Gingival Papillomatosis as the Oral Sign of Cowden Syndrome: A Case Report

Cowden syndrome (CS) is a rare autosomal dominant, hereditary, multiorgan disease with higher risk for malignancies (breast, thyroid, endometrium). Mucocutaneous lesions occur in 90% of cases and are characterized by facial trichilemmomas, oral mucosal papillomas, and benign acral keratoses. We present the case of a 39-year-old female patient with the chief complaint of “white spots” on the upper and lower attached gingiva accompanied with skin changes on the face, hands, and soles. The patient’s family medical history revealed that her mother had an endometrial polyp and the sister had thyroid cancer. In the patient’s medical personal history she reported follicular thyroid adenoma, thyroid abnormalities (i.e. lymphocytic thyroiditis), fibrocystic changes and juvenile breast papillomatosis, lipoma, multiple fibromas, and genitourinary tumors. Based on extensive family and personal medical history, physical examination and histopathological findings, diagnostic criteria were fulfilled for the diagnosis of Cowden syndrome

Giant Perianal Angiomyofibroblastoma – A Case Report

A 45-year old female had a long history of slow growing perianal tumor at the right side of her anus. Encapsulated tumour was found intraoperatively and completely excised using the Harmonic Scalpel. Tumour was well-circumscribed and relatively firm; measuring 12x6x4 cm. Histologically it was composed of oval to spindle cells with minimal nuclear atypia, set in mucous matrix with numerous thin-walled blood vessels. Immunohistochemically, expression of smooth- -muscle actin and desmin, as well as estrogen and progesterone receptor were found in the tumour cells. The diagnosis of angiomyofibroblastoma was established. This rare benign tumour typically involves vulvovaginal, pelvic and perinal region. It is important to separate this neoplasm from locally invasive aggressive angiomyxoma and low grade fibromyxoid sarcoma, which can arise in the the same localisation. The patient was discharged on the third postoperative day and no recurrence was noted in 18 months follow-up

ANALIZA OPĆEG PREŽIVLJENJA BOLESNIKA S KARCINOMOM PLUĆA PRIJE UVOĐENJA INHIBITORA TIROZIN KINAZE I IMUNOTERAPIJE U REPUBLICI HRVATSKOJ – STUDIJA IZ JEDNE USTANOVE

We analyzed outcome in patients with lung cancer (LC) in the period before the introduction of tyrosine kinase inhibitors and immunotherapy in the Republic of Croatia in comparison to similar studies abroad and created a basis for future analysis. At the Pathology Department, Split University Hospital Center, 1165 patients were diagnosed with LC during the 2012-2016 period. Data on age, gender, biopsy specimen, histologic type, and stage of disease were collected. Overall survival of each patient was calculated from the date of biopsy until death or the last day of follow-up.There were 74% of male and 26% of female patients. Median age was 66 years, younger than in other similar studies. In 78% of patients, the diagnosis of LC was based on brochoscopic biopsy. Adenocarcinoma (ADC) was diagnosed in 42.9%, squamous cell carcinoma (SCC) in 32.7%, and small cell lung carcinoma (SCLC) in 16.7% of cases. In females, ADC was more common than SCC (p<0.001). The mean survival was 22.3 months, median 10 months, and 5-year survival rate was 16.5%. Patients older than 74 years had shorter mean survival compared to younger patients, with the risk of death 1.1 times higher for each increasing age range group (p<0.001). The risk of death was 1.34 times higher in males than females (p<0.001), and 1.12 times higher for SCLC than ADC/SC (p=0.005). Gender, age, and histologic type were confi rmed as independent prognostic factors. Women lived on average 8 months longer than men (28 vs. 20.4 months). The 5-year survival rate of 16.5% in the Split-Dalmatia County was better than the one recorded at the national level (10%).Analizirali smo ishod ispitanika s karcinomom pluća u razdoblju prije uvođenja inhibitora tirozin kinaze i imunoterapije u Republici Hrvatskoj, rezultate usporedili sa sličnim studijama i stvorili osnovu za buduće analize. Na Odjelu za patologiju KBC-a Split od 2012. do 2016. godine karcinom pluća je dijagnosticiran u 1165 bolesnika. Prikupljeni su podatci o dobi, spolu, bioptičkom uzorku, histološkom tipu karcinoma i stadiju bolesti. Ukupno preživljenje za svakog bolesnika izračunato je od datuma biopsije do datuma smrti, odnosno posljednjeg dana praćenja. Sedamdesetčetiri posto ispitanika bili su muškarci, a 26 % žene, medijan dobi 66 godina (manji nego u sličnim studijama). U 78 % slučajeva dijagnoza je postavljena bronhoskopskom biopsijom. Adenokarcinom (ADC) je dijagnosticiran u 42,9 %, skvamozni karcinom (SCC) u 32,7 % i karcinom malih stanica (SCLC) u 16,7 % slučajeva. U žena je ADC bio češći od SCC (p<0,001). Prosječno preživljenje bilo je 22,3 mjeseca, medijan 10 mjeseci, a stopa petogodišnjeg preživljenja 16,5%. Bolesnici u skupini starijih od 74 godine imali su kraće prosječno preživljavanje u odnosu na mlađe skupine, s rizikom smrti 1,1 puta većim za svaku višu dobnu skupinu (p<0,001). Rizik smrti bio je 1,34 puta veći za muškarce nego za žene (p<0,001), a 1,12 puta veći za SCLC od ADC/SC (p=0,005). Spol, dob i histološki tip karcinoma potvrđeni su kao neovisni prognostički čimbenici. Žene su u prosjeku živjele 8 mjeseci duže od muškaraca, 28 naspram 20,4 mjeseca. Petogodišnja stopa preživljenja od 16,5 % u našoj kohorti bila je bolja nego na nacionalnoj razini, 10 %

KLINIČKI I PATOFIZIOLOŠKI PRIKAZ BOLESNIKA S OROFARINGEALNIM RAKOM PLOČASTIH STANICA POZITIVNIH NA HUMANI PAPILOMAVIRUS – ISTRAŽIVANJE U JUŽNOJ HRVATSKOJ

Objective: The objective of this study was to analyze the influence of human papilloma virus (HPV) in patients with oropharyngeal squamous cell carcinoma (OPSCC) from southern Croatia on survival, clinical outcomes, and pathological features. Methods: We analyzed HPV DNA presence and p16 immunohistochemistry staining in 68 formalin-fixed paraffin-embedded samples from patients diagnosed with OPSCC at the Split University Hospital Center between 2013 and 2017. Histologic features were analyzed using a light microscope. Clinical data were retrospectively collected from patient records and analyzed for HPV status. Results: In this study, 10.29% of patients were HPV positive (HPV+). Lymphocyte invasion was more prominent in p16 positive OPSCC. Overall survival (OS) was better in HPV+ and p16+ patients. HPV status is a significant prognostic variable for patients from south Croatia with OPSCC. Conclusion: HPV seems to have a minor influence on OPSCC in south Croatia in comparison to other Western European countries and the USA. Although the influence of HPV on survival was significant, traditional risk factors were more important in the carcinogenesis of OPSCC in our population.Cilj: Svrha ovog istraživanja bila e analizirati utjecaj humanog papilomavirusa (HPV) na preživljavanje, kliničke pokazatelje i patohistološke značajke u ispitanika oboljelih od orofaringealnog raka pločastih stanica (OPSCC) u južnoj Hrvatskoj. Metode: Istražili smo prisutnost HPV DNK i imunohistokemijsko bojanje na p16 u 68 u parafinske blokove uklopljenih uzoraka tkiva ispitanika oboljelih od OPSCC-a i liječenih u Kliničkom bolničkom centru Split u razdoblju od 2013. do 2017. godine. Svjetlosnim mikroskopom utvrđene su histološke značajke tkiva. Retrospektivno smo prikupili kliničke podatke ispitanika i proučili ih s obzirom na HPV status. Rezultati: U ovom je istraživanju 10,29% pacijenata pozitivno na HPV (HPV+). Invazija limfocita značajnija je u ispitanika s p16 pozitivnim (p16+) OPSCC-om. Ukupno preživljavanje (OS) bolje je u HPV+ i p16+ ispitanika. HPV je značajan prognostički čimbenik u ispitanika koji boluju od OPSCC-a iz južne Hrvatske. Zaključak: Čini se da je HPV manje utjecajan uzročni čimbenik nastanka OPSCC-a u južnoj Hrvatskoj u usporedbi sa zapadnoeuropskim zemljama i SAD-om. Iako je HPV značajan čimbenik preživljavanja, tradicionalni čimbenici rizika pokazali su se važnijim karcinogenima za nastanak OPSCC-a u našoj populaciji

C1Q NEPHROPATHY: CASE REPORTS AND LITERATURE REVIEW

C1q-nefropatija oblik je glomerulonefritisa definiran dominantnim nalazom C1q-imunosnih depozita u glomerulima. Bolest je rijetka. Najčešće se javlja u djece i mlađih odraslih. Klinički se najčešće očituje nefrotskim sindromom premda su opisani i drugi klinički sindromi kojima se ova bolest može manifestirati. Etiologija bolesti nije poznata, a patogeneza je najvjerojatnije imunosne prirode. Bolest je često rezistentna na glukokortikoide i druge imunosupresive i tada obično uzrokuje kronično zatajenje bubrega. U ovom radu prikazano je deset bolesnika s C1q-nefropatijom koja je potvrđena karakterističnim histološkim promjenama u tkivu bubrega koje je dobiveno biopsijom. Nijedan bolesnik nije imao kliničkih ni laboratorijskih nalaza karakterističnih za sistemski eritemski lupus. U svih su bolesnika komponente komplementa C3 i C4, kao i nalaz ANA, anti-dsDNA te ANCA-protutijela bili uredni.C1q nephropathy is considered a form of glomerulonephritis, defined by histological findings of dominant C1q immune deposits in renal biopsy. It is a rare disease, most often manifested in children and young adults. The most common clinical manifestation of the disease is nephrotic syndrome, but other renal syndromes could also be found. The cause of the disease is not known, but the immune pathogenesis could be assumed. Often, resistance to glucocorticoid or other immunosuppressive therapy is present, potentially leading to chronic renal insufficiency. We present ten patients with renal biopsy and clinical findings of C1q nephropathy. None of the patients had clinical or serological manifestations of systemic lupus. All patients had normal findings of C3 and C4 components of complement, as well as normal ANF, anti-dsDNA and ANCA antibodie

C1Q NEPHROPATHY: CASE REPORTS AND LITERATURE REVIEW

C1q-nefropatija oblik je glomerulonefritisa definiran dominantnim nalazom C1q-imunosnih depozita u glomerulima. Bolest je rijetka. Najčešće se javlja u djece i mlađih odraslih. Klinički se najčešće očituje nefrotskim sindromom premda su opisani i drugi klinički sindromi kojima se ova bolest može manifestirati. Etiologija bolesti nije poznata, a patogeneza je najvjerojatnije imunosne prirode. Bolest je često rezistentna na glukokortikoide i druge imunosupresive i tada obično uzrokuje kronično zatajenje bubrega. U ovom radu prikazano je deset bolesnika s C1q-nefropatijom koja je potvrđena karakterističnim histološkim promjenama u tkivu bubrega koje je dobiveno biopsijom. Nijedan bolesnik nije imao kliničkih ni laboratorijskih nalaza karakterističnih za sistemski eritemski lupus. U svih su bolesnika komponente komplementa C3 i C4, kao i nalaz ANA, anti-dsDNA te ANCA-protutijela bili uredni.C1q nephropathy is considered a form of glomerulonephritis, defined by histological findings of dominant C1q immune deposits in renal biopsy. It is a rare disease, most often manifested in children and young adults. The most common clinical manifestation of the disease is nephrotic syndrome, but other renal syndromes could also be found. The cause of the disease is not known, but the immune pathogenesis could be assumed. Often, resistance to glucocorticoid or other immunosuppressive therapy is present, potentially leading to chronic renal insufficiency. We present ten patients with renal biopsy and clinical findings of C1q nephropathy. None of the patients had clinical or serological manifestations of systemic lupus. All patients had normal findings of C3 and C4 components of complement, as well as normal ANF, anti-dsDNA and ANCA antibodie

C1q-nefropatija: prikazi bolesnika i pregled literature [C1q nephropathy: case reports and literature review]

C1q nephropathy is considered a form of glomerulonephritis, defined by histological findings of dominant Clq immune deposits in renal biopsy. It is a rare disease, most often manifested in children and young adults. The most common clinical manifestation of the disease is nephrotic syndrome, but other renal syndromes could also be found. The cause of the disease is not known, but the immune pathogenesis could be assumed. Often, resistance to glucocorticoid or other immunosuppressive therapy is present, potentially leading to chronic renal insufficiency. We present ten patients with renal biopsy and clinical findings of Clq nephropathy. None of the patients had clinical or serological manifestations of systemic lupus. All patients had normal findings of C3 and C4 components of complement, as well as normal ANF, anti-dsD-NA and ANCA antibodies

EPIDEMIOLOŠKI PODATCI BUBREŽNIH BIOPSIJA U JUŽNOJ HRVATSKOJ – IZVJEŠTAJ O 22-GODIŠNJEM ISKUSTVU KBC-A SPLIT

The Croatian Registry of Native Renal Biopsy (CRNRB) was established in 2019. Thus, in this study, we present retrospective data on kidney biopsies in adult patients performed at the Split University Hospital Center from 1994 to 2019 before the CRNRB establishment. The aim of the study was to show epidemiological data on glomerular diseases in southern Croatia in order to compare them with others and provide data for the establishment of the CRNRB. During the study period, 110 patients (mean age 46.6±15.4, age range 17-76 years), 68 men and 42 women, underwent renal biopsy at the Department of Internal Medicine, Split University Hospital Center in Split. Data on age, sex, serum creatinine, urinalysis, daily proteinuria, and complications after biopsy were collected and related to indication for biopsy and pathological diagnosis. Light and immunofluorescence analysis was supplemented by electron microscopy in 63.5% of cases. Indications for biopsy were nephrotic syndrome (64.5%), asymptomatic urinary tract abnormalities (12.7%), and acute renal failure of unknown cause (9.1%). The most common diagnosis was IgA nephropathy (IgAN) (20.9%), the prevalence of which decreased during the study period. IgAN was followed by focal segmental glomerulosclerosis (FSGS) (19.1%), membranous nephropathy (13.6%), lupus nephritis and minimal change disease (8.2%), crescentic glomerulonephritis (5.4%), embranoproliferative glomerulonephritis (4.5%), mesangial proliferative glomerulonephritis (3.6%), amyloidosis (3.6%), Henoch-Schönlein nephritis (3.6%), and Alport syndrome (2.7%). Other forms of glomerular diseases were rarely found. IgAN was most frequently found in men (26.5%) and FSGS in women (21.4%). These data can be included in the historical epidemiological observation of glomerular diseases in Southeastern Europe. The guidelines for performing biopsies need to be constantly updated to improve preventive and therapeutic strategies.Hrvatski registar nativne bubrežne biopsije (CRNRB) uspostavljen je 2019. godine. Stoga u ovom istraživanju prikazujemo retrospektivne podatke biopsija bubrega odraslih bolesnika KBC-a Split obavljenih od 1994. do 2019. godine prije uspostave CRNRB-a. Cilj rada bio je prikazati epidemiološke podatke o glomerularnim bolestima u južnoj Hrvatskoj radi usporedbe s drugima i dobivanja podataka za uspostavu CRNRB-a. U promatranom razdoblju 110 bolesnika (raspon dobi 17-76 godina, srednja dob 46,6±15,4 godina), 68 muškaraca i 42 žene, bilo je podvrgnuto biopsiji bubrega na Klinici za unutarnje bolesti KBC-a Split. Podatci o dobi, spolu, kreatininu u serumu, analizi mokraće, dnevnoj proteinuriji i komplikacijama nakon biopsije prikupljeni su i povezani s indikacijom za biopsiju i patološkom dijagnozom. Analiza svjetlosnom mikroskopijom i imunofluorescencijom dopunjena je elektronskom mikroskopijom u 63,5 % slučajeva. Indikacije za biopsiju bile su nefrotski sindrom (64,5 %), asimptomatske abnormalnosti mokraćnog sustava (12,7 %) i akutno zatajenje bubrega nepoznatog uzroka (9,1 %). Najčešća dijagnoza bila je IgA nefropatija (IgAN) (20,9 %), učestalost koje se smanjila tijekom promatranog razdoblja. Nakon IgAN-a slijede žarišna segmentna glomeruloskleroza (FSGS) (19,1 %), membranska nefropatija (13,6 %), lupusni nefritis i bolest minimalnih promjena (8,2 %), polumjesečasti glomerulonefritis (5,4 %), membranoproliferativni glomerulonefritis (4,5 %), mezangijski proliferativni glomerulonefritis (3,6 %), amiloidoza (3,6 %), Henoch-Schönleinov nefritis (3,6 %) i Alportov sindrom (2,7 %). Drugi oblici glomerularnih bolesti rijetko su nađeni. IgAN je najčešće nađen u muškaraca (26,5 %), a FSGS u žena (21,4 %). Ti se podatci mogu uključiti u povijesno epidemiološko promatranje glomerularnih bolesti u jugoistočnoj Europi. Smjernice za izvođenje biopsije bubrega potrebno je stalno ažurirati kako bi se poboljšale preventivne i terapijske strategije

Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 – 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients

Henoch-Schönlein purpura nephritis in children: experience of the two tertiary care centers for pediatric and adolescent rheumatology of the Republic of Croatia from 2006 to 2017

Cilj istraživanja: Valjalo je utvrditi vrste bubrežnih komplikacija, indikacije za biopsiju, načine liječenja te moguće ishode u bolesnika s Henoch-Schönleinovim purpurnim nefritisom (HSPN). Ispitanici i metode: Retrospektivna analiza podataka bolesnika s Henoch Schönleinovom purpurom (HSP) liječenih u Klinikama za pedijatriju Kliničkoga bolničkog centra Zagreb i Kliničkoga bolničkog centra Split, u razdoblju od 2006. do 2017. godine, u kojih se razvila bubrežna bolest prema kriterijima EULAR/PRINTO/PRES-a. Rezultati: Od 378 bolesnika s HSP-om u 81 (21,4%) razvila se bubrežna bolest, u 43 dječaka (53,1%) i 38 djevojčica (46,9%), s medijanom dobi 8,4 godine (2,5 – 16,8). Uočen je statistički značajan porast broja bolesnika s HSP-om tijekom jeseni i zime. Dob bolesnika pri dijagnozi pokazala se kao mogući prognostički čimbenik bubrežne bolesti. S povišenjem dobi bolesnika veći su izgledi za razvoj bubrežne bolesti, pri čemu se u dobi od 1 do 17 godina sa svakom godinom vjerojatnost razvoja nefritisa povećava u prosjeku oko 2,25%. Jednak broj bolesnika imao je istodobno hematuriju i proteinuriju (44,45%) te izoliranu hematuriju (44,45%), a njih samo 11,1% izoliranu proteinuriju. Biopsija bubrega obavljena je u 37 bolesnika (45,7%), a najviše bioptiranih bolesnika bilo je iz skupine s istodobnom hematurijom i proteinurijom (70,3%). Djeca s izoliranom hematurijom odnosno s izoliranom proteinurijom najčešće su liječena glukokortikoidima, dok su djeca s istodobnom hematurijom i proteinurijom najčešće liječena glukokortikoidima i inhibitorima enzima koji konvertira angiotenzin. Imunosupresivnim lijekovima liječeno je ukupno 16% bolesnika, među kojima je najviše onih iz skupine s istodobnom hematurijom i proteinurijom (69,2%). Samo se u jednog bolesnika (1,2%) razvilo bubrežno zatajenje uz potrebu za primjenom dijalize, dok je ishod ostalih ocijenjen kao dobar. Zaključak: Najvažniji čimbenik konačnog ishoda bolesnika s HSP-om jesu bubrežne komplikacije. Da bi se ovi bolesnici mogli optimalno liječiti, potrebno je donijeti konsenzus o indikacijama za biopsiju bubrega u HSPN-u te validirati postojeće patohistološke klasifikacije radi utvrđivanja koja od njih najbolje korelira s nepovoljnim ishodom bolesti.Aim: To determine types of renal complications, indications for biopsy, treatment methods and possible outcomes in patients with Henoch-Schönlein purpura nephritis. Patients and methods: Retrospective analysis of medical data of HSP patients treated at the Department of Paediatrics, University Hospital Centre Zagreb, and the Department of Paediatrics, University Hospital Centre Split, during the period from 2006 to 2017, who developed kidney disease according to EULAR/PRINTO/PRES criteria. Results: Out of 378 patients diagnosed with HSP, 81 (21.4%) developed kidney disease, out of whom 43 boys (53.1%) and 38 girls (46.9%), with the median age 8.4 years (2.5 16.8).. A statistically significant increase of patients with HSP was during autumn and winter. There is a greater chance of nephritis with the increase of patients age at diagnosis. For every year (from 1 to 17 years) the chances increase by around 2.25%. Equal number of patients, 44.45%, had both hematuria and proteinuria or isolated hematuria, and only 11.1% isolated proteinuria. Renal biopsy was performed in 37 patients (45.7%), and most biopted patients were from concurrent hematuria and proteinuria group (70.3%). Children with isolated hematuria or with isolated proteinuria were most often treated with corticosteroids while children with hematuria and proteinuria were most often treated with corticosteroids and angiotensin- -converting enzyme inhibitors. Immunosuppressives were used in 16% of the patients, including most of those in the group with concurrent hematuria and proteinuria (69.2%). Only one patient (1.2%) developed renal insufficiency with the need for dialysis, while the outcome of the others was evaluated as good. Conclusion: Renal complications are the most important factor in the outcome of patients with HSP. For the optimal treatment of these patients it is necessary to bring consensus about the indications for kidney biopsy in HSP, and also to validate the existing pathohistological classification to affirm which one best correlates with the adverse outcome of the disease