Vuka Katic

Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia.

Background:  The association between celiac disease (CD) and type 1 diabetes mellitus (T1DM) is well known. Up to now, CD prevalence in children and adolescents with T1DM in Serbia has not been reported. The aim of the present study was to determine CD prevalence and its clinical manifestations in patients with T1DM.

Primary colorectal lymphomas

BACKGROUND/AIM Colorectal lymphoma is a rare tumor representing 1.4% of human lymphomas, 10-20% of gastrointestinal lymphomas, namely 0.2-0.6% of all malignancies in the colon. The aim of this study was to review clinical characteristics of primary colorectal lymphoma and overall survival. METHODS A detailed analysis of 16 surgically treated patients included patients age, symptoms and signs, tumor site, type of surgery, histopathologic findings, diagnosis of the disease, disease stage, type of surgery related to the degreee of emergency (elective or urgent), applied adjuvant therapy, patient follow-up and treatment outcomes. Survival was expressed by the Kaplan-Meier curve, while the difference in survival among the two groups by the Log-rank test. RESULTS The all patients were on an average followed-up for a median of 29 months (range 2-60 months), while those with chemotherapy 48 months (range 4-60 months). An overall mean survival time was 38.65 months. CONCLUSION Primary colorectal lymphoma is a rare malignant tumor of the large bowel. Therapy usually involves resection of the affected colon or rectum and regional lymphovascular structures, followed by adjuvant therapy. Survival period is short and, therefore, timely diagnosis is crucial in early disease stages when the probability of cure is high.

Celiac disease with diffuse cutaneous vitamin K-deficiency bleeding

This article describes a 4-y-old girl with spontaneous, generalized bruising, abdominal distention, and signs of malnutrition. She had been treated previously with an antibiotic for diarrhea. Laboratory analyses showed the presence of irondeficiency anemia, mild hypoalbuminemia, and considerably prolonged prothrombin time and activated thromboplastin time. Tests revealed that hemostasis improved after the patient received fresh frozen plasma. A coagulation profile showed a decrease in clotting factors II, VII, IX, and X. The patient was given intravenous vitamin K therapy (5 mg/d) for 3 d. All coagulation tests were normalized, and bruising started to disappear. Positive serology (immunoglobulin A antitissue transglutaminase and immunoglobulin A antiendomysial antibodies) and smallbowel mucosal histopathology confirmed the presence of celiac disease (CD). The girl recovered completely after she was put on a gluten-free diet. Vitamin K-deficiency bleeding is a rare complication that occurs almost exclusively in patients with typical CD manifestations. In addition to antibiotic therapy, treatment with other drugs that influence vitamin K resorption and metabolism may increase the risk of bleeding in patients with CD with hypoprothrombinemia.

An approach to malignant mammary phyllodes tumors detection.

BACKGROUND/AIM Mammary phyllodes tumors (MPT) are uncommon fibroepithelial (biphasic) neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH) together with the mast cell analysis. METHODS We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman). The used methods were classical hematoxylin-eosin (H & E); histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation). Ki-67, c-kit, vimentin, estrogen receptor (ER), progesterone receptor (PR) and Her-2 oncoprotein immunohistochemistry was performed on all tumors. RESULTS The patients were ranged per age from 30--62 years (mean 43.3 years, median 39 years). A total of 35 cases of MPT were included: 20 benign (57%), 6 borderline malignant (17%) and 9 malignant (26%). Twenty-two patients (62.8%) underwent segmental mastectomy, while 13 (37.2%) had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm) was larger than that of benign MPT (4.5 cm). Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical Leucine Amino Peptidase (LAP) activity in both epithelial and stromal components while it was weak or absent in the epithelial parts of the malignant tumors. Acid mucopolysacharides were present in the stromal component of all types of these tumors. Benign MPT had a lower Ki-67 than did borderline malignant MPT (4 versus 28). Malignant MPT had a greater than 8-fold higher Ki-67 activity than did benign tumors (35 versus 4). Intracyto-plasmatic c-kit expression was associated with a pathological diagnosis of malignant MPT, correlating with increasing grade (p < 0.05). In hypercellular stroma of borderline malignant and especially malignant forms of MPT, high activity of ER in mast cells was confirmed. Oncoprotein Her-2 activity, mostly in epithelial components, correlated with the degree of malignant progression of MPT (p < 0.05). CONCLUSION Besides the well-known malignant features additional parameters have been found to be high Ki-67 and c-kit stromal expressions, and weak LAP activity in the epithelial part of malignant MPT, as well as mast cells with a high expression of ER.

Histological, mucinohistochemical and immunohistochemical features of gastric signet ring cell carcinoma.

Gastric cancer is the fourth most common cancer and the second cause of cancer-related death worldwide . Various types of gastric cancers differ in their epidemiology, pathogenesis, genetic profile and clinical outcome . There has been the overall decline in the total incidence of gastric cancer in the last few decades worldwide, but the decline of signet ring cell (SRC) type of gastric carcinoma has been more gradual and some studies have even reported an increase of SRC type carcinoma . As a result, there are different data about incidence of SRC carcinoma it has been reported that 3.4 – 29% of patients with gastric cancer had SRC type histology and the newest data say that SRC carcinoma accounts for more than 30% of gastric carcinomas in some reported series . Comparing with other types of gastric cancer, SRC gastric carcinoma has a tendency to involve the entire stomach and to extend directly into neighboring organs. It has the poorest prognosis, is more common in females than males and occurs at a comparatively younger age . Although most researchers believe that SRC carcinoma is characterized by poor differentiation, strong invasive tendency and poor prognosis, the clinicopathologic parameters of this type of malignancy are still controversial . Controversial reported data on gastric SRC cancer incidence, prognosis, histogenesis, metastasis, phenotipic histologic and immunohistochemical features, and confusion induced by the presence of morphologic patterns other than the conventional appearance, are the facts that require further investigations . Classifications of gastric carcinoma

MALT lymphoma of the parotid salivary gland

BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma was described for the first time in 1983 by Isaacson and Wright. It was classified into extranodal non-Hodkins lymphomas of B-cell lymphocytes of the marginal zone of reactive lymphe follicles. It is characterized by both hyperplasia and colonization of plasmocytic, centrocytoid and monocytoid cells, by the infiltration of interfollicular and parafollicular parts of interstitium, as well as by the invasion of clusters of neoplastic lymphoid cells of the glandular epithelium, forming the pathognomic lymphoepithelial MALT limphoma lesions. CASE REPORT In this paper we presented the two female patients, 59 and 75 years of age, with MALT lymphomas, associated with Miculiczs and Sjögrens syndromes. The paper also underlined rather many-month-long, indolent clinical course, evalution of both tumors, massive in size, as well as two-sided localization in the case of the Miculiczs syndrome. After the subtotal parotidectomy, using conservation of nerve facialis, the tissue blocks were fixed in 10% formaldehyde. The paraffine sections were stained by routine histochemical and an immunohistochemical method by using monoclonal antibodies for both B-cell and T-cell lymphomas, due to the verification of lymphoepithelial lesions. The MALT lymphoma diagnosis was based on the histological criteria and confirmed by an immunohistochemical method. After the surgical therapy accompanied by chemotherapy, the patients were controlled at regular intervals, and residual MALT lymphoma did not appear. CONCLUSION MALT lymphoma is a rare tumor of the salivary glands, with the most frequent localization in the parotide gland. It had a slow clinical course, without metastases in both patients. The diagnosis was made pathohistologically and confirmed immunohistochemically. The surgical therapy was accompained by adjuvant chemotherapy.

Intracystic Papillary Carcinoma in a Male Breast: Thirty Years after Orchiectomy

Summary Papillary carcinoma of the breast is an extremely rare form of breast carcinoma in males. We report a case of an 83-year-old man who presented with a retroareolar palpable mass, associated with bloody nipple discharge. Cytological characteristics were rare clusters and papillary formations with enlarged hyperchromatic nuclei, surrounded by erythrocytes. Having in mind that a reliable cytological diagnosis of papillary carcinoma cannot be made and that all papillary lesions observed in cytological material should be excised for histological examination, breast conserving surgery (BCS) was performed. Histologically, cystic ducts were lined with atypical papillary formations bridging the duct lumen, but with the absence of both myoepithelial cells and stromal invasion. Prolactin and testosterone serum levels were decreased. Immunohistochemical examination on actin, estrogen and progesteron receptors was negative. The authors have pointed out that the patient had left orchiectomy, induced by tuberculous orchiepididymitis with scrotal fistula, performed thirty years before. Twelve months after breast conserving surgery, the patient is still alive.

A Thirty-Seven-Year Follow-Up of Peutz–Jeghers Syndrome across Three Generations / Tridesetsedmogodišnje praćenje Pojc-Jegersovog sindroma kroz tri generacije

Abstract Peutz-Jeghers syndrome (PJS) is a rare genetic disorder with autosomal-dominant pleiotropic inheritance, variable penetrance and characteristic signs of the disease that predisposes persons to increased risk of developing cancer, particularly in the gastrointestinal tract and the breast. Due to genetic nature of disease, in the familial Peutz-Jeghers syndrome, a multiplication of symptoms in the three-generation family members was established. This paper represents an insight into the anamnesis of PJS in one family over thirty-seven years of follow-up, and is part of the broader study of this disorder. Article presents family history, clinical and histological findings and multiplication of symptoms of PJS across three generations. Over thirty-seven years, PJS has been present in this family in the form of only mucocutaneous pigmentation but without clinically manifested signs (father), or with both melanine hyperpigmentation and gastrointestinal hamartomatous polyposis (his daughter and her son). The symptoms rose suspicion of the existence of PJS complication, i.e. carcinoid-like syndrome with watery diarrheas accompanied by constipations in the affected mother and son who were surgically treated. Diagnosis of PJS was histopathologically confirmed in both cases: the presence of the polyps with hamartomatous pattern and conspicuous hyperplasia of chromogranin-positive (EC and L cells) and serotoninpositive (EC) cells. Malignant transformation of PJ- removed polyps was not found. Besides hamartoma, polyps as well as a tubular adenoma were found, with a low degree dysplasia without malignant transformation (son). The authors discuss the findings in relation to the important role of the gastrointestinal endocrine cell hyperplasia, not only for better understanding of the growth and clinical symptoms of the PJ polyposis, but also for new approach and the possible application of anti-hormonal therapy in the treatment of these patients in the future, that is not currently in use. Sažetak Pojc-Jegersov (Peutz-Jeghers) sindrom (PJS) je redak genetski poremećaj sa autozomno-dominantnim plejotropnim nasleđivanjem, promenljivom penetrantnošću i karakterističnim znacima bolesti, koji predisponira obolele na povećani rizik od dobijanja karcinoma, naročito organa gastrointestinalnog trakta i dojke. Kod postojanja familijarnog PJS-a je zbog genetske prirode bolesti utvrđena multiplikacija simptoma kod članova porodice iz različitih generacija. U radu je prezentovana porodična istorija, umnožavanje simptoma PJS-a, kliničke manifestacije i patohistološki nalaz bolesti kod obolelih članova porodice iz tri generacije. Tokom 37 godina praćenja nađeni su različiti simptomi prisustva PJS-a, od samo mukokutanih pigmentacija, ali bez kliničkih manifestacija bolesti (otac), i sa melaninskom hiperpigmentacijom i hamartomatoznom gastrointestinalnom polipozom (njegova ćerka i njen sin). Klinički znaci suspektni na postojanje komplikacija PJS-a, tj karcinoidni sindrom sa vodenim dijarejama, praćenim opstipacijama kod obolelih, majke i sina, hirurški su i patohistološki potvrđeni. Nađeno je prisustvo polipa sa hamartomskom strukturom i utvrđena hiperplazija hromogranin-pozitivnih (EC i L) i serotonin pozitivnih (EC) ćelija. Osim hamartomskih polipa nađen je i jedan tubularni adenom sa niskim stepenom displazije bez maligne transformacije. Autori naglasavaju važnu ulogu hiperplazije endokrinih ćelija gastrointestinalnog trakta, ne samo sa aspekta boljeg razumevanje pojave kliničkih simptoma i rasta PJ polipa, nego i zbog moguće primene anti - hormonske terapije ovih pacijenata u budućnosti.

Intestinal and extraintestinal manifestations in familial adenomatous polyposis

U radu su opisane intestinalne i ekstraintestinalne manifestacije familijarne adenomatozne polipoze koje mogu imati dijagnosticki i prognosticki znacaj. Pojava tumora izvan kolona znacajna je za razvoj ozbiljnih simptoma bolesti (opstrukcija, krvarenje), ali i za malignu alteraciju i razvoj karcinoma, posebno u duodenumu (karcinom duodenuma i dezmoidni tumori su najcesci uzrok smrti kod bolesnika sa familijarnom adenomatoznom polipozom nakon kolekotmije). Poseban znacaj imaju dezmoidni tumori, koji su benigni po svojoj prirodi, ali koji lokalnom invazijom mogu dovesti do smrtnog ishoda, a najcesce ispoljavaju tendenciju rasta nakon hirurske resekcije creva. Kongenitalna hipertrofija pigmentnog epitela retine je prediktivni marker koji omogucava postavljanje dijagnoze familijarne adenomatozne polipoze i pre otkrivanja adenoma debelog creva.

Morphological markers of secretory activity in prostatic adenocarcinoma

BACKGROUND/AIM The vast majority of prostatic tumors developing in adult males are adenocarcinomas (ACP). Histological diagnosis of prostate cancer relies on the infiltrative growth pattern, presence of macronucleoli, and absence of basal cell layer. In the last few years a special attention has been focused on investigation of cancerous glands lumen content. The aim of the study was to determine the presence of intraluminal (crystaloids, blue-tanged mucinous secretions and distension of glands) and extracellular markers of pathological secretions in ACP, as well as the type of intraluminal and extracellular mucinous secretions. METHODS Micromorphological and hystochemical (PAS, HID-AB pH 2.5) analysis was done in 96 patients to detemine differentiation by Gleason and markers of secretory activity. RESULTS In ACP neoplastic glands distension (53.12%), crystalloids (30.2%), basophilic secretions (26.04%) and presence of extracellular mucins (8.3%) were found. All morphological signs were detected in carcinoma of Gleason grade 1-4A. There was significant presence of crystalloids ((G1+G2)/G4 p < 0.05; G3/G4A p < 0.05), basophilic secretions (G3/G2 p < 0.05; G3/G4A p < 0.05) and extracellular mucins (G3/G4A p < 0.001). The association of these morphological features with neutral and acidic mucins secretion was statisticaly significant (p < 0.0001). CONCLUSION This study showed that intraluminal and extracellular markers of secretory activity in ACP were significantly more often associated by mixed type of mucin secretion with predominace of sialomucins.