Otitis media with effusion in preschool children with adenoid hypertrophy: Risk factors and nursing care.

AIM: To evaluate the influencing factors of otitis media with effusion (OME) in children with adenoid hypertrophy and to provide evidence for clinical treatment and care of children with adenoid hypertrophy. DESIGN: A retrospective study. METHODS: Preschool children with adenoid hypertrophy treated in our hospital from 1 January 2021 to 30 July 2022 were included. We analysed the characteristics of OME and non-OME children with adenoid hypertrophy. Pearson correlation analysis and logistic regression analysis were performed to evaluate the risk factors for OME in children with adenoid hypertrophy. CONCLUSION: A total of 166 children with adenoid hypertrophy were included; the incidence of OME in children with adenoid hypertrophy was 34.94%. The incidence of OME decreased significantly with the increase in age (p = 0.014). Logistic regression analysis showed that age < 3 years (OR = 3.149, 95%CI: 2.812-3.807) and duration of adenoid hypertrophy ≥12 months (OR = 2.326, 95%CI: 2.066-2.612) were the risk factors of OME in children with adenoid hypertrophy (all p < 0.05). PATIENT CONTRIBUTION: The incidence of adenoid hypertrophy with OME is high in preschool children, and it is related to the age and duration of adenoid hypertrophy.

Effects of adenoid hypertrophy on nasopharyngeal airway ventilation: A computational fluid dynamics study.

OBJECTIVES: Adenoid hypertrophy causes impaired nasopharyngeal airways (NA) ventilation. However, it is difficult to evaluate the ventilatory conditions of NA. Therefore, this study aimed to analyze the nasopharyngeal airway resistance (NARES) based on computational fluid dynamics simulations and the nasopharyngeal airway depth (NAD) and adenoid hypertrophy grade measured on cephalometric cone-beam computed tomography images and determine the relationship between NAD and grade and NARES to ultimately assess using cephalometric measurements whether NA has airway obstruction defects. METHODS: Cephalogram images were generated from cone-beam computed tomography data of 102 children (41 boys; mean age: 9.14 ± 1.43 years) who received orthodontic examinations at an orthodontic clinic from September 2012 to March 2023, and NAD and adenoid grade and NARES values were measured based on computational fluid dynamics analyses using a 3D NA model. Nonlinear regression analyses were used to evaluate the relationship between NARES and NAD and correlation coefficients to evaluate the relationship between grade and NARES. RESULTS: NARES was inversely proportional to the cube of NAD (R2 = 0.786, P < 0.001), indicating a significant relationship between these variables. The resistance NARES increased substantially when the distance NAD was less than 5 mm. However, adenoid Grade 4 (75 % hypertrophy) was widely distributed. CONCLUSIONS: These study findings demonstrate that the ventilatory conditions of NA can be determined based on a simple evaluation of cephalogram images. An NAD of less than 5 mm on cephalometric images results in NA obstruction with substantially increased airflow resistance.

Risk factors of sleep-disordered breathing and poor asthma control in children with asthma.

BACKGROUND: Sleep-disordered breathing (SDB) may lead to poor asthma control in children. OBJECTIVE: To identify risk factors of SDB in children with asthma and assess its impact on asthma control. METHODS: In this cross-sectional study, we collected data of outpatients with asthma at the Children's Hospital of Chongqing Medical University from June 2020 to August 2021. The Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder and the age-appropriate asthma control tests Childhood Asthma Control Test and Test for Respiratory and Asthma Control in Kids were completed. RESULTS: We enrolled 397 children with a male-to-female ratio of 1.7:1 and a mean age of 5.70 ± 2.53 years. The prevalence of SDB was 21.6%. Allergic rhinitis (odds ratio OR = 3.316), chronic tonsillitis (OR = 2.246), gastroesophageal reflux (OR = 7.518), adenoid hypertrophy (OR = 3.479), recurrent respiratory infections (OR = 2.195), and a family history of snoring (OR = 2.048) were risk factors for the development of combined SDB in children with asthma (p < 0.05). Asthma was poorly controlled in 19.6% of the children. SDB (OR = 2.391) and irregular medication use (OR = 2.571) were risk factors for poor asthma control (p < 0.05). CONCLUSIONS: Allergic rhinitis, chronic tonsillitis, gastroesophageal reflux, adenoid hypertrophy, recurrent respiratory infections, and a family history of snoring were independent risk factors for the development of SDB in children with asthma. SDB and irregular medication use were independent risk factors for poor asthma control.

Successful Antiviral Treatment for Chronic Adenoiditis Caused by Herpes Virus in a Pediatric Patient: A Case Report.

BACKGROUND The adenoids are lymphatic tissue located in the nasopharynx and play a role in upper-airway immunity. Inflammation of the adenoids is called adenoiditis, which can cause a variety of symptoms. This is a common condition and is due to acute viral or bacterial infection. Most patients experience mild symptoms of upper-respiratory tract infection with a self-limiting course. CASE REPORT A 5-year-old female patient was brought into the clinic by her parents with concerns regarding hearing and sleep. Clinical assessment was consistent with persistent otitis media with effusion and sleep-disordered breathing. She was scheduled for surgery, including nasendoscopy, adenoidectomy, and bilateral grommet insertion. During surgery, direct visualization of the postnasal space showed complete obstruction by hypertrophic, inflamed adenoids covered in a thick, white film. A biopsy was taken, which detected herpes virus cytopathic effect. A diagnostic workup excluded a neoplastic process and other bacterial or fungal infections. A trial of oral antiviral medication was successful and follow-up nasendoscopy showed resolution of adenoid hypertrophy. CONCLUSIONS Direct visualization of the postnasal space, with a transoral mirror or 120-degree endoscope, prior to adenoidectomy can aid diagnosis. Adenoiditis may be caused by a wide range of organisms, including herpes virus. Active mucopurulent discharge should raise concern for infection by bacteria, fungi, or virus. Previous research on viral infection of the adenoids have been in asymptomatic patients with presumed latent infection and undergoing elective adenoidectomy. To our knowledge, this is the first paper to report on successful treatment with antiviral medication alone.

Causal association of gastroesophageal reflux disease with chronic sinusitis and chronic disease of the tonsils and adenoids.

BACKGROUND: Exploring bidirectional causal associations between gastroesophageal reflux disease (GERD) and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively. METHODS: We first conducted a TSMR (two-sample mendelian randomization) study using the results of the inverse variance weighting method as the primary basis and bidirectional MR to rule out reverse causation. Subsequently, MVMR (multivariate MR) analysis was performed to identify phenotypes associated with SNPs and to explore the independent effect of GERD on two outcomes. Finally, we calculated MR-Egger intercepts to assess horizontal polytropy and Cochran's Q statistic to assess heterogeneity and ensure the robustness of the study. RESULTS: For each standard deviation increase in genetically predicted GERD rate, there was an increased risk of chronic disease of the tonsils and adenoids (OR 1.162, 95% CI 1.036-1.304, P: 1.06E-02) and of developing chronic sinusitis (OR 1.365, 95% CI 1.185-1.572, P: 1.52E-05), and there was no reverse causality. Causality for TSMR was obtained on the basis of IVW (inverse variance weighting) and appeared to be reliable in almost all sensitivity analyses, whereas body mass index may be a potential mediator of causality between GERD and chronic sinusitis. CONCLUSION: There is a causal association between GERD and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively, and the occurrence of GERD increases the risk of developing chronic disease of the tonsils and adenoids and chronic sinusitis.

A Comparative Evaluation of TRPS1 and GATA3 in adenoid cystic, secretory, and acinic cell carcinomas of the breast and salivary gland.

GATA3 is the most used marker to determine tumors' breast origin, but its diagnostic value in triple-negative breast cancer (TNBC) is limited. The newly identified TRPS1 is highly sensitive and specific for breast carcinoma, especially TNBC. Here, we compared the utility of TRPS1 and GATA3 expression in a subset of salivary gland-type breast tumors (including adenoid cystic, acinic cell, and secretory carcinomas [AdCC, ACC, and SC, respectively]), and we compared TRPS1 and GATA3 expression of such tumors with head and neck (H&N) and AdCC of upper respiratory tumors. TRPS1 was strongly expressed in basaloid TNBC and AdCCs with solid components, including 100 % of mixed and solid breast AdCCs. However, TRPS1 was positive in only 50 % cribriform AdCCs. Expression patterns of TRPS1 in H&N and upper respiratory AdCC were similar. TRPS1 was positive in 30 % of H&N cribriform AdCCs but was strongly expressed in mixed AdCC (67 %) and solid AdCC (100 %). In the upper respiratory AdCCs, TRPS1 was positive in 58.4 % of cribriform AdCCs and positive in 100 % of AdCCs with solid components. On the contrary, GATA3 was negative in predominant AdCCs of the breast, H&N, and upper respiratory tract. These data show that GATA3 and TRPS1 expression varies AdCCs. In addition, TRPS1 and GATA3 expression patterns were similar SC and ACC of breast and H&N. Both markers were positive in SC and negative in ACC. Therefore, TRPS1 and GATA3 cannot be used to differentiate salivary gland-type carcinomas of breast origin from those of upper respiratory or H&N origin.

Cervical Adenoid Basal Carcinoma With High-grade Squamous Component: True Mixed Carcinoma or Colonization of Adenoid Basal Carcinoma by High-grade Squamous Intraepithelial Lesion?

Adenoid basal carcinoma (ABC) is a rare clinically indolent human papillomavirus-associated cervical neoplasm with uniformly bland morphology which in pure form does not metastasize. Many cases co-exist with a human papillomavirus-associated high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma (SCC). The ABC and high-grade squamous components may be clearly separate, albeit intermingled, and when the high-grade squamous component is invasive, the tumor is designated a mixed carcinoma, with clinical behavior determined by the non-ABC component. In other cases, discrete nests of high-grade atypical squamous cells are intimately admixed and incorporated within the ABC. These are more difficult to classify but are also usually reported as mixed carcinomas. Herein, we report a series of 9 cases of ABC in patients aged 33 to 89 years (mean age: 63 y) with a high-grade squamous component. In 7 cases, the high-grade squamous cells partly replaced and expanded the nests of ABC, sometimes with a residual cuff of ABC cells, while in the other 2 cases the ABC and SCC were clearly separate. We propose that the aforementioned 7 cases represent colonization of ABC by HSIL rather than mixed carcinomas; as far as we are aware, this concept has not been proposed before. In all cases which we feel represent colonization of ABC by HSIL, the tumors were confined to the cervix (stages IA1 [3 tumors], IA2 [2 tumors], IB1 [2 tumors]) and follow-up was unremarkable with no evidence of metastasis. One case with separate components of ABC and SCC was stage IVA at diagnosis and the patient died of disease. The other was stage IB1 at diagnosis and the patient died of unrelated causes at 13 months. We discuss the clinical implications of distinguishing true mixed carcinomas from colonization of ABC by HSIL and provide an approach to diagnosis. We also report a unique case of colonization of so-called cervical ectopic prostatic tissue by HSIL.

Nasopharyngeal cyst in an adolescent boy: differential diagnosis - embryological and anatomical considerations.

In the current article, we present a case of an adolescent boy with a nasopharyngeal cyst that induced nasal and Eustachian tube obstruction. Nasopharyngeal cysts can be found incidentally during imaging examinations such as MRI; however, a symptomatic nasopharyngeal cyst is a rare finding in the paediatric population. The cyst was treated successfully by marsupialisation, and the histological diagnosis revealed an adenoidal retention cyst. The differential diagnosis of a nasopharyngeal cyst is always challenging since developmental cysts such as Rathke's pouch cysts, Torwaldt's and branchial cleft cysts may be encountered at the nasopharynx. The current article also intends to present the diagnostic and therapeutic approach to a nasopharyngeal cyst, emphasising anatomical and embryological considerations that address its differential diagnosis.

Olfactory disorders in childhood: A comparative study of olfaction in children with adenoid hyperplasia versus a control group and the postoperative effects of adenoidectomy with respect to olfactory ability.

PURPOSE: Hyposmia in childhood is poorly characterized. The "U-Sniff Test", validated for children with anosmia, can be used to objectify olfactory impairment but has not been used to distinguish between hyposmia and normosmia. Therefore, we investigated children with enlarged adenoids with respect to hyposmia, its correlation with adenoid size, and the sensitivity of questionnaires to predict olfactory impairment. METHODS: In a prospective comparison, olfaction was assessed by "U-Sniff Test" (score 0-12; <8 hyposmia) in 41 children (5-18 years) with adenoid hyperplasia and compared with 196 children without any respiratory affection (control) after exclusion of previous SARS-Cov2-infection from December 2020 to December 2021. ENT-related complaints were collected using a self-designed questionnaire. We were able to include 13 children in a follow-up examination to compare preoperative performance in the "U-Sniff Test" with postoperative outcome after adenoidectomy. STATISTICS: chi-square-test (p < 0.05), odds-ratio, Spearman's rho, ROC-, cluster analysis. RESULTS: Severe hyposmia was present in 36.6% of children with adenoid-hyperplasia compared to 3.1% of the control-group. Adenoid-children scored significantly more often between 8 and 10 points (58.5%) than the control (31.6%; p < 0.01). Adenoid size and olfactory performance correlate significantly (r: 0.83; CI -0.89 … -0.72). Hyposmia in the adenoid group is characterized predominately by loss of the odors banana, butter and rose. None of children with hyposmia or parents reported impaired olfactory performance. Postoperatively, olfactory function improved significantly in 85% of cases (p 0.01, SD ± 1.71, Δ3.54points). CONCLUSION: Questionnaires are insufficient to detect hyposmia in this cohort. In contrast, the "U-Sniff Test" detects even reduced olfactory performance without reaching the cut-off value, which represents the majority of test results in the adenoid group. Therefore, we recommend the classification of moderate hyposmia (8-10 points) to be included for our study population.

A Systematic Review of Adenoid Ameloblastoma: A Newly Recognized Entity.

BACKGROUND: Recently, a new odontogenic tumor has been described, the so-called adenoid ameloblastoma (AdAM). The aim of this review was to determine the clinical and imaging features of AdAM and to describe its main histopathological findings. METHODS: The systematic review included published cases with a diagnosis of AdAM in the gnathic bones, which had sufficient clinical, imaging, and histopathological data to confirm its diagnosis. The following histopathological diagnostic criteria were adopted: presence of ameloblastoma-like components, duct-like structures, spiral cellular condensations, and a cribriform architecture. RESULTS: Fifteen articles, corresponding to 30 cases of AdAM, were selected. Most cases affected men (63.3%), with a slight preference for the mandible (16:14) and the posterior region of gnathic bones was the most commonly affected site. The mean age at diagnosis was 40.8 years. Clinically, the lesions usually presented as a swelling (53.3%) and, radiographically, as a well-defined radiolucency (33.4%). Surgical resection (40%) was the most frequently adopted treatment and recurrence occurred in 30% of cases. Microscopic examination showed cribriform areas in most AdAM cases (93.3%); duct-like structures and spiral cellular condensations were seen in 100% of the cases. CONCLUSION: The small number of reported cases, the existence of erroneous diagnoses, and the adoption of initial conservative management make it difficult to determine whether AdAM has a higher risk of recurrence or more aggressive biological behavior than conventional ameloblastomas.

Adenoid 'ameloblastoma': Clinicopathological description of 4 additional BRAF-negative cases.

OBJECTIVE: Adenoid ameloblastoma (AA) is an epithelial odontogenic tumor that was recognized as a separate entity in the last odontogenic classification of WHO in 2022. The etiology is unknown, and the pathogenesis remains controversial. The objective of this study is to contribute the clinicopathological features of 4 additional BRAF-negative cases to the existing literature, aiming to enhance the molecular understanding of this unique tumor in the forthcoming classification. MATERIALS AND METHODS: This study consists of a case series of four patients diagnosed with AA. The patients' demographic and clinical information were collected from the universities' medical achieves. Histopathologically, all cases were reexamined according to the latest update of the WHO odontogenic tumor classification. In addition to H&E and immunohistochemical stains, cytogenetics was also evaluated. RESULTS: Well-defined unilocular radiolucent lesions were observed in all cases. Ameloblastoma-like components exhibited reserved nuclear polarity, suprabasal stellate reticulum-like epithelium, duct-like structure, whorls/morules, and cribriform architecture were common features. Variable immunoreactivity to CK7, CK19, CK14, p63, and p40 were determined, and proliferative activity was greater than 15%. The BRAF molecular study revealed no mutations. CONCLUSIONS: When diagnosing AA, the essential histopathological characteristics must be rigorously applied, and a significant portion of the lesion should contain these features. Additionally, despite limited molecular data, since the BRAF mutation commonly observed in ameloblastomas is not present in the majority of AA cases, we propose changing the term "ameloblastoma" to "ameloblastic" and referring to it as "adenoid ameloblastic tumor" in the forthcoming classification.

Oropharyngeal microbiome in children with adenotonsillar hypertrophy and after adenotonsillectomy.

BACKGROUND: The microbiome of tonsils and adenoid in adenotonsillar hypertrophy (ATH) has been profiled. Adenotonsillectomy (AT) is widely used for ATH in children. The variation of the oropharyngeal microecology in children with ATH or after AT have never been studied. OBJECTIVES: Here we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. MATERIALS AND METHODS: In this cross-sectional study, throat swabs for microbiome analysis were collected from ATH, AT and control groups. Using 16s rDNA sequencing, this study investigated the characteristics of oropharyngeal microbiome. RESULTS: The α-diversity showed a statistical difference in richness and the ß-diversity was significantly different among the three groups. The relative abundance of Haemophilus (member of Proteobacteria) increased but that of Actinomyces (member of Actinobacteriota) decreased in the ATH group compared to those in the AT and control groups, but their abundances showed no statistical difference between the AT and control groups. CONCLUSIONS: The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT. This microbiome analysis provides a new understanding about the pathogenesis of ATH in children.SummaryIn this study, we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT.

Adenoid hypertrophy-​diagnosis and treatment: the new S2k guideline.

Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with a permanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.

Role of Mesenchymal Stem Cells on Tonsillar Hypertrophy: An Unexplored Enigma.

Tonsillar or adenoid hypertrophy is a common childhood finding which can cause significant health problems like respiratory infections and sleep apnea. Though normal growth of children is also attributed to such enlargement, infection, environmental pollutants, allergens, and gastroesophageal reflux are proposed triggering factors for tonsillar hypertrophy. While tonsilar enlargement in adults is more associated with malignancy and chronic infections like the human immunodeficiency virus, the immunology of childhood adenotonsillar hypertrophy is less understood. We postulate that upon stimulation, mesenchymal stem cells are found to reduce the secretion of interferon-gamma but increase the secretion of interleukin-4 from activated T cells. Both of these factors inhibit apoptosis in the tonsillar tissue leading to its hypertrophy. Under the umbrella of evidence, it implicates the role of mesenchymal stem cells in tonsillar hypertrophy. However, further longitudinal large studies are needed to validate the proposition. Keywords: interleukin-4; mesenchymal stem cell; tonsillar hypertrophy.

[Adenoids-diagnosis and treatment: the new German S2k guideline]. / Adenoide Vegetationen ­ Diagnostik und Therapie ­ die neue S2k-Leitlinie.

Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with a permanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.

Adenoid Ameloblastoma with BRAF p.V600E Mutation Revealing Ameloblastomatous Origin: A First Case Report.

BACKGROUND: Adenoid ameloblastoma (AdAM) is a frequently recurrent tumor that shows hybrid histological features of both ameloblastoma and adenomatoid odontogenic tumor (AOT). AdAM is expected to be classified as a new subtype of ameloblastoma in the next revision of the World Health Organization (WHO) odontogenic tumor classification. However, whether AdAM is a histologic variant of ameloblastoma or AOT remains unclear. To establish a new category, genetic evidence indicating the tumor category is necessary. METHODS: We present a case of a 23-year-old Japanese woman with AdAM who underwent genetic/DNA analysis for ameloblastoma-related mutation using immunohistochemical staining, Sanger sequencing, and next-generation sequencing (NGS) analyses with reliable clinicopathological evidence. RESULTS: Immunohistochemical expression of BRAF p.V600E was diffusely positive for both ameloblastoma- and AOT-like components. Sanger sequencing and NGS analyses showed missense mutations in BRAF p.V600E (c.1799T > A), a gene that is commonly altered in ameloblastomas but not in KRAS, another gene associated with AOT. CONCLUSION: This case report is the first to provide genetic evidence on the ameloblastomatous origin of AdAM with a BRAF p.V600E mutation. A larger series of AdAM groups' molecular testing is needed to aptly classify them and prognosticate the best treatment.

Adenoid hypertrophy in children: a narrative review of pathogenesis and clinical relevance.

Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the nasopharynx. Adenoids play an important role in the development of the immune system and serve as a defence against infections, being the first organs that come into contact with respiratory and digestive antigens. The causes of adenoid hypertrophy are not fully known. They are most likely associated with aberrant immune reactions, infections, environmental exposures and hormonal or genetic factors. The aim of this review is to summarise the current knowledge of adenoid hypertrophy in children and associated diseases. Adenoid hypertrophy has many clinical manifestations that are frequent in the paediatric population and is accompanied by various comorbidities.

A case of metastatic adenoid cystic (basal cell) carcinoma of the prostate: Systemic therapy for a rare disease.

BACKGROUND: Metastatic adenoid cystic (basal cell) carcinoma of the prostate is an exceedingly rare disease entity. As a result, no current consensus exists for optimal systemic therapy. METHODS: We present a patient with metastatic adenoid cystic (basal cell) carcinoma of the prostate who subsequently received systemic treatment, including chemotherapy and immunotherapy. We comprehensively reviewed all published data on therapy outcomes in advanced disease. RESULTS: Our patient benefited from combination chemotherapy (carboplatin and paclitaxel), with objective radiographic response and reduction in cancer-related pain. However, chemotherapy was stopped due to cumulative neurotoxicity, and subsequent immunotherapy with atezolizumab did not produce any response. Our literature review revealed inconsistent outcomes with various treatments but showed most promise with chemotherapy. Targeted therapy and immunotherapy seem to benefit specific cases, and androgen deprivation therapy had minimal evidence of benefit. CONCLUSION: Based on the findings of our case report and literature review, we suggest platinum-based chemotherapy doublets as first-line treatment for metastatic cases of adenoid cystic (basal cell) carcinoma of the prostate, reserving targeted therapy or immunotherapy for select cases based upon molecular profiles.