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- Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm?Publication . Hellquist, Henrik; Skalova, Alena; Azadeh, BahramSalivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of salivary gland neoplasms greatly influences macroscopic and microscopic evaluation of the specimen but also, given the high incidence of metastases and morbidity, carries significant treatment implications.
- Lymphomas of the head and neck region: an updatePublication . Cabecadas, Jose; Martinez, Daniel; Andreasen, Simon; Mikkelsen, Lauge Hjorth; Molina-Urra, Ricardo; Hall, Diane; Strojan, Primoz; Hellquist, Henrik; Bandello, Francesco; Rinaldo, Alessandra; Cardesa, Antonio; Ferlito, AlfioThe field of haematopathology is rapidly evolving and for the non-specialized pathologist receiving a specimen with the possibility of a lymphoid malignancy may be a daunting experience. The coincidence of the publication, in 2017, of the WHO monographies on head and neck and haematopoietic and lymphoid tumours prompted us to write this review. Although not substantially different from lymphomas elsewhere, lymphomas presenting in this region pose some specific problems and these are central to the review. In addition, differences in subtype frequency and morphological variations within the same entity are discussed. The difficulty in diagnosis related to some specimens led us to briefly mention common subtypes of systemic lymphomas presenting in the head and neck region.
- Sinonasal undifferentiated carcinoma (SNUC): from an entity to morphologic pattern and back again-a historical perspectivePublication . Agaimy, Abbas; Franchi, Alessandro; Lund, Valerie J.; Skalova, Alena; Bishop, Justin A.; Triantafyllou, Asterios; Andreasen, Simon; Gnepp, Douglas R.; Hellquist, Henrik; Thompson, Lester D. R.; Rinaldo, Alessandra; Ferlito, AlfioSince the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.
- Some considerations on the WHO Histological classification of laryngeal neoplasmsPublication . Ferlito, Alfio; Devaney, Kenneth O.; Hunt, Jennifer L.; Hellquist, HenrikA 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.
- Update on neuroendocrine carcinomas of the larynxPublication . Strosberg, Carolina; Ferlito, Alfio; Triantafyllou, Asterios; Gnepp, Douglas R.; Bishop, Justin A; Hellquist, Henrik; Strojan, Primoz; Willems, Stefan M; Stenman, Göran; Rinaldo, Alessandra; Hernandez-Prera, Juan C.Laryngeal neuroendocrine carcinomas are heterogeneous neoplasms characterized by neuroendocrine differentiation. Their prognoses are dependent on tumor type, therefore different classifications have been developed. Moreover, other tumors have overlapping pathologic features posing a range of diagnostic possibilities.
- How phenotype guides management of the most common malignant salivary neoplasms of the Larynx?Publication . Lopez, Fernando; Williams, Michelle D.; Skalova, Alena; Hellquist, Henrik; Suarez, Carlos; Nixon, Iain J.; Rodrigo, Juan P.; Cardesa, Antonio; Strojan, Primoz; Quer, Miquel; Hunt, Jennifer L.; Rinaldo, Alessandra; Ferlito, AlfioSalivary gland carcinomas of the larynx are uncommon. Adenoid cystic carcinoma is the most prevalent type of salivary gland carcinoma in this region, although other histologies such as mucoepidermoid carcinoma and adenocarcinomas have been reported. These tumors may present with advanced-stage due to nonspecific symptoms and their relatively slow-growing nature. The index of suspicion for a non-squamous cell carcinoma entity should be high when a submucosal mass is present. An accurate diagnosis is mandatory due to the impact each biologic entity has on treatment and outcome. Data concerning treatment and outcome are scarce, but primary surgery with utmost focus on free surgical margins is the treatment of choice. The role of adjuvant radiotherapy has not been well defined, although there is an agreement that it should be considered in advanced-stage or high-grade disease. This review considers only the most common malignant salivary neoplasms of the larynx with a focus on clinical management of these tumors.
- High-grade transformation/dedifferentiation in salivary gland carcinomas: occurrence across subtypes and clinical significancePublication . Skalova, Alena; Leivo, Ilmo; Hellquist, Henrik; Agaimy, Abbas; Simpson, Roderick H. W.; Stenman, Goran; Vander Poorten, Vincent; Bishop, Justin A.; Franchi, Alessandro; Hernandez-Prera, Juan C.; Slouka, David; Willems, Stefan M.; Olsen, Kerry D.; Ferlito, AlfioHigh-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.
- Cervical lymph node metastasis in adenoid cystic carcinoma of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal: a collective international reviewPublication . Bishop, J. A.; Devaney, K. O.; Barnes, L.; Slootweg, P. J.; Cardesa, A.; Gnepp, D. R.; Williams, M. D.; Triantafyllou, A.; de Bree, R.; Robbins, K. T.; Coca-Pelaz, A.; Vander Poorten, V.; Suarez, C.; Shah, J. P.; Bradley, P. J.; Kowalski, L. P.; Silver, C. E.; Rodrigo, J. P.; Pitman, K. T.; Teymoortash, A.; Eloy, J. A.; Takes, R. P.; Hamoir, M.; Medina, J. E.; Mendenhall, W. M.; Strojan, P.; Hellquist, Henrik; Skalova, A.; Rinaldo, A.; Ferlito, A.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.
- Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international reviewPublication . Suarez, Carlos; Barnes, Leon; Silver, Carl E.; Rodrigo, Juan P.; Shah, Jatin P.; Triantafyllou, Asterios; Rinaldo, Alessandra; Cardesa, Antonio; Pitman, Karen T.; Kowalski, Luiz P.; Robbins, K. Thomas; Hellquist, Henrik; Medina, Jesus E.; Bree, Remco de; Takes, Robert P.; Coca-Pelaz, Andres; Bradley, Patrick J.; Gnepp, Douglas R.; Teymoortash, Afshin; Strojan, Primoz; Mendenhall, William M.; Eloy, Jean Anderson; Bishop, Justin A.; Devaney, Kenneth O.; Thompson, Lester D. R.; Hamoir, Marc; Slootweg, Pieter J.; Vander Poorten, Vincent; Williams, Michelle D.; Wenig, Bruce M.; Skalova, Alena; Ferlito, AlfioThe purpose of this study was to suggest general guidelines in the management of the NO neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0-14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not relaied to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
- Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid glandPublication . Bradley, Patrick J.; Stenman, Göran; Thompson, Lester D. R.; Skálová, Alena; Simpson, Roderick H. W.; Slootweg, Pieter J.; Franchi, Alessandro; Zidar, Nina; Nadal, Alfons; Hellquist, Henrik; Williams, Michelle D.; Leivo, Ilmo; Agaimy, Abbas; Ferlito, AlfioPrimary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should only be made after the exclusion of mSCCP. Moreover, all of the histological diagnostic criteria proposed to be in favor of pSCCP (such as, for example, dysplasia of ductal epithelium) can be encountered in unequivocal mSCCP, thereby representing secondary growth along preexistent ducts. Squamous cell differentiation has also been reported in rare genetically defined primary parotid carcinomas, either as unequivocal histological squamous features (e.g., NUT carcinoma, mucoepidermoid carcinoma), by immunohistochemistry (e.g., in NUT carcinoma, adamantinoma-like Ewing sarcoma, basal-type salivary duct carcinoma, mucoepidermoid carcinoma), or a combination of both. Another major issue in this context is that the International Classification of Diseases (ICD) coding system does not distinguish between primary or metastatic disease, resulting in a large number of patients with mSCCP being misclassified as pSCCP. Immunohistochemistry and new molecular biomarkers have significantly improved the accuracy of the diagnosis of many salivary gland neoplasms, but until recently there were no biomarkers that can accurately distinguish between mSCCP and pSCCP. However, recent genomic profiling studies have unequivocally demonstrated that almost all SCCP analyzed to date have an ultraviolet light (UV)-induced mutational signature typical of mSCCP of skin origin. Thus, mutational signature analysis can be a very useful tool in determining the cutaneous origin of these tumors. Additional molecular studies may shed new light on this old diagnostic and clinical problem. This review presents a critical view of head and neck experts on this topic.
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