Primarni mukoepidermoidni karcinom štitne žlijezde s agresivnim ponašanjem - prikaz slučaja

This report describes a primary high-grade mucoepidermoid carcinoma of the thyroid in a 33-year-old male. The patient presented with a rapidly enlarging mass in the left thyroid lobe. Cytologic analysis suggested a poorly differentiated thyroid carcinoma. Total thyroidectomy was performed. On gross examination, a poorly circumscribed, gray-white tumor measuring up to 5.5 cm in the largest diameter was found. Light microscopy showed atypical, large epithelial cells forming solid islands and nests with variable, focal production of mucin and up to 5 mitotic figures per 10 high-power fields. Squamous cell foci without keratinization were also observed. Tumor cells were immunohistochemically negative for thyroglobulin and calcitonin, and positive for cytokeratin. Electron microscopy showed squamous cells with intracytoplasmic aggregates of tonofilaments, well-developed desmosomal attachments and mucous cells characterized by numerous mucin granules. Six months after the initial treatment, ipsilateral radical neck dissection revealed 25 positive out of 44 lymph nodes. Computed tomography performed a month later revealed a large tumor located behind the larynx, compressing the trachea, with retrosternal spread into the mediastinum. The patient underwent radiotherapy for a widespread metastatic disease. We think that primary thyroid mucoepidermoid carcinoma may show an aggressive clinical course.Prikazan je 33-godišnji bolesnik s primarnim mukoepidermoidnim karcinomom štitne žlijezde vrlo agresivnog ponašanja. Bolesnik se javlja liječniku poradi brzorastućeg tumora lijevog režnja štitne žlijezde. Citološka analiza je upućivala na slabo diferencirani karcinom štitnjače. Učinjena je totalna tiroidektomija. Makroskopski je nađen slabo ograničeni, sivo bijeli tumor promjera do 5,5 cm. Histološki je tumor građen od atipičnih, krupnih epitelnih stanica koje tvore otočiće i gnijezda. Tumorske stanice mjestimice pokazuju stvaranje sluzi. Usto se nalaze žarišta pločastih stanica bez izraženog orožnjavanja. Imunohistokemijski tumorske stanice pokazuju pozitivnu reakciju na citokeratin i negativnu na tiroglobulin i kalcitonin. Elektronsko mikroskopska analiza pokazala je pločaste stanice s intracitoplazmatskim nakupinama tonofilamenata, dobro razvijenim dezmosomima i mucinozne stanice s brojnim mucinskim granulama. Šest mjeseci nakon prvog zahvata učinjena je istostrana disekcija vratnih limfnih čvorova, pri čemu je patohistološki većina čvorova bila zauzeta metastatskim tumorom. Kompjutoriziranom tomografijom učinjenom mjesec dana kasnije utvrđene su tumorske mase iza grkljana i traheje, koje se šire iza prsne kosti u medijastinum. Bolesnik je liječen zračenjem zbog raširenih metastaza. Ovakav tijek bolesti upućuje na to da primarni mukoepidermoidni karcinom štitnjače može pokazivati vrlo agresivan tijek

Patogeneza bronhijalne hiperreaktivnosti u bolesnika s alergijskim rinitisom

Bronchial hyperreactivity denotes an enhanced bronchial response to usual physiological stimuli, and can manifest with cough or paroxysmal cough through tussive syncope and bronchospasm. Bronchial hyperreactivity can be transient or permanent. Transient bronchial hyperreactivity occurs in acute inflammation of the upper and lower airways, and manifests with dry irritation cough that may persist for up to two months. Permanent bronchial hyperreactivity is found in 10% - 50% of patients with allergic rhinitis, 50% of patients with chronic bronchitis, and 100% of patients with asthma. The pathophysiological mechanism of bronchial hyperreactivity in patients with allergic rhinitis has not yet been fully clarified, however, the following theories have been implicated: loss of nasal function, direct aspiration of inflammatory secretion and antigens, aerogenic transfer of antigens depending on particle size, gastroesophageal reflux, neurogenic mechanisms including the action of neuropeptides in the onset of neurogenic inflammation, and the concept of allergic reaction as a systemic response to local antigen presentation. It should be noted that bronchial hyperreactivity is not asthma; however, the clinical manifestation of asthma is just a matter of time. Therefore, allergic rhinitis should be considered a predisposing factor for the occurrence of asthma.Pod bronhijalnom hiperreaktivnošću podrazumijeva se pojačan odgovor bronha na uobičajene fiziološke podražaje, koji se može očitovati kašljem, paroksizmom kašlja, sve do tusigene sinkope i bronhospazma. Bronhijalna hiperreaktivnost može biti prolazna i trajna. Prolazna bronhijalna hiperreaktivnost pojavljuje se kod akutnih upala gornjih i donjih dišnih putova, očituje se suhim podražajnim kašljem koji može potrajati i do dva mjeseca. Trajna bronhijalna hiperreaktivnost nalazi se u 10% - 50% bolesnika s alergijskim rinitisom, 50% bolesnika s kroničnim bronhitisom, te u 100% bolesnika s astmom. Patofiziološki mehanizam nastanka bronhijalne hiperreaktivnosti u bolesnika s alergijskim rinitisom nije u potpunosti jasan, a spominju se slijedeće teorije: gubitak funkcije nosa, izravna aspiracija upalnog sekreta i antigena, aerogeno prenošenje antigena ovisno o veličini cestica, gastroezofagusni refluks, neurogeni mehanizmi uključujući i djelovanje neuropeptida u nastanku neurogene upale, te shvaćanje alergijske reakcije kao sistemske reakcije na lokalno prikazivanje antigena. Valja istaknuti da bronhijalna hiperreaktivnost nije astma, ali je pitanje dana kada će se astma klinički očitovati. Stoga se alergijski rinitis može smatrati predisponirajućim čimbenikom u pojavi astme

RADIOIODINE VERSUS SURGERYIN THE TREATMENT OF GRAVES’ HYPERTHYROIDISM

Najčešći uzrok hipertireoze u djece i odraslih osoba je autoimunosna Gravesova (Basedowljeva) bolest. U liječenju Gravesove hipertireoze primjenjuju se više od 60 godina tireostatici, kirurški zahvat i radiojodna terapija. Najraširenija je primjena tireostatika. Međutim, remisija uz tireostatike može se očekivati u 20–50% odraslih osoba i 20–30% djece. Metode definitivnog liječenja Gravesove hipertireoze su jod-131 (radiojod) ili kirurški zahvat. Obje metode liječenja imaju prednosti i nedostatke, a odabir uglavnom ovisi o dobi, osobnom izboru, popratnim bolestima i drugim individualnim osobinama bolesnika, ali i dostupnosti pojedine metode liječenja. Radiojodna terapija je jednostavan, siguran, efikasan i ekonomičan postupak definitivnog liječenja Gravesove hipertireoze. Primjenjuje se ambulantno i može se primijeniti u bolesnika u hipertireozi. Zbog toga se u odraslih osoba s Gravesovom hipertireozom večinom preferira liječenje jodom-131, a vrlo malo bolesnika upućuje se na kirurški zahvat. Radiojod je osobito metoda izbora u starijih bolesnika i kardiopata u kojih je indiciran odmah nakon postizanja eutireoze tireostaticima. Kirurški zahvat uglavnom je indiciran u mla|ih bolesnika, u slučaju individualnog izbora ili u osebnim indikacijama. Jasne indikacije za operativno liječenje Gravesove hipertireoze su: suspektni ili dokazani malignitet, koegzistiraju}a patologija koja zahtijeva kirurški zahvat, trudnoća ili dojenje, velika guša (te`a od 80 grama) ili guša sa simptomima i znakovima kompresije, te{ke toksi~ne nuspojave na tireostatike, potreba brze kontrole bolesti, dob do 5 godina i aktivna oftalmopatija. Rizik od kirurškog liječenja obrnuto je proporcionalan s iskustvom operatera, a danas se preferira gotovo totalna odnosno totalna tireoidektomija. Konačni ishod obaju oblika liječenja često je hipotireoza koju ne treba smatrati posljedicom liječenja jer se nadomjesnom terapijom hormonima štitnjače postiže hormonski ekvilibrij.The most common etiologic cause of thyrotoxicosis in children and adults is autoimmune Graves’ (Basedow’s) disease. Anti thyroid medications, surgery and radioactive iodine have been used in the treatment of Graves’ hyperthyroidism for more than six decades. The use of antithyroid drugs is the most common therapeutic approach. However, long-term remission with antithyroid drugs can be expected in 20–50% of adults and 20–30% of children. The methods for definitive treatment of Graves’ hyperthyroidism are iodine-131 (radioiodine) and surgery. Both treatment modalities have benefits and risks and the decision is made according to the age, patient preference and the presence of other co-morbidities, individual characteristics of patients and the availability of certain treatment modality. Radioiodine is simple, safe, effective and economic procedure for definitive treatment of Graves’ hyperthyroidism. It is administered ambulatory and can be given to the patient in thyrotoxicosis. Due to many benefits, radioiodine is preferred in most of the adult patients with Graves’ hyperthyroidism while only small proportion of patients is sent to surgery. Radioidine is especially the treatment of choice in elderly patients and patients with heart disease. In these patients radioiodine is indicated immediately after reaching euthyroidism with antithyroid drugs. Surgery is mainly indicated in younger patients, in the case of patient preference or in special indications. Clear indications for surgical treatment of Graves’ hyperthyroidism are: suspected or confirmed malignancy, coexisting pathology that demands surgical treatment, pregnancy and breastfeeding, large goiter (> 80 grams) or goiter with symptoms and signs of compression, severe toxic side effects of antithyroid medications, requirement for immediate control of disease, age younger than 5 years and active ophtalmopathy. The risk of surgical treatment is negatively correlated with the surgeon’s experience and nowadays, total or near-total thyroidectomy is preferred surgical approach. End point of both treatment modalities is usually hypothyroidism that should not be considered as the consequence of treatment. Moreover, due to thyroid hormones replacement therapy equilibrium can be easily achieved

Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics

Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.Skoltech CenterNational Institutes of Health (U.S.) (Grant R01-NS088538)National Institutes of Health (U.S.) (Grant MH104610