Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck.

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.

Toxocariasis affecting brain stem and skull base.

BACKGROUND: Toxocariasis is a helminthic infection caused by a nematode that mainly affects populations in tropical and subtropical latitudes. Humans are potential paratenic hosts, and clinical disease occurs as a result of parasite migration through intestinal tissue. We present a clinical case of otorhinolaryngological affectation by Toxocara canis. CASE PRESENTATION: A 60-year-old male from Ecuador, resident in Spain for 5 years, evaluated in the emergency department for presenting headache, otorrhea and left ear pain. Computed tomography (CT) and magnetic resonance imaging (MRI) reported a large mass of the nasopharynx with infiltration of the skull base, intracranial extension and a lesion in the left pons without being able to exclude metastases. Two Functional Endoscopic Sinus Surgery (FESS) biopsies were negative for malignancy. Despite not meeting the diagnostic criteria established by the existing literature, the clinical and radiological presentation, the presence of risk factors, a positive serology for Toxocara canis (IgGELISA) and the absence of alternative diagnosis were considered sufficient criteria to establish toxocariasis with inflammatory lesions in the nasopharynx and pons as the most probable diagnosis. Treatment with albendazole (400 mg / 12 h) and corticosteroids (1 mg / kg for 5 days) was started and continued for one month. Post treatment negative serology, and MRI and CT post treatment controls were performed after one year, both showing a decrease in lesion of the clivus as well as the pons. CONCLUSIONS: With the appropriate personal history, toxocariasis should be included in the differential diagnosis of infiltrating lesions of the skull base with a negative study of tumor histology. Albendazole treatment has been shown to control and cure the disease.

Use of pectoralis major myofascial flap on the prevention of pharyngocutaneous fístula in salvage laryngectomy after chemoradiotherapy.

Background: Pharyngocutaneous fístula (PCF) is a major complication of salvage laryngectomies, mainly secondary to the effect of radiotherapy. Aims/objectives: Our main objective is to study the effect of pectoralis major myofascial flap (PMMF) on the prevention of PCF. Materials and methods: We studied all total laryngectomies (TL) performed between 2001 and 2018, noting the use of previous chemoradiation, the type of suture and the use of flaps. We recorded and compared the incidence of PCF in all groups. Results: A total of 146 patients were included, divided into a primary TL group (117 patients) and salvage TL (29 patients). PMMF was used in 62% of salvage TLs. The rates of PCF were 5.98% in primary TL and 17.2% in salvage procedures. Among the salvage TL group, in patients with pharyngeal closure alone, a PCF developed in 36.4% of cases, compared to 5.56% in the PMMF group. We found a similar rate of fistulae when comparing primary TL and salvage TL with PMMF, highlighting the protective effect of the flap. Conclusions and significance: The use of PMMF in salvage TL reduces the incidence of PCF, achieving a rate similar to that attained with primary TL.

Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer.

BACKGROUND: Recently, nivolumab was approved in the second-line setting of squamous cell cancer of the head and neck (SCCHN). The benefits of PD-(L)1 inhibitors in PD-L1(-) tumors are unclear, and no reports exist on the activity of these agents in brain metastases from SCCHN. Little is known regarding the mechanisms underlying acquired resistance to PD-(L)1 inhibition. METHODS: A patient with PD-L1(-) metastatic SCCHN progressing to cetuximab-based chemotherapy received third-line nivolumab. T cell infiltration and mRNA expression of immune-related genes were compared in prenivolumab and postnivolumab biopsies from a progressing tumor lesion. RESULTS: An exceptional local and systemic response was achieved, including complete devitalization of brain metastases that lasted for more than a year. Increased T cell infiltration and upregulation of genes related to T cell exhaustion and resistance to PD-1 inhibition were found. CONCLUSION: Durable responses to PD-(L)1 inhibitors may be observed in biomarker-negative SCCHN. Mechanisms of resistance should be studied.

Utilidad de la Beta2-transferrina y la proteína Beta-traza en el diagnóstico de fístula de líquido cefalorraquídeo / Beta2-transferrin and Beta-trace protein in the diagnosis of cerebrospinal fluid fistula

Introducción. El diagnóstico precoz de las fístulas de líquido cefalorraquídeo (LCR) minimiza el riesgo de que los pacientes desarrollen graves complicaciones. Una herramienta diagnóstica es demostrar la presencia de LCR en las secreciones nasales, óticas y heridas quirúrgicas mediante el uso de marcadores bioquímicos específicos. El objetivo del trabajo es evaluar la utilidad de la β2-transferrina (β2-Tr) y la proteína β-traza (p-βT) en el diagnóstico de la fístula de LCR. Material y métodos. Se realizó la detección de β2-Tr y la medición de p-βT en 68 muestras de secreciones nasales, óticas y heridas quirúrgicas, procedentes de 54 pacientes con sospecha de presentar una fístula de LCR. El diagnóstico fue confirmado por criterios clínicos y otras pruebas diagnósticas. Se calcularon la sensibilidad y la especificidad diagnóstica, el valor predictivo positivo (VPP) y negativo (VPN). Para la p-βT se obtuvo el punto de corte óptimo mediante un análisis de curva ROC. Resultados. Para la β2-Tr se obtuvo una sensibilidad del 83%, especificidad del 96%, VPP del 95% y VPN del 86%. Para la p-βT, se obtuvo un área bajo la curva de 0,981. Para un punto de corte óptimo de 1,14mg/L, se obtuvo una sensibilidad del 92%, especificidad del 95%, VPP del 96% y VPN del 91%. El punto de corte con un VPN del 100% fue de 0,64mg/L. Conclusiones. La β2-Tr y la p-βT pueden utilizarse como marcadores de la existencia de fístula de LCR por su elevada sensibilidad y especificidad diagnóstica. Se concluye que un valor de p-βT ≥ 1,14mg/L indica fístula de LCR y un valor ≤ 0,64mg/L la descarta. Valores entre 0,64 y 1,14mg/L no son concluyentes y sería necesario realizar la detección de β2-Tr (AU)

Introduction. Early diagnosis of cerebrospinal fluid (CSF) fistula minimizes the risk of severe complications for patients. A diagnostic approach consists in revealing the presence of CSF in nasal, ear, and surgical wound secretions. The aim of this work is to evaluate the usefulness of β2-transferrin (β2-Tr) and β-trace protein (p-βT) as markers for the diagnosis of a CSF fistula. Material and methods. A total of 68 samples of nasal, ear, and surgical wound secretions were taken and analysed from 54 patients with clinical suspicion of a CSF fistula. β2-Tr and p-βT were determined in all fluids. The CSF fistula was diagnosed by clinical criteria and other diagnostic procedures. Sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values, were calculated. The optimal cut-off point for p-βT was obtained using a ROC curve analysis. Results. For β2-Tr, a sensitivity of 83%, a specificity of 96%, a PPV of 95% and a NPV of 86% were obtained. For the p-βT ROC curve analysis, the area under the curve was 0.981, with an optimal cut-off value of 1.14mg/L. For this cut-off point, a sensitivity of 92%, a specificity of 95%, a PPV of 96%, and a NPV of 91% were calculated. The p-βT cut-off point obtained for 100% NPV was 0.64mg/L. Conclusions. β2-Tr and p-βT can be used as CSF fistula markers, since both proteins have high sensitivity and specificity diagnostic values. It is concluded that, ≥ 1.14mg/L p-βT values are indicative of CSF fistula, and values ≤ 0.64mg/L rules it out. Values>0.64 and<1.14mg/L are not conclusive, and in these cases it would be necessary to determine β2-Tr (AU)

Cartilage invasion patterns in laryngeal cancer.

The cartilaginous invasion determines the T and is one of the most common sources of mistake in tumor staging. Also it is of great importance when planning any therapeutic alternative. In the latest revision of the TNM classification a clear distinction is made between infiltration of cartilage without going through it, considered a T3 recently and that would be a T4 according to the previous classification, and those going through the cartilage, classified as T4a. While this classification makes the difference in depth of infiltration, it does not emphasize the extent of invasion. This paper provides a detailed description of the laryngeal cartilage tumor infiltration by whole organ serial section in which the invasion is considered both horizontal (transcartilaginous) and vertical (extent of invasion) and establishing patterns of three-dimensional infiltration of the cartilage. This is a cross-sectional study of prevalence. 275 records of patients treated for laryngeal squamous cell carcinoma between 1995 and 2000 were reviewed. The pathological processing of laryngectomy surgical specimens was performed following the method of whole organ serial section described by G. F. Tucker. The following patterns of cartilaginous infiltration were defined: (1) transcartilaginous infiltration; (2a) partial focal infiltration of the cartilage: infiltration not going through the cartilage but occupying one third or less of its extent; (2b) partial extensive infiltration of the cartilage: infiltration occupying two thirds or more of its length and (3) no cartilage infiltration: tumor in contact with the cartilage (paraglottic space) but without affecting it. 161 patients met the inclusion criteria. The most frequent tumor location was supraglottic (58 cases) followed by glottic (47). 109 patients (67.7 %) were treated with total laryngectomy. Partial surgical techniques were performed in the remaining cases. TNM tumor staging was performed according to the results of pathological study (pTNM). 72.06 % (116) were classified as advanced laryngeal tumors (pT3 and pT4). 46 % of patients showed some extent of laryngeal cartilage infiltration (thyroid, cricoid, arytenoids, epiglottis). The cartilage most frequently infiltrated was the thyroid in 48 patients (29.8 %) and when it is affected, in most cases (66.7 %), the infiltration is transcartilaginous. The next most common pattern is partial focal infiltration (27 %). In the cricoid cartilage, the most common pattern of infiltration is focal partial infiltration (52.6 %). Of the 19 cases with infiltration of the cricoid, there are 12 cases with extra laryngeal invasion through a cricothyroid membrane perforation. The study of laryngeal cancer by laryngeal whole serial section has been proved to be very useful in offering a high precision pTNM staging and a detailed description of the infiltration of cartilage. We have seen that when the thyroid cartilage is infiltrated the tumor often passes through the cartilage. However, there are cases where the tumor is extremely aggressive, being very widespread in cartilage thickness without actually crossing it. The isolated infiltration of the cricoid cartilage is exceptional.

External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve.

BACKGROUND: Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non-traumatic external nasal nerve neuralgia. CASE: A 76-year-old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity. CONCLUSION: External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition.

Pharyngo-cutaneous fistula: an old problem revisited.

CONCLUSION: Pharyngo-cutaneous fistula is the most common complication after total laryngectomy (TL), with many factors linked to its emergence. However, it has rarely been associated with the type of pharyngeal suture. We conclude that the technique of surgical closure of the pharynx and care in the tightness of the suture seem to be fundamental factors for pharyngo-cutaneous fistula development. OBJECTIVE: The aim of present work was to determine whether the type of pharyngeal suture can be considered as a major risk factor for developing a pharyngo-cutaneous fistula following TL. METHODS: We carried out a series of 157 consecutive TLs. In the first 90 procedures, we performed a pharyngeal closure technique with T-shaped interrupted stitches reinforced with constrictors. In the other 67 cases, a doubled continuous suture technique with reinforcement with the cutaneous flap was developed. RESULTS: In all, 25.5% of the cases sutured with the interrupted stitches developed a fistula while only 2.9% of the patients that underwent continuous suture developed a fistula.

The impact of comorbidity on the survival of patients with laryngeal squamous cell carcinoma.

UNLABELLED: Abstract Conclusions: In survival analysis, the combined Charlson comorbidity index (CCI) can be considered as a prognostic factor independent of the tumor node metastasis (TNM) classification, tumor stage, and tumor location. Severe comorbidity was the factor that had the greatest impact on prognosis in cases of initial tumor. OBJECTIVE: To study the influence of comorbidity on the survival of patients undergoing surgery for larynx cancer. METHODS: This was a retrospective study of the survival of 231 patients with laryngeal cancer who underwent surgery between 1995 and 2002. The CCI was used to assess comorbidity, the Kaplan-Meier method was used for survival analysis, and the Cox proportional risk regression model was used to identify independent prognostic factors. RESULTS: The multivariate analysis of specific mortality showed that patients classified as having severe comorbidity (CCI) were more likely to die (adjusted hazard ratio (adjHR) 1.85, 95% confidence interval (CI) 1.07-3.17). This difference was more important in patients with early tumor stages than in those with advanced stages.

Estenosis congénita del orificio piriforme y megaincisivo central único / Congenital nasal pyriform aperture stenosis and solitary maxillary central incisor: Case report

La estenosis congénita del orificio piriforme es una anomalía descrita recientemente en la literatura, provocada por un crecimiento excesivo de la apófisis ascendente del hueso maxilar, pudiendo ocasionar problemas respiratorios y alimenticios desde el periodo neonatal. Presentamos el caso de una recién nacida diagnosticada de esta patología asociada a un megaincisivo central único. La actitud elegida fue la observación, junto con la aplicación de medidas conservadoras. Un año después del diagnóstico, la paciente tiene un adecuado desarrollo ponderoestatural (AU)

Congenital nasal pyriform aperture stenosis has recently been described in the literature. It is caused by an upward overgrowth of the maxillary bone apophysis and may cause breathing and feeding problems from the neonatal period on. We present the case of a newborn girl diagnosed with this pathology associated with a solitary maxillary central incisor. Observation with conservative measures was the attitude chosen. One year after diagnosis the patient shows adequate height and weight development (AU)

[Congenital nasal pyriform aperture stenosis and solitary maxillary central incisor: case report]. / Estenosis congénita del orificio piriforme y megaincisivo central único.

Congenital nasal pyriform aperture stenosis has recently been described in the literature. It is caused by an upward overgrowth of the maxillary bone apophysis and may cause breathing and feeding problems from the neonatal period on. We present the case of a newborn girl diagnosed with this pathology associated with a solitary maxillary central incisor. Observation with conservative measures was the attitude chosen. One year after diagnosis the patient shows adequate height and weight development.