The fluorescence imaging for laparoscopic and laparotomic endometrial sentinel lymph node biopsy (FILLES) trial: Siriraj gynecologic sentinel node of endometrial cancer (SiGN-En) study.

BACKGROUND AND OBJECTIVES: The objective of this study is to establish the detection rate of sentinel lymph node (SLN) biopsies and to determine the sensitivity and false-negative rate of SLN biopsies compared with those of systematic pelvic and para-aortic lymphadenectomies in endometrial cancer. METHODS: This prospective cohort study enrolled patients with endometrial cancer who were scheduled for surgical staging. Patients with a history of chemotherapy or radiotherapy, an abnormal liver function test, or an allergy to indocyanine green (ICG) were excluded. All patients underwent surgical staging with an ICG injection at the cervix. SLNs were identified by a near-infrared fluorescent camera. All SLNs were sent to a pathologist for ultrastaging. RESULTS: From November 2019 to June 2023, 142 patients underwent SLN mapping and surgical staging. SLNs were not detected bilaterally in 8 patients. The detection rate of the SLN biopsies in this study was 91.2%. Thus, the accuracy of the SLN biopsies was 97.6%. The sensitivity for finding metastatic SLNs was 84.2%, with a negative predictive value of 97.22%. CONCLUSIONS: A SLN biopsy in endometrial cancer has a high detection rate and high accuracy. However, surgical expertise and a learning curve are required.

High-risk human papillomavirus genotyping in women with atypical squamous cells of undetermined significance.

We conducted a prospective study to evaluate the prevalence of high-risk human papillomavirus (hr-HPV) positivity in women with atypical squamous cells of undetermined significance (ASC-US). Additionally, we assessed the association of hr-HPV positivity with the pathology of high-grade squamous intraepithelial lesions or worse (HSIL+) and the risk of subsequent detection of squamous intraepithelial lesions. A total of 376 women were included, with 242 (64.4%) exhibiting hr-HPV positivity. The predominant HPV genotypes were 16, 52 and 58. Factors associated with the immediate detection of HSIL+ pathology included a colposcopic impression of high-grade lesions, hr-HPV positivity, HPV 16 positivity, HPV 18 positivity, HPV 58 positivity, age less than 40 years, and biopsy of two or more pieces. However, only the first three factors were statistically significant in multivariate analysis. Among the 291 women who continued surveillance for 6 months or more, the median follow-up period was 41.8 months (interquartile range [IQR] 26.5-54.0). The prevalence of subsequent HSIL in women with hr-HPV positivity versus negativity was 3.6% versus 0.98%, respectively. The median time to the subsequent detection of SIL was 28.7 months (IQR 14.9-41.7). In conclusion, women with ASC-US in our study had a high proportion of hr-HPV positivity. Type-specific HPV testing could play a pivotal role in the development of specific management protocols for women with ASC-US.Clinical trial registration: https://thaiclinicaltrials.org , TCTR20161017002.

Ablative effect of the interstitial laser setting in the human placental model.

AIM: To assess the impact of laser power and time on interstitial ablation generated by neodymium-doped yttrium aluminium garnet (Nd:YAG) and diode laser in the human placental model. METHODS: The experiment was carried out in a simulation model of interstitial laser ablation on ex-vivo placental tissue. One-hundred and forty-four pieces of fresh placentae were interstitially ablated with Nd:YAG or diode laser at various power (15, 20, 25, 30 W)-time (5, 10, 15 s) combinations. The ablation tissues were evaluated using both sonographic and histopathologic measurements. RESULTS: Laser generator, power, and time significantly affected the ablation size (p < 0.001). The coagulation zone continuously increased with extending time at the power of 15, 20, and 25 W. When adjusting to the power of 30 W, increased time from 10 to 15 s did not induce the larger coagulation diameter. The maximal diameter was obtained at the laser power of 20 W for 15 s. The ablation from the diode laser was greater than that from Nd:YAG laser. The sonographic evaluation overestimated the ablation size by an average of 24%. CONCLUSION: Diode laser destroys greater tissue than Nd:YAG laser. Different power settings of interstitial laser ablation produce diverse patterns of correlation between laser time and coagulation size.

Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis.

PURPOSE: To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis. METHODS: A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998-March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death. RESULTS: Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group. CONCLUSIONS: Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer.

ASCCP Risk-Based Colposcopy Recommendations Applied in Thai Women With Atypical Squamous Cells of Undetermined Significance or Low-Grade Squamous Intraepithelial Lesion Cytology.

OBJECTIVE: To compare the proportion of cervical intraepithelial neoplasia (CIN) 2 or worse pathology among different risk strata according to the ASCCP when applied in women who had atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cervical cytology; to assess performance of colposcopy; and to assess the independent predictors for detected CIN 2 or worse pathology. METHODS: This is a secondary analysis of a previous prospective study, which included Thai women with ASC-US or LSIL cytology who underwent high-risk human papillomavirus (HPV) testing and subsequent colposcopy with directed biopsy. Patients were classified as lowest-risk, intermediate-risk, or highest-risk based on cervical cytology, high-risk HPV testing, and colposcopic impression. The proportion of CIN 2 or worse pathology and associated prognostic factors were analyzed. RESULTS: Of 697 women, 103 (14.8%), 573 (82.2%) and 21 (3%) were classified into lowest-risk, intermediate-risk, and highest-risk groups, respectively. The proportion of CIN 2 or worse pathology was 1%, 11.2%, and 61.9% in those same groups, respectively (P<.001). Colposcopy to detect CIN 2 or worse pathology had a sensitivity, specificity, positive predictive value, and negative predictive value of 98.7%, 18%, 13.2%, and 99.1%, respectively. Independent predictors for detecting CIN 2 or worse pathology were positive high-risk HPV, HPV 16/18 positivity, and high-grade colposcopic impression. CONCLUSION: This study supports a no biopsy with follow-up strategy in the lowest-risk group, inconsistent with ASCCP recommendations, but is in alignment with a strategy of multiple targeted biopsies in the intermediate-risk and highest-risk groups.

Sectioning and extensively examining the fimbriated end (SEE-FIM) of the fallopian tube in routine practices, is it worth the effort?

AIM: To determine the prevalence of fallopian tube high-grade serous carcinoma (HGSC) and to analyze the benefit of the sectioning and extensively examining the fimbriated end (SEE-FIM) protocol. METHODS: Fallopian tubes from 450 patients with risk-reducing salpingo-oophorectomy, or tumor of the ovary, endometrium, fallopian tube or peritoneum were examined using the SEE-FIM protocol. Microscopic tubal pathology and the number of paraffin blocks used were evaluated. Immunostaining for p53 was performed to confirm TP53 mutation. Cost effectiveness was determined by equation of incremental cost-effectiveness ratio. RESULTS: Tubal HGSC were detected in 25 out of 70 cases of pelvic extrauterine HGSC, in 1 case of endometrioid carcinoma, and 4 cases of uterine serous carcinoma out of 250 cases of endometrial neoplasm. The mean number of tissue blocks per case was 6. The incremental cost for detecting one case of coexisting fallopian tube HGSC in the study population was 94 Thai baht/3 USD per case. CONCLUSION: The SEE-FIM protocol facilitates identification of lesions that are not distinguishable by classical sampling protocol, and this results in more accurate tumor staging and a better understanding of the carcinogenesis. The benefit of the SEE-FIM protocol was demonstrated, especially in cases at high risk for coexisting fallopian tube carcinoma.

Fetal and Placental Pathology in Congenital Syphilis: A Comprehensive Study in Perinatal Autopsy.

INTRODUCTION: At autopsy, without available serologic information, diagnosing congenital syphilis (CS) relies on identification of Treponema pallidum in tissues. Recognition of clues leading to detection of the organism is important. MATERIALS AND METHODS: Autopsy cases with CS were studied for fetal and placental abnormalities. RESULTS: Twenty-one cases were recruited: 12/21 with identifiable T. pallidum and 9/21 with positive serology and characteristics of CS. 20/21 (95%) demonstrated ≥1 fetal abnormalities. Chronic stress involution of thymus was most common. Hydrops and hepatosplenomegaly were found in >50%. Metaphyseal abnormalities and organ inflammation were found in <30%. Mucocutaneous lesions were lacking. Placental abnormalities were identified in 20/21 (95%). Placentomegaly was most common. Amniotic fluid infection (AFI) was noted in >50%. CONCLUSION: Common findings in CS at autopsy include chronic stress involution of thymus, hydrops, and hepatosplenomegaly. Mucocutaneous lesions are uncommon. Common placental findings in fetal deaths due to CS include placentomegaly and AFI.

Coexistence of Fungal Infections in Psoriatic Nails and their Correlation with Severity of Nail Psoriasis.

BACKGROUND: Nail involvement in psoriasis is often complicated by concomitant fungal infections. The aim of this study was to investigate the prevalence of fungal infections in nail psoriasis and correlate it with the severity of nail psoriasis. MATERIALS AND METHODS: This retrospective study included patients with nail psoriasis aged ≥18 years with at least one fingernail and one toenail involvement who were treated at Siriraj Hospital from September 2012 to January 2014. Severity of nail psoriasis was assesed by Nail Psoriasis Area Severity Index (NAPSI) score. The nail clippings from the the least and most severely involved psoriatic fingernails and toenails were cultured to determine the presence of coexisting fungal infections and isolate the fungal species. RESULTS: Sixty-two patients (33 males, 29 females) fulfilling the inclusion criteria were included in the study. The mean age at the time of presentation was 51.3 years mention SD. The most common nail change consistent with psoriasis was onycholysis, followed by subungual hyperkeratosis. The most commonly isolated fungi in the most severely affected fingernails were Candida spp. (41.9%) manifesting as paronychia in 5 patients (19.2%). The most commonly isolated fungi in the most severely affected toenails were nondermatophytes (NDMs) other than candida (32.3%). Dermatophytes were not detected from any of the psoriatic nails. The fungal species isolated from the most severely affected fingernails were significantly different than the isolated fungal species in the most severely affected toenails (P = 0.026). Fungal organisms were identified in 32.3% of the most severely affected fingernails and in 27.4% of the most severely affected toenails. The overall rate of isolation of fungus was significantly significantly higher in severely affected nails than in the least affected nails (P < 0.005). CONCLUSION: A high rate of concomitant fungal infections, especially yeasts and NDMs, was found in psoriatic nail patients. The rate of isolation of fungal species was higher in severely involved psoriatic nails than mildly involved ones. The spectrum of fungal species isolated from the the severely involved toenails and fingernails were also different from each other. These organisms may be true pathogens that cause onychomycosis or their presence may reflect colonization, contamination, or concurrent infection.

Time and temperature dependence of radiofrequency ablation in the human placenta.

OBJECTIVE: The objective of the study is to compare radiofrequency (RF) effects on fresh placentae with varying levels of sustained time (Ts) and degrees of target temperature (°t). METHOD: A total of 108 pieces of fresh placentae were coagulated with a 2-cm RF needle at 60 W in an organ bath. The vertical and horizontal diameters (Vd, Hd) of tissue coagulation visualized by ultrasound were measured. The impacts of 12 different Ts-°t combinations on the ablation size ascertained on pathological examination (Vdp , Hdp ) were compared using 2-way ANOVA. The agreement between sonographic and pathological findings was assessed using Bland-Altman analysis. RESULTS: Considerable changes in the Vdp and Hdp were associated with increasing the Ts and °t. The impact of RF on tissue coagulation was greatest when the °t was set at 100°C, with further destruction as the Ts progressed to 7 minutes of exposure. The ablation size estimated by ultrasound exhibited an overestimation by an average of 5.65% and 21.02% for Vd and Hd, respectively. CONCLUSION: A prolonged Ts at a higher °t contributes to progressive placental tissue destruction by RF, with maximum destruction at 100°C for 7 minutes in an ex vivo nonperfused placenta. Tissue injury that is apparent on ultrasound may extend beyond pathological damage.

Interobserver reliability of histopathological features for distinguishing between cutaneous polyarteritis nodosa and superficial thrombophlebitis.

AIMS: Interobserver reliability of histopathological features in differentiation between cutaneous polyarteritis nodosa (cPAN) and superficial thrombophlebitis (ST) by assessment of inter-rater agreement of five histological features was investigated. METHODS AND RESULTS: All sections of cPAN and ST were evaluated independently by three experienced pathologists and one resident of pathology. The histopathological features studied included elastic fibre distribution in the vascular wall, a smooth muscle arrangement pattern, an internal elastic lamina pattern, fibrinoid necrosis and luminal thrombosis. Agreement analysis was performed using the kappa coefficient. Sensitivity, specificity, positive predictive value (PPV), positive likelihood ratio (PLR) and 95% confidence interval (95% CI) of the useful histopathological features were analysed. Of all 62 biopsies, 28 were cPAN and 34 were ST. Reproducibility between four observers was in substantial agreement (κ = 0.73). Elastic fibre distribution in the vascular wall (κ = 0.68), fibrinoid necrosis (κ = 0.63), an internal elastic lamina pattern (κ = 0.51) and a smooth muscle arrangement pattern (κ = 0.46) showed high specificity and PPV for differentiating between cPAN and ST. The smooth muscle arrangement pattern, internal elastic lamina pattern and elastic fibre distribution in the vascular wall may be obscured when extensive inflammation and necrosis occurs. CONCLUSIONS: These aforementioned histopathological features are useful in differentiation between cPAN and ST. The Verhoeff-van Gieson (VVG) elastic stain is an important histochemical study for differentiating between cPAN and ST, particularly in cases with extensive inflammation and necrosis.

Undiagnosed Uterine Sarcomas Identified During Surgery for Presumed Leiomyoma at a National Tertiary Hospital in Thailand: A 10-Year Review.

OBJECTIVES: The aim of this study was to evaluate the rate, clinical characteristics, and survival outcomes of an undiagnosed uterine malignancy in patients who underwent surgical treatment for presumed leiomyomas. METHODS: Medical records of patients who underwent surgical treatment for presumed leiomyomas, from January 2004 to September 2013, were retrospectively reviewed, and the data were followed until September 2016. Demographic data, tumor characteristics, oncologic treatment, and response rate were analyzed by descriptive statistics. Kaplan-Meier method was used for survival analysis. This study includes follow-up data through December 31, 2016. RESULTS: A total of 11,258 medical records of presumed leiomyoma patients undergoing hysterectomy during the studied period were reviewed. Pathology of uterine sarcoma was found in 22 patients (0.2%), all of whom were included. Nineteen patients had leiomyosarcoma, and 3 had endometrial stromal sarcoma. Mean age of patients was 48.3 ± 6.9 years. All patients underwent total abdominal hysterectomy, with 20 patients undergoing concurrent bilateral salpingo-oophorectomy. Uterine sarcoma was classified as stage IB in 21 patients and stage IIIC in 1 patient. Fifteen patients were prescribed the following adjuvant treatment: chemotherapy in 13 patients and megestrol acetate in 2 patients. Thirteen patients had recurrent disease, and 3 patients died of their disease. The mean progression-free survival was 50.1 ± 41.3 months, and overall survival was 59.3 ± 43.0 months. CONCLUSIONS: One in 512 patients who underwent hysterectomy because of presumed uterine leiomyomas had inadvertent uterine sarcomas. Even with adjuvant therapy, treatment outcome was rather poor, with almost 60% recurrence rate and median progression-free survival and overall survival of less than 5 years.

Does Microinvasive Adenocarcinoma of Cervix Have Poorer Treatment Outcomes than Microinvasive Squamous Cell Carcinoma?

BACKGROUND: To compare the pathological findings and oncologic outcomes of stage IA cervical carcinoma patients, between adenocarcinoma and squamous cell carcinoma cases. MATERIALS AND METHODS: A total of 151 medical records of stage IA cervical carcinoma patients undergoing primary surgical treatment during 2006-2013 were reviewed. Information from pathological diagnosis and recurrence rates were compared with descriptive statistical analysis. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. RESULTS: The median age was 48.9 years. There was no significant difference in rates of lymph node, parametrium, uterine, vaginal, or ovarian metastasis, when comparing adenocarcinoma with squamous cell carcinoma. Overall recurrence rates of adenocarcinoma (5.7%) and squamous cell carcinoma (2.6%) were not statistically significant different, even when stratified by stage. When comparing progression free survival with squamous cell carcinoma, adenocarcinoma had an HR of 0.448 (0.073-2.746), p=0.386. CONCLUSIONS: Microinvasive adenocarcinoma of cervix has similar rate of extracervical involvement and oncologic outcomes to squamous cell carcinoma.

p16ink4 and cytokeratin 7 immunostaining in predicting HSIL outcome for low-grade squamous intraepithelial lesions: a case series, literature review and commentary.

p16ink4 and cytokeratin 7 (CK7) have been proposed to identify low-grade squamous intraepithelial lesions (LSIL) at greater or lesser risk for an outcome of high-grade squamous intraepithelial lesion (HSIL). We correlated CK7 and p16ink4 staining in LSILs with outcome on follow-up and placed this information in the context of prior reports. Cervical LSIL biopsies with at least 1-year follow-up information were immunostained for CK7 and p16ink4. Follow-up outcomes included no SIL, LSIL (persistence) or HSIL (CIN2+). In all, 109 LSILs were studied and 18.3% stained positive for CK7. Ninety-one percent of CK7-negative LSILs regressed, 4.5% persisted, and 4.5% had an HSIL outcome, versus 60, 20, and 20% of CK7-positive LSILs, respectively (P=0.036). p16ink4 status did not significantly associate with outcome. Review of the literature revealed a highly variable rate of both positive p16ink4 immunoreactivity in LSIL and CIN2+ outcome for p16-positive LSIL but a consistently high negative predictive value (>90%) in the case of no/low p16 expression. Inter-observer reproducibility for the diagnosis of CIN2 in the literature ranged from poor to good, with unanimous agreement on the diagnosis of CIN2 occurring in less than 25% of cases. As with high-risk human papillomavirus testing, the most clinically useful result of p16ink4 staining is a negative test, implying no lesion or CIN1 and conferring a low risk of HSIL outcome. HSIL outcomes ('progression') are highly variable and are subject to wide differences in inter-observer interpretation for CIN2. This argues against the wisdom of relying on p16ink4 to both predict CIN2+ or upgrade CIN1 to CIN2. It also begs the question of whether CIN2 should be replaced by an alternate and less pejorative term (SIL of intermediate grade) for lesions that are not reproducibly classified as LSIL or HSIL, with an appropriate management scheme.

Thermal Response of In Vivo Human Skin to Fractional Radiofrequency Microneedle Device.

Background. Fractional radiofrequency microneedle system (FRMS) is a novel fractional skin resurfacing system. Data on thermal response to this fractional resurfacing technique is limited. Objectives. To investigate histologic response of in vivo human skin to varying energy settings and pulse stacking of a FRMS in dark-skinned subjects. Methods. Two female volunteers who were scheduled for abdominoplasty received treatment with a FRMS with varying energy settings at 6 time periods including 3 months, 1 month, 1 week, 3 days, 1 day, and the time immediately before abdominoplasty. Biopsy specimens were analyzed using hematoxylin and eosin (H&E), Verhoeff-Van Gieson (VVG), colloidal iron, and Fontana-Masson stain. Immunohistochemical study was performed by using Heat Shock Protein 70 (HSP70) antibody and collagen III monoclonal antibody. Results. The average depth of radiofrequency thermal zone (RFTZ) ranged from 100 to 300 µm, correlating with energy levels. Columns of cell necrosis and collagen denaturation followed by inflammatory response were initially demonstrated, with subsequent increasing of mucin at 1 and 3 months after treatment. Immunohistochemical study showed positive stain with HSP70. Conclusion. A single treatment with a FRMS using appropriate energy setting induces neocollagenesis. This wound healing response may serve as a mean to improve the appearance of photodamaged skin and atrophic scars.

Coexistence of Graves' disease and unilateral functioning Struma ovarii: a case report.

BACKGROUND: Coexisting of Graves' disease and functioning struma ovarii is a rare condition. Although the histology of struma ovarii predominantly composed of thyrocytes, the majority of the patients did not have thyrotoxicosis. The mechanism underlying the functioning status of the tumor is still unclear but the presence of thyroid stimulating hormone receptor (TSHR) is thought to play a role. Here we describe the patient presentation and report the TSHR expression of the tumor. CASE PRESENTATION: A 56-year old Asian woman presented with long standing thyrotoxicosis for 23 years. She was diagnosed with Graves' disease and thyroid nodules. She had bilateral exophthalmos and had high titer of plasma TSHR antibody. Total thyroidectomy was performed and the histologic findings confirmed the clinical diagnosis. The patient had persistent thyrotoxicosis postoperatively. Thyroid uptake demonstrated the adequacy of the thyroid surgery and the whole body scan confirmed the presence of functioning thyroid tissue at pelvic area. The surgery was scheduled and the patient had hypothyroidism after the surgery. The pathological diagnosis was struma ovarii at right ovary. We performed TSHR staining in both the patient's struma ovarii and in 3 cases of non-functioning struma ovarii. The staining results were all positive and the intensity of the TSHR staining of functioning struma ovarii was the same as that in other cases of non-functioning tumors, suggesting that the determinant of functioning struma ovarii might be the presence of TSHR stimuli rather than the intensity of the TSHR in the ovarian tissue. CONCLUSION: In patients with Graves' disease with persistent or recurrent thyrotoxicosis after adequate ablative treatment, the possibility of ectopic thyroid hormone production should be considered. TSHR expression is found in patients with functioning and non-functioning struma ovarii and cannot solely be used to determine the functioning status of the tumor.

Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed model for anatomical differences in HPV-related cancer risk.

Human papilloma virus (HPV) infection causes cancers and their precursors (high-grade squamous intraepithelial lesions) near cervical and anal squamocolumnar junctions. Recently described cervical squamocolumnar junction cells are putative residual embryonic cells near the cervical transformation zone. These cells appear multipotential and share an identical immunophenotype (strongly CK7-positive) with over 90% of high-grade squamous intraepithelial lesions and cervical carcinomas. However, because the number of new cervical cancers discovered yearly world wide is 17-fold that of anal cancer, we posed the hypothesis that this difference in cancer risk reflects differences in the transition zones at the two sites. The microanatomy of the normal anal transformation zone (n=37) and topography and immunophenotype of anal squamous neoplasms (n=97) were studied. A discrete anal transition zone was composed of multilayered CK7-positive/p63-negative superficial columnar cells and an uninterrupted layer of CK7-negative/p63-positive basal cells. The CK7-negative/p63-positive basal cells were continuous with-and identical in appearance to-the basal cells of the mature squamous epithelium. This was in contrast to the cervical squamocolumnar junction, which harbored a single-layered CK7-positive/p63-negative squamocolumnar junction cell population. Of the 97 anal intraepithelial neoplasia/squamous cell carcinomas evaluated, only 27% (26/97) appeared to originate near the anal transition zone and only 23% (22/97) were CK7-positive. This study thus reveals two fundamental differences between the anus and the cervix: (1) the anal transition zone does not harbor a single monolayer of residual undifferentiated embryonic cells and (2) the dominant tumor immunophenotype is in keeping with an origin in metaplastic (CK7-negative) squamous rather than squamocolumnar junction (CK7-positive) epithelium. The implication is that, at birth, the embryonic cells in the anal transition zone have already begun to differentiate, presenting a metaplasia that-similar to vaginal and vulvar epithelium-is less prone to HPV-directed carcinogenesis. This in turn underscores the link between cancer risk and a very small and discrete population of vulnerable squamocolumnar junction cells in the cervix.

Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma.

Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

Diagnosis of Xp11.2 Translocation Renal Cell Carcinomas in the Thai Patients.

BACKGROUND: Xp11.2 translocation renal cell carcinomas (TRCCs) are rare tumors recently accepted as a separated tumor type in 2004 WHO classification. To diagnose these tumors, histological recognition and confirmation of translocation are necessary. While the incidence of overall renal cell carcinomas (RCCs) is increased after the age of 40, Xp11.2 TRCCs are predominantly reported in young patients. The incidence of these tumors in Thailand has not been evaluated. OBJECTIVE: To identify the frequency of Xp11.2 TRCCs, clinical presentation and follow-up information in 40 year-old or younger patients by using TFE3 immunostaining to confirm the translocation. MATERIAL AND METHOD: All cases of 0- to 40-years-old patients diagnosed as RCCs from nephrectomy specimens between 2001 and 2011 at Siriraj Hospital were reviewed by one pathology resident and two pathologists. Immunohistochemical staining for TFE3 was performed on cases morphologically suspected for TRCC or showing unusual histology. RESULTS: Four cases consistent with Xp11.2 TRCC were identified by TFE3 immunostaining from all 31 cases (12.9%). Three cases were females and one was male. Two cases were at stage 4 and passed away several months after the operation. The other two patients were at stage 2. One patient is alive without recurrence for at least 36 months after surgery alone. The other died from underlying SLE. CONCLUSION: TFE3 immunostaining is a useful andpractical toolfor screening and diagnosis of Xp11.2 TRCCs, but staining results can be difficult to interpret. Thus, genetic analysis is still necessary especially when immunostaining shows problematic result. Fresh tumor tissue sampling in all young patients is recommended in case of further genetic studies needed.

The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium.

The oviducts contain high-grade serous cancer (HGSC) precursors (serous tubal intraepithelial neoplasia or STINs), which are γ-H2AX(p) - and TP53 mutation-positive. Although they express wild-type p53, secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer; moreover, both STINs and SCOUTs share a loss of PAX2 expression (PAX2(n) ). We evaluated PAX2 expression in proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs, Walthard cell nests (WCNs), STINs, and HGSCs, and the expression of genes chosen empirically or from SCOUT expression arrays. Clones generated in vitro from embryonic gynaecological tract and adult Fallopian tube were Krt7(p) /PAX2(n) /EZH2(p) and underwent ciliated (PAX2(n) /EZH2(n) /FOXJ1(p) ) and basal (Krt7(n) /EZH2(n) /Krt5(p) ) differentiation. Similarly, non-ciliated cells in normal mucosa were PAX2(p) but became PAX2(n) in multi-layered epithelium undergoing ciliated or basal (WCN) cell differentiation. PAX2(n) SCOUTs fell into two groups: type 1 were secretory or secretory/ciliated with a 'tubal' phenotype and were ALDH1(n) and ß-catenin(mem) (membraneous only). Type 2 displayed a columnar to pseudostratified (endometrioid) phenotype, with an EZH2(p) , ALDH1(p) , ß-catenin(nc) (nuclear and cytoplasmic), stathmin(p) , LEF1(p) , RCN1(p) , and RUNX2(p) expression signature. STINs and HGSCs shared the type 1 immunophenotype of PAX2(n) , ALDH1(n) , ß-catenin(mem) , but highly expressed EZH2(p) , LEF1(p) , RCN1(p) , and stathmin(p) . This study, for the first time, links PAX2(n) with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs, and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumour suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2), calcium binding (RCN1), and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention.

Extramedullary hematopoiesis in the uterine cervix associated with tissue repair.

Extramedullary hematopoiesis (EMH) is the presence of hematopoietic precursors outside the bone marrow. This condition is usually associated with hematologic disorders. Although EMH can be found in almost every site in the body, female genital tract involvement is rare. The authors report EMH in the uterine cervix from a 64-year-old patient following cervical biopsy due to abnormal cervical cytology. Neither neoplasm nor hematologic disorder was detected before the diagnosis and after 1 year of follow up. To the best of our knowledge, this is the first reported case of EMH involving the uterine cervix which showed an association with tissue repair.