Well-differentiated Neuroendocrine Carcinoma of the Larynx: Confusion of Terminology and Uncertainty of Early Studies.

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.

Differing characteristics of cartilaginous lesions of the larynx.

INTRODUCTION: 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. MATERIALS AND METHODS: We reviewed the salient histological features of cartilaginous laryngeal lesions to provide differential diagnostics and guidelines for distinguishing the benign from the malignant ones. RESULTS: 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. CONCLUSION: 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.

Salivary myoepithelial cells: an addendum.

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.

Preoperative diagnostic of parotid gland neoplasms: fine-needle aspiration cytology or core needle biopsy?

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.

Collision tumors of the larynx: A critical review.

Problems related to definition of collision tumors are briefly examined in conjunction with etiology and natural history. Examples of genuine collision tumors in larynx are rare in the literature and are herein identified and tabulated. Aspects related to diagnosis and therapeutic strategies are also explored.

Should patients with laryngeal small cell neuroendocrine carcinoma receive prophylactic cranial irradiation?

While small cell neuroendocrine carcinomas (SCNCs) most often arise in the lung, extrapulmonary SCNCs arise in a variety of locations-including the head and neck region. In particular, laryngeal SCNCs-while rare tumors-are nevertheless recognized as distinct lesions. The rarity of laryngeal SCNC gives rise to two distinct difficulties: first (particularly with small biopsy specimens), laryngeal SCNC can be difficult to diagnose by routine light microscopy; second, limited experience with these tumors can make the crafting of a treatment plan for individual patients difficult. As regards the first problem, pathologic diagnosis is greatly enhanced by the application of immunohistochemistry. The second problem-crafting a successful treatment strategy-presents a much larger difficulty. It is tempting to extrapolate from experience with the (more common) pulmonary SCNC in search of a strategy applicable to laryngeal SCNC; such an extrapolation, however, may not be uniformly successful. In particular, while a combination of radiation therapy and chemotherapy appears to be as valuable in the treatment of extrapulmonary as it is in the treatment of pulmonary SCNC, prophylactic cranial irradiation (PCI)-which has enjoyed some success in the treatment of some patients with pulmonary SCNC-does not appear to have similar utility in patients with laryngeal SCNC. Accordingly, the use of PCI does not appear to have a role to play at this point in time in the treatment of patients with laryngeal SCNC.

Incidental findings of thyroid tissue in cervical lymph nodes: old controversy not yet resolved?

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.

Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance.

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.

The role of sentinel lymph node biopsy for thin cutaneous melanomas of the head and neck.

From 18% to 35% of cutaneous melanomas are located in the head and neck, and nearly 70% are thin (Breslow thickness ≤ 1 mm). Sentinel lymph node biopsy (SLNB) has an established role in staging of intermediate-thickness melanomas, however its use in thin melanomas remains controversial. In this article, we review the literature regarding risk factors for occult nodal metastasis in thin cutaneous melanoma of the head and neck (CMHN). Based on the current literature, we recommend SLNB for all lesions with Breslow thickness ≥ 0.75 mm, particularly when accompanied by adverse features including mitotic rate ≥ 1 per mm(2), ulceration, and extensive regression. SLNB should also be strongly considered in younger patients (e.g. < 40 years old), especially in the presence of additional adverse features. All patients who do not proceed with sentinel lymph node biopsy must be carefully followed to monitor for regional relapse.

A perspective of comparative salivary and breast pathology. Part I: microstructural aspects, adaptations and cellular events.

This is the first part of a review comparing the pathology of salivary and mammary glands. Here, less obvious similarities and differences in functional histology and their influences on pathology are examined with emphasis on myoepithelial cells, stromal components, analogues of mucosa-associated lymphoid tissue, steroid receptors, and intraparenchymal cells of monocytic lineage. Particular cell phenotypes (oncocytic, apocrine, neuroendocrine and clear) are critically evaluated and responses to atrophy, infarction and fine-needle aspiration biopsy procedures are highlighted together with aspects of metaplasia, regeneration, ageing and microcalcification. Areas of controversy or uncertainty which may benefit from further investigations are also discussed.

Causes of death of patients with laryngeal cancer.

Despite remarkable advances in the care of patients with laryngeal cancer over the past several decades, including a growing awareness of therapeutic complications and attention to quality of life, little is known about the causes of mortality in this population. In addition to the laryngeal malignancy itself, acute and late or chronic treatment-associated causes, second primary cancers, intercurrent disease and psychosocial factors are all responsible for patient morbidity and mortality. We examine the current literature related to the causes of death in patients with laryngeal cancer, in the hope of guiding future interventions to improve the longevity and quality of life of individuals with this cancer.

Molecular diagnostic alterations in squamous cell carcinoma of the head and neck and potential diagnostic applications.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that continues to be difficult to treat and cure. In many organ systems and tumor types, there have been significant advances in the understanding of the molecular basis for tumorigenesis, disease progression and genetic implications for therapeutics. Although tumorigenesis pathways and the molecular etiologies of HNSCC have been extensively studied, there are still very few diagnostic clinical applications used in practice today. This review discusses current clinically applicable molecular markers, including viral detection of Epstein-Barr virus and human papillomavirus, and molecular targets that are used in diagnosis and management of HNSCC. The common oncogenes EGFR, RAS, CCND1, BRAF, and PIK3CA and tumor suppressor genes p53, CDKN2A and NOTCH are discussed for their associations with HNSCC. Discussion of markers with potential future applications is also included, with a focus on molecular alterations associated with targeted therapy resistance.

Prognostic biological features in neck dissection specimens.

The superior prognostic value offered by routine histopathological staging of neck dissections, as compared to clinical staging using palpation and modern imaging techniques, is well established in the literature concerning the management of squamous cell carcinoma of the head and neck. In this review, we discuss the definitions and criteria used in standardised routine histopathological reporting and explore additional potential nodal prognostic features. In addition, we critically appraise the value of immunohistochemistry, histochemistry, molecular and other non-morphological techniques and suggest tumour and host features that merit further investigations.

Sinonasal tumors: a clinicopathologic update of selected tumors.

The sinonasal cavities show a wide variety of neoplasms of epithelial, mesenchymal, neural/neuroectodermal or hematopoietic origin. The differential diagnosis for these tumors may be difficult due to overlapping morphologies, variable patterns in ancillary studies, and potentially confusing terminology. In this report, an updated review of the spectrum of neoplasia is provided, using the World Health Organization 2005 classification as a guide. Classic tumors that are generally limited to the sinonasal tract are described and new information regarding molecular pathogenesis is reviewed. Also new entities that have the sinonasal tract as a site of predilection, such as sinonasal renal cell-like adenocarcinoma and NUT midline carcinoma are highlighted.

Inflammatory myofibroblastic tumors of the head and neck: evaluation of clinicopathologic and prognostic features.

Head and neck lesions composed of spindle cells evoke a differential diagnosis which includes a host of benign and malignant entities. One of the less common spindle cell lesions in this region is the inflammatory myofibroblastic tumor (IMT). Although IMTs were originally regarded as "pseudotumors", they are now recognized to be true neoplasms. Local recurrence, and, rarely, malignant change have been reported. Currently, the definitive means of diagnosing IMTs is the identification of a rearrangement of the anaplastic lymphoma kinase gene (at chromosome 2p23) by fluorescence in situ hybridization. The histopathologic differential diagnosis includes infectious processes, other fibro-inflammatory lesions, lymphoma, the inflammatory variant of malignant fibrous histiocytoma, and sarcomatoid (spindle cell) carcinoma. Complete surgical excision is the treatment of choice.

Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review.

Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions. We conducted a thorough review of the published literature to identify those studies using biomarkers to predict malignant progression of laryngeal epithelial precursor lesions. Of the 336 studies identified in this systematic search, 15 met the inclusion criteria and form the basis of this review. Limited studies suggest that certain biomarkers are potentially reliable predictors of malignant progression including various regulators of cell adhesion and invasion (e.g. FAK, cortactin, osteopontin, and CD44v6) and proliferation-associated markers such as TGF-ßRII and Kv3.4. The predictive value of these markers, however, has yet to be confirmed in large-scale prospective studies. Although the cell cycle-related proteins are the most frequently studied markers, none have been consistently reliable across multiple studies. The absence of standardization in methodologies, test interpretation, and other parameters may contribute to study inconsistencies. Various biomarkers have proved to have potential prognostic value and could be clinically relevant. The utility and prognostic power of these biomarkers should be confirmed in large, well-designed, standardized prospective studies.

Adult rhabdomyoma in the parapharyngeal space: report of 2 cases and review of the literature.

Rhabdomyomas are rare benign mesenchymal tumors with skeletal muscle differentiation. They are less commonly encountered than are their malignant counterparts, rhabdomyosarcomas. Rhabdomyomas fall into 2 general categories: cardiac and extracardiac types. Extracardiac rhabdomyomas are among the rarest tumors in humans and can be subclassified as fetal, juvenile, and adult types depending on the individual tumor's degree of differentiation by light microscopy. Adult extracardiac rhabdomyoma has a strong predilection for occurrence in the head and neck, mainly in the area of larynx and pharynx. In this article, 2 cases of parapharyngeal rhabdomyoma are reported together with a review of the world literature.

A survey of metastatic central nervous system tumors to cervical lymph nodes.

In the realm of head and neck diseases, one particularly common clinical presentation is that of the patient with a cervical mass. In children, neck masses often prove to be developmental cysts; in adults, the recent onset of a neck mass can signal a metastasis from a head and neck squamous carcinoma. Less often, both adults and children may present with cervical masses caused by either non-Hodgkin's lymphoma or Hodgkin's disease. There are, of course, less frequently encountered differential diagnostic possibilities; one of the most uncommon of all is the possibility of metastasis from an intracranial tumor. Intracranial tumors rarely give rise to cervical node metastases. The present review examines the published experience with 128 tumors that gave rise to cervical node metastases in both adult and in pediatric patients. While it is presumed that the blood-brain barrier blocks the spread of most tumors beyond the intracranial locale, this is speculative. Although many of the cervical node metastases reported here arose after craniotomy (and, presumably, after breaching of the blood-brain barrier), some arose in the absence of any preceding surgical procedure. Cervical node metastases may arise from glial tumors (including glioblastoma multiforme, in both adult and pediatric patients) and non-glial tumors (such as medulloblastoma in pediatric patients). The history of a previous intracranial lesion is often the key to correct diagnosis, since, without prompting, neither the pathologist nor the radiologist is likely to think of a cervical node metastasis from a brain tumor when assessing a cervical mass of unknown etiology.

Thyroid incidentalomas: to treat or not to treat.

Incidental lesions of the thyroid gland are an increasing problem facing clinicians. While asymptomatic palpable lesions are detected in only 4-7% of the population, currently available imaging modalities are sensitive enough to detect lesions in 20-30% of the population. Guidelines for managing these incidentalomas are limited, largely due to lack of well-powered prospective studies. This review will address the currently available data on thyroid incidentalomas, detected through clinical examination, cross-sectional imaging, ultrasound, and PET scans. We will focus on the modalities of detection and risk of malignancy, further investigation and management options and the deficiencies therein. We propose a pragmatic algorithm when faced with this clinical dilemma under differing circumstances.