Issue No. 29 - Jan 2019

Spectrum of Breast Diseases: Histopathological and Immunohistochemical Study from North India

Sumyra Khurshid Qadri1, Pranjali Sejwal2, Rashmi Priyadarshni2, Milan Jaiswal2, Ruchi Khandewal2, Manisha Khanna2, Tanu Agarwal2, Hema Pant2, Ratana Saxena2
1 Department of Pathology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J & K, India
2 Department of Pathology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, UP, India
Issue No. 29, Jan 2019 Abstract
Online ISSN 2521-3881

Introduction: Breast disorders commonly present as masses, which are mostly benign. However, breast cancer is the most common form of cancer and second leading cause of death among women. The study aimed at analyzing the spectrum of breast diseases especially breast cancers and assess the estrogen and progesterone receptor (ER/PR) and Her2/neu status of breast cancers on immunohistochemistry (IHC).

Materials and Methods: This was a descriptive study of 2 years (Jan 2014 - Dec 2015). All specimens of primary breast diseases received during this period at the Department of Pathology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, UP, India, were analyzed.

Results: A total of 148 breast specimens from 10 males and 133 females, (age range, 15 - 75 years; mean age, 36 years) were selected. Majority of patients presented in 4th (29.7%) and 3rd (27.7%) decades with breast lumps (97.3%), affecting mostly right breast (52%). Benign diseases (60.1%) were the commonest followed by malignant (28.4%) and inflammatory lesions (11.5%). Fibroadenoma (52.6%) and fibrocystic change (21.8%) were the commonest benign diseases and granulomatous mastitis (23.5%), the commonest inflammatory lesion. Malignancy contributed 30.6% of female breast lesions (age range, 25-75 years and mean age, 48.2 years) with 97.6% of cases being infiltrating ductal carcinomas. ER expression was seen in 58%, PR in 54.8% and Her2/neu positivity in 45.2% cases. In males, gynecomastia was the most common breast lesion (90.9%).

Conclusion: Breast diseases affected mostly young people with fibroadenoma and infiltrating ductal carcinoma being the commonest diseases. Malignant breast diseases affected females only. ER/PR hormone receptor expressions are lower compared to western countries.

Keywords: Breast diseases, benign breast diseases, breast cancer, north India

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2 14-21

Concurrent Paclitaxel and Radiotherapy for Node Positive Breast Cancer


Asmaa Ali Hassan1, Noha Yehia Ibrahim1, Mohamed Abdel Rahman Kassem1, Abdel Aziz Mostafa Toeama2
1 Clinical Oncology Department (NEMROCK), Kasr Al-Ainy School of Medicine, Cairo University, Egypt
2 Clinical Oncology Department, Al-Azhar University, Egypt


Background: Concurrent chemo-radiotherapy in breast cancer (BC) may yield better local control with minimal toxicity in node positive patients. The feasibility of paclitaxel with radiotherapy was assessed for tolerability, cosmetic outcome as well as local control.

Methods: A prospective feasibility study on forty-three female breast cancer with stage II-III was conducted after definite surgery (modified radical mastectomy and breast conservative surgery). Adjuvant chemotherapy given was 4 cycles AC (Doxorubicin 60mg/m2+ cyclophosphamide 600mg/m2) followed by 4 cycles of Paclitaxel 60mg/m2 weekly for 12 weeks concurrent with 3D Conformal radiotherapy in a dose of 5Gy/20ttt/4wks to the whole breast and supraclavicular nodal region. Boost of 10Gy/5ttt was given to the tumor bed in conservative cases. Evaluation of lung function was done by carbon monoxide diffusion. Radiotherapy toxicity and breast cosmesis were assessed by the RTOG and Harvard criteria respectively. The cosmesis was assessed and scored at the beginning and end of RT and every 6 months thereafter. This was done by patient (subjective score) and physician (objective score) by comparing it with the contralateral untreated breast.

Results: After a median follow up of 36 months, the overall survival and disease-free survival were 95% and 92.5% respectively with no local relapse or radiation pneumonitis. There was no significant change in carbon monoxide diffusion after radiotherapy (p: 0.55). There was 15% delay in radiotherapy mainly due to acute GIII skin toxicity (10%), followed equally by mucositis and wound gap (2.5%). The volume of the irradiated breast was correlated with acute cosmetic effect (p = 0.057) but not on the late skin toxicity (p = 0.56). At the last follow up, the majority of patients declared excellent score in 62.5%, good in 20%, fair in 10% and poor in 7.5%. Subjective patient’s satisfaction for the shape, color and size of the treated breast was 93%.

Conclusion: Concurrent chemo-radiotherapy with weekly paclitaxel minimized the treatment duration with acceptable tolerance, cosmesis and good local control.

Keywords: Paclitaxel, chemo-radiotherapy, breast cancer, node positive

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3 22-30

Cancer Control Priorities and Challenges in Saudi Arabia: A Preliminary projection of Cancer Burden

  Maha T. Alattas
Department of Community Medicine, King Abdul-Aziz University, Saudi Arabia

Introduction: Saudi Arabia faces a rapid growth in cancer cases and deaths despite the rapid development and expansion of its healthcare system. No applied national strategies exist, limiting cancer control efforts. Saudi Cancer Registry data lacks cancer specific mortality rates and available data to project the future cancer burden is inadequate.

Methods: This review paper examines the extent which cancer burden will increase by providing an estimate projection of cancer cases and deaths for the year 2025 and 2050. Current cancer burden and gaps are discussed. Saudi population projections were used to predict the burden of cancer types with the highest mortality. Rough estimates of the burden were calculated using incidence and mortality rates adopted from available UK cancer data and population figures from Office for National Statistics.

Findings: For most common cancers in Saudi Arabia, it is expected that the number of new cancer cases will reach 151,719 by the year 2025 and 30,718 cancer deaths are expected for the same year. Evidence from other countries’ efforts to control cancer demonstrates reduced mortality and points out the substantial need to urgently update cancer control strategy.

Discussion and Conclusion: Reviewing current trends in cancer burden in Saudi Arabia and projecting the future burden, especially of breast and colon cancers, proves the need to prioritize cancer control efforts. Planning a multidisciplinary evidence based national cancer control strategy will alleviate the burden and improve cancer outcomes.

Keywords: Cancer control, Cancer burden, Projection, Saudi health system

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4 31-38

A Novel Approach to Obtain Follow-up Data on the Vital Status of Registered Cancer Patients: The Kuwait Cancer Registry Experience

  Eiman Alawadhi1, Ahmed Al-Awadi2, Amani Elbasmi2, Michel P. Coleman1, Claudia Allemani1
1 Cancer Survival Group, London School of Hygiene and Tropical Medicine, London, UK
2 Kuwait Cancer Control Center, Ministry of Health, State of Kuwait

Objective: We present an approach to obtain accurate and complete data on the last known vital status, and the date of last known vital status of all Kuwaiti cancer patients. These data are essential for robust estimation of population-based cancer survival.

Methods: Government-issued Civil ID numbers (IDs) of patients registered during 2000-2013 were obtained from the Kuwait Cancer Registry. Missing IDs were traced using the Ministry of Health’s Information System or the patient’s medical records. IDs were manually entered in the Public Authority of Civil Information (PACI) database to ascertain vital status for patients whose vital status was not known in the registry. To obtain the date of death for deceased patients, IDs were then manually entered and searched in the electronic archive of “Death Announcements” at the Ministry of Health’s Central Records Department of Births and Deaths. Patients not found in the “Death Announcements” archive were considered alive as on 31 December 2015.

Results: The traditional method to obtain data on cancer patients’ vital status, restricted to patients whose death was certified as due to cancer, had captured only 62% of all patients’ deaths. This new approach resolved the vital status for 98.3% of patients for whom it was previously unknown. The impact was substantial: the proportion of patients known to be dead rose from 27.9% to 45.0%, while the proportion presumed alive dropped from 72.1% to 53.7%. Only 1.3% of the patients remained lost to follow-up.

Conclusion: This approach substantially improved the quality and completeness of follow-up data for all Kuwaiti cancer patients. We recommend that this approach should be performed routinely in Kuwait to enable accurate estimation and monitoring of population-based survival trends.

Keywords: population-based cancer registry, net survival, vital status, date of last known vital status

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5 39-52

Cancer survival trends in Kuwait, 2000-2013: A population-based study


Eiman Alawadhi1, Ahmed Al-Awadi2, Amani Elbasmi2, Michel P. Coleman1, Claudia Allemani1
1 Cancer Survival Group, London School of Hygiene & Tropical Medicine, London, UK
2 Kuwait Cancer Control Center, Ministry of Health, State of Kuwait

  Objective: To examine population-based cancer survival trends in Kuwait; to facilitate public assessment of cancer control.

Methods: Data were obtained from the Kuwait Cancer Registry for Kuwaiti adults (15-99 years) and children (0-14 years) diagnosed with one of 18 common cancers during 2000-2013 and followed up to 31 December 2014. Net survival was estimated at 1, 3, and 5 years by sex. To control for background mortality, life tables of all-cause mortality in the general population were constructed by single year of age, sex, and calendar year of death (“complete” life tables). Net survival estimates were age-standardised using the International Cancer Survival Standard weights.

Results: Cancers with the highest net survival throughout the 14-year period were prostate, breast (women) and rectum in adults, and lymphoma in children. Survival was lowest for liver, pancreas and lung cancer in adults, and brain tumours in children. During 2010-2013, one year survival was over 80% for cancers of the prostate, breast, rectum, cervix and colon. Five-year survival was above 80% only for prostate cancer. For children, one and five-year survival was above 80% only for acute lymphoblastic leukaemia (ALL) and lymphoma. Survival
was generally higher for women than men, and declined faster in women than men between 1 and 3 years after diagnosis. Differences between boys and girls were small.

Conclusion: Cancer survival improved for most Kuwaiti adults and children over the 14-year period, with women generally having a more favourable prognosis than men. Continuous surveillance is required to monitor cancers for which survival did not improve, and to dissect the underlying causes for the differences in survival between Kuwait and other countries.

Keywords: population-based, net survival, cancer registries, Kuwait

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6 53-59

Triple Negative Breast Cancer: 10-Year Survival Update of The Applied Treatment Strategy in Kuwait


Salah Fayaz, Gerges A. Demian, Mustafa El-Sherify, Heba Eissa, Mary Aziz, Sadeq Abuzallouf
Radiation Oncology Department, Kuwait Cancer Control Center, Kuwait


Background: Triple negative breast cancer (TNBC) is recognized as a distinct clinical and biological entity of poor outcome for almost two decades, yet its treatment strategy still needs to be better specified. The study aim is to update the 10-year survival data of our TNBC patients and to find its association with different treatment modalities.

Patients and Methods: We updated the 10-year survival data of 359 women diagnosed with TNBC between 1999 and 2009 in the Kuwait Cancer Control Center (KCCC). The overall survival (OS), disease free survival (DFS), distant metastasis free survival (DMFS) and loco-regional recurrence free survival (LRFS) were estimated using Kaplan Meier method. Survival was correlated with different prognostic factors and treatment modalities. Statistical significance was calculated using the log-rank test and defined as p < 0.05. Cox regression is used for Multivariate analysis.

Results: TNBC represented 12% of breast cancer in Kuwait with a median age of 48 years. The stage distribution was as follow: stage I, II, III, IV in 15%, 43%, 35% and 7% of patients respectively. Regarding surgery, 33% had Conservative surgery; 67% had mastectomy; 82% had axillary clearance. Chemotherapy was neoadjuvant in 25%, adjuvant in 56% and palliative in 5% of patients. Two-thirds of patients (67%) received adjuvant radiotherapy. After a median follow-up of 108 months, the 10-year OS, DFS, DMFS and LRFS were 66%, 59%, 72% and 77% respectively. The 10-year OS was 92%, 80%, 49% and 0% for Stage I, II, III and IV respectively (p =< 0.0001). OS was significantly worse with the presence of lymphovascular invasion (LVI) with p = 0.003. OS was not significantly affected by age, grade or treatment modality. In multivariate analysis, the clinical stage and LVI were still significant (P<0.0001 and 0.04 respectively).

Conclusion: In the absence of biological biomarkers, clinical stage and LVI seem to be the only significant prognostic factors for survival of TNBC patients in our study population. Timing of chemotherapy as well as the extent of surgery do not seem to affect the TNBC patients’ outcome.

Keywords: Triple Negative Breast Cancer; Long-term Survival; Prognostic Factors

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7 60-65

Early Calcium Supplementation After Total Thyroidectomy Can Prevent Symptomatic Hypocalcemia - Findings from a Retrospective Study

  Manu Santosh, Sajith Babu Thavarool, Sandeep Vijay , Adharsh Anand, Guru Charan Sahu,v Satheeshan Balasubramaniam
Department of Surgical Oncology, Malabar Cancer Centre, Thalassery, Kannur, Kerala, India

Introduction: Thyroidectomy for thyroid cancers and central neck dissection are considered as independent predictors of postoperative hypocalcemia. Post-surgical hypocalcemia is the most common and often the most difficult long-term consequence of thyroid surgeries. Management of hypocalcemia is done with calcium supplementation, but there is no consensus on the timing and the amount of calcium supplementation.

Materials and Methods: A retrospective study of all thyroid cancer patients who underwent total thyroidectomy at our Centre, from August 2009 to August 2017 was done to evaluate the prevalence of symptomatic hypocalcemia. The patients were grouped into two based on the early and late supplementation of calcium in the form of intravenous calcium gluconate and oral calcium with calcitriol.

Results: There were 133 patients of which 109 had papillary carcinoma, 11 had follicular, 3 had hurthle cell and 10 had medullary carcinoma. Of these, 49.6% underwent total thyroidectomy alone and the rest with neck dissection. 38 patients (28.6%) had a unilateral neck dissection and 16 patients (12%) had a bilateral neck dissection. 14 out of the 67 patients (20.9%) who underwent neck dissection developed symptomatic hypocalcaemia, in contrast to only 2 patients out of the 66 (3%) without neck dissection. 31.7% of lateral neck dissection and 7.7% of central compartment dissection had symptomatic hypocalcaemia (p value = 0.0053). 22.5% of patients whose parathyroid were not identified had more symptomatic hypocalcaemia than in whom at least one parathyroid gland was seen (p value=0.0004). Eleven out of 73 patients (15.1%) who were treated late with calcium and calcitriol, and one out of 60 (1.7%) who had early calcium supplementation developed symptoms
(p value=0.0073).

Conclusion: Central compartment and lateral neck dissection were significantly associated with higher incidence of symptomatic hypocalcemia. Early intervention with calcium supplementation reduced the symptoms of hypocalcemia. Identification and preservation of parathyroid glands significantly reduces the hypocalcemia.

Keywords: Hypocalcemia, Thyroidectomy, Calcium supplementation

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8 66-71

Association between nodal metastasis and histopathological factors in postoperative gingivo-buccal complex squamous cell carcinoma: A Retrospective Study


Sweta Soni1, Tej Prakash Soni2, Nidhi Patni2
1 Department of Radiation Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Radiation Oncology, Bhagwan Mahaveer Cancer hospital and Research Centre, Jaipur,
Rajasthan, India

  Objective: To evaluate association between histopathological factors and cervical lymph node metastasis in postoperative gingiva-buccal complex squamous cell carcinoma.

Methods: We retrospectively analyzed 98 postoperative gingiva buccal complex squamous cell carcinoma patients’ clinical and histopathological findings. The variables assessed were age, sex, tumour site, tumour size, degree of differentiation (grade), depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI) and extracapsular extension (ECE) and their relation with nodal metastasis.

Results: Out of 98 patients, 76 patients were pathologically node positive (pN+), including 39 of the 53 patients who were classified as cN0 (clinically node negative). The prevalence of occult neck metastasis was 73.5 %. Various parameters like tumour size, LVI, PNI, ECE and Grade showed statistically significant association with lymph node metastasis (p value: 0.029, 0.007, 0.003, 0.001 and 0.001 respectively) on bivariate analysis. Depth of invasion increases incidence of nodal metastasis but was not statistically significant (p value: 0.166). On multivariate logistic regression analysis male gender and presence of PNI were found as independent predicting factors for nodal metastasis (Odds Ratio 7.0826 to 8.65 respectively) while poorly differentiated carcinoma grade appeared non-inferior factor paradoxically (Odds Ratio 0.1033, overall 82.65 % cases were correctly classified by this model and area under ROC curve (AUC) was 0.794 of the model.

Conclusion: Male gender, poorly differentiated carcinoma and presence of PNI were found as independent predicting factors for nodal metastasis. Male gender and PNI were found risk factors while poorly differentiated carcinoma grade appeared non-inferior factor (protective) paradoxical.

Keywords: Histo-pathological factors, Gingivo buccal complex, Squamous cell carcinoma, Oral cavity
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9 72-75

Impact of HPV on the Pathobiology of Cancers

  Ritesh Kumar1, Pranay Tanwar2, Angel Rajan Singh3, Showket Hussain4, G.K. Rath1
1 Department of Radiotherapy, Dr. BRAIRCH, AIIMS, New Delhi-29, India
2 Laboratory Oncology Unit- Dr. BRAIRCH, AIIMS, New Delhi-29, India
3 Department of Hospital Administration, AIIMS, New Delhi-29, India
4 National Institute of Cancer Prevention & Research, Noida, India
  Human papilloma virus (HPV) associated cancers represents a special subgroup of cancers which are potential targets of screening strategy to reduce the burden of HPV-associated cancers. The viruses have different molecular pathways which ultimately lead to the immortalization of cells. The unique pathobiology and detailed discovery of molecular signaling pathways have paved the new dimensions and advancements in both early detection and development of newer treatment strategy in terms sensitivity towards radiotherapy in HPVinduced cancers versus others. Their clinical behavior suggests good prognosis when compared to Non-HPV positive group cancers. The better prognosis between HPV positive and Non-HPV positive cancer demands a timely diagnosis of HPV status to stratify high risk cases to promote personalized management.

Keywords: HPV, pathology of cancers
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10 76-82

Cancer Immunotherapy: An Updated Overview of Current Strategies and Therapeutic Agents

  Osama Abu-Shawer1, Tariq Bushnaq1, Mohammad Abu-Shawer2
1 School of Medicine University of Jordan, Amman, Jordan
2 Clinical Research Office King Hussein Cancer Center, Amman, Jordan
  After several years of discouraging results, immunotherapy finally becomes a powerful, clinically valid and approved treatment for numerous types of cancer. Immunotherapy involves treatment approaches that work in various ways; some boost the body’s immune system while others help guide and direct the immune cells to attack cancer cells specifically. In this review article, we summarize the current cancer immunotherapy strategies; immune checkpoint blockade, adoptive cellular therapy, cancer vaccines, oncolytic viruses, and the monoclonal antibodies and discuss the recent progress and future trends of the combination therapies.

Keywords: Immunotherapy, T-Cell, PD-L1, CTLA-4 and CAR-T
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11 83-86

An Extremely Giant Ovarian Mucinous Cystadenoma

  Abdulaziz Alobaid1, Heba Elamir1, Mohammed Abuzaid1, Ahmed Abu-Zaid2,3
1 Department of Obstetrics and Gynecology, King Fahad Medical City, Riyadh, Saudi Arabia
2 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
3 College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  Ovarian mucinous cystadenomas are cystic neoplasms lined by mucin-producing epithelial cells. They are mostly benign (80%) and frequently asymptomatic at early stages. The average diameter of ovarian mucinous cystadenomas ranges from 15 to 30 cm. Herein, we report the case of a giant benign ovarian mucinous cystadenoma in a 53-year-old postmenopausal woman. The patient presented with a very huge pelvi-abdominal distention that started ten months ago and was progressively increasing in size. It was associated with on-off abdominal pain, nausea and urinary retention. The case was discussed with a multidisciplinary team. Subsequently, the patient was consented for exploratory laparotomy. The origin of the mass was identified to be the right ovary, and right salpingo-oophorectomy was done. The resected mass measured 73x51x42 cm and weighed 108 kg. The left ovary had a multilocular mass of 15 cm in diameter, and left salpingo-oophorectomy was successively performed. There was no ascites. Histopathological examination confirmed the diagnosis of bilateral benign mucinous cystadenoma. At a postoperative 9-month follow-up in the outpatient clinic, the patient showed up in good condition without evidence of recurrence. To the best of our knowledge, we report the largest benign ovarian cyst in Saudi Arabia, and one of the largest (probably the third) in the English medical literature. It is technically feasible to manage an extremely large-sized benign mass with satisfactorily perioperative outcomes. This should be done through a multidisciplinary approach that demands an orchestrated collaboration between different specialists to yield an optimized perioperative care.

Keywords: Ovary; mucinous cystadenoma; giant ovarian cyst; case report
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12 87-90

Hemorrhagic Brain Metastasis as the Initial Manifestation of Esophageal Adenocarcinoma

  Hussein Algahtani1, Bader Shirah2, Yehya Seddeq1, Hatim Al-Maghraby3
1 King Abdulaziz Medical City/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
2 King Abdullah International Medical Research Center / King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
3 Department of Pathology and Lab Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
  Esophageal carcinoma metastasis to the brain is very rare with less than 300 cases published worldwide. The reported incidence rates of esophageal carcinoma metastases to the brain range from 0.3% to 13%. It is associated with a worse prognosis than brain metastases from other solid tumors. The most common form of metastasis is cystic lesions while hemorrhagic metastasis represents a rare subset of an infrequent entity. It is extremely rare for esophageal carcinoma to present as an isolated brain metastasis with only three cases reported worldwide. These cases were misdiagnosed as meningitis, a pituitary tumor, and glioma. This paper reports the first case of hemorrhagic brain metastasis as the initial and only manifestation of esophageal adenocarcinoma worldwide. Although extensive work up to search for malignancy is a routine procedure in patients with metastatic brain disease, upper gastrointestinal endoscopy, which is rarely done as part of the work up should be included. Esophageal cancer continues to be challenging to manage with very limited therapeutic options. To date, the clinical outcome after treatment is unsatisfactory, and prognosis is poor. Further research is required to identify better treatment approaches and improve the survival of patients. This paper is an urgent call for action to design chemotherapeutic agents that target tumor cells in the blood and different body organs and has the ability to cross the blood-brain barrier with an acceptable side effect profile. This is mainly because metastatic brain disease has become more common in young age group.

Keywords: Brain Hemorrhagic Metastasis; Esophageal Adenocarcinoma; Initial Manifestation
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