The VEGF-Hypoxia Signature is Upregulated in Basal like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer.

PURPOSE: Black women experience the highest breast cancer mortality rate compared to women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. EXPERIMENTAL DESIGN: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n=182) and the University of Chicago (n=161). We also analyzed RNA sequencing data from Nigeria (n=84) and TCGA datasets (n=863). Patient prognosis was analyzed using multiple datasets. RESULTS: The VEGF-hypoxia signature was highest in the basal-like subtype compared to other subtypes, with greater expression in Black women compared to White women. In the TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared to non-necrosis tumors (p<0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation and necrosis. T cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in the TCGA dataset. Lastly, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (p<0.0001) and SCAN-B datasets (p=0.002). CONCLUSIONS: These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora.

Diffuse Large B-cell Lymphoma Mimicking Pancreatic Carcinoma and the Use of Immunohistochemistry in Resolving the Diagnostic Dilemma After Postmortem Examination: A Case Report.

Diffuse large B-cell lymphoma is the most common lymphoma, accounting for 30% of all non-Hodgkin lymphomas; they can grow rapidly and often present as masses infiltrating tissues or obstructing organs. We report the case of a 58-year-old female who presented with a one-month history of generalized body weakness and weight loss with a two-week history of yellowness of the eyes, fever, dyspnea, and bilateral leg swelling. Examination at presentation revealed pallor, fever, jaundice, hepatomegaly, and bilateral pitting pedal edema. Laboratory investigations revealed severe anemia, deranged clotting profile, azotemia, elevated liver enzymes, and elevated tumor markers CA125, CEA, and CA 19.9. Abdominal ultrasound showed hepatomegaly and a large head of the pancreas. The initial diagnosis was obstructive jaundice due to carcinoma of the head of the pancreas. Despite all care offered, her clinical condition deteriorated until she died on the 12th day of admission. A postmortem examination showed a mass in the head of the pancreas and bile duct, enlarged para-aortic and mesenteric lymph nodes with ascites, pericardial nodules, and bronchopneumonia. Histological and immunohistochemical analysis of postmortem biopsies confirmed the diagnosis of a diffuse large B cell lymphoma.  This case highlights the diagnostic dilemma often seen in disseminated diffuse large B-cell lymphoma. The patient presented with features referable to different organs and systems. If detected early, most cases respond to standard immuno-chemotherapy. However, it can also become rapidly fatal and ultimately lead to death, as seen in this case.

Programme death ligand 1 expressions as a surrogate for determining immunotherapy in cervical carcinoma patients.

BACKGROUND: The programme death ligand1 and its receptor (PD-1/PD-L1) interaction is a target for blockage by immunotherapy that uses the body's own immune system. Some studies show that PD-L1 expressing tumours are also more aggressive with poor prognosis. This study evaluated the immunohistochemical expression of PD-L1 in uterine cervical carcinomas. Women with cervical cancer would benefit from its use as a marker in therapy and prognosis. METHODS: Hospital-based cross-sectional retrospective study was conducted. The study materials included 183 archived formalin fixed and paraffin embedded (FFPE) tissue blocks with histological diagnosis of cervical carcinoma diagnosed in our facility within a five-year period (January 2012 and December 2016) that met the study criteria. Data were extracted from records in the Department and immunohistochemistry was done using polyclonal antibodies to PD-L1 (GTX104763, Genetex). Obtained data were analysed using SPSS version 23. P < 0.05 was considered significant. RESULTS: A hundred and eighty-three cases of cervical cancer were studied. PD-L1 was positive in 57.4% of all cases. The diffuse pattern of staining was the major pattern accounting for 88.5% of positive cases. Poorly differentiated cervical carcinomas are less likely to express PD-L1. Within the histologic types, the squamous cell carcinomas expressed PD-L1 in 58.7%, and 50% of adenocarcinomas were positive. PD-L1 was not expressed in all cases of adenoid cystic carcinomas and basaloid squamous cell carcinomas. CONCLUSION: A significant population of cervical carcinoma expresses PD-L1 by immunohistochemistry. PD-L1 prevalence is lower amongst the poorly differentiated cancers compared to other grades.

Histomorphological assessment of non-neoplastic renal diseases at autopsy: an institutional experience in Southwestern Nigeria.

Background: Autopsy remains an invaluable resource for medical education and establishing diagnosis of diseases that were missed prior to death. Many patients on admission in hospitals suffer kidney diseases that may contribute to their morbidity and/or mortality. The kidneys from autopsies provide opportunity to diagnose and understand some of these non-neoplastic renal lesions. This study aimed to present the frequency of non-neoplastic renal diseases at autopsy. Methods: We conducted a five-year retrospective review of post-mortem records of deceased who had autopsy. Data such as age, sex, cause of death, and kidney lesions were extracted from the post-mortem records and clinical details were gotten from the clinical summaries in the autopsy reports. The kidneys were examined for pathological findings that were then classified into glomerular, tubulointerstitial (tubulointerstitial nephritis and other tubular lesions such as tubular necrosis, casts and fibrosis) and vascular lesions. Results: A total of seventy (70) cases met the inclusion criteria with 91.4% having significant non-neoplastic renal lesions. The mean age of the deceased was 57.7years (18years - 91years). Males accounted for 65.7% of the cases. Glomerular lesions were seen in 84.3% of the cases, tubulointerstitial nephritis in 41.6% of cases, vascular lesions were seen in 30% of the cases and other tubular lesions (such as stones, casts and tubular necrosis) were seen in 52.9% of the cases. Cardiovascular diseases and infections were the major causes of death in these patients, accounting for 40% and 27% respectively. Renal diseases were attributed to immediate cause of death in 10% of the cases. Conclusion: The kidney at autopsy provides a valuable renal pathology educational tool, as a wide range of medical renal lesions can be seen from kidneys examined at post mortem.

P57kip2 immunohistochemical marker as a diagnostic tool for cases of hydatidiform moles in a tertiary health facility in Southwestern Nigeria.

BACKGROUND: Hydatidiform mole (HM) is the most common gestational trophoblastic disease. P57kip2 has been reported to be helpful in differentiating between partial and complete HMs. OBJECTIVES: The study aims to evaluate the P57kip2 immunohistochemical (IHC) marker as a useful ancillary investigation to differentiate complete hydatidiform mole (CHM) from partial hydatidiform mole (PHM). MATERIALS AND METHODS: A retrospective study of all histologically diagnosed HM cases over a 20 year period was undertaken. Clinicopathological parameters were extracted from the surgical day book and medical record archives. Archival haematoxylin- and eosin-stained slides and formalin-fixed paraffin-embedded tissue blocks of all cases of HM diagnosed within the study period were retrieved and reviewed. Cases of HM were reclassified using the P57kip2 IHC marker. The data obtained were analysed using the SPSS version 23. RESULTS: One hundred cases of HMs were studied. CHM accounted for 68%, while PHM accounted for the remaining 32%. The incidence of HM was 2.98 cases per 1000 deliveries. The ratio of CHM to PHM was found to be 2.1:1. Seventy-two per cent of the cases were diagnosed in the first trimester, while the remaining 28% were diagnosed in the second trimester of pregnancy. Based on the P57kip2 IHC staining pattern, HM cases were finally reclassified into 68 cases of CHM and 32 cases of PHM. The age range for all the HM cases was 18-50 years with the majority of the cases seen in the third and fourth decades of life. CONCLUSION: P57kip2 could be useful as an ancillary investigation in confirming the diagnosis of CHM and differentiating it from PHM, particularly in difficult and challenging cases.

Mortality patterns in patients with diabetes mellitus at a Nigerian tertiary hospital: A 10-Year autopsy study.

OBJECTIVES: Diabetes mellitus (DM) is a global health problem with associated high morbidity and mortality. This study was a retrospective review of post-mortem examination findings of hospitalised patients with DM for causes of death. MATERIALS AND METHODS: A retrospective, cross-sectional autopsy review of all the patients with DM in our hospital between January 2008 and December 2017 was conducted. The causes of death were classified into cardiovascular, cerebrovascular, acute diabetic emergencies, infection, cancers and unnatural deaths. The demographic data and clinicopathological parameters were extracted, and the data were analysed using the SPSS software version 23. RESULTS: A total of 1092 cases of autopsy were done within the study period, of which 91 cases were on patients with diabetes accounting for 8.3%. Infections with sepsis were the major cause of death, accounting for 51.6% followed by cardiovascular diseases (16.5%), cancers (14.3%), acute diabetic emergencies (6.6%) and cerebrovascular accidents (6.6%), with renal complications and road traffic accidents accounting for 2.2% each. Patients' age ranged from 31 to 84 years, with a modal age of 57 years. There was a male predominance with a male-to-female ratio of 1.5:1. Systemic hypertension co-morbidity was statistically significantly more common in patients aged 60 and above (P = 0.035). The most common lesion observed in the kidneys was benign nephrosclerosis (43.2%). CONCLUSIONS: This study suggests that majority of our patients with diabetes mellitus die from infections with attendant sepsis. Older patients appear to have co-morbid systemic hypertension. Patient education on infection prevention and prompt treatment might be life-saving.

Diagnostic Accuracy of Fine-Needle Aspiration Cytology in Head and Neck Lesions from a Tertiary Health Facility in Southwestern Nigeria.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is widely employed as an initial investigative tool in the diagnosis of various lesions in the body, however, it is limited in the provision of precise architectural detail of lesions. This is said to be responsible for the wide variation in the documented usefulness and accuracy relative to histopathology. This study aimed to correlate cytopathological and histopathological examination (HPE) of head and neck lesions, and assess the usefulness and accuracy of FNAC in our center. MATERIALS AND METHODS: This was a retrospective study that utilized historical data obtained from case notes and histopathology records of 91 patients that had both FNAC and HPE done for head and neck lesions in our center during the study. The FNAC results were correlated with that of the histopathological diagnosis to obtain the accuracy of the FNAC diagnosis. Diagnostic validity of FNAC in terms of sensitivity, specificity, and predictive value were also evaluated. RESULTS: A total of 91 FNAC-HPE sample pairs were included. The Sensitivity and specificity for benign lesion was 95.4% and 42.3%, respectively, while for sensitivity and specificity for malignant lesion was 31.8% and 96.9%, respectively. The overall Sensitivity and specificity for cytology was 96.8% and 30.4%, respectively. CONCLUSION: FNAC appears to be a useful tool in the initial assessment of head and neck lesions in our center, however, the high rate of missed diagnosis especially as concerned malignancies has dire negative treatment implications. There is need to develop capacity for improved skill in making cytopathologic diagnoses among anatomical pathologists involved in the use of FNAC as diagnostic and screening tool.

Parathyroid Adenoma with Unusual Presentations of Rib Bone and Thoracic Vertebrae Fractures in a Premenopausal Female in Ibadan, Nigeria.

Parathyroid adenoma is the most common cause of primary hyperthyroidism which leads to abnormal calcium homeostasis, hypercalcemia, and reduction in bone density. A 37-year-old female referred from a private health facility with a 1-year history of upper back swelling and pain. The pain was worse when sitting down for long periods and with movement and relieved by rest. There was no antecedent history of trauma, but the patient had noticed poor appetite and weight loss. There were no constipation, no abdominal discomfort, and no symptom suggestive of hyperthyroidism or hypothyroidism. General physical examination revealed kyphoscoliosis, and vital signs were within normal limits. Spine X-ray showed features of cervical spondylosis. Computed tomography (CT) scan and magnetic resonance imaging showed pathologic fractures of the right 9 thrib, anterior wedge compression, and reduction of T4 vertebrae with other abnormalities at T4-T5, T5-T6, T7-T8, T10-T11, and L4-L5 vertebrae. Bone marrow aspiration and serum electrophoresis were within normal limits. Serum calcium showed hypercalcemia. A CT scan of the neck was done which showed features of a right superior parathyroid adenoma. Blood count, other serum electrolytes, and thyroid function tests were all normal. A parathyroidectomy with right thyroid lobectomy was done. Histopathological examination of the resected parathyroid gland showed a diagnosis of parathyroid adenoma. A high index of suspicion is needed to diagnose this unusual presentation of parathyroid adenoma. Radiological imaging is an important tool for early diagnosis.

Histopathological profile of childhood thyroid carcinoma in Ibadan, Southwestern Nigeria.

Background: Thyroid carcinoma is a common endocrine malignancy. It is however rare in childhood and often occurs as a result of radiation exposure or inherited genetic mutations. Most childhood thyroid carcinomas are well differentiated. There are very few epidemiological studies of this disease in Nigeria and our study aimed to determine the frequency in a subset of our population. The study aimed to determine the prevalence and histopathological characteristics of childhood thyroid carcinoma in our environment. Methods: This was a retrospective review of histopathologically diagnosed thyroid carcinoma in children less than 18 years of age in the Department of Pathology, University College Hospital, Ibadan over a 40-year period. Histopathological diagnosis, age, sex and other relevant clinical information were extracted from the hospital records and surgical pathology records of the department. All cases of patients under18 years old had their slides re-examined and reclassified by two pathologists according to the World Health Organization histopathological classification of thyroid tumours. Results: There were 25 cases of thyroid carcinomas seen in children within the study period. Papillary thyroid carcinoma was the most common, accounting for 80% of the cases. Follicular carcinoma accounted for 12%, and medullary and anaplastic carcinoma accounted for 4% each. The mean age at presentation was 13 years. There was a female preponderance with females accounting for 60% of cases. Tumours with distant metastasis made up 20% of the cases. Conclusion: Childhood thyroid carcinomas are rare in our environment, with a minority of cases presenting with metastases.

Histopathology of Head and Neck Lymphomas in Ibadan.

Background: Lymphomas are a heterogeneous group of tumors of lymphoid tissue in which there is a malignant proliferation of cells of the lymphatic system. They are the most frequent nonepithelial malignancy in the head and neck region. Objectives: The aim of this study was to evaluate the histological pattern of the disease in the head and neck region and trends in presentation seen in our center. Materials and Methods: This was a retrospective study of cases of head and neck lymphoma (HNL) seen in the Pathology Department of the University College Hospital Ibadan, Nigeria over a period of 37 years (1981-2017). Information extracted from the records included the sociodemographics of the patients, tumor location, and histological type among others. Data were analyzed and results were presented as frequencies and percentages. Results: There were a total of 373 cases of histologically and/or cytologically diagnosed HNL seen during the study period (an average of 10 cases per year). The mean age of patients was 33.5 ± 21.9 years with male:female ratio of 1.6:1. Most HNL were non-Hodgkin's lymphomas (NHL), accounting for 91% of cases. Nodal disease was seen in 39% of cases. The bone (prominently, the jaws) predominated (25%) in extranodal lesions. Burkitt's lymphoma was the most common specific subtype of NHL, occurring in 25.5% of cases. Conclusion: There has been an apparent upward trend in the prevalence of HNL over the past four decades, although other parameters such as age and sex predilection appear unaffected. Factors responsible for this trend need to be interrogated and ascertained.

Pediatric Meningiomas in Southwestern Nigeria: A Single-Institutional Experience.

BACKGROUND: Meningiomas are the second commonest intracranial tumors in many places worldwide. They are rare in the pediatric age group, however, and most studies have been able to document only a few patients. Meningiomas in pediatric patients have also been shown to behave differently from those in the adult population. This study was done to examine histologic types of meningiomas seen in pediatric patients from a predominantly African population using the 2016 World Health Organization (WHO) grading system for intracranial tumors. METHODS: Data from the operating logs of patients and histology reports of the samples sent to the pathology department during the study period were extracted. The data obtained were the age, sex, location of the intracranial tumor, histologic diagnosis, WHO grade, and tumor recurrence. RESULTS: Nine pediatric age patients were found among the 166 surgically excised meningiomas received at the pathology department in our institution over a 19-year period. The age range was from 8 months to 17 years. There was a male-to-female ratio of 1:2 with a female predominance. Six tumors were basally located. All tumors were WHO grade I with transitional meningiomas being the commonest followed by meningothelial. There was no history of recurrence in any of the tumors after complete surgical excisions. CONCLUSIONS: Our study showed the rarity of meningiomas in the study population, and there was a predominance of basally located tumors.

Bilateral breast cancer among three Yoruba women in a Nigerian teaching hospital.

Breast cancer is the most common cancer among females in Nigeria. Bilateral breast cancer can occur synchronously or metachronously. We report three different cases of bilateral breast cancer in three female patients managed by the Ibadan Multidisciplinary Breast Tumour Board, domiciled at the University College Hospital (UCH), over a 3-year period. Two of these patients had synchronous bilateral breast cancer and developed cancer in the second breast during the course of management. These case reports may therefore stimulate further research on the clinicopathological features and the progression of bilateral breast cancer among females, especially in our environment. Our patients were premenopausal and the immunochemistry of the tumours showed a triple-negative immunophenotype. The other features of presentation, investigation, diagnosis and follow-up care are the highlights of this presentation.