ABSTRACT
Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died.
ABSTRACT
CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.
Subject(s)
Head and Neck Neoplasms , Paraganglioma , Humans , Middle Aged , Male , Female , Adult , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Aged , Retrospective Studies , Adolescent , Young Adult , Aged, 80 and over , Paraganglioma/therapy , Paraganglioma/genetics , Paraganglioma/pathology , Succinate Dehydrogenase/genetics , Treatment Outcome , MutationABSTRACT
Gastric-type adenocarcinoma is the commonest human papillomavirus (HPV)-independent adenocarcinoma of the cervix. We report a rare case of a primary cervical gastric-type adenocarcinoma with malignant squamous elements (gastric-type adenosquamous carcinoma) in a 64-yr-old female. This is only the third report of a cervical gastric-type adenosquamous carcinoma. The tumor was p16 negative and molecular studies for HPV were negative. Next-generation sequencing showed pathogenic variants in BRCA1 and KRAS , as well as variants of unknown significance in CDK12 and ATM and homozygous deletion of CDKN2A/CDKN2B . Pathologists should be aware that not all cervical adenosquamous carcinomas are HPV-associated and the term gastric-type adenosquamous carcinoma is recommended when malignant squamous elements are present within a gastric-type adenocarcinoma. In reporting this case, we discuss the differential and the possible therapeutic options raised by the presence of pathogenic variants in BRCA1 .
Subject(s)
Adenocarcinoma , Carcinoma, Adenosquamous , Carcinoma, Squamous Cell , Papillomavirus Infections , Stomach Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Cervix Uteri , Carcinoma, Adenosquamous/diagnosis , Carcinoma, Adenosquamous/genetics , Homozygote , Sequence Deletion , Uterine Cervical Neoplasms/genetics , Stomach Neoplasms/genetics , Adenocarcinoma/genetics , BRCA1 Protein/geneticsABSTRACT
Plasma cell dyscrasias (PCDs) are a heterogeneous group of diseases, and the most common is monoclonal gammopathy of undetermined significance (MGUS). This premalignant PCD consistently precedes multiple myeloma (MM), with a 1% risk of progression per year. Evading and suppressing the host immune system is an important step in the progression of MGUS to MM. This pilot study was designed to assess whether MGUS and MM have a distinct microenvironment, characterized by a unique distribution of immune cells, including tumor-associated macrophages. Evaluation of bone marrow (BM) tumor microenvironment was performed using immunohistochemical quantification of T cells (CD3), macrophages (CD68), and a macrophage subtype (CD163). The findings were compared between MGUS and MM to determine whether differences existed. The results suggest that there is a significantly lower percentage of CD3-positive, CD68-positive and CD163-positive immune effector cells in BM trephine biopsy samples from patients with MGUS than in those from patients with untreated MM (p < 0.001). Interestingly, in a patient treated for MM, the percentages of CD3+ and CD68+ cells were the same as those in other patients with untreated MM; however, the percentage of CD163+ cells reduced and correlated with low plasma cell count. Future studies are required to investigate whether the percentage of CD163+ cells is correlated with disease burden in patients with MM. If this is the case, then the level of soluble CD163 in plasma could be a potential biomarker of disease burden in patients with nonsecretory myelomas, in whom measurements of levels of paraprotein and free light chains are inconclusive.
Subject(s)
Monoclonal Gammopathy of Undetermined Significance , Multiple Myeloma , Paraproteinemias , Humans , Multiple Myeloma/pathology , Tumor-Associated Macrophages/pathology , Pilot Projects , T-Lymphocytes/pathology , Tumor MicroenvironmentSubject(s)
CA-19-9 Antigen/metabolism , Cystadenocarcinoma, Serous/metabolism , Fallopian Tube Neoplasms/metabolism , Fallopian Tubes/metabolism , Ovarian Neoplasms/metabolism , Ovary/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Cystadenocarcinoma, Serous/pathology , Fallopian Tube Neoplasms/pathology , Fallopian Tubes/pathology , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Ovary/pathology , Retrospective StudiesABSTRACT
Ovarian endometrioid carcinoma, more than any other type of ovarian epithelial malignancy, demonstrates a varied morphology which can cause problems in diagnosis. In tubo-ovarian tumor pathology, WT1 is a commonly used marker as it is consistently expressed in low-grade and high-grade serous carcinomas and is often considered a specific marker of a serous phenotype. However, ovarian endometrioid neoplasms may also express WT1 which may contribute to misdiagnosis. We report our experience with 23 ovarian endometrioid neoplasms (4 borderline tumors, 19 carcinomas), mainly received in consultation, which were WT1 positive (diffuse in 11 cases) which often contributed to misdiagnosis. Endometriosis was identified in the same ovary in 6 cases and squamous elements in 7. We describe strategies for distinguishing such neoplasms, which may exhibit morphologic overlap with serous tumors, from low-grade and high-grade serous carcinomas and stress that a diagnosis of HGSC is unlikely with two grossly and histologically normal fallopian tubes. We also stress that a panel of markers should always be used rather than relying on a single marker and that when the morphology is classical of an endometrioid carcinoma, diagnostic immunohistochemistry is not needed given the potential for confusion in cases showing "aberrant" staining. We also discuss the phenomenon of "aberrant" immunohistochemical staining in endometrioid carcinomas which appears more common than in other ovarian carcinomas.
Subject(s)
Carcinoma, Endometrioid , Cystadenocarcinoma, Serous , Ovarian Neoplasms , Biomarkers, Tumor , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/pathology , Female , Humans , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Referral and Consultation , WT1 ProteinsABSTRACT
We report 10 cases of a previously undescribed lesion within ovarian teratomas which we designate bronchus-like structures. The lesions occurred in patients aged 16 to 56 yr (mean: 36) and involved the left ovary (n=5) or right ovary (n=5). Nine cases were mature teratomas (dermoid cysts/mature cystic teratomas or mature solid teratomas), 1 with somatic malignant transformation, and 1 was an immature teratoma. The bronchus-like structures ranged in size from 2.5 to 10 mm and were unifocal (7 cases) or multifocal (3 cases). The morphology was relatively constant in all cases and characterised by a well-formed bronchus surrounded by glandular structures, some of which were dilated, separated by stroma containing a variable amount of smooth muscle. In all but 1 case, a proportion of the glands contained abundant foamy cytoplasm. There was little or no nuclear atypia or mitotic activity. At low-power, the glands often had a somewhat "infiltrative" appearance and one case was originally diagnosed as a "pulmonary-type" adenocarcinoma arising in a dermoid cyst. In all cases, there was diffuse staining of the bronchus and glands with TTF1 and Napsin A, confirming the cell lineage. Follow-up in 4 cases (18-130 mo; median: 64 mo) showed no evidence of recurrence; 1 patient died from an unrelated malignancy. In reporting this apparently rare but possibly underrecognized benign lesion arising within ovarian teratomas, we discuss the differential diagnosis and stress that pathologists should be aware of this phenomenon in order to avoid an erroneous diagnosis of malignancy.
Subject(s)
Ovarian Neoplasms , Teratoma , Adolescent , Adult , Bronchi/pathology , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Teratoma/diagnosis , Teratoma/pathology , Young AdultABSTRACT
The growth of digital pathology over the past decade has opened new research pathways and insights in cancer prediction and prognosis. In particular, there has been a surge in deep learning and computer vision techniques to analyse digital images. Common practice in this area is to use image pre-processing and augmentation to prevent bias and overfitting, creating a more robust deep learning model. This generally requires consultation of documentation for multiple coding libraries, as well as trial and error to ensure that the techniques used on the images are appropriate. Herein we introduce HistoClean; a user-friendly, graphical user interface that brings together multiple image processing modules into one easy to use toolkit. HistoClean is an application that aims to help bridge the knowledge gap between pathologists, biomedical scientists and computer scientists by providing transparent image augmentation and pre-processing techniques which can be applied without prior coding knowledge. In this study, we utilise HistoClean to pre-process images for a simple convolutional neural network used to detect stromal maturity, improving the accuracy of the model at a tile, region of interest, and patient level. This study demonstrates how HistoClean can be used to improve a standard deep learning workflow via classical image augmentation and pre-processing techniques, even with a relatively simple convolutional neural network architecture. HistoClean is free and open-source and can be downloaded from the Github repository here: https://github.com/HistoCleanQUB/HistoClean.
ABSTRACT
The development of a somatic neoplasm within an ovarian dermoid cyst (mature cystic teratoma) is a rare, but well described, phenomenon which occurs in approximately 1% of all cases. Any of the tissue components of a dermoid cyst has the potential to undergo neoplastic transformation with carcinoid tumors and squamous cell carcinomas being among the most common neoplasms. We report a case of a ganglioneuroblastoma arising within an ovarian dermoid cyst, an association which, as far as we are aware, has not been described previously.
Subject(s)
Dermoid Cyst/diagnostic imaging , Ganglioneuroblastoma/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Teratoma/diagnostic imaging , Cell Transformation, Neoplastic , Dermoid Cyst/pathology , Dermoid Cyst/surgery , Female , Ganglioneuroblastoma/pathology , Ganglioneuroblastoma/surgery , Humans , Immunohistochemistry , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Salpingo-oophorectomy , Teratoma/pathology , Teratoma/surgery , Ultrasonography , Young AdultABSTRACT
Cervical gastric-type adenocarcinomas are aggressive non-human papillomavirus-related carcinomas with a propensity for extracervical spread, including unusual sites such as the omentum, peritoneum, and ovary. We report 7 cases of cervical gastric-type adenocarcinoma with fallopian tube involvement predominantly in the form of mucosal colonization without underlying invasion. As far as we are aware, this has not been previously described and this report adds to the literature regarding metastatic neoplasms, which may exhibit tubal mucosal involvement and mimic an in situ lesion at this site. In all cases, there was associated ovarian involvement and in 6 of 7 cases, there was endometrial colonization. We speculate that the fallopian tube (and ovarian) involvement is secondary to transuterine spread. Given the occasional occurrence of multifocal gastric-type glandular lesions (benign or malignant) involving different sites in the female genital tract, we discuss the distinction between synchronous independent and metastatic lesions.
Subject(s)
Adenocarcinoma/secondary , Fallopian Tube Neoplasms/secondary , Fallopian Tubes/pathology , Mucous Membrane/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/chemistry , Adenocarcinoma/surgery , Adult , Aged , Biomarkers, Tumor/analysis , Biopsy , Fallopian Tube Neoplasms/chemistry , Fallopian Tube Neoplasms/surgery , Fallopian Tubes/chemistry , Fallopian Tubes/surgery , Female , Humans , Immunohistochemistry , Middle Aged , Mucous Membrane/chemistry , Mucous Membrane/surgery , Neoplasm Invasiveness , Northern Ireland , Ovarian Neoplasms/secondary , United States , Uterine Cervical Neoplasms/chemistry , Uterine Cervical Neoplasms/surgeryABSTRACT
INTRODUCTION: Primary epispadias is a rare congenital malformation involving the urogenital system. In patients with epispadias, bladder closure enhances bladder growth and continence. METHODS: Several steps were carried out to bring the bladder neck to the midline and allow tension-free bladder neck reconstruction and recreation of the natural angulation of urethra. The urethral plate and penile shaft were dissected and the corpora cavernosa separated, and then the bladder neck repair was performed. The urethral plate was tubularised and brought ventrally. The separated corpora were reapposed, avoiding torsion. The skin was reoriented to provide cover to the penis. RESULTS: The Kelly procedure improves cosmesis and continence by reconstructing a tension-free bladder neck repair and lengthening the penis. CONCLUSION: The video demonstrates the Kelly procedure for primary epispadias in a male child.
Subject(s)
Epispadias/surgery , Child , Humans , Male , Penis/surgery , Urethra/surgery , Urinary Bladder/surgery , Urologic Surgical Procedures, Male/methodsSubject(s)
Abdominal Pain/parasitology , Antinematodal Agents/therapeutic use , Enterobiasis/diagnosis , Enterobius/isolation & purification , Mebendazole/therapeutic use , Adolescent , Animals , Appendicitis/diagnosis , Diagnosis, Differential , Enterobiasis/complications , Enterobiasis/drug therapy , Female , Granuloma/complications , Granuloma/parasitology , Humans , Laparoscopy , Treatment OutcomeABSTRACT
Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. However, known pharmacological inhibitors of autophagy could not enhance cytotoxicity. In this study, we have examined two well known, clinically approved autophagy inducers, rapamycin and lithium, for their effects on chemosensitivity in apoptosis incompetent cancer cells. Both lithium and rapamycin were shown to induce autophagosomes in esophageal and colorectal cancer cells by western blot analysis of LC3 isoforms, morphology and FACS quantitation of Cyto-ID or mCherry-GFP-LC3. Analysis of autophagic flux indicates inefficient autophagosome processing in lithium treated cells, whereas rapamycin treated cells showed efficient flux. Viability and recovery was assessed by clonogenic assays. When combined with the chemotherapeutic agent 5-fluorouracil, rapamycin was protective. In contrast, lithium showed strong enhancement of non-apoptotic cell death. The combination of lithium with 5-fluorouracil or oxaliplatin was then tested in the syngenic mouse (balb/c) colorectal cancer model--CT26. When either chemotherapeutic agent was combined with lithium a significant reduction in tumor volume was achieved. In addition, survival was dramatically increased in the combination group (p < 0.0001), with > 50% of animals achieving long term cure without re-occurrence (> 1 year tumor free). Thus, combination treatment with lithium can substantially improve the efficacy of chemotherapeutic agents in apoptosis deficient cancer cells. Induction of compromised autophagy may contribute to this cytotoxicity.
Subject(s)
Autophagy/drug effects , Colorectal Neoplasms/pathology , Esophageal Neoplasms/pathology , Lithium Chloride/pharmacology , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Drug Synergism , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Female , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Genes, Reporter , Humans , Lithium Chloride/therapeutic use , Mice , Mice, Inbred BALB C , Microscopy, Confocal , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Sirolimus/pharmacology , Sirolimus/therapeutic use , Transplantation, HeterologousABSTRACT
Priapism is a rare condition in children and can be classified as high or low flow. We present a case of traumatic high-flow priapism that was successfully managed by selective embolisation of a branch of the internal pudendal artery. The pertinent clinical features are antecedent trauma and prolonged painless partial erection. The investigation of choice is Doppler ultrasound. Management can either be conservative, radiological or surgical. While conservative management can be safely attempted for 6â weeks, given the nature of the condition, early intervention is often required. Radiological embolisation is the first line and is successful in 97% of cases. Surgery carries a higher morbidity and is only reserved in cases where repeated embolisation has failed. This case highlights the importance of a thorough history and careful interpretation of imaging with protocolised follow-up of patients by a paediatric urologist for early and accurate diagnosis of erectile dysfunction and prompt intervention to prevent future complications.
Subject(s)
Penis/injuries , Perineum/injuries , Priapism/etiology , Arteries , Child , Diagnosis, Differential , Embolization, Therapeutic/methods , Humans , Male , Penis/diagnostic imaging , Priapism/diagnostic imaging , Priapism/therapy , Treatment Outcome , UltrasonographyABSTRACT
BACKGROUND: Colorectal cancer is the second leading cause of cancer-related mortality and frequently presents with locally advanced or metastatic disease. Adenovirus (Ad) vectors are important gene delivery agents because they offer efficient and broad tissue transduceability. However, their ability to penetrate through multicell layers in colorectal cancers and maintain expression in colon tumor-related hypoxic conditions has yet to be analyzed. Furthermore, their broad tissue tropism presents safety concerns. MATERIALS AND METHODS: An ex vivo cultured patient tumor sample model was employed to examine Ad transduction of colorectal tumors. RESULTS: Results obtained from Ad delivery of the firefly luciferase (FLuc) reporter gene indicated that colon tumor tissue was more amenable to Ad transduction than other tumor histologic types examined (breast and ovary). Ad transduction levels were significantly higher than a range of viral and nonviral methods examined in patient colon tissue. Control of transgene expression using the CXC chemokine receptor 4 (CXCR4) promoter was examined as a strategy to confine expression to tumor cells. An Ad construct carrying FLuc under the control of the human CXCR4 promoter demonstrated low reporter gene expression compared with the ubiquitously expressing cytomegalovirus promoter in normal colon and liver tissue while providing high expression in tumors, demonstrating a 'tumour-on' and 'normal-off' phenotype in patient tissue. The effects of changing hypoxia on Ad-related transgene expression were examined in an in vitro model of hypoxic conditions relevant to clinical colorectal tumors. Reporter gene expression varied depending on the level of hypoxia, with significantly reduced levels observed with prolonged hypoxia. However, transgene expression was robust in the cycling hypoxic conditions relevant to colorectal tumors. CONCLUSION: This study provides novel, clinically relevant data demonstrating the potential for efficient gene delivery to colorectal tumors using Ad.