Association of molecular subgroups with pathological parameters in endometrial carcinomas.

BACKGROUND: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters. METHODS: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers (p53, mismatch repair proteins,MutS homolog6 and Postmeiotic seggregation 2 respectively[MSH6, and PMS2]), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA). RESULTS: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE, and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal (P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype (P = 0.001) and low-grade type (90.5%; P = 0.005). CONCLUSION: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.

Endometriosis in clear cell and endometrioid carcinoma ovary: its impact on clinicopathological characteristics and survival outcomes.

Background: Malignant transformation in endometriosis was first described by Sampson in 1925. There is now sufficient evidence of its association specifically with endometrioid (EOC) and clear cell ovarian cancer (CCOC). Whether endometriosis-associated ovarian cancer (EAOC) is a distinct clinicopathological entity from non-endometriosis-associated ovarian cancer (NEAOC) remains uncertain. Objectives: This study aimed to assess the impact of endometriosis on clinical characteristics and survival outcomes in EOC and CCOC. Methods: This is a retrospective single-institution analysis of patients diagnosed with CCOC AND EOC between 2010 and 2021. Demographic and clinical presentation data were obtained from medical records. Patients were followed up till March 2023. Statistical analysis was done using the IBM SPSS Statistics 20 Windows. Results: Of the 77 cases of CCOC and EOC ovary, 38 had histopathologically proven endometriosis. There was no difference in age (51.62 and 50.05 years, respectively), body mass index, parity, menopausal status and CA 125 levels at presentation. Ascites was more frequent in the absence of endometriosis (30% versus 8.1%, p = 0.015). However, this did not translate to a statistical difference in the stage, with the majority presenting in the early stage. (94% versus 83%). All 78 patients underwent primary cytoreduction with equal rates of optimal resection.There was no difference in the mean disease-free interval between EAOC and NEAOC (107.6 and 109.4 months, p 0.484). Recurrences were predominantly pelvic in both groups. The disease-specific survival was 111.7 and 120.1 months, respectively, with and without endometriosis. This was however not statistically significant (p 0.751). Conclusion: In the Indian population, endometriosis did not have any impact on the age at presentation, CA 125 levels, stage of the disease and survival outcomes in EOC and CCOC ovary.

How hairfall saved the patient from cancer twice - A postmenopausal patient with synchronous endometrial and endocervical carcinomas presenting with endocrine symptoms.

Ovarian stromal hyperthecosis is an uncommon nonneoplastic cause of ovarian hyperandrogenism mainly in postmenopausal women. Here, we present a case of a postmenopausal woman who presented with features of virilization like alopecia and hirsutism. During its workup, two malignancies were diagnosed at a very early stage. Microscopic focus of endometrial adenocarcinoma in a polyp and similar focus of endocervical adenocarcinoma in the subsequent hysterectomy specimen were noted. Presence of synchronous malignancies in the uterus is very rare and it being detected in a patient who presented with a non-related symptom of hairfall makes it an interesting case scenario.

Recurrent extramedullary plasmacytomas without multiple myeloma: A case report with review of the literature.

BACKGROUND: Extramedullary plasmacytoma (EMP) is an uncommon presentation and usually occurs in conjunction with multiple myeloma (MM). An EMP without developing MM at any point is an extremely rare presentation, and only seven such cases have been reported in the literature to date. PRESENTATION OF CASE: We present a case of EMP, who presented with multiple recurrent lesions in rare sites like nasal cavity, testis and skin without the involvement of bone marrow at any point of disease course. He was treated with multiagent chemotherapy (DT-PACE) and continues to be in remission at 29 months post-chemotherapy, which is the longest amongst all the cases reported so far. DISCUSSION AND CONCLUSIONS: There are no clearly defined guidelines to treat EMP. Our case had a clinical presentation at very unusual sites and was treated with DT-PACE regimen as against the previous seven reported cases and had the most prolonged period of remission.

Impact of Intraoperative Tumor Spillage in Uterine Leiomyosarcoma: a Retrospective Single-Institution Analysis.

Uterine leiomyosarcoma is a rare female reproductive system tumor which is difficult to distinguish from uterine leiomyoma preoperatively. Manual and power morcellation are used to remove the large uterus through the vagina or small abdominal incision. Worse outcome with use of power morcellation is now clear but impact of manual morcellation on survival outcome not established till date. The objective of the present study was to find impact of tumor spillage and to evaluate influencing factors for oncological outcome and prognosis in uterine leiomyosarcoma patients. This is a single-institutional retrospective cohort study including all uterine leiomyosarcoma patients from January 2005 to December 2017. Role of intraoperative tumor spillage and other influencing factors on oncological outcome were assessed. Thirty-three patients with median follow-up period of 49.7 months were evaluated. Stage 1 and absence of tumor spill had significant association with prolonged progression-free survival. Stage 1 uterine leiomyosarcoma (56.8 vs 6.8 months, p = < 0.001), intraoperative tumor spillage (p = 0.03) and progression-free survival > 15 months (68.5 vs 12.2 months, p = < 0.001) were favourable prognostic factors to predict better survival outcome but unable to establish significance on multivariate analysis. Survival plot did not reach median limit for stage I uterine leiomyosarcoma patients with preoperative suspicion. Age, site of recurrence and mitotic index had no significant association with better survival in the present study. Stage I disease and absence of tumor spillage during surgery improved progression-free survival but did not affect overall survival. Progression-free survival more than 15 months can predict better overall survival.

Long-term survival outcome of advanced epithelial ovarian cancer: A single institutional study.

BACKGROUND: A number of patients with advanced-stage epithelial ovarian cancer do survive beyond 5 years. The long-term follow-up data are limited, especially for the Indian setting. We evaluated the 10-year survival outcome and influencing clinicopathological factors. METHODS: A retrospective analysis of advanced-stage epithelial ovarian cancer patients who underwent primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) from 2005 to 2008 was conducted. Survival analysis was performed with the Kaplan-Meier method, and the Cox proportional hazards model was used for prognostic clinicopathological factors analysis. RESULTS: Ninety-four patients with a median age of 54.5 (18-79) years were evaluated. The median follow-up period was 11.2 years. The overall survival (OS) rates at 5, 7, and 10 years were 37%, 23%, and 18%, respectively. The median OS (MOS) was 46 (95% confidence interval [CI], 36-55.8) months and progression-free survival (PFS) was 19.5 (15.3-23.6) months. Long-term survival was significantly predicted by R0 resection (complete cytoreduction with no macroscopic residual disease) and PFS >20 months while prolonged PFS was influenced by age ≤55 years and R0 resection. For the R0 resection group, patients who underwent PCS had better overall survival in comparison with ICS [72.1(25.2-119) months vs 47.4 (34.9-59.9)months] on 10 years follow-up but was not significant statistically. CONCLUSION: Patients with age ≤55 years, R0 resection, PFS >20 months have a better 10-year survival outcome. Among R0 resection, patients undergoing PCS have clinically a better outcome on 10-year follow-up.

Lethal Cenani Lenz syndrome in two consecutive pregnancies: Further extension of phenotype from Maldives.

Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development. Mutations in the APC gene have also been occasionally associated with CLS. The phenotypic spectrum ranges from mild to very severe perinatal lethal type depending on the type of variant. We report a pathogenic variant, c.2710 del T (p.Trp904GlyfsTer5) in theLRP4 gene, in a fetus with lethal Cenani Lenz syndrome with antenatal presentation of tetraphocomelia and symmetrical involvement of hands and feet.

Clinicopathologic spectrum of necrotizing lymphadenitis.

BACKGROUND: Necrotizing lymphadenitis represents a group of diseases characterized by non-granulomatous inflammation and necrosis of the lymph node, caused by a variety of infective and inflammatory diseases, most common being Kikuchi-Fujimoto disease, acute Epstein Barr viral infection and systemic lupus erythematosis (1). OBJECTIVES: To study the morphological features in lymph nodes in cases of necrotizing lymphadenitis, to correlate them with specific etiological conditions.Materials and methods-58 cases of necrotizing lymphadenitis were reviewed and categorized into different etiological sub types, i.e. acute EBV lymphadenitis, lupus lymphadenitis and the rest as Kikuchis lymphadenitis. Morphological features studied were presence of vascular proliferation, periadenitis, foamy macrophage, neutrophil and plasma cell infiltrate. Clinical follow up was done. RESULTS: 62.2% of cases were Kikuchis lymphadenitis. Both lupus and Kikuchis had a female preponderance (78% and 62% respectively). Among the morphological parameters, plasma cell infiltration and vascular proliferation showed significant association with lupus lymphadenitis. Kikuchis and EBV lymphadenitis showed self-limiting course, with only 2 cases of Kikuchis developing recurrence .4 cases developed complications. All cases of lupus lymphadenitis needed long term therapy. CONCLUSION: Kikuchis lymphadenitis is the most common cause of necrotizing lymphadenitis, followed by lupus and acute EBV lyphadenitis.Young females were commonly affected in the first 2 groups. It is worthwhile to classify the cases of necrotizing lymphadenitis into etiological subgroups as the prognosis and treatment differ (2). Among the morphological features studied, plasma cell infiltrate and vascular proliferation were significantly associated with lupus lymphadenitis, hence can be used to predict etiology.

Retrospective Analysis of Factors Affecting Recurrence in Borderline Ovarian Tumors.

Background Borderline ovarian tumors (BOTs) are an intermediate form of neoplasia, between benign and malignant. The aim of this retrospective analysis is to evaluate the clinicopathological characteristic profile of BOTs and to determine the predictors of recurrence in BOTs. Methods A retrospective review of all patients diagnosed, treated, and followed up for BOTs between 2010 and 2017 at Amrita Institute of Medical Sciences, Kerala, India, was conducted. Clinicopathological details and details of management, outcome, and survival were retrieved, and data were analyzed descriptively and for survival. Results A total of 103 patients were identified. During the median follow-up of 46.0 months, 15 (14.6%) patients developed recurrent disease, 6 (5.82%) had recurrence with progression to invasive carcinoma, and 9 had recurrent disease with borderline or benign histology. Mucinous tumors were found to have more recurrences than serous BOT (17.8 vs. 12.3%). Disease-related deaths (5/103 [4.9%]) were observed only in patients with progression to invasive carcinoma. Univariate analysis indicated that staging surgery was the most important prognostic factor that affected the disease-free survival ([DFS] 103 vs. 97 vs. 71 months, respectively, for complete staging vs. fertility-preserving staging vs. conservative surgery; p < 0.05). Conclusions Conservative surgery was associated with a higher risk of recurrence. Fertility-preserving staging surgery is an acceptable option in younger patients. The overall survival is not affected by the mode of surgery.

A Prospective Observational Study Evaluating the Accuracy of MRI in Predicting the Extent of Disease in Endometrial Cancer.

This prospective study looks into the accuracy of magnetic resonance imaging (MRI) in predicting the depth of MI, cervical invasion, lymph node metastasis, and extrauterine spread (EUS) of disease in endometrial cancer. Between June 2014 and December 2015, 58 patients with biopsy-proven endometrial cancer who underwent MRI prior to surgery were included in the study. MRI findings like myometrial invasion, extrauterine spread, lymph nodal metastasis, and cervical invasion were compared against the histopathology report. Sensitivity, specificity, PPV, NPV, and overall accuracy of MRI for myometrial depth assessment were 75.0%, 73.08%, 77.2%, 70.37%, and 74.14 respectively. Sensitivity, specificity, PPV, NPV, and overall accuracy of MRI in assessing lymph node spread were 88.64%, 66.67%, 95.12%, 44.44%, and 86.0% respectively. As for predicting extrauterine spread and cervical invasion, MRI showed poor sensitivity (37.5% and 50% respectively) and a high specificity (92% and 100% respectively). Our study shows that preoperative MRI has high sensitivity and specificity to predict myometrial invasion and lymph node involvement. But, it is not sensitive enough to predict cervical involvement or extrauterine spread.

A retrospective analysis of the pattern of care and survival in patients with malignant ovarian germ cell tumors.

OBJECTIVE: The objective of this study is to evaluate the pattern of care and survival outcome in patients with malignant ovarian germ cell tumors (MOGCTs). MATERIALS AND METHODS: Between January 2004 and August 2017, 50 patients with MOGCT were identified at Amrita Institute of Medical Sciences and 48 included in analyses. Histologic subtypes were as follows: dysgerminoma 11; immature teratoma 16; yolk sac tumor 3; and mixed germ cell tumor 18. 31 (64.6% patients belonged to Stage I and 17 (35.4%) patients were advanced stage (Stage II-IV). RESULTS: Median follow-up period was 34 months (range: 1-241 months). The 5- and 10-year disease-free survival (DFS) and overall survival (OS) for the entire cohort were 87.5% and 94.4%, respectively. DFS and OS of incomplete surgery Stage I patients 28.6% and 68.6%, respectively, were significantly lower than completely staged patients 100%. Out of 8 incomplete surgery patients, 5 recurred of which 2 died of disease within 4 and 9 months of recurrence. There was no survival difference with comprehensive surgical staging (CSS) and pediatric surgical staging (PSS) in Stage I MOGCT (DFS and OS 100%). Stage I dysgerminoma kept on active surveillance after PSS had equivalent survival of 100%. There was no survival difference in advanced stage MOGCT treated with primary debulking surgery and neoadjuvant chemotherapy (NAC) followed by fertility-sparing surgery (DFS and OS 100%). CONCLUSION: Incomplete surgery in Stage I MOGCT was associated with poor survival. There was no survival difference with CSS and PSS. NAC followed by surgery could be a reasonable option for patients of advanced stage MOGCT.

Endometrial stromal sarcoma-A retropsective analysis of factors affecting recurrence.

OBJECTIVE: To assess the factors associated with disease free survival and overall survival in endometrial stromal sarcoma (ESS). METHODS: This was a single institution retrospective analysis done at Amrita Institute of Medical Sciences. Records from January 2005 to October 2016 were analysed and 42 patients with ESS were identified. Clinicopathological, surgical management, adjuvant treatment and outcome data were collected. Disease free and overall survivals were analysed using Kaplan-Meier method and compared using log rank test. RESULTS: Out of 38 patients included in analysis 28 (73.7%) had low grade ESS (LGESS) and 10 (26.3%) had high grade ESS (HGESS). The median follow up period was 28 months (range 1-110 months). The 5year disease free survival (DFS) and overall survival (OS) for the entire cohort were 62.9 and 89.1% respectively. High grade ESS was significantly associated with recurrence on univariate analysis (p=0.045). Complete staging surgery in both HGESS and LGESS and adjuvant treatment in HGESS and advanced stage LGESS (cohort 1) were associated with improved 5-year DFS of 90.9% (p<0.001). Completion staging surgery in patients with initial incomplete surgery (cohort 3) was associated with improved 5-year DFS of 100% (p<0.001). Complete Staging surgery but no adjuvant treatment in HGESS and advanced stage LGESS (cohort 2) was associated with significantly poor 2-year DFS of 20% (5-year DFS rate 0%; as all patients recurred within 27 months) (P<0.001). Significantly reduced 5-year DFS rate of 25% (p<0.001) was also seen in cases where initial incomplete surgery was not followed by complete staging and adjuvant treatment (cohort 4). Adjuvant treatment in HGESS was associated with improved 5-year DFS of 66.7% (p=0.043). Resection of recurrent lesions were associated with improved mean survival of 41.2 months. CONCLUSION: Incomplete surgery and no adjuvant treatment in ESS are associated with poor DFS. Complete staging surgery is associated with improved DFS. Resection of recurrent disease is associated with survival advantage.

Recent advances in granulosa cell tumor ovary: a review.

Granulosa cell tumors constitute less than 5 % of all ovarian tumors. Unlike epithelial ovarian tumors, they occur in a younger age group, are usually detected in an early stage and often have features of hyperestrogenism. The presenting symptoms are usually nonspecific with abdominal pain or distension. They follow an indolent course and are characterized by a long natural history. Mutation of FOXL2 (402C->G) seen in 97 % of adult GCT may be pathognomonic for adult GCT. Only stage of the disease has been consistently shown in various studies to affect survival of patients with GCT. The initial management of patients, for whom fertility is not an issue, is total abdominal hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Nodal dissection is not a significant factor for survival and is not recommended in surgical staging of GCT. Fertility preserving surgery with unilateral salpingo-oophorectomy is feasible in young patients with stage Ia GCT. Patients with early stage disease (stage I and II) have a very good prognosis with 5 year DFS and OS of 89 % and 99 % respectively and these groups of patients usually don't require any postoperative treatment. Patients with stage Ic disease associated with poor prognostic factors like large tumor size or high mitotic index and stage II, have a higher chance of relapse, and may benefit with postoperative treatment but role of chemotherapy is still debatable. In advanced stage disease (stage III and IV) the 5 year DFS and OS disease was 72 % and 80 % respectively hence the option of postoperative treatment with 6 cycles of BEP should be considered in this group. Recently paclitaxel is being investigated as an effective tool in GCT. The efficacy of radiation in GCT is not well defined but in optimally debulked cases postoperative radiation is a viable option. Due to high chance of recurrence even years after apparent clinical cure of the primary tumor, lifelong follow up with clinical examination and tumor markers like inhibin B is recommended. About 25 % GCT develop recurrence and the median time to recur is usually 4-5 years. Most recurrences are intraperitoneal and usually a complete debulking of the disease is feasible even in the recurrent setting. Postoperative chemotherapy (platinum based) is usually given after surgery more so in cases with widespread disease or after suboptimal cytoreduction. Recurrent chemoresistant, progressive non-responding GCT or patients with high surgical risk are ideal candidates for targeted therapy.