Clear cell adenocarcinoma of the cervix and its mimickers - A series of 19 cases from a tertiary care referral centre in India.

ABSTRACT: Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2 years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6 months for patients with an initial positive margin, but 36 and 58.2 months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36 months for DFS, p = 0.117 and 19.6 vs. 58.2 months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases.

BACKGROUND: Advances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. METHODS: At the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. RESULTS: At a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. CONCLUSION: Tumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.

High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR-A report of two cases of a novel tumor entity.

Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

Conventional versus Liquid-based Cytology: "Man versus Machine".

Background: Liquid-based cytology (LBC) can improve adequacy, monolayer quality with a clean background compared to conventional smears (CS). Aims and Objectives: The objective was to compare the quality and diagnostic yield of CS and LBC in routine cytological investigations. Materials and Methods: This retrospective study consisted of 306 samples (255 gynecological, 39 nongynecological, and 12 fine needle aspiration cytology [FNAC]) during a 2-year period (2019-2020). From each patient, two samples were collected in the same manner in the same sitting and processed by CS and LBC (ThinPrep® 2000, Hologic Inc.). Both CS and LBC were compared for adequacy, quality, representativeness, inflammation, hemorrhage, necrosis, preservation, reactive changes, organisms, atypia/dysplasia/malignancy, and preparation/screening time. Statistical analysis was performed. Results: No statistically significant difference was noted for adequacy, representativeness, reactive changes, preservation, and atypia/dysplasia/malignancy. CS was better in cellularity and diagnosis of inflammation and organisms, whereas LBC had a clean background and the difference was statistically significant (P = 0.0005). Conclusions: CS was equivalent to LBC in adequacy, representativeness, reactive changes, and atypia/dysplasia/malignancy. Adequacy comparable to LBC can be achieved in CS by careful sample collection, processing, and screening by trained cytotechnologists. CS was better in detecting organisms and inflammation than LBC. The advantages of LBC were monolayer smear, clean background, and lesser screening time, but the demerit was higher cost and longer processing time. Therefore, LBC is best suited to those laboratories having high sample inadequacy rates, lack of competent cytotechnologists, and no financial constraints. Either man or machine, appropriate and adequate sample collection by trained personnel forms the cornerstone for ensuring adequacy in both CS and LBC.

IgG4-related disorders of the gastrointestinal tract: Experience from a tertiary care centre with systematic review of Indian literature.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. METHODS: Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. RESULTS: Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. CONCLUSION: One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers.

PURPOSE: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. METHODS AND MATERIALS: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. RESULTS: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. CONCLUSION: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Heat Induced Processing of Cellblocks with Significant Reduction in Overall Turn Around Time.

Introduction: Cellblock (CB) with immunohistochemistry (IHC) is practically indispensable in the diagnostic workup of serous effusions; however, CB requires a minimum of 15-20 h for routine histopathological processing. A reduction in processing time can expedite a faster diagnosis. Aim: This study was undertaken to evaluate the utility of the heat-induced CB (HICB) technique. Material and Methods: Two sets of agar-embedded CBs were processed from 50 effusion samples. CBs were further processed by conventional and rapid methods. Conventional CBs (CCB) were processed in a histoprocessor, whereas rapid CB was processed in a heated water bath with an agitation facility. For HICB processing, dehydration and clearing were performed at 50°C followed by paraffin wax impregnation at 65°C temperature. From both CBs, sections of 5 um thickness were cut and stained with hematoxylin and eosin (H and E). Cell morphology, cost, and time were compared between the two methods. The feasibility of IHC was attempted in a few cases. Results: HICB was completed within 4.30 h compared with CCB. Diagnoses on both CBs were concordant in all the cases. Incomplete dehydration was noted in six (12%) cases, but the diagnosis was not compromised. No additional cost was involved in HICB. On IHC, both HICB and CCB exhibited equivalent expression. Conclusions: HICB is a rapid, innovative, simple, and cost-effective technique and expedites faster diagnosis. It does not require any advanced equipment.

Epithelioid trophoblastic tumor: A case series.

An epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic tumor. Cases of ETT present with abnormal vaginal bleeding in women of reproductive age group with marginally elevated beta human chorionic gonadotrophin (B-hCG) levels. Here, we describe a series of four patients (all were females) including histomorphology, immunoprofiles, and diagnostic difficulty of this rare entity. All cases were in their reproductive age group. The mean pre-treatment hCG level was 665.24 (mIU/mL). Microscopically, all cases had a tumor showing an epithelioid appearance arranged in large nests and sheets. Individual tumor cells were round to polygonal with abundant eosinophilic cytoplasm, with central vesicular nuclei and prominent nucleoli. Areas of hemorrhage, necrosis, and intercellular hyaline-like material deposition were identified in all cases (100%). Immunohistochemically, tumor cells in all cases showed diffuse positivity for AE1/AE3 and p63 (100%). GATA3 was available in one case (25%), which was positive in the tumor cells. In one case (25%), hPL was focally positive, and in one case (25%), it was negative. SALL4 was performed in two cases (50%) and was negative in tumor cells. The mean Ki67 labeling index was 19.2 (range 10-30%). All four patients underwent surgical intervention and were treated with hysterectomy. The mean follow-up in this series was 39.4 months (range 6-70), and all patients are alive to date with a mean survival of 32.8 months (range, 4-67).

Killer cell immunoglobulin-like receptor (KIR) gene contents: Are they associated with cervical cancer?

Killer cell immunoglobulin-like receptors (KIRs) are required for natural killer cell function against virus-infected cells or tumor cells. KIR gene content polymorphisms in Indian women with cervical cancer (CaCx) remain unexplored. Hence, we analyzed the frequencies of KIR genes, KIR haplotypes, and Bx subsets to draw their association with CaCx. The polymerase chain reaction-sequence-specific primer method was used for KIR genotyping in three groups of women: healthy controls (n = 114), women with human papillomavirus (HPV) infection (n = 70), and women with CaCx (n = 120). The results showed that the frequency of KIR2DS5 was significantly higher in women with CaCx compared to women with HPV infection (p = 0.02) and healthy controls (p = 0.01). Whereas the frequency of KIR2DL5B was significantly higher in healthy controls than in women with HPV infection (p = 0.02). The total number of activating KIR genes was higher in women with CaCx than in healthy controls (p = 0.006), indicating their positive association with CaCx. Moreover, the C4T4 subset was higher in women with CaCx than in women with HPV infection, though not significant. In conclusion, our findings highlight KIR2DS5, the C4T4 subset, and activating KIR genes are susceptible factors or positively associated with CaCx. Besides KIR2DL5B, this study also reported for the first time significantly high frequency of KIR2DL1 in healthy controls, indicating its possible protective association against CaCx. Further, significantly high frequency of KIR2DL3 observed in HPV-infected women might be also a promising biomarker for viral infections. Thus, the study confirms the association of KIR genes with cervical cancer in women with HPV infection.

Oxaliplatin-Induced Sinusoidal Obstruction Syndrome Masquerading as Colorectal Liver Metastasis: A Case Report.

INTRODUCTION: Oxaliplatin-based chemotherapy is commonly used in adjuvant treatment of colon cancer as well as in neoadjuvant setting in patients with liver metastases. However oxaliplatin can cause damage to non-tumor bearing liver which presents as sinusoidal obstructive syndrome (SOS). These changes are difficult to differentiate from metastasis clinic-radiologically and manifests as sinusoidal dilatation, peliosis and nodular regenerative hyperplasia. CASE: The present study reports the case of a patient with oxaliplatin-induced SOS which mimicked colo-rectal liver metastasis on follow up imaging studies after receiving neoadjuvant oxaliplatin based chemotherapy. After multidisciplinary discussion, patient was planned for simultaneous resection of rectal primary and right hepatectomy for metastasis. Final histopathology revealed no tumour in liver but the liver lesions seen radiologically were actually changes of oxaliplatin induced focal SOS and mimicked metastatic nodules. CONCLUSION: In patients with colo-rectal cancer having received oxaliplatin-based chemotherapy, SOS may be considered as one of the causes of newly developed liver lesions, and should be subjected to additional radio-pathologic evaluation to prevent overtreatment and avoiding potentially morbid surgeries.

Utility and limitations of intraoperative frozen section diagnosis to determine optimal surgical strategy in suspected gallbladder malignancy.

BACKGROUND: Preoperative diagnosis of gallbladder cancer (GBC) remains a challenge. Unwarranted extensive surgery for benign disease and undertreatment for GBC pose challenges. We aimed to analyze the utility, diagnostic accuracy, and limitations of intraoperative frozen section (FS), for primary diagnosis of suspected gallbladder malignancy. METHODS: Patients with suspected GBC underwent a cystic-plate cholecystectomy and FS for primary diagnosis. The procedure was considered adequate if FS suggested a benign pathology. A radical cholecystectomy was performed if FS favoured GBC, or in patients with high intra-operative suspicion of malignancy. All FS records were compared with final histopathology. RESULTS: FS guided the surgical strategy in 491 of 575 resections (85.4%). FS had a sensitivity of 88.3%, specificity of 99.6%, a positive predictive value of 99.4% and a negative predictive value of 92.7%. The diagnostic accuracy of FS was 95.1%. With routine use of intraoperative FS, only 10 out of 491 patients (2%) required a revised surgical strategy. CONCLUSIONS: For radiologically suspected GBC it is prudent to confirm the histological diagnosis by use of intraoperative FS before undertaking radical resections. This study emphasizes the safety and accuracy of FS as an adjunct for directing optimal surgical strategy in suspected GBC.

Endometrial serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival.

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS). Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis. Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ≥50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ≥7.0 mm, DOI ≥6.0 mm and MI% ≥40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (≥6.0 mm) and MI% (≥40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (≤7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively. Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC.

Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates.

Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country. Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution. Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review. Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2-40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs. Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications.

An audit of frozen sections for suspected gastrointestinal malignancies in a tertiary referral hospital in India.

Background: Frozen Sections (FS) are used to assess margins, for staging, and primary diagnosis. FS guide intraoperative treatment decisions in oncological gastro-intestinal tract surgeries and further management of the patients. Aim: To analyze the distribution, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of frozen sections in gastrointestinal pathology in our institution during the period of 3 years (2016-2018). Material and Methods: This study was an audit to determine the accuracy of FS reports by comparing them with the paraffin section (PS) reports. The FS diagnoses and their PS diagnoses were noted in 1704 gastrointestinal surgeries during the period from 2016 to 2018. Discrepancies were noted and slides of discrepant cases were reviewed to determine the cause. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated using the standard formulae. Results: Out of 1704 cases, correct diagnosis on frozen section was made in 1649 cases (96.77%), 20 (1.17%) were deferred cases, and 35 (2.05%) were discrepant cases. The commonest discrepancies were seen in the primary diagnosis of the gall bladder and gastrectomy margins. The commonest causes for discrepancies were interpretation errors and technical errors. Sensitivity was 91.71%, specificity was 99.69%, positive predictive value was 98.84%, negative predictive value was 97.68%, and accuracy was 97.92%. Conclusion: FS diagnosis is a reliable guide to surgeons for intraoperative management. Studying deep cuts and careful sampling at frozen sections will help reduce discrepancies.

Diagnostic accuracy of menstrual blood for human papillomavirus detection in cervical cancer screening: a systematic review.

Globally, cervical cancer is the fourth most common cancer among females and a major public health problem in low- and middle-income countries (LMICs). There are several screening tests available for cervical cancer screening; however, due to a lack of organised screening facilities as well as factors such as low participation rates in screening programmes, many women die due to cervical cancer. To reach out to a large number of women, an easy, non-invasive and time-saving screening method is required. Evidence supports that cervical cancer screening with human papillomavirus deoxyribonucleic acid (HPV DNA) testing is the most effective technique for lowering the incidence and mortality associated with cervical cancer when compared to other screening methods. Furthermore, a small number of studies have reported that menstrual blood can be used as an alternative sample for HPV detection for cervical cancer screening. We have done a systematic review of the studies that have reported the diagnostic accuracy of menstrual blood to detect HPV. We found five studies in our literature search. The studies showed the diagnostic accuracy of menstrual blood in terms of sensitivity ranging from 82.8% to 97.7% and specificity ranging from 50.0% to 98.0% in cervical intraepithelial neoplasia or HPV infection detection. This review supports the use of menstrual blood as a screening tool for cervical cancer especially in LMICs where women are reluctant to participate in cervical cancer screening due to issues such as embarrassment and discomfort to test procedures as well as busy schedules. However, further studies are required to compare the diagnostic accuracy of menstrual blood in detecting HPV compared to other self-sampled HPV detection methods. This is one of the methods that can be explored further for use as a cervical cancer screening test.

Ensuring quality in contextualised cancer management guidelines for resource-constraint settings: using a systematic approach.

To address the wide variation in access to cancer care in India requires strengthening of infrastructure, trained oncology workforce, and minimisation of out-of-pocket expenditures. However, even with major investments, it is unlikely to achieve the same level of infrastructure and expertise across the country. Therefore, a resource stratified approach driven by evidence-based and contextualised clinical guidelines is the need of the hour. The National Cancer Grid has been at the forefront of delivery of standardised cancer care through several of its initiatives, including the resource-stratified guidelines. Development of new guidelines is resource and time intensive, which may not be feasible and can delay the implementation. Adaptation of the existing standard guidelines using the transparent and well-documented methodology with involvement of all stakeholders can be one of the most reasonable pathways. However, the adaptation should be done keeping in mind the context, resource availability, budget impact, investment needed for implementation and acceptability by clinicians, patients, policymakers, and other stakeholders. The present paper provides the framework for systematically developing guidelines through adaptation and contextualisation. The process can be used for other health conditions in resource-constraint settings.

Study of histopathology reports of loop electrosurgical excision procedure of cervical transformation zone and their correlation with preprocedural cervical biopsy and/or cytology: An audit.

Introduction: Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial.

INTRODUCTION: In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS). METHODS AND ANALYSIS: Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained. TRIAL REGISTRATION NUMBER: The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Unusual Presentation of Helicobacter pylori Infection as PSMA-Avid Gastric Mass.

ABSTRACT: 68 Ga-PSMA PET/CT is one of the most common imaging uses for prostate cancer imaging. Although initially thought to be specific for prostate cancer, there are many evidences that are coming of its concentration in many other neoplastic and nonneoplastic pathologies. Helicobacter pylori is the most common bacteria causing gastric inflammation and usually presents with gastroduodenal ulcer. Here we present one unusual case of benign gastric mass formation caused by H. pylori infection with PSMA concentration.