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1.
Sci Rep ; 14(1): 8832, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632256

RESUMO

Warthin tumor (WT) is a benign tumor usually affecting the parotid gland. The main diagnostic tool remains ultrasound combined with fine-needle aspiration cytology (FNAC). This study aims to examine how reliably FNAC indicates WT for clinical decision making regarding surgical versus conservative management. We included all patients who underwent FNAC from a parotid gland lesion between 2016 and 2018 at our institution, and whose FNAC revealed WT suspicion. The FNACs were divided into three groups based on the cytology report: certain, likely, and possible WT. The patients were divided into two groups based on having had either surgery or follow-up. We sent a questionnaire to patients who had not undergone surgery in order to obtain follow-up for a minimum of four years. Altogether, 135 FNAC samples, from 133 tumors and 125 patients, showed signs of WT. Of the 125 patients, 44 (35%) underwent surgery, and 81 (65%) were managed conservatively. Preoperative misdiagnosis in FNAC occurred in three (7%) surgically treated tumors. Their FNACs were reported as possible WTs, but histopathology revealed another benign lesion. In the conservatively treated group, two patients underwent surgery later during the follow-up. Cytological statements of WT were seldom false, and none were malignant. The majority of the patients were only followed-up and rarely required further treatment. A certain or likely diagnosis of WT in the FNAC report by an experienced head and neck pathologist is highly reliable in selecting patients for conservative surveillance.


Assuntos
Adenolinfoma , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/patologia , Adenolinfoma/patologia , Estudos Retrospectivos , Glândula Parótida/patologia , Tomada de Decisão Clínica , Sensibilidade e Especificidade
2.
APMIS ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623593

RESUMO

Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total N = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000-2016. For HPV determination, HPV mRNA in situ hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.

3.
Head Neck Pathol ; 17(3): 647-657, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37335526

RESUMO

BACKGROUND: Liprin-α1 is a scaffold protein involved in cell adhesion, motility, and invasion in malignancies. Liprin-α1 inhibits the expression of metastatic suppressor CD82 in cancers such as oral carcinoma, and the expression of these proteins has been known to correlate negatively. The role of these proteins has not been previously studied in human papillomavirus (HPV)-related head and neck cancers. Our aim was to assess the clinical and prognostic role of liprin-α1 and CD82 in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) in comparison to HPV-negative OPSCC. METHODS: The data included 139 OPSCC patients treated at the Helsinki University Hospital (HUS) during 2012-2016. Immunohistochemistry was utilized in HPV determination and in biomarker assays. Overall survival (OS) was used in the survival analysis. RESULTS: Stronger expression of liprin-α1 in tumor-infiltrating lymphocytes (TILs) was linked to lower cancer stage (p < 0.001) and HPV positivity (p < 0.001). Additionally, we found an association between elevated expression of liprin-α1 and weak expression of CD82 in tumor cells (p = 0.029). In survival analysis, we found significant correlation between favorable OS and stronger expression of liprin-α1 in TILs among the whole patient cohort (p < 0.001) and among HPV-positive patients (p = 0.042). CONCLUSIONS: Increased liprin-α1 expression in the TILs is associated with favorable prognosis in OPSCC, especially among HPV-positive patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Orofaríngeas/patologia , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Papillomaviridae
4.
Transl Oncol ; 33: 101677, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37099957

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common cancer with a high heterogeneity and few approved treatments. OSCC is one of the least explored areas for precision oncology. In this study, we aimed to test the reliability of our three established rapid cancer systemic treatment-testing assays: human tumour-derived matrix (Myogel)-coated well-plates, zebrafish xenografts, and 3D microfluidic chips. METHODS: Chemo-, radio- and targeted-therapy testing in Myogel-coated wells and zebrafish xenografts was conducted nine times using five samples; two primary and three metastatic lymph node samples from three OSCC patients. Peripheral blood mononuclear cells (PBMNCs) were isolated from the patients' blood. The response of the tumour cells to radio-, chemo-, and targeted therapy was tested using Myogel-coated wells and zebrafish larvae xenografts. The tumour cells' response to immunotherapy was tested using 3D microfluidic chips. The cells' sensitivity to the treatments was compared with the patients' clinical response. Primary and metastatic lymph node tissue-derived DNA samples from two patients underwent whole exome sequencing to compare the mutational profiles of the samples. RESULTS: Test results were in line with patients' responses in 7/9 (77%) zebrafish xenograft assays and 5/9 (55%) Myogel-coated wells assays. Immunotherapy testing was done using one metastatic patient sample which matched the patients' response. Differences in responses to treatments between primary and metastatic samples of the same patient were detected in 50% of the zebrafish larvae assays. CONCLUSIONS: Our results show the potential of using personalized cancer treatment testing assays - specifically zebrafish xenografts that revealed promising results - in OSCC patient samples.

5.
Int J Cancer ; 151(11): 1989-1996, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35716139

RESUMO

High risk human papillomavirus (hrHPV) based screening provides the possibility of vaginal self-sampling as a tool to increase screening attendance. In order to evaluate the impact and feasibility of opt-in self-sampling in the Finnish setting, we invited a randomized population of 5350 women not attending screening after age group invitation or after reminder, to attend HPV self-sampling-based screening in the autumn of 2018 in Helsinki. Out of those, 1282 (24.0%) expressed their interest and ordered the sampling package. Eventually 787 women (14.7% of the total invited population) took part in screening, 770 women by providing a vaginal sample within 2 months from invitation and 17 by providing a pap smear in the laboratory. Self-taken samples were collected in Aptima Multitest vials and tested using the Aptima HPV mRNA assay. A high proportion, 158/770 (20.5%) of the samples were positive in the Aptima HPV assay. One hundred and forty-one samples were further submitted to Aptima HPV Genotyping and extended genotyping by a Luminex based assay. Of those, 23 samples (16.3%) were HPV 16 positive and 7 (5.0%) were positive for HPV 18/45; extended genotyping revealed multiple high-risk and low-risk HPV genotypes. At follow-up seven cases of high-grade squamous intraepithelial lesion (HSIL) were diagnosed, which represents 4.4% of HPV positive women and 0.9% of screened women, whereas the rate was 0.5% in routine screening. Our findings suggest that self-sampling with HPV mRNA testing is a feasible approach to improve screening efficacy in a high-risk population among original nonattendees.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Alphapapillomavirus/genética , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Papillomaviridae/genética , RNA Mensageiro , Manejo de Espécimes , Esfregaço Vaginal
6.
Mod Pathol ; 35(10): 1423-1430, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35606412

RESUMO

Chronic sclerosing sialadenitis is commonly regarded as a manifestation of IgG4-related disease. We previously found that a high IgG4 expression or IgG4-related disease could accompany nonspecific sialadenitis, whereas chronic sclerosing sialadenitis was not directly associated with IgG4-related disease. Our previous findings lead us to hypothesize that these inflammatory conditions of the submandibular gland signify a continuous progression of disease rather than different disease entities. We, therefore, aimed to determine the presence of IgG4-positivity and genuine IgG4-related disease in a cohort of 165 submandibular gland specimens from patients who underwent surgery due to chronic nonspecific sialadenitis or sialolithiasis. To do so, we re-evaluated histopathological features and divided samples into three groups: (A) nonspecific sialadenitis without known sialolithiasis, (B) sialadenitis with sialolithiasis, and (C) sialolithiasis without sialadenitis. We performed immunohistochemical staining for IgG4, IgG, and CD31, and assessed the Boston consensus statement criteria for IgG4-related disease in IgG4-positive samples. We also reviewed patient records and supplemented follow-up data with a questionnaire among patients with IgG4-positive samples. IgG4-positive plasma cells (range 1-344) were found in 131 samples. Among these, 19 samples were classified as IgG4-positive (≥70 IgG4-positive plasma cells/high-power field). Two IgG4-positive samples were histologically highly suggestive of IgG4-related disease, but only one had a clinically confirmed diagnosis of IgG4-related disease. Our results indicate that patients with sialadenitis and sialolithiasis often present with IgG4-positive lymphoplasmacytic infiltrates, but exceedingly rarely present with genuine IgG4-related disease. In sialolithiasis without sialadenitis, IgG4-positive plasma cells are often absent or appear in small numbers. These results support our hypothesis of a continuum of disease, and indicate that progressive inflammation of the submandibular gland leads to the development of more specific pathological features over time.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Cálculos das Glândulas Salivares , Sialadenite , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/patologia , Plasmócitos/patologia , Cálculos das Glândulas Salivares/patologia , Sialadenite/patologia , Glândula Submandibular/patologia
7.
Acta Otolaryngol ; 142(2): 132-139, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35148225

RESUMO

BACKGROUND: Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. AIMS/OBJECTIVES: To review the management and outcome of ear canal and middle ear tumors at an academic referral center. MATERIALS AND METHODS: Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. RESULTS: Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. CONCLUSIONS AND SIGNIFICANCE: EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.


Assuntos
Meato Acústico Externo , Neoplasias da Orelha , Meato Acústico Externo/patologia , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/cirurgia , Orelha Média/patologia , Orelha Média/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
8.
Eur Arch Otorhinolaryngol ; 279(6): 3147-3155, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34773167

RESUMO

BACKGROUND: Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. METHODS: This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. RESULTS: The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. CONCLUSIONS: Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Biópsia , Humanos , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia
10.
J Craniofac Surg ; 33(3): 803-808, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34855632

RESUMO

ABSTRACT: Plexiform variants of neurofibromas and schwannomas are rare and typically arise in superficial soft tissues in the head and neck region. The treatment of these tumors is challenging and no generally accepted guidelines exist for their optimal management. The purpose of this study was to review the management and longterm prognosis of head and neck plexiform neurofibromas and schwannomas at 2 tertiary care academic hospitals in Finland over a 31-year period. The pathology files were searched for plexiform neurofibromas and schwannomas between the years 1990 and 2020. The case notes were reviewed for full management details. Two plexiform schwannomas and 6 plexiform neurofibromas were identified. Five of the 6 plexiform neurofibromas were managed operatively. All patients with a surgically managed plexiform neurofibroma underwent multiple operations. Sclerotherapy abolished 1 patient's cutaneous plexiform neurofibromas. The management of plexiform neurofibromas and plexiform schwannomas remains challenging. Sclerotherapy may offer a promising management option for cutaneous plexiform neurofibromas.


Assuntos
Neoplasias de Cabeça e Pescoço , Neurilemoma , Neurofibroma Plexiforme , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Neurilemoma/cirurgia , Neurofibroma Plexiforme/cirurgia , Prognóstico
11.
Laryngoscope Investig Otolaryngol ; 5(4): 694-702, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32864441

RESUMO

BACKGROUND: The nature of parotid tumors often remains unknown preoperatively and final histopathology may reveal unexpected malignancy. Still, the use of fine-needle aspiration cytology (FNAC) and imaging varies in the management of these tumors. METHODS: We evaluated the preoperative examinations and management of all 195 parotid gland tumors diagnosed within our catchment area of 1.6 million people during 2015. RESULTS: Altogether 171 (88%) tumors were classified as true salivary gland neoplasms. FNAC showed no false malignant findings, but it was false benign in 5 (2.6%) cases. Preoperative MRI was utilized in 48 patients (25%). Twenty (10%) malignancies included 16 salivary gland carcinomas. Pleomorphic adenomas accounted for 52% of all adenomas. For 24 (40%) Warthin tumors, surgery was omitted. CONCLUSION: The proportion of malignancies was lower than generally presented. Our proposed guidelines include ultrasound-guided FNAC with certain limitations. MRI is warranted in selected cases, but seems unnecessary routinely.

12.
Mod Pathol ; 33(4): 551-559, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680120

RESUMO

Chronic sclerosing sialadenitis may represent one of many manifestations of an immunoglobulin G4-related disease. However, existing studies typically consist of small patient cohorts rarely conducted in Western populations. The clinical behavior of chronic sclerosing sialadenitis, including follow-up data, warrants further study. Thus, we aimed to determine whether chronic sclerosing sialadenitis always presents as IgG4-related disease or associates with autoimmune diseases and to determine which additional examinations patients may require. Between 2000 and 2017, 51 patients undergoing submandibular gland resection within the Helsinki University Hospital area were diagnosed with chronic sclerosing sialadenitis. We re-evaluated all specimens and performed immunostaining for IgG4. IgG and CD31 stainings were performed for IgG4-positive specimens. IgG4-related disease diagnosis was defined by the Boston consensus statement criteria. We revised clinical data, distributing a follow-up questionnaire to patients to register symptoms of IgG4-related disease or autoimmune disease during follow-up. The chronic sclerosing sialadenitis criteria were fulfilled in 34 patients, whereby 17 were diagnosed as non-sclerosing chronic sialadenitis. In 19 cases, a sialolith associated with a salivary gland lesion. In total, 12 of 51 cases were recognized as IgG4-positive, while two met the criteria for IgG4-related disease. These two cases belonged to the non-sclerosing chronic sialadenitis group, and both involved other organs. The histopathological features between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis overlapped regarding the degree of fibrosis and inflammatory infiltrates. In the Finnish population, chronic sclerosing sialadenitis of the submandibular gland does not appear to present as IgG4-related disease. Non-sclerosing chronic sialadenitis can associate with IgG4-related disease. A histopathological distinction between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis is not always unequivocal and the presence of a sialolith does not exclude IgG4-positivity. Therefore, immunostaining for IgG4 should be performed when dense plasma cell infiltration is present in either non-sclerosing chronic sialadenitis or chronic sclerosing sialadenitis.


Assuntos
Autoimunidade , Doença Relacionada a Imunoglobulina G4/imunologia , Imunoglobulina G/análise , Sialadenite/imunologia , Doenças da Glândula Submandibular/imunologia , Glândula Submandibular/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Finlândia , Humanos , Doença Relacionada a Imunoglobulina G4/patologia , Doença Relacionada a Imunoglobulina G4/cirurgia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esclerose , Sialadenite/patologia , Sialadenite/cirurgia , Glândula Submandibular/patologia , Glândula Submandibular/cirurgia , Doenças da Glândula Submandibular/patologia , Doenças da Glândula Submandibular/cirurgia
13.
Cancer Immunol Immunother ; 68(8): 1263-1272, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240326

RESUMO

BACKGROUND: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. MATERIALS AND METHODS: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. CONCLUSION: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Metaloproteinase 8 da Matriz/sangue , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Análise de Sobrevida
14.
Hum Pathol ; 90: 97-105, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121191

RESUMO

Current human papillomavirus (HPV) detection methods in oropharyngeal squamous cell carcinoma (OPSCC) have varying sensitivity and specificity. We aimed to compare different HPV-detection methods against the test used in clinical practice, ie, p16 immunohistochemistry (IHC) and to evaluate whether another HPV-detection test additional to p16 IHC would be worthwhile in OPSCC specimens. The study cohort comprised 357 consecutive OPSCC patients during two time periods: 2000-2009 and 2012-2016. From tumor tissue slides, HPV mRNA via in situ hybridization (ISH), HPV DNA via ISH and HPV DNA via polymerase chain reaction (PCR) were detected. The results of these methods were compared with p16 IHC results. Additionally, clinicopathological factors were compared with the methods studied. The sensitivity of HPV mRNA ISH, HPV DNA ISH and HPV DNA PCR were 93.4%, 86.3%, and 83.5%, respectively. The corresponding specificity was 92.4%, 95.3%, and 89.1%, respectively. The negative predictive value for p16 IHC was highest (89.0%) when using mRNA ISH, and followed by DNA ISH (83.5%). ISH for high-risk HPV E6/E7 mRNA was found to be a highly specific and sensitive method for detecting HPV in OPSCC. As p16 protein may be overexpressed due to HPV-independent mechanisms, all p16 IHC-positive OPSCCs should be considered for retesting using mRNA ISH in order to verify transcriptionally active HPV. This is especially critical when considering de-escalated treatment approaches for patients with HPV-positive tumors and still maintaining favorable outcomes for this subgroup of patients.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , RNA Viral/genética , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Hibridização In Situ , Masculino , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/patologia , Sensibilidade e Especificidade
15.
Strahlenther Onkol ; 194(8): 759-770, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29774396

RESUMO

PURPOSE: To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients. METHODS: The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). RESULTS: pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III-IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I-II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses. CONCLUSION: pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.


Assuntos
Biomarcadores Tumorais/fisiologia , Papillomavirus Humano 16 , Neoplasias Orofaríngeas/radioterapia , Infecções por Papillomavirus/radioterapia , Radioterapia de Intensidade Modulada/métodos , Carga Tumoral/fisiologia , Carga Tumoral/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática/patologia , Metástase Linfática/fisiopatologia , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/fisiopatologia , Orofaringe/patologia , Orofaringe/efeitos da radiação , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/fisiopatologia , Prognóstico
16.
Acta Otolaryngol ; 138(5): 513-518, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29161981

RESUMO

OBJECTIVES: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. METHODS: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. RESULTS: Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV−/p16− patients but also rather common among HPV+/p16+ patients [corrected]. CONCLUSIONS: This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/metabolismo , Estudos Retrospectivos
17.
Head Neck ; 40(1): 154-162, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29083518

RESUMO

BACKGROUND: In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series. METHODS: We included all patients with resected submandibular gland cancer treated at the Helsinki University Hospital from 2000 to 2010 with a 5-year minimum follow-up. RESULTS: Twenty-five patients with cancer represented 30% of submandibular gland neoplasms, and most were adenoid cystic carcinomas (ACCs; 56%). At presentation, 3 patients showed clinical signs of probable malignancy. Of 22 neck dissection specimens, 5 patients (20%) had metastases with an occult metastasis rate of 4%. Cancer recurred in 11 patients (44%), of which 7 (28%) were only at a distant site. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 76%, and disease-free survival (DFS) was 68%. CONCLUSION: Most tumors were ACCs differing from the histological pattern of parotid gland cancers. Occult metastases were rare. The rarity of submandibular gland cancer, its variable histological pattern, and varying biological behavior warrant centralized management.


Assuntos
Carcinoma Adenoide Cístico/terapia , Carcinoma de Células Escamosas/terapia , Glândula Parótida/cirurgia , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/mortalidade , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/métodos , Estudos de Coortes , Intervalo Livre de Doença , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Finlândia , Hospitais Universitários , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Glândula Parótida/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Submandibular/diagnóstico por imagem , Neoplasias da Glândula Submandibular/mortalidade , Análise de Sobrevida , Resultado do Tratamento
18.
Oncol Rep ; 38(4): 2062-2068, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849066

RESUMO

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53ß, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53ß revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53ß as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Glote/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Proteínas Inibidoras de Apoptose/biossíntese , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/terapia , Telomerase/biossíntese , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Glote/efeitos dos fármacos , Glote/efeitos da radiação , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço , Survivina
19.
Head Neck ; 39(6): 1071-1077, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28370782

RESUMO

BACKGROUND: Roughly half of submandibular gland neoplasms are malignant. Because preoperative information on the nature of these tumors remains limited, both preoperative evaluation and assessment of the extent of primary surgery warrant guidelines that are more accurate. METHODS: We evaluated the preoperative examinations and management of all submandibular gland neoplasms treated surgically at the Helsinki University Hospital between 2000 and 2010. RESULTS: Of the 83 tumors, 58 (70%) were benign and 25 (30%) were malignant. Of the benign tumors, 54 (93%) were pleomorphic adenomas. The cytology in 8 patients (10%) was class IV or V, and in 12 patients was class III; the tumors in 9 of these 12 patients turned out to be malignant. Of all malignancies, 10 (40%) required additional more extensive surgery. CONCLUSION: Ultrasound-guided fine-needle aspiration cytology (FNAC) proved useful, with limitations, in preoperative examination. Surgeons should always obtain wide margins whenever possible, even when clinical means or cytology indicates no malignancy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1071-1077, 2017.


Assuntos
Biópsia Guiada por Imagem/métodos , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/cirurgia , Glândula Submandibular/cirurgia , Adenoma Pleomorfo/mortalidade , Adenoma Pleomorfo/patologia , Adenoma Pleomorfo/cirurgia , Adulto , Idoso , Biópsia por Agulha Fina/métodos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Finlândia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Planejamento de Assistência ao Paciente , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Ultrassonografia Doppler
20.
J Neurol Surg Rep ; 77(3): e144-e149, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28078198

RESUMO

Background Giant cell tumors (GCTs) are rare osseous tumors that rarely appear in the skull. Methods We review the clinical course of a 28-year-old previously healthy woman with a complicated GCT. Results The reviewed patient presented with a middle cranial fossa tumor acutely complicated by reactive mastoiditis. Left tympanomastoidectomy was performed for drainage of the mastoiditis and for biopsies of the tumor. Due to the challenging tumor location, the patient was treated with denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, for 7 months, which resulted in significant preoperative tumor shrinkage. Extensive temporal craniotomy and resection of the tumor followed utilizing a temporomandibular joint total endoprosthesis for reconstruction. A recurrence of the tumor was detected on computed tomography at 19 months after surgery and treated with transtemporal tumor resection, parotidectomy, and mandible re-reconstruction. Conclusion A multidisciplinary approach resulted in a good functional result and, finally, an eradication of the challengingly located middle cranial fossa tumor.

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