Accuracy of World Health Organisation-grade parameters (necrosis and mitotic activity) and foci of vascular invasion in predicting prognosis of papillary thyroid carcinoma. A case-control validation study.

AIMS: Tumour necrosis and/or increased mitoses define high-grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut-offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non-anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. METHODS: We analysed 50 consecutive PTC cases with distant metastases (DM-PTC): 16 synchronous and 34 metachronous. A total of 108 non-metastatic PTC (N-DM-PTC, 15.0-year median follow-up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut-offs predictive of distant metastases. RESULTS: Metastases correlated with necrosis (any extent = 43.8% all DM-PTC, 53.1% metachronous DM-PTC versus 5% N-DM-PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut-off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM-PTC (AUC = 0.78), 18.8%/97.2% synchronous DM-PTC (AUC = 0.63), 54.6%/97.2% metachronous DM-PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut-off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM-PTC (AUC = 0.75), 25%/91.7% synchronous DM-PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM-PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM-PTC. CONCLUSION: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM-PTC.

Resistance of Primary Photosynthesis to Photoinhibition in Antarctic Lichen Xanthoria elegans: Photoprotective Mechanisms Activated during a Short Period of High Light Stress.

The Antarctic lichen, Xanthoria elegans, in its hydrated state has several physiological mechanisms to cope with high light effects on the photosynthetic processes of its photobionts. We aim to investigate the changes in primary photochemical processes of photosystem II in response to a short-term photoinhibitory treatment. Several chlorophyll a fluorescence techniques: (1) slow Kautsky kinetics supplemented with quenching mechanism analysis; (2) light response curves of photosynthetic electron transport (ETR); and (3) response curves of non-photochemical quenching (NPQ) were used in order to evaluate the phenomenon of photoinhibition of photosynthesis and its consequent recovery. Our findings suggest that X. elegans copes well with short-term high light (HL) stress due to effective photoprotective mechanisms that are activated during the photoinhibitory treatment. The investigations of quenching mechanisms revealed that photoinhibitory quenching (qIt) was a major non-photochemical quenching in HL-treated X. elegans; qIt relaxed rapidly and returned to pre-photoinhibition levels after a 120 min recovery. We conclude that the Antarctic lichen species X. elegans exhibits a high degree of photoinhibition resistance and effective non-photochemical quenching mechanisms. This photoprotective mechanism may help it survive even repeated periods of high light during the early austral summer season, when lichens are moist and physiologically active.

Medullary Thyroid Carcinomas Classified According to the International Medullary Carcinoma Grading System and a Surveillance, Epidemiology, and End Results-Based Metastatic Risk Score: A Correlation With Genetic Profile and Angioinvasion.

Due to the lack of a standardized tool for risk-based stratification, the International Medullary Carcinoma Grading System (IMTCGS) has been proposed for medullary thyroid carcinomas (MTCs) based on necrosis, mitosis, and Ki67. Similarly, a risk stratification study using the Surveillance, Epidemiology, and End Results (SEER) database highlighted significant differences in MTCs in terms of clinical-pathological variables. We aimed to validate both the IMTCGS and SEER-based risk table on 66 MTC cases, with special attention to angioinvasion and the genetic profile. We found a significant association between the IMTCGS and survival because patients classified as high-grade had a lower event-free survival probability. Angioinvasion was also found to be significantly correlated with metastasis and death. Applying the SEER-based risk table, patients classified either as intermediate- or high-risk had a lower survival rate than low-risk patients. In addition, high-grade IMTCGS cases had a higher average SEER-based risk score than low-grade cases. Moreover, when we explored angioinvasion in correlation with the SEER-based risk table, patients with angioinvasion had a higher average SEER-based score than patients without angioinvasion. Deep sequencing analysis found that 10 out of 20 genes frequently mutated in MTCs belonged to a specific functional class, namely chromatin organization, and function, which may be responsible for the MTC heterogeneity. In addition, the genetic signature identified 3 main clusters; cases belonging to cluster II displayed a significantly higher number of mutations and higher tumor mutational burden, suggesting increased genetic instability, but cluster I was associated with the highest number of negative events. In conclusion, we confirmed the prognostic performance of the IMTCGS and SEER-based risk score, showing that patients classified as high-grade had a lower event-free survival probability. We also underline that angioinvasion has a significant prognostic role, which has not been incorporated in previous risk scores.

Foreign Body in the Cervical Oesophagus: A Case Report.

BACKGROUND: Foreign bodies in the upper aerodigestive tract represent an uncommon cause of visits to emergency departments. In the majority of cases, foreign bodies do not go beyond the pharynx. They cause dyspnoea or pneumonia if they reach the tracheobronchial tree. If ingested, they will pass spontaneously through the gastrointestinal canal in the majority of cases. Nevertheless, especially in the case of sharp-pointed or large objects, the foreign bodies can stop in the oesophagus. In case of dysphagia, stinging sensation and/or odynophagia occurring after eating a meal, a foreign body in the upper aerodigestive tract should be suspected. If not clinically visible, imaging is required. CASE PRESENTATION: A 72-year-old woman presented to the Emergency Department with pharyngodynia, odynophagia, stinging, dysphagia, and sialorrhea for 12 hours. Her symptoms started after eating a meal involving meat. The patient underwent a standard two-projection radiogram of the neck. The antero-posterior projection radiogram was unremarkable. The lateral projection radiogram showed 16 millimetres in maximum length radiopaque foreign body within the cervical oesophagus. The patient underwent transoral flexible oesophagoscopy under general anaesthesia, which resulted in successful removal of the foreign body (bony fragment). Her symptoms improved rapidly after the procedure, and the patient was discharged after 48 hours in good health. CONCLUSION: A foreign body in the cervical oesophagus may lead to visceral perforation. Once suspected, every effort should be made to identify and remove the foreign body to avoid potentially catastrophic consequences. In some cases, imaging could be necessary to detect the foreign body.

Hemithyroidectomy and ipsilateral central neck dissection for T1 low-risk papillary thyroid cancer: single-institution retrospective observational study.

Objective: The aim of this study was to report the rationale and selection criteria for hemithyroidectomy and ipsilateral central neck dissection in patients with selected papillary thyroid cancer and to report the surgical and oncological outcomes. Design: Single-institution retrospective observational study. Methods: The clinical records of patients with a histopathological diagnosis of low-risk pT1 papillary thyroid cancer who underwent hemithyroidectomy with or without ipsilateral central neck dissection between March 2000 and April 2018 at a tertiary referral center were retrospectively reviewed. Demographic, clinical, and histopathological data were collected. Results: During the study period, 176 patients underwent hemithyroidectomy for PTC. Thirteen patients (13/176, 7.39%) were lost to follow-up and 74 patients (74/163 45.40%) underwent completion thyroidectomy within 1 month because they were classified intermediate ATA initial risk based on definitive pathology. The final study group was composed of 89 patients, who had a median follow-up of 5.3 years. The mean follow-up was 6.3 years (range: 36-207 months). Eighty-four patients (94.38%) did not experience recurrence in the follow-up period. A total of 5/89 patients (5.62%) underwent delayed completion thyroidectomy with or without neck dissection for recurrent malignancy in the residual lobe (3/5) or regional lymph nodes (2/5). The median time from surgery to recurrence was 24.8 months (range: 6-60). The follicular variant was an independent risk factor for recurrence. Conclusions: Hemithyroidectomy with or without prophylactic ipsilateral central neck dissection is a valuable treatment option in selected low-risk papillary thyroid cancers and ensures a low risk of recurrence. Prophylactic ipsilateral central compartment dissection could have a role in improving cancer staging, and accurate ultrasonographic follow-up is essential to identify local recurrence.

Congenital Nasal Pyriform Aperture Stenosis: Successful Management of Restenosis After Primary Surgery by Stent Placement.

Congenital nasal pyriform aperture stenosis (CNPAS) is a rare anomaly causing respiratory distress in newborns. While the primary surgical technique is well established, the timing of the removal of the stents and the management of restenosis remain a matter of debate. We report a case of a female newborn affected by CNPAS with the recurrence of respiratory distress after primary surgery due to the early removal of nasal stents, causing an overgrowth of granulation tissue. This report notes that restenosis was successfully managed by repeating the procedure over a 14-day period, with soft polyvinyl chloride uncuffed tracheal tubes acting as nasal stents.

Postoperative hypoparathyroidism after completion thyroidectomy for well-differentiated thyroid cancer.

OBJECTIVE: Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged. DESIGN: Single-institution retrospective observational study. METHODS: The clinical records of 786 patients treated at the Otolaryngology Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Patients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delayed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the primary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes. RESULTS: Rates of transient HPT in group TT were higher than those observed in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transient HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and permanent HPT for group TT (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: This study suggests that the risk of transient postoperative HPT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid neoplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications.

Pneumolabyrinth: a systematic review.

PURPOSE: The aim of this study is to provide a systematic review of the literature about the etiology, clinical and radiological presentation, surgical management, and outcomes of pneumolabyrinth (PNL). METHODS: A systematic review of the literature was performed including studies published up to September 2020 in electronic databases (PubMed/MEDLINE, EMBASE, Cochrane Library, and Scopus). The PRISMA standard was applied to identify English, Italian, or French-language studies mentioning PNL. Full texts lacking information on the etiology were excluded. Data concerning the cause, site of air bubbles/fistula, clinical presentation, treatment, and outcome were collected. A qualitative synthesis of the results was performed. RESULTS: Seventy-eight articles were eventually included; 132 patients were involved in the qualitative synthesis. The most common causes were: stapes surgery (24/132, 18.2%), temporal bone fracture (42/132, 31.8%), head trauma without temporal bone fracture (19/132, 14.4%), penetrating trauma (21/132, 15.9%), and barotrauma (15/132, 11.4%). The site most commonly involved was the vestibule (102/107, 95.3%), followed by cochlea (43/107, 40.2%) and semicircular canals (25/107, 23.4%). CONCLUSION: The etiopathogenesis of PNL can be summarized in traumatic, iatrogenic, or inflammatory/infective. Its management consists in exploratory tympanotomy and sealing the fistula, but also conservative treatments can be attempted. Vestibular symptoms disappear in the majority of cases. Instead, the prognosis of hearing function is widely variable, and complete recovery is less probable. The certainty of evidence is still too low to make it useful for clinical decision-making.

Differentiated Thyroid Cancer: The Role of ATA Nodal Risk Factors in N1b Patients.

OBJECTIVES/HYPOTHESIS: Nodal involvement is frequent in patients with differentiated thyroid cancers (DTCs), but its prognostic relevance is not univocal. Some characteristics of nodal metastases can increase the risk of recurrence. We attempted to quantify the impact on survival of nodal factors included in the American Thyroid Association (ATA) risk stratification system in N1b patients with DTC. STUDY DESIGN: Retrospective study. METHODS: A retrospective analysis of patients affected by DTC who underwent therapeutic lateral neck dissection (ND) was performed. The impact on the prognosis of the number of positive lymph nodes (LNs), dimension of nodal metastasis, and microscopic and macroscopic extranodal extension (miENE and maENE, respectively) was investigated. RESULTS: The study included 347 N1b patients who underwent 401 therapeutic lateral NDs. Mean number of positive LNs was nine, mean nodal ratio was 0.27, and mean diameter of metastasis was 15.5 mm. ENE was detected in 25.9% of patients (22.5% miENE and 3.5% maENE). In univariate analysis, the presence of maENE had an impact on disease specific survival (DSS) (P = .023); increasing number of positive LNs affected DSS and locoregional control (LRC) (P = .009 and =.006, respectively); increasing metastatic node dimension was a risk factors for overall survival, DSS, and metastases free survival (MFS) (P = .05, =.013 and =.016). In multivariate analysis, number of positive LNs and LN dimension were independent risk factors for LRC and MFS, respectively (HR 1.1, P = .028; HR 1.1, P = .026). CONCLUSIONS: In our analysis on a cohort of N1b patients, the number of positive LNs and LN dimension were confirmed as independent risk factors for locoregional and distant recurrence, respectively. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1029-E1034, 2021.

Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature.

Anaplastic carcinoma (AC) is a rare but highly aggressive form of thyroid cancer. It mostly arises on a background of pre-existing well-differentiated cancer (WDC); however, whether it evolves directly from a WDC or originates as a second independent neoplasm is still to be defined. To obtain further insights into these mechanisms, we performed morphological, immunohistochemical, and next-generation sequencing analyses to compare AC and its associated WDC in a subset of 13 surgically resected specimens. Histologically, most WDC were of aggressive subtypes. Papillary carcinomas (8 cases; 62%) were tall cell (4/8), columnar (1/8), classic with hobnail features (1/8), classic and follicular variant in the remaining 2 cases; Hürthle cell and follicular carcinomas were present in 5 (38%) and in 1 (8%) patient, respectively. One patient harbored both a PTC, follicular variant, and a Hürthle cell carcinoma. We did not find any correlation between a histotype of WDC and a specific anaplastic growth pattern. Immunohistochemically, ACs retained pankeratin/PAX8 expression but with significantly lower levels than WDCs, and they tended to lose TTF1 expression, as can be expected within a dedifferentiation process. In addition, AC showed a more frequent expression of p63 and/or SMA, a mutated pattern of p53, and an abnormal expression of p16. Genetic analysis showed that the number of mutations was higher in AC than in the associated WDC, confirming a role of the progressive accumulation of genetic damage in this transition. We observed that mutations found in the WDCs were consistently identified in the anaplastic counterparts, further supporting the hypothesis of a developmental link.

Cost-effectiveness in transient hypocalcemia post-thyroidectomy.

BACKGROUND: Three different strategies to manage transient hypocalcemia after total thyroidectomy were compared to evaluate cost-effectiveness. The reliability of total serum calcium (TSCa), ionized calcium (ICa), and intact parathyroid hormone (iPTH) were investigated to achieve this goal. METHODS: A multicenter, prospective randomized study was carried out with 169 patients. The strategies were "preventive" (oral calcium + vitamin D supplementation), "reactive" (therapy in hypocalcemia), and "predictive" (therapy if iPTH <10 pg/mL). RESULTS: TSCa had higher accuracy in identifying patients who developed hypocalcemia-related symptoms than ICa (84.6% vs 50.0%). TSCa 24 h after surgery showed 24.8% of patients with hypocalcemia, whereas TSCa 48 h after surgery identified a further 10.6% with hypocalcemia (only in the "reactive" and "predictive" groups). iPTH showed low sensitivity as a predictor of hypocalcemia. Between the 3 groups, there was no significant difference in hospitalization time or number of symptomatic hypocalcemic patients. Interestingly, the cost-per-patient was significantly different among the groups. CONCLUSIONS: None of the discussed strategies allowed for early discharge of patients without any risk of transient hypocalcemia. The "preventive" strategy was the most cost-effective, despite overtreatment.

Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma.

The NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell-cell interactions. NOTCH family members play a fundamental role in a variety of processes during development in particular in cell fate decisions. As other crucial factors during embryogenesis, NOTCH signaling is aberrantly reactivated in cancer where it has been linked to context-dependent effects. In thyroid cancer, NOTCH1 expression has been associated to aggressive features even if its in vivo expression within the entire spectrum of thyroid tumors has not definitively established. A series of 106 thyroid specimens including non-neoplastic lesions, benign and malignant tumors of common and rare histotypes, were investigated by immunohistochemistry to assess NOTCH1 expression. Extent of positivity and protein localization were investigated and correlated with clinical and morphological parameters. NOTCH1 positivity was predominantly associated with papillary carcinomas and only occasionally found in follicular carcinomas. Poorly differentiated and undifferentiated thyroid carcinomas showed only a partial positivity. NOTCH1 expression pattern also seemed differently distributed according to histotype. Our data confirm a role of NOTCH1 in thyroid cancer and highlight for the first time the specific involvement of this pathway in papillary carcinomas. Our data also indicate that other thyroid malignancies do not rely on NOTCH1 signaling for development and progression.

LATERAL NECK DISSECTION FOR AGGRESSIVE VARIANTS OF WELL-DIFFERENTIATED THYROID CANCER.

Objective: Well-differentiated thyroid cancer (WDTC) is characterized by favorable disease course and excellent survival. However, some histologic subtypes, known as aggressive histologic variants (AHVs), present a more aggressive behavior than conventional WDTC. The aim of this study was to evaluate the pattern of nodal involvement and factors influencing prognosis in N1b patients with AHVs. Methods: A multicentric retrospective analysis of patients who underwent therapeutic lateral neck dissection (ND) for WDTC between 1994 and 2015 was accomplished. AHVs included the following subtypes: tall cell, Hürtle cell, diffuse sclerosing, and poorly differentiated papillary thyroid cancer. Results: The study included a total of 352 N1b patients, 40 (11.4%) of whom had AHVs. AHVs present a similar distribution of positive nodes if compared with conventional WDTC. In AHV patients, 5-year overall survival (OS), disease-specific survival (DSS), locoregional control, and metastasis-free survival were 82.2%, 93.6%, 80.3%, and 87.3%, respectively. Advanced age (>55 years) was the only significant factor affecting survival (OS, P<.001; DSS, P = .011) in this group. In the AHV group, there were 9 (22.5%) recurrences; patients with regional recurrence and without distant metastases were effectively treated by surgery. Conclusion: The distribution of positive lymph nodes in case of AHVs is similar to that of conventional WDTC, with only level V at a relatively greater risk of harboring metastases in the former group. Survival outcomes in N1b patients with AHVs remain optimal. Total thyroidectomy, ND, and adjuvant radioiodine administration have been demonstrated to be effective treatments in the setting of AHVs. Abbreviations: AHV = aggressive histologic variant; DOD = died of disease; DSS = disease-specific survival; DSV = diffuse sclerosing variant; ETE = extrathyroidal extension; HCC = Hürthle cell carcinoma; LRC = locoregional control; LVI = lymphovascular invasion; MFS = metastasis-free survival; ND = neck dissection; NED = no evidence of disease; OS = overall survival; PDA = poorly differentiated areas; PTC = papillary thyroid carcinoma; RAI = radioiodine therapy; TCV = tall cell variant; WDTC = well-differentiated thyroid cancer.

HIV-related non-Hodgkin Lymphoma. Case report and review of the literature.

BACKGROUND: HIV-related Burkitt's lymphoma with initial oropharyngeal presentation is rarely reported. The aim of this paper is to report the clinical findings of an unusual case of a patient with extranodal oropharyngeal Burkitt's lymphoma as presenting disease of an unknown HIV positivity and acquired immunodeficiency syndrome. METHODS: We reported the case of a hispanic patient with extranodal oropharyngeal Burkitt's lymphoma as presenting disease of an unknown HIV positivity and acquired immunodeficiency syndrome. We describe the diagnostic work-up and treatment of this rare case of extranodal oropharyngeal Burkitt's lymphoma. RESULTS: Histological exam on oropharyngeal incision biopsy documented a Burkitt's lymphoma. The patient underwent highly active antiretroviral therapy and chemotherapy. After two years of follow-up the patient shows no signs of recurrence from disease. CONCLUSIONS: HIV-related Burkitt's lymphoma presenting with primary oropharyngeal involvement is rare, with rapidly progressing dysphagia, and does not respond to antibiotherapy. Patients should undergo incision biopsy to rule out a malignancy. In young adults, diagnosis of Burkitt's lymphoma should suggest HIV infection. The importance of a prompt diagnosis in such cases is essential to correctly adequately staging the disease to start highly active antiretroviral therapy and chemotherapy as soon as possible.

Isolated horizontal canal hypofunction differentiating a canalith jam from an acute peripheral vestibular loss.

OBJECTIVES: To describe a unique case of acute vertigo presenting with spontaneous horizontal nystagmus (SHN) and a clinical picture consistent with right acute peripheral vestibular loss (APVL) in which an isolated hypofunction of a horizontal semicircular canal (HSC) permitted to detect a spontaneous canalith jam and treat the patient accordingly. METHODS: Case report and literature review. RESULTS: A 74-year old woman presented with acute vertigo, left-beating SHN and a clinical picture consistent with right APVL. Nevertheless, vestibular evoked myogenic potentials were normal with symmetrical amplitudes and the video head impulse test (vHIT) revealed an isolated hypofunction of the right HSC. After repeated head shakings, the supine roll test evoked bilaterally a positioning paroxysmal geotropic horizontal nystagmus suggesting benign paroxysmal positional vertigo involving the non-ampullated arm of the right HSC. vHIT and caloric testing confirmed restitution of HSC function after repositioning maneuvers. CONCLUSIONS: In case of acute vertigo with SHN, a complete functional assessment of vestibular receptors and afferents should always be given in order to avoid misdiagnosis. Canalith jam should be considered in case of spontaneous nystagmus and isolated canal hypofunction.