions. ERBB3 over-expression was associated with NRG1 fusions and EGFR and ERBB3 expressions were anti-correlated. Of the remaining three cases, one had a small duplication fully encompassing ERBB2 and was accompanied with a pathogenic mutation. CONCLUSION: Chromoanasynthesis involving chromosome 17 can lead to ERBB2 amplifications in HER2+ breast cancer. However, additional large genomic alterations contribute to a high level of genomic complexity, generating the hypothesis that worse outcome could be associated with multiple chromoanasynthetic events.
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Neoplasias da Mama/genética , Cromotripsia , Amplificação de Genes , Receptor ErbB-2/genética , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Cromossomos Humanos Par 17 , Estudos de Coortes , Feminino , Humanos , Estadiamento de Neoplasias , Receptor ErbB-2/análiseRESUMO
The 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) recommendations for HER2 testing contain a recommendation for pathologists with respect to invasive micropapillary carcinoma. The guidelines suggest that HER2 immunohistochemical staining that is intense but incomplete and would be considered 1+ may actually be HER2-amplified by fluorescence in situ hybridization. Thus, pathologists should consider reporting the immunohistochemistry as equivocal (2+) and employ an alternative testing methodology. This recommendation is based largely on one paper wherein the authors tested a series of 22 micropapillary carcinomas that were considered 1+ by immunohistochemistry and identified HER2 amplification in one case (5%). In order to assess for a possible discordance between HER2 immunohistochemistry and fluorescence in situ hybridization, we evaluated a series of invasive carcinomas with micropapillary features using both methodologies. As described by the WHO, invasive carcinomas with micropapillary features have small, hollow, or morula-like clusters of cells surrounded by clear stromal spaces. All cases had HER2 immunohistochemistry and fluorescence in situ hybridization performed, and for cases with equivocal fluorescence in situ hybridization results, an alternative Chromosome 17 probe (RAI1) was employed. All assays were scored according to the 2013 ASCO/CAP guidelines. Specifically for this study, immunohistochemistry was scored irrespective of the presence of micropapillary features. Overall, we identified HER2 amplification in 21 (47%) of the cases assayed, with the corresponding immunohistochemistry being 1+ (n=9), 2+ (n=11), and 3+ (n=1). The ASCO/CAP recommendation that this morphology may deviate from the typical staining pattern is highlighted, as we found that 43% of cases with micropapillary features and HER2 staining that would otherwise be scored as 1+ were HER2-amplified by fluorescence in situ hybridization. This study supports the ASCO/CAP recommendation that pathologists should consider reporting immunohistochemistry in this morphology as equivocal and perform reflex testing using in situ hybridization.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/genética , Carcinoma Papilar/genética , Receptor ErbB-2/análise , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Receptor ErbB-2/genéticaRESUMO
Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT are key to improving survival rates in EAC. In this study we performed global microRNA (miRNA) profiling of pre-treatment EAC biopsies and identified 67 miRNA significantly altered in patients who are resistant to CRT. One of these miRNA, miR-187, was significantly decreased in pre-treatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR-187 as a potential mechanism of treatment resistance in EAC. In vitro, miR-187 was demonstrated to play a functional role in modulating sensitivity to X-ray radiation and cisplatin in EAC and its dysregulation was demonstrated to be due to chromosomal alterations. In vitro, miR-187 altered expression of a diverse array of pathways, including the immune regulator complement component 3 (C3), serum levels of which we have previously demonstrated to predict patient response to CRT. In vivo, expression of C3 was significantly increased in tumors from patients having a poor response to CRT. This study highlights for the first time a role for miR-187 as a novel biomarker of response to CRT and a potential therapeutic target for enhancing the efficacy of CRT in EAC.
Assuntos
Adenocarcinoma/genética , Cisplatino/farmacologia , Complemento C3/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Linhagem Celular Tumoral , Quimiorradioterapia , Regulação para Baixo , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Neoplasias Hematológicas , Histiocitose , Leiomiossarcoma , Rabdomiossarcoma , Histiócitos , HumanosRESUMO
BACKGROUND: DNA copy number variation is associated with genetic disorders and cancer. Available methods to discern variation in copy number are typically costly, slow, require specialized equipment, and/or lack precision. METHODS: Multiplex PCR with different primer pairs and limiting deoxynucleotide triphosphates (dNTPs) (3-12 µmol/L) were used for relative quantification and copy number assessment. Small PCR products (50-121 bp) were designed with 1 melting domain, well-separated Tms, minimal internal sequence variation, and no common homologs. PCR products were displayed as melting curves on derivative plots and normalized to the reference peak. Different copy numbers of each target clustered together and were grouped by unbiased hierarchical clustering. RESULTS: Duplex PCR of a reference gene and a target gene was used to detect copy number variation in chromosomes X, Y, 13, 18, 21, epidermal growth factor receptor (EGFR), survival of motor neuron 1, telomeric (SMN1), and survival of motor neuron 2, centromeric (SMN2). Triplex PCR was used for X and Y and CFTR exons 2 and 3. Blinded studies of 50 potential trisomic samples (13, 18, 21, or normal) and 50 samples with potential sex chromosome abnormalities were concordant to karyotyping, except for 2 samples that were originally mosaics that displayed a single karyotype after growth. Large cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) (CFTR) deletions, EGFR amplifications, and SMN1 and SMN2 copy number assessments were also demonstrated. Under ideal conditions, copy number changes of 1.11-fold or lower could be discerned with CVs of about 1%. CONCLUSIONS: Relative quantification by restricting the dNTP concentration with melting curve display is a simple and precise way to assess targeted copy number variation.
Assuntos
Dosagem de Genes , Reação em Cadeia da Polimerase Multiplex/métodos , Fosfatos/químicaRESUMO
PURPOSE: Chromosome band level is the primary quality indicator for G-banded metaphase chromosome analysis. Although current professional guidelines address the minimum necessary band level for constitutional studies, there is no study documenting the comparative performance of different band-level estimation methods. METHODS: This study compared 5 band-level estimation methods (Stallard, Vancouver, Welborn, United Kingdom External Quality Assurance Scheme, and Ford) in a multicenter study in which 82 readers from 7 different clinical cytogenetics laboratories evaluated the same 10 karyotypes (5 from amniotic fluid and 5 from peripheral blood) by each method. RESULTS: There was a 94% correlation between the five band-level estimation methods. The Welborn method yielded significantly lower scores for amniotic fluid karyotypes (P < 0.01) but not for peripheral blood karyotypes (P = 0.75). The distribution of scores obtained from different readers suggests a high level of subjectivity in chromosome band-level assessment. The variation in band-level estimation did not correlate with reader experience or study center, except for readers from one laboratory, for which the distribution of scores was significantly lower (P < 0.01). CONCLUSION: The results from this study suggest that the consistent use of one method is more important than the actual method employed for monitoring karyotype quality.
Assuntos
Líquido Amniótico/citologia , Células Sanguíneas/citologia , Bandeamento Cromossômico/métodos , Cariótipo , Citogenética , Humanos , Reino UnidoRESUMO
The 22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion disorder. Most of the patients show the common 3 Mb deletion but proximal 1.5 Mb deletion and unusual deletions located outside the common deleted region, have been detected particularly with the advance of comparative cytogenomic microarray technologies. The individuals reported in the literature with unusual deletions involving the 22q11 region, showed milder facial phenotypes, decreased incidence of cardiac anomalies, and intellectual disability. We describe two sibs with an atypical 0.8 Mb microdeletion of chromosome 22q11 who both showed myelomeningocele and mild facial dysmorphisms. The association between neural tube defect and the clinical diagnosis of Di George anomaly/velocardiofacial syndrome is well documented in the literature, but not all cases had molecular studies to determine breakpoint regions. This report helps to narrow a potential critical region for neural tube defects associated with 22q11 deletions.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Defeitos do Tubo Neural/genética , Exoma , Fácies , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Cariotipagem , Imageamento por Ressonância Magnética , Masculino , Meningomielocele/diagnóstico , Meningomielocele/genética , Defeitos do Tubo Neural/diagnóstico , Fenótipo , IrmãosRESUMO
The accurate diagnosis of a juvenile granulosa cell tumor (JGCT) can be challenging, as these neoplasms often exhibit morphologic features that overlap other ovarian neoplasms. In addition, the immunohistochemical profile exhibited by JGCT is fairly nonspecific and typically includes reactivity for CD99. Recently, we noted that JGCTs can show immunohistochemical expression of Fli-1, a transcription factor expressed by Ewing sarcoma, a neoplasm that is occasionally in the differential diagnosis of JGCT. We evaluated a series of JGCTs to determine whether Fli-1 is commonly expressed by these tumors and whether they demonstrate chromosomal arrangements in EWSR1. Cases diagnosed as JGCT (n=11) were immunohistochemically evaluated for expression of Fli-1 and CD99. Fluorescence in situ hybridization was performed on all cases to search for chromosomal rearrangements in EWSR1. All 11 of our cases exhibited positive immunohistochemical staining for Fli-1 and CD99. None of the cases demonstrated rearrangement in EWSR1 by fluorescence in situ hybridization. In cases of JGCT that cannot be reliably distinguished from Ewing sarcoma based on morphology and immunohistochemistry alone, fluorescence in situ hybridization testing for EWSR1 rearrangements seems to be a useful diagnostic adjunct for their separation.
Assuntos
Biomarcadores Tumorais/análise , Tumor de Células da Granulosa/genética , Tumor de Células da Granulosa/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Antígeno 12E7 , Antígenos CD/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a Calmodulina/genética , Moléculas de Adesão Celular/biossíntese , Criança , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas dos Microfilamentos/biossíntese , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Receptores Citoplasmáticos e Nucleares/biossíntese , Transativadores , Translocação GenéticaRESUMO
Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.
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OBJECTIVE: Chromosome analysis is the traditional method for detecting genetic abnormalities in products of conception, but it is prone to a high failure rate because of the requirement for cell culture. Molecular genetic tests do not require cell culture, but are either more expensive (e.g. chromosomal microarray) or less sensitive than chromosome analysis (e.g. fluorescence in situ hybridization, multiplex ligation mediated amplification). The KaryoLite™ BACs-on-Beads™ (KL-BoBs™) assay is highly multiplexed with low resolution coverage and is designed to detect aneusomy for any chromosome. METHODS: We retrospectively tested 100 products of conception samples previously characterized by karyotype (n = 90), and/or microarray (n = 61) using KL-BoBs™. We included samples extracted from either cultured or direct specimens from placental villi or fetal somatic tissue, with a variety of chromosomal abnormalities typically identified in our clinical cytogenetics laboratory. RESULTS: KL-BoBs™ and microarray results were concordant for all cases of aneusomy. On the basis of a review of 3794 consecutive cases in our laboratory, aneusomy accounts for 74.3% of abnormalities detected. Polyploidy and structural abnormalities were not detected by KL-BoBs™. CONCLUSION: KL-BoBs™ is potentially very useful as a first line test for aneusomy detection because of its lower cost, rapid detection, and ability to generate a molecular karyotype for samples that fail to grow in culture.
Assuntos
Aborto Espontâneo/genética , Aberrações Cromossômicas/embriologia , Cariotipagem , Análise em Microsséries , Aneuploidia , Reações Falso-Negativas , Feminino , Feto/química , Humanos , Masculino , Microesferas , Placenta/química , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Dissection of specific Areas Of Interest (AOIs) of slide-mounted tumor samples is often used to enrich for cancer cells in order to generate better signal to noise ratios in subsequent biochemical characterization. Most clinical laboratories utilize manual dissection for practical reasons and to avoid the expense and difficulties of laser microdissection systems. Unfortunately, manual methods often lack resolution and process documentation. The goal of this project was to design a dissection system for slide-mounted tissue with better precision than manual methods that also provides digital image guidance and electronic process documentation. METHODS: An instrument that is essentially a micro tissue mill was developed. It employs a specialized disposable mill bit that simultaneously dispenses liquid, cuts tissue from the slide surface, and aspirates the liquid along with the displaced tissue fragments. A software package was also developed that is capable of transferring digitally annotated AOIs between images of serially cut tissue sections to guide dissection and generate an electronic record of the process. RESULTS: The performance of this "meso" dissection system was tested using post dissection visual examination for resolution and accuracy, fluorescence based DNA quantitation for recovery efficiency, and dissection of closely situated mouse-human tissue sections followed by PCR amplification for purity determination. The minimum resolution is a dissected circle smaller than 200 microns in diameter, edge dissection accuracy is tighter than 100 microns, recovery efficiency appears greater than 95%, and recovery purity is greater than 99% relative to a different tissue located 100 microns from the dissection boundary. The system can dissect from both paraffinized and deparaffinized FFPE tissue sections that are mounted on plain glass slides, and it is compatible with DNA, RNA, and protein isolation. CONCLUSIONS: The mesodissection system is an effective alternative to manual dissection methods and is applicable for biomarker analysis of anatomical pathology samples, where enrichment of AOIs from the tissue section is helpful, but pure cell populations are not required.
RESUMO
Autosomal trisomy is the most common genetic abnormality observed in pregnancy loss. We designed a panel of mini-short tandem repeats (mini-STRs) for aneuploidy detection in chromosomes 13, 16, 18 and 21 from fresh and formalin fixed, paraffin embedded (FFPE) samples from products of conception (POC). FFPE POCs with trisomy 13 (n = 6), trisomy 18 (n = 6), trisomy 21 (n = 12), 6 euploid for the chromosomes of interest and two trisomy 16 samples from fresh tissue were tested. Concordance between cytogenetics and genotyping was 100% for non-mosaic samples. Mini-STR genotyping is a viable method for targeted aneuploidy detection in low quality DNA samples.
Assuntos
Aneuploidia , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Técnicas de Genotipagem/métodos , Repetições de Microssatélites/genética , Aborto Espontâneo/genética , Feminino , Genótipo , Humanos , Masculino , Microdissecção , Inclusão em Parafina , Reação em Cadeia da Polimerase/métodos , GravidezRESUMO
BACKGROUND: The clear-cell variant of mucoepidermoid carcinoma (MEC) involving minor salivary glands is extremely rare in children. CASE REPORT: We report a case of clear-cell variant MEC in the minor salivary gland in a 10-year-old boy who presented with a mass of the right hard palate. Fine-needle aspiration showed features suggestive of clear-cell variant of MEC. Microscopically, the tumor cells showed predominant clear cells and scattered mucous cells. There was increased mitotic activity (6/mm2). No tumor necrosis or nuclear pleomorphism was identified. The tumor cells were positive for cytokeratin 7 (CK7), tumor protein p63, P40 (ΔNp63), CK5/6 and mucicarmine. Rearrangement of mastermind-like transcriptional coactivator 2 (MAML2) (11q21) gene was present in the tumor cells by fluorescence in situ hybridization, supporting the diagnosis of an intermediate-grade clear-cell variant of MEC. A right infrastructure maxillectomy for palate carcinoma with negative margins was performed. Grossly, the tumor was a 2.1 cm well-circumscribed, friable, pale tan mass with focal areas of cystic change. The final pathological diagnosis was clear-cell variant of MEC, intermediate grade, pT2. Post surgery, the patient recovered and was doing well, with no tumor recurrence or metastasis at the 6-month follow-up. CONCLUSION: To the best of our knowledge, this is the first documented case of clear-cell variant MEC in a child. Due to low to intermediate tumor grade, an overtly aggressive treatment should be avoided in a child.
Assuntos
Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Masculino , Criança , Humanos , Proteínas de Ligação a DNA/genética , Transativadores/genética , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/cirurgia , Hibridização in Situ Fluorescente , Recidiva Local de Neoplasia , Fatores de Transcrição/genética , Palato/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/químicaRESUMO
HER2 (ERBB2) overexpression and/or HER2 gene amplification has been well established in several tumors types and when present HER2 directed therapy may be to be efficacious. While recent findings suggests that HER2 overexpression and HER2 amplification are a relatively common in serous endometrial carcinoma, similar data regarding clear cell endometrial carcinoma (CCC) is difficult to interpret due to issues such as diagnostic criteria, sample type and HER2 interpretation criteria. Our goals were to study HER2 expression and HER2 copy number status in hysterectomy specimens from a large series of patients with pure CCC to determine the frequency of HER2 overexpression and HER2 amplification and evaluate applicability of current HER2 interpretation criteria. Pure CCC specimens derived from hysterectomy specimens from 26 patients were identified. All diagnoses were confirmed by two gynecologic pathologists. Immunohistochemistry for HER2 protein and fluorescence in situ hybridization (FISH) studies for HER2 were performed on whole-slide sections from all cases. Results were interpreted according to the 2018 ASO/CAP HER2 guidelines for breast cancer and International Society of Gynecologic Pathologists (ISGyP) HER2 guidelines for serous endometrial carcinoma. Additional testing was performed when indicated by the guidelines. HER2 expression by immunohistochemistry was 3+ in 4% and 0% of cases, and 2+ in 46% and 52% of cases, by 2018 ASCO/CAP and ISGyP criteria, respectively, while the remaining cases were negative. HER2 testing by FISH showed a positive result in 27% of tumors with 2018 ASCO/CAP guidelines, while 23% were positive with the ISGyP criteria. Our findings indicate that HER2 overexpression and HER2 amplification occur in a subset of CCC. Therefore, additional study into the potential benefit of HER2 targeted therapy in patients with CCC is warranted.