A rare case of carcino-sarcoma of the esophagus with huge intrathoracic metastasis.

Carcinosarcoma of the esophagus constitutes only 0.5%-2.8% of all malignant esophageal cancers. It is identified by the presence of both carcinomatous and sarcomatous components. A clear regimen of treatment has not been established due to the limited understanding of the disease. We present a case of carcinosarcoma of the esophagus with rapid recurrence and invasion to the intrathoracic cavity only 6 weeks after esophagectomy. Carcinosarcoma carries a poor prognosis, as it has a late tendency of hematogenous spread with a high growth rate.

Imaging Patterns in Breast Cancer for Women Under 40 Years: A Descriptive Cohort Study.

BACKGROUND AND AIM: Breast cancer is the most frequently occurring malignant disease in women and remains the leading cause of cancer-related deaths among females worldwide. The aim of this study is to evaluate the imaging findings of breast cancer in women under the age of 40 and analyze their pathological patterns. METHOD: A retrospective study was conducted from 2013 to 2019, involving 120 patients below 40 years of age with pathologically confirmed primary epithelial breast cancers. The data were collected from the electronic records of a tertiary hospital in Riyadh, Saudi Arabia. Mammograms were performed for 115 patients, ultrasounds were conducted for all patients, and MRI scans were carried out for 47 patients. RESULTS: All radiological findings and clinical characteristics of the 120 cases were retrieved from our digital-based system. The majority of breast cancer patients (83.4%) were between 30 and 40 years old, and the most common clinical presentation was a mass (45.8%). Out of the 73 patients who underwent genetic tests, 32.9% tested positive for gene mutations. No statistically significant correlation was found between specific age groups and breast composition (P = 0.216), specific mammogram abnormalities such as masses (P = 0.262), or microcalcifications (P = 0.421). Ultrasonography was performed for all patients, with abnormalities detected in only one patient who was diagnosed with Paget's disease of the nipple. Masses, with or without parenchymal changes, were the predominant feature in 88.3% of cases. CONCLUSION: The imaging findings in breast cancer cases typically involve masses with suspicious features, irregular shape, and spiculated margins on mammograms, and irregular shape with microlobulated or angular margins on ultrasound. MRI features commonly include masses with irregular shape and heterogeneous enhancement. The luminal B subtype was identified as the most prevalent pathological feature, characterized by a high proliferative index (Ki-67%).

Assessing the Correlation of Rate of Pathological Complete Response and Outcome in Post Neoadjuvant Chemotherapy Setting and Molecular Subtypes of Breast Cancer.

Background Neoadjuvant chemotherapy (NAC) is being widely used in treating breast cancer (BC). This study aimed to analyze the correlation between clinicopathological features, immunohistochemistry (IHC)-based molecular subtypes, and the pathological response to NAC and its relationship with disease-free survival (DFS) and overall survival (OS). Materials and methods A retrospective analysis of 211 breast cancer patients who received NAC between 2008 and 2018 was performed. Tumors were classified by IHC into luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative subtypes. The chi-square test was used to assess the association between pathological response and clinicopathological parameters. Cox regression analysis was used to assess factors related to DFS and OS. Results Post NAC, 19.4% of patients achieved a pathologic complete response (pCR). Estrogen receptor (ER), progesterone receptor (PR), HER2 (p<0.001, 0.005, and 0.02), Ki67 (p=0.03), molecular subtypes (p<0.001), T stage (p=0.04), and N stage (p=0.01) were significantly associated with pathological response. The rate of pCR was highest among HER2-enriched and triple-negative tumors (45.2% and 28%, respectively) with OR=0.13 and p<0.001 for the HER2-enriched subtype. Patients with pCR were 61% less likely to develop metastasis (adjusted hazard ratio [aHR]=0.39, p=0.06, 95% CI=0.14-1.06) and were significantly associated with better OS (aHR=0.07, p=0.02, 95% CI=0.01-0.61). Patients who were ≤40 years old (aHR=2.1, p=0.01), with T4 (aHR=3.4, p=0.02), grade 3 (aHR=2.5, p=0.01), and node-positive disease (HR=2.24, p=0.02) were at an increased risk of developing metastasis. High Ki67 was found to be significantly associated with better DFS (p=0.006). Conclusion HER2-enriched and triple-negative BC were associated with a higher rate of pCR. Patients with pCR had significantly better DFS and OS. Younger age, advanced stage, higher grade, and lymph node involvement were risk factors for metastasis.

Pelvic Radiation-Induced Sarcoma With Rhabdomyoblastic Differentiation Following Treatment of Cervical Cancer.

Radiation-induced sarcomas (RIS) are a rare long-term complication of radiation therapy, with a reported incidence of 2.5-5.5%. They usually develop several years following exposure to radiotherapy. The most common reported subtypes are undifferentiated pleomorphic sarcoma, angiosarcoma, and leiomyosarcoma. Breast cancer is the most common primary malignancy preceding RIS, followed by uterine cervical carcinoma. Only a few cases of RIS with rhabdomyoblastic differentiation have been reported in the literature, usually following the treatment of retinoblastoma. Herein, we report a rare case of RIS with rhabdomyoblastic differentiation in the pelvic region developing 12 years after cervical cancer radiation therapy.

Sebaceous carcinoma of the vulva: a case report and review of the literature.

Sebaceous carcinoma is a rare malignant cutaneous neoplasm that is most commonly arises in the ocular region. Although it can occur in extraocular sites, sebaceous carcinoma is rarely encountered in the vulva. The use of immunohistochemical staining is very crucial to exclude other differential diagnoses including primary cutaneous and metastatic neoplasms. Unlike ocular sebaceous carcinoma, little is known about the clinical behavior and the prognostic factors in vulvar sebaceous carcinoma. Herein, we present a case of vulvar sebaceous carcinoma in a 27-year-old female, who presented with a labial tumor with lung metastases. To the best of our knowledge, only 11 similar cases were previously reported in the literature.

Phyllodes tumor of the breast clinical experience and outcomes: A retrospective cohort tertiary hospital experience.

BACKGROUND: Phyllodes tumor (PT) accounts for <1% of all breast tumors worldwide. Based on their microscopic features, these tumors are classified into benign, borderline, and malignant. This study aimed at evaluating the clinical experience and the clinicopathologic features of PT. METHODS: A retrospective cohort study of 46 female patients with histologically diagnosed PT. Data collection and evaluation was done on patient demographics, preoperative radiological assessment and pathology, surgical procedure, post-surgery pathological evaluation, radiation therapy (RT), and follow-up. RESULTS: The median age at diagnosis was 42 years and young premenopausal patients (median age 35 years) had malignant PT. Forty-five patients underwent core needle biopsy (CNB) with high sensitivity and the positive predictive value (82.2% and 97.4% respectively). Thirty-nine patients (86.7%) underwent conservative surgery and 6 (13.3%) had a mastectomy. Twenty-seven (58.6%) were classified as benign, 11 (23.9%) as borderline and only 8 (17.4%) as malignant PT. Malignant PT had the greatest median tumor size (13 cm). Mortality and recurrence rates were 4.3% and 2.2% respectively. RT was administered in 6 patients (13.0%), 5 having malignant and 1 borderline PT. The metastatic rate was found to be 6.5%. CONCLUSION: PT are rare breast tumors with variable biologic behavior and heterogenous clinicopathological findings. Young, premenopausal women with large tumors may have malignant PT with a risk of recurrence and metastasis. Core needle biopsy is a reliable tool for diagnosis of PT with strict follow-up recommended for large tumors diagnosed as fibroadenoma on CNB. Surgical management must ensure a tumor-free margin on excision to reduce recurrence.

Predictability of 21-Gene Recurrence Score Assay by Using Pathological and Immunohistochemical Parameters in Breast Cancer.

BACKGROUND: Oncotype Dx is used to predict the long-term recurrence risk in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer (BC). This study aimed at establishing a correlation between clinicopathological parameters and recurrence score (RS), subsequently improving predictability and ultimately justifying the use of the multigene assay. MATERIALS AND METHODS: A retrospective analysis of the pathology and clinical data of 114 female patients with BC who had Oncotype Dx testing between 2012 and 2019. The pathological parameters included are tumor cell type, tumor grade, pathological stage, and mitotic index (MI). The expression of ER, progesterone receptor (PR), HER2, and Ki67 was assessed by immunohistochemistry. A univariate and multivariate linear regression analysis was performed to assess the correlation between these parameters and the RS. RESULTS: In univariate analysis, age (˂40 years), higher tumor grade, and low PR expression were significantly associated with higher RS (P = .02; ˂.001; and ˂.001, respectively). Both MI and Ki67 were also strongly correlated with an increase in the RS with a P value of .01 (Spearman correlation 0.34 and 0.33). In multivariate linear regression analysis, age, MI, and Ki67 lost their significance, but both higher grade and PR remained significantly associated with a higher RS along with the tumor stage (P ˂ .001; ˂.001; and .04, respectively). CONCLUSIONS: Tumor grade and PR immunohistochemical expression are the main predictors of RS in our study population. Other clinicopathological features were not significant predictors of change in RS in multivariate analysis.

Uterine cervix rhabdomyosarcoma: an uncommon entity in an adult patient.

Embryonal rhabdomyosarcoma (ERMS) is a malignant neoplasm mostly affecting the genitourinary system of children and is rarely seen in adults. ERMS in uterine cervix is rare and can be misdiagnosed in adult as adenosarcoma or carcinosarcoma. The use of immunohistochemical staining is highly recommended to make sure that the correct diagnosis is reached. To the best of our knowledge, only seven cases of cervical ERMS in women above the age of 50 have been reported in English literature. Herein, we report a rare case of cervical ERMS in a 50-year-old woman that was initially misdiagnosed as an adenosarcoma.

Modelling risk assessment for cervical cancer in symptomatic Saudi women.

OBJECTIVES: To assess whether the utility of cervical cancer screening could be improved by combining multiple factors in addition to the pap test. Methods: A retrospective cohort study of 300 symptomatic women who were suspected to have cervical cancer and referred for biopsy examination at King Abdulaziz Medical City, Riyadh, Saudi Arabia between February 2017 and December 2017. Results: A high risk of cervical cancer in Saudi women was associated with 4 risk factors: family history (adjusted odds ratio [aOR], 4.216; 95% confidence intervals [CI], 1.433-12.400), vaginal bleeding (aOR, 3.959; 95% CI, 1.272-12.318), hypertension (aOR, 4.554; 95% CI, 1.606-12.912), and an abnormal pap smear test (aOR, 13.985; 95% CI, 5.108-38.284). The model yields an adequate utility (area under the curve, 87.5%, 95% CI, 80.9-94.0%) with acceptable goodness-of-fit (p=0.6915). Conclusion: The pap smear test alone is inadequate to assess high risk for cervical cancer in our center. Early detection of cervical cancer may require consideration of a combination of factors including the pap test. This study has shown that using a combination of abnormal family history, vaginal bleeding, hypertension, and the pap smear test improved the effectiveness of cervical cancer screening.

Anaplastic Sarcoma of the Kidney: A Rare Unique Renal Neoplasm.

Anaplastic sarcoma of the kidney (ASK) is an extremely rare tumor, which usually presents as a large renal mass. Microscopically, the tumor is composed of pleomorphic mesenchymal spindle cells with marked atypia, associated with chondroid differentiation and focal round primitive mesenchymal cells. Herein, we present a case of anaplastic sarcoma of the kidney in a 3-year-old female, who presented with a large abdominal mass. To the best of our knowledge, less than 25 cases are reported in the literature. In addition, this is the first case reported from the Middle East.

Can problematic fibroepithelial lesions be accurately classified on core needle biopsies?

Fibroepithelial lesions (FEL) of the breast are notoriously difficult to classify on core needle biopsies. The goal of this study was to evaluate interobserver variability and accuracy of subclassifying difficult FELs into fibroadenoma (FA) and phyllodes tumors (PTs). We identified 50 breast core needle biopsies, initially diagnosed generically as FEL, with subsequent excision and final diagnosis of either FA or benign PT. Five surgical pathologists from one institution independently reviewed these in 3 rounds. The pathologists were blinded to the final excisional diagnosis. Two diagnostic categories were allowed: FA and PT. A set of histologic criteria was provided including the presence of subepithelial condensation, stromal heterogeneity, overgrowth, pleomorphism, fragmentation, cellularity, adipose tissue entrapment, and mitotic count and asked to review the slides for the second round. A third round of interpretations was conducted after each criterion was defined. Interobserver agreement for the diagnosis and each criterion was evaluated using the κ level of agreement. Accuracy of ratings to final diagnosis was calculated using Wilcoxon signed-rank test. κ Values for interobserver agreement were fair for the first and second rounds varying from 0.20 to 0.22, respectively. This increased to 0.27 in round 3. When considering each category, the κ value varied from 0.26 to 0.29 for FA and 0.28 to 0.14 for PT. Overall, there was fair agreement between the pathologists in all categories. The rate of correctly diagnosed cases ranged from 40% in the first round, to 48% in the second round, to 67% in round 3. Overall the pathologists performed better in identifying FA than PT. The accuracy of interpretations was significantly different between the first (40%), second (48%), and third rounds (67%).

Testicular adrenal rest "tumor" or Leydig cell tumor? A report of a challenging case with literature review.

Congenital adrenal hyperplasia (CAH) refers to group of inherited diseases resulting from impaired adrenal steroidogenesis, and its most common cause is 21-hydroxylase deficiency. Testicular adrenal rest tumors (TARTs) are an important complication of CAH, which probably develop from ectopic remnants of intra-testicular adrenal tissue stimulated by Adrenocorticotropic hormone (ACTH) hypersecretion. These lesions are typically located within the rete testis and are bilateral, synchronous, nodular and multiple. TART usually, but not always, responses to suppressive medical therapy. TART leads to testicular structural damage, spermatogenesis disorders, infertility and most importantly, mass-forming lesions that could be mistaken for Leydig cell tumor (LCT). The later has a significantly different behavior with up to 10% of being malignant. Nowadays, due to advances in diagnosing and treating CAH, mass-forming TART is rarely encountered. As a result, there is the paucity in the medical literature regarding its features from pathological perspective. We herein present a case of mass-forming TART and we discuss the clinical, radiological, and morphological features as well as the major differential diagnosis of this rare lesion.

Prognosis and reproducibility of new and existing binary grading systems for endometrial carcinoma compared to FIGO grading in hysterectomy specimens.

BACKGROUND: The current International Federation of Gynecology and Obstetrics (FIGO) grade in endometrial carcinomas requires the evaluation of histologic features with proven prognostic value but with questionable reproducibility. This study tests the prognostic power and reproducibility of a new binary grading system. STUDY DESIGN: Specimens from 254 hysterectomies were graded according to the new 3- and 2-tiered FIGO grading systems described by Alkushi et al. The selected morphologic parameters for the new grading system included the presence of predominant solid or papillary architecture pattern, severe nuclear atypia, tumor necrosis, and vascular invasion. The Cox proportional hazards and κ statistics were used for comparisons. RESULTS: On multivariate analysis, and looking at all tumor cell types, the 4 tested grading systems were independent predictors of survival, with the 3-tiered FIGO grading system being the most predictive (P = 0.005). In the subset of endometrioid tumors, the 3- and 2-tiered FIGO grading systems and the new grading system retained their statistical significance as predictors of survival (P = 0.004, P = 0.03, and P = 0.007, respectively), whereas the grading system of Alkushi et al did not (P = 0.1). In nonendometrioid tumors, the new grading system proved to be the best predictor of survival, reaching near statistical significance (P = 0.06). The new grading system had acceptable intraobserver and interobserver reproducibility assessment (κ = 0.87 and κ = 0.45, respectively). CONCLUSION: The 3-tiered FIGO grading system retained its superior prognostic power. However, available binary grading systems remain an attractive option by being highly reproducible and by eliminating the clinical ambiguity of intermediate grades of disease.

Molecular typing of epithelial ovarian carcinomas using inflammatory markers.

BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P = .0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P = .029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P = .005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy.

Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction.

OBJECTIVE: GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma. MATERIALS AND METHODS: Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined. RESULTS: There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p=0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p=0.01). CONCLUSION: Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction.

Prognostic analysis of ovarian cancer associated with endometriosis.

OBJECTIVE: The objective of the study was to evaluate the prognosis of ovarian cancer arising in endometriosis. STUDY DESIGN: We retrospectively compared 42 cases of endometriosis-associated ovarian cancer (EAOC) with 184 cases of ovarian carcinoma without endometriosis (OC). RESULTS: The median age in the EAOC group was 52 vs 59 years in OC (P < .05). In comparison with OC, the EAOC patients were more likely to have low-grade (21% vs 8%; P = .04) and early-stage tumors (International Federation of Gynecology and Obstetrics I and II combined) (49% vs 24%; P = .002). Clear cell (21% vs 2%) and endometrioid (14% vs 3%) tumors were more frequent in EAOC, whereas mucinous tumors were more prevalent in OC (P = .001). The median survival (199 vs 62 months) and the 5 year survival (62% vs 51%) were better for EAOC when compared with OC (P = .038). After controlling for age, stage, grade, and treatment, association with endometriosis was not an independent predictor of better survival in ovarian cancer. CONCLUSION: As such, EAOC has a much better survival rate than OC. This could be explained by the higher prevalence of early-stage and low-grade tumors in EAOC when compared with OC.

Analysis of the expression of human tumor antigens in ovarian cancer tissues.

Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.

Hyperammonemic encephalopathy: a rare presentation of fibrolamellar hepatocellular carcinoma.

Fibrolamellar carcinoma (FLC) is a rare malignant hepatocellular tumor of unknown etiology, arising almost exclusively from noninfected, noncirrhotic liver of young adults. FLC has traditionally been considered to have better survival than hepatocellular carcinoma; however, this notion might be highly erroneous. Patients with metastatic disease at presentation have a dismal prognosis with 5-year survival of only 15%. We describe a case of highly aggressive metastatic FLC that presented as hyperammonemic encephalopathy, which has never been previously reported in the literature.