CLINICAL VALUE OF TRANSVAGINAL ULTRASONOGRAPHY IN COMPARISON TO HYSTEROSCOPY WITH HISTOPATHOLOGIC EXAMINATION IN DIAGNOSING ENDOMETRIAL ABNORMALITIES.

The aim of our retrospective study was to compare the performance of transvaginal sonography in relation to histologic diagnosis of samples obtained by hysteroscopy through analysis of data collected over 16 years. Data on suspected formation of endometrial polyp or submucosal fibroid found on ultrasound examination were extracted. The study included a total of 3679 women examined during the 2000-2015 period. All women underwent ultrasound examination preoperatively for better planning the type and scope of operation to be performed. The study included only women with samples for histopathologic analysis collected during the operation. Ultrasound diagnosis of polyps compared with histology showed 89.6% sensitivity and 39.1% specificity. For submucosal myomas, sensitivity was 69.2% and specificity 91.3%. In conclusion, ultrasound is not reliable method for definitive diagnosis but it is an excellent orientation method.

Subcutaneous Dirofilariasis in Female Pubic Region - Case Report.

BACKGROUND: Number of reported cases of human dirofilariasis in the last couple of decades has been increasing. Dogs are the main reservoir hosts, while various mosquito species represent/serve as vectors. Human infections are caused by two different parasites: Dirofilaria immitis and Dirofilaria repens. Dirofilaria repens is currently considered to be one of the most rapidly-spreading human and animal parasite species in Europe. Clinical features are characterised by subcutaneous or ocular lesions which can persist for months without any symptoms. The disease is considered to be endemic in Mediterranean countries, central Asia, Israel, and Sri Lanka with increased incidence in Central and East Europe. Apart from the local population, tourists are also susceptible to this disease. Export of domestic animals can transfer parasites between different countries. This disease is rare in Croatia. CASE PRESENTATION: We are presenting a case of a 58-year-old female patient with dirofilariasis of the genital region caused by Dirofilaria repens, confirmed with PCR and sequencing. CONCLUSION: From the clinician point of view, subcutaneous dirofilariasis should be considered as a differential diagnosis in cases of long-lasting subcutaneous swellings.

HISTOPATHOLOGIC FINDINGS IN WOMEN UNDERGOING HYSTEROSCOPIC RESECTION OF ENDOMETRIAL POLYPS AND UTERINE MYOMAS.

The aim of our study was to determine the prevalence of endometrial premalignant and malignant lesions in women undergoing hysteroscopy and to identify anthropologic factors related to the presence of malignancy. Data on 3470 women with submucosal myomas or endometrial polyps suspected on ultrasound were retrospectively analyzed. Hysteroscopy was performed in all these women in order to make a more precise diagnosis. Histologic analysis of endometrial samples obtained during hysteroscopy was used to confirm the diagnosis. Statistical analysis was performed using the SPSS 20.0.0 software. The mean age of study women was 49.1±13.3 years. The number of procedures performed due to the referral diagnosis of endometrial or submucosal myoma significantly increased over the 16-year study period. A significantly higher number of women had a benign histopathologic diagnosis. Histologic analysis revealed malignancy in 67 women. The youngest woman and oldest woman with malignant findings was aged 32 and 75, respectively. A significantly higher number of women with atypical hyperplasia and malignancy were in menopause. A comparable number of women with different histologic findings lived in urban and rural areas. There were a significantly larger proportion of widows among women with the histologic diagnosis of atypical hyperplasia or malignancy. The prevalence rate of malignancy in women having undergone hysteroscopy for polyps and myoma found by ultrasound was 1.93%. Postmenopausal status and older age were associated with an increased risk of malignancies, but premalignant changes and malignancies were also found in young and premenopausal women. Therefore, diagnostic hysteroscopy can be recommended in women of all age groups.

Ovarian Teratoma in Routine Biopsy Material During a Five-Year Period.

Teratomas are tumors derived from germ cells, most frequently arising in the gonads. The aim of this study was to determine the number of ovarian teratomas diagnosed in the routine biopsy material at Ljudevit Jurak Clinical Department of Pathology, Sestre milosrdnice University Hospital Center during a 5-year period, as well as their clinical, gross and microscopic characteristics. Teratomas accounted for 48.6% (n=166) of primary ovarian tumors. The patient mean age was 34.74±12.37 years. Difference in the incidence of teratoma between the left and right ovary was not significant; bilateral teratoma was found in 13 patients. Teratomas were detected by ultrasonography in 115 (69.27%) cases and the rest were found during surgery performed for other indications. Most teratomas (n=161; 96.9%) were mature and cystic (dermoid cysts). Mature and solid teratomas were diagnosed in 5 (3.01%), ovarian struma in 2 (1.8%) cases and strumal carcinoid in 1 (1.2%) case. Mature cystic teratomas contained sebaceous material in 123 (76.8%) cases, and a total of 16 teeth were found; 157 (94.5%) teratomas measured <10 cm in largest diameter. Microscopically, mature cystic teratomas most frequently contained ectodermal (skin with appendages, mature glia and nerve ganglia) and mesodermal (fi brous, fat tissue, cartilage and bone) tissues. Frequently found tissues of endodermal origin were respiratory and intestinal epithelia. Small foci of thyroid tissue were found in 20 (12%) teratomas. Chronic granulomatous foreign body reaction in the wall of mature cystic teratomas was found in 11 (6.8%) tumors.

Expression of growth hormone receptor, plakoglobin and NEDD9 protein in association with tumour progression and metastasis in human breast cancer.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths among female population worldwide. Metastases are the common cause of morbidity and mortality in breast cancer and can remain latent for several years after surgical removal of the primary tumour. Thus, the identification and functional characterisation of molecular factors that promote oncogenic signalling in mammary tumour development and progression could provide new entry points for designing targeted therapeutic strategies for metastatic breast cancer. In the present study, we investigated the expression of proteins involved in cell signalling (growth hormone receptor (GHR) and NEDD9) and cell-cell adhesion (plakoglobin) in epithelial and stromal compartments of primary ductal invasive breast carcinomas and their axillary lymph node metastases versus non-metastatic tumours. Obtained data revealed remarkable increase in the expression levels of GHR and NEDD9 proteins in both epithelial and stromal components of axillary lymph node metastases in comparison with those of non-metastatic tumours, suggesting that the expression of these two proteins may provide biomarkers for tumour aggressiveness.

Expression of growth hormone and growth hormone receptor in fibroadenomas of the breast.

Fibroadenoma is the most prevalent benign breast tumor. It consists of epithelial and stromal components. In general, breast tumors are highly hormonally dependent and growth hormone by its physiology may have a possible oncogenic potential. Therefore, the aim of this study was to determine the expression of growth hormone and growth hormone receptor in epithelial and stromal components of fibroadenomas. Study group included 30 randomly chosen fibroadenomas from female patients aged between 18 and 69 years. The expression of growth hormone and growth hormone receptor was defined in both histologic components of fibroadenomas. Growth hormone was expressed in 96.7% of both epithelial and stromal components of fibroadenomas, with stronger expression in the stromal component. The same percentage of positive reaction (96.7%) was obtained in the epithelial component of fibroadenomas for growth hormone receptor expression. Only 6.7% of stromal components tested for growth hormone receptor were positive. The high expression of growth hormone and growth hormone receptor in fibroadenoma tissue indicates their possible role in the pathogenesis of this tumor. Follow up of patients with high expression of growth hormone and growth hormone receptor may be suggested.

Periacinar retraction clefting and d2-40 expression in prostatic adenocarcinoma.

Retraction clefting is known to appear in various types of tumors, but it has only recently been recognized as a specific histological phenomenon. Previously, it was considered merely a laboratory procedure artifact, but lately, there have been some assumptions that peritumoral retractions actually represent lymphatic spaces. In our study, we analyzed neoplastic glands in 52 specimens of prostatic adenocarcinoma. Immunohistochemical analysis was performed using D2-40 antibody, to highlight lymphatic endothelium and thereby differentiate actual lymph vessels or lymphovascular invasion from periacinar retractions. Our results showed that the number of lymph vessels was significantly lower in tumorous tissue compared to adjacent normal prostatic tissue. On the other hand, the number of lymph vessels in tumorous tissue was significantly higher than the number of lymph vessels mimicking periacinar retractions. Overall, the number of lymph vessels mimicking periacinar clefts was particularly low. These results are in accordance with our previous studies, which had shown that periacinar clefting appears due to lack of basal cells and stromal changes around tumorous acini. Also, these results support our hypothesis that retractions do not represent lymph vessels but should be considered a distinct entity, which is proven to be helpful both as diagnostic and predictive factor.

Strumal carcinoid of the ovary: report of two cases.

Primary carcinoid tumors of the ovary account for 5% of ovarian teratomas. They are frequently components of mature cystic teratomas or, less commonly, mucinous cystadenomas. Most tumors are seen in peri- or postmenopausal women with symptoms of enlarging mass, or are incidental findings. Microscopically, there are four major variants of ovarian teratomas of carcinoid type: insular, trabecular, strumal and mucinous. One-third of patients with the insular type of carcinoids have symptoms of the carcinoid syndrome. Strumal carcinoid is an unusual form of ovarian teratoma composed of an intimate admixture of thyroid and carcinoid tissues that vary in their relative proportions. Two patients with ovarian tumors showing typical morphology of primary ovarian strumal carcinoid are described.

Higher apoptotic cell rate in Balkan endemic nephropathy--stereologic analysis.

The aim of this study was to correlate apoptotic cell rate from different nephron segments between control group and groups of patients with Balkan endemic nephropathy (BEN). Kidney specimens of20 patients with clinically and epidemiologically confirmed BEN were compared with biopsy material of 10 patients (group I, non BEN) without glomerular or tubulointerstitial disease. Out of 20 patients with BEN, 10 suffered and died from BEN (group II, BEN) and 10 patients (group III, BEN/CV) suffered from BEN but died from cardiovascular disease. Patient age ranged from 40 to 50 years. The apoptotic cell rate was measured in proximal and distal tubules and in collecting ducts using the 40X objective with a calibrated eyepiece multipurpose M 42 test system according to Weibel. Comparison of all three nephron segments yielded statistically significant differences in volume density of apoptotic cells in proximal tubules and in collecting ducts among all three patient groups (non BEN vs. BEN, non BEN vs. BEN/CV and BEN vs. BEN/CV, P<0.001 all). Statistically significant difference in apoptotic cell rate was also found in distal tubules between non BEN and BEN groups and non BEN and BEN/CV groups, but not between BEN and BEN/CV groups. Our results showed a statistically significant increase of apoptotic cells in all three nephron segments in patients with BEN (BEN and BEN/CV) compared to control group. The highest number of apoptotic cells was found in distal tubules in the groups of patients with BEN and BEN with coexisting cardiovascular disease, suggesting that these cells might be most frequently and most severely injured in patients with BEN.

Primary osteosarcoma of bladder diverticulum mimicking intradiverticular calculus: a case report.

There is a well-documented relationship between urinary bladder diverticula and intradiverticular neoplasms. The great majorities of these tumors are urothelial carcinomas, but may also be of glandular or squamous type. Sarcomas occurring within bladder diverticula are exceptionally rare and highly malignant lesions, with only 20 well documented cases published in the literature to date (including carcinosarcomas). We report a case of osteosarcoma of the bladder diverticulum in a 68-year old man, which clinically mimicked intradiverticular calculus. To our knowledge, this is the second case described in the literature to date, and the first in English literature.

Superoxide dismutase and cytochrome P450 isoenzymes might be associated with higher risk of renal cell carcinoma in male patients.

Literature data support the hypothesis that oxidative stress and the accompanying antioxidant defense might play an important role in renal cell carcinoma (RCC) growth and progression. It is also known that the incidence of renal tumors is two times higher in men than in women. Thus, the aim of this study was to determine whether the oxidant/antioxidant profile of renal cell carcinoma tissue, adjacent to tumor tissue and nontumor tissue was different in male and female patients. Significantly higher lipid peroxidation (LPO) in renal cell carcinoma tissue compared to nontumor tissue was demonstrated only in male patients. Besides, gender-related difference in copper zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) in nontumor and renal cell carcinoma tissue was obtained at the level of transcription, translation and activity of these antioxidant isoenzymes. Morever, we demonstrated that the gene expression of 3 CYPs out of 7 was altered; CYP2D6 mRNA was decreased in both sexes while gender-related suppression of mRNA for CYP2E1 (women) and CYP2C19 (men) was observed. Taken together, these parameters might be potentially responsible for higher risk of renal cell carcinoma in men than in women.

CD138-positive plasmacytoid urothelial carcinoma of urinary bladder with focal micropapillary features.

Both the plasmacytoid and micropapillary types of urothelial carcinoma of the urinary bladder are uncommon, distinct clinical and pathological findings. To date, several reports in the English medical literature have been published on either of these variants. CD138 is commonly used as a marker for tumors of plasma cell origin. However, few authors have described positive immunoreactivity of plasmacytoid cells in urothelial carcinoma. Mixed histological differentiation is thought to be a phenotype of locally aggressive and advanced urothelial carcinoma. Therefore, a precise histopathological diagnosis should be made and awareness of all the entities is crucial. We report a case of CD138-positive plasmacytoid urothelial carcinoma of the bladder with focal micropapillary features. To our knowledge this is the first case of these two rare subtypes of urothelial carcinoma combined in a single cystectomy specimen.

Primary ovarian leiomyoma associated with endometriotic cyst presenting with symptoms of acute appendicitis: a case report.

BACKGROUND: Ovarian leiomyoma is a rare benign tumor that accounts for 0.5 to 1% of all benign ovarian tumors. It probably arises from smooth muscle cells in the ovarian hilar blood vessels but there are other possible origins including cells in the ovarian ligament, smooth muscle cells or multipotential cells in the ovarian stroma, undifferentiated germ cells, or cortical smooth muscle metaplasia. Additionally, smooth muscle metaplasia of endometriotic stroma, smooth muscle present in mature cystic teratomas, and smooth muscle in the walls of mucinous cystic tumor may explain their occurrence in the ovary in some cases. CASE PRESENTATION: A 31-year-old woman was admitted to our surgical emergency service with a one-day history of appendicitis-like symptoms. Upon laparotomy, there was a solid, oval left-sided ovarian tumor located behind the uterus. The tumor was sent to the pathology department. A diagnosis of primary ovarian leiomyoma associated with an endometriotic cyst was established. CONCLUSION: The origin of ovarian leiomyoma is still unresolved. In our case, the tumor probably arose from smooth muscle cells derived from myofibroblasts that originate from metaplastic ovarian stromal cells present in the rim of the endometriotic cyst. Despite its rarity, ovarian leiomyoma should be considered in the differential diagnosis of ovarian spindle cell tumors. Appropriate diagnosis may require additional immunohistochemical analysis in some cases.

Peritumoral retraction clefting correlates with advanced stage squamous cell carcinoma of the esophagus.

The present study was designated to analyze correlation between the presence and extent of peritumoral retraction clefting and various clinicopathologic features in esophageal squamous cell carcinoma (ESCC), and to possibly establish the significance of this phenomenon in ESCC. Fifty-four consecutive patients with advanced ESCC were included in the study. The presence of peritumoral retraction clefting was classified on the basis of the proportion of tumor nests exhibiting this phenomenon. Tumors with clefts that affected up to 25% of tumor nests were classified as group I; with clefts that affected >25% to 50% of tumor nests as group II; with clefts that affected >50% to 75% of tumor nests as group III; and tumors with clefts that affected more than 75% of tumor nests were classified as group IV. Statistical analysis showed a correlation between presence and extent of peritumoral clefting and lymph node metastasis. T3 tumors and tumors with lymph node metastasis had significantly more pronounced peritumoral clefting compared with T2 tumors and tumors without lymph node metastasis. The presence of peritumoral clefting was not associated with the number of affected lymph nodes. There was no correlation between the presence and extent of peritumoral clefting with patient age and sex, and tumor location, diameter and grade. The association of peritumoral retraction clefting in ESCC with local invasiveness and lymph node metastasis indicated that peritumoral clefting could be a simple and useful morphological feature of tumor aggressiveness and may contribute to the pathological and clinical assessment of patients with ESCC.

Comparison of occurrence of upper urinary tract carcinomas in the region with endemic villages and non-endemic nephropathy region in Croatia.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial renal disease of a still unknown etiology, associated with an increased frequency of urothelial carcinoma, particularly of the upper urinary tract (UUT). The aim of the study was to compare the occurrence of UUT carcinomas between Brodsko-Posavska Region (BPR) which is the region with endemic villages and the non-endemic region of Zagreb (ZG) in two six-year periods with a 20 year period separating the two, pointing out a possible difference in occurrence regarding war in Croatia (1991-1995). Comparing BPR and ZG regions we found a more then 5 times higher frequency of UUT carcinomas in BPR in the first period and more than 4.5 times higher frequency in the second period. Women in BPR were more frequently affected with UUT carcinomas.

Axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia.

Apocrine carcinomas represent a rare group of tumors with a potential for destructive local invasion, regional and distant metastases, and are equally common in both sexes. A case of a 79-year-old woman with axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia is presented. To our knowledge, this is the first case diagnosed in a Caucasian and also the first case diagnosed in a female patient. Grossly, the tumor measured 3.2x1.5x1.2 cm and on cut section appeared granular, white to gray-tanned. Microscopically, the tumor was located in the dermis, poorly demarcated, focally necrotic with ulcerated overlying skin. It was predominantly composed of complex, closely packed tubuloglandular structures but in few areas papillary structures were also observed. The cells contained abundant eosinophilic, finely granular cytoplasm with pleomorphic nuclei and showed apocrine-like decapitation. The cytoplasm contained periodic acid Schiff diastase resistant granules. Mitoses were frequent and some were atypical. In one area, the tumor was lobular and composed of tubular structures lined with one layer of uniform cuboidal or columnar eosinophilic cells, indicating a pre-existing apocrine adenoma. Beneath the tumor, in the deep dermis and subcutaneous tissue, hyperplastic apocrine glands were also found. No additional therapy was used, and one year after the surgery the patient was alive and showed no signs of tumor spread. This and previously reported cases suggest that apocrine hyperplasia and apocrine adenoma may represent successive steps in the development of apocrine carcinoma.

Pleomorphic ductal carcinoma of the breast with predominant micropapillary features.

An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.

[Change in the occurrence of breast cancer in hospital registries (1980-2000)]. / Promjene u pojavnosti raka dojke u bolnickom registru (1980-2000).

The aim of our retrospective study was to analyze distribution of histological types, age of patients and hormonal dependency of breast cancer cases in the period 1980-2000 using computer database "Thanatos". This period was divided with regard to the war into a pre-war (1980-1990), war (1991-1995) and post-war period (1996-2000). We also paid attention to the Chernobyl accident (pre-Chernobyl from 1980-1986 and post-Chernobyl from 1987-2000). Special attention was focused on the period during the war mainly due to the fact that very little data exist in literature dealing with the war as a stress factor that may have induced and promoted carcinogenesis. During this twenty-one year period 2296 patients were diagnosed with breast cancer. In the female population of 2274, 2228 (98%) of these were ductal and only 46 (2%) were invasive lobular carcinomas. In all of the male cases (22) the cancer was pathohistologically verified as the invasive ductal type. The male:female ratio was 1:103. Comparing the pre-war and war periods we found a more than double increase in the male:female ratio (from 1:131 to 1:66). We observed similar results when we looked at the period after the Chernobyl incident where the ratio increased from 1:139 to 1:79. When we analyzed the distribution of histological types we found a significant increase in lobular carcinomas during the post-war period, from 1.1% to 5.5%; this increase was less significant for the post-Chernobyl period (1.0% to 3.3%). The average age of the patients with invasive ductal carcinomas increased from 56.7 yrs during the pre-war period to 59.7 yrs during the war and finally to 61.1 yrs during the post-war period. The average age of males with breast cancer decreased from 63.6 and 63.5 during the pre-war and war periods to 58.8 yrs during the post-war period. These results suggest that the war could have influenced the shift in the age of occurrence of breast cancer in both sexes appearing in younger males and in females in their postmenopausal period. The most commonly diagnosed stage of invasive ductal carcinoma during the war and post-war periods was T1N0MX, but in the controlled pre-war period the most frequently diagnosed stage was T2N1MX. With this we see that the increase in the age of the patient is not due to a more advanced pTNM stage which suggests that the increased age of our patients seeking medical help is not due to the incapacitating effects that the war may have on people needing medical attention. Our results showed that most of the patients were ER positive (72% throughout the twenty-one year period) and their average rate and number increase with the age of the patient. We found a significant drop in hormone dependent tumors in the period from 1991-95, which could mean that tumors in a war environment manifest a more aggressive phenotype. Our results show that the war within our region most likely had an effect on some clinical parameters involving breast cancer patients. Possible effects caused by "Chernobyl" could not be proved due to the overwhelming effect that war had upon the patients within this region.