Research Articles (Anatomical Pathology)

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From incidence to intervention : a comprehensive look at breast cancer in South Africa
(Springer, 2024-03) Dlamini, Zodwa; Molefi, Thulo; Khanyile, Richard; Mkhabele, Mahlori; Damane, Botle Precious; Kokoua, Alexandre; Bida, Meshack; Saini, Kamal S.; Chauke-Malinga, Nkhensani; Luvhengo, Thifhelimbilu Emmanuel; Hull, Rodney; zodwa.dlamini@up.ac.za
The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities. These concerning trends underscore the urgency of enhancing breast cancer screening while mitigating treatment delays, although obstacles within the healthcare system impede progress. The intersection of breast cancer and human immunodeficiency virus (HIV) further complicates matters and particularly affects the Black population. Tackling the aforementioned disparities in breast cancer in South Africa mandates a multifaceted strategy. Robust screening efforts, particularly those targeting marginalised communities, are crucial for early detection. Concurrently, expedited treatment initiation is imperative. Addressing HIV-related complexities requires tailored interventions to ensure effective care. These multifaceted disparities require pan African research and cooperation as well as tailored interventions to enhance breast cancer care within the African region.
Tumor-infiltrating lymphocytes in melanoma : from prognostic assessment to therapeutic applications
(Frontiers Media, 2024-12) Bida, Nndweleni Meshack; Miya, Thabiso Victor; Hull, Rodney; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Malignant melanoma, the most aggressive form of skin cancer, is characterized by unpredictable growth patterns, and its mortality rate has remained alarmingly high over recent decades, despite various treatment approaches. One promising strategy for improving outcomes in melanoma patients lies in the early use of biomarkers to predict prognosis. Biomarkers offer a way to gauge patient outlook early in the disease course, facilitating timely, targeted intervention. In recent years, considerable attention has been given to the immune response’s role in melanoma, given the tumor’s high immunogenicity and potential responsiveness to immunologic treatments. Researchers are focusing on identifying predictive biomarkers by examining both cancer cell biology and immune interactions within the tumor microenvironment (TME). This approach has shed light on tumor-infiltrating lymphocytes (TILs), a type of immune cell found within the tumor. TILs have emerged as a promising area of study for their potential to serve as both a prognostic indicator and therapeutic target in melanoma. The presence of TILs in melanoma tissue can often signal a positive immune response to the cancer, with numerous studies suggesting that TILs may improve patient prognosis. This review delves into the prognostic value of TILs in melanoma, assessing how these immune cells influence patient outcomes. It explores the mechanisms through which TILs interact with melanoma cells and the potential clinical applications of leveraging TILs in treatment strategies. While TILs present a hopeful avenue for prognostication and treatment, there are still challenges. These include understanding the full extent of TIL dynamics within the TME and overcoming limitations in TIL-based therapies. Advancements in TIL characterization methods are also critical to refining TIL-based approaches. By addressing these hurdles, TIL-focused research may pave the way for improved diagnostic and therapeutic options, ultimately offering better outcomes for melanoma patients.
Overcoming the challenges of phytochemicals in triple negative breast cancer therapy : the path forward
(MDPI, 2023-06-16) Alaouna, Mohammed; Penny, Clement; Hull, Rodney; Molefi, Thulo; Chauke-Malinga, Nkhensani; Khanyile, Richard; Makgoka, Malose; Bida, Meshack; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC.
In silico bioinformatics analysis on the role of long non-coding RNAs as drivers and gatekeepers of androgen-independent prostate cancer using LNCaP and PC-3 cells
(MDPI, 2023-09-01) Mbeje, Mandisa; Kandhavelu, Jeyalakshmi; Penny, Clement; Kgoebane-Maseko, Minah; Dlamini, Zodwa; Marima, Rahaba; zodwa.dlamini@up.ac.za
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of 2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsamiR- 4429 and hsa-miR-320b. This interaction in turn activates TGF- -signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets.
Transorbital neuroendoscopy-assisted resection of a giant optic pathway glioma in a neonate
(Springer, 2023-09) Maseko, Rodney; Mabogo, Maanda; Lockhat, Zarina I.; Makunyane, P.S. (Priscilla); Ahmad, Samia; Bida, Meshack; Padayachy, Llewellyn; lc.padayachy@up.ac.za
Congenitalgiant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of a transorbital neuroendoscopy-assisted resection of such a lesion. While this approach is increasingly gaining popularity for certain anterior and middle skullbase lesions in adults, this report represents the youngest patient reported on where this minimally invasive approach has been successfully used to resect the intracranial tumor. This surgical approach obviated the need for a separate craniotomy, with the additional benefit of minimizing blood loss.
Renal papillary necrosis (RPN) in an African population : disease patterns, relevant pathways, and management
(MDPI, 2023-01) Gaudji, Guy Roger; Bida, M.; Conradie, Marius; Damane, Botle Precious; Bester, Megan; megan.bester@up.ac.za
Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids and papillae. Multiple conditions and toxins are associated with RPN. Several RPN risk factors, or POSTCARDS, have been identified, with most patients presenting with RPN having at least two contributing risk factors. Currently, there is no specific test to diagnose and confirm RPN; however, several imaging tools can be used to diagnose the condition. RPN is currently underdiagnosed in African populations, often with fatal outcomes. In African clinical settings, there is a lack of consensus on how to define and describe RPN in terms of kidney anatomy, pathology, endourology, epidemiology, the identification of African-specific risk factors, the contribution of oxidative stress, and lastly an algorithm for managing the condition. Several risk factors are unique to African populations including population-specific genetic factors, iatrogenic factors, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). Oxidative stress is central to both GIVASSH and POSTCARDS-associated risk factors. In this review, we present information specific to African populations that can be used to establish an updated consensual definition and practical grading system for radiologists, urologists, nephrologists, nuclear physicians, and pathologists in African clinical settings.
Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria, South Africa
(South African Medical Association, 2023-07) Maroga, N.; Mokoena, Taole; Musekiwa, Alfred; Bida, Meshack; Kgomo, Mpho K.; Lebelo, R.; taole.mokoena@up.ac.za
BACKGROUND : The association between human papillomavirus (HPV) and cervical cancer is well established, and cervical cancer can be prevented through HPV vaccination. Little has been reported on the association between HPV and breast carcinoma (BC) or oesophageal squamous cell carcinoma (OSCC) in Africa. It is possible that use of appropriate HPV vaccines against genotypes responsible for these cancers may also prevent their development. OBJECTIVES : To investigate HPV genotype prevalence in BC and OSCC patients in Pretoria, South Africa (SA). METHODS : A retrospective cross-sectional study of BC and OSCC patients managed at Steve Biko Academic Hospital from 2015 to 2019 was undertaken. Patient medical records were analysed, and DNA was extracted from their archived pathology material and amplified by polymerase chain reaction before hybridisation for HPV genotypes. RESULTS : There were 101 patients with BC and 50 with OSCC. The prevalence of HPV infection in BC patients was 77.2%, with 35.6% highrisk (HR) genotypes, and that in OSCC patients 90.0%, with 56.0% HR genotypes. The most prevalent HPV genotypes (>20% each) were HPV 16, 70 and 51 for BC and HPV 51, 70, 16 and 82 for OSCC, with 31.7% and 60.0% of patients, respectively, having co-infection with ≥2 genotypes. CONCLUSION : The high prevalence of infection with multiple HPV genotypes in BC and OSCC patients, with HPV 16, 51, 70, 35 and 82 the most common genotypes in these cancers, warrants expansion of the current SA bivalent HPV 16/18 vaccine for girls to include boys, and inclusion of HPV 51, 70, 35 and 82, in order to prevent BC and OSCC as well as cervical cancer.
Superficial spreading cervical squamous cell carcinoma in situ with extensive endomyometrial infiltration masquerading as a primary endometrial cancer
(MedPharm Publications, 2022-12) Olivier, H.J.; Snyman, Leon Cornelius; Oliva, E.; Slavik, Tomas
The presence of squamous cell carcinoma (SCC) on endometrial histology raises the possibility of a primary endometrial carcinoma, as well as secondary endometrial involvement by SCC from another site, especially the cervix. This distinction relies on numerous cardinal clinical and pathologic findings and may occasionally be problematic. We document an unusual tumour in a postmenopausal woman who presented with clinical and radiologic features of a primary endometrial cancer, confirmed on endometrial histology as a keratinising SCC. Subsequent pathologic evaluation of the hysterectomy specimen, however, demonstrated an exclusively in situ cervical SCC, with extensive endometrial intramucosal spread and widespread infiltration of the myometrium, macroscopically mimicking a primary endometrial neoplasm. We review the pathologic distinction between primary endometrial SCC and secondary corpus involvement of cervical SCC, as well as the broader differential diagnosis when SCC is identified on endometrial histology.
New horizons in the diagnosis of tuberculosis of the spine : the role of whole genome sequencing
(Korean Society of Spine Surgery, 2023-06) Ngcelwane, M.V. (Mthunzi); Omar, Shaheed V.; Said, H.M. (Halima Mohammed); Bida, Nndweleni Meshack; mthunzi.ngcelwane@up.ac.za
STUDY DESIGN : Prospective study. PURPOSE : To evaluate the utility of whole genome sequencing (WGS) in drug resistance testing, lineage of the organisms, and organism-related factors responsible for bacilli settling in the spine. OVERVIEW OF LITERATURE : The workstream for the diagnosis of tuberculosis (TB) involves isolation and culture of the organism and drug resistance testing using phenotypic methods. Xpert MTB/RIF Ultra is a genetic-based method that detects for Mycobacterium tuberculosis DNA in the rpoB gene. Meanwhile, WGS is a newer genetic-based method that assesses the whole genome of the bacterium. Very few studies have reported the use of WGS for extrapulmonary TB. Herein, we used WGS to diagnose spinal TB. METHODS : Tissues from 61 patients undergoing surgery for spinal TB underwent histologic examination, Xpert MTB/RIF Ultra, and culture and sensitivity testing. DNA from the cultured bacteria was sent for WGS. The test bacterial genome was compared to a reference strain of pulmonary TB. RESULTS : Acid-fast bacilli were observed in 9/58 specimens. Meanwhile, histology confirmed TB in all the patients. Bacilli were cultured in 28 patients (48.3%), and the average time to culture was 18.7 days. Xpert MTB/RIF Ultra was positive in 47 patients (85%). WGS was performed in 23 specimens. Overall, 45% of the strains belonged to lineage 2 (East Asian). There was one case of multidrug-resistant TB and two cases of non-tuberculous mycobacteria on WGS. We could not confirm any genomic difference between pulmonary and spinal TB strains. CONCLUSIONS : Xpert MTB/RIF Ultra of tissues or pus is the investigation of choice when diagnosing spinal TB. Meanwhile, WGS can diagnose multidrug-resistant TB and non-tuberculous mycobacteria more accurately. No mutations were identified in spinal and pulmonary TB bacteria.
Underdiagnosis of iron deficiency anaemia in HIV-infected individuals : a pilot study using soluble transferrin receptors and intensive bone marrow iron stores to improve the diagnosis
(BMJ Publishing Group, 2023-08) Mankgele, Mahlatse; Variava, Ebrahim; Moloantoa, Tumelo; Otwombe, Kennedy; Hlongwane, Khuthadzo; Disenyane, Dineo; Bida, Meshack; Chikwati, Raylton; Snyman, Tracy; Martinson, Neil; Mahlangu, Johnny
AIM : We compared soluble transferrin receptors (sTfR), serum ferritin, mean cell volume (MCV) of red cells and the sTfR-ferritin index with the intensive method bone marrow trephine (BMT) iron stores in the diagnosis of iron deficiency anaemia (IDA) in Human Immunodeficiency Virus (HIV)-positive hospitalised participants. METHODS : In this cross-sectional study, we recruited hospitalised HIV-positive and coronavirus of 2019 (COVID-19)-negative adults with anaemia who required a bone marrow examination as part of their diagnostic workup. We measured the full blood count, ferritin, sTfR and assessed iron using the intensive method in Haemotoxylin and Eosin (H&E)-stained BMT core biopsies of consenting participants. RESULTS : Of the 60 enrolled participants, 57 were evaluable. Thirteen (22.80%) had IDA on H&E BMT iron stores assessment, and 44 (77.19%) had anaemia of chronic diseases (ACD). The sTfR and the sTfR-ferritin index had sensitivities of 61.54% and 53.85%, respectively, for IDA diagnosis. The sensitivity and specificity of ferritin was 7.69% and 92.31%, respectively. The sTfR and sTfR-ferritin index’s diagnostic specificity was relatively low at 46.15% and 38.46%, respectively. CONCLUSION : In this pilot study in HIV-positive participants, the prevalence of iron deficiency using the BMT assessment was low. Both the sTfR and the sTfR-ferritin index had a better quantitative correlation to bone marrow iron stores when compared with the MCV and ferritin and, may be more accurate surrogate markers of IDA.
Interobserver agreement of estimating the extent of intestinal metaplasia in patients with chronic atrophic gastritis
(Springer, 2022-06) Lerch, Julia M.; Pai, Rish K.; Brown, Ian; Gill, Anthony J.; Jain, Dhanpat; Kovari, Bence; Kushima, Ryoji; Sheahan, Kieran; Slavik, Tomas; Srivastava, Amitabh; Lauwers, Gregory Y.; Langner, Cord
The extent of gastric intestinal metaplasia (GIM) can be used to determine the risk of gastric cancer. Eleven international gastrointestinal expert pathologists estimated the extent of GIM on haematoxylin and eosin (H&E)- and Alcian blue-Periodic acid Schiff (AB-PAS)-stained slides of 46 antrum biopsies in 5% increments. Interobserver agreement was tested with the intraclass correlation coefficient (ICC). Correlation between standard deviation and extent of GIM was evaluated with the Spearman correlation. The interobserver agreement was very good (ICC = 0.983, 95% confidence interval (CI) 0.975–0.990). The use of AB-PAS did not increase the agreement (ICC = 0.975, 95% CI 0.961–0.985). Cases with a higher amount of metaplastic epithelium demonstrated a higher standard deviation (rs = 0.644; p < 0.01), suggesting lower diagnostic accuracy in cases with extensive GIM. In conclusion, estimating the extent of GIM on H&E-stained slides in patients with chronic atrophic gastritis can be achieved satisfactorily with high interobserver agreement, at least among international expert gastrointestinal pathologists.
Discrepancies between clinical diagnoses and autopsy findings : a comparative study conducted in South Africa
(Health and Medical Publishing Group, 2022-11) Joubert, Doret M.; Rossouw, Servaas Hofmeyr; Solomon, C.; Meyer, Pieter Willem Adriaan
BACKGROUND. The anatomical pathology autopsy serves several purposes, notably as a quality management tool for evaluation of accuracy in clinical diagnosis. Despite its value, for various reasons there has been an international decline in autopsies conducted. In the modern medical era, with all its advances in technology, diagnostic techniques and interventions, there is still a high discrepancy between clinical diagnoses and postmortem findings. OBJECTIVES. To establish the discrepancies between clinical diagnoses and postmortem findings in anatomical pathology autopsies. METHODS. A retrospective, descriptive study was conducted over the 4-year-period 2014 - 2017. The clinical diagnoses and postmortem findings of cases referred to the Department of Anatomical Pathology at the University of Pretoria, South Africa, were evaluated and compared using the modified Goldman criteria. RESULTS. A total of 288 cases qualified for the study and were evaluated. The gender distribution was 155 (53.8%) male and 133 (48.2%) female, with the majority of cases in the age group 19 - 60 years (mean 36.4). The majority of the cases were referred by internal medicine, followed by paediatrics. The most common cause of death in major missed diagnoses was pulmonary conditions. Of the cases, 115 (39.3%) had a major discrepancy and 62 (21.5%) a minor discrepancy. CONCLUSION. This study showed that there is still a high discrepancy between clinical diagnoses and postmortem findings, similar to studies conducted globally. The current COVID-19 pandemic may be a driver for revival of the anatomical pathology autopsy, and future studies are recommended to evaluate whether the decline can be reversed.
Subtyping intestinal metaplasia in patients with chronic atrophic gastritis : an interobserver variability study
(Elsevier, 2022-04) Lerch, Julia M.; Pai, Rish K.; Brown, Ian; Gill, Anthony J.; Jain, Dhanpat; Kovari, Bence; Kushima, Ryoji; Sheahan, Kieran; Slavik, Tomas; Srivastava, Amitabh; Lauwers, Gregory Y.; Langner, Cord
Incomplete gastric intestinal metaplasia (GIM) is associated with an increased risk of gastric cancer. We aimed to examine the interobserver variability of GIM subtyping (incomplete vs complete) in histological diagnosis of patients with chronic atrophic gastritis and to identify factors with potential impact on agreement. Nine international gastrointestinal expert pathologists assessed 46 cases with complete, incomplete or mixed-type GIM on scanned haematoxylin and eosin (H&E)-stained slides. Results were compared with the consensus diagnosis driven by two experts. Interobserver variability was evaluated by kappa statistics. Focusing on the predominant pattern, the agreement between each observer and the consensus diagnosis ranged from 78% to 98%. The level of agreement was moderate to almost perfect (weighted kappa=0.464–0.984). The participating pathologists reached substantial overall agreement (Fleiss' kappa=0.716, 95% confidence interval 0.677–0.755). Misclassification with potential impact on clinical decision making occurred in 5.7% of case ratings. The pattern of GIM (pure GIM versus mixed-type GIM) differed significantly between cases with high and low agreement (p=0.010), while the number of biopsy pieces per sample and the portion of mucosal surface involved by GIM did not. Pathologists who apply subtyping in daily routine performed better than those who do not (p=0.040). In conclusion, subtyping GIM on H&E-stained slides can be achieved satisfactorily with high interobserver agreement. The implementation of GIM subtyping as a risk stratifying tool in current practice guidelines by the European Society of Gastrointestinal Endoscopy (ESGE) and the American Gastroenterological Association (AGA) carries a low rate of misclassification, at least among gastrointestinal expert pathologists.
Primary giant cell tumour of the breast with recurrence : a rare case report
(AOSIS, 2022-04-20) Suleman, Farhana Ebrahim; Vilakazi, Moipone N.; Bida, Nndweleni Meshack; Edwards, Richard
Giant cell tumour (GCT) arising from the soft tissues of the breast is a rare disease with only eight cases previously reported in the literature. We present a case of histologically proven GCT of the breast, which demonstrated recurrence a few months after resection.
Concomitant congenital intraoral dermoid cyst and heterotopic gastrointestinal cyst
(Springer, 2021-03) Robinson, Liam; Sengoatsi, Tshepang; Van Heerden, Willem Francois Petrus; willie.vanheerden@up.ac.za
Sublingual dermoid cysts and oral heterotopic gastrointestinal cysts are well-documented causes of sublingual swellings in infants. However, the simultaneous occurrence of both cysts is an extremely rare phenomenon, with only two previous cases reported in literature. We present a case of 1-month-old neonate with a cystic ventral tongue mass that on histologic examination showed a dermoid cyst with co-existing heterotopic gastric-type epithelium in the wall. Additional histochemical stains revealed focal areas of colonic metaplasia within the heterotopic gastric epithelium. CDX2 immunohistochemical staining confirmed derivation from colonic epithelium.
Suprasellar cyst presenting with bobble-head doll syndrome
(Elsevier, 2020-01) George, Roshan; Gaxa, Luvo; Lockhat, Zarina I.; Hlahla, Stevens Kgomotso; Van der Meyden, Cornelis Hendrikus; Kisten, Ravendran; Bida, Nndweleni Meshack
BACKGROUND : Bobble-head doll syndrome is a rare neurological syndrome presenting with repetitive anteroposterior head movements. It is usually associated with expansile cystic lesions in the third ventricular region. CASE DESCRIPTION : An 8-year-old boy presented with involuntary bobbling head movements. Magnetic resonance imaging of the brain revealed an extensive suprasellar cyst resulting in obstructive hydrocephalus. Endoscopic ventriculo-cysto-cisternostomy resulted in improved clinical outcome. CONCLUSIONS : Endoscopic ventriculo-cysto-cisternostomy is an effective, less-invasive technique in the treatment of suprasellar cysts that results in resolution of the bobbling head movements.
Potato tuber corky cracks caused by multiple Rhizoctonia species
(Plaas Media, 2020-07) Gush, Sasha-Lee
Potato (Solanum tuberosum L.) is the most consumed and economically important vegetable crop in the world. Nutritionally, potato is ideal for human consumption and provides a balanced source of starch, high-quality proteins, vitamins, trace elements and dietary fibre. This makes it an ideal crop to feed many communities and ensure food security. To increase potato production, research is focused on disease control, soil health, good farm management practices, seed quality and breeding of high-yielding varieties. However, the potato crop, as with many other agricultural crops, is susceptible to devastation by various diseases. Potato diseases reduce the yield and quality of fresh produce and therefore pose a threat to food security. Potato tuber blemishes constitute a persistent quality problem in the production of potato and contribute to major economic losses in South Africa and globally. They can cause severe yield losses, rejection of seed batches, downgrading of potatoes on the market, or rejection of potatoes for processing. The demand for washed potatoes by South African consumers highlights the problem of blemished tubers. It is important for farmers to optimise their disease management strategies to avoid yield losses and downgrading of tubers in the fresh produce market in South Africa.
A de novo 2.2 Mb recurrent 17q23.1q23.2 deletion unmasks novel putative regulatory non-coding SNVs associated with lethal lung hypoplasia and pulmonary hypertension : a case report
(BioMed Central, 2020-03-06) Karolak, Justyna A.; Gambin, Tomasz; Honey, Engela M.; Slavik, Tomas; Popek, Edwina; Stankiewicz, Paweł
BACKGROUND : Application of whole genome sequencing (WGS) enables identification of non-coding variants that play a phenotype-modifying role and are undetectable by exome sequencing. Recently, non-coding regulatory single nucleotide variants (SNVs) have been reported in patients with lethal lung developmental disorders (LLDDs) or congenital scoliosis with recurrent copy-number variant (CNV) deletions at 17q23.1q23.2 or 16p11.2, respectively. CASE PRESENTATION : Here, we report a deceased newborn with pulmonary hypertension and pulmonary interstitial emphysema with features suggestive of pulmonary hypoplasia, resulting in respiratory failure and neonatal death soon after birth. Using the array comparative genomic hybridization and WGS, two heterozygous recurrent CNV deletions: ~ 2.2 Mb on 17q23.1q23.2, involving TBX4, and ~ 600 kb on 16p11.2, involving TBX6, that both arose de novo on maternal chromosomes were identified. In the predicted lung-specific enhancer upstream to TBX4, we have detected seven novel putative regulatory non-coding SNVs that were absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. CONCLUSIONS : Our findings further support a recently reported model of complex compound inheritance of LLDD in which both non-coding and coding heterozygous TBX4 variants contribute to the lung phenotype. In addition, this is the first report of a patient with combined de novo heterozygous recurrent 17q23.1q23.2 and 16p11.2 CNV deletions.
The diagnosis of clinically significant oesophageal Candida infections : a reappraisal of clinicopathological findings
(Wiley, 2020-04) Hissong, Erika; Schechter, Shula; Mowers, Jonathan; Yantiss, Rhonda.K.; Slavik, Tomas; Cheng, Jerome; Lamps, Laura W.
AIMS : Distinguishing true oesophageal Candida infections from oral contaminants is a common diagnostic issue. Historically, histological features believed to indicate true infection included epithelial invasion by pseudohyphae and intraepithelial neutrophils. Whether or not these features correlate with endoscopic lesions, symptoms and response to therapy has never been tested in a large cohort. The aim of this study was to determine whether specific histological features correlate with clinical and endoscopic findings when Candida is found in oesophageal biopsies. METHODS AND RESULTS : We reviewed 271 biopsies in which Candida was detected. Cases were evaluated for the presence of desquamated epithelial cells, location/type of fungal forms, neutrophils, and ulceration. Medical records were reviewed for clinical history, endoscopic lesions, and response to antifungal therapy. Statistical analysis was used to determine whether any histological features significantly correlated with clinical variables. There were 120 males and 151 females with a mean age of 42 years. Fifty‐nine per cent had symptoms referable to the oesophagus, particularly dysphagia (36%). Most (73%) patients had abnormal endoscopic findings, with plaques, ulcers, or macroscopic evidence of oesophagitis. Seventy‐one per cent of patients with documented antifungal therapy showed symptomatic improvement. Overall, there was no statistically significant correlation between any histological feature and presenting symptoms, endoscopic findings, or response to therapy. Importantly, the lack of pseudohyphae, demonstrable invasion of intact epithelium or neutrophilic infiltrates did not exclude clinically significant infection. CONCLUSIONS : We conclude that detection of Candida in oesophageal biopsies is always potentially clinically significant. Treatment decisions should be made on the basis of an integration of clinical, endoscopic and histological findings.
Merkel cell carcinoma of the head in a young African Albino woman with HIV/HTLV-1 coinfection associated with multiple squamous cell carcinomas
(Karger, 2019) Tenea, Daniela; Dinkel, Jurgen Erich; Becker, Jurgen C.; Van der Walt, Elizabeth
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm of presumed neuroendocrine origin, with aggressive behavior and poor prognosis, that tends to have an increased incidence among elderly Caucasians and immunosuppressed individuals. MCC is either associated with a clonal integration of the Merkel cell polyoma virus into the host genome or with genomic alterations caused by chronic UV exposure. Tumors of either carcinogenesis show epithelial, neuroendocrine, and B-lymphoid lineage markers. HIV-infected African albinos have a higher risk of developing skin cancers, including MCC, in comparison with the general population. We report a case of MCC of the head in a young albino woman with a HIV/HTLV-1 coinfection. The patient also suffered from multiple squamous cell carcinomas of the scalp, face, lip, and ears, suggesting an UV carcinogenesis of MCC. The purpose of this case report is to emphasize the relationship between immunosuppression (HIV/HTLV-1 coinfection, chronic sun exposure, ocular-cutaneous albinism, pregnancy) and MCC. It highlights the importance of early diagnosis, dermatological screening with a risk-stratified surveillance, particularly in immunosuppressed albino patients in sub-Saharan Africa, and multidisciplinary management of this biologically unique cutaneous cancer.

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