ACTH-producing adrenocortical carcinoma: an exceedingly rare diagnosis.

BACKGROUND: Adrenocortical carcinoma is a very rare endocrinopathy that has a poor prognosis and is frequently associated with ACTH-independent Cushing's syndrome. Despite having an adrenocortical carcinoma, our patient surprisingly had an ACTH-dependent Cushing's syndrome. CASE REPORT: A 26-year-old female presented with Cushing's syndrome and an abdominal mass. Imaging studies revealed an adrenal mass consistent with a high-grade malignancy. Laboratory workup showed hypercortisolism, hyperandrogenism, and hypokalemia with normal levels of metanephrines. Unexpectedly, her ACTH levels were remarkably elevated. The pathological analysis of a tumor sample was conclusive for adrenocortical carcinoma with immunopositivity for ACTH. CONCLUSIONS: Our patient suffered from an adrenocortical carcinoma that was ectopically producing ACTH. This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies.

Comparison of Cytological Adequacy between 23- and 25-Gauge in Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules: A Single-Center Prospective Study.

INTRODUCTION: Approximately 15% of fine-needle aspiration (FNA) of thyroid nodules are considered nondiagnostic. Several factors are potentially involved, including clinical and nodule features but also the gauge (G) of the needle used. However, few studies have compared the cytological adequacy obtained with different gauge needles and the data are controversial. We aimed to evaluate cytological adequacy results using 23- or 25-G needles. METHODS: This study is an observational and prospective study of thyroid nodules submitted to ultrasound-guided FNA. The procedure was performed randomly using 23- or 25-G needles. The samples were reported by different cytopathologists who were blinded to the information of the gauge of the needle used. Statistical analysis was performed to compare cytological adequacy of FNA between the two groups. RESULTS: A total of 177 thyroid nodules were included - 98 (55.4%) using 23-G and 79 (44.6%) using 25-G needles. The 23-G group presented a higher rate of cytological adequacy (69.4% [68/98] vs. 46.8% [37/79], p = 0.002). No differences were found between the two groups regarding patient or nodule characteristics. On logistic regression, 23-G needles correlated with better cytological adequacy (unadjusted OR 2.57 [95% CI: 1.39-4.77]), even after adjusting for nodule dimension, location, and type of cytology (slides +/- additional liquid-based cytology) (adjusted OR 2.44 [95% CI: 1.23-4.84]). CONCLUSION: The gauge of the needle used was found to be an independent predictor of cytological adequacy, with 23-G needles providing more adequate samples. Further investigation is needed to confirm our results in order to stablish the optimal diagnosis technique.

Metastatic Myoepithelial Carcinoma Ex Pleomorphic Adenoma of the Sublingual Salivary Gland.

Myoepithelial carcinoma ex pleomorphic adenoma is a very rare malignant neoplasm of the salivary gland. Owing to its rarity, its clinical features and treatment are not well characterized. We describe a case of a patient who was referred to our department with a six-month history of a bulge on the right side of the floor of the mouth and a submandibular mass with progressive enlargement. The mass was resected, and an elective level I neck dissection was performed. Histological examination revealed myoepithelial carcinoma ex pleomorphic adenoma of the sublingual salivary gland. Thoracic computed tomography and biopsy revealed lung metastases. The patient died two years after the diagnosis.

Intrasphenoidal Rathke's Cleft Cyst: An Uncommon Feat.

Usually occurring entirely intrasellarly or extending suprasellarly (intra-suprasellar), Rathke's cleft cysts (RCCs) can present with an intrasphenoidal location. Extrasellar positions are rare. To date, only seven patients with intrasphenoidal RCC have been reported in the literature. Despite the rarity of the condition and the lack of pathognomonic radiological features, preoperative diagnosis remains challenging. A trans-sphenoidal approach can be adopted to treat this type of cyst, which has great clinical relevance. Awareness of this different presentation of RCC before respective management may be of value in its approach. Intrasphenoidal RCC should be diagnosed preoperatively and the surgical approach should be changed accordingly by aspiration and partial removal before the histological examination.

Merkel Cell Carcinoma: An Otolaryngological Point of View of An Unusual Sinonasal Mass.

Merkel cell carcinoma is a pathologic diagnosis mainly observed in sun-exposed cutaneous areas, like the head and neck. Ultraviolet (UV) exposure and immunosuppression are the common predisposing factors. Merkel cell carcinoma of the head and neck is quite an uncommon disease. This case report involves a 56-year-old man who exhibited a skin lesion on the nasal dorsum with a mass in the right maxillary sinus. The biopsies from both sides were diagnostic for Merkel cell carcinoma. The patient underwent endoscopic sinus surgery and removal of the skin lesion with free margins. The patient has been free of disease for the last 20 months now and maintains follow-up with endoscopy and imaging in the Ear Nose Throat office. Only a few cases of Merkel cell carcinoma of the nasal mucosa have been reported in the literature. We report our approach and management of this rare pathologic presentation.

Colon tumor CD31 expression is associated with higher disease-free survival in patients with metabolic syndrome.

Metabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, how does the interplay between metabolic dysfunction caused by MS and its individual components affect CC microenvironment and prognosis remains unexplored. Angiogenesis and lymphangiogenesis are fundamental processes for tumor progression and dissemination, ensuring oxygen and nutrient delivery and supporting one of the most important pathways of tumor dissemination, contributing to metastasis. Thus, our aim was to evaluate whether the expression of molecular biomarkers involved in angiogenic and lymphangiogenic processes influenced CC clinicopathological features and prognosis in patients with MS. Clinical and pathological data of 300 patients submitted to CC surgical resection at a single tertiary hospital were retrospectively retrieved from hospital records. Tumor tissue microarrays of archived paraffin-embedded blocks were used to assess CD31, VEGF-A and D2-40 tissue expression by immunohistochemistry. The percentage of stained area was quantified by computerized morphometric analysis. No association between tissue expression of angiogenesis and lymphangiogenesis biomarkers and tumor clinical and pathological characteristics was found. However, in subgroup analysis of patients with MS, dysglycemia was associated with lower D2-40 expression (p = 0.007) and high waist-circumference was associated with higher D2-40 (p = 0.0029) and VEGF-A expression (p = 0.026). In an adjusted Cox proportional hazard model CD31 expression was significantly associated with greater disease-free survival (HR=0.62; 95% CI: 0.41-0.95, p = 0.028). No association was found between D2-40 and VEGF-A expression and CC prognosis. Our data reinforces previous reports that suggest the potential use of CD31 as a CC prognostic biomarker. Additionally, our data further supports the evidence for an interplay between metabolic dysfunction, tumor microenvironment, and vascularization pathways.

Papillary thyroid carcinoma: the impact of histologic vascular invasion.

OBJECTIVE: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in PTC. METHODS: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors. RESULTS: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4 - 23.6%), these individuals had larger tumors (median 19mm vs 12 mm, p < 0.001) with more frequent extraglandular invasion (54.0% vs 17.1%, p<0.001), regional lymph nodes involvement (29.8% vs 12.6%, p = 0.003)and distant metastasis (10.9% vs 1.9%, p = 0.003) at diagnosis. Vascular invasion was an independent predictor for regional lymph node and/or distant metastasis at diagnosis [OR 2.93 (IC95% 1.16 - 7.41, p = 0.008)]. After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence. CONCLUSIONS: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Hereditary Leiomyomatosis and Renal Cell Cancer-Recognizing Patterns May Save Lives.

In 2001, Finish investigators described a rare familiar syndrome characterized by an inherited susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). Hereditary leiomyomatosis and renal cell cancer (HLRCC) is now linked to a germline mutation in the fumarate hydratase (FH) gene that encodes a Krebs cycle enzyme, transforming fumarate to malate. The accumulation of fumarate, an oncometabolite, promotes tumorigenesis. We present a case of a 41-year-old female diagnosed with HLRCC after a radical nephrectomy due to renal cell cancer. Genetic analyses confirmed a novel FH mutation. Close follow-up allowed for a precocious diagnosis of a metachronous renal tumor and later a hepatic metastasis. Her family was also counseled and offered genetic testing. As observed in this case, the diagnosis of HLRCC is of paramount importance for patients and their families: there is a 15% cumulative lifetime risk of developing RCC, which frequently occurs in young patients and metastasizes at an early stage. Implementing a regular follow-up with adequate imaging examinations may help save lives.

Pleural effusion and multiple myeloma - more than meets the eye: A case report.

Multiple myeloma (MM) accounts for 1% of all cancers. It consists of malignant proliferation of plasma cells, which is often associated with hypersecretion of a monoclonal protein. Pleural effusion (PE) in MM is not an uncommon finding, comprising about 6-14% of patients with MM. The most common causes of MM-associated PE are congestive heart failure, renal failure, parapneumonic effusion and amyloidosis. In <1% of cases, the effusion is a direct result of MM, designated as myelomatous PE (MPE). MPE is usually a diagnosis of exclusion and carries a poor prognosis. Therefore, efforts should be made to optimally detect MPE. The present report describes an MPE associated with IgG/λ MM presenting as a septic shock and renal failure in which a rare diagnosis was made after excluding all other possible etiologies in a complex intensive care patient.

Hair cross-sectioning in uncombable hair syndrome: An epoxy embedding technique.

Uncombable hair syndrome is a rare disorder of the hair shaft that leads to silvery and unruly hair. The hair shaft anomaly is characterized by a longitudinal groove that is detected by scanning electronic microscopy-considered to be the gold standard for diagnosis. Recently, hair cross-sectioning has been reported as a viable alternative, but currently available methods still have some flaws, especially because of hair samples' processing specificities. Here, we present two cases of uncombable hair syndrome and a new embedding technique using epoxy to perform the diagnosis.

The Canadian Primary Health Care Systems from a Brazilian perspective: discussing Starfield's Attributes. / O(s) Sistema(s) Primário(s) de Saúde Canadense sob uma perspectiva brasileira: discutindo os Atributos Starfield.

This paper reviews the Starfield pillars and the Canadian health system. An objective and subjective evaluation are applied to the system through the lenses of access, longitudinality, integrality, and coordination of care. System vulnerabilities, actions, and proposals that are underway to improve these aspects, both nationally and in the province of Ontario, are discussed. Worth highlighting is the opportunity to establish a national free drug system, and the several challenges to advance the agenda of reforms.

Os pilares Starfield são revistos assim como o sistema de saúde canadense. Avaliação objetiva e subjetiva são aplicadas ao sistema sob as lentes do acesso, longitudinalidade, integralidade e coordenação de cuidados. Discutem-se as vulnerabilidades do sistema e as ações e propostas que estão em curso para tentar melhorar esses aspectos, tanto nacionalmente como na província de Ontário. Destaque para a oportunidade de se criar um sistema gratuito de medicamentos e os diversos desafios para avançar a agenda de reformas.

O(s) Sistema(s) Primário(s) de Saúde Canadense sob uma perspectiva brasileira: discutindo os Atributos Starfield / The Canadian Primary Health Care Systems from a Brazilian perspective: discussing Starfield's Attributes

Resumo Os pilares Starfield são revistos assim como o sistema de saúde canadense. Avaliação objetiva e subjetiva são aplicadas ao sistema sob as lentes do acesso, longitudinalidade, integralidade e coordenação de cuidados. Discutem-se as vulnerabilidades do sistema e as ações e propostas que estão em curso para tentar melhorar esses aspectos, tanto nacionalmente como na província de Ontário. Destaque para a oportunidade de se criar um sistema gratuito de medicamentos e os diversos desafios para avançar a agenda de reformas.

Abstract This paper reviews the Starfield pillars and the Canadian health system. An objective and subjective evaluation are applied to the system through the lenses of access, longitudinality, integrality, and coordination of care. System vulnerabilities, actions, and proposals that are underway to improve these aspects, both nationally and in the province of Ontario, are discussed. Worth highlighting is the opportunity to establish a national free drug system, and the several challenges to advance the agenda of reforms.

Fatty Liver Caused by Glycogen Storage Disease Type IX: A Small Series of Cases in Children.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) affecting children and adolescents has increased dramatically in recent years. This increase is most probably related to the obesity pandemic and the high consumption of fructose. However, hepatic steatosis has some rare causes (e.g., some metabolic diseases) of which clinicians should be aware, particularly (but not only) when patients are non-obese or non-overweight. Differential diagnosis is notably important when pathologies have a specific treatment, such as for glycogenosis type IX (GSD-IX). AIMS: To contribute to the knowledge on the differential diagnosis of NAFLD in paediatric age and to the clinical, biochemical, molecular, and histological characterisations of GSD-IX, a rare metabolic disorder. METHODS: We performed a retrospective study of a small series of cases (n = 3) of GSD-IX diagnosed in the past 6 years, who were currently being followed up in the Units of Gastroenterology or Metabolic Diseases of the Paediatric Division of our hospital and whose clinical presentation was NAFLD in paediatric age. RESULTS: Three male patients were diagnosed with NAFLD before 2 years of age, 2 with confirmed diagnosis before the age of 3 years (alanine aminotransferase [ALT], liver ultrasound, and molecular analysis) and 1 whose diagnosis was confirmed at 11 years (ALT, liver ultrasound, liver histology, and molecular analysis). None of the patients were obese or overweight, and the daily fructose consumption was unknown. The outcome was favourable in all 3 patients, with follow-up periods ranging from 2 to 6 years. CONCLUSION: The decision on how far the search for secondary causes of NAFLD should go can be difficult, and GSD-IX must be on the list of possible causes.

Fatty Liver and Autoimmune Hepatitis: Two Forms of Liver Involvement in Lipodystrophies.

INTRODUCTION: Lipodystrophies are a heterogeneous group of rare diseases (genetic or acquired) characterized by a partial or generalized deficit of adipose tissue, resulting in less energy storage capacity. They are associated with severe endocrine-metabolic complications with significant morbidity and mortality. In the pathogenesis of the acquired forms, immunological disorders may be involved. CASE 1: A 13-year-old female was diagnosed with acquired generalized lipodystrophy and observed for suspicion of portal hypertension. She presented with generalized absence of adipose tissue, cervical and axillary acanthosis nigricans, and massive hepatosplenomegaly. Laboratory tests revealed AST 116 IU/L, ALT 238 IU/L, GGT 114 IU/L, HOMA-IR 28.2, triglycerides 491 mg/L, and leptin < 0.05 ng/mL. Upper gastrointestinal endoscopy saw no signs of portal hypertension. Hepatic histology showed macrovesicular fatty infiltration (60% of hepatocytes) and advanced fibrosis/cirrhosis. Her clinical condition worsened progressively to diabetes requiring treatment with subcutaneous insulin and hepatopulmonary syndrome. CASE 2: A 15-year-old female, diagnosed with acquired partial lipodystrophy, Parkinson syndrome, autoimmune thyroiditis, and autoimmune thrombocytopenia was observed for hypertransaminasemia since the age of 8 years. She had absence of subcutaneous adipose tissue in the upper and lower limbs and ataxia. Laboratory tests showed AST 461 IU/L, ALT 921 IU/L, GGT 145 IU/L, HOMA-IR 32.6, triglycerides 298 mg/dL, normal leptin levels, platelets 84,000/µL, IgG 1,894 mg/dL, positive anti-LKM and anti-LC-1. Hepatic histology was suggestive of autoimmune hepatitis, without steatosis. She progressed favorably under metformin and immunosuppressive treatment. CONCLUSION: Early recognition and adequate characterization of liver disease in lipodystrophies is essential for a correct treatment approach. In acquired generalized lipodystrophy, the severe endocrine-metabolic disorder, which leads to steatohepatitis with cirrhotic progression, may benefit from recombinant leptin treatment.

INTRODUÇÃO: As lipodistrofias sao um grupo heterogeneo de doencas raras (formas geneticas e adquiridas) caracterizadas por defice parcial ou generalizado de tecido adiposo, resultando em menor capacidade de armazenamento energetico. Estao associadas a complicacoes endocrino-metabolicas graves com morbilidade e mortalidade significativas. Na patogenese das formas adquiridas poderao estar envolvidos disturbios imunologicos. CASO 1: Adolescente de 13 anos, sexo feminino, com diagnostico de lipodistrofia generalizada adquirida, observada por suspeita de hipertensao portal. Apresentava ausencia generalizada de tecido adiposo, acantose nigricans cervical e axilar, e hepatoesplenomegalia volumosa. Do estudo destacavam-se: AST 116 UI/L, ALT 238 UI/L, GGT 114 UI/L, HOMA-IR 28.2, triglicerideos 491 mg/L e leptina < 0.05 ng/mL. A endoscopia digestiva alta nao evidenciou sinais de hipertensao portal. Histologia hepatica com esteatose macrovesicular (60% dos hepatocitos) e fibrose avancada/cirrose. A sua condicao clinica evoluiu progressivamente para diabetes com necessidade de tratamento com insulina subcutanea e sindrome hepatopulmonar. CASO 2: Adolescente de 15 anos, sexo feminino, com diagnostico de lipodistrofia parcial adquirida, sindrome parkinsonico, tiroidite autoimune, e trombocitopenia autoimune, observada por elevacao das transaminases desde os 8 anos. Apresentava ausencia de tecido adiposo subcutaneo nos membros superiores e inferiores, ataxia e tremor das maos, sem sinais de doenca hepatica. Do estudo destacavam-se: AST 461 UI/L, ALT 921 UI/L, GGT 145 UI/L, HOMA-IR 32,6, triglicerideos 298 mg/dL, leptina normal, plaquetas 84,000/µL, IgG 1,894 mg/dL, anticorpos anti-LKM e anti-LC1 positivos. Histologia hepatica sugestiva de hepatite autoimune, sem esteatose. A doente evoluiu favoravelmente com metformina e tratamento imunossupressor. DISCUSSAO: O reconhecimento precoce e a caracterizacao adequada da doenca hepatica nas lipodistrofias sao fundamentais para uma correta abordagem terapeutica. Na lipodistrofia generalizada adquirida, o disturbio endocrino-metabolico grave responsavel por esteatohepatite com evolucao cirrogenea podera beneficiar do tratamento inovador com leptina recombinante.

Araucaria angustifolia chloroplast genome sequence and its relation to other Araucariaceae.

Araucaria angustifolia is endemic to southern Brazil. Known as Brazilian pine, A. angustifolia is the only native conifer species with economic and social relevance in this country. Due to massive exploitation, it has suffered a significant population decline and currently is classified as critically endangered. This encouraged the scientific community to investigate genetic features in Brazilian pine to increase resources for management and preservation. In this work, RNA-Seq data was used to determine the complete nucleotide sequence of the A. angustifolia chloroplast genome (cpDNA). The cpDNA is 146,203 bp in length and contains 122 genes, including 80 protein-coding genes, 5 ribosomal RNA genes, and 37 tRNA genes. Coding regions comprise 45.02%, 4.96% correspond to rRNAs and tRNAs, and 50.02% of the genome encompasses non-coding regions. Genes found in the inverted repeat (IR) are present as single copy, with exception of the rrn5 and trnI-CAU loci. The typical LSC, SSC, IRa and IRb organization reported in several land-plant groups is not present in A. angustifolia cpDNA. Phylogenetic analyses using Bayesian and Maximum Likelihood methods clustered A. angustifolia in the Araucariaceae family, with A. heterophylla and A. columnaris as congeneric species. The screening of A. angustifolia cpDNA reveled 100 SSRs, 14 of them corresponding to tetrapolymer loci.

Autogenous Bone Graft Versus Bovine Bone Graft in Association With Platelet-Rich Plasma for the Reconstruction of Alveolar Clefts: A Pilot Study.

OBJECTIVE: To compare the outcomes of 2 different bone graft materials: autogenous bone grafts from mandibular symphysis and bovine bone grafts associated with platelet-rich plasma (PRP). METHODS: Twenty individuals met the inclusion criteria and accepted to participate in the study. Group A patients underwent alveolar bone grafting using autologous bone and group B patients using a bovine bone graft associated with PRP. Cone beam computed tomography scans were taken and reconstructed 3-dimensionally for all patients preoperatively and 1 year postoperatively. RESULTS: A significant reduction was detected for area and volume within group A and group B. Between groups, no significant difference was found for area or volume. CONCLUSIONS: Bovine grafts associated with PRP are a good option for the reconstruction of alveolar clefts and provide good results such as autologous bone grafts.