Stromal or intraepithelial tumor-infiltrating lymphocytes: which one has more prognostic significance in cervical cancer?

PURPOSE: To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated. RESULTS: Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively). CONCLUSION: sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.

The expression of BMP, integrin, ZEB2 in ovarian high-grade serous carcinoma in relation with lymph node metastasis.

Ovarian cancer (OC) is clinically important because it is diagnosed late and has metastasis when it is diagnosed. Mortality risk increases 2.75 times in the presence of lymph node (LN) metastasis. During metastasis, many molecules including BMPs originated from stroma, and tumor cells participate through transcription factors and integrins for cytoskeleton regulation during cell migration. We hypothesized an inverse correlation between BMP2 and BMP7 along with changes in ZEB2, and integrin α5ß1 in high-grade OCs in relation to LN metastasis. The BMP2 immunoreactivity was strong along with strong ZEB2 and weak integrins' immunoreactivity in samples with LN metastasis. Strong immunoreactivity of BMP7 was accompanied by strong immunoreactivity of integrins in the samples without LN metastasis. Study results showed BMP2's strong positive immunoreactivity and weak BMP7 immunoreactivity in tumor cells with a significantly weak inverse correlation. This inverse correlation should be considered as both BMPs have different effects in the window of cancer progression and invasion.

Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes.

INTRODUCTION: To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. METHODS: The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). RESULTS: Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. CONCLUSION: PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

The evaluation of laparotomy results in breast cancer patients with gynecological pathologies.

AIM: The aim of the study was to evaluate the results of the laparotomies due to gynecological pathologies in breast cancer patients and to assess the distribution of gynecological pathologies and the clinical and laboratory findings contributing to the diagnosis. METHODS: This study was conducted between years 2002 and 2011 at Hacettepe University Hospital. We obtained information about 86 consecutive breast cancer patients, including age, time of diagnosis and pathology of breast cancer, hormone receptor status, history of endocrine therapy, presenting symptoms, ultrasonography findings, CA 125 levels, endometrial biopsy results, type of gynecological surgery and pathology results. Data were analyzed with the use of SPSS software. RESULTS: Twenty-one (24.4%) out of 86 patients had endometrial pathology, and 24 (27.9%) had adnexal pathology. Fourteen patients (16.2%) had malignant pathology, and of them, 11 had ovarian cancer 3 had endometrial cancer. There were five abnormal cytological findings: 2 ASCUS, 1 LSIL, 1 ASC-H and 1 adenocarcinoma. The patient with the cytology report of adenocarcinoma had the final diagnosis of endometrial cancer. Of the patients, 67 (77.9%) used tamoxifen, whereas 19 (22.1%) did not. Thirty-three patients (38.4%) with gynecological pathologies were detected incidentally during routine follow-up of breast cancer. CONCLUSION: This study supports the increase of the gynecological pathology incidence in breast cancer patients and the recommendation of close gynecological follow-up in these patients. Asymptomatic patients might also develop genital cancer. The ultrasonographic appearance of the adnexal masses or endometrial thickness and any abnormal vaginal bleeding or high CA 125 levels are important parameters for evaluating breast cancer patients.

Clinical and histopathological comparative study of two equine-derived bone graft: a human study.

OBJECTIVE: To compare the performance of collagenated bone graft substances with different collagen ratios after sinus floor augmentation. METHODS: The cross-sectional study was conducted at Hacettepe University, Ankara, Turkey, from September 2011 to September 2013. Sinus floor augmentation was done with two different equinederived xenografts in patients before dental implant application. Of the two randomised groups, one was treated with 100% collagenated bone mix (Group A), and the other half with 90% collagenated bone mix + 10% collagen gel (Group B).Six months after sinus augmentation, prior to dental implant surgery, a specimen was taken from the implant socket with trephine drill for histopathological evaluation of new bone, connective tissue and residual graft material at each augmented site. SPSS 19 was used for data analysis. RESULTS: Of the 19 patients, 12(63%) were females and 7(37%) were males. The overall mean age was 51.68±11,96 years (range: 24-69 years). A total of 30 sinus floor augmentations were done. New bone formation was significantly better in Group A(15 sinus floor augmentation) than in Group B (the other 15 sinus floor augmentation) (p<0.05), but there was no significant difference in connective tissue formation and residual graft materials between the groups (p>0.05). CONCLUSIONS: Collagenated bone mix was found to be a suitable graft material for sinus floor augmentation, but increased collagen ratio did not improve new bone formation over the 6-month healing process.

Comparison of Mayo and Milwaukee Risk Stratification Models for Predicting Lymph Node Metastasis in Endometrial Cancer.

OBJECTIVE: The aim of this study was to compare Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination in patients with endometrial cancer (EC). METHODS: A total of 904 patients with EC underwent surgical treatment between 2004 and 2016 at Hacettepe University Hospital, and clinicopathological data of patients were retrieved from the computerized database of the Hacettepe University. Patients who did not undergo lymphadenectomy and who had nonendometrioid histology, stage-IV disease, and synchronous epithelial ovarian and EC were excluded. All slides of the cases were reviewed by the same gynecologic pathology subspecialist. RESULTS: The study group consisted of 307 consecutive patients with a mean age of 59.4 years (range, 26-86 years). Lymph node metastasis was detected in 28 subjects (9.1%). Primary tumor diameter, depth of myometrial invasion, lymphovascular space invasion, and cervical stromal and glandular involvement were associated with lymph node metastasis. Patients with low-risk histological features based on Mayo risk stratification system in our study group had a 0% rate of lymph node positivity. However, of the 28 patients with lymph node metastasis, 3 (10.7%) had low-risk features based on Milwaukee model. The sensitivity, specificity, false negative rate (FNR) and false positive rate of Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination among women with endometrioid EC were 100%, 27.3%, 0%, and 72.7%; and 89.3%, 61.3%, 10.7%, and 38.7%, respectively. CONCLUSIONS: Although Milwaukee risk stratification model had a lower false positive rate and can decrease the number of lymphadenectomies, FNR of this new model was found as 10.7% in the present study. Furthermore, we found that Mayo model had a lower FNR and higher sensitivity. Therefore, Mayo model still looks more beneficial to predict lymph node metastasis in patients with endometrioid EC and Milwaukee risk stratification model still requires external validation.

The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential: Centralized Review Can Purify the Diagnosis.

OBJECTIVE: The objective of this study was to investigate the clinicopathological features and factors associated with recurrence in patients with uterine smooth muscle tumor of uncertain malignant potential (STUMP). METHODS: Forty-six cases diagnosed between 2000 and 2014 from 2 tertiary centers underwent blind slide review. Initial diagnosis included smooth muscle tumors with equivocal diagnosis, STUMPs, and cases that were named as leiomyosarcomas (LMS) or low-grade LMS despite not fulfilling the Stanford criteria. RESULTS: In total, 21 patients with a final diagnosis of STUMP were available. Fifteen (68.1%) of 22 patients with an initial diagnosis of STUMP, 4 (22.2%) of 18 cases with an equivocal smooth muscle tumor diagnosis, and 2 (33.3%) of 6 cases with an initial diagnosis of LMS were interpreted as STUMP after slide review. The mean age at diagnosis was 43 years (range, 20-64 years). The mean follow-up time was 65.9 months (range, 10-154 months). Four patients (19.0%) developed recurrent disease. Recurrent tumors were LMS in 3 patients (75%). One patient (4.8%) with recurrence succumbed to disease. There was no difference in patients' age (P = 1.0) or type of initial surgery (uterus conserving versus hysterectomy) (P = 0.57) between patients who recurred and did not recur. CONCLUSIONS: Uterine STUMPs can harbor significant uncertainty regarding the original diagnosis and clinical outcomes. Recurred cases may have an aggressive clinical course associated with multiple relapses and death. Uterine mesenchymal tumors other than ordinary myomas and overt sarcomas deserve a second opinion in centers with experience because the real diagnosis may vary significantly.

Wilms' tumor 1 protein expression in endometrial adenocarcinoma and endometrial intra-epithelial neoplasia.

AIM: To investigate the expression of Wilms' tumor 1 (WT1) protein in endometrial adenocarcinoma (EC) and endometrial intra-epithelial neoplasia (EIN). METHODS: WT1 protein expression was determined on immunohistochemistry in 30 EC patients and in 20 EIN patients. WT1 protein expression in proliferative (n = 7), secretory (n = 9) and atrophic endometrium (n = 9) and benign endometrial polyps (n = 28) was used as the control group. Cellular and vascular WT1 staining was scored semiquantitatively. RESULTS: Cellular WT1 staining was 67% and vascular positivity was 73% in the EC group. In the EIN group the cellular staining was 100% and vascular staining was 85%. Although all EIN samples were positive for cellular WT1 staining, median cellular staining score was similar to that of EC (median, 2; range, 1-3; IQR, 1.75 vs 2, 0-3, 0.75, respectively). Increasing EC grade and stage were not associated with cellular or vascular WT1 staining score. CONCLUSION: WT1 is expressed in EIN.

Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation.

We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve,  statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The  values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.

Intraoperative Ex Vivo High-Resolution Sonography: A Novel Technique for the Assessment of Myometrial Invasion in Endometrial Cancer.

OBJECTIVE: This study aims to assess the diagnostic performance of a novel intraoperative ex vivo ultrasonography technique in determining deep myometrial invasion (MI) in patients with apparently low-risk endometrial cancer (EC). METHODS: This prospective study included patients with type I EC who underwent staging laparotomy at Hacettepe University Hospital from December 2011 to September 2014. After hysterectomy, a radiologist with special training in gynecology examined the uterus ex vivo using a 12-MHz superficial linear probe. The specimen was sent for intraoperative frozen section (FS) analysis. The results were compared with permanent section reports. RESULTS: In total, 45 female patients were eligible for analysis. Intraoperative ex vivo high-resolution sonography (IEVHS) correctly assessed depth of MI in 39 of 45 cases (86.6%) and overestimated it in 5 cases (11.1%). Only 1 case with deep infiltration was underestimated by IEVHS as invasion of less than one half of the myometrium. Frozen section correctly identified depth of MI in 41 of 46 cases (91.1%), overestimated it in 1 case (2.2%), and underestimated it in 3 cases (6.6%). The sensitivity, specificity, positive predictive value, and negative predictive value of IEVHS and FS for assessment of deep MI were 87.5%, 86.4%, 58.3%, and 96.9%, and 62.5%, 97.3%, 83.3%, and 92.3%, respectively. CONCLUSIONS: Intraoperative ex vivo high-resolution sonography is a novel technique for assessing MI in EC. Its high sensitivity for deep MI could be useful as an adjunct to FS (enabling pathologists to obtain targeted FS slices) and could improve the accuracy of FS.

PREVENTION OF RADIATION-INDUCED RETINOPATHY WITH AMIFOSTINE IN WISTAR ALBINO RATS.

PURPOSE: To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina. METHODS: A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10. RESULTS: At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001). CONCLUSION: This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.

A Low-Risk HPV-Associated Well-Differentiated Squamous Cell Carcinoma of the Cervix with Low-Grade Squamous Intraepithelial Lesion Morphology: Clinical and Pathologic Diagnostic Difficulties and Review of the Literature.

Approximately 95% of cervical squamous cell carcinomas are associated with high-risk HPV, with a small number of HPV-independent tumors. However, low-risk HPV types have also been detected in rare cervical squamous cell carcinomas. Low-grade squamous intraepithelial lesion-related changes are a rare morphologic finding in cervical squamous cell carcinoma. We present the case of a 30-yr-old woman who presented with pelvic pain and foul-smelling vaginal discharge showing an exophytic lesion protruding from the cervix. Repeated superficial biopsies showed a low-grade squamous intraepithelial lesion (LSIL) characterized by binucleation and koilocytosis. Chromogenic in-situ hybridization revealed the presence of HPV6/11. The absence of high-risk HPV was confirmed by PCR. After following the patient for nine months without intervention, type III hysterectomy and bilateral pelvic paraaortic lymphadenectomy were performed. Microscopic examination showed well-differentiated squamous cell carcinoma with solid epithelial islands and extensive eosinophilic cytoplasm without pleomorphism. HPV 6 and 11 were also detected with chromogenic in-situ hybridization. Neoplasm invaded the full-thickness of the cervical wall and infiltrated the vagina, parametrium, the proximal ureter and bladder. The patient who received chemoradiotherapy is disease-free at 36 months follow-up. Low-risk HPV-related well-differentiated invasive squamous lesions exist, and such lesions could be a diagnostic pitfall for gynecologists and pathologists; in these cases, radiologic-pathologic correlation and radiologic guided biopsy are mandatory.

Effect of hypoxia-inducible factor-1 alpha expression on survival in patients with metastatic cervical squamous cell carcinoma treated with first-line chemotherapy and bevacizumab.

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor (VEGF)-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer.

PURPOSE: To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC). METHODS: Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed. RESULTS: Two hundred and sixty-one patients were included. There were 26 patients (10.0%) with lymph node metastasis. Of these, 14 (5.4%) had pelvic lymph node metastasis, 8 (3.1%) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5%) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95% confidence interval 3.8-59.0; p < 0.001, and odds ratio 20.9; 95% confidence interval 1.9-69.9; p = 0.013, respectively). CONCLUSION: Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.

High-grade Endometrial Stromal Sarcoma: Morphologic and Clinical Features, the Role of Immunohistochemistry and Fluorescence in Situ Hybridization in Diagnosis.

Introduction. High-grade endometrial stromal sarcomas (HGESS) are rare malignant mesenchymal tumors of the uterus with aggressive poor clinical outcome, which frequently exhibit YWHAE::NUTM2 and ZC3H7B::BCOR fusions. In this study, we aimed to investigate HGESSs with YWHAE and BCOR translocations through our archive materials, and to identify morphological, immunohistochemical and molecular features of these tumors. We also assessed the diagnostic value of BCOR immunohistochemistry (IHC) in HGESSs, low-grade endometrial stromal sarcomas (LGESS) and uterine leiomyosarcomas. Methods. One hundred fifty-one uterine sarcomas diagnosed between 2000-2019 were reevaluated, and tumors of 39 patients with specific features were included in the study. Fluorescence in situ hybridization (FISH) studies using YWHAE and BCOR break-apart probes and BCOR IHC were performed. BCOR IHC was also performed in 20 leiomyosarcomas and 19 LGESSs. Results. In six HGESSs, translocations involving YWHAE or BCOR were detected. Five tumors showed high-grade morphology and revealed YWHAE translocation. One HGESS with myxoid morphology revealed BCOR translocation. In immunohistochemistry, three (3/4) YWHAE translocated HGESSs showed BCOR expression. However, the BCOR translocated HGESS was BCOR negative. The study showed that all LGESSs were immunohistochemically negative with BCOR. Although 15% (3/20) leiomyosarcomas reveal focal weak-moderate BCOR expression. Conclusion. BCOR IHC is a useful marker to distinguish LGESS from HGESS. A small percentage of uterine leiomyosarcomas reveal BCOR expression; however, it is not as diffuse and strong as in HGESSs. Strong and diffuse BCOR IHC expression is highly suggestive for HGESS. The diagnosis of HGESS should be supported by molecular studies such as FISH.

Small Cell Carcinoma of Ovary, Hypercalcemic Type: A Rare Case Report.

BACKGROUND: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare neoplasm that occurs mostly in women younger than 40 years of age. The unknown histogenesis makes the diagnosis of SCCOHT difficult. SCCOHT was recently shown to be associated with SMARCA4 gene mutation. Serum calcium levels can be used as a marker of treatment response and relapse in SCCOHT. CASE REPORT: Here we report on a 16-year-old girl who presented with pelvic mass and hypercalcemia. SCCOHT was diagnosed histopathologically. However, loss of neither BRG1 nor INI1 expression was detected. SUMMARY AND CONCLUSION: The diagnosis of SCCOHT should be among the differential diagnoses in adolescents presenting with pelvic mass and hypercalcemia. We would like to share our experience with this rare case, discuss recent management, and emphasize the importance of a multidisciplinary approach. Although it is known that almost all cases have a loss of BRG1 expression and a small group exhibit loss of INI1, our patient indicates that there could be exceptional cases with hitherto undescribed genetic abnormalities.

Gestational trophoblastic neoplasia of intermediate trophoblasts: Epithelioid trophoblastic tumor and placental site trophoblastic tumor, a study of morphologic, immunohistochemical, and next generation sequencing.

Objective: Gestational trophoblastic tumors are very rare neoplasms. We determined the distinctive morphological, immunohistochemical, and clinical features of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) in our cohort. Materials and Methods: Nine cases of PSTT and four cases of ETT were retrieved from the archives. Histomorphologic, immunohistochemical, and clinical features were noted. A molecular study was performed on one PSTT and one ETT case using next-generation sequencing. Results: While the nodular pattern, geographic necrosis, and extracellular eosinophilic globules were peculiar to ETTs, vessel wall affinity, marked pleomorphism, intranuclear pseudoinclusion, spindle tumor cell, and vacuolar degeneration were more specific for PSTTs in our series. An immunohistochemical panel of p63, hPL, and CD146 were helpful for the exact typing of the tumor. p63 positivity supports the ETT and diffuse staining of hPL and CD146 supports the PSTT diagnosis. Three of the patients with metastatic disease (lung and brain metastasis) except one have a high mitotic count (12 and 8) and a long interval between (8 and 10 years) antecedent pregnancy and diagnosis. While KIT and TP53 mutations were observed only in PSTT, amino acid changes in KDR, APC, and SMAD4 genes were detected both in the ETT and PSTT cases. Conclusion: In the prediction of metastasis, the long intervals between antecedent pregnancy and diagnosis, deep myometrial invasion, mitotic count, and Ki67 proliferation index were involved rather than other histomorphological parameters, but none of the parameters is an absolute predictor of the metastasis.

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

Recurrent mucinous neoplasm arising in cesarean scar: A case report and review of literature.

Ovarian mucinous tumors are one of the common epithelial tumors in the ovary, but their recurrence is extremely rare. In a 37-year-old female patient who had had five operations in 7 years due to recurrent mucinous neoplasms, a mass extending to the umbilicus was recently detected during a routine examination. With this finding the patient underwent cystectomy, total abdominal hysterectomy, and left salpingo-oophorectomy. Two of the five operations were performed during cesarean delivery. In the recent surgical procedure, two cysts were removed. A 20 cm cyst in the pelvic region was diagnosed as a mucinous cystadenoma. The other cyst located in the myometrium was a mucinous cystadenoma with focal borderline change and arose in the previous cesarean scar. The authors present what is believed to be the first case of recurrent mucinous neoplasm arising within a cesarean scar. A review of the literature concerning the topic is also presented.