Clinicopathological characteristics of young versus older patients with breast cancer: A retrospective comparative study from the Madinah region of Saudi Arabia.

OBJECTIVES: To compare the clinicopathological, histological and immunohistochemical features of breast cancer (BC) in between young (≤40 years) and older (>40 years) patients. METHODS: This retrospective study included histopathological reports of all patients with primary BC diagnose at the King Fahad Hospital, Madinah, Saudi Arabia between January 2006 and November 2020. RESULTS: During the study period, a total of 708 patients with BC were identified; 173 cases (24.4%) were ≤40 years old and 535 (75.6%) were above 40 years. There were significant differences in tumor size (p=0.046), tumor grade (p<0.0001), tumor stage (p=0.047), lymphovascular invasion (p<0.0001), and distant metastasis (p<0.0001) between the 2 groups. Comparing the status of the hormone receptors and molecular subtypes between the 2 age groups, BCs in the younger patients were triple-negative (p=0.008) in majority of the cases and less likely to be estrogen receptor (ER) and progesterone receptor (PR) hormone receptors-positive (p=0.0001, p<0.0001). Young patients exhibited the HER2/neu type with more frequent statistical significance (p=0.016) and the tumor type luminal A (p=0.002) with less frequent statistical significance compared to old patients. CONCLUSION: Although BC in young women is uncommon, it may be different with regards to poor prognostic outcomes, which are attributed to more aggressive histopathological features and less favorable receptor status when compared to the cases diagnosed in older women.

Pattern of cancers in adolescent and young adults.: A 15-year retrospective study at King Fahad Hospital, Al-Madinah Al-Munawwarah, Saudi Arabia.

OBJECTIVES: To evaluate the incidence and pattern of cancer in adolescents and young adults (AYAs) age group in Al-Madinah Al-Munawwarah region of Saudi Arabia. METHODS: This retrospective histopathology-based study was conducted at a tertiary care center in Al-Madinah Al-Munawwarah, Saudi Arabia and comprised cases of cancers for 15 years between January 2006 and December 2020. RESULTS: During the last 15-year period, 8,769 cases of cancers were diagnosed out of which 475 (5.4%) cases were registered in AYAs. Of these cases, 232 (48.8%) were males while 243 (51.2%) were females, with a male-to-female ratio of 0.9:1. The 3 most common cancer groups in the entire cohort were carcinomas (n=165; 34.7%), lymphomas (n=135; 28.4%), and leukemias (n=91; 19.2%). The most common sites in carcinomas were thyroid (n=60; 12.6%), breast (n=35; 7.4%), and gastrointestinal (n=18; 3.8%). The leading cancers in males were the lymphomas (n=74; 15.6%), leukemias (n=57; 12%), bone (n=21; 4.4%), and central nervous system (n=20; 4.2%), while in females, the most common cancers were the lymphomas (n=61; 12.8%), thyroid (n=40; 8.4%), breast (n=34; 7.2%), and leukemias (n=34; 7.2%). CONCLUSION: Our findings are in concordance with studies in national and international literature and we believe that our study provides a baseline tool for future population-targeted studies.

Nasopharyngeal carcinoma metastasis to the breast.

Breast metastases from extra-mammary neoplasms are rare, accounting for less than 2% of breast cancer cases. A 43-year-old female patient presented with a mass in her left breast and swelling in her left axillary region. A histopathological examination of the mass showed enlarged polygonal tumor cells with scant to moderate, eosinophilic to amphophilic cytoplasm and enlarged, hyperchromatic and pleomorphic nuclei with irregular nuclear membranes. An immunohistochemistry (IHC) examination was positive for pan cytokeratin and negative for CK7, CK20, S-100, LCA, HMB45, CD 20, desmin, myogenin, GCFDP-15, transcription factor-1, villin, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. As she was a known case of nasopharyngeal carcinoma, and based on the histopathology ndings and IHC profile, the patient was diagnosed with breast metastasis from NPC. The patient was deceased 3 months after refusing the recommended medical intervention.

The trends and patterns of congenital heart diseases at Madinah Cardiac Center, Madinah, Saudi Arabia.

OBJECTIVES: To characterize the pattern of congenital heart diseases (CHDs) in Madinah, Saudi Arabia. METHODS: We retrospectively collected and analyzed the demographic and diagnostic details of all patients with CHDs referred at Madinah Cardiac Center (MCC) over a period of 3 years from January 2017 to December 2019. RESULTS: During the study period, 1,127 patients with CHDs were identified. The male to female ratio was 1.1:1, with a mean age of 8.4±2.4 years. The acyanotic CHDs were the predominant lesions, accounting for 84.8% of all cases, while the cyanotic types accounted for 13%. Patent ductus arteriosus (PDA), ventricular  septal defects (VSD), atrial septal defects (ASD), coarctation of the aorta (CoA), and atrioventricular septal defect (AVSD) were the most common acyanotic CHDs and represented 27.9%, 24.8%, 18.9%, 6.4%, and 4.4% of the total cases, respectively. Tetralogy of Fallot (ToF) (8.7%), followed by transposition of the great arteries (TGA) (1.7%) and truncus arteriosus (1.1%), were the most common cyanotic CHDs. There was a male predominance of VSD, ToF, CoA, TGA, and truncus arteriosus. In contrast, PDA, ASD, and AVSD were more common in females.  Conclusion: The pattern of CHDs observed in our study and age at which the diagnosis of CHDs was made were different from the other national and international studies, which points to a diagnostic issue along with problems of awareness on the part of the general population.

Clinicopathological and prognostic significance of androgen receptor overexpression in colorectal cancer. Experience from Al-Madinah Al-Munawarah, Saudi Arabia.

OBJECTIVES: To examine the androgen receptor (AR) status in colorectal cancer (CRC) patients by the immunohistochemical method and to correlate the findings with all available clinicopathological parameters of prognostic significance. METHODS: Archival tumor samples were studied using immunohistochemistry for AR expression in 324 patients with CRC. Patients were diagnosed at the Pathology Department at a tertiary care Hospital, Al-Madinah Al-Munawarah, Saudi Arabia, between January 2006 and December 2017. RESULTS: There is a complete lack of AR expression in normal colonic mucosa; however, AR was expressed in 16 cases (40%) of colorectal adenoma. In CRC, AR expression was high in 118 cases (36.4%). There were no significant correlations between AR expression and gender, age, tumor histologic type, and tumor location. However, AR expression revealed a significant correlation with tumor size (p=0.026), tumor differentiation (p=0.047), American Joint Committee on Cancer (AJCC)  staging (p=0.043), lymph node positivity (p=0.018), lymphovascular invasion (p=0.018), and distant metastasis (p=0.049). In univariate Kaplan-Meier survival analysis, there was a significant (p=0.002) difference in overall survival between AR positive and negative tumors in favor of the latter. In multivariate (COX) models, high AR expression (p=0.002), AJCC (p less than 0.001), and lymphovascular invasion (p less than 0.001) were the only significant independent prognostic indicators of overall survival in CRC.Conlusion: Our study showed that the patients with higher AR expression had a significantly poorer survival rate, AR expression had the potential to be a prognostic marker of CRC.

The histopathological pattern of benign and non-neoplastic skin diseases at King Fahad Hospital, Madinah, Saudi Arabia.

OBJECTIVES: To characterize and compare the histopathological pattern of benign skin diseases in patients from Madinah region of Saudi Arabia. METHODS: This retrospective study was conducted at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia, and contained cases of benign skin diseases for 11 years (from January 2006 to December 2017). The findings were tabulated in Microsoft Excel sheet and classified based on histopathological diagnosis. RESULTS: Of 1,125 skin tissues reviewed, 579 (51.5%) specimens were from male patients and 546 (48.5%) specimens were from females giving a male: female ratio of 1.1:1. The ages ranged from 1 to 101 years with a mean age of 36.9±9.8 years. Most of the skin diseases (n=639; 57%) were seen in the age group 20-49 years. The most common skin diseases observed were disorders of skin appendages (29.6%) followed by benign tumors (18.3%), disorders of pigmentations (11.9%), papulosquamous lesions (11.4%), and dermatitis/eczema (10%). In the group of skin appendages disorders, epidermal inclusion cyst was the most common disease entity representing 20.4% of cases, followed by trichilemmal cyst accounting for 9.2% of the total cases. Mean ages of the patients were 35±8.5 years and 36.7±9.7 years respectively. CONCLUSION: A variety of benign skin lesions were seen in the present study in a wide age distribution range. The most common skin diseases observed in this study were skin appendage disorders, benign skin and adnexal tumors, pigmentation disorders, and papulosquamous lesions.

The prognostic significance of p63 cytoplasmic expression in colorectal cancer. An immunohistochemical study.

OBJECTIVES:   To evaluate p63 expression pattern in Saudi colorectal cancer (CRC) patients and correlate that with clinicopathological parameters and its role in carcinogenesis and prognosis. METHODS: Archival tumor samples were analyzed by immunohistochemistry for p63 expression in 324 consecutive Saudi patients diagnosed with CRC between January 2006 and December 2017 at the Pathology Department of a tertiary care Hospital, Madinah, Saudi Arabia. RESULTS: P63 over-expression was absent in normal mucosa, while 12.5% cases of adenoma showed its over-expression. In CRC, p63 expression was high in 24.1% of cases. There were no significant correlations between p63 expression and gender, tumor location, tumor size and tumor histologic differentiation. However, high p63 expression revealed a significant correlation with age (p=0.035), tumor type (p=0.004), American Joint Committee on Cancer stage (p=0.046), lymph node metastasis (p=0.006), lymphovascular invasion (p=0.006), distant metastasis (p=0.049), high Ki67 expression (p=0.000) and K-ras expression (p=0.002). The Kaplan-Meier analysis revealed a shorter period of survival with p63 over-expression (p less than 0.001). The Cox-regression model analysis showed that p63 over-expression was an independent prognostic marker in CRC (p=0.000). CONCLUSION: P63 expression was increased from normal to adenoma to carcinoma sequence. Moreover, p63 cytoplasmic expression seems to be related to high Ki67 indexing, K-ras expression, advanced tumor stage and poor clinical outcome of CRC. These findings suggest a significant role of cytoplasmic p63 expression in tumor progression and prognosis.

A histopathological analysis of lung cancers. An 11-year retrospective study from Al-Madinah Al-Munawwarah, Saudi Arabia.

OBJECTIVES: To determine the histopathological pattern of lung cancers in Madinah, Saudi Arabia. METHODS: This retrospective histopathology-based study was conducted at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia and comprised cases of lung cancers for 11 years  between January 2006 and December 2017. The data was obtained from histopathologic reports and evaluated for age, gender, site of tumor, and histopathological patterns with grade.  Results:  A total of 138 patients with lung cancers were identified, 103 (74.6%) patients were males and 35 (25.4%) patients were females with a male to female ratio of 2.9:1. The ages ranged from 6 to 97 years with a mean age of 60.6 ± 14.7 years. Adenocarcinoma (AC) was the most common pathological type (47.8%), followed by squamous cell carcinoma (SCC) (25.3%), neuroendocrine tumor (8.7%) and metastatic carcinoma (8%). Both ACs and SCCs showed a male predominance with a ratio of 2.9:1 (male) and  4.8:1 (female). The majority of ACs (56.5%) and SCCs (65.7%) were moderately differentiated. Conclusion: The study established a baseline of lung cancer pattern on the basis of histopathological experience in a tertiary referral hospital in Al-Madinah Al-Munawwarah, Saudi Arabia. The results obtained showed similarities with that in the world literature and Saudi national studies.

Histopathological pattern of skin cancer in Western region of Saudi Arabia. An 11 years experience.

OBJECTIVES: To determine the histopathological pattern of skin cancer in Madinah region of Kingdom of Saudi Arabia (KSA). Methods: This is a retrospective study including all cases with a histological diagnosis of skin cancer diagnosed at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia, between January 2006 and December 2017. Data included  age, gender, site and histology of the tumor were collected from histopathological reports and analyzed using Statistical Package for the Social Sciences  (SPSS) Version 21. Results: Among the 202 cancer cases studied in our series, there were 124 (61.4%) cases of basal cell carcinoma (BCC), 33 (16.3%) cases of squamous cell carcinoma (SCC), 14 (6.8%) cases of mycosis fungoides (MF), 12 (5.8%) cases of dermatofibrosarcoma protuberans (DFSP) and 7 (3.7%) cases of malignant melanomas (MM). The male to female ratio for all cases was 2.2:1. The ages ranged from 5 to 100 years with a mean age of 60.1±15 years. The peak age distribution was in the 60-69 year group. The most common site involved in BCC and SCC was the head and neck (92.7% and 66.7%) respectively). Acral distribution of MM was seen in 57.1% of the cases. Conclusion: Our data based on the histopathology history in the Madinah region match that in the world literature and Saudi national studies.

Primary mucinous adenocarcinoma of the eyelid: A case report and literature review.

Primary mucinous adenocarcinoma (PMA) of the eyelid is an exceptionally rare clinical entity. Often, it mimics with benign lesions on clinical examination and with metastatic mucinous adenocarcinoma on histological examinations. We report a case of PMA in a 60-year- old male patient who came with a slow-growing, painless swelling near the lower lid of the left eye. Excisional biopsy from the mass revealed a mucinous adenocarcinoma. To differentiate it from a metastatic mucinous adenocarcinoma, a wide range of immunohistochemistry panel was run. The tumor cells showed strong positivity for cytokeratin7, cytokeratin5/6, P63, estrogen receptor, progesterone receptor and negativity for cytokeratin20. Moreover, extensive metastatic work-up did not show any primary malignancy elsewhere, hence a final diagnosis of PMA was made. We believe that, this is the second reported case from the Middle East and the first in the Madinah region of Saudi Arabia.

Impact of cyclooxygenase-2 over-expression on the prognosis of colorectal cancer patients. An experience from Western Saudi Arabia.

OBJECTIVES: To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal cancer (CRC) and its role in carcinogenesis and prognosis. METHODS: It was a retrospective study. Archival samples were obtained from Pathology Department at King Fahad Hospital, Madinah, Saudi Arabia, over 11 years' period (January 2006 to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20 cases of normal colonic mucosa. RESULTS: Cyclooxygenase-2 over-expression was observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of CRC cases. There were no significant correlations between COX-2 over-expression and age, gender, tumor site, or tumor size. However, COX-2 over-expression revealed highly significant correlations with tumor differentiation, lymph node metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that patients with high COX-2 expression had significantly shorter periods of survival. Multivariate analysis by means of the COX-2 regression model revealed that high COX-2 over-expression, AJCC, and Ki67 expression were the only significant independent prognostic indicators. CONCLUSION: Cyclooxygenase-2 over-expression increases during normal-adenoma-carcinoma sequence, moreover COX-2 over-expression is associated with advanced tumor stage and Ki67 over-expression. These findings suggest a significant role of COX-2 in the carcinogenesis and prognosis of CRC in our study population.

Histopathological pattern of testicular diseases in western Saudi Arabia.

OBJECTIVES: To determine the histopathological pattern of testicular diseases among Saudi patients in Madinah, Saudi Arabia. METHODS: This retrospective histopathology-based study was conducted in a tertiary care hospital in Madinah, Saudi Arabia, from January 2006 to December 2017. The data collected were entered into MS-Excel and  analyzed using the Statistical Packages for Social Sciences Version 19. RESULTS: Of the 199 testicular specimens received, 108 (54.3%) of the biopsies were taken for diagnostic test, while 91 (45.7%) were for therapeutic test. The male infertility was the only indication in the diagnostic group, accounting for 108 (54.3%) with a mean age of 28±7.9 years. Benign conditions of the testes were the most common indication in the therapeutic group accounting for 76 cases (38.2%), followed by 15 cases (7.5%) of testicular tumors. Hemorrhagic infarction from testicular torsion was the most common histologic patterns in benign testicular conditions group, accounting for 46 (23.2%) of the cases with a mean age of patients 32.1±8.1 years. Mixed non-seminomatous germ cell tumor was the most common primary tumor in 7 (3.5%) cases, followed by seminoma occurring in 5 (2.5%) cases. Mean ages for these patients were 33.7±8.1 years for primary tumor and 35.6±9.1 years for seminoma. CONCLUSIONS: The pattern of testicular diseases on the basis of histopathology experience in the Madinah region appears to conform to world literature and KSA.

Clinicopathologic Patterns of Adult Renal Tumors.

BACKGROUND AND AIM: Adult renal tumors (ARTs) are rare as compared with tumors of other organs and systems; however, it is important to have demographic and pathology data of rare tumors, including ART. No such data are available from the Kingdom of Saudi Arabia (KSA). Therefore, we aimed to study the demographic and pathological data of ART from King Fahad Hospital, Al-Madinah, KSA. MATERIALS AND METHODS: This is a retrospective study of computerized data from the histopathology laboratory of King Fahad Hospital during a 10-year period (January 2006-September 2015). RESULTS: There were 42 cases of ART, comprising 28 males and 14 females (male:female ratio of 2:1). The study group ranged in age from 17 to 83 years, with a mean of 54.5 years. In the study cohort, 93% of the patients had malignant tumors and 7% had benign lesions. Renal cell carcinoma (RCC) accounted for 85.8% of cases, followed by squamous cell carcinoma and sarcoma. The benign tumors recorded in our series were oncocytoma (4.7%) and angiomyolipoma (2.4%). The tumor size of RCC ranged from 4 to 17 cm, with a mean of 7.4 cm. The majority of patients (68%) had Fuhrman Grade II tumor. Gross capsular invasion, renal vein invasion and lymph node metastases were present in one case each. CONCLUSION: We conclude that the pathological findings of ART from the Madinah region are in concordance with studies in national and international literature.

Ki67 expression in breast cancer. Correlation with prognostic markers and clinicopathological parameters in Saudi patients.

OBJECTIVES: To evaluate Ki67 immunoexpression pattern in Saudi breast cancer (BC) patients and investigate any possible predictive or prognostic value for Ki67. METHODS: This is a retrospective study designed to quantitatively assess the Ki67 proliferative index (PI) in retrieved paraffin blocks of 115 Saudi BC patients diagnosed between January 2005 and March 2015 at the Department of Pathology, King Fahd Hospital, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. The Ki67 PI was correlated with individual and combined immunoprofile data of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) with their clinicopathological parameters.   RESULTS: Ki67 immunoreactivity was highly expressed (greater than 25% of the tumor cells were positive) in 85 (73.9%) patients. The Ki67 PI was significantly associated with poor prognostic clinicopathological parameters including old age (p less than 0.02), high tumor grade (p less than 0.01), lymph node metastasis (p less than 0.001), and Her-2/neu positivity (p less than 0.009). However, the association with ER positivity, PR positivity, tumor size, and lymphovascular invasion were not statistically significant. The Ki67 PI was significantly associated with BC molecular subtypes that were Her2/neu positive (luminal B and HER-2) subtypes compared with the Her2/neu negative (luminal A) subtype (p less than 0.04). CONCLUSION: The Ki67 PI is significantly higher in Saudi BC patients comparing with the reported literature. Ki67 PI was highest in the HER-2 and luminal-B molecular subtypes. Along with other prognostic indicators, Ki67 PI may be useful in predicting prognosis and management of Saudi BC patients.

High quality tissue miniarray technique using a conventional TV/radio telescopic antenna.

BACKGROUND: The tissue microarray (TMA) is widely accepted as a fast and cost-effective research tool for in situ tissue analysis in modern pathology. However, the current automated and manual TMA techniques have some drawbacks restricting their productivity. Our study aimed to introduce an improved manual tissue miniarray (TmA) technique that is simple and readily applicable to a broad range of tissue samples. MATERIALS AND METHODS: In this study, a conventional TV/radio telescopic antenna was used to punch tissue cores manually from donor paraffin embedded tissue blocks which were pre-incubated at 40oC. The cores were manually transferred, organized and attached to a standard block mould, and filled with liquid paraffin to construct TmA blocks without any use of recipient paraffin blocks. RESULTS: By using a conventional TV/radio antenna, it was possible to construct TmA paraffin blocks with variable formats of array size and number (2-mm x 42, 2.5-mm x 30, 3-mm x 24, 4-mm x 20 and 5-mm x 12 cores). Up to 2-mm x 84 cores could be mounted and stained on a standard microscopic slide by cutting two sections from two different blocks and mounting them beside each other. The technique was simple and caused minimal damage to the donor blocks. H and E and immunostained slides showed well-defined tissue morphology and array configuration. CONCLUSIONS: This technique is easy to reproduce, quick, inexpensive and creates uniform blocks with abundant tissues without specialized equipment. It was found to improve the stability of the cores within the paraffin block and facilitated no losses during cutting and immunostaining.

Profile of benign breast diseases in western Saudi Arabia. An 8-year histopathological review of 603 cases.

OBJECTIVES: To describe the histopathological patterns of benign breast diseases (BBD) among Saudi patients. METHODS: This is a retrospective review of BBD reports of Saudi patients of both genders and all age  groups seen between January 2006 and December 2013 at King Fahad Hospital, Madinah, Kingdom of Saudi Arabia. RESULTS: Out of the total 1005 breast biopsies, 603 cases (60%) were BBD. The female to male ratio was 30.7:1. The overall mean age for BBD was 27.5 years, with an age range of 14-80 years. The most common lesion was fibroadenoma (FA) accounting for 44.3% of cases (mean age: 23.5 years), followed by 23.4% fibrocystic change (FCC) (mean age: 37.1 years). Both lesions had a peak occurrence in the third decade. Inflammatory lesions constituted 13.9% of cases. Most common were granulomatous mastitis (3.5%), chronic mastitis (3.3%), and acute mastitis with abscess (3.1%). Other major lesions encountered were fibroadenomatoid hyperplasia (3.1%), intraductal papilloma (2.8%), and benign phylloides tumor (2.6%). All benign diagnoses in male patients were gynecomastia and most patients (68.4%) were under 40 years. CONCLUSION: In this study, BBD constituted 60% of breast lumps, and were mostly FA and FCC. The BBD peaked at the 20-29 year age range.