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AIMS: The formal pathogenesis of salivary carcinosarcoma (SCS) remained unclear, both with respect to the hypothetical development from either preexisting pleomorphic adenoma (PA) or de novo and the clonal relationship between highly heterogeneous carcinomatous and sarcomatous components. METHODS AND RESULTS: We performed clinicopathological and molecular (targeted RNA sequencing) analyses on a large series of 16 cases and combined this with a comprehensive literature search (111 cases). Extensive sampling (average 11.6 blocks), combined with immunohistochemistry and molecular studies (PA-specific translocations including PLAG1 or HMGA2 proven in 6/16 cases), enabled the morphogenetic identification of PA in 15/16 cases (93.8%), by far surpassing a reported rate of 49.6%. Furthermore, we demonstrated a multistep (intraductal/intracapsular/extracapsular) adenoma-carcinoma-sarcoma-progression, based on two alternative histogenetic pathways (intraductal, 56.3%, versus myoepithelial pathway, 37.5%). Thereby, early intracapsular stages are identical to conventional carcinoma ex PA, while later extracapsular stages are dominated by secondary, frequently heterologous sarcomatous transformation with often large tumour size (>60 mm). CONCLUSION: Our findings strongly indicate that SCS (almost) always develops from PA, with a complex multistep adenoma-carcinoma-sarcoma-sequence, based on two alternative histogenetic pathways. The findings from this novel approach strongly suggest that SCS pathogenetically is a rare (3-6%), unique, and aggressive variant of carcinoma ex PA with secondary sarcomatous overgrowth. In analogy to changes of terminology in other organs, the term "sarcomatoid carcinoma ex PA with/without heterologous elements" might be more appropriate.
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Adenocarcinoma , Adenoma Pleomórfico , Carcinosarcoma , Neoplasias de las Glándulas Salivales , Neoplasias de los Tejidos Blandos , Humanos , Adenoma Pleomórfico/patología , Neoplasias de las Glándulas Salivales/patología , Hibridación Fluorescente in Situ , Biomarcadores de Tumor/genéticaRESUMEN
A novel DEK::AFF2 fusion carcinoma was recently described in 29 patients who originally presented with non-viral-associated nonkeratinizing squamous cell carcinoma. The tumors occurred at multiple sites in the head and neck including in the sinonasal tract, middle ear, and temporal bone. This tumor behaves aggressively involving adjacent vital structures, frequently recurs, and is inclined to develop lymph node and distant metastasis. This review aims to summarize the demographic, clinical, pathologic, immunophenotypic features, and pattern of molecular alterations as well as to discuss the differential diagnosis of DEK::AFF2 fusion carcinoma.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Ganglios Linfáticos/patología , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas Cromosómicas no Histona , Proteínas Oncogénicas/genética , Proteínas NuclearesRESUMEN
AIMS: There is a widespread perception among clinicians and pathologists that the histomorphological assessment of minor salivary gland (MinSG) tumours is more difficult and hampered by more misdiagnoses than that of major salivary gland tumours. This is based on a vague, subjective clinical impression, lacking scientific proof. The aim of the present study was to identify and statistically verify potential reasons that could explain this difference. METHODS AND RESULTS: We identified 14 putative clinical, pathological and combined clinicopathological reasons that, altogether, could explain the phenomenon of the perceived greater diagnostic difficulty associated with MinSG tumours. We performed a comprehensive literature search and a statistical comparison of data from a large personal consultation series (biased for difficult cases) with cumulated data from straightforward, unselected (non-consultation) series from the literature. By performing this comparison, we identified, with statistical significance, a comprehensive series of reasons, as well as of consequences, of the greater difficulty in diagnosing MinSG tumours. CONCLUSIONS: Among the 14 criteria, high frequencies of initial incisional biopsies and of a low-grade category in malignant tumours emerged as the two most important reasons for enhanced diagnostic difficulty. Very rare entities, unusual locations, shortcomings in clinicopathological communication, and pecularities of the special anatomical location of the hard palate, such as tumour necrosis, mucosal ulceration, pseudoinvasion, and the peculiar phenomenon of 'tumoral-mucosal fusion', contribute to further diagnostic difficulties. The awareness of these shortcomings and pitfalls enables us to provide a series of recommendations for clinicians and pathologists that might aid in assessment and reduce the rate of misdiagnosis of MinSG tumours.
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Neoplasias de las Glándulas Salivales , Adenoma Pleomórfico/diagnóstico , Adenoma Pleomórfico/patología , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/patología , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Clasificación del Tumor , Patología Molecular , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patologíaRESUMEN
Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma AIMS: The majority of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OpSCC) have favourable survival outcomes, but a significant minority of individuals will die of their disease. There are currently no definitive criteria with which to identify HPV-associated OpSCC patients with poor outcomes. Recent reports suggest that quantitative evaluation of T-cell subpopulations in OpSCC may be of prognostic value, but the methods used have limited utility in a clinical diagnostic setting. We therefore sought to determine the clinical prognostic utility of tumour-infiltrating lymphocyte (TIL) evaluation in patients with HPV-associated OpSCC within the context of a diagnostic histopathology setting. METHODS AND RESULTS: Representative diagnostic haematoxylin and eosin (H&E)-stained slides from 232 consecutive HPV-associated OpSCC patients were classified as containing a high (TILHi ; diffuse, lymphocytes in >80% of tumour and stroma), moderate (TILMod ; patchy, present in 20-80% of tumour and stroma) or low (TILLo ; sparse or absent, present in <20% of tumour and stroma) TILs. Interobserver reliability was assessed, and TIL category was then correlated with overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses showed statistically significant differences in OS and DFS estimates when TILHi and TILMod patients were compared with TILLo patients (P < 0.0001 for TILHi versus TILLo ; P < 0.0001 for TILMod versus TILLo ). Statistical significance was retained when TILHi and TILMod patients were grouped into a single category (TILHi ) and compared with TILLo patients (P < 0.0001). CONCLUSION: We demonstrate the prognostic utility of TILs in patients with HPV-associated OpSCC in clinical practice. A binary system classifying HPV-associated OpSCC into TILHi and TILLo on the basis of routine H&E staining stratifies patients into those with potentially favourable and unfavourable survival outcomes, respectively.
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Carcinoma de Células Escamosas/patología , Linfocitos Infiltrantes de Tumor/patología , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/etiología , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/etiología , Pronóstico , Estudios Retrospectivos , Subgrupos de Linfocitos T/patologíaRESUMEN
The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b(+) Ly6C(high) inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa(-/-) mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b(+) Ly6C(high) inflammatory monocytes in C1qa(-/-) mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model.
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Complemento C1q/deficiencia , Complemento C1q/inmunología , Lupus Eritematoso Sistémico/inmunología , Macrófagos Peritoneales/inmunología , Terpenos/administración & dosificación , Receptor Toll-Like 7/inmunología , Animales , Artritis/inmunología , Autoanticuerpos/biosíntesis , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Inductores de Interferón/farmacología , Interferón-alfa/metabolismo , Lupus Eritematoso Sistémico/fisiopatología , Activación de Macrófagos , Macrófagos Peritoneales/efectos de los fármacos , Ratones Endogámicos BALB C , Monocitos/inmunología , Poli I-C/farmacologíaRESUMEN
Laryngeal carcinogenesis is a multistep process, characterized by an accumulation of genetic changes associated with architectural and cytologic alterations, ranging from squamous hyperplasia to carcinoma in situ and encompassed by the terminology of squamous intraepithelial lesions (SILs). The etiology, classification, genetic changes, and malignant progression of these lesions are reviewed. Tobacco remains the principal etiological factor with gastroesophageal reflux disease recently considered as a possible factor. In contrast, there is little evidence that microbiological agents, especially human papillomavirus infection, are frequently involved in laryngeal carcinogenesis and probably <10% of SILs are driven by biologically active human papillomavirus infection. Light microscopy, despite a degree of subjectivity, remains the mainstay of accurate diagnosis, prognosis, and guidance for a patient's treatment. The currently used classifications, the dysplasia system, squamous intraepithelial neoplasia, and the Ljubljana classification, reflect different standpoints on this important topic. The modified Ljubljana classification, with good interobserver agreement, could be considered as a proposal for a unified classification of laryngeal SILs. This review also briefly discusses recently discovered genetic changes, such as CDKN2A and CTNNB1 genes, and chromosome instability of chromosomes 1 and 7; however, none of these can at present improve histologic diagnosis. Malignant progression of precursor lesions varies from 2% to 74%, according to different studies. Cold-steel microinstruments, CO2 laser, and radiotherapy are used to treat the different grades of precursor lesions. There is as yet no worldwide agreement on the treatment of high-grade lesions and carcinoma in situ.
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Neoplasias Laríngeas/etiología , Lesiones Precancerosas/etiología , Humanos , Neoplasias Laríngeas/clasificación , Neoplasias Laríngeas/terapia , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/terapiaRESUMEN
Relapsing-remitting sixth nerve palsy is usually due to ophthalmoplegic migraine (recurrent cranial nerve palsy) in younger patients and microvascular disease in older patients. There have been isolated reports, however, of it occurring in the presence of a skull base tumour. We report a 20-year-old woman with Ollier's disease who presented with a relapsing-remitting sixth nerve palsy. Neuro-imaging revealed a skull base enchondroma.
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AIMS: To verify the applicability, reproducibility and predictive value of a proposed unified classification (amended Ljubljana classification) for laryngeal squamous intraepithelial lesions (SILs). METHODS AND RESULTS: Six internationally recognized experts and three pathologists from Ljubljana contributed to this study by evaluating a set of laryngeal SILs using the new system: low-grade SIL, high-grade SIL, and carcinoma in situ (CIS). The overall agreement among reviewers was good. Overall unweighted and weighted κ-values and 95% confidence intervals were 0.75 (0.65-0.84) and 0.80 (0.71-0.87), respectively. The results were stratified between the international reviewers and the Ljubljana pathologists. The former had good overall agreement, and the latter had very good agreement. Kaplan-Meier survival curves showed a significant difference (P < 0.0001) between patients with low-grade and high-grade SILs; 19 of 1204 patients with low-grade SILs and 30 of 240 patients with high-grade SILs progressed to malignancy in 2-15 years and in 2-26 years, respectively. CONCLUSIONS: The proposed modification to the Ljubljana classification provides clear morphological criteria for defining the prognostic groups. The criteria facilitate better interobserver agreement than previous systems, and the retrospective follow-up study demonstrates a highly significant difference in the risk of malignant progression between low-grade and high-grade SILs.
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Células Epiteliales/patología , Mucosa Laríngea/patología , Neoplasias Laríngeas/patología , Clasificación del Tumor/métodos , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , Progresión de la Enfermedad , Humanos , EsloveniaRESUMEN
Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.
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Inhibidores de la Ciclooxigenasa 2 , Erupciones por Medicamentos , Etoricoxib , Piridinas , Sulfonas , Humanos , Etoricoxib/efectos adversos , Erupciones por Medicamentos/etiología , Piridinas/efectos adversos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Sulfonas/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Mucosa Bucal/efectos de los fármacos , Hipersensibilidad Tardía/inducido químicamenteRESUMEN
BACKGROUND: Hypoxia may contribute to the pathogenesis of various diseases of the vascular wall. Hypoxia-inducible factors (HIFs) are nuclear transcriptional factors that regulate the transcription of genes that mediate cellular and tissue homeostatic responses to altered oxygenation. This article reviews the published literature on and discusses the role of the HIF pathway in diseases involving the vascular wall, including atherosclerosis, arterial aneurysms, pulmonary hypertension, vascular graft failure, chronic venous diseases, and vascular malformation. METHODS: PubMed was searched with the terms "hypoxia-inducible factor" or "HIF" and "atherosclerosis," "carotid stenosis," "aneurysm," "pulmonary artery hypertension," "varicose veins," "venous thrombosis," "graft thrombosis," and "vascular malformation." RESULTS: In atherosclerotic plaque, HIF-1α was localized in macrophages and smooth muscle cells bordering the necrotic core. Increased HIF-1α may contribute to atherosclerosis through alteration of smooth muscle cell proliferation and migration, angiogenesis, and lipid metabolism. The expression of HIF-1α is significantly elevated in aortic aneurysms compared with nonaneurysmal arteries. In pulmonary hypertension, HIF-1α contributes to the increase of intracellular K(+) and Ca(2+) leading to vasoconstriction of pulmonary smooth muscle cells. Alteration of the HIF pathway may contribute to vascular graft failure through the formation of intimal hyperplasia. In chronic venous disease, HIF pathway dysregulation contributes to formation of varicose veins and venous thromboembolism. However, whether the activation of the HIF pathway is protective or destructive to the venous wall is unclear. Increased activation of the HIF pathway causes aberrant expression of angiogenic factors contributing to the formation and maintenance of vascular malformations. CONCLUSIONS: Pathologic vascular wall remodelling of many common diseases of the blood vessels has been found to be associated with altered activity of the HIF pathway. Therefore, understanding the role of the HIF pathway in diseases of the vascular wall is important to identify novel therapeutic strategies in the management of these pathologies.
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Vasos Sanguíneos/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Enfermedades Vasculares/metabolismo , Animales , Vasos Sanguíneos/patología , Humanos , Oxígeno/metabolismo , Pronóstico , Transducción de Señal , Enfermedades Vasculares/patología , Enfermedades Vasculares/terapiaRESUMEN
Cellular niches in adult tissue can harbour dysregulated microenvironments that become the driving force behind disease progression. The major environmental change when metastatic cells arrive in the bone is the destruction of mineralized type I collagen matrix. Once metastatic niches establish in bone, the invading tumour cells initiate a vicious cycle of osteolytic lesion formation via the dysregulation of paracrine signals and uncoupling of normal bone resorption and production. Here we report that the collagen receptor Endo180 (CD280, MRC2, uPARAP) participates in collagen deposition by primary human osteoblasts during de novo osteoid formation. This newly recognized function of Endo180 was suppressed in osteoblasts following heterotypic direct cell-cell contact in co-culture with prostate tumour cells. Reciprocal Endo180 up-regulation in osteolytic prostate tumour cells (PC3 and DU145) followed their direct contact with osteoblasts and promoted de novo collagen internalization, which is a previously characterized function of the constitutively recycling Endo180 receptor. The osteoblastic suppression and tumour cell-associated enhancement of Endo180 expression were equally sustained in these direct co-cultures. These findings are the first to demonstrate that increased tumour cell participation in collagen degradation and decreased collagen formation by osteoblasts in the osteolytic microenvironment are linked to the divergent regulation of a collagen-binding receptor. Immunohistochemical analysis of core biopsies from bone metastasis revealed higher levels of Endo180 expression in tumour cell foci than cells in the surrounding stroma. Additional experiments in prostate cell-osteoblast co-cultures indicate that divergent regulation of Endo180 is the result of dysregulated TGFß1 signalling. The findings of this study provide a rationale for targeting collagen remodelling by Endo180 in bone metastases and other collagen matrix pathologies.
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Neoplasias Óseas/metabolismo , Colágeno Tipo I/metabolismo , Lectinas de Unión a Manosa/metabolismo , Glicoproteínas de Membrana/metabolismo , Osteoblastos/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Mitogénicos/metabolismo , Células del Estroma/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Comunicación Autocrina , Biopsia , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Línea Celular Tumoral , Técnicas de Cocultivo , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Masculino , Lectinas de Unión a Manosa/genética , Glicoproteínas de Membrana/genética , Osteoblastos/efectos de los fármacos , Osteoblastos/patología , Comunicación Paracrina , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Superficie Celular/genética , Receptores Mitogénicos/genética , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transducción de Señal , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Transfección , Microambiente TumoralRESUMEN
An adult male presented to the ENT clinic with a 1-year history of unilateral nasal blockage. He had presented to another institution 5 years previously with the same issue, undergoing resection of what was reported to be a benign inflammatory polyp with osseous metaplasia. Detailed examination revealed a large mass filling the left nasal cavity. Excisional biopsy and secondary specialist review of pathology revealed nasal chondromesenchymal hamartoma (NCMH) with associated DICER1 mutations. NCMH is a rare, benign tumour of the sinonasal tract, presenting more often in the early childhood, with symptoms related to the site and extent of the tumour. As highlighted in this case, complete excision is mandatory for definitive diagnosis and treatment of NCMH, and an awareness of the association with DICER1 mutation, which can predispose individuals to a range of neoplasia, is key to providing appropriate genetic counselling.
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Hamartoma , Obstrucción Nasal , Senos Paranasales , Humanos , Masculino , Preescolar , Adulto , Hamartoma/diagnóstico , Hamartoma/genética , Hamartoma/cirugía , Obstrucción Nasal/patología , Cavidad Nasal/patología , Senos Paranasales/patología , Mutación , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genéticaRESUMEN
OBJECTIVE: To review the clinical presentation, diagnosis, pathology and management strategies in a modern cohort of patients with thyroglossal duct cyst carcinoma. STUDY DESIGN: Retrospective case series following PROCESS Guidelines. SETTING: Comprehensive cancer centre. METHODS: Data recorded included: gender, age at diagnosis, clinical presentation, thyroid function, diagnostic investigations, cytological results, final histology, staging and follow up status. The risk of malignancy in cytological analysis was stratified according to the Royal College of Pathologists classification in United Kingdom. RESULTS: Twelve patients were included. The majority of patients (66.7%) presented with an isolated thyroglossal duct cyst. Only 4 patients had preoperative cytological suspicion of carcinoma (sensitivity: 33.3%). At the time of presentation all patients were euthyroid. Following diagnosis of malignancy, a total thyroidectomy was performed in all patients, with the exception of 2, who had a thyroglossal duct cyst carcinoma of less than 10mm. Among the 10 patients who underwent total thyroidectomy, 7 (70%) patients had proven carcinoma in the thyroid gland, 3 with deposits of less than 10mm. The average size of the thyroid cancer deposits was 7.2mm (1-20mm). With a mean follow-up of is 44 months (5-120), all patients were alive and free of recurrence at the end of the study period. CONCLUSION: Thyroglossal duct cyst carcinoma is a rare condition and its management should be discussed in a multidisciplinary meeting. As with differentiated thyroid cancer originating in the thyroid gland, it bears extraordinary survival rates. Accordingly, the management of these cancers has shifted towards a more conservative approach although its peculiarities must be taken into account: ease of extracystic invasion and possible different lymph node invasion.
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Carcinoma Papilar , Carcinoma , Quiste Tirogloso , Neoplasias de la Tiroides , Humanos , Quiste Tirogloso/cirugía , Quiste Tirogloso/diagnóstico , Quiste Tirogloso/patología , Estudios Retrospectivos , Carcinoma Papilar/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
AIMS: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. CONCLUSION: Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.
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Carcinoma in Situ/clasificación , Carcinoma Ductal/clasificación , Carcinoma/clasificación , Neoplasias de las Glándulas Salivales/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma/genética , Carcinoma/patología , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma Ductal/genética , Carcinoma Ductal/patología , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Receptores Androgénicos/análisis , Receptores Androgénicos/biosíntesis , Receptores Androgénicos/genética , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Análisis de Matrices Tisulares , TranscriptomaRESUMEN
In the recently published 5th Edition of the World Health Organisation Classification of Head and Neck Tumours, there are relatively few changes to report in terms of nomenclature in lesions of ear and temporal bone and fewer developments in molecular pathogenesis in comparison to other sites, particularly in sinonasal tract. Ear and temporal bone tumours are rare and biopsy material is limited. As a result, resources in the literature are scarce with few large series, no controlled clinical trials and the approaches to staging and management are not standardised. New entities are difficult to characterise. The number of entries has, however, increased for tumours of the ear and temporal bone (thirteen) compared to the 4th Edition (eleven). Some lesions previously included in the 4th Edition considered to have no site-specific features have been excluded to be discussed elsewhere and other benign lesions that are specific to this site have been included. The tumours and tumour-like entities of ear and temporal bone are discussed here mindful that the chapter in the 5th edition better correlates disease processes with clinical information and imaging and as far as possible standardises nomenclature.
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Neoplasias Óseas , Neoplasias del Oído , Neoplasias de Cabeza y Cuello , Neoplasias Óseas/patología , Neoplasias del Oído/patología , Humanos , Hueso Temporal/patología , Organización Mundial de la SaludRESUMEN
Metal artifact reduction sequence magnetic resonance imaging findings are reported in a prospective series of 31 patients with unexplained painful metal-on-metal (MOM) hips. The abnormalities identified were fluid collection (20 patients), solid mass (2 patients), moderate to severe muscle atrophy (23 patients), and muscle edema (8 patients). In conclusion, soft tissue lesions and muscle atrophy appear to be prevalent in unexplained painful MOM hips. Metal artifact reduction sequence magnetic resonance imaging may be useful to diagnose and monitor at-risk hips but requires validation in well-functioning MOM hips before it can guide clinical decision making.
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Artroplastia de Reemplazo de Cadera/instrumentación , Edema/patología , Prótesis de Cadera/efectos adversos , Metales , Atrofia Muscular/patología , Enfermedades Musculares/patología , Traumatismos de los Tejidos Blandos/patología , Adulto , Anciano , Edema/epidemiología , Edema/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Atrofia Muscular/epidemiología , Atrofia Muscular/etiología , Enfermedades Musculares/epidemiología , Enfermedades Musculares/etiología , Prevalencia , Estudios Prospectivos , Diseño de Prótesis , Falla de Prótesis , Estudios Retrospectivos , Traumatismos de los Tejidos Blandos/epidemiología , Traumatismos de los Tejidos Blandos/etiologíaRESUMEN
A 32-year-old man was found to have a nasal mass on DOTATATE positron emission tomography (PET) scan to investigate the cause of his syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient presented 6 years earlier with malignant hypertension followed by a second emergency admission for hyponatraemia. Multiple scans and blood tests over 6 years yielded no cause for his SIADH. Nasendoscopy was unremarkable. A PET scan prompted endoscopic sinus surgery which resulted in the resection of a mass in the anterior hiatus semilunaris. The histological findings were fitting with a diagnosis of a neurocytic-type tumour favouring an olfactory neurocytoma. Following resection, the patient remains well and is cured of his SIADH. An olfactory neurocytoma although rare should be considered as a benign differential for a mass in the nasal space. This case demonstrates how an olfactory neurocytoma can present as a cause of SIADH.
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Neoplasias Encefálicas/diagnóstico , Síndrome de Secreción Inadecuada de ADH/etiología , Neurocitoma/diagnóstico , Bulbo Olfatorio , Adulto , Neoplasias Encefálicas/complicaciones , Enfermedad Crónica , Humanos , Masculino , Neurocitoma/complicaciones , Bulbo Olfatorio/diagnóstico por imagen , Bulbo Olfatorio/patologíaRESUMEN
We report a novel case of multiple paragangliomas in a patient who was identified with pathogenic variants in both NF1 and SDHD genes. The proband is a man with known familial NF1 disease, diagnosed clinically in childhood. Multiple head and neck paragangliomas (HNPGL) were found during investigations for acute left sided neurological symptoms, in the region of his known plexiform neurofibroma. He was referred for genetic counselling. He underwent surgery to remove a left carotid body tumor (CBT). A pheochromocytoma and paraganglioma gene panel was tested. Blood and HNPGL tumor DNA were analyzed by whole exome sequencing. In addition to the NF1 truncating variant c.5107delA, p.(Ser1703AlafsTer7), the SDHD truncating pathogenic variant c.3G > A, p.(Met1?) was found. Tumor sequencing showed no LOH of SDHD or NF1, but monoallelic loss of 11p15 and 11q12.2-q12.3 was observed. Co-occurrence of pathogenic variants in multiple cancer susceptibility genes is rare but possible, identified by the increased use of panel testing. This is the first description of a patient presenting with NF1 and SDHD dual pathology, with HNPGL development due to SDHD. This case illustrates the central role of genetic sequencing in PPGLs and the strong genotype-phenotype correlations of different genes.
Asunto(s)
Mutación de Línea Germinal/genética , Neoplasias de Cabeza y Cuello/genética , Neurofibromina 1/genética , Paraganglioma/genética , Succinato Deshidrogenasa/genética , Adulto , Secuencia de Bases , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Masculino , Paraganglioma/diagnóstico por imagen , Paraganglioma/patología , LinajeRESUMEN
BACKGROUND: Sentinel lymph node (SLN) biopsy is an accurate staging modality in early oral squamous cell carcinoma (OSCC), but its accuracy relies on labor-intensive histopathology protocols. We sought to determine whether serial step sections with immunohistochemistry (SSSIHC) at narrow intervals of the entire SLN are required to accurately exclude metastasis. METHODS: Consecutive SLN biopsies over a 13-year period were retrospectively evaluated. If the index section was negative for carcinoma, the entire SLN was subjected to SSSIHC at 150 µm intervals. The first section level and total number of section levels to contain carcinoma were recorded. RESULTS: One hundred and eighteen SLN+ from 90 patients were included. SSSIHC upstaged the nodal status in 19.5% of patients. Metastasis was identified in 16.7% and 10.2% beyond section levels 4 and 6, respectively. Among SLNs requiring SSSIHC, 47.5% contained carcinoma in a single section level. CONCLUSION: SSSIHC of the entire SLN at 150 µm intervals are required to identify occult metastasis in OSCC.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/patología , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Metástasis Linfática , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. This study aims to characterize a larger cohort of carcinomas with DEK-AFF2 fusions to assess whether they truly constitute a distinctive entity. Among 27 sinonasal and skull base nonkeratinizing squamous cell carcinoma that were negative for human papillomavirus and Epstein-Barr virus, RNA sequencing identified DEK-AFF2 fusions in 13 cases (48%). Nine were centered in the nasal cavity, 2 in the middle ear/temporal bone, 1 in the nasopharynx, and 1 in the orbit. These tumors displayed recurrent histologic features including (1) complex endophytic and exophytic, frequently papilloma-like growth, (2) transitional epithelium with eosinophilic to amphophilic cytoplasm, (3) absent or minimal keratinization with occasional compact keratin pearls, (4) monotonous nuclei, and (5) prominent tumor-infiltrating neutrophils or stromal lymphocytes. This appearance not only overlaps with high-grade basaloid sinonasal carcinomas but also with benign papillomas and tumors reported as low-grade papillary Schneiderian carcinoma. However, DEK-AFF2 carcinomas showed frequent local recurrence, cervical lymph node metastases, and distant metastasis with 2 deaths from disease, confirming they are aggressive malignancies despite relatively bland histology. Overall, the distinctive molecular, histologic, and clinical features of DEK-AFF2 carcinomas suggest they represent a unique entity in the sinonasal region. This tumor merits increased pathologic recognition to better understand its prognostic and therapeutic implications.