RESUMO
The risk of suffering from gonadal germ cell tumors (GCT) is increased in some patients with different sexual development (DSD), mainly in those with Y chromosome material. This risk, however, varies considerably depending on a multitude of factors that make the decision for prophylactic gonadectomy extremely difficult. In order to make informed recommendations on the convenience of this procedure in cases where there is potential for malignancy, this consensus guide evaluates the latest clinical evidence, which is generally low, and updates the existing knowledge in this field.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Desenvolvimento Sexual , Humanos , Consenso , Neoplasias Embrionárias de Células Germinativas/cirurgia , CastraçãoRESUMO
The volume of ubiquitous chemicals with estrogenic properties is on the rise and some reports relate the increase in hormonal diseases to these compounds. A morphological and immunohistochemical analysis has been performed on 42 bilateral orchiectomy specimens from adult individuals who underwent gender reassignment surgery after receiving crossed-sex hormone therapy to give insight into vascular, inflammatory and epididymal changes following long-term treatment with estrogens and antiandrogens and raise awareness of the consequences of hormone therapy. The present study confirms previously reported findings in testicular parenchyma and epididymis, such as identification of three histological patterns according to lesion severity and cell dedifferentiation, and reports for the first time vascular and inflammatory lesions (atherosclerosis and vasculitis), both on testicle and epididymis. Cross-sex hormone therapy should be provided in specialized units in order to systematize treatments and ensure adequate follow-up.
Assuntos
Antagonistas de Androgênios/efeitos adversos , Epididimo/efeitos dos fármacos , Estrogênios/efeitos adversos , Testículo/efeitos dos fármacos , Adulto , Aterosclerose/induzido quimicamente , Aterosclerose/patologia , Epididimo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia de Readequação Sexual , Testículo/patologia , Pessoas Transgênero , Vasculite/induzido quimicamente , Vasculite/patologia , Adulto JovemRESUMO
IGSF1 (Immunoglobulin Superfamily 1) gene defects cause central hypothyroidism and macroorchidism. However, the pathogenic mechanisms of the disease remain unclear. Based on a patient with a full deletion of IGSF1 clinically followed from neonate to adulthood, we investigated a common pituitary origin for hypothyroidism and macroorchidism, and the role of IGSF1 as regulator of pituitary hormone secretion. The patient showed congenital central hypothyroidism with reduced TSH biopotency, over-secretion of FSH at neonatal minipuberty and macroorchidism from 3 years of age. His markedly elevated inhibin B was unable to inhibit FSH secretion, indicating a status of pituitary inhibin B resistance. We show here that IGSF1 is expressed both in thyrotropes and gonadotropes of the pituitary and in Leydig and germ cells in the testes, but at very low levels in Sertoli cells. Furthermore, IGSF1 stimulates transcription of the thyrotropin-releasing hormone receptor (TRHR) by negative modulation of the TGFß1-Smad signaling pathway, and enhances the synthesis and biopotency of TSH, the hormone secreted by thyrotropes. By contrast, IGSF1 strongly down-regulates the activin-Smad pathway, leading to reduced expression of FSHB, the hormone secreted by gonadotropes. In conclusion, two relevant molecular mechanisms linked to central hypothyroidism and macroorchidism in IGSF1 deficiency are identified, revealing IGSF1 as an important regulator of TGFß/Activin pathways in the pituitary.
Assuntos
Ativinas/metabolismo , Subunidade beta do Hormônio Folículoestimulante/metabolismo , Hipotireoidismo/patologia , Imunoglobulinas/genética , Proteínas de Membrana/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Análise Mutacional de DNA , Subunidade beta do Hormônio Folículoestimulante/genética , Seguimentos , Deleção de Genes , Humanos , Hipotireoidismo/genética , Recém-Nascido , Masculino , Camundongos , Hipófise/metabolismo , Hipófise/patologia , Regiões Promotoras Genéticas , Ratos , Ratos Wistar , Receptores do Hormônio Liberador da Tireotropina/genética , Proteínas Smad/metabolismo , Testículo/metabolismo , Testículo/patologiaRESUMO
Testicular tumors in the prepubertal age are relatively rare, representing only 9.4% of the total testicular and paratesticular specimens from a 20-year review performed at a large pediatric hospital [ 1 ]. They account for 1% to 2% of all solid tumors in the pediatric age group, with an annual incidence between 0.5/100 000 and 2/100 000 boys according to Coppes et al [ 2 ] and data from the Prepubertal Testicular Tumor Registry [ 3 ]. Similar to other neoplasms afflicting children, a bimodal age distribution is observed. The first peak is between birth and 3 years of age, and a second one occurs at the onset of puberty, extending to the fourth decade. Reports on their frequency vary because some investigators include the adolescent period, while others do not [ 4 ]. The vast majority of testicular tumors are germ cell neoplasms, accounting for 95% across all ages [ 5 ]. In children, germ cell tumors also predominate, representing 71% of all testicular neoplasms. These include yolk sac tumors (49%), teratomas (13%), seminomas and mixed germ cell tumors (9%), and sex-cord stromal tumors (29%). Malignant potential is significantly lower (less than 70%) in the pediatric age group compared to adults (90%) [ 6 ]. According to Pohl et al, 74% of prepubertal testicular tumors are benign [ 7 ].
Assuntos
Neoplasias Testiculares/patologia , Adolescente , Criança , Pré-Escolar , Humanos , Incidência , Masculino , Neoplasias Testiculares/epidemiologiaRESUMO
Acute scrotal pain in children represents a major diagnostic and therapeutic challenge. An important initial differentiation should be made between epididymitis and other processes that cause acute scrotal pain, such as testicular torsion and tumor. Infectious agents disseminating through the blood flow can damage the testis by causing orchitis. On the other hand, infections ascending via spermatic pathways typically lead to epididymitis [ 1 ].
Assuntos
Inflamação , Doenças Testiculares , Criança , Humanos , MasculinoRESUMO
Testicles can be damaged by a variety of physical and chemical agents, ranging from trauma suffered in accidents or athletic activities, to diverse drugs or radiation used in cancer treatment. The immediate and long-term effects of these damaging agents at the testicular morphologic and functional levels are quite varied and may have significant impact on the fertility of the pediatric patient once reproductive age is reached.
Assuntos
Doenças Testiculares/induzido quimicamente , Testículo/lesões , Testículo/patologia , Pré-Escolar , Humanos , MasculinoRESUMO
Normal testicular physiology requires appropriate function of endocrine glands and other tissues. Testicular lesions have been described in disorders involving the hypothalamus-hypophysis, thyroid glands, adrenal glands, pancreas, liver, kidney, and gastrointestinal tract. Testicular abnormalities can also associate with chronic anemia, obesity, and neoplasia. Although many of the disorders that affect the above-mentioned glands and tissues are congenital, acquired lesions may result in hypogonadism in children and adolescents.
Assuntos
Doenças Testiculares/etiologia , Doenças Testiculares/patologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Doenças do Sistema Endócrino/complicações , Humanos , MasculinoAssuntos
Calcinose/patologia , Doenças Testiculares/patologia , Testículo/patologia , Calcinose/epidemiologia , Criança , Epididimo/patologia , Doenças dos Genitais Masculinos/epidemiologia , Doenças dos Genitais Masculinos/patologia , Humanos , Incidência , Masculino , Doenças Testiculares/epidemiologia , Ducto Deferente/patologiaRESUMO
One of the most challenging areas in pediatric testicular pathology is the appropriate understanding and pathological diagnosis of disorders of sexual development (DSD), and in particular, the issue of gonadal dysgenesis. Here we present the main concepts necessary for their understanding and appropriate classification, with extensive genetic correlations.
Assuntos
Disgenesia Gonadal/patologia , Testículo/patologia , Biópsia , Cromossomos Humanos X , Cromossomos Humanos Y , Feminino , Predisposição Genética para Doença , Disgenesia Gonadal/classificação , Disgenesia Gonadal/genética , Humanos , Masculino , Ovário/patologia , Fenótipo , Valor Preditivo dos Testes , Terminologia como AssuntoRESUMO
Normal male development requires three conditions: (1) adequate differentiation of the fetal testis; (2) synthesis and secretion of testicular hormones; and (3) effective action of these hormones on target organs. This requires the combined action of the inhibitory anti-müllerian hormone (AMH, secreted by Sertoli cells) to block the development of the uterus and fallopian tubes from the müllerian duct, together with the trophic stimulus of testosterone (a Leydig cell product), which leads to virilization of the wolffian ducts. Additionally, the development of external genitalia depends on the conversion of testosterone to dihydrotestosterone by the enzyme 5-α-reductase. Failure of any of these mechanisms leads to deficient virilization or the so-called "male pseudohermaphroditism" syndromes.
Assuntos
Transtornos do Desenvolvimento Sexual/patologia , Masculinidade , Processos de Determinação Sexual , Testículo/patologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Hormônio Antimülleriano/metabolismo , Biópsia , Diferenciação Celular , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Fenótipo , Valor Preditivo dos Testes , Transdução de Sinais , Testículo/metabolismo , Testosterona/metabolismo , VirilismoAssuntos
Coristoma/patologia , Disgenesia Gonadal 46 XY/patologia , Patologia , Pediatria , Doenças Testiculares/patologia , Testículo/anormalidades , Coristoma/classificação , Disgenesia Gonadal 46 XY/classificação , Humanos , Masculino , Patologia/métodos , Pediatria/métodos , Doenças Testiculares/classificação , Testículo/patologiaRESUMO
Inflammatory pseudotumor (IPT) of the spleen is an uncommon entity with an uncertain aetiology. Inflammatory pseudotumors present diagnostic difficulties because the clinical and radiological findings tend to suggest a malignancy. The symptoms include weight loss, fever, and abdominal pain. Most cases of splenic IPT present solitary relatively large well circumscribed masses on imaging. The diagnosis in the majority of the cases is made after histopathologic study of splenectomy specimens. The IPTs that occur in the spleen and liver are typically associated with Epstein-Barr virus. Thirty-seven percent of all new cases of active tuberculosis infection are extrapulmonary tuberculosis and tuberculous lymphadenitis the most commonly occurring form of extrapulmonary tuberculosis. We report the case of an inflammatory pseudotumor of the spleen associated with splenic tuberculous lymphadenitis in a 50-year-old female patient who was preoperatively diagnosed with a malignant spleen tumour based on her history of breast of carcinoma.
RESUMO
Myxoid/round cell liposarcoma is a soft tissue sarcoma that is extremely rare in the brachial plexus. We report a case of a myxoid/round cell liposarcoma originating in the brachial plexus that was surgically resected and evolved well, with no deficit or recurrence after 2 years of follow-up. To date, there has been no other case of this sarcoma in the literature.
Assuntos
Plexo Braquial , Lipossarcoma Mixoide/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Studies over the last years show an increase in testicular cancer, hypospadias and cryptorchidism in industrial countries, leading to the concept of testicular dysgenesis syndrome (TDS). It is hypothesized that TDS is caused by estrogen and antiandrogen exposure during fetal life, accompanied by incomplete maturation of testicular Sertoli cells (SC). However, it is not known if SC disruption is a primary cause or a response to fetal Leydig cell testosterone production changes. To determine if SC differentiation is directly affected by estrogens, we compared SC maturation between adult gender reassignment cases exposed to estrogen and antiandrogen therapy, and those of typical TDS in adult cryptorchidism. We found similar expression of immature SC markers M2A antigen, inhibin bodies and Anti Mullerian Hormone, and the absence of maturation marker androgen receptor in SC of both types of patients. These data supports the occurrence of true SC dedifferentiation caused by estrogen exposure in adult humans. Our data also suggests that SC maturation is directly disrupted in TDS.
Assuntos
Antagonistas de Androgênios/farmacologia , Criptorquidismo/patologia , Estrogênios/farmacologia , Células de Sertoli/efeitos dos fármacos , Procedimentos de Readequação Sexual , Adulto , Hormônio Antimülleriano/metabolismo , Calbindina 2/metabolismo , Desdiferenciação Celular , Criptorquidismo/metabolismo , Feminino , Humanos , Masculino , Troca Materno-Fetal , Pessoa de Meia-Idade , Gravidez , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patologia , Células de Sertoli/patologia , Proteínas WT1/metabolismo , Adulto JovemRESUMO
Hearing loss is the most common symptom in patients with vestibular schwannoma (VS). In the past, compressive mechanisms caused by the tumoral mass and its growth have been regarded as the most likely causes of the hearing loss associated with VS. Interestingly, new evidence proposes molecular mechanisms as an explanation for such hearing loss. Among the molecular mechanisms proposed are methylation of TP73, negative expression of cyclin D1, expression of B7-H1, increased expression of the platelet-derived growth factor A, underexpression of PEX5L, RAD54B, and PSMAL, and overexpression of CEA. Many molecular mechanisms are involved in vestibular schwannoma development; we review some of these mechanisms with special emphasis on hearing loss associated with vestibular schwannoma.
RESUMO
With the completion of the human genome sequence, biomedical sciences have entered in the "omics" era, mainly due to high-throughput genomics techniques and the recent application of mass spectrometry to proteomics analyses. However, there is still a time lag between these technological advances and their application in the clinical setting. Our work is designed to build bridges between high-performance proteomics and clinical routine. Protein extracts were obtained from fresh frozen normal lung and non-small cell lung cancer samples. We applied a phosphopeptide enrichment followed by LC-MS/MS. Subsequent label-free quantification and bioinformatics analyses were performed. We assessed protein patterns on these samples, showing dozens of differential markers between normal and tumor tissue. Gene ontology and interactome analyses identified signaling pathways altered on tumor tissue. We have identified two proteins, PTRF/cavin-1 and MIF, which are differentially expressed between normal lung and non-small cell lung cancer. These potential biomarkers were validated using western blot and immunohistochemistry. The application of discovery-based proteomics analyses in clinical samples allowed us to identify new potential biomarkers and therapeutic targets in non-small cell lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Oxirredutases Intramoleculares/metabolismo , Neoplasias Pulmonares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Proteômica/métodos , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , Oxirredutases Intramoleculares/genética , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Espectrometria de Massas , Modelos Genéticos , Dados de Sequência Molecular , Fosfopeptídeos/genética , Fosfopeptídeos/metabolismo , Proteínas de Ligação a RNA/genética , Reprodutibilidade dos TestesRESUMO
Small cell lung cancer is the most aggressive lung cancer subtype. The standard treatment approach is based on cisplatin regimens. Although response rates to treatment are approximately 60-80%, the median survival is still very poor. Excision repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced DNA adducts and has been related with prognosis and cisplatin response. Topotecan is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and immunohistochemistry. A significant association was found between the inmunohistochemistry expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In the survival analysis, a significant correlation between a better PFS with a low TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary, our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis to predict cisplatin response and prognosis in SCLC patients.