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Parkinson's disease is associated with an increased risk of melanoma (and vice versa). Several hypotheses underline this link, such as pathways affecting both melanin and neuromelanin. For the first time, the fluorescence of melanin and neuromelanin is selectively accessible using a new method of nonlinear spectroscopy, based on a stepwise two-photon excitation. Cutaneous pigmentation and postmortem neuromelanin of Parkinson patients were characterized by fluorescence spectra and compared with controls. Spectral differences could not be documented, implying that there is neither a Parkinson fingerprint in cutaneous melanin spectra nor a melanin-associated fingerprint indicating an increased melanoma risk. Our measurements suggest that Parkinson's disease occurs without a configuration change of neuromelanin. However, Parkinson patients displayed the same dermatofluorescence spectroscopic fingerprint of a local malignant transformation as controls. This is the first comparative retrospective fluorescence analysis of cutaneous melanin and postmortem neuromelanin based on nonlinear spectroscopy in patients with Parkinson's disease and controls, and this method is a very suitable diagnostic tool for melanoma screening and early detection in Parkinson patients. Our results suggest a non-pigmentary pathway as the main link between Parkinson's disease and melanoma, and they do not rule out the melanocortin-1-receptor gene as an additional bridge between both diseases.
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Melaninas/metabolismo , Melanoma/patologia , Doença de Parkinson/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Fatores de Risco , Pele/patologia , Pigmentação da Pele , Substância Negra/patologiaRESUMO
Parkinson's disease (PD) comprises a spectrum of disorders with differing subtypes, the vast majority of which share Lewy bodies (LB) as a characteristic pathological hallmark. The process(es) underlying LB generation and its causal trigger molecules are not yet fully understood. α-Synuclein (α-syn) is a major component of LB and SNCA gene missense mutations or duplications/triplications are causal for rare hereditary forms of PD. As typical sporadic PD is associated with LB pathology, a factor of major importance is the study of the α-syn protein and its pathology. α-Syn pathology is, however, also evident in multiple system atrophy (MSA) and Lewy body disease (LBD), making it non-specific for PD. In addition, there is an overlap of these α-synucleinopathies with other protein-misfolding diseases. It has been proven that α-syn, phosphorylated tau protein (pτ), amyloid beta (Aß) and other proteins show synergistic effects in the underlying pathogenic mechanisms. Multiple cell death mechanisms can induce pathological protein-cascades, but this can also be a reverse process. This holds true for the early phases of the disease process and especially for the progression of PD. In conclusion, while rare SNCA gene mutations are causal for a minority of familial PD patients, in sporadic PD (where common SNCA polymorphisms are the most consistent genetic risk factor across populations worldwide, accounting for 95% of PD patients) α-syn pathology is an important feature. Conversely, with regard to the etiopathogenesis of α-synucleinopathies PD, MSA and LBD, α-syn is rather a bystander contributing to multiple neurodegenerative processes, which overlap in their composition and individual strength. Therapeutic developments aiming to impact on α-syn pathology should take this fact into consideration.
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Doença de Parkinson/patologia , alfa-Sinucleína , Animais , HumanosRESUMO
BACKGROUND: Conventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX®, a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction. The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test. METHODS: The results of Ki67, uPA/PAI-1 and OncotypeDX® were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed. RESULTS: With a proliferation index Ki67 of < 14%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9%); p = 0.054, Student's t-test. When Ki67 was > 14% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14% with non-raised uPA/PAI-1 (p < 0.03, Student's t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values. CONCLUSION: A combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).
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Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Antígeno Ki-67/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
Objective Most tumors of the internal auditory canal and cerebellopontine angle (CPA) are vestibular schwannomas (VSs). Preoperative diagnosis is based on typical clinical symptoms and radiological findings. In rare cases, histopathology can, however, show different results. Design This is a retrospective chart and database review. Setting The study was conducted at a tertiary skull base referral center at a university hospital. Participants A total of 207 consecutive cases of VS surgery via the middle cranial fossa approach performed between December 2005 and January 2015 were reviewed. Main Outcome Measures The main outcome measures were definitive histologic findings in 198 specimens, analysis of preoperative magnetic resonance imaging (MRI) and computed tomography. Results Histopathology revealed three meningiomas and two cases of lipochoristomas. Clinical presentation was typical for VS in all five cases. In preoperative MRI, all tumors were suspected to be VSs. Retrospective analysis of the preoperative imaging did not lead to a modification of the diagnosis. Intraoperative findings showed increased adherence of the tumor to the adjacent tissue in two of the five cases. Conclusion CPA lesions other than VSs are unusual but have to be taken into account. In very small tumors, imaging still remains difficult.
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BACKGROUND: Inflammatory myofibroblastic tumors (IMFTs) of the larynx are rare. We report the clinical presentation, histomorphology, and new molecular findings of 2 cases. METHODS: Paraffin-embedded specimens were stained immunohistochemically (eg, vimentin, AE1/3, Alk-1, smooth muscle [sm-]actin, p53, Rb1, immunoglobulin G4 [IgG4]). Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and HHV8-polymerase chain reaction (PCR) were done. Comparative genomic hybridization (CGH) was performed. RESULTS: Case 1 was that of a 56-year-old man with an infiltrating plasma-cell-rich tumor (Alk-1-, sm-actin+). Plasma cells were strongly positive for IgG4. CGH was unsuspicious. Case 2 was that of a 34-year-old woman with an exophytic tumor (Alk-1+). CGH revealed losses on 13q14-22. The few plasma cells were negative for IgG4. The proliferation (Ki67) was low in both cases. CONCLUSION: Different types of IMFTs may exist and could indicate different therapeutic strategies. Alk-1-positive cases with only scattered inflammatory cells could represent the neoplastic variant, whereas cases rich in plasma cells could be associated with IgG4 sclerosing diseases.
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Granuloma de Células Plasmáticas/patologia , Doenças da Laringe/patologia , Receptores de Activinas Tipo II/metabolismo , Adulto , Antígeno CD56/metabolismo , Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Hibridização Genômica Comparativa , Feminino , Granuloma de Células Plasmáticas/metabolismo , Granuloma de Células Plasmáticas/cirurgia , Humanos , Imunoglobulina G/metabolismo , Antígeno Ki-67/metabolismo , Doenças da Laringe/metabolismo , Doenças da Laringe/cirurgia , Laringoscopia , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Proteínas S100/metabolismoRESUMO
BACKGROUND: The authors report on leiomyosarcoma after previously treated squamous cell carcinoma (SCC) at the glottis. METHODS: Primary tumor and relapses were investigated morphologically, immunohistochemically, and with molecular methods. RESULTS: The SCC was typical, but few cells showed a spindle-shaped pattern. The relapse tumor was a spindle-shaped and epitheloid tumor with the morphological and immunohistochemical appearance of leiomyosarcoma (sm-actin+, desmin+, caldesmon+, vimentin+, keratin-).The comparative genomic hybridization (CGH) revealed some gains and losses in the leiomyosarcoma. Because of altered material, the investigation failed in the primary. A fluorescence in situ hybridization (5p) focally detected 3 chromosmomal copies, corresponding to gains on 5p in CGH of leiomyosarcoma. CONCLUSION: Leiomyosarcoma after SCC is very uncommon. A connection between both seems likely in this case. Transdifferentiation, also seen in other tumors or carcinosarcomas, could be based on aberrant differentiation of a pluripotent stem cell.
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Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Leiomiossarcoma/patologia , Segunda Neoplasia Primária/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/cirurgia , MasculinoRESUMO
BACKGROUND: Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies. METHODS: Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1. Proliferation was investigated by staining with Ki67. The tumors were located at the major or minor salivary glands. Only the typical cribriform subtype was investigated. The initial tumor stage was pT1 or pT2. RESULTS: Expression of p-AKT was significantly (P = 0.036) associated with a higher relapse risk in multivariate analysis. Low expression of M2PK was non-significantly (P = 0.065) predictive for a higher risk. TKTL-1 and GLUT-1 were expressed in the majority of cases, albeit not associated with relapse risk. CONCLUSION: Adenoid cystic carcinomas positive for p-AKT show a higher relapse risk. However, other parameters of glucose metabolism investigated here or proliferation (Ki67) were not predictive in this entity. Our findings demonstrate a possible background for therapeutic approaches targeting the inhibition of PI3K/AKT pathway.
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Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status. Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value. Therefore, we investigated the role of these factors in ACC. Immunohistochemical analysis was performed on tissue microarrays of paraffin-embedded tissue samples from 167 ACCs, 15 adrenal adenomas and 4 normal adrenal glands. Expression was correlated with baseline parameters and clinical outcome. GLUT1 and -3 were expressed in 33 and 17% of ACC samples respectively, but in none of the benign tumours or normal adrenals glands. By contrast, TKTL1 and M2-PK were detectable in all benign tissues and the vast majority of ACCs. GLUT1 expression was strongly associated with prognosis in univariate and multivariate analysis (P<0.01), whereas GLUT3, TKTL1 and M2-PK did not correlate with clinical outcome. Patients with strong GLUT1 staining showed a considerably higher overall mortality (hazard ratio (HR) 6.34 (95% confidence interval 3.10-12.90) compared with patients with no GLUT1 staining. When analysing patients in their early stages and advanced disease separately, similar results were obtained. HR for survival was 5.31 (1.80-15.62) in patients with metastatic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2.16-16.94). In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC.
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Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Recent studies revealed a predictive value of lymphatic vessel invasion (L1) for the nodal metastasizing and poor prognosis in malignant tumors at different sites. The monoclonal antibody D2-40 (podoplanin) stains specifically endothelial cells of lymphatic vessels and improves the search for L1. However, the importance of this immunohistochemical staining was not investigated in squamous cell carcinomas (SCC) of larynx and hypopharynx. AIM: This study was performed to compare the diagnostic potential of conventional and immunohistochemical determination of L1 in SCC of larynx and hypopharynx with special respect to the predictive value for nodal metastasizing and prognosis. METHODS: 119 SCCs of the larynx (n = 70) respectively hypopharynx (n = 49) were investigated. The lymphatic vessel invasion was assessed by conventional method (HE stain) and immunohistochemical staining with an antibody against D2-40 (DAKO, Germany). Immunohistochemistry was performed in accordance with manufacturer's protocol. L1 was searched microscopically in a standardized magnification (x200) in serial sections of tumor samples (1 section per cm tumor diameter). RESULTS: The immunohistochemical investigation did not show significant advantages for the prediction of regional nodal metastases. Despite a low sensitivity (< 50%) in both methods, the specificity can reach 80%. The negative predictive value in both methods seems acceptable (up to 80%), whereas the positive predictive value is not higher than 64%. Cases with L1 detected either conventionally or immunohistochemically did not show a significant shorter survival than cases with L0. However, a non-significant shorter survival was found. Only in SCC of hypopharynx, a combination of both methods revealed patients with a significant worse prognosis. CONCLUSION: The status of lymphatic vessel invasion should be documented in standardized tumor reports. A benefit of an additional immunohistochemical investigation was not found, for the daily routine HE-stain seems sufficient.
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Anticorpos Monoclonais , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Laríngeas/diagnóstico , Linfangiogênese/imunologia , Doenças Linfáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Feminino , Alemanha , Humanos , Neoplasias Hipofaríngeas/imunologia , Neoplasias Hipofaríngeas/metabolismo , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/imunologia , Neoplasias Laríngeas/metabolismo , Doenças Linfáticas/imunologia , Doenças Linfáticas/metabolismo , Metástase Linfática , Vasos Linfáticos/imunologia , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Masculino , PrognósticoRESUMO
CONTEXT: Chronic low back pain (LBP) has been reported with a high incidence in elite rowers. It results in less effective training, long interruptions in training, and a drop in performance. OBJECTIVE: The authors hypothesized that exercise-induced LBP in rowers is caused by a chronic functional compartment syndrome (CFCS) of the multifidus muscle. DESIGN: Controlled clinical trial. SETTING: The rowers were tested in their training camp. The control group was tested at a university hospital. PARTICIPANTS: 14 volunteer elite rowers complaining of LBP and 16 healthy volunteer amateur athletes. MAIN OUTCOME MEASUREMENTS: Intramuscular pressure (IMP), tissue oxygenation pressure (pO2), and median frequency (MF) shift in the electromyographic power density spectrum during isometric fatiguing extension at 60% of maximum voluntary contraction. RESULTS: At the beginning (controls 186.6 mm Hg vs rowers 60.2 mm Hg, P = .002) and the end (controls 224.1 mm HG vs rowers 77.1 mm Hg, P < .001) of the endurance exercise the median IMP was significantly higher in the healthy controls. Nearly identical resting pO2 was measured in both groups (controls 37.6 mm Hg vs rowers 37.3 mm Hg, P = .740). Rowers showed higher median MF shift (rowers -11.5 Hz vs controls -8.5 Hz, P = .079) during contraction. CONCLUSIONS: These observations cannot sufficiently be explained by the CFCS model and suggest that factors other than IMP have an additional effect on pain generation during exercise in elite rowers.
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Síndromes Compartimentais/complicações , Contração Isométrica/fisiologia , Dor Lombar/etiologia , Fadiga Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Esportes/fisiologia , Adolescente , Adulto , Síndromes Compartimentais/etiologia , Eletromiografia , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Dor Lombar/reabilitação , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiologia , Medição da Dor , Pressão , Fatores de RiscoRESUMO
INTRODUCTION: Pneumatosis coli is a rare disease with heterogeneous symptoms which can be detected in the course of various acute and chronic intestinal diseases in children, such as necrotizing enterocolitis, intestinal obstruction and intestinal bacteriological infections. CASE PRESENTATION: We report the case of a 12-month-old boy who died of pneumatosis coli caused by an acute intestinal gas gangrene after prolonged artificial alimentation. CONCLUSION: While intestinal gas gangrene is a highly uncommon cause of pneumatosis coli, it is important to consider it as a differential diagnosis, especially in patients receiving a prolonged artificial food supply. These patients may develop intestinal gas gangrene due to a dysfunctional intestinal barrier.
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BACKGROUND: Adult granulosa cell tumors of the ovary (GCTs) are sex cord stromal tumors of unpredictable behaviour. Up to now, the prediction of the relapsing/malignant potential remains difficult. CD56 (NCAM) in GCTs was previously described in only two studies. However, the expression of its isoforms was not examined. METHODS: 30 GCTs (16 primaries, 14 relapses) were investigated immunohistochemically with antibodies against Pan-CD56 (CD56Pan) and the isoform with 140/180 kDa length (CD56140/180 kDa). The reaction was assessed with respect to percentage of positive cells and intensity of staining. RESULTS: In all GCTs, CD56Pan was expressed, but differences were found between primaries and relapses. The percentage of CD56Pan positive tumor cells was lower in relapses, whereas CD56140/180 kDa showed a higher staining intensity in the latter. CONCLUSION: Expression of CD56 is an additional sensitive and helpful immunohistochemical tool for histopathologists diagnosing a GCT. It does not seem possible to provide a validly individual risk assessment. However, the different expression of CD56 isoforms might indicate important changes in the course to a more malignant behaviour.
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Transketolases link the Embden-Meyerhof pathway to the pentose phosphate pathway. An influence of p-Akt on this metabolism was described. This study was performed to compare the expression of transketolase-like 1 (TKTL1) and p-Akt in glioblastoma multiforme (GBM) and other astrocytic gliomas (AGs, grades II and III). We analyzed 15 GBMs, 15 AGs (grade II), and 3 normal brain samples for TKTL1 expression by semiquantitative reverse transcription-polymerase chain reaction and Western blotting and 23 GBMs, 9 grade III AGs, and 7 grade II AGs immunohistochemically (TKTL1 and p-Akt). On the protein level, TKTL1 was significantly overexpressed in tumors. Immunohistochemically, the tumor grade significantly correlated with expression of TKTL1. Compared with grades II and III AGs, GBMs showed higher expression of TKTL1, more positive tumors, and a higher percentage of positive tumor cells. The percentage of positive cells for TKTL1 and p-Akt was significantly correlated. These observations could lead to additional therapeutic options targeting a specific blockade of TKTL1 enzyme activity.
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Astrocitoma/enzimologia , Glioblastoma/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transcetolase/biossíntese , Astrocitoma/patologia , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , RNA Mensageiro/metabolismo , Regulação para CimaRESUMO
The current World Health Organization classification recommends the usage of the term sarcomatoid carcinoma (SC) for all biphasic malignant neoplasms of the urinary tract exhibiting morphologic and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. While most SC have been described in the urinary bladder, ureteral SC are extremely rare tumors. Here, we report on the clinical, morphological, and molecular biological findings of two cases in this unusual location. The genetic alterations investigated by comparative genomic hybridization in the epithelial and the mesenchymal component of both cases showed considerable but not complete overlap. Moreover, in spite of many morphological differences between the two cases, both cases shared some genetic gains and losses. Our findings are compatible with the concept that SC originates from a common pluripotent progenitor cell with a potential for epithelial and mesenchymal differentiation.
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Carcinossarcoma/genética , Carcinossarcoma/patologia , Células-Tronco Pluripotentes/patologia , Neoplasias Ureterais/genética , Neoplasias Ureterais/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/classificação , Diferenciação Celular , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Hibridização de Ácido Nucleico , Neoplasias Ureterais/classificação , Organização Mundial da SaúdeRESUMO
In the opinion of soldiers and unit surgeons, specific environmental and climatic conditions in the mission in the former Yugoslavia increase the incidence of severe infections of the respiratory tract (so-called "Kosovo Cough"). Proof is pending. Thus, colds were analyzed during Bundeswehr operations in the province of Kosovo. Over a period of 4 weeks in January 2003, all German soldiers who reported for medical treatment or requested medicine were registered. Patients provided information about their disease as well as information about smoking habits, etc. Two hundred three soldiers (9.2% of all) were treated for a cold. Although 72 soldiers (35.5%) complained about a subjectively perceived unusually long and severe clinical course, all infections proved uncomplicated from an objective viewpoint. The findings are inconsistent with an increased incidence of colds. There was no indication of the existence of the so-called "Kosovo Cough."
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Militares , Missões Religiosas , Humanos , Incidência , Kosovo , Medicina Militar , IugosláviaRESUMO
Coincidence of pulmonal sarcoidosis and progressive multifocal leukoencephalopathy (PML) rarely occurs. So far an entire course has been recorded in only very few cases. We demonstrate the case of a 49-year-old male developing an infratentorial localized PML in the setting of advanced pulmonal sarcoidosis. PML was not included in the diagnostic considerations in the first instance. Regarding the diagnosis of pulmonal sarcoidosis proved by lung biopsy, the neurological impairment was first thought to be due to a neurosarcoidosis. But magnetic resonance tomography (MRI) clearly showed a demyelination process in the cerebellum. Because of the inconsistency of the radiological findings with a neurosarcoidosis the diagnosis of an acute disseminated encephalomyelitis (ADEM) was favoured. Therefore, the patient was initially treated with corticosteroids. Because of increasing deterioration further diagnostic testings were performed. In the cerebrospinal fluid (CSF) as well as in the paraffin-embedded tissue of a stereotactical brain biopsy JCV-DNA was successfully demonstrated by PCR. Cidofovir was administered. The progression of the disease could not be influenced. The patient died 5 months after the first neurological symptoms. This report stresses the diagnostic difficulties considering patients with sarcoidosis and neurological symptoms.
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Encefalomielite Aguda Disseminada/complicações , Leucoencefalopatia Multifocal Progressiva/complicações , Sarcoidose Pulmonar/complicações , Biópsia , Encéfalo/patologia , Núcleo Celular/patologia , Cerebelo/patologia , Diagnóstico Diferencial , Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/patologia , Humanos , Vírus JC/ultraestrutura , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/patologia , Pulmão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/patologia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Vírion/ultraestruturaRESUMO
Tumorigenesis involves energy production by aerobic glycolysis ("Warburg effect") in malignant tumors. One of the key enzymes is transketolase. Transketolase, transketolase-like-1 (TKTL1), and transketolase-like-2 are known. Antibodies against TKTL1 exist for immunohistochemical investigations. This study investigated the influence of TKTL1 on survival and metastasizing in 40 laryngeal squamous cell carcinomas (SCCs, T2-T4, 27 metastasized). Staining was assessed by an immunoreactive score (IRS) with values from 0 to 12 in primaries and their nodal metastases. The highest IRS was 8. Normal epithelium did not show an expression. Three SCCs were negative. Advanced SCCs had a higher IRS than lower stages. An IRS>4 was associated with a shorter disease specific survival, independent on the tumor stage in the multivariate analysis. Significant differences between metastasized and non-metastasized SCCs were absent, but poorly differentiated SCCs had a higher IRS in their metastases than moderate differentiated SCCs. TKTL1 overexpression is associated with a more aggressive behavior and shorter survival of laryngeal SCCs. These observations could lead to additional therapeutic options targeting a blocking of the enzyme activity.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/mortalidade , Transcetolase/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/secundário , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
BACKGROUND: Spindle cell tumors of the larynx are rare. In some cases, the dignity is difficult to determine. We report two cases of laryngeal spindle cell tumors. CASE PRESENTATION: Case 1 is a spindle cell carcinoma (SPC) in a 55 year-old male patient and case 2 an inflammatory myofibroblastic tumor (IMT) in a 34 year-old female patient. A comprehensive morphological and immunohistochemical analysis was done. Both tumors arose at the vocal folds. Magnified laryngoscopy showed polypoid tumors. After resection, conventional histological investigation revealed spindle cell lesions with similar morphology. We found ulceration, mild atypia, and myxoid stroma. Before immunohistochemistry, the dignity was uncertain. Immunohistochemical investigations led to diagnosis of two distinct tumors with different biological behaviour. Both expressed vimentin. Furthermore, the SPC was positive for pan-cytokeratin AE1/3, CK5/6, and smooth-muscle actin, whereas the IMT reacted with antibodies against ALK-1, and EMA. The proliferation (Ki67) was up to 80% in SPC and 10% in IMT. Other stainings with antibodies against p53, p21, Cyclin D1, or Rb did not result in additional information. After resection, the patient with SPC is free of disease for seven months. The IMT recurred three months after first surgery, but no relapses were found eight months after resurgery. CONCLUSION: Differential diagnosis can be difficult without immunohistochemistry. Therefore, a comprehensive morphological and immunohistochemical analysis is necessary, but markers of cell cycle (apart from the assessment of proliferation) do not help.
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Pressure ulcers are frequently seen dermal lesions, but little is known about their pathophysiology. It is generally assumed that prolonged tissue pressure impairs blood circulation thus causing ischemic damage to tissue. Therefore, subcutaneous oxygen partial pressure was measured to confirm this hypothesis. In the past, various authors have conducted tests on healthy subjects to determine oxygen partial pressure transcutaneously during periods not exceeding 20 minutes. All found a decrease at susceptible sites, e.g., the sacrum. The present study was the first one to measure oxygen partial pressure subcutaneously above the sacrums of four test subjects during a period of 5 hours. In all cases, the values first decreased to a minimum of 37% of baseline before they returned to the initial values. This observation is in contradiction to former studies, which start from the assumption of critical ischemia due to interface pressure, measured on healthy volunteers too.