Molecular-based classification of endometrial carcinoma in Northern Thailand: impact on prognosis and potential for implementation in resource-limited settings.

BACKGROUND: Endometrial carcinoma is molecularly categorized into four subgroups: polymerase-E exonuclease domain-mutant (POLE-mut), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), and no specific molecular profile (NSMP). This classification scheme has been included into clinical recommendation for post-operative risk-based management, although there have been few Asian studies on this topic. The present study aimed to evaluate the prevalence and clinical outcomes of endometrial carcinoma using this classification in Northern Thailand and the feasibility of implementation in resource-limited settings. METHODS: Endometrial carcinomas from hysterectomy specimens were classified using immunohistochemistry for MMR proteins and p53, as well as POLE mutation testing. Clinicopathological variables and outcomes were analyzed. The costs of the molecular information-based approach were compared to those incurred by the conventional approach (without molecular classification). RESULTS: Of 138 patients, 52.9% in the NSMP subgroup, 28.2% were in the MMR-d, 13.8% in the p53-abn, and 5.1% in the POLE-mut. After adjusting for other variables, patients with POLE-mut showed the most favorable outcomes, while those with p53-abn had the poorest survival. When estimating the costs for post-operative management, the use of molecular classification resulted in a 10% increase over the conventional approach. However, the cost increased only by 1% if only POLE testing was used to identify patients for treatment omission. CONCLUSION: In Northern Thailand, endometrial carcinoma had comparable subgroup distribution and prognostic implications to previous reports, supporting the implementation of management guidelines that incorporate molecular information. In resource-limited settings, at least POLE mutation testing in early-stage patients should be considered.

Clear-Cell Mesothelioma of Uterine Corpus: Diagnostic Challenges in Intraoperative Frozen Sections.

The clear-cell variant of epithelioid mesothelioma is an extremely rare neoplasm of the peritoneum. It shares histomorphologic features overlapping with a wide variety of tumors including carcinomas and other non-epithelial neoplasms. The diagnosis of peritoneal clear-cell mesothelioma is not always straightforward, despite known immunohistochemistry (IHC) markers. Due to its rarity, this entity may be diagnostically confused with other clear-cell neoplasms, particularly in intraoperative frozen sections. Here, we present a case of clear-cell mesothelioma originating in the uterine serosa that was initially misdiagnosed as clear-cell adenocarcinoma in the intraoperative frozen section. Microscopically, the tumor showed diffuse tubulocystic spaces of variable size lined by clear cells with moderate nuclear atypia. Immunohistochemical staining confirmed the diagnosis of clear-cell mesothelioma. Recognition of this entity, albeit rare, is important as the diagnosis may significantly affect the management considerations. The judicious use of an IHC panel helps to distinguish this tumor from other mimickers.

Microcystic Stromal Tumor with Predominant Bizarre Nuclei of Ovary in a Pregnant Woman.

Microcystic stromal tumor (MST) is a rare type of pure stromal tumor in the category of ovarian sex cord-stromal tumors. It is characterized by a distinctive microcystic appearance with bland tumor cells. Although the pathological diagnosis can be straightforward based on the typical histomorphology in most MSTs, the cases with morphologic variation can pose a diagnostic challenge due to unfamiliarity of pathologists with the histologic spectrum of MST and its negativity for inhibin and calretinin, the commonly used sex cord-stromal markers. The coexistence between MST and mucinous epithelial tumor is extremely rare. We present the first case, to our knowledge, of ovarian MST with predominant bizarre nuclei coexisting with mucinous cystadenoma in a pregnant woman. The histomorphology in this case presents a diagnostic challenge and raises differential diagnosis for a wide variety of ovarian malignant neoplasms including nonneoplastic lesions.

Small cell neuroendocrine carcinoma of vagina: Report of a unique case with literature review.

Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been reported in only 3 previous cases of SCC of vagina. Herein, we present a unique case of vaginal small cell carcinoma with discordant HPV testing results between vaginal and cervical samples. We also review and discuss findings from previously reported cases of small cell carcinoma of vagina.

Comparison of Cervical HSIL Outcome between Pregnant and Non-Pregnant Women.

OBJECTIVE: Variables predicting outcome of high-grade squamous intraepithelial lesion (HSIL) in pregnancy are unknown. The HSIL is usually managed conservatively during pregnancy. We aim to assess morphological features of HSIL diagnosed during pregnancy and identify variables predicting HSIL outcome in pregnant and non-pregnant women. METHODS: ThinPrep pap smears with HSIL in pregnant (2014-2019) and non-pregnant females (2017-2019) were identified. The pathology material from follow-up cervical samples was reviewed by two participating pathologists (TP and KS). Regression was defined as benign or residual low-grade squamous intraepithelial lesion. Histological findings were recorded and compared between pregnant and non-pregnant cohort. RESULTS: The HSIL regression rate was higher in colposcopic samples (16% vs. 0%; p=0.05) and follow up excisions (27% vs. 23%) from pregnant cohort. Overall regression rate was higher in pregnant versus non-pregnant cohort (34% vs. 23%; p=0.1). The stromal inflammation was prominent in biopsies from pregnant cohort (p=0.02). Presence of CIN 2 (versus CIN 3) in non-pregnant cohort predicted HSIL regression (p=0.04). The time to biopsy and excision (from pap smear) was significantly higher in pregnant cohort (p=0.0001). HSIL histological features (nuclear pleomorphism, hyperchromasia, nuclear contour irregularity, nuclear to cytoplasmic ratio, and mitosis) and HPV types were similar in both cohorts and did not predict regression. CONCLUSION: The higher rate of benign findings during HSIL follow up in pregnancy is likely related to duration and stromal inflammation. HSIL regression is frequently noted following CIN2 diagnosis in non-pregnant setting. HSIL histology is similar in postpartum and non-pregnant females.

Adenomatoid Tumor of Fallopian Tube With "Deciduoid" Morphology and Atypical Nuclear Features.

Adenomatoid tumor is a benign neoplasm of mesothelial origin. Adenomatoid tumor in female genital tract shows typical morphologic features with bland nuclei. Deciduoid morphology has not been reported in adenomatoid tumor. Tumors with deciduoid cells and atypical nuclear features may pose a diagnostic challenge and raise the suspicion of malignancy. We present a case of fallopian tube adenomatoid tumor with deciduoid morphology and atypical nuclear features in a 39-year-old woman with prolonged progestin therapy. We hypothesize that the unusual morphological changes in adenomatoid tumor, like deciduoid morphology and nuclear atypia, may be secondary to hormone effects.

Sporadic uterine Lymphangioleiomyomatosis (LAM): Report of a unique case arising in the lower uterine segment with short review.

•Extrapulmonary lymphangioleiomyomatosis is rare and can be associated with tuberous sclerosis.•Recognition of lymphangioleiomyomatosis is important for early disease screening and genetic testing.•Lymphangioleiomyomatosis in lower uterine segment is very rare and can be overlooked.

Primary signet ring cell carcinoma with neuroendocrine differentiation arising in mucinous borderline tumor of the ovary.

•Primary signet ring cell carcinoma in ovarian mucinous tumor is rare.•The most important differential diagnosis is metastatic carcinoma.•We report a case of primary ovarian signet ring cell carcinoma in mucinous tumor.•Clinicopathological correlation is essential to establish the correct diagnosis.

Leiomyosarcoma and Squamous Cell Carcinoma Arising in Mature Cystic Teratoma of the Ovary.

The occurrence of malignant transformation in mature cystic teratoma of the ovary is rare, with squamous cell carcinoma being the most common histologic type. Sarcomatous transformation has been rarely described in the literature. We present a case of leiomyosarcoma with a minor component of squamous cell carcinoma arising in mature cystic teratoma of ovary in a 65-year-old woman. The malignant tumor showed two distinct components of sarcomatous and invasive epithelial elements, which were confirmed by immunostaining. To our knowledge, only four cases of leiomyosarcoma in ovarian mature cystic teratoma have been reported and this is a unique case report of leiomyosarcoma and squamous cell carcinoma arising in a mature cystic teratoma of ovary.

Prognostic Value of Tumor Budding in Early-Stage Cervical Adenocarcinomas

Background: Tumor budding has recently been reported as an independent adverse prognostic factor for colorectal adenocarcinomas and other types of carcinoma in the digestive tract. This study aimed to evaluate the prognostic value of tumor budding in patients with early-stage cervical adenocarcinomas and any associations with other clinical and pathological features. Methods: Histological slides of patients with early-stage (IB-IIA) usual-type endocervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection, without preoperative chemotherapy, between January 2006 and December 2012 were reviewed. Tumor budding was evaluated in routinely-stained sections and defined as detached single cells or clusters of fewer than 5 cells in a tumor invasive front and was stratified based on the number of bud counts in 10-high-power fields as low (<15 buds) and high (≥15 buds). Correlations between tumor bud count and other clinical and pathological variables including follow-up outcomes were assessed. Results: Of 129 patients, a high tumor bud count was observed in 15 (11.6%), positively associated with histologic grade 3 (p<0.001), invasive pattern C (Silva System) (p=0.004), lymph node metastasis (p=0.008), stage IB2-IIA (p=0.016), and tumor size >2 cm (p=0.036). Kaplan-Meyer analysis showed a significant decrease in both disease-free survival and cancer-specific survival for patients with a high tumor bud count (p=0.027 and 0.031, respectively). On multivariate analysis, histologic grade 3 was the only independent predictor for decreased disease-free survival (p=0.004) and cancer-specific survival (p=0.003). Conclusions: A high tumor budding count based on assessment of routinely-stained sections was found to be associated with decreased disease-free and cancer-specific survival in patients with early-stage cervical adenocarcinomas. However, it was not found to be an independent prognostic predictor in this study.

Angiosarcoma Arising in Ovarian Mucinous Tumor: A Challenge in Intraoperative Frozen Section Diagnosis.

Angiosarcoma of the ovary is rare but represents an aggressive type of malignant ovarian neoplasms. The purpose of this report is to describe the features of angiosarcoma arising in mucinous tumor that was misinterpreted as a benign vascular proliferation during the intraoperative consultation. A 45-year-old woman presented with an abdominal mass for 1 month. Exploratory laparotomy was performed. A 35 cm right ovarian mass submitted for intraoperative consultation was a multicystic mucinous tumor with an 8 cm area of hemorrhagic lesion between cystic locules. The frozen section diagnosis was at least mucinous borderline tumor. The hemorrhagic area, which was intraoperatively interpreted as organizing vessels associated with previous hemorrhage, represented angiosarcoma in permanent sections. Angiosarcoma may present a challenge in intraoperative frozen section diagnosis of an ovarian mass. The presence of ectatic anastomosing vessels with dissecting growth appears to be the clue to a suspicion of angiosarcoma. The presence of endothelial atypia provides further support for the diagnosis. A macroscopic hemorrhagic area in an ovarian mucinous tumor should be evaluated with care, and the possibility of angiosarcoma should be borne in mind.

Rapid recovery from catastrophic paraneoplastic anti-NMDAR encephalitis secondary to an ovarian teratoma following ovarian cystectomy.

This report is aimed to describe a life-threatening case of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis secondary to ovarian teratoma with rapid recovery in 1 day after the removal of the tumour. A 23-year-old woman presented with sudden headache, personality changes and seizure. After neurological assessment, limbic or herpes encephalitis was provisionally diagnosed and treated with intravenous immunoglobulin, acyclovir and steroids. The patient had progressive severe neurological symptoms, requiring prolonged intubation and mechanical ventilation. An anti-NMDAR antibody test revealed positive in serum and cerebrospinal fluid at 3 weeks of admission. Pelvic ultrasound examination and CT scan revealed bilateral small ovarian teratomas. Bilateral ovarian cystectomy was performed by open surgery. The patient showed rapid improvement and no longer needed intubation 2 days after the operation. In conclusion, we described a catastrophic case of ovarian teratoma-associated encephalitis with delayed diagnosis but rapid recovery after ovarian cystectomy. This information can probably be helpful to neurologists and gynaecologists.

Prognostic evaluation of tumor-stroma ratio in patients with early stage cervical adenocarcinoma treated by surgery.

BACKGROUND: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. MATERIALS AND METHODS: Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (≥50%). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. RESULTS: Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. CONCLUSIONS: Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study.

Ovarian teratoma with predominant hemangiomatous component in early childhood.

BACKGROUND: Ovarian teratoma with predominant hemangiomatous component in pediatric patients is very rare and its presentation may mimic that of malignancy. CASE: A 2-year-old girl presented with proptosis of the right eye. A right ovarian mass was detected on the physical examination. The right orbital lesion was consistent with venolymphatic-type vascular malformation on magnetic resonance imaging. The abdominal computed tomographic scan revealed a solid ovarian mass that raised a suspicion for malignancy. A 5.5-cm right ovarian solid hemorrhagic mass was resected. Microscopically, the mass was almost exclusively composed of variable-sized blood vessels, with few microscopic mature teratomatous foci. SUMMARY AND CONCLUSION: Hemangiomatous lesion of the ovary may have a presentation mimicking a malignant neoplasm, and may be associated with multiple vascular lesions.

Accuracy of frozen-section diagnosis of ovarian mucinous tumors.

OBJECTIVE: The objective of the study was to evaluate the diagnostic accuracy of intraoperative frozen sections of ovarian mucinous tumors and to identify the features associated with an inaccurate diagnosis. METHODS: Cases of ovarian mucinous tumors (benign, low malignant potential [LMP] or borderline, primary malignant, and metastatic) diagnosed by frozen section or final histology were recruited. Frozen-section diagnoses were compared with the final histologic diagnoses. Possible variables associated with diagnostic discrepancy were analyzed. RESULTS: A comparison of the diagnoses was done in 195 cases (102 benign, 61 LMP, 18 primary malignant, and 14 metastatic). Diagnostic agreement was observed in 164 cases (84.1%) and discrepancy in 31 cases (15.9%). The sensitivity of frozen-section diagnosis was low in LMP (67.2%) and malignant tumors (55.6%). The specificity was the lowest in the benign category (78.5%). The positive predictive values of all categories were less than 90% (range, 83.3%-85.7%). Diagnostic discrepancy was associated with tumor size of greater than 13 cm (P = 0.019) and the number of frozen sections of 4 or more (P = 0.035). However, in a multivariate analysis, there was no independent predictor of diagnostic discrepancy. The number of frozen sections 4 or more was strongly associated with tumor size of greater than 13 cm (P = 0.004). CONCLUSIONS: The sensitivity of frozen-section diagnosis of LMP and malignant mucinous tumors was low. The inaccuracy of a frozen-section diagnosis of ovarian mucinous tumors may be related to a tumor size of greater than 13 cm. Increasing the number of intraoperative samples over 3 sections per case may not effectively increase the accuracy of frozen-section diagnosis in mucinous tumors.