Jamshed Ali¹, Ayesha Rahat¹, Muhammad Hassan Shah¹, Mashall Sajjad¹, Iqra Malik¹, Shameen Ikram², Muhammad Fawad Ul Qamar³

¹ Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospitaland Research Centre (SKMCH&RC) Peshawar, Pakistan

Objective: Gastroentero-pancreatic neuroendocrine tumor (GEP NETs) are a heterogeneous group of tumors with variable behaviors. Our aim was to study the baseline characteristics and outcomes of GEP-NETs and to establish the impact of tumor grade and resectability on the survival.

Methods: A single center retrospective review of patients registered at SKMCH & RC Pakistan with the diagnosis of GEP-NETs was carried out from the Hospital Information System. The baseline characteristics of 134 diagnosed patients from January 2006 to August 2020 were analyzed. Overall survival (OS) and Disease Free Survival (DFS) was calculated using Kaplan-Meier curve. The impact of tumor grade and resectability was seen on the OS and DFS. Data was analyzed through SPSS version 23. Categorical parameters were computed using ChiSquare test, keeping p-value =0.05 significant.

Results: A large majority had Grade 1 disease (59%) along with localized stage at presentation (73.1%) as compared to Grade 2 (23.9%) and Grade 3 (17.1%) disease with metastatic stage at presentation (26.9%). The 5 year OS according to tumor grade was, 88%, 57% and 0% in low, intermediate and high grade respectively. The 5-year OS was 94%, 79% and 43% in the completele, incomplete and in unresectable disease group, respectively.

Conclusion: GEP-NETs are rare tumors with good outcomes in Grade I and II and poor outcomes in grade III Neuroendocrine Carcinomas (NEC). Tumor grade and complete surgery of the primary tumor are important predictors of response outcomes and prognosis.

Keywords: Neuroendocrine Tumors, Outcomes, Resectability, Neuroendocrine Carcinoma

The Prognostic Significance of CD10 Expression in Invasive Breast Carcinoma in Tunisian Patients

Saadia Makni^1,2, Manel Mellouli^1,2, Ines Saguem^1,2, Ons Boudawara^1,2, Naourez Gouiaa^1,2, Tahya Sallemi Boudawara^1,2, Jihene Feki^2,3, Rim Kallel^1,2

¹ Department of Pathology and Research Laboratory, Habib Bourguiba University Hospital, 3029, Sfax, Tunisia.
² Medical School of Sfax, University of Sfax, 3029, Sfax, Tunisia.
³ Department of Medical Oncology, Habib Bourguiba University Hospital, 3029, Sfax, Tunisia.

Background: Breast cancer is the first female cancer worldwide. Its prognosis depends mainly on pathological stage and histological grade. These classical prognostic factors are essential but may be insufficient to predict the outcome of the disease. Research focuses on identifying new prognostic factors such as CD10, which is a cell surface metalloproteinase.

Objective: This study aims to evaluate CD10 expression on stromal and tumor cells in invasive breast carcinomas and its correlations with other clinicopathological factors and survival.

methods: A series of 100 cases of breast carcinoma of no special type diagnosed from 2009 to 2011, was investigated in this study. CD10 expression was detected by immunohistochemistry. Stromal CD10 expression (=10% stromal positivity was considered positive) and tumor cells expression (=1% stained carcinomatous cells) were noted. Statistical correlations were analyzed with different known prognostic parameters; survival analysis were performed using SPSS 22.0.

Results: Stromal CD10 expression was seen in 60% of the cases. It showed positive correlation with high tumor grade (p=0,012) and distant metastasis (p=0,02). CD10 expression on tumor cells was observed in 10% of the cases. It was associated with high tumor grade (p=0,009), hormone receptor negativity (estrogen receptor: p<0,0001), progesterone receptor: p=0,005), triplenegative phenotype (p=0,001), and Ki67 overexpression (p=0,046). Stromal CD10 expression was significantly associated to a shorter overall survival (p=0,029) and disease-free survival (p=0,05) in univariate analysis.

Conclusion: Given these results, it can be concluded that CD10 expression predict an aggressive behavior of breast cancer. This marker can be introduced as a determinant prognostic factor.

Keywords: Invasive breast carcinoma; CD10; Stromal cell; prognosis

Mahesh Sultania¹, Mohammed Imaduddin¹, Dillip K Muduly¹, Saroj K D Majumdar², Amit K Adhya³, Dillip K Parida², Madhabananda Kar¹

Introduction: Despite the development of targeted therapies for the management of oral cancer patients, the cost of treatment is a concern in middle- and low-income countries. The present study assessed the feasibility of low-cost metronomic therapy as an alternative treatment modality in patients with unresectable or inoperable oral cancers.

Methodology: The study was a prospective, single-arm study. Unresectable, inoperable, and metastatic lip and oral cavity cancers were started on metronomic therapy, a combination of oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily, as palliative therapy. The primary endpoint was overall survival. The secondary endpoints were a response to metronomic therapy, compliance, and toxicity.

Results: From June 2018 to May 2020, 25 patients were started on metronomic therapy. The median age was 60 years. The median overall survival was 8.8 months. At eight weeks of therapy, 11 patients (44%) had a partial response, ten patients had stable disease (40%), and four patients had progressive disease (16%). The compliance with the therapy was 100%, and one patient (4%) developed grade III toxicity.

Conclusions:Considering the resource constraints and cost limitations in low and middle-income countries, oral metronomic therapy in the form of methotrexate and celecoxib should be regarded as a suitable regimen in the palliative treatment of patients with unresectable, metastatic, or advanced, recurrent cancers.

Keywords: Metronomic therapy, Oral cancer, palliative care, methotrexate, celecoxib

Immunohistochemical Study of p16INK4A, MIB-1 and CK17 in Pre-neoplastic and Neoplastic Epithelial Lesions of Cervix

Piyush D. Sahu¹, Siddhi Gaurish Sinai Khandeparkar¹, Avinash R. Joshi¹, Maithili M. Kulkarni¹, Bageshri P.Gogate¹, Neha D. Newadkar¹, Prajakta A. Shinde¹, Shivani S. Battin¹

Background: Cervical intraepithelial neoplasia (CIN) II and CIN III have a high progression rate to invasive squamous cell carcinoma (SCC). Histopathological assessment is known to have intra and inter-observer diagnostic discrepancies even among two panels of pathologist. Subsequently, to improve on the accuracy of histopathological examination, various IHC biomarkers have been evaluated in the biopsy of cervix.

Aim: The present study was undertaken to evaluate the immunoexpression and interrelationship of p16INK4A, MIB-1 and CK17 in histopathologically diagnosed cases of CIN and invasive cervical carcinoma (ICC) which could aid in differentiating CIN and ICC from benign cervical lesions.

Materials and Methods: This study included 120 cases of cervical lesions; out of which 20 cases were each of negative for malignancy/dysplasia (NED), CIN I and CIN III, 10 cases of CIN II and 50 cases of ICC. A technique of manual tissue microarray was employed for the study of immunohistochemical markers such as p16INK4A, CK17 and MIB-1 in all cases. Results were subjected to statistical analysis.

Results: The difference in p16 immunoexpression between NED (0/20, 0%) and CIN+ICC (97/100, 97%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of p16 immunoexpression in comparison to histopathological diagnosis was 97%, 100%, 100%, 86.96% and 97.5% respectively. The overall agreement of p16 staining with histopathological diagnosis was 97.5% (?=0.9151 i.e. very good) The difference in MIB-1 immunoexpression between CIN-I (6/20, 30%) and CIN II+III (30/30, 100%), CIN (36/50,72%) and ICC (50/50, 100%) cases was statistically highly significant. (p<0.01) The difference in MIB-1 immunoexpression between NED (0/20, 0%) and CIN+IC (86/100, 86%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of MIB-1 immunoexpression in comparison to histopathological diagnosis was 86%, 100%, 100%, 58.82% and 88.33% respectively. The overall agreement of MIB-1 staining with H&E diagnosis was 88.33%. (?=0.6719 i.e. good) The difference in CK17 immunoexpression between CIN-I (11/20, 55%) and CIN-II+III (26/30, 86.67%) cases was statistically significant. (p=0.030) The difference in CK17 immunoexpression between CIN (37/50, 74%) and ICC (46/50, 92%) cases was statistically significant.(p=0.033) The difference in CK17 immunoexpression between NED (0/20, 0%) and CIN+ICC (83/100, 83%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of CK 17 immunoexpression in comparison to histopathological diagnosis was 82%, 100%, 100%, 52.63% and 85% respectively. The overall agreement of CK 17 staining with histopathological diagnosis was 85% (?=0.6029 i.e. moderate) The agreement between p16 and MIB-1 immunostaining was 89.16%. (?= 0.7 i.e., good) The agreement between CK17 and MIB-1 immunostaining was 86.6%. (?= 0.683 i.e., good) The agreement between p16 and CK17 immunostaining was 84.16%. (?= 0.5908 i.e., moderate)

Conclusion: The findings of the present study indicate that the IHC report of p16, MIB-1 and CK-17 in CIN and ICC cases if included in each histopathology report could aid in accurate diagnosis which could facilitate in better patient management.

Keywords: p16, MIB-1, CK-17, cervical carcinoma, Ki67

From 17,000 new cases of esophageal cancer worldwide during last year, 16,000 proved to be fatal. Late or incorrect diagnosis of esophageal cancer cases increases its fatality rate. Today, a data-mining technique can predict the course of the disease with the help of an upto-date technology. With this knowledge, we can reduce esophageal cancer mortality. This study aims to find an association between general characteristics, screening tests, and esophageal cancer based on raw data from the Cancer Research Center within-person interviews, using data mining and classification techniques on mortality. The 5-year medical records of 512 esophageal cancer patients and those with problems related to this cancer, with 50 functional characteristics, were included in this model. In order to provide a prognostic and rule discovery model for esophageal cancer suffering, we used preprocessing EM Algorithm. After accurate identification of the data, WEKA Software tools and Java programming language was used to create Association Rule Classifier and Apriori algorithm for the associated rule discovery. We created 6 significant rules of the association for classification generated by rule miner with 95% and 91% confidence based on screening tests and general attributes, respectively. These substantial rules showed significant association between age, history of medication, smoking, gender, carcinoembryonic antigen (CEA), creatinine, WBCs, and Platelets. The findings of this study can be used as a clue for physicians to consider patients with these characteristics as people who are more likely to develop esophageal cancer and help them for early diagnosis of patients.

Keywords: Data mining, esophageal cancer, association rule, healthcare

Nada A S Alwan¹, Faris Lami², Mohannad Al Nsoor³, David Kerr⁴

Cancer is the second leading cause of death in Iraq following heart and cerebrovascular diseases. Assessment of incidence and mortality trends is essential for prioritizing cancer control in the national health policies and plans.

Aim: To determine the patterns and trends in the incidence and mortality of the leading types of cancers affecting the Iraqi population during the last two decades.

Materials and Methods: This is a descriptive retrospective study based on the available data of the Iraqi Cancer Registry for the years (1999 - 2019). The analyzed information included the annual total number of new cancer cases and cancer deaths during the assigned period categorized by site, age, gender and morphology of each cancer. The data was coded according to Cancer Registry Program 4 (Can Reg4) and the International Classification of Diseases for Oncology (ICD-O). The estimated total annual number of Iraqi populations for the same period was retrieved from the Iraqi Ministry of Planning. The incidence and mortality rates were calculated per 100,000 Iraqi population and classified by ICD-O, site of the tumor, gender and age group.

Results: The overall cancer incidence rate (IR) in 2019 was 91.66/100,000 population (78.14 and 105.46/100,000 in males and females, respectively). The age standardized rate (ASR) was 155.60/100,000. The top five cancers in terms of IR were those of the breast (18.17/100,000; ASR:29.93/100,000), lung (7.24/100,000; ASR:14.81 /100,000), colorectum (5.95/100,000; ASR:10.77 /100,000), brain/CNS (5.83/100,000, ASR:8.39/100,000) and leukemia (5.05/100,000; ASR:6.83/100,000). The peak IR was observed among patients of both genders in the eighth decade of life (1127.37/100,000). The trend of IR for all cancers has significantly increased from 43.95/100,000 in 1999 to 91.66/100,000 in 2019 (more than 100%, p <0.0001). The highest increase was demonstrated in cancers of the colorectum (from 1.2 to 5.90, p<0.001), breast (from 6.6 to 18.2, p<0.001) and brain (from 2.0 to 5.80, p=0.032). On the other hand, the mortality rate (MR) was 28/100,000 population in 2019 (28.45 and 27.55/100,000 in males and females, respectively). The highest MR was observed in cancers of the lung (4.48/100,000), breast (3.16/100,000) and leukemia (2.42/100,000). Whereas a non-significant increase in the mortality trends of leukemia, colorectum, breast and lung cancers were noted, our data revealed a decline in the trend of brain/CNS cancer mortality (from 3.2 to 2.3/100,000).

Conclusions: The top leading cancers in Iraq are steadily increasing in upward trends though they remain lower than the global rates. The underestimated IRs and MRs are possibly attributed to suboptimum registration and missing data due to the lack of a national surveillance system. Efforts should be directed to prioritize the adoption of the national cancer control plan focusing on strengthening the population-based cancer registry.

Keywords: Trends, incidence; mortality, Iraq; common cancers.

Fenny Tjuatja^1,6,, Handoko^1,6, Henry Kodrat^1,6, Reyhan E. Yunus^2,6, Eka Susanto^3,6, Tiara Anindhita^4,6, Renindra A.Aman^5,6, Soehartati Gondhowiardjo^1,6, Sri M. Sekarutami^1,6

¹ Department of Radiation Oncology, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
² Department of Radiology, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
³ Department of Pathological Anatomy, dr. Cipto Mangunkusumo Hospital, Jakarta,Indonesia.
⁴ Department of Neurology, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
⁵ Department of Neurosurgery, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
⁶ Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Purpose: This systematic review aimed to identify the role of Ki-67 as a prognostic factor in estimating tumor grade and the radiation response in meningiomas.

Methods: A systematic search of the literature on meningiomas was carried out through the PubMed, Scopus, and EBSCOhost databases according to the PRISMA guidelines.

Results: Our search resulted in 465 collected articles, 15 of which satisfied the eligibility criteria. Twelve studies reported the correlation between Ki-67 and meningioma grade. Two other investigations reported the relationship between Ki-67 and the radiation response in meningioma, and one failed to capture the association between Ki-67 and the radiation response in meningioma.

Conclusion: The Ki-67 proliferation index has a uniform correlation with meningioma grade. Two of the 3 studies on the correlation of Ki-67 with the radiation response in meningioma patients reported that patients with a higher Ki-67 responded better to radiation therapy.

Keywords: Ki-67, Meningioma grade, Radiation therapy response, Systematic review

Sameer Ahmed Ansari¹, Khalid Al-Sindi¹, Fatima Aldoseri¹

¹King Hamad University Hospital, Kingdom of Bahrain

Ovarian cystadenofibroma is a rare benign tumor comprised of both epithelial and stromal components. It is one the unique tumors which is usually mistaken for malignancy on imaging because of partly solid and partly cystic appearance. Frozen section and subsequent histopathological examinations play a vital role in arriving at definite diagnosis and thus avoiding unnecessary extensive surgical procedure. We described a case of bilateral ovarian cystadenofibroma in a 64 years old female with the clinical impression of malignancy and posted for radical surgical procedure.

Keywords: cystadenofibroma, bilateral, malignant, ovary

Jihene Feki¹, Sana Ennouri¹, Rim Frikha², Leila Keskes³, Tahya Boudawara⁴, Hassen Kammoun², Tarek Rebai³, Mourad Haj Slimen⁵, Afef Khanfir¹

¹ medical oncology department, Habib Bourguiba Hospital -Sfax-
² Genetic department, Hedi Chaker Hospital -Sfax-
³ Histology and embryology department, Hedi Chaker Hospital -Sfax-
⁴ Pathology department, Habib Bourguiba Hospital -Sfax-
⁵ Urology department, Habib Bourguiba Hospital -Sfax

Persistent Mullerian duct syndrome (PMDS) is a congenital disorder related to male sexual development. PMDS is usually diagnosed during an inguinal hernia cure. The diagnosis of PMDS following a testicular germ cell tumor is less common. We report the cases of three infertile male patients who were diagnosed with PMDS after surgery for germ cell tumors. They were 39, 27, and 37 years old men with a medical history of neglected cryptorchidism. All patients had a male karyotype and the ELISA test for the anti-Mullerian hormone was undetectable. Patients underwent chemotherapy followed by resection of residual mass in one patient. One patient is currently alive and disease-free. The two other patients died of systemic relapse. These cases highlight how early recognition and treatment of PMDS can prevent malignant germ cell tumors. The diagnosis of PMDS relies on a systemic assessment and analysis of mutations in the gene coding for AMH and AMHR-II.

Keywords: Persistent Müllerian duct syndrome (PMDS), anti mullerian hormone, germ cell neoplasm

Yasmine Alqattan¹, Salha Ali¹, Rawan Almohammad², Noura Kayali ², Ahmad Alhuraiji ¹

¹ Department of Hematology, Kuwait Cancer control center, Kuwait
² Department of Medicine, Amiri Hospital, Kuwait

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used in the first- and second-line treatment of chronic myeloid leukemia (CML). Chylothorax is a rare presentation that results in chyle leakage from the lymphatic system into the pleural space as a consequence of thoracic duct damage. Pleural effusion has been reported frequently in patients treated with Dasatinib however chylothorax has been rarely reported. Here we report an 18year old female presenting with chylothorax after 63 months of Dasatinib intake along with a review of the relevant literature. Currently there are no standard guidelines regarding the approach to chylothorax management after the initial discontinuation of Dasatinib. Since the TKI options after stopping Dasatinib are limited, and most patients would have already failed the trial of first generation TKI, we suggest implementing a complete treatment strategy for this patient population.

Keywords: chronic myeloid leukemia, Dasatinib, Pleural effusion, Chylothorax

Yamini Krishnan¹, Gazel S¹, Aswin Joy¹, Sreedharan . P.S¹, Reshmi J S¹, Sandhya S¹

¹ MVR Cancer Centre and Research Institute, Calicut, Kerala , India -673601

The translocation t (12;17) (p13; q21) is a rare cytogenetic event most commonly described in pre-B- acute lymphoblastic leukaemia and acute myeloid leukaemia. We identified a child with an immunophenotype of Early T Cell Precursor Acute Lymphoblastic Leukaemia ETP- ALL having t (12;17) (p13; q21) translocation as the primary karyotypic anomaly. The association of t (12;17) (p13; q21) with ETP-ALL has not been described previously in literature. The possibility of it being a novel genetic abnormality or a part of the newly described entity of ETP/myeloid MPAL is being discussed. Detection of such abnormalities can alter the prognosis of ETP-ALL.

Keywords: ETP-ALL , t(12;17) (p13;q21) translocation, ETP- MPAL

Satya Narayan¹, Vineet Talwar¹, Pallavi Redhu¹, Varun Goel¹, Arpit Jain¹, Satyajeet Soni¹, Krushna Chaudhary¹, Dharmishtha Basu¹

Persistent serpentine supra-venous hyperpigmentation (PSSH) describes a hyperpigmentation of the skin overlying peripheral veins with characteristic of underlying vessels that are patent. It has been described most commonly after injection of chemotherapeutic drugs. We describe a 44 year old man with diagnosed case of Ca stomach on FOLFOX based chemotherapy. After the 1st cycle of Chemotherapy he developed serpentine supra-venous hyperpigmentation.

Introduction: Conventional chemotherapy agents commonly cause infusion-site lesions, such as chemical cellulitis due to drug extravasation and evanescent eruptions.(1) 5-Fluorouracil (5-FU) is a cytotoxic agent used mostly in combination to treat a variety of malignant disorders. Hyperpigmentation is a rare side effect occurring with 5-FU infusions; it has been reported in 2-5% of patients. Various types of pigmentary abnormalities have been reported with 5-FU use such as diffuse hyperpigmentation of the face and palms, macular pigmentary changes on the palms and soles, hyperpigmentation overlying the superficial venous network also called serpentine supravenous hyperpigmentation (SSH) and persistent supravenous erythematous eruptions (PSEE).(2)

Keywords: Serpentine Supra-venous Hyperpigmentation, Dermatological toxicity, Fluorouracil