ABSTRACT
INTRODUCTION: Breast cancer poses a significant health challenge in Sub-Saharan Africa, particularly in Ghana, where late-stage diagnoses and limited healthcare access contribute to elevated mortality rates. This study focuses on the crucial role of pathology and laboratory medical (PALM) services in the timely diagnosis of breast cancer within Ghana. METHODS: A cross-sectional survey of hospitals was completed from November 2020 to October 2021, with 94.8% of identified in-country hospitals participating. Pathology service-related parameters assessed included whether pathology was available for the diagnosis of breast cancer on-site or via external referral, the number of pathology personnel, additional breast cancer diagnostic capabilities including estrogen and progesterone and/or HER2 testing, and the time from biopsy to patients receiving their results. Geospatial mapping was used to identify areas of limited access. RESULTS: Of the 328 participating hospitals, 136 (41%) reported breast cancer pathology services, with only 6 having on-site capabilities. Pathology personnel, comprising 15 consultants and 15 specialists, were concentrated in major referral centers, particularly in Greater Accra and Kumasi. An assessment of referral patterns suggested that 75% of the population reside within an hour of breast cancer pathology services. Among the 136 hospitals with access to breast cancer pathology, only a limited number reported that results included ER/PR (38%) and HER2 testing (33%). CONCLUSION: Ghana has been able to ensure significant pathology service availability through robust referral pathways with centralized labs. Despite this, difficulties persist with the majority of pathology results not including hormone receptor testing which is important in providing tumor specific treatment.
Subject(s)
Breast Neoplasms , Health Services Accessibility , Humans , Ghana/epidemiology , Breast Neoplasms/pathology , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnosis , Female , Health Services Accessibility/statistics & numerical data , Cross-Sectional Studies , Referral and Consultation/statistics & numerical dataABSTRACT
EGFR amplification in gliomas is commonly defined by an EGFR/CEP7 ratio of ≥2. In testing performed at a major reference laboratory, a small subset of patients had ≥5 copies of both EGFR and CEP7 yet were not amplified by the EGFR/CEP7 ratio and were designated high polysomy cases. To determine whether these tumors are more closely related to traditionally defined EGFR-amplified or nonamplified gliomas, a retrospective search identified 22 out of 1143 (1.9%) gliomas with an average of ≥5 copies/cell of EGFR and CEP7 with an EGFR/CEP7 ratio of <2 displaying high polysomy. Of these cases, 4 had insufficient clinicopathologic data to include in additional analysis, 15 were glioblastomas, 2 were IDH-mutant astrocytomas, and 1 was a high-grade glial neoplasm, NOS. Next-generation sequencing available on 3 cases demonstrated one with a TERT promoter mutation, TP53 mutations in all cases, and no EGFR mutations or amplifications, which most closely matched the nonamplified cases. The median overall survival times were 42.86, 66.07, and 41.14 weeks for amplified, highly polysomic, and nonamplified, respectively, and were not significantly different (p = 0.3410). High chromosome 7 polysomic gliomas are rare but our data suggest that they may be biologically similar to nonamplified gliomas.
Subject(s)
Brain Neoplasms , Gene Amplification , Glioblastoma , Glioma , Humans , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Chromosome Aberrations , ErbB Receptors/genetics , Glioblastoma/genetics , Glioblastoma/pathology , Glioma/genetics , Glioma/pathology , In Situ Hybridization, Fluorescence , Isocitrate Dehydrogenase/genetics , Mutation/genetics , Retrospective Studies , Chromosomes, Human, Pair 7/geneticsABSTRACT
Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. SIGNIFICANCE: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.
Subject(s)
Brain Edema , Brain Neoplasms , Glioma , Adult , Humans , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Edema/genetics , Brain Edema/diagnosis , Brain Edema/pathology , Glioma/pathology , Edema , Mutation , Tumor MicroenvironmentABSTRACT
The new ASCO/CAP guidelines on hormone receptor testing in breast cancer recommends standard operating procedures (SOPs) established to confirm or adjudicate estrogen receptor (ER) results with weak or ≤10% staining, and the status of internal controls (ICs) reported for cases with 0% to 10% staining. The aim of this study is to determine the frequency of ER testing with weak or ≤10% staining that may require additional steps following SOPs and to identify any correlation between hormone receptor status of the tumor and the likelihood of finding IC. Breast cancer cases between January 2014 and April 2019 were included to identify negative, low-positive and weak-positive cases. The presence/absence of IC was correlated to tumor type. Following ASCO/CAP guidelines, 29.8% of cases (374/1261) will need additional steps to confirm/adjudicate results due to negative, low, or weak positive ER status. The probability of finding IC is ~50% lower in cases of ER and progesterone receptor (PgR) negative tumors. Repeat testing may be warranted in 13.1% (92/700) of all cases due to lack of IC. In conclusion, the new ASCO/CAP guidelines recommend laboratories to establish and follow SOP to confirm or adjudicate ER results for about 30% of the cases before reporting hormone receptors status. Over 40% of cases with <10% tumor ER positivity lacked IC that may need a comment per the guidelines indicating a repeat testing may be warranted. However, the presence/absence of IC may be related to the subtype of breast cancer and should not necessarily bring into question the validity of the test.
Subject(s)
Breast Neoplasms , Neoplasm Proteins/biosynthesis , Receptors, Cell Surface/biosynthesis , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Laboratories , Practice Guidelines as TopicABSTRACT
Primary esophageal angiosarcoma is an extremely rare cancer. Thus, evidence-based guidance on diagnosis and treatment is lacking. The current workup and management is extrapolated from other esophageal and angiosarcoma pathology. We describe a case report that depicts unique diagnostic and therapeutic challenges.
Subject(s)
Esophageal Neoplasms/diagnosis , Hemangiosarcoma/diagnosis , Biopsy , Combined Modality Therapy/methods , Endoscopy, Gastrointestinal/methods , Endosonography , Esophageal Neoplasms/therapy , Female , Hemangiosarcoma/therapy , Humans , Middle AgedABSTRACT
BACKGROUND: Researchers are debating if fecal calprotectin results are useful for infant patients, especially in screening for necrotizing enterocolitis (NEC). Currently, none of the FDA-approved calprotectin assays provide a cut-off for infant patients. We retrospectively analyzed data from a reference laboratory and university hospital to investigate if a cut-off could be established for infant patients. METHODS: Data from a national reference laboratory of 5144 test results for fecal calprotectin were analyzed for infant patients, and a cut-off was estimated based on the distribution of results. Additionally, a literature proposed cut-off of 226 µg/g was also considered. Validation of either cut-off was attempted by review of the electronic medical record of our university hospital for 110 infant patients with results for fecal calprotectin. RESULTS: Infants had a high percentage of elevated fecal calprotectin results when using the adult cut-offs set by the manufacturer. A cut-off of 247 µg/g was estimated based on the reference laboratory results for infants 0-2 months old, which is similar to a literature proposed cut-off of 226 µg/g. However, the positive predictive value (PPV) for both cut-offs was <0.6 when retrospectively analyzing data from a university hospital. CONCLUSION: Due to the low PPVs, the two infant-specific cut-offs for fecal calprotectin would not be useful to screen for NEC in infants at our university hospital.