Surgical pathology

Kirurška patologija najznačajniji je i vremenski najzahtjevniji dio prakse većine patologa. Ima za cilj dati/isključiti definitivnu dijagnozu bolesti temeljeći se na uzorcima tkiva. Dva su glavna tipa tkivnih uzoraka za patološku analizu: biopsije i kirurške resekcije. Četiri su glavna dijela kirurške patologije koji se koriste u konačnoj dijagnostici tkivnih uzoraka: makroskopski pregled, patohistološki pregled koji se temelji na svjetlosnoj mikroskopiji, imunohistokemija i molekularne/citogenetske analize. Rezultat rada patologa je patohistološko izvješće. Ono sadrži makroskopski i mikroskopski opis lezije, dijagnozu ili diferencijalnu dijagnozu. Postoje situacije kada je potrebno dijagnozu postaviti za vrijeme kirurškog zahvata, dok je pacijent pod anestezijom. Tada se koristi hitna ili intraoperacijska biopsija, na smrznutim tkivnim rezovima. Hitna ili intraoperacijska biopsija je hitno stanje u patologiji koje zahtijeva dobru suradnju između kirurga i patologa te iskusnog i dobro educiranog patologa koji je svjestan mogućnosti, ali i ograničenja hitne biopsije. Resekcijski rubovi su rubovi ili površine koje je napravio kirurg. Udaljenost između tumora i resekcijskog ruba naziva se kirurški rub. Kirurški rubovi izuzetno su važni jer pozitivnost rubova korelira s recidivom bolesti. Definicija pozitivnog kirurškog ruba ovisi o vrsti tumora, njegovoj biologiji i lokalizaciji bolesti. Jedan od najvažnijih ciljeva kirurške patologije je dijagnostika malignih bolesti i procjena proširenosti bolesti, odnosno klasifikacija tumora, prema odrednicama Svjetske zdravstvene organizacije. Patološka klasifikacija (p) malignih bolesti označava se kao pTNM (primarni tumor – T, regionalni limfni čvorovi – N, udaljene metastaze – M). Ona se temelji na podacima dobivenim prije kirurškog liječenja uz modifikaciju proizašlu iz patohistološke analize tkiva.The most important part of pathology work is surgical pathology. Its goal is to diagnose or exclude the clinical diagnosis based on tissue samples. Two main types of tissue samples for pathohistologic analyses are biopsies and surgical resections. There are four main parts used in final diagnosis of tissue samples in surgical pathology: macroscopic exam, pathohistologic analysis, immunohistochemistry and molecular/cytogenetic analysis. The result of pathologists’ work is pathohistologic report, which contains macroscopic and microscopic description of a lesion, diagnosis or differential diagnosis. There are situations when diagnosis needs to be established during surgical procedure, while the patient is under anesthesia, so pathologist uses so called intraoperative biopsy or frozen tissue sections. This is an emergency in pathology practice and it requires good cooperation between surgeons and pathologists. The surgical margins are surfaces that were cut by the surgeon. The distance between the tumour and the margin is called surgical margin. Margins are important as an incompletely removed disease process may lead to reccurrence. What defines a positive surgical margin is dependent on the tumour and its biology; definitions of positive margin are dependent on the anatomical site. One of the most important goals of surgical pathology is diagnosis of malignant diseases and assessment of extent of disease, and not less important, tumour classification, defined by World Health Organization. Pathological classification (p) of malignant diseases (or postsurgical pathohistologic classification) is defined as pTNM (T – tumour, N – lymph node, M – distant metastasis). It is based on presurgical clinical data modified by pathohistological data analysis

Role of Bone Morphogenetic Proteins in Human Prostate Cancer Pathogenesis and Development of Bone Metastases: Immunohistochemical Study

Bone morphogenetic proteins (BMP) have the ability to induce ectopic bone formation1–10. The findings of their expression in prostate cancers have been linked with specifically tumor progression to bone and development of osteosclerotic metastases7–15. We investigated the expression pattern of BMP-2/4, -6 and -7 and the receptors BMPR-IA,-IB and -II in normal human prostate, organ-localized and metastatic prostate cancers. The expression we also examined in skeletal metastases caused by prostate cancer. In localized prostate cancers we found increased expression of BMP-6 and decreased expression of BMP-2/4 and -7. In metastatic prostate cancers the expression of examined BMPs decreased. The expression of BMPRs showed the tendency to be lower with progression of prostate cancer but the expression of BMPR-II was completely absent in metastatic prostate cancers. In bone metastases caused by prostate cancer we found high expression of BMP-2/4, -6 and -7. Decreased expression of BMPs and lose of BMPR-II expression, could suggest that the influence of BMPs on prostate cancer cells is inhibited and plays an important role in prostate cancer pathogenesis. High expression of osteogenic BMPs in prostate cancer bone metastases could explain their osteosclerotic properties

Increased Bone Turnover Markers after Renal Transplantation

Bone remodeling is a process that occurs continuously in a seemingly inactive tissue like bone. Because of decreased vitamin D synthesis, phosphorus retention and decreased calcium blood concentration, patients with chronic renal failure (CRF) develop secondary hyperparathyroidism1–5. Elevated PTH levels shifts balance between osteoblast and osteoclast activity in favor of osteoclast activity and, therefore, bone resorption. Bone metabolic disorder that affects patients with CRF is called renal osteodystrophy (ROD)1–5. We presume that renal transplantation reverses bone metabolism disorder and our goal was to establish whether osteoblast and osteoclast activity returns to the levels of healthy individuals

Bone Morphogenetic Protein-7 Expression in Human Pyelonephritis

Bone morphogenetic protein 7 (BMP-7) is a member of the transforming growth factor (TGF) beta superfamily and is involved in regeneration, repair, and development of specific tissues, for example kidney and skeleton1–5. The experimental studies have shown its protective role against fibrotic processes. Tubulointerstitial changes are present in the pyelonephritic kidney which progresses to fibrosis4–6. Renal fibrosis may lead to the loss of renal function. The aim of this study was to investigate BMP-7 expression in acute and chronic pyelonephritis in humans. Seven patients with acute pyelonephritis and 7 with chronic pyelonephritis were treated in Department of Nephrology Clinical Hospital, Rijeka. Tissue biopsy was taken and renal tissue was studied histopathologically by use of hematoxylin and eosin and scored for diagnosis of pyelonephritis. BMP-7 expression was studied by imunohistochemical staining. BMP-7 expression was observed in the tubular area of the pyelonephritic kidneys. The expression of BMP-7 was stronger in the acute pyelonephritic group and less in the chronic pyelonephritic group of patients. The results imply that BMP-7 has a role in chronic pyelonephritis. Tubular BMP-7 expression had a negative correlation with fibrosis and tubular, atrophy. Our results are suggesting that BMP-7 plays an important protective role in renal inflammatory diseases preventing greater damage and fibrosis

Expression of Matrix Metalloproteinase 9 in Primary and Recurrent Breast Carcinomas

The matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases that are secreted as inactive precursors, which are activated by cleavage of an N-terminal pro-peptide. Their basic mechanisms of action include cancer cell growth, differentiation, apoptosis, migration and invasion, and the regulation of tumour angiogenesis and immune surveillance. The expression of MMP2 and MMP9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. The 29 female patients, 9 premenopausal and 20 postmenopausal, aged from 37 to 79 years were included in this study. Tissue samples were examined in 29 primary and 48 recurrent carcinomas using the tissue microarrays which included 102 cores of primary breast carcinomas and 96 of recurrent breast carcinomas. Immunohistochemistry determined a pattern of expression for MMP9. The staining was diffuse cytoplasmic, strong, moderate, faint/weak and negative. The majority of the breast carcinomas stained homogenously for MMP9 on tumor cells. Statistically significant correlation was found for the expression of MMP9 between primary and recurrent breast carcinomas in general (p<0.001) and in tumors that were grouped as recurrence before (p=0.039) and after 24 months (p<0.001). Strong expression of MMP9 was observed in primary tumors that recurred after 24 months, median: 162.5 (score range 0–300) and those tumors that recurred before 24 months of the initial diagnosis, median: 102.5 (score range 0–250) (p=0.026)

The Effect of 5α-reductase Inhibition with Finasteride and Dutasteride on Bone Mineral Density in Older Men with Benign Prostatic Hyperplasia

Testosterone is converted to dihyrotestosterone by two isoenzymes of 5α-reductase. Finasteride and dutasteride are 5α-reductase inhibitors commonly used in the treatment of benign prostatic hyperplasia. We compared indices of bone mineral density in 50 men treated with finasteride, 50 men treated with dutasteride and 50 men as control. Bone mineral density of spine and hip were measured using dual energy X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorption by measuring serum C-terminal telopeptide of collagen type 1. In addition serum total testosteron and estradiol were determined. The dutasteride group had significantly higher mean bone mineral density, mean bone mineral content, mean T score, mean Z score at femoral neck and mean total hip Z score than control. Mean total testosterone and estradiol levels were higher in the dutasteride group. There were no significant differences between the groups in lumbar spine bone density parameters or bone turnover markers. Our results provide evidence that long-term 5α-reductase suppression does not adversely affect bone mineral density. Dutasteride therapy could have beneficial effect on bone density

Stress Cardiomyopathy in a Patient with Advanced Stage Amyotrophic Lateral Sclerosis

Stres kardiomiopatija entitet je nepoznate etiologije karakteriziran prolaznom sistoličkom disfunkcijom lijeve klijetke i regionalnim poremećajima kontraktilnosti, koji upućuju na infarkt miokarda, ali bez angiografski značajne opstruktivne koronarne bolesti srca. Klinički, u bolesnika se očituje boli u prsima i/ili dispnejom, a promjene u EKG-u upućuju na akutni infarkt miokarda s elevacijom ST-segmenta. Bitan čimbenik razvoja stres kardiomiopatije povišene su razine katekolamina u plazmi kao rezultat hiperaktivnosti simpatikusa izazvane stresnim događajem. Amiotrofična lateralna skleroza (ALS) progresivna je neurodegenerativna bolest koja zahvaća gornji i donji motoneuron, a najčešće završava smrću zbog paralize mišića za disanje i respiratornog zatajenja. U bolesnika s ALSom opisane su povišene razine katekolamina i aktivnosti simpatikusa, što čini rizik za razvoj stres kardiomiopatije. U radu je prikazana bolesnica u uznapredovaloj fazi ALS-a s razvojem stres kardiomiopatije.Stress cardiomyopathy is an entity of unknown etiology characterized by transient systolic dysfunction of the left ventricle and regional wall motion abnormality which suggest myocardial infarction, but with an absence of angiographic evidence of obstructive coronary artery disease. Patients present with chest pain or/and dyspnea, while ECG changes are similar to acute myocardial infarction with ST-elevation. An important factor in the development of stress cardiomyopathy are high catecholamine levels in the blood as a result of the hyperactivity of the sympathetic nervous system caused by a stressful event. Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease that causes muscle weakness and ultimately ends in death due to respiratory muscle paralysis and respiratory failure. High catecholamine levels and increased sympathetic activity have been described in patients with ALS, which suggests that ALS is a risk factor for developing stress cardiomyopathy. In this article, we present a patient at an advanced stage of ALS who developed stress cardiomyopathy

Epidemiology of Prostate Cancer in the Mediterranean Population of Croatia – A Thirty-Three Years Retrospective Study

Prostate cancer is a major public health problem of the male population in all the developed countries1. This non-skin cancer is the foremost one facing man today. Prostate cancer has become the second leading cause of cancer death2. In this study we investigated changes in the prostate carcinoma incidence and manifestation during a thirty-three years period. The study included 1,226 cases of prostate cancer diagnosed from 1972 to 2005 in the Primorsko-Goranska County, Croatia. The age-adjusted incidence of prostate cancer increased from 1.69 per 100,000 men annually in 1972 to 137.58 per 100,000 men annually in 2005, which is an 81.4-fold increase. The percentage of patients with bone metastases on the first medical examination decreased from 1972 (75%) to 2005 (15%). The most of the patients with bone metastases at the first medical examination were between 30 and 50 years old. Early detection measures, such as prostate specific antigen testing and transrectal ultrasound guided prostate biopsy combined with the raised public awareness of the disease, most probably resulted in an increase of incidence

Review of gastrointestinal stromal tumors and contribution of dog1 immunohistochemical marker in diagnostics: A single tertiary centerb experience

Cilj: Prikazati patohistološko dijagnostičko iskustvo Kliničkog bolničkog centra (KBC) Rijeka u pacijenata s gastrointestinalnim stromalnim tumorom (GIST) dijagnosticiranim u razdoblju od 10 godina te pružiti pregled temeljnih karakteristika ovog mezenhimalnog tumora. Cilj je bio i prikazati osjetljivost DOG1 markera (engl. Discovered on GIST) te ga usporediti s osjetljivošću CD117 i vimentina. Materijali i metode: Iz baze podataka Zavoda za patologiju od 2005. do 2015. godine prikupljeni su podaci o 89 pacijenata s dijagnozom GIST-a. Podaci koje smo statistički analizirali obuhvaćali su dob, spol, lokalizaciju tumora, vrstu stanica (vretenaste ili epiteloidne), imunohistokemijske karakteristike te veličinu i mitotički indeks kao dva najvažnija parametra za određivanje prognostičke skupine. Rezultati: Medijan dobi iznosio je 64 godine, s rasponom od 17 do 93 godine. Značajna razlika u incidenciji među spolovima nije pronađena. Najčešća lokalizacija bio je želudac s postotkom od 48,3 %. Vretenastu morfologiju imalo je 84,3 % tumora, epiteloidnu 3.4 %, a miješanu (epiteloidno-vretenastu) 12,3 %. Podjelom GIST-ova u prognostičke skupine ustanovili smo da je 65,2 % tumora bilo benigno, 33,7 % maligno, a 1,1 % imalo je nesigurni maligni potencijal. Na uzorku od 25 tumora određivali smo osjetljivost imunohistokemijskih markera i dobili sljedeće rezultate: DOG1 imao je osjetljivost 100 %, CD117 88 %, a vimentin 60 %. Zaključci: DOG1 najosjetljiviji je imunohistokemijski marker korišten za GIST. Njegovo uvođenje u rutinsku imunohistokemijsku analizu pružilo je snažan doprinos u postavljanju dijagnoze. Prikazano iskustvo našeg centra moglo bi pružiti doprinos u napredovanju patološkodijagnostičke obrade GIST-ova na razini Republike Hrvatske.Aim: To present the experience of Clinical Hospital Center (CHC) Rijeka, Department of Pathology in diagnosing gastrointestinal stromal tumors (GIST) in a 10-year period and to demonstrate consequential characteristics of this mesenchymal tumor. Also the aim was to present the sensitivity of DOG1 (Discovered on GIST) immunohistochemical marker, and to compare it with CD117 and vimentin results. Materials and methods: Searching the Pathology Department database, 89 GISTs were found in the period from 2005 to 2015. Epidemiologic and clinicopathological data: age, gender, dimension, localization, immunohistochemical charachteristics, also mitotic rate and malignant potential as two most important parameters for prognostic group estimation, were statistically analyzed. Results: Median age was 64, range from 17 to 93. 48.3 % of patients were male and 51.7 % were female. Most GISTs (48.3 %) were localized in stomach. Spindle cell morphology was present in 84.3 % GISTs, epitheloid in 3.4 % and mixed in 12.3 % tumors. According to the prognostic groups, malignant potential was assigned. The biggest portion, 65.2 % of tumors, were benign. Malignant potential was present in 33.7 % of cases, while 1.1 % had insecure malignant potential. 25 GISTs were stained with DOG1 and this marker has shown 100 % sensitivity, while CD117 (88 %) and vimentin (60 %) have given inferior results. Conclusions: DOG1 is the most sensitive marker in immunohistochemical staining of GISTs. Hence, it’s usage has provided a step forward in differentiation of GISTs from other mesenchymal tumors. This review, based on a 10-year experience of CHC Rijeka, may make an important progress in pathohistological diagnostics of GISTs in Croatia

Expression of Bone Morphogenetic Proteins, Cartilage-Derived Morphogenetic Proteins and Related Receptors in Normal and Osteoarthritic Human Articular Cartilage

Newborn and adult articular cartilage expresses bone (BMPs) and cartilage derived morphogenetic proteins (CDMPs). These morphogenetic proteins act over membrane receptors (BMPRs). We examined the expression pattern of BMP-7, BMP-3, CDMP-1, CDMP-2 and their receptors in adult normal and osteoarthritic, articular, knee cartilage. Immunostaining was carried out using polyclonal antibodies. The expression of BMP-7,-3, CDMP-1,-2 was detected in all layers of normal articular cartilage with the strongest expression in chondrocytes of the transitional layer. BMP-7 and CDMPs expression decreased in osteoarthritic articular cartilage whereas BMP-3 expression was absent. BMPR-IA and BMPR-II were strongly expressed in both normal and osteoarthritic articular cartilage. BMPR-IB was not expressed in osteoarthritic (OA) cartilage. BMPs and CDMPs with intact signalling play an important role in articular cartilage homeostasis, preventing cartilage degeneration