PROPROTEIN CONVERTASE 1/3 DEFICIENCY WITH PELVIC EWING SARCOMA.

Proprotein convertase 1/3 (PC 1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene. The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies such as hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. Ewing's sarcoma is a rare tumor, usually of small dimensions of neuroectodermal origin that is difficult to distinguish pathologically from a primitive neuroectodermal tumor. A 22-year-old female patient with PC 1/3 deficiency was admitted to our clinic with recurrent urinary tract infections. Magnetic resonance imaging (MRI) revealed an 11x12 cm pelvic mass displacing the uterus. A core-needle biopsy was performed on the pelvic mass. As a result of the pathological evaluation, it was diagnosed with pelvic Ewing's sarcoma. The patient was started on the VAC-IE chemotherapy protocol. We report a case of pelvic Ewing's sarcoma in a patient with PC 1/3 deficiency. Further research is needed to assess malignancy risk in metabolic disorders including very rare disorders like PC 1/3 deficiency.

Recurrence rate of odontogenic keratocyst treated by enucleation and peripheral ostectomy: Retrospective case series with up to 12 years of follow-up.

BACKGROUND: Odontogenic keratocysts have been reported with high recurrence rates in the literature so various treatment modalities from simple enucleation to resection have been performed to achieve the cure. The purpose of this retrospective study was to investigate the recurrence rate of odontogenic keratocysts (OKCs) treated by enucleation and peripheral ostectomy. MATERIAL AND METHODS: An electronic search of the database of the Hacettepe University, Faculty of Medicine, Department of Pathology, was undertaken to identify patients histologically diagnosed with OKCs treated at Department of Oral and Maxillofacial Surgery between 2001 and 2015. RESULTS: In total, 81 patients were studied. The mean age at the time of diagnosis was 42 years, and the male:female ratio was 1:0.7. OKCs were located primarily in the posterior mandibular region (41%). Twenty-seven patients were re-examined to determine the recurrence rate. The mean follow-up period was 5 years (range, 1-12 years). The recurrence rate was 14.8%. The relationship between location of the lesion and recurrence was not statistically significant (p = 0.559). There was also no statistically significant relation between the recurrence rate and treatment option of teeth involved in the lesion (p = 0.579). CONCLUSIONS: The authors conclude that treatment of OKCs by enucleation with peripheral ostectomy is associated with minimal morbidity and is preferred over other aggressive treatment modalities. Meticulous radiographic examination and careful surgical resection may decrease the recurrence rate of OKCs.

Diagnostic accuracy of intraoperative consultation (frozen section) in borderline ovarian tumours and factors associated with misdiagnosis.

The objective of our study was to evaluate the accuracy of frozen section (FS) in borderline ovarian tumours (BOT) and to define the factors associated with misdiagnosis during FS evaluation. We performed a retrospective review of patients who underwent exploratory laparotomy for an adnexal mass, from January 2007 to July 2012, at a tertiary oncology centre in Turkey. Patients with a diagnosis of BOT either in FS or in permanent pathology were identified. Agreement between FS diagnosis and permanent histology was observed in 37/59 patients (62.7%), which gave a sensitivity and a positive predictive value of 71.2% and 84.1%, respectively. In patients with a diagnosis of BOT by frozen section only (n = 44), the diagnosis was consistent with permanent histopathology in 37/44 patients (84.1%). Frozen section interpreted a malignant tumour as BOT (under-diagnosis) in 6/44 (13.6%) of cases and interpreted a benign lesion as BOT (over-diagnosis) in 1/44 (2.3%) of cases. Slide review of discrepant cases revealed that major pathological causes of under-diagnosis were misinterpretation and sampling errors. Univariate analysis showed that presence of bilateral tumour and positive peritoneal cytology were associated with under-diagnosis. We concluded that, despite significant risk of under-diagnosis, FS analysis is an accurate method for intraoperative diagnosis of BOTs.

Tumor apelin immunoreactivity is correlated with body mass index in ovarian high grade serous carcinoma.

Ovarian cancer has a high mortality rate. Serous carcinoma is the most common subtype and can be detected by distant or lymph node metastasis in advanced stages. Apelin, an adipokine associated with obesity, and its receptor, APJ, participate in lymphatic invasion. Angiogenesis also can affect lymph node involvement in serous ovarian carcinomas. We investigated apelin/APJ receptor immunoreactivity in stages III and IV ovarian cancer with or without lymph node involvement and correlated the results with body mass index (BMI) to determine whether the potential relation of the two affects the outcome of the cancer. We investigated 30 patients diagnosed between 2014 and 2016 with high grade serous ovarian cancer. Tumor:stroma ratio, indirect immunoperoxidase method, H-score and MATLAB analysis were performed. In obese and pre-obese patients, tumor apelin immunoreactivity was stronger than for patients with normal BMI. Tumor:stroma ratio was correlated with survival and lymph node involvement. Strong apelin and moderate APJ immunoreactivity was detected in both lymph node negative and positive patients. BMI was related to both survival outcome and apelin immunoreactivity. BMI, adipokines such as apelin, and the stromal compartment play critical roles in advanced stage serous carcinomas.

The accuracy of frozen section analysis at hysterectomy in patients with atypical endometrial hyperplasia.

PURPOSE OF INVESTIGATION: To evaluate the accuracy of frozen section analysis in patients with atypical endometrial hyperplasia. METHODS: Women who underwent hysterectomy with frozen section analysis for atypical endometrial hyperplasia were identified. Frozen section evaluation aimed to give information about the presence of malignancy. Also, myometrial or cervical involvement was assessed in cases with malignancy to reveal the need for staging. Final pathological evaluation results were compared with intraoperative frozen section analyses. RESULTS: Twelve patients (34.3%) had endometrial cancer on final pathologic examination and eight required a staging procedure due to either myometrial invasion or cervical involvement; 75% of patients with endometrial cancer were successfully detected by frozen section analysis. Moreover, among women with cancer, frozen section examination revealed 75% of cases who required surgical staging. CONCLUSION: Frozen section analysis of hysterectomy specimens in patients with atypical endometrial hyperplasia is necessary to determine the presence of cancer and the need for surgical staging.

Radiotherapy in congenital vulvar lymphangioma circumscriptum.

Congenital lymphangioma circumscriptum (LC) of the vulva is a rare disorder with unknown etiology. Treatment options include ablative approaches such as laser therapy, sclerotherapy, and surgery. Radiotherapy has been shown to be effective in the management of congenital lymphangioma especially in the thoracic and abdominal lesions. In this report, we describe a patient with persistent vulvar LC despite sclerosing therapy and several surgical excisions. She was treated with a course of external radiotherapy and showed a dramatic objective response with relief of all symptoms.

Vaginal high dose rate brachytherapy alone in patients with intermediate- to high-risk stage I endometrial carcinoma after radical surgery.

The objective of this study was to analyze the efficacy and morbidity of vaginal cuff brachytherapy alone in intermediate- to high-risk stage I endometrial cancer patients after complete surgical staging. Between October 1994 and November 2005, 128 patients with intermediate- to high-risk stage I endometrial adenocarcinoma were treated with high dose rate (HDR) brachytherapy alone after complete surgical staging. The intermediate- to high-risk group was defined as any stage I with grade 3 histology or stage IB grade 2 or any stage IC disease. The comprehensive surgery was in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy in addition to infracolic omentectomy, and routine pelvic and para-aortic lymphadenectomy. The median number of the lymph nodes dissected was 33. The median age at the time of diagnosis was 60 years. Forty patients were staged as IB (grade 2: 25 and grade 3: 15), and 88 patients were staged as IC (grade 1: 31, grade 2: 41, and grade 3: 16). A total dose of 27.5 Gy with HDR brachytherapy, prescribed at 0.5 cm, was delivered in five fractions in 5 consecutive days. Median follow-up was 48 months. Six (4.7%) patients developed either local recurrence (n = 2) or distant metastases (n = 4). Five-year overall survival and disease-free survival (DFS) rates are 96% and 93%, respectively. Only age was found to be significant prognostic factor for DFS. Patients younger than 60 years have significantly higher DFS (P = 0.006). None of the patients experienced grade 3/4 complications due to the vaginal HDR brachytherapy. Vaginal cuff brachytherapy alone is an adequate treatment modality in stage I endometrial adenocarcinoma patients with intermediate- to high-risk features after complete surgical staging with low complication rates.

Well differentiated mesothelioma complicating endometrial carcinoma; a case report.

Peritoneal mesothelioma is a rare cancer of the abdominal cavity which has low malignant potential. Peritoneal mesothelioma can mimic other types of gynecologic malignancies. Careful clinical and pathologic evaluation is essential for an accurate diagnosis and treatment.

PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature.

Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.

An incidentally diagnosed epithelioid trophoblastic tumor in hysterectomy.

Epithelioid trophoblastic tumor is a rare non-molar gestational trophoblastic disease. A 40-year-old multiparous woman was incidentally diagnosed with epithelioid trophoblastic tumor after hysterectomy. Hysterectomy specimen revealed multiple small, tan to yellow nodules measuring 0.3-0.8 cm just below the endometrium. In the microscopic examination uniform neoplastic cells with varying cellularity were accompanied by necrotic zones and eosinophilic hyaline material. Immunohistochemically neoplastic cells were diffusely stained with CK 7, inhibin-alpha, p63, hPL, and CD146. There was no staining with beta-HCG, SMA, PLAP, or h-caldesmon. Ki-67 proliferative index was approximately 10% and cyclin E was stained in approximately 10% of the neoplastic cells. Although immunohistochemical studies are helpful in classifying gestational trophoblastic lesions, borderline values can cause diagnostic confusion between neoplastic and reactive lesions, particularly in inadequate endometrial biopsies.

nm23 protein expression in renal cell tumors: the role of the cell type.

This study investigated nm23 protein expression in renal cell carcinomas to determine the relationship between nm23 protein expression and grade, stage, prognosis and the cell type. 89 cases were examined by immunohistochemistry. Tubular epithelia were homogeneously stained. Cytoplasmic nm23 protein levels were reduced in renal cell carcinoma. nm23 protein levels persisted in oncocytomas, which are accepted to be benign. Cytoplasmic nm23 staining intensity did not show any correlation with stage and grade of tumor nor prognosis. Reduction in nm23 protein levels may have a role during renal cell carcinoma pathogenesis but not in progression or metastasis suppression.

Epidermolysis bullosa acquisita: clinical manifestations, microscopic findings, and surgical periodontal therapy. A case report.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an uncommon, acquired, chronic subepidermal bullous disease. This report describes a case of EBA with gingival involvement. A 43-year-old woman with EBA was referred to our clinic for periodontal therapy because of gingival tenderness and bleeding. She has been on cyclosporin A therapy for the last 2 years. METHODS: Clinical findings were analyzed. Anterior gingivectomy operations were performed in 2 stages. The samples obtained during the surgery were examined using histopathologic, immunohistologic, and electronmicroscopic methods. Long-term effects of the surgical periodontal treatment on gingiva were evaluated both clinically and microscopically. RESULTS: The dentition displayed minimal enamel hypoplasia. Decayed, missing, and filled surfaces score was found to be elevated. Periodontal examination showed generalized diffuse gingival inflammation and gingival enlargement localized mainly to the anterior region. Nikolsky's sign was positive. However, wound healing was uneventful after the operations. Microscopic findings were similar to those obtained from the skin. Twenty-one months after the operations, Nikolsky's sign was negative and no remarkable gingival inflammation was noted. Microscopic examination revealed that the blisters were fewer in number and smaller in size. CONCLUSIONS: These results indicate that gingival tissues may also be involved in EBA. Uneventful wound healing after periodontal surgery in this case suggests that periodontal surgery can be performed in patients with EBA. Moreover, both our clinical and histopathologic findings imply that gingivectomy proves useful in maintaining gingival integrity in these patients. Our data may also suggest that the patients with EBA are highly likely to develop dental caries.

Search for problem areas in endometrial biopsies to achieve quality assurance.

The aim of this study was to underline the frequently seen problems in diagnosing the lesions seen in the hyperplasia-carcinoma sequence by evaluating the variances between the observers. Four pathologists re-evaluated 137 endometrial biopsies and grouped them into diagnostic categories. The results were analyzed by Kappa statistics. Full agreement was reached in 89 cases (64.96%), with Kappa values ranging between 0.63-0.74. Three observers rendered the same diagnosis in 34 (24.81%) cases, and only one pathologist disagreed. Two or more observers held different views in 16 cases (10.95%). The problem areas were as follows: criteria distinguishing simple hyperplasia from other benign lesions, discrimination between atypical hyperplasia and carcinoma, and decision-making regarding the presence of atypia. There was a tendency towards overdiagnosis of hyperplasia in our department. Since the progression to carcinoma is a sequential event, borderline cases will exist if categories based on simple and clear cut off points are not defined.

Prognostic factors and the role of nephrectomy in metastatic renal cell carcinoma.

The objective of this study is to evaluate the prognostic factors and the role of nephrectomy in metastatic renal cell carcinoma. We reviewed 62 cases of metastatic renal cell carcinoma to document the factors influencing survival and to evaluate the role of nephrectomy. Sex and age of patients, size of primary tumor, site and number of metastases, nephrectomy, cell type and grade of tumor and medical treatment were analyzed as prognostic factors. Age and sex, cell type and type of medical treatment cannot be considered reliable predicting factors. However, improved survival was correlated with tumor size < or = 7 cm in diameter, low grade histology, metastasis limited to single organ and removal of the primary tumor. When these parameters were analyzed in a multivariate model, the presence of nephrectomy was the sole significant parameter. We therefore suggest that nephrectomy should be considered in all patients with metastatic renal cell carcinoma, as long as the morbidity of the operation is acceptable.

Prognostic factors in renal cell carcinoma.

In this study we evaluated some morphological and clinical prognostic factors in 166 patients with renal cell carcinoma (RCC). Patients' ages, sex and localization of the tumor had no effect on survival. Tumor diameter and the weight of the nephrectomy specimen revealed prognostic value. Stage of the tumor, especially the presence of metastasis, is the most important prognostic factor for RCC (p < 0.001). Tumor grade had prognostic value (p = 0.0146). The survival difference between cell types was not significant (p > 0.05). Renal vein invasion, the presence of pseudocapsules and tumor in the intravascular space, mitotic rate, the presence and the number of lymphocytes and macrophages, along with the presence of calcifications had no prognostic value (p > 0.05). The presence of necrotic areas was significant (p = 0.0102). The patients with "infiltrative growth pattern" showed poorer prognosis than patients with "pushing type growth pattern", regardless of the existence of a pseudo capsule (p = 0.0045).

Management of ovarian dysgerminoma during a pregnancy complicated by preeclampsia; a case report.

A case of a 25-year-old primigravid woman at 31 weeks' gestation with the diagnosis of preeclampsia, malignant pelvic mass, fetal growth restriction and postpartum pulmonary thromboembolism is reported. Fertility preserving surgery for ovarian carcinoma following cesarean delivery was carried out. Final histopathology revealed Stage IC dysgerminoma. After eight months of initial surgery she became pregnant spontaneously. After two years of initial surgery she is still alive without any evidence of disease.

Recurrent extraperitoneal low grade leiomyosarcoma with unusual localization.

Primary extragenital leiomyosarcoma is rarely found in pelvic localization. A 33-year-old multiparous woman who had recurrent low-grade leiomyosarcoma presented with the complaints of dyspareunia, pelvic pain and gait disturbance. Her past medical history revealed she had been subjected to maximal excision of a paravaginal mass by using vaginal and suprapubic transverse incision three years before. The pathology report showed that she had leiomyoma. Three years after the initial surgery, a paravaginal fixed mass was observed at the initial tumor bed and removed by the perineal approach. The histological examination of the specimen revealed a low grade leiomyosarcoma. She was discharged from hospital without any complications.

Prognostic factors and the role of nephrectomy in metastatic renal cell carcinoma.

The objective of this study was to evaluate the prognostic factors and role of nephrectomy in metastatic renal cell carcinoma. We reviewed 62 cases of metastatic renal cell carcinoma (RCC) at presentation to document the factors influencing the survival and to evaluate the role of nephrectomy. Sex and age of the patients, size of the primary tumour, site and number of the metastases, nephrectomy, cell type and grade of the tumour and type of the medical treatment were analyzed as prognostic factors. The age and sex of the patients, cell type and type of the medical treatment did not appear to be significant predictors of prognosis. However, improved survival was correlated with tumours < or =7 cm in diameter, low grade tumours, metastasis limited to single organ and removal of the primary tumour. When these parameters were analyzed in a combined manner patients who had undergone nephrectomy showed consistently longer survival. We suggest that nephrectomy should be considered in all patients with metastatic RCC, as long as the morbidity of the operation is predicted to be acceptable.

Comparison of grading systems for estimating the prognosis of renal cell carcinoma.

In this study histologic slides of 165 patients who were diagnosed as RCC between 1983 and 1993 were re-evaluated and each tumour was graded according to Thoenes, Fuhrman, Arner and Skinner's grading systems. According to Thoenes' system, patients with grade (G) 2 and 3 tumours had significantly shorter survival compared to patients with G 1 tumours. The survival difference between the subgroups of Fuhrman and Skinner's grading systems did not reach statistical significance. When the histologic differentiation was grouped as low grade (G 1&2) and high grade (G 3&4) tumours in Fuhrman and Skinner's systems, a statistically significant difference was noted between the groups in terms of survival.