Perineural Infiltration: A Comprehensive Review of Diagnostic, Prognostic, and Therapeutic Implications.

ABSTRACT: Perineural infiltration refers to a neoplastic cell involvement in, around, and through the nerves. It is considered as one of the neoplastic dissemination pathways. Thus, its identification is crucial to establish the prognosis of some malignant skin neoplasms, such as squamous cell carcinoma, and explains the locally aggressive behavior of cutaneous neoplasms, such as microcystic adnexal carcinoma. We have conducted a review of malignant and benign skin tumors in which perineural infiltration has been described, and we also discuss some histopathological findings that may simulate perineural infiltration.

Combined Merkel cell carcinoma and cutaneous squamous cell carcinoma with lymph node metastases: Report of two cases.

Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.

Identification of potential invasive alien species in Spain through horizon scanning.

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.

Usefulness of ultrasound in dermatofibrosarcoma protuberans and correlation with histopathological findings: A series of 30 cases.

BACKGROUND: Small series of ultrasound findings in dermatofibrosarcoma protuberans (DFSP) have been published, but the usefulness of this technique as a preoperative planning tool for tumor resection has not been studied. MATERIALS AND METHODS: We retrospectively reviewed patients with DFSP at our hospital that underwent ultrasound examination. Depth of invasion was evaluated by ultrasound and histopathology. Accuracy of ultrasound for assessing depth of tumor invasion was estimated. RESULTS: Thirty histopathologically confirmed DFSPs were studied. Classic finger-like projections were observed in 73.3% of cases. A posterior hyperechoic area extending deep into the subcutaneous tissue correlated with the honeycomb DFSP pattern and was observed in 53.3% of patients. Concordance between ultrasound and histopathologic depth measurements was excellent. Lateral tumor extension and Doppler activity were not evaluated in our series. CONCLUSION: Ultrasound showed excellent prediction of depth of invasion. Further studies are required to define the usefulness of ultrasound for determining lateral tumor extension.

Effects of sex ratio on different biological parameters of Engytatus varians (Distant) (Hemiptera: Miridae) adults and their offspring: prey preference for Bactericera cockerelli (Sulcer) (Hemiptera: Triozidae).

In the present study, the influence of three sex ratios (1:1, 1:2, and 1:3; female:male) of the mirid Engytatus varians (Distant) (Hemiptera) on different biological parameters and on its offspring was evaluated. The prey preference of different developmental stages of this predator for different nymphal instars (N) of Bactericera cockerelli (Sulcer) (Hemiptera: Triozidae) was also evaluated. The fertility was significantly higher (24 nymphs/female) in the 1:3 sex ratio than in the 1:1 and 1:2 sex ratios (14 and 16 nymphs/female, respectively). The females in the 1:1 and 1:2 sex ratios lived 1.14 and 1.43 days more (27 and 28 days, respectively) than those in the 1:3 sex ratio (26 days). The nymphs derived from the females of the three sex ratios (first filial generation, F1) had five instars and a duration of 17 or 18 days. The ratio of the F1 generation females was not affected by the sex ratio of their parents. In choice tests, independent of whether the preys were placed on a single or multiple tomato (Solanum lycopersicum L.) leaflets, the consumption of females and males and N3, N4, and N5 nymphs of E. varians on B. cockerelli, generally showed the order of N2>N3>N4>N5. In conclusion, the findings revealed in this study can help to improve the rearing methodology for increasing populations of E. varians. In addition, they can serve as a guideline for releasing this predator in times when there is an abundance of early instar nymphs of B. cockerelli.

Lethal and sublethal effects of pesticides on Chrysoperla carnea larvae (Neuroptera: Chrysopidae) and the influence of rainfastness in their degradation pattern over time.

The predator Chrysoperla carnea is a model species for the study of non-target effects of pesticides under different scenarios: registration of plant protection products under the European Union and effects of the Bt toxin. Laboratory and persistence studies were carried out with six pesticides currently used in corn crops in Spain that were applied at their maximum field recommended concentrations. The assessed end-points were larval mortality, survivorship until adult stage, duration of the larval and pupal periods, fecundity, fertility and sex ratio of the emerged adults. Based on the total effect (lethal and sublethal) caused to L3 larvae in contact with fresh residues in the laboratory, pendimethalin was harmless (IOBC 1), lambda-cyhalothrin, abamectin, and hexythiazox were slightly harmful (IOBC 2), deltamethrin was moderately harmful (IOBC 3) and chlorpyrifos was harmful (IOBC 4). Afterwards, the residues of the two most toxic pesticides in the lab (deltamethrin and chlorpyrifos) were aged under greenhouse conditions (22 ± 2 °C, 40 ± 10 % R.H., 16.9 µmol m(-2) s(-1) UV radiation) in the presence and absence of artificial rainfall (10 l m(-2) h(-1), applied 24 h after pesticide application). Deltamethrin was classified as short lived (IOBC A) in both cases. However, degradation of chlorpyrifos residues was accelerated in the presence of rainfall, leading to the classification as slightly persistent (IOBC B), while in absence of rainfall it behaved as persistent (IOBC D). Every pesticide can be recommended for inclusion in corn IPM programs where the predator is present except chlorpyrifos that exhibited high direct toxicity in the lab and prolonged residual action even in the presence of rainfall.

Impact of Feeding on Contaminated Prey on the Life Parameters of Nesidiocoris Tenuis (Hemiptera: Miridae) Adults.

Insecticide selectivity to natural enemies is an important concern in integrated pest management programs. Although there is a wide range of information concerning pesticide lethal and sublethal effects on contaminated surfaces, little is known when the route of exposure occurs at a trophic level. This study evaluates this route of pesticide intake on the omnivorous predator Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) for the first time. Under laboratory conditions, prey treated with six insecticides (flubendiamide, spirotetramat, deltamethrin, flonicamid, metaflumizone, and sulfoxaflor) were offered to N. tenuis adults for 3 days. Mortality (24, 48, and 72 h after treatment), offspring production (third until eighth day) and longevity were documented. Metaflumizone and sulfoxaflor were classified as moderately harmful products because although the percentage of mortality was only 28 and 36%, respectively, both products caused a severe decrease in offspring production and longevity. Flonicamid and flubendiamide were classified as slightly harmful products; although they did not have a lethal effect, sublethal impact was important on the parameters studied. Spirotetramat and deltamethrin were insecticides categorized as harmless. This information could be useful for selecting the most appropriate insecticides to control pests in tomato crops in which N. tenuis is a relevant biological control agent.

Are Mummies and Adults of Eretmocerus mundus (Hymenoptera: Aphelinidae) Compatible With Modern Insecticides?

The parasitic wasp Eretmocerus mundus (Mercet) is an important natural enemy of the widespread key pest Bemisia tabaci (Gennadius). The toxicity of 11 modern insecticides applied at their maximum field recommended rate in Spain was tested in two life stages of E. mundus: adults and mummies. Laboratory and persistence tests were conducted and effects assessed not only in terms of mortality but on reproductive performance as well. Some insecticides caused the same effect to both life stages: flubendiamide, methoxyfenozide, spiromesifen, and flonicamid were harmless, while spinosad and sulfoxaflor were harmful. The last two insecticides cannot be used jointly with E. mundus under any condition because they were highly persistent. The rest of tested insecticides (spirotetramat, metaflumizone, deltamethrin, abamectin, and emamectin) caused some direct mortality to one or both life stages and/or affected reproduction of the parasitic wasp and their harmful effect in the field ranged from short lived (metaflumizone and spirotetramat) to slightly persistent (emamectin) and to moderately persistent (abamectin and deltamethrin). Therefore, they could be recommended for use in integrated pest management programs together with the natural enemy if appropriate safety intervals after insecticide application are observed.

Combined Merkel Cell Carcinoma and Squamous Cell Carcinoma: A Systematic Review.

Combined Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) have classically been regarded as more aggressive than conventional, pure, Merkel cell polyomavirus (MCPyV)-positive MCC. It is still unknown whether combined MCC and SCC are more aggressive than pure, MCPyV-negative MCC, and the origin of both the SCC and MCC elements of these combined tumors has not been elucidated. The main objective of this systematic review was to assess whether combined MCC and SCC tumors are associated with a worse prognosis than pure MCC; the secondary goals were the characterization of the clinical and histopathological features of these combined neoplasms. A total of 38 studies, including 152 patients, were selected for review. In total, 76% of the cases were MCPyV-negative, whereas 4% were MCPyV-positive. The most frequent histopathological pattern was that of an SCC in situ combined with a dermal MCC (36%), followed by both an in situ and invasive SCC combined with a dermal MCC (20%). Forty-seven percent of all cases fitted in the morphology of the so-called "collision tumors". Three combined MCC cases that would fit in the morphological category of collision tumors presented both squamous and neuroendocrine elements in their respective nodal metastases. The mean overall survival was 36 months, comparable to that of pure, MCPyV-negative MCC. This review found similarly aggressive behavior for combined MCC and SCC and pure, MCPyV-negative MCC. Preliminary data strongly suggest that all MCPyV-negative MCC tumors, whether combined or pure, are part of a common spectrum.

Retrospective Case Series of Cocaine-Associated Plasma Cell Orificial Mucositis.

Importance: Plasma cell orificial mucositis (PCOM) associated with cocaine use is an emerging, rare condition that has become a concern in Spain in recent years. Limited knowledge exists regarding this novel condition. Objectives: To delineate the clinicopathologic characteristics of this emerging entity and establish a novel approach in the differential diagnosis of cocaine-associated lesions. Design, Setting, and Participants: A descriptive, retrospective, multicenter case series of 10 patients diagnosed with cocaine-associated PCOM was conducted in Spain from April 2020 to March 2023. Main Outcomes and Measures: Patient demographic, clinical, histopathologic, and treatment data were collected. Results: A total of 10 patients (6 [60%] male; median [range] age, 45.5 [36-66] years) presenting with exudative ulcerated plaques were identified for this study. The lesions had raised and erythematous edges over the nostril and a median (range) evolution time of 9 (2-24) months. Septal or palate perforations were observed in 4 (40%) of the patients. Biopsies revealed a dense inflammatory infiltrate of plasma cells in the dermis without atypia and with eosinophils. All patients reported recent cocaine use. Three urine tests detected cocaine but found no presence of amphetamines or opiates. Six patients improved with corticosteroid therapy. Up to 60% of patients were lost to follow-up. Conclusions and Relevance: This case series describes the clinicopathologic characteristics of PCOM, an emerging entity associated with cocaine use in Spain, and demonstrates a novel approach in the differential diagnosis of cocaine-associated lesions. To date, cocaine-associated skin lesions have been reported as neutrophilic dermatoses and vasculitis. The appearance of a plasma cell infiltrate changes what has been described in the medical literature so far. PCOM is a benign condition of unknown cause characterized by a proliferative polyclonal plasma cell infiltrate. A comprehensive differential diagnosis workup is required to reach this exclusionary diagnosis. Several irritants have been documented in cases of PCOM, and a hypersensitivity mechanism has been proposed. Since the initial report of cocaine-associated PCOM in Spain, its incidence has experienced a surge in the country. The cause of this phenomenon may be attributed to newly unidentified adulterants. The administration of corticosteroids and discontinuation of cocaine use are the sole treatments that have demonstrated efficacy. Clinicians should be vigilant regarding this emerging condition and conduct inquiries into cocaine use. Additional research is required to clarify the pathophysiology of this emerging condition.

Pesticide residues in nectar and pollen of melon crops: Risk to pollinators and effects of a specific pesticide mixture on Bombus terrestris (Hymenoptera: Apidae) micro-colonies.

Residues detected in pollen collected by honey bees are often used to estimate pesticide exposure in ecotoxicological studies. However, for a more accurate assessment of pesticides effect on foraging pollinators, residues found directly on flowers are a more realistic exposure approximation. We conducted a multi-residue analysis of pesticides on pollen and nectar of melon flowers collected from five fields. The cumulative chronic oral exposure Risk Index (RI) was calculated for Apis mellifera, Bombus terrestris and Osmia bicornis to multiple pesticides. However, this index could underestimate the risk since sublethal or synergistic effects are not considered. Therefore, a mixture containing three of the most frequently detected pesticides in our study was tested for synergistic impact on B. terrestris micro-colonies through a chronic oral toxicity test. According to the result, pollen and nectar samples contained numerous pesticide residues, including nine insecticides, nine fungicides, and one herbicide. Eleven of those were not applied by farmers during the crop season, revealing that melon agroecosystems may be pesticide contaminated environments. The primary contributor to the chronic RI was imidacloprid and O. bircornis is at greatest risk for lethality resulting from chronic oral exposure at these sites. In the bumblebee micro-colony bioassay, dietary exposure to acetamiprid, chlorpyrifos and oxamyl at residue level concentration, showed no effects on worker mortality, drone production or drone size and no synergies were detected when pesticide mixtures were evaluated. In conclusion, our findings have significant implications for improving pesticide risk assessment schemes to guarantee pollinator conservation. In particular, bee pesticide risk assessment should not be limited to acute exposure effects to isolated active ingredients in honey bees. Instead, risk assessments should consider the long-term pesticide exposure effects in both pollen and nectar on a range of bees that reflect the diversity of natural ecosystems and the synergistic potential among pesticide formulations.

Topical Imiquimod in Primary Cutaneous Extramammary Paget's Disease: A Systematic Review.

Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three-four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443.

Comparison of the Parasitization of Chelonus inanitus L. (Hymenoptera: Braconidae) in Two Spodoptera Pests and Evaluation of the Procedure for Its Production.

Chelonus inanitus (L.) is an egg-larval parasitoid of noctuids Spodoptera exigua (Hübner) and S. littoralis (Boisduval), whose mass rearing or real potential has not been targeted yet. To improve the rearing in the factitious host Ephestia kuehniella Zeller, we investigated the influence of host age and number of females parasitizing simultaneously on the overall rearing success, the influence of host age on the life cycle, and the influence of host species on the parasitoid body size. The proportion of emerging C. inanitus was higher from young host eggs, but more females emerged from mature eggs. Under high parasitoid competition, we observed a reduction in non-parasitized hosts without reducing parasitoid emergence. The parasitoid life cycle was longer in females, but the mismatch between sexes was smaller in mature eggs. The parasitoid size was smaller in the factitious host than in the natural hosts. Under semi-field conditions, we investigated the competition among parasitoid females on the overall parasitism success. The reproductive parasitism was more successful in S. exigua than in S. littoralis, and the maximum emergence was reached with three and four females, respectively. The control of S. littoralis may be attributed to the high developmental mortality, a non-reproductive parasitism that is often underestimated.

Lethal and sublethal toxicity of fipronil and imidacloprid on Psyttalia concolor (Hymenoptera: Braconidae).

Psyttalia concolor (Szèpligeti) (Hymenoptera: Braconidae) is a koinobiont endoparasitoid of several species of tephritid (Diptera) larvae, such as Bactrocera oleae (Gmelin) and Ceratitis capitata (Wiedemann). Here, we report on the effects of imidacloprid and fipronil on P. concolor females, when different routes of exposure were evaluated: residual contact (cover and bait sprays) and via treatment of host species. Moreover, the persistence of the bait formulated compound also was studied. For each experiment, lethal (mortality) and sublethal effects (parasitization rate or longevity) were studied. Fipronil produced 100% mortality irrespective of exposure route, and it was very persistent, because 34-d-old residues still produced this high mortality rate, being as toxic or even more toxic than the reference product dimethoate. Toxicity of imidacloprid depends on the mode of exposure, although always remained less toxic than dimethoate. Imidacloprid caused high mortality or sublethal effect to the progeny in cover sprays and when applied via treated host, being harmless in bait sprays application. In conclusion, our results suggest that fipronil should not be used in the field when the parasitoid is present. On the contrary, although imidacloprid is physiologically active against females of P. concolor, ecological selectivity may result through the use of bait treatment.

Long-term effects of methoxyfenozide on the adult reproductive processes and longevity of Spodoptera exigua (Lepidoptera: Noctuidae).

The long-term effects of methoxyfenozide on the longevity and reproductive processes of beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), adults were assessed after exposure by ingestion. Methoxyfenozide significantly reduced adult male longevity compared with females by 1.1 and 1.5 d at 75 and 150 mg (AI)/liter, respectively. Fecundity decreased by >60% with both concentrations at 72 and 96 h after treatment, but at 48 h, no significant effect was observed. The carbohydrate, protein, and lipid content in the eggs were determined as representatives of the biochemical effects of methoxyfenozide associated with the disruption of reproductive processes. The content of carbohydrates in the eggs laid 48 h at treatment was similar to that of controls, but it increased by approximately 1.5 and 2-fold in eggs laid after 72 and 96 h, respectively, compared with controls (15 microg per egg). Protein content was reduced approximately 2.5 and approximately 3-fold for each treatment concentration, respectively, compared with the controls (25 and 23 microg per egg for 75 and 150 mg [AI]/liter, respectively) in eggs collected 72 and 96 h after treatment. Lipid content significantly decreased by approximately 1.6-fold in both treatment concentrations in eggs collected at 48 and 96 h after treatment compared with the controls (24 and 21 microg per egg for 48 and 96, respectively), but it was similar to controls (approximately 19 microg per egg) at 72 h (approximately 15 microg per egg) for both concentrations. The biochemical effects of methoxyfenozide on S. exigua egg formation detected in this work are consistent with the reduction in fertility observed, as reported previously.

Changes in melon plant phytochemistry impair Aphis gossypii growth and weight under elevated CO2.

Elevated CO2 (eCO2) modifies plant primary and secondary metabolism that subsequently impacts herbivore insect performance due to changes in its nutritional requirements. This laboratory study evaluated interactions between Aphis gossypii Glover (Hemiptera: Aphididae) and melon (Cucumis melo L., Cucurbitaceae), previously acclimated two or six weeks to different CO2 levels, eCO2 (700 ppm) or ambient CO2 (400 ppm). Under eCO2, melon plants decreased nitrogen foliar concentration and increased carbon to nitrogen ratio, independently of acclimation period, significantly reducing the content of some amino acids (alanine, asparagine, glycine, isoleucine, lysine, serine, threonine, and valine) and increasing the carbohydrate (sucrose) content in melon leaves. The dilution in some essential amino acids for aphid nutrition could have aggravated the reduction in A. gossypii population growth reared on melon previously acclimated two weeks to eCO2, as well as the loss of aphid body mass from two successive generations of A. gossypii reared under eCO2 on plants previously acclimated two or six weeks to eCO2. The response to eCO2 of phloem feeders, such as aphids, is actually variable, but this study highlights a negative response of A. gossypii to this climate change driver. Potential implications on control of this pest in a global change scenario are discussed.