Aims
Genetic heterogeneity can pose a challenge to identifying eligible cases for targeted therapy in the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 2+ breast ...carcinoma group. In this study, we characterised this subset of tumours according to clinicopathological parameters.
Methods and results
We assessed 1000 tumour cells per case and recorded the number of HER2 and chromosome enumeration probe 17 (CEP17) copies using gene–protein assay slides. HER2 status was determined based on ASCO/CAP 2013 guidelines. Tumours with 5–50% of cancer cells with amplification were considered to be heterogeneous, whereas those with >50% were considered to be non‐heterogeneous. In a study cohort of 110 HER2 IHC 2+ carcinomas, 93 (84.5%) were non‐amplified, 12 (10.9%) were amplified and five (4.5%) were ISH‐equivocal. All the HER2‐amplified and two of ISH‐equivocal cases (12.7%) corresponded to non‐heterogeneous tumours, with highly significant differences evident in the average HER2/CEP17 ratio (P = 0.0002) and the proportion of cells with HER2 >6 copies (P < 0.0001) compared with heterogeneous lesions. NST grade 3 and HER2‐amplified carcinomas average HER2/CEP17 ratio correlated with an increased number of cells with HER2/CEP17 ≥2.0 (P < 0.014). Triple‐negative CEP17 polysomic carcinomas showed increased metastatic capacity (P = 0.003) compared with other tumour types.
Conclusion
Non‐heterogeneous HER2 IHC 2+ tumours tend to be HER2‐amplified. Adding the percentage of cells with HER2 >6 copies to the average HER2/CEP17 ratio may facilitate assessment of amplification status in ISH‐equivocal cases. The proportion of cells with HER2/CEP17 ≥2.0 contributes information concerning the actual average HER2/CEP17 ratio, depending on tumour type.
Aims
To determine the volume of tumoral and normal breast tissue containing sufficient DNA (>2 μg/sample) for genetic platforms and biobanking, with a focus on multifocality, tumoral heterogeneity, ...and factors that critically influence sample acceptability.
Methods and results
We examined 57 breast surgical specimens with multifocal (46/57) and unifocal (11/57) cancers. Punch biopsies were obtained from tissue slices under multimodal radiological guidance, and the colour‐coded sampling sites were identified in large‐format histology slides. The study comprised 415 DNA isolations from tumour (n = 105) and normal (n = 283) tissue, including skin (n = 27) samples. A single 2‐mm core from invasive tumour contained sufficient DNA in 91.4% (96/105) of cases, depending on tumour type (3.8–108.2 μg/sample), number and size of additional foci in multifocal cases (P = 0.001), tumour consistency, and degree of necrosis. Three biopsies obtained with a 4‐mm device were required from normal breast tissue, at least 10 mm from the tumour. Cold ischaemia for up to 82 min did not influence the yield of DNA.
Conclusions
Radiological disease mapping is useful for guiding optimal specimen slicing and for targeting breast lesions. A single 2‐mm core from tumour and multiple 4‐mm cores from normal breast tissue yield adequate DNA in the majority of samples.
Pityriasis rubra pilaris is an inflammatory dermatologic disorder of unknown cause and often confounded with psoriasis. It is characterised by hyperkeratotic follicular papules, scaly erythematous ...plaques, palmoplantar keratoderma, and a progression to generalised erythroderma. Here, we report the case of a 68-year-old man with pityriasis rubra pilaris, who was successfully treated with ixekizumab, an interleukin-17A inhibitor.
Although virus-negative Merkel cell carcinoma (MCC) is characterized by a high frequency of UV-induced mutations, the expression of two viral oncoproteins is regarded as a key mechanism driving ...Merkel cell polyomavirus‒positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC), suggesting (i) coincidental collision, (ii) one providing a niche for the other, or (iii) one evolving from the other. Whole-exome sequencing of four combined tumors consisting of SCC in situ and Merkel cell polyomavirus‒negative MCC showed many mutations shared between SCC and MCC in all cases, indicating a common ancestry and thereby a keratinocytic origin of these MCCs. Moreover, analyses of the combined cases as well as of pure SCC and MCC suggest that RB1 inactivation in SCC facilitates MCC development and that epigenetic changes may contribute to the SCC/MCC transition.
Decorative tattooing is a procedure in which exogenous pigment and/or dye is introduced into the dermis with the aim of creating a permanent skin decoration. The increasing prevalence of tattooed ...individuals leads to more reported tattoo-related complications. Pseudolymphomatous reaction is a benign reactive proliferation of lymphocytes that may uncommonly occur secondary to tattooing. We describe the clinical, histological, and molecular aspects of a pseudolymphomatous reaction to red tattoo pigment.
An update on cutaneous vascular tumours Marušić, Zlatko; Pekar-Lukacs, Agnes; Calonje, Eduardo
Diagnostic histopathology (Oxford, England : 2008),
January 2022, 2022-01-00, Letnik:
28, Številka:
1
Journal Article
Recenzirano
The classification of vascular lesions is complex. There is a slight overlap between reactive, developmental and benign vascular tumours, and some conditions defy precise classification. This review ...follows the most recent World Health Organization (WHO) classification of cutaneous vascular tumors and provides the framework for a systematic study, incorporating as many recent advances in molecular and immunohistochemical diagnostics as possible at this moment in time.
The adaptive matched filter (AMF) is a method widely used in spectral unmixing to classify different tissue chromophores in photoacoustic images. However, a threshold needs to be applied to the AMF ...detection image to distinguish the desired tissue chromophores from the background. In this study, we propose an automatic threshold selection (ATS) algorithm capable of differentiating a target from the background, based on the features of the AMF detection image. The mean difference between the estimated thickness, using the ATS algorithm, and the known values was 0.17 SD (0.24) mm for the phantom inclusions and -0.05 SD (0.21) mm for the tissue samples of malignant melanoma. The evaluation shows that the thickness and the width of the phantom inclusions and the tumors can be estimated using AMF in an automatic way after applying the ATS algorithm.
Radical excision of periorbital skin tumors is difficult without sacrificing excessive healthy tissue. Photoacoustic (PA) imaging is an emerging non-invasive biomedical imagi--ng modality that has ...potential for intraoperative micrographic control of surgical margins. This is the first study to assess the feasibility of PA imaging for the detection of periocular skin cancer. Eleven patients underwent surgical excision of periocular skin cancer, one of which was a malignant melanoma (MM), eight were basal cell carcinomas (BCCs), and two squamous cell carcinomas (SCCs). Six tumors were located in the eyelid, and five in periocular skin. The excised samples, as well as healthy eyelid samples, were scanned with PA imaging postoperatively, using 59 wavelengths in the range 680-970 nm, to generate 3D multispectral images. Spectral unmixing was performed using endmember spectra for oxygenated and deoxygenated Hb, melanin, and collagen, to iden--tify the chromophore composition of tumors and healthy eyelid tissue. After PA scanning, the tumor samples were examined histopathologically using standard hematoxylin and eosin staining. The PA spectra of healthy eyelid tissue were dominated by melanin in the skin, oxygenated and deoxygenated hemoglobin in the orbicularis oculi muscle, and collagen in the tarsal plate. Multiwavelength 3D scanning provided spectral information on the three tumor types. The spectrum from the MM was primarily reconstructed by the endmember melanin, while the SCCs showed contributions primarily from melanin, but also HbR and collagen. BCCs showed contributions from all four endmembers with a predominance of HbO
and HbR. PA imaging may be used to distinguish different kinds of periocular skin tumors, paving the way for future intraoperative micrographic control.
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