Diagnosis and Treatment of Kaposi Sarcoma Schneider, Johann W; Dittmer, Dirk P
American journal of clinical dermatology,
08/2017, Letnik:
18, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present ...with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy. Standard KS therapy has not changed in 20 years, but newer modalities are on the horizon and will be discussed.
Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for ...remaining LM poses a diagnostic challenge.
To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining.
This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME.
The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia (P = 0.009). The presence of melanocyte nests (P = 0.29) and pagetoid spread (P = 0.003) was the most reliable histological findings distinguishing LM from its mimics.
SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.
Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp ...viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.
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•Kaposi sarcoma (KS)-associated herpesvirus transgenic mice develop angiosarcomas•The murine angiosarcomas resemble human KS based on protein and RNA-seq analysis•All latent and some lytic viral genes are transcribed in murine KS
Kaposi sarcoma (KS)-associated herpesvirus causes KS. Sin et al. create an immunocompetent mouse model of KS using the entire 170,000 bp herpesvirus genome as transgene. Latent and some lytic viral genes are expressed in the tumor. By histology, protein markers, and RNA-seq, the murine angiosarcomas resemble human KS.
Superficial CD34 positive fibroblastic tumor is a rare low-grade neoplasm of the skin and subcutis with indolent behavior. This entity has been included in the current World Health Organisation (WHO) ...classification of soft tissue tumors. Pathological diagnosis can be challenging due to significant morphological overlap with other entities and the large spectrum of CD34 positive tumors. We report a case in a twenty-five male which showed characteristic diagnostic features, but in addition showed myxoid stroma. The presence of myxoid stroma has not been previously emphasized in this entity and broadens the histologic differential diagnosis significantly to include myxoid soft tissue tumors. A subset of these tumors harbor PRDM10-rearrangements, but a defining molecular feature has not yet been described, highlighting the need for further molecular characterization of this potentially genetically heterogenous tumor. Awareness of this entity among surgeons and pathologists is important to prevent misclassification as an aggressive sarcoma and avoid over-treatment.
A pathology-supported genetic testing (PSGT) framework was established in South Africa to improve access to precision medicine for patients with breast carcinomas. Nevertheless, the frequent ...identification of variants of uncertain significance (VUSs) with the use of genome-scale next-generation sequencing has created a bottleneck in the return of results to patients. This review highlights the importance of incorporating functional genomics into the PSGT framework as a proposed initiative. Here, we explore various model systems and experimental methods available for conducting functional studies in South Africa to enhance both variant classification and clinical interpretation. We emphasize the distinct advantages of using in vitro, in vivo, and translational ex vivo models to improve the effectiveness of precision oncology. Moreover, we highlight the relevance of methodologies such as protein modelling and structural bioinformatics, multi-omics, metabolic activity assays, flow cytometry, cell migration and invasion assays, tube-formation assays, multiplex assays of variant effect, and database mining and machine learning models. The selection of the appropriate experimental approach largely depends on the molecular mechanism of the gene under investigation and the predicted functional effect of the VUS. However, before making final decisions regarding the pathogenicity of VUSs, it is essential to assess the functional evidence and clinical outcomes under current variant interpretation guidelines. The inclusion of a functional genomics infrastructure within the PSGT framework will significantly advance the reclassification of VUSs and enhance the precision medicine pipeline for patients with breast carcinomas in South Africa.
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•Pathology-supported genetic testing can improve precision medicine in oncology.•Identifying variants of uncertain significance limits sequencing implementation.•Cross-disciplinary efforts are needed between healthcare and research facilities.•Access to functional genomics infrastructures will improve variant reclassification.•Accurate variant interpretations will enhance precision medicine outcomes.
Aims. Epstein-Barr virus (EBV) is causally associated with many hematolymphoid malignancies. This laboratory-based study aimed to establish the prevalence of EBV in plasma cell neoplasms in a large ...South African cohort and to determine whether there is any correlation between EBV-positivity and human immunodeficiency virus (HIV) status in patients with plasma cell neoplasms, including plasma cell myeloma and plasmacytoma (solitary plasmacytoma of bone and extraosseous plasmacytoma). Methods. This single-institution retrospective study included all patients with a histopathologic diagnosis of plasma cell neoplasm between 2003 and 2020. EBV-expression in the plasma cell neoplasms was assessed by EBV-encoded RNA (EBER) in situ hybridization (ISH) and correlated with HIV status. HIV status was determined by retrieving prior serologic results. Formalin-fixed paraffin-embedded tissue from HIV-unknown patients underwent HIV-1 p24 antibody testing. Results. Sixteen of 89 plasma cell neoplasms (18%) were EBV-positive. There was a significant correlation between EBV and HIV infection in plasma cell neoplasms, with 6/10 tumors from HIV positive patients showing EBV-positivity in tumor cells. The EBV-positive cohort was significantly younger than the EBV-negative group. Conclusion. EBV-positivity in plasma cell neoplasms in this study is higher than previously reported. The significant occurrence of EBV in plasma cell neoplasms from HIV-positive patients suggests a co-carcinogenic relationship between the two viruses.
Background
To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic ...features of HPV-associated lip SCC.
Methods
Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV.
Results
p16 was positive in 22% (
n
= 11) and equivocal in 4% (
n
= 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%.
Conclusion
Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.
Observations from Raman backscatter-based Fiber-Optic Distributed Sensing (FODS) require reference sections of the fiber-optic cable sensor of known temperature to translate the primary measured ...intensities of Stokes and anti-Stokes photons to the secondary desired temperature signal, which also commonly forms the basis for other derived quantities. Here, we present the design and the results from laboratory and field evaluations of a novel Solid-Phase Bath (SoPhaB) using ultrafine copper instead of the traditional mechanically stirred liquid-phase water bath. This novel type is suitable for all FODS applications in geosciences and industry when high accuracy and precision are needed. The SoPhaB fully encloses the fiber-optic cable which is coiled around the inner core and surrounded by tightly interlocking parts with a total weight of 22 kg. The SoPhaB is thermoelectrically heated and/or cooled using Peltier elements to control the copper body temperature within ±0.04 K using commercially available electronic components. It features two built-in reference platinum wire thermometers which can be connected to the distributed temperature sensing instrument and/or external measurement and logging devices. The SoPhaB is enclosed in an insulated carrying case, which limits the heat loss to or gains from the outside environment and allows for mobile applications. For thermally stationary outside conditions the measured spatial temperature differences across SoPhaB parts touching the fiber-optic cable are <0.05 K even for stark contrasting temperatures of ΔT> 40 K between the SoPhaB’s setpoint and outside conditions. The uniform, stationary known temperature of the SoPhaB allows for substantially shorter sections of the fiber-optic cable sensors of less than <5 bins at spatial measurement resolution to achieve an even much reduced calibration bias and spatiotemporal uncertainty compared to traditional water baths. Field evaluations include deployments in contrasting environments including the Arctic polar night as well as peak summertime conditions to showcase the wide range of the SoPhaB’s applicability.
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