Filippo Valentini

Preoperative differentiation between pathological T3 (pT3) disease, representing locally advanced tumor confined to the larynx, and pathological T4 (pT4) disease, characterized by extension through the laryngeal cartilage and/or beyond the larynx, remains challenging in laryngeal squamous cell carcinoma (LSCC). This single-center retrospective study investigated the association between primary-tumor apparent diffusion coefficient (ADC) and pathological T stage and explored whether ADC could complement MRI-based morphological T classification. Twenty-eight patients with surgically confirmed, moderately differentiated LSCC were included (13 pT3 and 15 pT4). Mean ADC values were compared using the Mann–Whitney U test, and discrimination of pT4 disease was evaluated using receiver operating characteristic (ROC) analysis. Leave-one-out cross-validation was performed for internal validation of the ADC threshold and exploratory combined MRI–ADC rule. Mean ADC was significantly lower in pT4 than in pT3 tumors (760 ± 209 versus 1150 ± 188 × 10⁻⁶ mm²/s; p < 0.001). ADC achieved an area under the ROC curve of 0.913 (95% confidence interval, 0.769–1.000). The apparent combined MRI–ADC rule yielded a sensitivity of 93.3%, specificity of 100%, and overall accuracy of 96.4%. Under leave-one-out cross-validation, the corresponding estimates were 93.3%, 92.3%, and 92.9%, respectively. No statistically significant association between primary-tumor ADC and pathological nodal status was detected. Primary-tumor ADC was associated with pathological T stage and showed potential complementary value to morphological MRI; however, the threshold and combined rule remain hypothesis-generating and require independent external validation.

Background Drug-drug interactions (DDIs) are an emerging issue in oncological patients, given the risk of increased toxicities and reduced efficacy from oncological treatments. This is particularly relevant in recurrent-metastatic (RM) head and neck cancer (HNC), where patients are often older, multimorbid, and receiving multiple home medications. While most DDIs are known for chemotherapy and targeted therapies, data on immune checkpoint inhibitors (ICIs) remain limited. Therefore, RM HNC patients represent a target population to investigate DDIs effects on ICIs. Material and Methods We conducted a retrospective, multicenter study to evaluate if polypharmacy affected safety and efficacy in RM HNC patients treated with ICIs, given alone (pembrolizumab or nivolumab) or in combination (combo) with chemotherapy (pembrolizumab-platinum-5-fluoruracil). DDIs were assessed using the Drug-PIN® platform, which provides for each patient two parameters: a Drug-PIN score, i.e. a continuous variable - the greater the number, the greater the likelihood of DDI; and a Drug-PIN level, with 5 levels ranging from green, meaning no interaction found, to red, meaning high potential for interaction. The relationship between Drug-PIN parameters and immune-related adverse events (irAEs) was tested using Student’s t-test. The correlation between Drug-PIN parameters and patients’ survival was assessed with the Kaplan-Meier method. Results We analysed 180 RM HNC (128 males) patients treated between June 2017 and July 2022 with ICIs (49 pembrolizumab alone, 89 nivolumab alone, 42 combo) at three different institutions. The median age was 65 years old (range: 33-89). Every patient took a median of 5 medications (0-15). Median Charlson Comorbidity Index score was 8 (2-14). IrAEs of any grade were observed in 55 patients (31%). Median PFS and OS were 5.9 and 6.5 months for pembrolizumab alone, 7.8 and 11.1 months for combo, 5 and 11.4 months for nivolumab. Median Drug-PIN score was 39.4 (0-214,3); Drug-PIN levels were green, light yellow, dark yellow, orange and red in 56, 27, 32, 9, 56 pts, respectively. Dichotomizing patients according to median Drug-PIN score, no difference was found in irAEs incidence (p 0.48), PFS (p. 0.82), or OS (p 0.89). No differences in irAEs incidence or in survival outcomes could be elucidated by stratifying patients according to Drug-PIN levels. Conclusions ICIs safety and efficacy in the treatment of RM HNC seem not to be affected by polypharmacy and DDIs.

Background: Isolated hypoglossal nerve palsy is a rare neurological condition with a broad differential diagnosis. Although neoplastic disorders are the most common cause, internal carotid artery dissection (ICAD) is an uncommon but clinically important and potentially reversible vascular etiology that is frequently underrecognized. This systematic review synthesized the available evidence regarding the clinical presentation, imaging findings, pathophysiological mechanisms, treatment, and outcomes of isolated hypoglossal nerve palsy associated with ICAD through a standardized patient-level descriptive analysis. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261364863). PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to April 2026. Manual reference screening and forward citation tracking were also performed. Studies reporting original, patient-level data on isolated hypoglossal nerve palsy associated with ICAD were eligible. Clinical, imaging, treatment, and outcome data were extracted and synthesized descriptively. In hybrid publications combining original case reporting with a narrative literature review, only eligible, original patient data were included in the quantitative synthesis, whereas the narrative review components were used for citation tracking and contextual comparison. Results: A total of 26 standalone primary publications were included, comprising 23 case reports and 3 case series. Two additional hybrid publications each contributed one eligible patient. One hybrid publication contained an original case-report component, whereas the other reported two original cases and was therefore considered to contain a case-series component, although only one of its patients fulfilled the eligibility criteria. Overall, the 28 publications contributed 32 eligible patients to the patient-level quantitative synthesis. The narrative review components of the two hybrid publications were used solely for citation tracking and contextual comparison. Patients were predominantly male (28/32, 87.5%), with a median age of 47 years. Tongue deviation (28/28, 100%) and tongue weakness (30/30, 100%) were the hallmark clinical features, followed by dysarthria (26/26, 100%) and dysphagia (18/22, 81.8%). All patients presented with isolated hypoglossal nerve palsy at presentation, without Horner syndrome or additional lower cranial nerve involvement. MRI was the most frequently reported imaging modality (29/32, 90.6%), whereas CTA was commonly used to characterize luminal abnormalities. Intramural hematoma (25/26, 96.2%), luminal stenosis (23/26, 88.5%), and external arterial enlargement (22/24, 91.7%) were the most consistent neuroradiological findings. Conservative medical management predominated (31/32, 96.9%). The available evidence was more consistent with a compressive mechanism related to subadventitial arterial wall expansion, although an ischaemic contribution involving the vasa nervorum could not be excluded. A favourable clinical outcome (complete recovery or marked improvement) was observed in 21/30 patients (70.0%). Overall, improvement of any degree, including partial recovery, was documented in 25/30 evaluable patients (83.3%). Outcome data should be interpreted cautiously because they derive predominantly from individual case reports. Conclusions: This systematic review provides an updated standardized synthesis of the available case-level evidence on isolated hypoglossal nerve palsy associated with ICAD. CTA and MRI/MRA provide complementary diagnostic information and may facilitate timely diagnosis when interpreted according to the clinical context. The available evidence identifies recurrent clinico-radiological patterns that may assist clinicians in recognizing this uncommon presentation while highlighting the need for prospective multicentre studies to better inform future diagnostic and therapeutic strategies.

Radiomics may aid the noninvasive characterization of adrenal incidentalomas; however, reproducibility is limited by methodological heterogeneity. In this retrospective, single-center, exploratory study, we tested whether radiomic features from baseline non-enhanced computed tomography (NECT) discriminate benign from malignant/metastatic adrenal lesions and contextualized results with a PRISMA 2020 systematic review (PubMed/Scopus 2017–2025; PROSPERO CRD420251276627). Thirty-three patients (36 lesions: 12 lipid-rich adenomas, 9 lipid-poor adenomas, 6 pheochromocytomas, 7 malignant/metastatic lesions, 2 myelolipomas) were included; myelolipomas were excluded from primary comparisons. Two abdominal radiologists performed consensus 3D segmentation on NECT. Using LIFEx (v7.8.0) and IBSI definitions, 42 features were extracted and z-score standardized. LASSO selected four heterogeneity descriptors: First-order Entropy, gray-level co-occurrence matrix (GLCM) entropy, gray-level size zone matrix (GLSZM) non-uniformity, and neighboring gray tone difference matrix (NGTDM) busyness. Heterogeneity increased from lipid-rich adenomas to pheochromocytomas and malignant/metastatic lesions (Kruskal–Wallis, all p < 0.001. Pairwise separability, measured using the Vargha–Delaney A index (VDA) as a rank-based measure of separability, was highest for lipid-rich adenomas versus malignant/metastatic lesions (0.93), intermediate for lipid-poor adenomas versus pheochromocytomas (0.73), and lowest for lipid-rich versus lipid-poor adenomas (0.64). The review identified 18 eligible CT radiomics studies that consistently reported higher entropy/non-uniformity in pheochromocytomas and malignant lesions than in lipid-rich adenomas. Global heterogeneity metrics on NECT may complement conventional CT criteria in indeterminate lesions; external validation with robust reference standards is needed in larger, multicenter cohorts with harmonization.

Background: Vestibular granuloma is a rare complication of a common surgical procedure, such as stapedotomy; it can significantly impact the outcome of surgery, leading to severe impairment and deterioration in the patient’s quality of life. Case report: A 59-year-old male underwent stapedotomy with a titanium prosthesis. Initially, hearing function improved but, within days, the patient developed vertigo and worsened hearing loss. HR CT of temporal bone revealed soft tissue in the tympanic cavity, prompting revision surgery. Granulomatous tissue surrounding the prosthesis was removed, leading to symptom relief. However, the patient later developed Persistent Postural-Perceptual Dizziness (PPPD), requiring SSRI therapy. Discussion: The sudden onset of persistent vertigo and hearing loss, that rapidly worsens in post-operative setting, represents a crucial red flag for the surgical team. Hearing assessments and imaging play a key role in quickly diagnosing the cause of these complications, which may be attributed to an inflammatory response at the surgical site, possibly due to granuloma formation. This enables the surgical équipe to swiftly implement appropriate care strategies for the patient, even in the presence of additional and subsequent complications like PPPD, which requires a comprehensive, multimodal approach to treatment. Conclusion: This case highlights the risk of a series of complications after surgery and even after reoperation, ultimately requiring conservative multimodal treatment and follow-up. Early recognition and coordinated care are essential for optimal long-term management of patients, even in the presence of unfavorable outcomes and complications.

Lymphoepithelial carcinoma (LEC) is a rare malignancy within the head and neck region, histologically akin to undifferentiated nasopharyngeal carcinoma. It is uncommon outside the nasopharynx, particularly in the oropharynx and salivary glands. Granular cell tumors (GCTs), or Abrikossoff’s tumors, are rare mesenchymal neoplasms of neural origin, frequently benign but with the potential for malignant transformation. This case report presents an unprecedented clinical scenario of a 62-year-old female patient diagnosed with an HPV/EBV-negative LEC of the right palatine tonsil, coupled with metachronous squamous dysplasia and a contralateral GCT of the true vocal cord. Following initial presentation with cervical swelling, hoarseness, and dysphagia, diagnostic imaging and histopathological analyses confirmed the distinct co-occurrence of these rare entities. The patient underwent multidisciplinary treatment, including transoral robotic surgery (TORS), radical neck dissection, and adjuvant chemoradiotherapy for LEC. Simultaneously, the GCT was managed surgically with close-margin excision, with ongoing surveillance for recurrence. A comprehensive treatment strategy meticulously addressed the unique pathological and therapeutic challenges posed by the simultaneous management of these neoplasms. This case underscores the critical importance of thorough diagnostic evaluation and multidisciplinary planning in managing complex oncological scenarios. The concurrent presentation of LEC and GCT in the head and neck region necessitates individualized approaches, integrating surgical precision and adjuvant therapies. The rarity of this co-occurrence highlights the need for further studies to refine diagnostic markers and therapeutic guidelines, improving patient outcomes.

Primary squamous cell carcinoma (SCC) of the temporal bone is an extremely rare malignancy, comprising only 0.2% of head and neck cancers. There is currently no universally accepted staging system for these tumors. This study evaluates the utility of the Pittsburgh staging system for temporal bone SCC, examines prognostic factors, and reports clinical outcomes. A retrospective review was conducted on a small cohort of 15 patients diagnosed with temporal bone SCC between 2020 and 2023. Imaging included high-resolution CT and MRI (T1W, T2W, and DWI). Staging accuracy was assessed, and Cohen’s Kappa coefficient was used to compare radiological and pathological staging. Results showed a 73% accuracy in preoperative radiological staging, with higher agreement for T3/T4 tumors (86%) compared to T1/T2 (63%). MRI provided additional information, revealing dural enhancement in two patients and parotid involvement in one. Survival analysis indicated 100% survival in T1/T2 patients, 25% in T3, and 0% in T4, supporting the prognostic value of the Pittsburgh system. While limited by the small sample size, the study confirms that the Pittsburgh staging system offers a reliable approach to stratifying patients with temporal bone SCC and underscores the importance of combined CT and MRI for accurate staging and treatment planning.

A cancer of unknown primary site of origin (CUP) is a definition for neoplasms whose first—and unique—presentation is of a neck mass. The urgent need to identify and characterize the primary tumor imposes a precise, prompt, and individualized diagnostic pathway to best guide the treatment. For the aim of this work, 5323 patients were identified from case series ranging from the year 2016 to 2023, selecting, from the 605 total cases in 2019, the clinical cases that met the characteristics of a CUP, which concerned 28 individuals. The 5-year follow-up of the 28 patients examined in 2019 revealed that, in more than half of the patients, the site of onset of primary tumors could not be revealed. Of these, 9 patients were classified as being affected by a CUP, and 9 patients died of carcinoma of uncertain origin; in the remaining 10 patients, the investigations were able to reveal the primary tumor. The lack of identification of a primary tumor prevents the patient from being treated with a curative intent. The identification of the primary tumor is achieved through a pathway of investigations that involves several approaches from a multidisciplinary perspective. The contribution of imaging and its increasingly important role, along with the implementation of its techniques and technologies, help make certain diagnoses in less time.