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Objectives: To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis., Design: Randomized, controlled, single-blinded trial., Setting: A comprehensive multidisciplinary cancer hospital in Jordan., Patients: Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours., Interventions: Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels., Measurements and Main Results: Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively., Conclusions: In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant global health burden. Chemotherapy was the mainstay treatment for TNBC patients until immunotherapy was introduced. Studies indicate a noteworthy prevalence (0.2% to 18.6%) of mismatch repair protein (MMRP) deficiency in TNBC, with recent research highlighting the potential of immunotherapy for MMRP-deficient metastatic breast cancer. This study aims to identify MMRP deficiency in TNBC patients using immunohistochemistry., Methods: A retrospective cohort study design was used and included TNBC patients treated between 2015 and 2021 at King Hussein Cancer Center. Immunohistochemistry was conducted to assess MMRP expression., Results: Among 152 patients, 14 (9.2%) exhibited deficient MMR (dMMR). Loss of PMS2 expression was observed in 13 patients, 5 of whom showed loss of MLH1 expression. Loss of MSH6 and MSH2 expression was observed in one patient. The median follow-up duration was 44 (3-102) months. Despite the higher survival rate (80.8%, 5 years) of dMMR patients than of proficient MMR patients (62.3%), overall survival did not significantly differ between the two groups., Conclusion: Approximately 9% of TNBC patients exhibit dMMR. dMMR could be used to predict outcomes and identify patients with TNBC who may benefit from immunotherapy., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background and Objectives : Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16 INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16 INK4a , and evaluated its prognostic value and association with HPV status. Materials and Methods : The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16 INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16 INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results : HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16 INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16 INK4a expression. A statistically significant association was identified between p16 INK4a expression and the pathological stage ( p = 0.029) but not with other variables. No survival impact of p16 INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases ( p = 0.033). Conclusions : This is the first study to assess HPV and p16 INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Pathologists use certain terminologies to communicate uncertainty in pathology reports. The message conveyed in pathology reports may be interpreted differently by clinicians leading to possible miscommunication. We aimed to compare the interpretation and impact of uncertainty phrases between pathologists and clinicians. A survey with examples of uncertain diagnoses containing ("suspicious for", "indefinite for", "favor", "cannot exclude", "suggestive of", "compatible with", "cannot rule out", "highly suspicious for" and "consistent with") was sent to pathologists and clinicians. For each diagnosis, participants assigned a level of certainty from 1 to 10 and were asked whether they would recommend treatment based on such phraseology. Thirty-six responses (from 7 pathologists, 10 surgeons, 8 pediatric oncologists, 8 medical oncologists, 2 radiation oncologists and 1 diagnostic radiologist) were received. Pathologists had a narrower range of uncertainty compared to clinicians. Wide variation between both groups was seen for all phrases except "compatible with" and "highly suspicious for". 'Indefinite for' showed the lowest mean of certainty (4.67 for pathologists; 4.00 for clinicians) whereas 'consistent with' had the highest (8.83 for pathologists and 9.38 for clinicians). There was a significant difference in the degree of certainty between both groups for "compatible with" (7.83 for pathologists and 9.06 for clinicians, p  = .009). For treatment decisions, pathologists and clinicians agreed on initiating treatment when "consistent with" and "compatible with" were used and gave variable responses for the other terms. They proposed opposing treatment recommendations for "favor". Pathologists and clinicians varied in interpretation of uncertainty phrases which may impact treatment., (© 2024 The Authors.)

Background: Cancer patients are at higher risk of serious complications of COVID-19. Few studies evaluated the impact of COVID-19 on cancer patients in low- and middle-income countries. Our study aims to evaluate the outcomes of COVID-19 infection in cancer patients treated at our institution.  Methods: Medical records of patients with a positive COVID-19 polymerase chain reaction (PCR) between April 2020 and October 2020 were reviewed. Fisher's exact test and logistic regression analysis were employed to correlate various variables with mortality. Survival estimates were generated using the Kaplan-Meier method., Results: A total of 317 patients were included, with a median age was 55 years (range: 19-88). 82 (25.9%) had hematological neoplasms while the remainder had solid cancers. At the time of infection, 220 (69.4%) had active cancer, and 99 (31.2%) had received systemic anticancer treatment (SACT) within four weeks. Hospitalization was required for 101 (31.8%), 17 (5.3%) were admitted to the ICU and 50 (15.8%) died. Among patients with active cancer, SACT was delayed or discontinued in 140 (63.6%) patients.  In the entire patient cohort, low albumin (p=<0.001) and leucocytosis (p=<0.001) correlated with mortality within six months of COVID-19 infection. The six-month mortality rate in patients with active cancer was significantly higher in patients with hypertension (p=0.024), no recent SACT (0.017), hematological cancer (p=0.029), low albumin (p=<0.001), leucocytosis (p=0.002) and lymphocyte count of less than 500/µL (p=0.004). Recent chemotherapy was associated with better 6-month survival rates (78.8% vs 89.9%, p=0.012) in patients with active cancer, patients with solid cancers (95.9% vs 82.2%, p=0.006) and was non-inferior in patient with hematological neoplasms (72% vs 65.4%, p=0.519).  Conclusion: COVID-19 infection in our cancer patients was associated with significant morbidity and mortality and adversely affected their treatment. The decision to delay or discontinue SACT should be individualized, considering other risk factors for mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Al-rabi et al.)

Background and Objectives: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied., Patients and Methods: We compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens., Results: Sixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups., Conclusion: ETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population., Competing Interests: Disclosure The authors have stated that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mixed sex cord-stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord-stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli-Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord-stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli-Leydig cell component may influence the prognosis of such a tumor.

Background: Human epidermal growth factor receptor 2 (HER2), a promising therapeutic target, can be mutated, amplified, or overexpressed in different malignancies, including non-small cell lung cancer (NSCLC). Although these alterations showed adverse prognostic effects in many cancers, their clinical significance in NSCLC is controversial. This study primarily assessed the prevalence of HER2 protein expression in NSCLC among Jordanian patients. In addition, the possible association between HER2 protein expression and clinicopathological variables was evaluated., Methods: A total of 100 surgically resected NSCLC cases treated at King Hussein Cancer Center (KHCC) between 2009 and 2021 were examined for HER2 protein expression using immunohistochemistry (IHC). The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for breast cancer were applied to interpret the results with a final score ranging from 0 to 3+, considering a score of 3 + as overexpression. Additionally, a separate subset of patients was tested for HER2 gene mutation. Fisher's exact test was used to assess the association between HER2 scores and the other variables. Kaplan-Meier method was used to calculate survival., Results: Of the 100 cases, Her2 overexpression (score 3+) was detected in 2 cases (2%), score 2 + in 10 cases (10%), score 1 + in 12 cases (12%), and score 0 in 76 cases (76%). The two positive cases were one adenocarcinoma and one squamous cell carcinoma; both patients were elderly male smokers. No significant association was identified between Her2 expression and age, gender, smoking, histological subtype, grade, stage, tumor size, and lymph node status. Our findings also showed no association between Her2 expression and survival; however, advanced tumor stages and positive lymph node metastasis were significantly associated with poor overall survival. All cases tested for the Her2 mutation were negative., Conclusions: Her2 overexpression is uncommon in NSCLC among the Jordanian population. However, when the same scoring criteria are used, the rates are similar to other results found in Asian cohorts. Due to our study's relatively small sample size, a larger one is required to investigate the prognostic value and the molecular associations between the different Her2 alterations., (© 2023. The Author(s).)

Objectives: We aimed to study the outcomes, severity, and seroconversion post SARS-CoV-2 infection in immunocompromised children and adolescents treated at our center., Method: For this observational study, all pediatric patients who had COVID-19 infection from Sep-22-2020 to Nov-10-2021were identified by reviewing our laboratory records. Their charts were reviewed to determine clinical severity and outcome. Blood samples were drawn for anti-SARS-CoV-2 antibody assay. Serious COVID-19 infection (SVI) was defined if the patient had moderate, severe, or critical illness. A cutoff of 100 U/mL anti-SARS-CoV-2 antibodies was used to categorize low and high titer seroconversion., Results: We identified 263 pediatric patients with COVID-19; most (68%) were symptomatic: 5% had severe or critical infection, 25% were hospitalized, 12 required respiratory support, 12 were admitted to the ICU, and five patients (2%) died. Multivariable analysis revealed several factors that predict SVI: Age above 12 years (p=0.035), body mass index above 95 th percentile (p=0.034), comorbid conditions (p=0.025), absolute neutrophil count ≤500(p=0.014) and absolute lymphocyte count ≤300 (p=0.022). Levels of anti-SARS-CoV-2 spike antibodies were obtained for 173 patients at a median of 94 days (range, 14-300) after PCR diagnosis; of them 142 (82%) patients seroconverted; the lowest seroconversion rate was observed in patients with hematological malignancies (79%). Our univariable model showed that the following factors were predictive of low titer: lower ANC, p=0.01; hematologic malignancy, p=0.023; receiving steroids in the last 14 days, p=0.032; time since last chemotherapy or immunosuppressive therapy less than 30 days, p=0.002; and being on active chemotherapy in the last 3 months prior to infection, p<0.001., Conclusions: SARS-CoV-2 antibodies developed in most immunocompromised patients with COVID-19 infection in our study. Mortality was relatively low in our patients. Our univariable and multivariable models showed multiple variables that predict severity of infections and antibody response post COVID-19 infection. These observations may guide choice of active therapy during infection and the best timing of vaccination in this high-risk population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abu Shanap, Sughayer, Alsmadi, Elzayat, Al-Nuirat, Tbakhi and Sultan.)

Background and Objectives: Little is known about the efficacy and durability of anti-RBD IgG antibodies induced by certain SARS-CoV-2 vaccines. It has been shown that neutralizing antibodies are associated with the protection against re-infection. This study aims to compare the mean titers, duration, and efficacy of generating protective anti-RBD IgG antibody response among recipients of Pfizer/BioNTech, AstraZeneca, Sputnik V, Johnson & Johnson, Moderna, and Sinopharm COVID-19 vaccines. In addition, we aimed to compare the susceptibility of getting COVID-19 breakthrough infections after various types of vaccines., Materials and Methods: Samples from 2065 blood bank donors and healthcare workers at King Hussein Cancer Center (KHCC) were collected between February and September 2021. Anti-Spike/RBD IgG levels were measured using Chemiluminescent microparticle-immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA)., Results: The mean titer of anti-RBD IgG levels was significantly diverse among different types of vaccines. The highest titer level was seen in participants who took a third booster vaccine shot, followed by Pfizer/BioNTech, AstraZeneca, and Sinopharm vaccine. The mean titer levels of anti-RBD IgG antibodies in the Pfizer vaccinated group was the highest after vaccination but started to drop after 60 days from vaccination unlike AstraZeneca and Sinopharm vaccine-induced antibodies where the mean titers continued to be stable until 120 days but their levels were significantly lower. Most of the breakthrough infections were among the Sinopharm vaccinated group and these breakthroughs happened at random times for the three main types of vaccines., Conclusions: Our data demonstrate that the mean-titer of anti-RBD IgG levels drop after four months which is the best time to take the additional booster shot from a more potent vaccine type such as mRNA vaccines that might be needed in Jordan and worldwide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients., Methods: Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020., Results: One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALL > T-ALL, p < 0.001) and with age group (adults > children, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL., Conclusions: The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.

Objective/background: Lymphoma is a common human cancer that shows a variable geographic incidence worldwide. It is the fourth most common cancer in Jordan. Systemic reports of descriptive epidemiology on lymphoma from the Middle East are limited., Methods: A nationwide multi-institutional retrospective study was conducted covering all major hospitals and laboratories that provide diagnostic services. We collected data on all cases diagnosed with lymphoma between 2014 and 2019. The included variables were patients' age, gender, anatomic site, and the histologic type according to the World Health Organization classification system., Results: A total of 4189 cases were diagnosed with lymphoma. There was a statistically significant gender difference (p < .05), as 57.5% of patients were males. The peak incidence occurred at age 25-55 years. There were 1,652 (39%) cases of Hodgkin lymphoma (HL) and 2,537 (61%) of non-Hodgkin lymphoma (NHL), where nodular sclerosis (67%) and diffuse large B-cell lymphoma (53%) were the most common subtypes, respectively. The average age-adjusted incidence rates per 100,000 population were 8.01 for all lymphomas, 4.33 for NHL, and 3.16 for HL and all remained stable over the 6 years., Conclusion: HL is the most common lymphoma in Jordan, with a percentage higher than most of reported studies in Asian and Western countries. It also shows a unimodal distribution of age-specific incidence rates, with a single peak in young adults. The incidence rate of HL is higher than Eastern countries but comparable to the West. In contrast, NHL demonstrates a lower incidence rate than Western countries but a similar distribution of subtypes, as mature T/natural killer-cell lymphomas were rare., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Purpose: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression., Methods: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity., Results: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001)., Conclusions: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.

Background: Viral cause of sporadic breast cancer (SBC) has been suggested based on the experimental murine model of mammary tumor caused by mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and human papillomavirus (HPV). While some studies have demonstrated the presence of viral sequences of MMTV, HPV, and EBV in breast cancer cells, others failed. These contradictions may be attributed to the geographical distribution of breast cancer incidence and/or technical variations. In the current study, we aimed to investigate the correlation of MMTV, HPV, and EBV infections with the development of breast cancer in Jordanian patients., Methods: One hundred SBC tissue samples were subjected to laser capture microdissection for the selection of tumor cells populations. Fluorescence polymerase chain reaction (PCR) was used to detect the presence of the MMTV env-like sequences. Real-time PCR was used for HPV and EBV detection, and EBV was further confirmed by chromogen in situ hybridization (CISH)., Results: Mouse mammary tumor virus, HPV, and EBV were detected in SBC in 11%, 21%, and 23%, respectively. Only 3 of 52 (5.7%) positive cases demonstrated multiple virus infections. However, 49 of 52 (94%) of the positive cases revealed the presence of 1 type of viral sequences. Consequently, 52% of the studied breast cancer cases were infected with at least 1 type of the aforementioned viruses., Conclusions: The current cohort suggests that MMTV, HPV, and EBV have a potential role in the development of breast cancer and adding more reasons to proceed with the quest of a possible viral origin of breast cancer., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

The role of Ki-67 index in determining the prognosis and management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has become more important yet presents a challenging assessment dilemma. Although the precise method of Ki-67 index evaluation has not been standardized, several methods have been proposed, and each has its pros and cons. Our study proposes an imaging semiautomated informatics framework [semiautomated counting (SAC)] using the popular biomedical imaging tool "ImageJ" to quantify Ki-67 index of the GEP-NETs using camera-captured images of tumor hotspots. It aims to assist pathologists in achieving an accurate and rapid interpretation of Ki-67 index and better reproducibility of the results with minimal human interaction and calibration. Twenty cases of resected GEP-NETs with Ki-67 staining that had been done for diagnostic purposes have been randomly selected from the pathology archive. All of these cases were reviewed in a multidisciplinary cancer center between 2012 and 2019. For each case, the Ki-67 immunostained slide was evaluated and five camera-captured images at 40 × magnification were taken. Prints of images were used by three pathologists to manually count the tumor cells. The digital versions of the images were used for the semiautomated cell counting using ImageJ. Statistical analysis of the Ki-67 index correlation between the proposed method and the MC revealed strong agreement on all the cases evaluates ( n = 20 ), with an intraclass correlation coefficient of 0.993, "95% CI: 0.984 to 0.997." The results obtained from the SAC are promising and demonstrate the capability of this methodology for the development of reproducible and accurate semiautomated quantitative pathological assessments. ImageJ features are investigated carefully and accurately fine-tuned to obtain the optimal sequence of steps that will accurately calculate Ki-67 index. SAC is able to accurately grade all the cases evaluated perfectly mating histopathologists' manual grading, providing reliable and efficient solution for Ki-67 index assessment., (© 2019 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma (CHL) are the most common large cell lymphomas arising in the mediastinum and are thought to be closely related histogenetically. Although the distinction between PMBL and CHL is usually straightforward, in some cases it is challenging and rarely these neoplasms have intermediate features and qualify for the diagnosis of mediastinal gray zone lymphoma (GZL). CD83 and fascin are markers of CHL and CD23 is a marker of PMBL. In this study we assess the utility of this combination of these immunohistochemical markers to distinguish CHL from PMBL. We retrospectively collected cases of PMBL, CHL and GZL from three centers. Tissue sections were stained with CD83, fascin and CD23. CD83 was expressed in the neoplastic cells of 100% of CHL (22/22), 93% of GZL (16/18) and 41% of PMBL (9/22). Similarly, fascin was positive in the neoplastic cells of 100% of CHL (22/22), 86% of GZL (18/21) and 32% of PMBL (7/22). CD23 was positive in 95% of PMBL (21/22), 67% of GZL (12/18) and 9% of CHL (2/22). CD83 and fascin are sensitive markers for CHL but not specific whereas CD23 is sensitive for PMBL and uncommon in CHL. The GZL cases in this study had an intermediate immunophenotype, but the results were closer to CHL than PMBL. A large panel of immunohistochemical studies is recommended to distinguish CHL from PMBL entities and we suggest that CD83, fascin and CD23 add value to panels designed for this differential diagnosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fine-needle aspiration (FNA) plays a fundamental role in determining the appropriate management for patients presenting with thyroid nodules., Aims: The aims of this study are to evaluate thyroid FNA test performance parameters through a cytohistological correlation., Materials and Methods: A retrospective analysis of all thyroid FNAs received over a period of 18 months was carried out. The findings were compared to their subsequent definite diagnoses on surgical specimens as well as to their follow-up repeat FNA results. A total of 499 thyroid FNAs were collected and reviewed against The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The percentage of each diagnostic category was calculated, and the implied risk of malignancy was determined by comparing the cytology results to their definite diagnoses obtained on the resection specimens. Analytical procedures were performed using Microsoft Excel., Results: Out of 499 thyroid FNAs, a benign interpretation was found in 273 patients (54.7%), atypia of undetermined significance in 81 (16.2%), follicular neoplasm in 20 (4%), suspicious for malignancy in 36 (7.2%), malignant in 32 (6.4%) and were nondiagnostic in 57 patients (11.4%). Only 101 patients (20.2%) underwent surgical resection and 47 (9.4%) underwent a follow-up FNA. After cytohistological correlation, FNA test performance, calculated by excluding the inadequate and undetermined categories revealed test sensitivity, specificity, and diagnostic accuracy of 95.6%, 54.8%, and 78.9%, respectively. The positive predictive value was 75.4%, and the negative predictive value was 89.5%., Conclusions: Our results are comparable to those previously published figures. The rate of atypia of undetermined significance/follicular lesion of undetermined significance is higher than what is currently recommended in TBSRTC.

Background: Breast cancer is one of the most prevalent cancers in women. Oncotype Dx is a multi-gene assay frequently used to predict the recurrence risk for estrogen receptor-positive early breast cancer, with values < 18 considered low risk; ≥ 18 and ≤ 30, intermediate risk; and > 30, high risk. Patients at a high risk for recurrence are more likely to benefit from chemotherapy treatment., Methods: In this study, clinicopathological parameters for 37 cases of early breast cancer with available Oncotype Dx results were used to estimate the recurrence score using the three new Magee equations. Correlation studies with Oncotype Dx results were performed. Applying the same cutoff points as Oncotype Dx, patients were categorized into low-, intermediate- and high-risk groups according to their estimated recurrence scores., Results: Pearson correlation coefficient (R) values between estimated and actual recurrence score were 0.73, 0.66, and 0.70 for Magee equations 1, 2 and 3, respectively. The concordance values between actual and estimated recurrence scores were 57.6%, 52.9%, and 57.6% for Magee equations 1, 2 and 3, respectively. Using standard pathologic measures and immunohistochemistry scores in these three linear Magee equations, most low and high recurrence risk cases can be predicted with a strong positive correlation coefficient, high concordance and negligible two-step discordance., Conclusions: Magee equations are user-friendly and can be used to predict the recurrence score in early breast cancer cases.

Background: The early introduction of complementary foods is common in Middle Eastern countries but little is known about the determinants of this practice in this region., Objectives: This prospective cohort study conducted from October 2007 to October 2008 investigated the determinants of the very early (before 17 weeks) introduction of complementary foods in Kuwait and compared rates of this practice against rates reported in the mid-1990s., Methods: A total of 373 women were recruited from maternity hospitals in Kuwait City and followed to 26 weeks postpartum. Data on complementary feeding practices were available from 303 women. Multivariate logistic regression was used to estimate the association of very early introduction of complementary foods with infant sex and maternal characteristics including age, years of education, employment intentions at 6 months postpartum, parity, prepregnancy body mass index, and prepregnancy smoking status., Results: All infants had received complementary foods by 26 weeks of age, with 30.4% receiving complementary foods before 17 weeks of age. Women born in other Arabic countries were less likely to introduce complementary foods before 17 weeks (adjusted odds ratio [adj OR] = 0.40; 95% confidence interval [CI], 0.22-0.73) than women born in Kuwait. Women who were exclusively formula feeding at 6 weeks postpartum were less likely to introduce complementary foods before 17 weeks (adj OR = 0.40; 95% CI, 0.23-0.71) than women who were still breastfeeding., Conclusion: Compared to the mid-1990s, fewer infants in Kuwait were receiving complementary foods before 17 weeks. Nevertheless, all infants had received complementary foods by 6 months of age., (© The Author(s) 2015.)

Individuals with biallelic truncating PRF1 mutations typically present with fulminant early-onset familial hemophagocytic lymphohistiocytosis (FHL). We report a 19-year-old male with a 5-year history of recurrent fever and headaches progressing to refractory seizures. Brain imaging revealed multiple ring enhancing lesions. Laboratory investigations demonstrated that the patient displayed defective lymphocyte cytotoxicity and carried a homozygous missense PRF1 mutation, c.394G > A (p.Gly132Arg). The patient was successfully treated with chemo-immunotherapy followed by matched related allogeneic hematopoietic stem cell transplantation (HSCT). Our findings demonstrate that prompt HSCT of late-onset FHL with primarily neurological manifestation can reverse central nervous system symptoms and improve long-term outcome., (© 2014 Wiley Periodicals, Inc.)

Synovial sarcoma is a rare type of sarcoma with poor prognosis. Data on relevant prognostic factors are inconsistent. The objective of this study was to determine the independent prognostic factors that govern local recurrence, distant metastasis and overall survival. A retrospective analysis of 51 patients treated for localized synovial sarcoma at a single institution by a multidisciplinary/multimodality approach over a period of 12 years. Patients, tumor and treatment characteristics were collected including age, sex, tumor site, location, depth, size, status of margins, histology subtype and involvement of bone or lymph nodes. Type of surgery, adjuvant chemotherapy and radiotherapy were also examined. The endpoints analyzed were local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Median age of patients was 26 years (range 3-64 years) with 73 % above the age of 20 year. All patients received surgery, 57 % received adjuvant radiotherapy and 45 % adjuvant chemotherapy. The median survival was 111 months, and 5-year OS was 73 %. Deep seatedness of the tumor was linked to OS as the only independent risk factor. Twelve patients had local recurrence, and the 5-year LRFS was 61 %. Multivariate analysis determined negative margins and adjuvant radiotherapy as independent predicting factors for LRFS. Five-year MFS was 48 %; multivariate analysis identified monophasic subtype and site other than lower extremity as the only independent factors associated with inferior MFS. The most important factors that govern LRFS and MFS are negative margins and adjuvant radiotherapy for LRFS and tumor histology and site for MFS, while deep seatedness of the tumor is the sole independent factor that governs OS.

The purposes of this paper are to report the prevalence of breastfeeding to six months among women in Kuwait and to determine the factors that are associated with the duration of breastfeeding. A cohort of 373 women recruited from maternity wards in four hospitals in Kuwait city were followed from birth to 26 weeks postpartum. The association of any and full breastfeeding duration and predictor variables were explored using multivariate Cox's proportional hazards models. At six months, 39% of all infants were receiving some breast milk and only 2% of infants had been fully breastfed to 26 weeks. Women born in other Arab countries were less likely to discontinue breastfeeding than women born in Kuwait. Other factors positively associated with breastfeeding duration were level of maternal education, higher parity, infant being demand fed in hospital and a preference for breastfeeding on the part of the infant's father and maternal grandmother. The introduction of a pacifier before four weeks of age and the mother intending to return to work by six months were negatively associated with duration. These findings present a number of opportunities for prolonging breastfeeding duration in Kuwait.

Bilateral breast cancer occurs in approximately 7% of surviving breast cancer patients. However, a dilemma exists concerning the notion of whether this represents a de novo second primary tumor versus a breast metastasis. We analyzed 81 patients with bilateral breast cancer, 47 (58%) synchronous tumors and 34 (42%) metachronous tumors. Additionally, charts were reviewed for age, family history, full histology data and biological receptors. We found there were no significant differences in concordance between the first and second primary tumors (in both synchronous and metachronous bilateral breast cancer) with respect to histology; grade; T-category; N-category; ER, PR and HER-2 status. In addition, there was no significant difference in the strength of correlation between ER and PR in the first and secondary primary tumors. Our findings suggest that the differentiation of the origin of contralateral breast cancer based on routine histological and biological concordance is inconclusive. Furthermore, the dilemma will continue to exist until additional molecular approaches are applied routinely for research purposes to resolve the debate.

Summary: The Memorial Sloan Kettering Cancer Center (MSKCC) breast nomogram has been validated in different populations. In this study, the nomogram was validated for the first time in a Middle East population sample. Although our sample was found to have significant differences from the dataset from which the model was derived, the nomogram proved to be accurate in predicting non sentinel axillary lymph node metastasis. An attempt to use the proportions of involved sentinel lymph nodes instead of absolute numbers of positive and negative sentinel lymph nodes, yet using the same online calculator to predict the probability of non sentinel axillary lymph node metastasis, improved the accuracy, specificity, negative predictive value, and false negative rate., Background: Axillary clearance is the standard of care in patients with invasive breast cancer and positive sentinel lymph node biopsy. However, in 40-60% of patients, the sentinel lymph nodes are the only involved lymph nodes in the axilla. The Memorial Sloan Kettering Cancer Center (MSKCC) breast nomogram serves to identify a subgroup of patients with low risk of non sentinel lymph node (NSLN) metastasis, in whom axillary lymph node dissection (ALND) could be spared, and thereby, preventing the unwarranted associated morbidity., Methods: The MSKCC nomogram was applied on 91 patients who met the criteria. A modified predictive model was developed by substituting proportions of positive and negative SLN for their absolute numbers. The accuracy was assessed by calculating the area under the receiver-operator characteristic (ROC) curve., Results: The MSKCC nomogram achieved an area under the ROC curve of 0.76. The area under the curve for the modified predictive model was 0.81. The specificity, negative predictive value, and false negative were 30%, 71%, 20% (MSKCC model) and 55%, 84%, 17% (modified model) at 20% predicted probability cut-off values., Conclusion: Although differences existed in characteristics of our breast cancer population, and in the methods of sentinel lymph node metastasis detection, the MSKCC model proved to be accurate. An attempt to replace the number of positive and negative SLNs with proportions in the MSKCC model raised the accuracy but did not achieve statistical significance (p = 0.09)., Keywords: Breast cancer, Sentinel lymph node, Non sentinel lymph node, Axillary clearance, Predictive model.

Background: There is scarcity of reports addressing patients with three or more malignancies. The aim of this study is to present a detailed analysis of patients presenting with at least three primary malignant tumors., Patients and Methods: Records of cancer patients presenting to King Hussein Cancer Center (Amman, Jordan) between June 2006 and March 2011 were retrospectively reviewed. Patients harboring multiple primary tumors were included for detailed analysis. Data relating to epidemiological features, pathological characteristics, and disease outcomes were extracted., Results: Out of 14,040 cases, 319 patients (2.3%) harbored two or more while 23 patients (0.16%) harbored three or more primary malignant tumors. This study included 17 males and six females between 4 and 78 years of age (median, 52 years) at the time of diagnosis of the first malignancy. The most prevalent tumor was colorectal adenocarcinoma found in nine, followed by lymphoma in seven, and prostate adenocarcinoma in six patients. The most common tumor combinations were colorectum-non-melanoma skin, colorectum-kidney, and non-melanoma skin-kidney all found in four patients, respectively. At a median follow-up of 96 months from the time of diagnosis of the first primary (range, 2-337 months) and 8 months from the time of diagnosis of the last primary (range, 1-48 months), 13 were alive with no evidence of disease, six were alive with residual disease, three were dead due to disease, and one patient was alive with unknown disease status., Conclusions: The possibility of multiple primary malignancies should always be considered during the treatment and follow-up of cancer patients. This case series could prove helpful to clinicians faced with similar, however, exceedingly rare scenarios. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

Background: Phyllodes tumors are classified as benign, borderline, and malignant according to a group of histological features. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The immunohistochemical expression of CD10 has been shown to discriminate between benign and other grades of phyllodes tumor but has not been evaluated as a predictor of metastasis. The purpose of this study was to evaluate the usefulness of immunohistochemical staining of stromal CD10 in predicting the likelihood of metastasis in phyllodes tumors., Methods: The expression of CD10 was studied in 43 phyllodes tumors (16 benign, 10 borderline, and 17 malignant) using immunohistochemistry to evaluate whether differences in expression correlated with the presence of, and or, development of distant metastasis., Results: Metastasis occurred in six malignant phyllodes tumors. The expression of CD10 significantly (P<0.05) correlated with the occurrence of distant metastasis., Conclusions: The expression of CD10 can be used to predict the occurrence of distant metastasis in phyllodes tumors of the breast.