Laryngeal sarcomas constitute an extremely rare entity among head and neck malignancies. Furthermore, most of them are chondrosarcomas, and the osteogenic form remains a true rarity. In general, there is a lack of information on the characteristics of laryngeal osteosarcoma. Thus, we sought to critically review the existing world literature on laryngeal osteosarcoma in order to develop a more accurate clinicopathological profile of this malignancy. Laryngeal osteosarcoma has a predilection for elderly male patients, as 87% were male in the present series and the mean age was 62 years (range 32–80), and without a direct association with tobacco exposure. Osteosarcoma of the larynx is typically a highly malignant neoplasm that metastasizes early, has a propensity for hematogenous spread and also has a marked tendency to recur. Twelve (41%) out of the 29 cases in the present review with follow-up data had metastatic disease. The aspects that distinguish osteosarcoma from its differential diagnostic alternatives are discussed in this review.

BACKGROUND:The current treatment results of laryngeal squamous cell carcinoma still remain modest. Various prognostic factors have been investigated and need to be included in the management decision making.METHODS:We reviewed the pertinent literature regarding host, tumor, and treatment factors as prognostic indicators that influence outcome in patients diagnosed with laryngeal squamous cell carcinoma.RESULTS:Host, tumor, and treatment factors all have an important impact upon an individual patient's prognosis with laryngeal squamous cell carcinoma, whereas staging systems only take into account tumor factors. There is much work yet to be done to establish reliable, independent biomarkers that predict survival and response to treatment.CONCLUSIONS:Optimal outcomes for an individual patient can be achieved when taking into account tumor, host, and treatment factors.

Well-differentiated neuroendocrine carcinoma (also known as “carcinoid”) of the larynx is an exceedingly rare tumor that has an epithelial origin. These tumors are malignant and have a low, but definite, risk of metastasis. Although it can be challenging, this tumor should be differentiated from moderately differentiated neuroendocrine carcinoma (also known as “atypical carcinoid”). The clinical and pathologic features of this tumor, as well as treatment and prognosis, are reviewed in detail.

Current knowledge of laryngeal neuroendocrine cells in man and other vertebrates is reviewed. Particular attention is paid to differences in the distribution of neuroendocrine cells between squamous and respiratory laryngeal mucosa, foetal versus post-natal spatial arrangements, relation to the laryngeal cavity and nerve fibres, and immunoreactivities of these cells. Methodological deficiencies and gaps in knowledge are outlined. Comparisons with neuroendocrine cells in lung and gut are drawn, caution with regard to existing histogenetic models of laryngeal neuroendocrine neoplasia is advised and lines of future research are suggested.

ImportanceSystematic reviews and meta-analyses are considered the best evidence for clinical decision making. Many reviews of intraoperative neuromonitoring (IONM) in thyroidectomy have conflicting results, owing in large part to methodological quality.ObjectiveTo assess the methodological quality and the causes of heterogeneous results of systematic reviews that compare routine IONM vs visual identification of the recurrent laryngeal nerve (RLN) in patients undergoing thyroidectomy.Data SourcesA systematic search was performed of MEDLINE (PubMed), Embase, the Cochrane Library, LILACS (Literatura Latino Americana e do Caribe em Ciências da Saúde), Web of Science, and Google from January 1, 1968, through June 30, 2018. Data were analyzed from July 17 to November 30, 2018.Study SelectionStudies that mentioned performance of a systematic review/meta-analysis during the search period.Data Extraction and SynthesisData including study characteristics, type of patients, numbers of nerves at risk, and temporary and definitive RLN paralysis by group were extracted. Data about methodological characteristics, type of statistical analysis and summary estimator, endorsement of systematic review/meta-analysis guidelines, heterogeneity, publication bias, funding, conflict of interest, and statistical analysis were also recorded. The methodological quality was measured with the AMSTAR2 (A Measurement Tool to Assess Systematic Reviews) tool by 2 independent evaluators.Main Outcomes and MeasuresMethodological quality.ResultsThe search identified 13 systematic reviews that included patients who underwent open or minimally invasive thyroidectomy, second operations, and a mixture of low- and high-risk procedures. The mean compliance with the AMSTAR2 overall criteria was 53% (range, 11%-83%); with critical criteria, 71% (range, 50%-94%). The percentage of nerves at risk from RCTs was 4.8%. The mean (SD) crude rate of definitive RLN paralysis was 0.81% (0.22%; median, 0.75% [range, 0.53%-1.30%]) in the monitoring group and 1.14% (0.56%; median, 0.96% [range, 0.57%-2.56%]) in the control group.Conclusions and RelevanceA substantial number of systematic reviews of IONM in thyroidectomy have conflicting results, but their mean methodological quality is critically low. Design of a systematic review should comply with methodological standards and recommendations to offer relevant and practical information for decision making.

A new edition of the World Health Organization (WHO) Histological classification of tumours of the hypopharynx, larynx, trachea and parapharyngeal space was published in 2017. We have considered this classification regarding laryngeal neoplasms and discuss the grounds for said revision. Many of the laryngeal neoplasms described in the literature and in the previous WHO edition from 2005 have been omitted from this current revision. Many are described elsewhere in the book but it may give the new generation of pathologists/surgeons/oncologists the false impression that these tumour entities do not exist in the larynx.

The tissues of the laryngeal region only rarely harbor primary cartilaginous lesions, and squamous cell carcinoma remains the most frequently encountered malignant tumor in this area. We reviewed the salient histological features of cartilaginous laryngeal lesions to provide differential diagnostics and guidelines for distinguishing the benign from the malignant ones. Cartilaginous neoplasms of the larynx include chondroma and chondrosarcoma. Among the overarching group of all forms of laryngeal sarcoma, chondrosarcoma forms the most common entity in the larynx, followed by rhabdomyosarcoma. Cartilaginous tumors comprise about 0.1%–1% of all laryngeal neoplasms with chondrosarcomas being more frequently encountered than chondromas. Several neoplasms earlier reported as giant-cell tumors of the larynx would most likely, using current terminology, be classified as cases of undifferentiated pleomorphic sarcoma (previously known as malignant fibrous histiocytoma, giant-cell variant) or aneurysmal bone cyst. When true laryngeal sarcomas do exist, they may prove to be challenging lesions both for the pathologist and the treating clinician. The diagnostic problems are mainly a result of the infrequent exposure of clinicians and diagnosticians to these lesions.

Well-differentiated neuroendocrine carcinoma (also known as "carcinoid") of the larynx is an exceedingly rare tumor that has an epithelial origin. These tumors are malignant and have a low, but definite, risk of metastasis. Although it can be challenging, this tumor should be differentiated from moderately differentiated neuroendocrine carcinoma (also known as "atypical carcinoid"). The clinical and pathologic features of this tumor, as well as treatment and prognosis, are reviewed in detail.

A preoperative cytologic or histologic diagnosis of parotid gland neoplasms is mandatory to decide which surgical procedure would be appropriate. Open biopsies are contraindicated because of the risk of recurrence secondary to tumour cell seeding; furthermore a subsequent curative parotid surgery can be complicated by a previous open biopsy. While fine-needle aspiration cytology (FNAC) was the only preoperative diagnostic procedure to distinguish benign versus malignant neoplasms over the past decades, core needle biopsy (CNB) has been increasingly used over the last few years. This created a debate as to whether FNAC or CNB should be the preoperative procedure of choice. The focus of this editorial is to analyse the advantages and disadvantages of FNAC and CNB, and to discuss which procedure is more appropriate in the preoperative work-up of parotid neoplasms.

Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.

An endolymphatic sac tumor (ELST) is a rare, indolent but locally aggressive tumor arising in the posterior petrous ridge. Patients present with sensorineural hearing loss and tinnitus. As the tumor progresses, patients may experience vertigo, ataxia, facial nerve paresis, pain and otorrhea. Most patients present in their 4th or 5th decade with a wide age range. Patients with von Hippel-Lindau disease have an increased likelihood of developing ELST. Histologically, ELST is a low-grade adenocarcinoma. As it progresses, it destroys bone and extends into adjacent tissues. The likelihood of regional or distant metastases is remote. The optimal treatment is resection with negative margins. Patients with positive margins, gross residual disease, or unresectable tumor are treated with radiotherapy or radiosurgery. Late recurrences are common, so long follow-up is necessary to assess efficacy. The likelihood of cure depends on tumor extent and is probably in the range of 50-75%.

Salivary myoepithelial cells bear particular appendages and are involved in processes that have received incomplete attention in previous reviews. Here, cilia on myoepithelial cells are reviewed as regards substructure, occurrence, detection (electron microscopy, double immunofluorescence together with confocal microscopy), and roles (sensory reception, evolutionary homology, paracrine interaction). Attention is drawn to regressive changes affecting those cells (e.g. accumulation of lipofuscin), possible alterations of their cytoskeleton, internalization of apoptotic bodies and haemosiderin, and role in salivary microcalcification. The ability of differentiated salivary myoepithelial cells to divide is re-examined, particularly its increase in chronic inflammation and under experimental conditions. Caution with regard to histogenetic models of salivary neoplasia is re-emphasized; methodological deficiencies and areas of controversy are outlined; and lines of future research are suggested.

ABSTRACTJuvenile angiofibroma is an uncommon, benign, locally aggressive vascular tumor. It is found almost exclusively in young men. Common presenting symptoms include nasal obstruction and epistaxis. More advanced tumors may present with facial swelling and visual or neurological disturbances. The evaluation of patients with juvenile angiofibroma relies on diagnostic imaging. Preoperative biopsy is not recommended. The mainstay of treatment is resection combined with preoperative embolization. Endoscopic surgery is the approach of choice in early stages, whereas, in advanced stages, open or endoscopic approaches are feasible in expert hands. Postoperative radiotherapy (RT) or stereotactic radiosurgery seem valuable in long‐term control of juvenile angiofibroma, particularly those that extend to anatomically critical areas unsuitable for complete resection. Chemotherapy and hormone therapy are ineffective. The purpose of the present review was to update current aspects of knowledge related to this rare and challenging disease. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1033–1045, 2017

Objective: To review reports of adenoid cystic carcinomas arising in the head and neck area outside of the major salivary glands, in order to enhance the care of patients with these unusual neoplasms.Methods: An international team of head and neck surgeons, pathologists, oncologists and radiation oncologists was assembled to explore the published experience and their own working experience of the diagnosis and treatment of adenoid cystic carcinomas arising in the vicinity of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal.Results: The behaviour of adenoid cystic carcinoma arising in head and neck sites exclusive of the major salivary glands parallels that of tumours with a similar histology arising in the major salivary glands-these are relentless, progressive tumours, associated with high rates of mortality. Of 774 patients reviewed, at least 41 (5.3 per cent) developed documented regional node metastases.Conclusion: The relatively low overall incidence of nodal metastases in adenoid cystic carcinomas arising in the head and neck region outside of the major salivary glands suggests that routine elective regional lymph node dissection might not be indicated in most patients with these tumours.

The sinonasal cavities are rare locations for metastases. Metastases to these locations are usually solitary and produce similar symptoms to those of a primary sinonasal tumor. Nasal obstruction and epistaxis are the most frequent symptoms. The maxillary sinus is most frequently involved. The most common primary tumor sites to spread to this region originate in the kidney, breast, thyroid, and prostate, although any malignancy could potentially lead to a metastasis to the paranasal sinuses. The patient's prognosis is usually poor because of the fact that the sinonasal metastasis is usually associated with widespread disseminated disease. In the majority of patients, palliative therapy is the only possible treatment option. Nevertheless, whenever possible, surgical excision either alone or combined with radiotherapy may be useful for palliation of symptoms and, rarely, to achieve prolonged survival. This review considers the most interesting cases reported in the literature that presents metastases to the sinonasal cavities. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1847-1854, 2016.

Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016.

The clinical significance of papillary or follicular thyroid tissue incidentally discovered in cervical lymph nodes during pathological assessment of neck dissections for non-thyroid cancers of the upper aero-digestive tract is critically reviewed. Special emphasis is given to controversies over normal-looking, nodal, thyroid follicles. Arguments for and against the benign nature of these follicles are considered together with processes that could be involved in their formation. The admittedly limited evidence suggests that benign, thyroid follicular inclusions rarely occur in cervical lymph nodes. Histological criteria that could be helpful in recognizing the inclusions, which include assessing their extent in conjunction with the size of the node, are discussed. Finally, an algorithm based on collaboration between specialists, correlating histological findings with imaging and loco-regional control of the upper aero-digestive tract cancer, is suggested for the management of patients with incidentally discovered, nodal thyroid tissue.

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991–2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended.