Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.

UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells' resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies.

Single bone metastasis from adenocarcinoma of the lacrimal gland: a case report.

Malignant tumors of the lacrimal gland are rare, and single bone metastases from lacrimal gland carcinoma are an exceptional event. We present the case of a 71-year-old man with a history of lumbar pain and left exophthalmos. Surgical resection of the lacrimal lesion and a bone biopsy gave a final histopathological diagnosis of primary ductal adenocarcinoma of the lacrimal gland with bone metastasis. The pathological tissue from both procedures was positive for androgen receptor expression. The patient underwent embolization and radiotherapy in association with total androgen blockade. After 20 months, the patient is still asymptomatic and has maintained the partial response at L1 with no progression to other sites. Our patient would appear to have a better prognosis and the disease a more indolent clinical course than the other cases of ductal adenocarcinoma of the lacrimal gland reported in the literature.

Family history of cancer and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).

Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers.

The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2'deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy.

Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a Western population.

BACKGROUND: Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. METHODS: We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. CONCLUSIONS: The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases.

Three-dimensional conformal postoperative radiotherapy in patients with parotid tumors: 10 years' experience at the European Institute of Oncology.

AIMS AND BACKGROUND: Salivary gland malignancies are rare. The aim of our study was to investigate radiotherapy-related toxicity and clinical outcome in patients treated at our division with postoperative radiotherapy (pRT) for parotid tumors. METHODS AND STUDY DESIGN: Forty-three consecutive patients (32 with primary parotid tumors, 9 with parotid metastases and 2 with recurrent benign diseases) were retrospectively analyzed. RESULTS: The median follow-up was 28 months. Twenty and 5 patients had a follow-up longer than 2 and 5 years, respectively. Thirty-seven patients were alive and most of them (78%) were free from disease. The local and distant control rates were higher in patients with primary parotid tumors (94% and 87.5%) than in patients with parotid metastases (87.5% and 75%). Grade 3 radiotherapy-related acute toxicity of skin and mucosa was recorded in 20.9% and 28% of patients, respectively. Two patients (4.7%) had grade 4 skin toxicity. Late toxicity data were available for 33 (77%) patients. None of the patients developed severe (grade 3 and 4) late toxicity of soft tissues, skin or temporomandibular joints. CONCLUSIONS: Postoperative radiotherapy is a feasible treatment that was found to be effective mainly in patients with primary parotid tumors. Toxicity was acceptable but could probably be further reduced using more advanced radiotherapy techniques. Longer follow-up is required to achieve definitive results.

Oral cancer: changing the aim of the biopsy in the age of precision medicine. A review.

Oral cancer is a heterogeneous disease that develops through a complex, multi-step process. Precision medicine should help to better understand its molecular basis, integrate traditional classifications and have a positive impact on cancer management. To apply this information in clinical practice, we need to define its histology and identify biomarkers expressed by the tumour that provide useful information for planning tailored treatment. The most reliable information currently derives from evaluation of biomarkers on post-operative samples. To plan personalised treatment, oncologists need to assess these markers on biopsy samples. We reviewed the recent literature and identified 6 of 184 publications that compared markers measured on biopsy and post-operative samples or assessed their predictivity for the development of lymph node metastases. Data from these studies suggest that markers measured on biopsy samples can provide useful indications for tailoring treatments. However, due to their heterogeneity and low level of evidence, these results need to be confirmed by clinical studies on a large population to standardise and validate biomarkers in biopsies and to assess their reliability in other diagnostic mini-invasive procedures such as radiomics and liquid biopsy.^ieng

Il cancro orale è una malattia eterogenea che origina ed evolve con un processo complesso e multifasico. La medicina di precisione permette di pianificare un trattamento personalizzato sulla base delle caratteristiche biologiche e molecolari delle singole neoplasie. Le informazioni oggi più affidabili sono fornite dalla valutazione post-operatoria dei biomarcatori, ma per pianificare un trattamento personalizzato è necessario valutare questi marcatori sulla biopsia. Per questo abbiamo rivisto la letteratura dell'ultimo quinquennio ed abbiamo identificato 6/184 articoli che valutano i marcatori sulla biopsia confrontandone i valori con quelli misurati sul pezzo operatorio di ciascun paziente o valutandone la predittività per lo sviluppo di metastasi linfonodali. I dati che emergono da questi studi suggeriscono che la valutazione dei marcatori sul campione bioptico potrebbe fornire indicazioni utili per programmare trattamenti personalizzati. Tuttavia, a causa della eterogeneità e del basso livello di evidenza dei lavori considerati, questi risultati devono essere confermati da studi clinici su un'ampia popolazione per standardizzare e validare i biomarcatori e la loro affidabilità in altre procedure mini-invasive, ad esempio radiomica e biopsia liquida.

US-guided transcutaneous tru-cut biopsy of laryngo-hypopharyngeal lesions.

OBJECTIVE: To evaluate the feasibility and performance of ultrasound-guided transcutaneous tru-cut biopsy (USGTCB) in selected patients (with stenosis of airways or difficult intubation or contraindication to general anaesthesia) with untreated or previously treated suspicious laryngo-hypopharyngeal masses. METHODS: Biopsies were performed with a free-hand technique by a single radiologist. Thirty-six USGTCBs were scheduled in 34 patients (24 males, 10 females; age range 47-95 years). Two USGTCBs were not performed, as lesions were not detectable: therefore, 16 USGTCBs were performed for an untreated mass suspicious for malignancy and 18 were performed for a mass suspicious for recurrence after radiotherapy alone, or associated with endoscopic laser surgery or chemotherapy. RESULTS: USGTCB diagnosed 25 squamous cell carcinomas (73.5%) and nine benign lesions (26.5%); no false positives and two false negatives were reported, both in patients previously treated with radiotherapy. The sensitivity, specificity, positive and negative predictive value of the technique was 92.5%, 100%, 100% and 77.7% respectively, with no major complications. CONCLUSION: Although biopsy under microlaryngoscopy remains the "gold-standard" technique, USGTCB is feasible, carries the advantages of avoiding general anaesthesia, is suitable for outpatients and is cost-effective. If applied to selected patients, it could be considered for the histological diagnosis of both primary and recurrent laryngo-hypopharyngeal masses.

Transoral CO2 laser microsurgery for Tis-T3 supraglottic squamous cell carcinomas.

Eighty patients affected by supraglottic cancer were treated by transoral carbon dioxide laser surgery between 1989 and 2006 in two Italian institutions. Patient staging was as follows: 2 pTis, 20 pT1, 38 pT2, and 20 pT3. Simultaneous or 1-month delayed neck dissection (ND) was performed on 27 (34%) patients, unilaterally in 10 and bilaterally in 17. The pN category was as follows: 9 pN0, 6 pN1, 8 pN2b, and 4 pN2c. A total of 16 (20%) patients received complementary radiotherapy (RT) and 5 (6%) were subjected to chemo-RT for persistent tumor after re-excision due to positive margins, multiple lymph nodes, and/or extracapsular spread after ND. The last follow-up was in December 2008. The 5-year overall, disease-specific and disease-free survivals, local control with laser alone, and organ preservation rates calculated by Kaplan-Meier analysis were 84.4, 97.4, 88.3, 96, and 97.2%, respectively. Univariate analysis showed a statistically significant impact on disease-free survival, local control with laser alone, and organ preservation of pT category (p = 0.009, p = 0.01, and p = 0.03, respectively), while pN category and tumor stage negatively influenced disease-free survival (p = 0.007 and p = 0.01, respectively). This series confirms the good overall oncologic outcomes obtained by transoral laser surgery for Tis, T1, T2, and selected T3 supraglottic cancer with minimal pre-epiglottic space involvement.

Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study.

Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000-2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.

Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume.

OBJECTIVE: The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. MATERIALS AND METHODS: Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. RESULTS: The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. CONCLUSIONS: In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.

Classification of GLOSSECTOMIES: Proposal for tongue cancer resections.

BACKGROUND: Surgery of tongue tumors includes different procedures ranging from mucosal resection to complex combined resection. Numerous terms have been used to describe such procedures, but there is no consensus between the terminology and the extent of resection. METHODS AND RESULTS: We searched the medical literature and found a lack of published information. We undertook to describe a new classification of surgical procedures for tongue tumor resection. We based it upon the surgical anatomy of the tongue and the spread of the cancer. We posited that there were five major types of glossectomy embracing all the methods of tongue cancer resection. This classification was reviewed and endorsed by an international team of experts. CONCLUSION: We propose a more precise classification than that currently in practice, thereby bringing clarity and consistency to the terminology, facilitating shared communication between surgeons, comparison between published research, and ultimately improving surgical practice and patient care.

Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients.

PURPOSE: The management of patients with cervical lymph-node metastases from unknown primary site (UPS) remains a matter of discussion. This study aimed to analyze the results and prognostic factors in a series of patients treated with radiotherapy. METHODS AND MATERIALS: Data from 113 patients who presented with cervical lymph nodes metastases from UPS treated from 1980 to 2004 were reviewed. Eighty-seven patients (77.0%) were squamous cell carcinoma (SCC). Ninety-one patients were treated with curative and 22 with palliative intent. Fifty-nine of 113 patients (52.2%) received surgery followed by radiotherapy and 54 of 113 (47.8%) received radiotherapy alone. Radiotherapy was delivered to the neck and pharyngeal mucosa in 67 patients and to the ipsilateral or bilateral neck in 45 patients. Twenty-one patients (18.5%) also received chemotherapy. RESULTS: The 5-year overall survival rates were 40.7% for the entire group and 46.6% for the SCC subgroup. The occurrence of the occult primary was observed in 23 of 113 patients (20.3%), 19 (82.6%) within the head and neck region. At multivariate analysis, treatment with curative intent and extensive irradiation of bilateral neck and pharyngeal mucosa were favorable prognostic factors for the whole series, and treatment with curative intent, extensive irradiation of bilateral neck and pharyngeal mucosa, and absence of extracapsular spread were favorable prognostic factors for the SCC subgroup. CONCLUSIONS: Patients with cervical lymph node metastases from UPS have a similar prognosis to those affected by other head and neck malignancies. Curative treatment strategies including neck dissection and extensive irradiation by three-dimensional conformal radiation therapy resulted in significantly better outcomes.

Endoscopic carbon dioxide laser surgery for glottic cancer recurrence after radiotherapy: oncological results.

OBJECTIVE: To evaluate local control, organ preservation, and complications after endoscopic laser surgery for early recurrent glottic cancer after radiotherapy. DESIGN: Retrospective study. SETTING: European Institute of Oncology, Milan, Italy. PATIENTS: The study, which was conducted between May 1999 and September 2005, included 37 consecutive patients (33 men and 4 women) with recurrent glottic cancer after radiotherapy. Selection criteria were as follows: rcTis, rcT1, or rcT2 with subglottic or supraglottic involvement of less than 5 mm and no arytenoid invasion; adequate laryngeal exposure; no previous open surgery; no contraindications to general anesthesia; and signed consent. INTERVENTIONS: Endoscopic laser surgery with curative intent using types III to V cordectomies according to the European Laryngological Association. MAIN OUTCOME MEASURES: Five-year actuarial recurrence-free and overall survival, complications, and rate of laryngeal preservation. RESULTS: The clinical classifications of the recurrences were rcTis (n = 4), rcT1a (n = 10), rcT1b (n = 11), and rcT2 (n = 12). The pathologic classifications of the recurrences were rpT0 (n = 2), rpTis (n = 5), rpT1a (n = 9), rpT1b (n = 3), rpT2 (n = 14), and rpT3 (n = 4). The median follow-up was 44 months (range, 18-88 months). New recurrences developed in 13 patients (35%): 11 were treated by total laryngectomy, 1 by supracricoid laryngectomy, and 1 by chemotherapy. Three patients died of laryngeal cancer, 1 is alive with disease, and 1 died of a second cancer. Five-year actuarial recurrence-free and overall survival rates were 58% and 86%, respectively. The larynx was preserved in 26 patients (70%). Laryngeal stenosis was the most common major complication (in 3 of 4 women and 1 of 33 men). CONCLUSIONS: Endoscopic laser surgery is a safe and effective salvage procedure in selected cases involving glottic recurrence after radiotherapy. Oncological results are satisfactory, and organ preservation can be achieved in a high proportion of cases; however, the risk of laryngeal stenosis is high in women.

Multicentric prospective study on the prevalence of sublevel IIb metastases in head and neck cancer.

OBJECTIVE: To evaluate the prevalence of sublevel IIB lymph node (LN) metastases for head and neck primary tumors in a large cohort of patients. DESIGN: Prospective study. SETTING: One referral university hospital and 2 national institutes of oncology. PATIENTS: Between 2003 and 2005, 297 patients (male to female ratio, 3.5:1; mean age, 58.8 years [range, 18-89 years]) affected by head and neck cancer were treated by surgery on the primary tumor and/or the neck. Primary site distribution included the following: oral cavity in 111 patients, larynx in 92, oropharynx in 32, thyroid gland in 22, skin of the lateral face or scalp in 16, hypopharynx in 11, unknown primary in 7, and parotid gland in 6. Sublevel IIB was evaluated for the number of LNs and pathologic N (pN) status. INTERVENTIONS: All patients underwent unilateral or bilateral neck dissection (ND) with therapeutic or elective intent according to the primary site and clinical T (cT) and clinical N (cN) status. Sublevel IIB was selectively dissected at the beginning of ND, labeled, and processed independently. MAIN OUTCOME MEASURES: The distribution of metastases among the different levels was analyzed. The influence of several factors (institution in which the surgical procedure was performed, sex of the patient, site of primary, histotype, pathologic T [pT] status, cN status, lower level involved in the neck together with sublevel IIB, association with sublevel IIA metastasis, ipsilateral number of involved levels, and previous surgical treatment limited on the primary site) on the prevalence of sublevel IIB metastasis was statistically evaluated by the Pearson chi(2) test or Fisher exact test. RESULTS: A total of 443 NDs were performed (unilateral in 151 patients and bilateral in 146). Among the patients, the tumors were staged cN0/pN0 in 27%, cN+/pN+ in 50%, cN+/pN0 in 7%, and cN0/pN+ in 16%. The mean number of LNs collected at sublevel IIB was 5.4 (range, 0-24). The overall prevalence of sublevel IIB metastases was 5.6% (26 neck sides). Tumor histologic type in the sublevel IIB+ population was squamous cell carcinoma in 80%, papillary carcinoma in 8%, melanoma in 8%, and adenocarcinoma in 4%. The chi(2) test showed a significantly higher risk for LN metastases at sublevel IIB in patients affected by parotid gland primary tumors (33%), tumors of the skin or scalp (25%), unknown primary tumors (14%), and cancers of the oral cavity (10%) (P = .02) and in those clinically staged as cN+ (P < .001). CONCLUSIONS: Sublevel IIB dissection is strongly recommended for all patients with cN+ tumors and in those affected by tumor of the parotid gland, skin, and scalp scheduled for elective ND. Patients affected by laryngeal cancer scheduled for elective ND can be considered the ideal candidates for preservation of sublevel IIB. However, whether this policy could be associated with a better functional outcome remains to be demonstrated by prospective studies on a large series of patients.

Retrospective analysis of factors influencing oncologic outcome in 590 patients with early-intermediate glottic cancer treated by transoral laser microsurgery.

BACKGROUND: The purpose of this study was to identify the factors influencing oncologic outcomes for patients with early-intermediate glottic cancer treated by transoral laser microsurgery (TLM). METHODS: This was a retrospective mono-institutional study. A total of 590 patients with cTis-cT3 glottic cancer underwent TLM with curative intent. RESULTS: TLM alone was performed in 538 patients (91.2%) and TLM followed by adjuvant radiotherapy (RT) was done in 52 (8.8%). Five-year recurrence-free survival (RFS) and 10-year overall survival (OS) were 85.3% and 74.7%, respectively. The larynx-preservation ratio was 95.9%. In particular, from our data, we found that occult metastases were rare (1.2%); preventive tracheotomy was not necessary; the local recurrence rate of Tis was similar to that in the T2 and T3 group; and no major or lethal complications were observed. CONCLUSION: Age (>60 vs ≤60), type of cordectomy (≥IV vs ≤III), status of margins, fixed arytenoid, and pathologic T classification, were the variables associated with RFS, OS, and organ-preservation rate. © 2016 Wiley Periodicals, Head Neck 39: 71-81, 2017.

Branchiogenic carcinoma--conceptual or true clinico-pathological entity?

The existence of branchiogenic carcinoma remains controversial. According to some authors, this malignancy is more conceptual than a true clinicopathologic entity. The originally proposed diagnostic criteria of branchiogenic carcinoma have been subsequently challenged. Many reports regarding primary branchiogenic carcinoma have failed to provide sufficient evidence to distinguish this entity from nodal metastases arising from unrecognized primary tumours. There is growing evidence that the majority of branchiogenic carcinomas are in fact cystic metastases from oropharyngeal carcinoma, most commonly originating in the tonsils, and not true carcinomas arising in a branchial cleft cyst. The missing link between branchial cyst and branchiogenic squamous cell carcinoma could be fulfilled by the occurrence of in situ branchial cyst carcinomas, yet such cases are extremely rare. Isolated cystic neck lesions, necessitate a thorough search for a primary tumour, similarly to other occult primaries presenting with cervical metastases. The treatment of cervical cyst with dysplasia or carcinoma in situ includes complete surgical excision. The true branchiogenic carcinomas should be approached with postoperative irradiation to the half neck. A cervical metastatic cystic squamous carcinoma of unknown origin should be treated as for other cases of occult primaries, i.e. with surgery and radiotherapy. The data on the prognosis of branchiogenic carcinoma are scarce, though long-term survival has been reported. Further histopathologic and clinical studies are warranted in order to better understand the biology and natural history of cervical cystic lesions. The existence of true branchiogenic carcinoma remains to be verified with new clinical and molecular criteria.

Algorithm to predict postoperative complications in oropharyngeal and oral cavity carcinoma.

BACKGROUND: Preoperative data in patients with oral cavity/oropharyngeal cancer may predict postoperative complications that may modify therapeutic choices and improve patient care. METHOD: We reviewed 320 consecutive patients with oral cavity/oropharyngeal cancer, operated on 2003 through 2006 at the European Institute of Oncology. By multivariate analysis of preoperative patient and tumor characteristics, we developed an algorithm to predict postoperative complications. We tested the algorithm on a new series of 307 patients operated on 2007 through 2010. RESULTS: The final algorithm used to produce a nomogram was comprised of: alcohol consumption (p = .01), site of primary (p = .03), interaction of clinical T classification to sex (p = .007), and type of neck dissection (p < .0001). The algorithm had good ability to predict complications (concordance index [c-index] 0.74) in the new series. CONCLUSION: The nomogram accurately predicts presurgical risk of postoperative local/systemic complications in patients with oral cavity/oropharyngeal cancer and can be used to adapt therapy to patient characteristics, optimize ward admissions, and improve care.

Major surgery in elderly head and neck cancer patients: immediate and long-term surgical results and complication rates.

BACKGROUND: Evaluation of immediate and long-term surgical results in major surgery for the head and neck tumours in elderly patients and identification of tumour and patient related factors that affect the incidence and severity of surgical and medical complications. METHODS: Retrospective analysis of a series of 24 consecutive patients aged 70 and over with head and neck tumours undergoing extensive surgical resections with reconstruction with/without osseous and/or soft tissue transfer. Patients' demographics and surgery and tumour related data were extracted from appropriate charts and recorded. Pre-existent comorbid conditions, immediate and long-term surgical and medical complications were analysed. Pre-existing comorbidities were graded and staged using the Comorbidity Data Collection Form. Postoperative surgical and medical complications were scored according to their severity. RESULTS: Overall complication rate in present study was 63% and 54% of patients experienced clinically important surgical and/or medical complications. However, medium admission time remained at 16 days. Presence of advanced comorbidity, longer operative times and advanced stage of disease seemed to influence the development of surgical or medical complications. CONCLUSIONS: Major surgery for head and neck tumours is of great value even in elderly patients providing very good surgical results with acceptable complication rates. The choice of treatment modality should be based on all factors affecting the treatment outcomes. In particular, the presence of the co-existent underlying diseases should be assessed meticulously and in cases with clinically important comorbidities the surgical treatment stress should be reduced to minimum.

Hypercalcitoninemia and thyroid nodules: when cytology (still) matters.

Medullary thyroid carcinoma (MTC) can assume various cytomorphological and architectural forms, mimicking other thyroid and extra-thyroid tumors and rendering the cytological and histological diagnosis challenging. Consequently, measurement of calcitonin (CT) levels is generally considered to be more accurate than cytology in diagnosing MTC. Here, we report on a patient with a multinodular goiter and significantly elevated basal CT levels; based on cytology examination and CT immunocytostains, neither MTC nor C-cell hyperplasia was detected upon final histopathological examination. CT testing has a high false-positive rate and low positive predictive value for detecting clinically relevant MTC. Judicious integration of cytological examination with immunocytochemical stains (when needed) may be useful for selecting the most appropriate therapy and avoiding overtreatment (i.e., central neck lymph node dissection in the present case). This case demonstrates that cytological examination with ancillary techniques is still valuable in patients with thyroid nodules and suspicious MTC.