Genetic association of MMP14 promoter variants and their functional significance in gallbladder cancer pathogenesis.

Gallbladder cancer (GBC) is relatively rare but shows high frequency in certain geographical regions and ethnic groups, which include Northern and Eastern states of India. Previous studies in India have indicated the possible role of genetic predisposition in GBC pathogenesis. Although matrix metalloproteinase-14 (MMP14) is known modulator of tumour microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in genetic predisposition for GBC is completely unknown. We explored MMP14 promoter genetic variants as risk factors and their implication in expression modulation and the pathogenesis of GBC. We genotyped all single nucleotide polymorphisms of MMP14 promoter by Sanger's sequencing in approximately 300 GBC and 300 control study subjects of Indian ethnicity and, in 26 GBC tissue samples. Protein expression of MMP14 in GBC tissue samples was checked by immunohistochemistry. In vitro luciferase reporter assay was carried out to elucidate role of promoter genetic variants on expression levels in two different cell lines. MMP14 promoter variants, rs1003349 (p value = 0.0008) and rs1004030 (p value = 0.0001) were significantly associated with GBC. Luciferase reporter assay showed high expression for risk alleles of both the SNPs. Genotype-phenotype correlation for rs1003349 and rs1004030, in patient sample, confirmed that risk allele carriers had higher expression levels of MMP14; moreover, the correlation pattern matched with genetic association models. Overall, this study unravels the association of MMP14 promoter SNPs with GBC which contribute to pathogenesis by increasing its expression.

Expression Pattern of Estrogen Receptor Alpha and Progesterone Receptor in Gallbladder Carcinoma and Their Association with Clinicopathological Parameters and Overall Survival.

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. PATIENTS AND METHODS: A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. RESULTS: The mean age of this study population was 55.47 ± 8.45 with range 28-87 years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50 years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50 years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. CONCLUSION: Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

Comparison of MRCP and ERCP in the evaluation of common bile duct and pancreatic duct pathologies.

Background: Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging modality that has high diagnostic accuracy for a wide range of bile duct and pancreatic duct pathologies. Endoscopic retrograde cholangiopancreatography (ERCP) is still the gold standard for the exploration of the biliopancreatic region. Aim: The aim of the study was to compare the diagnostic accuracy of MRCP with that of ERCP in the diagnosis of bile duct and pancreatic duct pathologies. Material and methods: A total of 60 patients with common bile duct (CBD) and pancreatic duct pathologies detected on MRCP were subsequently evaluated by ERCP in this observational study. A comparison of MRCP findings with ERCP was made. Results: MRCP had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 88.1%, 94.4%, 97.3%, 72.7%, and 90%, respectively, in diagnosing choledocholithiasis in comparison to ERCP. For CBD dilation, the sensitivity was 90.91%, specificity was 93.75% and the PPV, NPV, and accuracy were 97.56%, 78.95%, and 91.67%, respectively, for MRCP. In CBD stricture, MRCP showed a sensitivity, specificity, PPV, NPV, and accuracy of 83.33%, 97.92%, 90.91%, 95.92%, and 95%, respectively. In pancreatic duct dilatation, the sensitivity, specificity, PPV, NPV, and accuracy were all 100%. Pancreatic duct stricture showed a sensitivity, specificity, PPV, NPV, and accuracy of 80%, 98%, 88.89%, 96.08%, and 95%, respectively. For the diagnosis of periampullary carcinoma, the sensitivity, specificity, PPV, NPV, and accuracy rate of MRCP were 80%, 98%, 88.89%, 96.08%, and 95%, respectively. Conclusion: No significant difference was found between MRCP and ERCP in diagnosing those six pathologies.

Significance of tumor-infiltrating lymphocytes in tumor regression in breast cancer: A study in a tertiary care cancer center in South India.

BACKGROUND: Tumor immunology plays a significant role in predicting tumor biology and how a tumor is going to respond to neoadjuvant chemotherapy (NACT). Tumor-infiltrating lymphocytes (TILs) are the easiest and by far the cheapest method of assessing tumor immunity. Many studies have suggested that TILs play an important role in tumor regression in breast cancer. AIM: The aim of the current study was to determine significance of TILs in tumor regression in breast cancer. MATERIALS AND METHODS: Patients with newly diagnosed and histologically proven breast cancer who were treated with both NACT and surgery in our institute were included in the study. TILs were assessed both before and after NACT, and were correlated with the relative amount of tumor regression and molecular subtypes based on the immunohistochemistry profile. RESULTS: The study included 43 specimens of carcinoma breast in females. 42 cases were diagnosed with invasive carcinoma, no special type (NST), and one with lobular carcinoma. Pathological complete remission (pCR) was noted in 6 cases, partial remission (PRe) in 12 cases, and no response in 25 cases. TILs were noted before and after NACT in all cases and were correlated with other clinicopathological parameters. CONCLUSION: The present study highlights that TILs play a vital role in tumor regression and can be included in routine reporting. It can provide an insight into tumor biology.

Intracranial tumor-to-tumor metastasis in an elderly female: An unusual case report.

Tumor-to-tumor metastasis is an extremely rare event, with only 150 reported cases in the literature. Meningioma, renal carcinoma, and tumors of the thyroid are the commonest sites of metastasis. Lung, breast, and GI-tract cancers are the most common types that undergo metastasis. Meningioma is the most common intracranial tumor as recipient of the tumor-to-tumor metastasis. Although breast carcinoma is the most common tumor to metastasize, adenocarcinoma from other organs can also spread to meningiomas, like the ovary and upper gastrointestinal (GI). We report a case of adenocarcinoma metastasis to meningioma with the possibility of primary involvement of the ovary or upper GI. A 77-year-old female patient presented to neurosurgery with episodes of multiple seizures and loss of consciousness. An MRI suggested a left frontotemporal meningioma. The patient underwent craniotomy with mass dissection. Microscopic examinations showed a dual tumor containing both components of meningioma with a metastatic adenocarcinomatous component. The tumor cells were positive for cytokeratin (CK7). Thus, the final diagnosis was made as meningothelial meningiomas (WHO grade I) with metastatic mucinous adenocarcinoma, possible primaries of the ovary or upper GI tract. The patient could not be followed up as we lost the patient a few days after surgery.

An unusual case series of synchronous primary malignancies: Carcinoma gallbladder with renal cell carcinoma, carcinoma gallbladder with carcinoma colon, carcinoma gallbladder with carcinoma breast.

ABSTRACT: Synchronous primary cancers are very rare. Due to their low incidence rate and insidious onset, they may be easily overlooked or misdiagnosed. In addition, there is currently no international consensus for their clinical diagnosis and treatment. Three exceedingly unusual synchronous primary malignancies, carcinoma gallbladder with renal cell carcinoma, carcinoma gallbladder with carcinoma colon, and carcinoma gallbladder with carcinoma breast, are presented here. Together with their clinical presentation, therapeutic options and outcomes are also presented. Curative radical surgery of each particular tumor, along with postoperative chemotherapy or radiotherapy improves disease-free survival.

Reproducibility of Cytomorphological Diagnosis and Assessment of Risk of Malignancy of Thyroid Nodules Based on the Bethesda System for Reporting Thyroid Cytopathology: A Tertiary Cancer Center Perspective.

Introduction: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was introduced for unifying the terminology and morphologic criteria along with the corresponding risk of malignancy, leading to more consistent management approaches. The aim of this study was to study the utility and reproducibility of TBSRTC in reporting thyroid cytology in a referral cancer center. Methods: The fine-needle aspiration (FNA) of all thyroid nodules were included for a period of 5 years, from January 2016 to December 2021, in this cancer center. They were retrospectively reviewed and recategorized according to TBSRTC by two experienced pathologists. Cytohistopathological correlation was done for the cases which underwent surgical resection. Results: 522 fine-needle aspiration cytology (FNAC) of thyroid swellings were evaluated and categorized according to TBSRTC. There was agreement in the cytological diagnosis of 512 cases, of which 260 (50.78%) were benign lesions, 189 (36.91%) were malignant, 5 (0.97%) were unsatisfactory/nondiagnostic, 41 (8.01%) were follicular neoplasm/suspicious for neoplasm, 13 (2.53%) were suspicious for malignancy, and 4 (0.78%) cases were reported as atypia of undetermined significance. Two cytopathologists were in agreement in 512 cases (98%) of cases. Almost complete concordance was noted in the malignant (99%) and benign categories (98%). Disagreement was seen in 10 cases. Histological follow-up was available in 201 cases with an overall malignancy rate of 62.68% (126/201). Conclusion: TBSRTC proved to be a very simple and effective reporting system for thyroid FNAC, especially in the setting of a cancer center. This enables proper triaging of cases with thyroid masses into those who require surgical intervention and those who can avoid it, thereby preventing unnecessary morbidity.

Diagnostic Utility of Ultrasound-Guided Fine-Needle Aspiration Cytology in Gall Bladder Lesions: An Experience from a Tertiary Care Cancer Center in Eastern India.

INTRODUCTION: Gallbladder cancer (GBC) is the most common malignancy, representing 80-95% of biliary tract cancers. Although ultrasonography-guided fine-needle aspiration cytology (USG-FNAC) has emerged as an effective diagnostic the tool for the precise diagnosis of gallbladder lesions, data on its diagnostic utility and cytomorphological categorization of gallbladder lesions are lacking. AIMS: To study the diagnostic utility of USG-FNAC in gallbladder lesions. MATERIALS AND METHODS: This study was the conducted prospectively on patients who came with clinical and radiological evidence of gallbladder space-occupying lesion and then advised to USG-FNAC over 2 years and 6 months from January 2018 to June 2020. RESULTS: A total of 314 cases were included. The mean age was 56 years, with a range of 17-88 years. Women predominated over men (Male:Female = 1:2.3). Primary adenocarcinoma of the gallbladder was most common. On cyto-histological correlation, the sensitivity, specificity, and diagnostic accuracy of USG-FNAC of gallbladder lesions were found to be 98.82, 87.23, and 96.3%, respectively. CONCLUSION: The USG-FNAC of gallbladder lesion was found to be an easy, quick, cost-effective, and presumptive diagnostic procedure. It should be opted as an initial preoperative diagnostic modality in high incidence areas to avoid inappropriate management with unnecessary morbidity and cost. Moreover, a close cytological examination of the architectural pattern and the cytomorphological features would help in the sub-typing and prognosticating the tumor.

Clinicopathological study of malignant melanoma in a regional cancer center.

BACKGROUND: : Malignant melanoma is a tumor of melanocytic origin. Although uncommon in India as compared with the west, its prevalence is increasing. OBJECTIVES: To document the pattern of clinicopathological features of malignant melanoma cases attending in a regional cancer center in eastern India. MATERIAL AND METHODS: The present study was a retrospective study of 182 cases diagnosed histopathologically as malignant melanoma during 2011-2016. RESULTS: Out of the total cases, 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous melanoma. The most common age group was sixth decade with a male predominance. Conventional melanotic melanomas were 176 (96.70%), and only 6 cases (3.30%) were amelanotic melanoma. Among noncutaneous melanomas, 6 were in anorectum, 2 in conjunctiva, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina. The acrallentigenous type was the most common variety, and the mixed epithelioid and spindle cell type was the most common histopathological pattern. Clark's level III was the most common level of invasion. CONCLUSION: The lower extremity is the most common site for melanoma, whereas extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB 45 can be used for definitive diagnosis.

Role of fine-needle aspiration cytology in diagnosis of disseminated histoplasmosis in an immunocompetent patient: A case report.

Histoplasmosis is a mycotic infection caused by dimorphic fungus, Histoplasma capsulatum. The organisms are usually found within the cells (macrophages). This organism mostly affects lungs in immunocompetent individuals and disseminated forms are seen in immunocompromised cases. Here, we describe a case of disseminated histoplasmosis in an immunocompetent, 35-year-old female with lymphadenopathy diagnosed by fine-needle aspiration cytology and cell block.

Utility of Tru-Cut Biopsy of Breast Lesions - An Experience in a Regional Cancer Center of a Developing Country.

INTRODUCTION: Tru-cut Needle Biopsy (TCB) is an integral part of triple assessment of breast cancer, which includes clinical assessment, mammography and TCB or Core Needle Biopsy (CNB). The technique is reliable, simple, and reproducible, and inexpensive, which can be adapted even for low-income group of patients and in developing countries. AIM: This study was done to establish the efficacy of TCB of palpable breast lesions in a developing country where mammography is not possible in all cases. MATERIALS AND METHODS: A retrospective analysis of 892 TCBs was done in AH Regional Cancer Centre, Cuttack, Odisha, India where TCBs were performed in patients presenting to outpatient department with palpable breast lesions. The H&E stained sections were interpreted by pathologists of the same centre. Diagnosis was classified into different categories. Immunohistochemistry (IHC) for Estrogen Receptor (ER), Progesterone Receptor (PR) and Her-2/neu was done and interpreted by Allred scoring system. RESULTS: A total 892 TCBs were analysed with 23 repeat TCBs. There were 13 (1.4%) male patients. A total of 747 cases (83.6%) were diagnosed as malignant, including 735 carcinomas, nine malignant phyllodes tumour, two angiosarcoma and one case of Non-Hodgkin' Lymphoma (NHL). It was possible to diagnose special histological types such as lobular carcinoma, metaplastic carcinoma and mucinous carcinoma on TCB. A total of 21 cases were diagnosed as carcinoma on repeat biopsy. Eight of the 735 TCBs diagnosed as carcinoma were bilateral breast cancers, hence actual number of carcinoma cases were 727. IHC was done successfully on the paraffin blocks in 260 cases. In this series out of 727 patients of carcinomas 30% were in young, i.e., below 40 years of age, including four cases of carcinoma below 20 years. There were no false positive case in this study giving a specificity of 100% and sensitivity was 97%. CONCLUSION: TCBs are well tolerated by patients, can be done in OPDs and reduce cost. It is possible to give histological diagnosis of carcinoma, lymphoma, phyllodes tumour and sarcomas on TCBs. The paraffin blocks of TCBs can be used for IHC study which helps the oncologists for preoperative adjuvant therapy.

Role of fine needle aspiration cytology and cell block in diagnosis of scar endometriosis: A case report.

Presence of endometrial glands and stroma in places other than the uterus is called endometriosis. It can be pelvic or extra-pelvic. Abdominal scar endometriosis is an extra-pelvic endometriosis that can occur after surgery involving the uterus. Post-caesarean section, scar endometriosis is a rare event. The diagnosis is frequently made only after excision of disease tissue. We present a case of post-caesarean section abdominal scar endometriosis presenting as a tumor on the abdominal wall, which was diagnosed by fine needle aspiration cytology and confirmed by cell block preparation.