Oral mucosal lesions associated with smokers and chewersa casecontrol study in chennai population. The lesion is acanthotic and hyperkeratotic with variable degree of papillomatosis and/or invagination (Figure 8, A).76,79 The histopathologic pattern is that of epidermolytic hyperkeratosis (EHK), in which the keratinocytes in the granular and spinous layers display cytoplasmic vacuolation, reticular degeneration, coarse keratohyalin granules, and perinuclear eosinophilic inclusions (Figure 8, B).73,76,79 Despite superficial resemblance to koilocytosis, these unique characteristics of EHK effectively exclude condyloma acuminatum and VV. Bookshelf The best inter-observer diagnostic agreement relative to PVL lesions were classified as corrugated ortho(para)hyperkeratotic lesion, not reactive and SCC (chi-square p=0.015). On the other hand, bulky squamous epithelial proliferation that expands the epithelial thickness at least three-fold is concerning for developing ED. [43], Many endophytes protect plants from herbivory from both insects and animals by producing secondary metabolites that are either unappetizing or toxic to the herbivore. [51], A 2008 experiment with an isolate of a fungus called NRRL 50072 found that this strain can produce a small amount of fuel-like hydrocarbon compounds which was promoted as "myco-diesel". [73] Despite this, the interest and use of bio-insecticides and using endophytes to aid in plant growth is increasing as organic and sustainable agriculture is considered more important. It is 3 times more common in men than women, with a predisposition for immunocompromised individuals.20 Giant condyloma acuminatum often covers multiple anatomic structures owing to its large size, most frequently involving the penis and the anorectum. This drug is important for the treatment of cancer. PubMed WebVerrucous carcinoma is a type of squamous cell carcinoma (SCC) that can develop in your gums and cheeks the oral cavity as well as your genitals and feet. Endophytic fungi are ubiquitous to plants and are mainly members of Ascomycota or their mitosporic fungi, and some taxa of Basidiomycota, Oral Surg Oral Med Oral Pathol Oral Radiol. [10] Endophytes may become active and reproduce under specific environmental conditions or when their host plants are stressed or begin to senesce, thereby limiting the amount of carbon provided to the endophyte. Carrard VC, Brouns ER, van der Waal I. Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria. Endophytic Fungus - an overview | ScienceDirect Topics [67], An endophytic fungus of the genus Pseudomassaria has been found in the rainforest of the Democratic Republic of the Congo. [43][44][45][46][47][48][49] Use of endophytes might potentially increase crop yields. [22] Specifically, evidence points to endophytes producing ABA to affect stomatal conductance as well as microbial respiration and plants recycling CO2. Demonstration of HPV 2 or other nongenital HPV types in the absence of HPV 6 or 11, either by in situ hybridization or by PCR-DNA sequencing, would support a diagnosis of VV and exclude condyloma acuminatum.6872. B, Fibrovascular cores are present. [39] Systemic endophytes are defined as organisms that live within plant tissues for the entirety of its life cycle and participate in a symbiotic relationship without causing disease or harm to the plant at any point. While the basaloid subtype rarely mimics condyloma acuminatum, it shares overlapping features with the warty-basaloid subtype, which has a condyloma-like, verruciform silhouette (Figure 4, C).37 The epithelium is basaloid due to a high nuclear to cytoplasmic ratio and nuclear hyperchromasia (Figure 4, C; inset). Class 2 endophytes can grow in plant tissues both above and below ground. EXPLANATIONS TO PATIENTS OF COMMON PATH Mller S. Oral epithelial dysplasia, atypical verrucous lesions and oral potentially malignant disorders: focus on histopathology. J Oral Pathol Med. Endophytic fungi produce many secondary compounds such as alkaloids, triterpenes and steroids which have been shown to have anti-tumor effects. [65], Some of the antimicrobial compounds produced by endophytic fungi are of interest in their effectiveness against pathogens which have developed resistances to antibiotics. Web18.2 Endophytic Fungal Diversity. The first method divides endophytes into two categories: systemic (true) and nonsystemic (transient). D, There is strong and diffuse p16 immunostaining within the lesion (hematoxylin-eosin, original magnifications 20 [A], 200 [B], 40 [C], and 200 [C, inset]; original magnification 100 [D]). Epub 2020 Oct 16. However, in contrast with condyloma acuminatum, which is typically caused by HPV types 6 and 11, VV is most commonly induced by HPV 2, followed by HPV 1, 4, 65, 27, and others.68,69 Distinction of VV and condyloma acuminatum has important clinical implication especially in the pediatric population, as condyloma acuminatum would raise suspicion for sexual abuse, whereas VV is nonsexually transmitted. Proliferative verrucous leukoplakia (PVL) is a spectrum disorder of the oral mucosa that shows characteristic, focal when early, adherent multifocal and 2019;13(4):5739. [42], Endophytes may have potential future applications in agriculture. 2010;15(6):e83945. They typically colonize plant shoots where they form a systemic intercellular infection. 2007;43(3):22431. Med Oral Patol Oral Cir Bucal. J Int Acad Periodontol. 2004;40(4):4403. [69] Piriformospora indica is an interesting endophytic fungus of the order Sebacinales, the fungus is capable of colonising roots and forming symbiotic relationship with many plants. These endophyte plant interactions are widespread and have been found in nearly all land plants and ecosystems. 2023 Springer Nature Switzerland AG. Indian J Dent Res. 2015;120(4):47482. PubMed Central Cases associated with high-grade intraepithelial neoplasia and warty/basaloid squamous cell carcinoma (SCC) are coinfected with high-risk HPV types.68. Pathol Res Pract. The histopathologic features of epidermolytic acanthoma frequently raise suspicion for condyloma acuminatum or VV to the untrained eye. Inter- and intra-observer variability in diagnosis of oral dysplasia. Condyloma acuminatum. Vulvar seborrheic keratosis: is there a relationship to human papillomavirus? [55], Two strains of the endophytic fungi Pestalotiopsis microspora isolated from stems of plants from the Ecuadorian rainforest were shown in laboratory experiments to be able to digest polyurethane plastic as the fungus's sole carbon source in anaerobic conditions, although many other non-endophytic fungi have demonstrated this ability, and most isolates of endophytic fungi in this experiment could perform this to some degree. Figure 7Verruca vulgaris. Clinically, warty and warty-basaloid HSIL and invasive SCC may mimic condyloma acuminatum when discrete papillomatous papules or plaques are present.44, On histopathology, warty HSIL and SCC mimic condyloma acuminatum by their verruciform architecture, conspicuous fibrovascular cores, and koilocytosis (Figure 4, A). Seborrheic keratoses that contain human papillomavirus are condylomata acuminata, MIB-1 immunostaining is a beneficial adjunct test for accurate diagnosis of vulvar condyloma acuminatum, P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction, Expression of p16 protein in lesional and perilesional condyloma acuminata and bowenoid papulosis: clinical significance and diagnostic implications, Detecting HPV in cutaneous lesions using anti-HPV antibody immunohistochemistry, Giant condyloma acuminatum of the anorectum: trends in epidemiology and management: report of a case and review of the literature, Giant condyloma acuminatum (Buschke-Lowenstein tumor) of the anorectal and perianal regions: analysis of 42 cases, Giant condyloma acuminata of the inguinal region, Giant condyloma acuminatum of the scrotum, bilateral groins, and suprapubic region: a treatment and reconstruction challenge, Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma, Anal verrucous carcinoma is not related to infection with human papillomaviruses and should be distinguished from giant condyloma (Buschke-Lwenstein tumour), Rapidly invasive Buschke-Lwenstein tumor associated with human papillomavirus types 6 and 52, Giant condyloma versus verrucous carcinoma: a case report, Morphologic and biologic studies on ten cases of verrucous carcinoma of the vulva supporting the theory of a discrete clinico-pathologic entity. doi: https://doi.org/10.5858/arpa.2018-0039-RA. London: Wiley; 1981. Compared to condyloma acuminatum, the fibrovascular cores in papillary SCC are more irregular, and the tumor base is ragged (owing to stromal invasion) as opposed to round.37,51 It also differs from condyloma acuminatum and warty/warty-basaloid squamous neoplasms by the absence of koilocytes (Figure 5, B). Davidova LA, Fitzpatrick SG, Bhattacharyya I, Cohen DM, Islam MN. This is a small series. Statistical analysis of inter-rater agreement was provided by Sijia Yue, MS at the University of Florida College of Public Health and Health Professions Department of Biostatistics. Proliferative verrucous leukoplakia: diagnosis, management and current advances. Capella DL, Gonalves JM, Abrantes AAA, Grando LJ, Daniel FI. [24] However, unique to this experiment was the mode by which this was thought to happen. Oral Surg Oral Med Oral Pathol Oral Radiol. There was moderate agreement (>0.41 kappa) for 35 of 48 cases. government site. Bagan JV, Murillo J, Poveda R, et al. Endophytes can extensively colonize plant tissues and competitively exclude other potential pathogens. [42] Class 3 endophytes are restricted to growth in above ground plant tissues and form in localized areas of plant tissue. Oral epithelial dysplasia and premalignancy. Biopsy shows an endophytic squamous cell proliferation extending to the deep margin. J Cutan Pathol. The large tumor mass compresses but does not infiltrate normal structures. [4] Vertically transmitted fungal endophytes are typically considered clonal and transmit via fungal hyphae penetrating the embryo within the host's seeds, while reproduction of the fungi through asexual conidia or sexual spores leads to horizontal transmission, where endophytes may spread between plants in a population or community. 2019;13(3):42339. Verrucous Carcinoma 2017;83(5):58593. The use of fungicides has a negative effect on endophytic fungi and fertilizers reduce a plant's dependence on its endophytic symbiont. Cabay RJ, Morton TH Jr, Epstein JB. [16] Studies have also shown that during experimental circumstances endophytes contribute significantly to plant growth and fitness under light-limited conditions, and plants appear to have increased reliance on their endophytic symbiont under these conditions. The adjacent epidermis is acanthotic but not dysplastic. B, Koilocytosis and cytologic atypia are readily appreciated in this warty squamous cell carcinoma. Head and Neck Pathology Mitoses are rare and confined to the basal layer.25 A band of lymphocytic infiltrate is usually found at the base of the tumor (Figure 3, A). This neoplasm typically This supports the hypothesis that plant signaling is required in order to induce expression of endophytic secondary metabolites. Keywords: Endophyte - Wikipedia This is a preview of subscription content, access via your institution. Zain RB, Kallarakkal TG, Ramanathan A, et al. Epub 2011 Feb 22. Part of Springer Nature. 2006;8(2):6770. Oral Surg Oral Med Oral Pathol Oral Radiol. Copyright 2017 American Academy of Dermatology, Inc. Woo SB, Grammer RL, Lerman MA. Proliferative verrucous leukoplakia and field cancerization: report of a case. The papillae have mostly rounded tips and prominent fibrovascular cores. sharing sensitive information, make sure youre on a federal Speight PM, Abram TJ, Floriano PN, et al. This enhanced survivability is largely attributed to endophytic production of secondary metabolites which protect against herbivory as well as increased uptake of nutrients. Papillomatous and endophytic squamous proliferation is present with keratin plug, parakeratin, and mild pleomorphism of keratinocytes extending to the base of the biopsy (a). Likewise, Ki-67 positivity is mainly observed in the basal layer.28 Absence of HPV may be confirmed by PCR-DNA sequencing, in situ hybridization, or immunohistochemistry.24,25,28,30, Infection by high-risk HPV, most commonly HPV 16 and less commonly HPV 18, 31, 33, 45, 51, 52, and 59 amongst others, causes undifferentiated intraepithelial neoplasia (-IN) of the vulva, vagina, penis, scrotum, and anus.3842 These HPV-related squamous intraepithelial lesions may be subclassified into warty, basaloid, and warty-basaloid types by histopathologic features. 2009 Aug;26(3):150-63. doi: 10.1053/j.semdp.2009.09.003. C, A defining feature is the presence of xanthomatous (foam) cells in the dermal papillae (hematoxylin-eosin, original magnifications 40 [A], 200 [B], and 400 [C]). [28] One group of fungal endophytes are the arbuscular mycorrhizal fungi involving biotrophic Glomeromycota associated with various plant species. Oral Dis. - 213.202.212.252. and transmitted securely. A, Portion of a large, mostly exophytic, and papillomatous lesion with a cauliflower-like silhouette. Gonzlez-Moles M, Ruiz-vila I, Gonzlez-Ruiz L, et al. Iocca O, Sollecito TP, Alawi F, et al. Bulky squamous epithelial proliferation with an exophytic and/or endophytic growth pattern (the former often associated with corrugated/verrucous/papillary architecture). Compared to the spiky papillae in verruca vulgaris (VV), the papillae in condyloma acuminatum have more rounded and undulating contours, with less robust hyperkeratosis (Figure 1, A). Upadhyaya JD, Fitzpatrick SG, Islam MN, Bhattacharyya I, Cohen DM. Squamous J Periodontol. To review the overlapping and distinguishing features of condyloma acuminatum and its mimics, and to clarify confusing terminology and diagnostic criteria for problematic entities. HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis, The association of lichen planus of the penis with squamous cell carcinoma in situ and with verrucous squamous carcinoma, Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma, Verrucous carcinoma of the skin and mucosa, Surgical treatment for 11 cases of penile verrucous carcinoma, Verrucous carcinoma: clinical and pathologic study of 105 cases involving oral cavity, larynx and genitalia, Diagnostic problems in precancerous lesions and invasive carcinomas of the penis, Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16(INK4A) overexpression and clinicopathological correlations, Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva, Prevalence and distribution of 15 high-risk human papillomavirus types in squamous cell carcinoma of the scrotum, Histologic classification of penile intraepithelial neoplasia, The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions, The Lower Anogenital Squamous Terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology, Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients, Warty (condylomatous) squamous cell carcinoma of the penis: a report of 11 cases and proposed classification of verruciform' penile tumors, Squamous cell carcinoma of the vulva: a subclassification of 97 cases by clinicopathologic, immunohistochemical, and molecular features (p16, p53, and EGFR), p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas, Distinctive association of p16INK4a overexpression with penile intraepithelial neoplasia depicting warty and/or basaloid features: a study of 141 cases evaluating a new nomenclature, Distinctive immunohistochemical profile of penile intraepithelial lesions: a study of 74 cases, Anal intraepithelial neoplasia: a single centre 19 year review, Papillary squamous cell carcinoma, not otherwise specified (NOS) of the penis: clinicopathologic features, differential diagnosis, and outcome of 35 cases, Bowenoid papulosis: a clinicopathologic study with ultrastructural observations, Bowenoid papulosis: clinical and histological study of eight cases, Bowenoid papulosis: presence of human papillomavirus (HPV) structural antigens and of HPV 16-related DNA sequences, Bowenoid papulosis of the vulva-immunotherapeutical approach with topical imiquimod, Photodynamic therapy for bowenoid papulosis using a novel incoherent light-emitting diode device, Extensive genital bowenoid papulosis responding to imiquimod, Aminolevulinic acid photodynamic therapy for bowenoid papulosis, Bowenoid papulosis: classification as a low-grade in situ carcinoma of the epidermis on the basis of histomorphologic and DNA ploidy studies, Bowenoid papulosis of the male and female genitalia: risk of cervical neoplasia, Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma, Morphometric assessment of nuclei in Bowen's disease and bowenoid papulosis, The presence of HPV types 6/11, 16/18, 31/33/51 in Bowenoid papulosis demonstrated by DNA in situ hybridization, Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin, Expression of p16 and hTERT protein is associated with the presence of high-risk human papillomavirus in Bowenoid papulosis, A genotype distribution of human papillomaviruses detected by polymerase chain reaction and direct sequencing analysis in a large sample of common warts in Japan, Development of a multiplex PCR method for detecting and typing human papillomaviruses in verrucae vulgaris, Verruca vulgaris of the vulva in children and adults: a nonvenereal type of vulvar wart, Human papillomavirus segregation patterns in genital and nongenital warts in prepubertal children and adults, Immunohistochemistry and polymerase chain reaction for detection human papilloma virus in warts: a comparative study, Multiple epidermolytic acanthomas must not be confused with genital human papillomavirus infection, Epidermolytic acanthoma of the scrotum: a rare mimicker of condyloma acuminatum, Multiple localized epidermolytic acanthomas of the vulva associated with vulvar pruritus: a case report, Multiple epidermolytic acanthomas mimicking condyloma: a retrospective study of 8 cases, Epidermolytic acanthoma does not contain human papillomavirus DNA. Reverse maturation and stromal invasion, when present, should raise concern for malignant transformation.21,27 Immunohistochemical profile, including negative, focal, or patchy staining for p16, is the same as described in ordinary condyloma acuminatum.24, Verrucous carcinoma is a unique variant of well-differentiated SCC. Endophytic type squamous cell papilloma, is continuous with the adjacent hyperplastic epidermis and a crater forms by invagination with no pedicle. This endophytic type has neither invasive nor compressive growth into surrounding tissues. official website and that any information you provide is encrypted Weba solid nodular form, which is largely endophytic with solid, lobulated masses of epithelium 4. an uncommon cystic type, with irregular clefts within the tumor and the formation of 2008 Apr;30(2):127-34. doi: 10.1097/DAD.0b013e318161310c. Patients typically present with multiple red-brown or violaceous papules on penile or vulvar skin, although any anogenital sites may be affected. [1], Endophytes were first described by the German botanist Johann Heinrich Friedrich Link in 1809. Histologic distinction between condyloma acuminatum and various benign and malignant condyloma-like lesions in the anogenital area poses a common diagnostic challenge to pathologists across subspecialties. [20] Specific endophyte species can also stimulate root growth by increasing the flux of auxin to where the endophyte is. Google Scholar. National Library of Medicine In this series, The author has no relevant financial interest in the products or companies described in this article. The presence of these metabolites in plants could be attributable to endophyte production alone, or to combined endophyte and plant production following transfer of the corresponding genes from endophyte to plant or vice versa. These features impart a firm and rigid appearance at low magnification, which contrasts with the soft appearance of giant condyloma acuminatum. Karabulut A, Reibel J, Therkildsen MH, et al. Template:Squamous-cell like skin proliferations - Patholines 1. PubMed J Oral Pathol Med. A case of multiple epidermolytic acanthoma of the scrotum: is the human papillomavirus a culprit? The keratinocytes are bland and without koilocytic change. Cutaneous Pseudoepitheliomatous Hyperplasia from a Displaced Because histopathologic findings can vary in women with multiple SCC lesions, from keratoacanthoma-like to well-differentiated SCC, we hypothesized that TP53 variants might shed light on the appropriate classification. Head and Neck Pathol 15, 572587 (2021). [62], Endophytes have been discovered with various anti-tumor properties. Both condyloma acuminatum and VV are caused by low-risk HPV. WebHistologically, it is characterized by stratified squamous epithelium with few atypical cells. Biopsy of a lesion in the right proximal pretibial region demonstrated an atypical endophytic squamous proliferation, consistent with SCC. [11][12], Endophytes may benefit host plants by preventing other pathogenic or parasitic organisms from colonizing them. The ecological roles of these fungi are diverse and still poorly understood. Frictional keratoses on the facial attached gingiva are rare clinical findings and do not belong to the category of leukoplakia. [19], There are various behaviors that have been studied that resulted from endophyte symbiosis with plants. Squamous keratinocytes are more common in this variant compared to basaloid cells. Case 2. Connolly M, Narayan S, Oxley J, de Berker DA. Histologic lichenoid features in oral dysplasia and squamous cell carcinoma. A lymphocytic band is present at the tumor base. Parakeratosis is usually more abundant than in condyloma acuminatum.37 The key distinguishing feature is the presence of cytologic atypia in that the keratinocytes in the lower epithelium are enlarged and pleomorphic (Figure 4, B). It was first misidentified as the endophyte Gliocladium roseum, but later research showed that it was in fact the saprophyte Ascocoryne sarcoides. Interobserver and intraobserver variability in the histologic assessment of oral lichen planus. These findings suggest that some cutaneous squamous proliferations on the legs of women with multiple lesions lack prominent cytologic atypia as well as TP53 mutations and might be more akin to keratoacanthoma than SCC or might represent a reactive phenomenon. 2019;96:12130. Woo SB. Proliferative Verrucous Leukoplakia: An Expert The .gov means its official. Non-clavicipitaceous endophytes are typically Ascomycota fungi. Oral Surg Oral Med Oral Pathol Oral Radiol. and have shown cytotoxicity against human leukemia (K-562). As a general rule, anogenital SK-like lesions with an undulating appearance (Figure 1, C), with or without pseudohorn cysts, are probably best treated as condyloma acuminatum, as opposed to those with a flat base.15, Pirog et al16,17 have found positive Ki-67 (MIB-1) immunostaining, defined as any cluster of at least 2 positive nuclei in the upper two-thirds of the epithelium, in all vulvar and anal condylomas examined, a finding that correlated well with positive HPV results by polymerase chain reaction (PCR) and DNA sequencing. 2007;36(5):25561. The most comprehensive study reported 35 cases of penile papillary SCC, most of which occurred on the glans with or without involvement of the coronal sulcus and foreskin.51 The tumors form white-grey, irregular masses with serrated surfaces. Background: Tongue squamous cell carcinoma (TSCC) is highly diverse, even in its early stages. Villa A, Menon RS, Kerr AR, et al. Conclusion: [30], One or more endophytic organisms are found in nearly every land plant. Endophytic proliferation composed of basaloid and 2017;30(s1):S5467. Oral Surg Oral Med Oral Pathol. Med Oral Patol Oral Cir Bucal. [42] These four groups are divided into clavicipitaceous endophytes (Class 1) and non-clavicipitaceous endophytes (Class 2, 3, and 4). Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Direct immunofluorescence testing results in cases of premalignant and malignant oral lesions. Aside from koilocytosis, cytologic atypia is absent (Figure 2, B). The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. Verrucous carcinoma of the oral cavity. Approximately 40% of warts in the genital area of young girls are VV (positive for HPV 2) while the rest are condylomas (positive for HPV 6 or 11).70 The clinical morphologies of VV and condyloma acuminatum are similar in that both are exophytic and verrucous papules, but VV tends to be more hyperkeratotic than condyloma acuminatum. Federal government websites often end in .gov or .mil. A, A typical papillomatous papule with only mild hyperkeratosis. Histopathologically, VV is characterized by marked verruciform acanthosis and hyperkeratosis. 2006;17(3):1215. Methods: B, The lesion is diffusely positive for p16 (hematoxylin-eosin, original magnifications 40 [A] and 200 [A, inset]; original magnification 100 [B]). Classification of these lesions is often challenging owing to significant histopathologic overlap and sometimes controversial and confusing diagnostic criteria. 1995;80(2):18891. In-situ means the skin cancer it is an early forming skin cancer and is limited to the upper layers of the skin. Oral Oncol. Current agriculture relies heavily on fungicides and high levels of chemical fertilizers. Kujan O, Khattab A, Oliver RJ, et al. 1980;46(8):185562. [2] In exchange the endophyte receives carbon for energy from the plant host. Of these subtypes, the endophytic tumours have the worst prognosis because of their invasiveness and higher frequency of [57][58] Endophyte bioprospecting has already yielded compounds with antibacterial,[59][60] antifungal,[61] antiviral,[61] antiparasitic,[62] cytotoxic,[59][63] neuroprotective,[62] antioxidant,[62] insulin-mimetic,[62] -glucosidase inhibitory,[61] and immunosuppressant[62] properties.