Context.—:The International Collaboration on Cancer Reporting is a not-for-profit organization whose goal is to develop evidence-based, internationally agreed standardized data sets for each anatomic site to be used throughout the world. Objective.—:To update the changes in the 2nd edition of the data set suite, including carcinomas of the hypopharynx, larynx and trachea, major salivary glands, nasal cavity and paranasal sinuses, oropharynx and nasopharynx, and oral cavity, and ear and temporal bone tumors, malignant odontogenic tumors, mucosal melanomas of the head and neck, and nodal excisions and neck dissection specimens. Design.—:International consensus by expert data set authoring committees, especially authors of the World Health Organization head and neck tumor classification. Results.—:The unique features have been updated based on current research and developments in histologic classification and standardized reporting guidelines. Separation between core and noncore elements is based on data meaningful to prognosis and stratification. The changes are in conjunction with publication of the 5th edition of the World Health Organization head and neck tumor classification. Conclusions.—:Increased harmonization of reporting and benchmarking improves patient outcomes and international collaborative research.

Well-differentiated squamous cell carcinoma (SCC) in the oral cavity often has limited pleomorphism. Commonly seen in patients with proliferative verrucous leukoplakia, barnaculate carcinoma (BC) is a newly recognized, distinct subtype of well-differentiated SCC which presents with obvious architecture abnormalities but lacks significant pleomorphism. As such, reaching this diagnosis can be extremely challenging. In this study, molecular analysis of six BC specimens from four different patients demonstrated recurrent alterations in telomerase reverse transcriptase (TERT) promoter region and Harvey rat sarcoma virus (HRAS) gene. The identification of these oncogenic variants may be a useful adjunct to reaching the diagnosis.

Adrenocortical carcinoma (ACC) in children is a rare and aggressive malignancy. Despite representing a small fraction of pediatric adrenal tumors, ACC poses distinct challenges due to its heterogeneous biological behavior, frequent hormone secretion, and the limited availability of standardized, pediatric-specific treatment protocols. Complete surgical resection remains the cornerstone of curative intent therapy, and complete adrenalectomy offers the best chance for long-term survival. Given the aggressiveness of ACC, particularly in advanced disease, adjuvant therapies are often considered to improve outcomes. The aim of this consensus meeting was to bring together international experts to develop international guidance based on the best available evidence and collective clinical experience to harmonize long-term management. A modified 3-step Delphi consensus method was used to finalize the statements from an international panel of pediatric ACC experts from 4 continents (Europe, the Americas, and Asia, and Oceania). An electronic survey was developed by the steering committee (ENSAT Kids) and distributed to the panel. Agreement and disagreement were rated using a 6-point Likert scale with the opportunity to provide structured feedback. Consensus was defined a priori as ≥75% agreement. This Delphi process yielded consensus statements for therapy guidance, comprising 12 surgical statements and 68 medical treatment statements, organized by strategy and disease stage. These statements are intended to support clinicians in delivering more consistent and standardized therapeutic strategies for pediatric ACC. Future efforts should prioritize the design and conduct of high-quality, collaborative research studies in order to provide more evidence and therapy improvements.

Parallel to and after publication of the WHO 2024 classification of head and neck tumors, several developments concerning known existing salivary gland tumor entities, but also proposing new evolving tumor entities have been published. This review article describes the most important new developments in salivary gland pathology published through 2022–2025, that were not included in the 5th edition of the WHO Classification of Head and Neck Tumours 2024. This review summarizes these recent developments in both the benign and the malignant tumor categories. Among the recently proposed entities are palisading adenocarcinoma, microcribriform adenocarcinoma, fenestrating adenocarcinoma and skin-analogue poroid carcinoma. Developments in existing carcinoma entities include recognition of mucoacinar carcinoma as subtype of mucoepidermoid carcinoma (MAML2-fused), mucoepidermoid carcinoma without squamous cell differentiation, metatypical adenoid cystic carcinoma, and adenoid cystic carcinoma with prominent tubular hypereosinophilia. In the benign tumor category, recognition of pleomorphic adenoma with canalicular/trabecular phenotype driven by HMGA2 fusions, triphasic basal cell adenoma with S100 protein-positive "stroma", characterized by CTNNB1 mutations, metaplastic Warthin tumor with KRAS mutations and delineation of thymus-like phenotype in non-sebaceous lymphadenoma with recurrent CYLD mutations are the main highlights. Emerging concepts include benign tumor with ductal and papillary morphology (sialadenopapillary ductal tumor). Finally, new grading schemes have been developed/ proposed for acinic cell carcinoma and secretory carcinoma.

Middle ear neuroendocrine tumor (MeNET) is a distinctive, uncommon neoplasm of the ear. Previously regarded as "middle ear adenoma" among other names, it was found to be consistently positive for neuroendocrine markers, with differentiation analogous to normal intestinal L cells, and has therefore been classified similarly to other neuroendocrine tumors throughout the body. Nevertheless, MeNETs have an unusual two-cell population and therefore may be unique among NETs. We sought to characterize a group of MeNETs by next-generation sequencing (NGS). Six MeNETs from the authors' archives were retrieved, with histologic and immunohistochemical results tabulated. Targeted DNA and RNA NGS were attempted on all cases. Clinical follow-up was obtained. The MeNETs arose in the middle ears of five men and one woman, ranging from 31 to 57 years (median, 47.5 years). Four cases were grade 1 and two cases grade 2 (one based on necrosis and one based on an elevated Ki67 index). DNA NGS was successful in five of six cases, with probable pathogenic variants including: ATRX mutations in two cases, chromosome 22 deletion, and DNMT3A, STAG2, RB1, HRAS, NF1, and SF3B1 mutations in one case each. In general, the variants were found at low allele frequencies. RNA NGS was successful in all cases, with one case harboring a fusion of unknown significance (R3HDM2::EP400). Follow up available in all cases, with five patients without disease (mean, 74 months; median, 17 months), with one patient (one of the grade 2 tumors) experiencing widespread distant metastases and dying 96 months after diagnosis. Despite the consistent appearance of MeNET, they are heterogeneous at the molecular level, with low mutational burdens but lacking consistent, recurrent alterations. This is similar to well-differentiated NETs of other organs, in particular the small intestine and lung. Overall, our findings support the grouped classification of MeNET within the larger NET scheme.

A variety of factors, including the extent of invasion, determine the clinical outcome in patients with carcinoma ex pleomorphic adenoma (Ca ex PA). A Head and Neck Consensus Language for Ease of Reproducibility (HN CLEAR) Steering Committee organized a working group (WG) to harmonize diagnostic and research approaches for assessing invasion in Ca ex PA.WG of head and neck pathologists and a radiation oncologist conducted 6 iterative rounds of online voting (Modified Delphi), using Google Forms, over an 8-month period on invasion in the setting of Ca ex PA. Agreement was defined by the same opinion of at least 50% of the responders. The list of parameters with predetermined options was developed.Minimally invasive Ca ex PA was defined as a pT1-2 pN0 carcinoma, resected en bloc with negative margins, with or without perineural invasion, without vascular invasion and without distant metastasis at presentation. Consensus was not reached on whether high grade histology is compatible with the concept of "minimal invasion". Diagnosis of minimal invasion is possible when tumor excision is complete (with negative margins), en bloc (without fragmentation), and requires sampling of the entire tumor capsule or tumor-normal interface. The consensus guidelines characterizing Ca ex PA and the list of challenging aspects are provided. The WG proposed a checklist for future research, aiming to refine the diagnosis of in situ and minimally invasive Ca ex PA.

In the past two decades, treatment for non-small-cell lung cancers (NSCLCs) and head and neck squamous cell carcinoma (HNSCC) has advanced considerably, owing largely to the characterization of distinct oncological subtypes, the development of targeted therapies for each subtype and the advent of immunotherapy. Data emerging over the past two decades suggest that NUT carcinoma, a highly aggressive malignancy driven by a NUT fusion oncoprotein and arising in the lungs, head and neck, and rarely in other sites, is a squamous cell carcinoma (SCC) based on transcriptional, histopathological, cell-of-origin and molecular characteristics. NUT carcinoma has an estimated incidence of 1,400 cases per year in the United States, surpassing that of some rare NSCLC and HNSCC subtypes. However, NUT carcinoma is currently not recognized as an SCC of the lungs or head and neck. The orphan classification of NUT carcinoma as a distinct entity leads to a lack of awareness of this malignancy among oncologists and surgeons, despite early diagnosis being crucial for this cancer type with a median survival of only ~6.5 months. Consequently, NUT carcinoma is underdiagnosed and often misdiagnosed, resulting in limited research and progress in developing effective treatments in one of the most aggressive forms of lung and head and neck cancer. With a growing number of targeted agents that can potentially be used to treat NUT carcinoma, improved recognition through reclassification and inclusion of NUT carcinoma as a squamous NSCLC or an HNSCC when arising in these locations will accelerate the development of effective therapies for this disease. Thus, in the Perspective, we propose such a reclassification of NUT carcinoma as an SCC and discuss the supporting evidence. Accumulating evidence indicates that NUT carcinoma, a highly aggressive malignancy driven by NUTM1 fusions, is a rare form of squamous cell carcinoma (SCC) of the lung or head and neck, calling into question its current classification as an entirely distinct disease entity. In this Perspective, the authors propose the reclassification of NUT carcinoma as an SCC, the supporting rationale, and the immediate implications for clinical practice and research

Ceruminous adenomas are benign neoplasms that arise from ceruminous glands in the external auditory canal. While these tumors are currently regarded as a single entity, they are divided into three histologically diverse subtypes: ceruminous syringocystadenoma papilliferum, ceruminous pleomorphic adenoma, and ceruminous adenoma not otherwise specified (NOS). Given the similarities of two of these subtypes to other tumors that occur at multiple anatomic sites, it is currently unclear whether ceruminous adenomas are truly a unified group. In this study, we performed targeted molecular profiling of 11 cases of ceruminous adenoma to clarify their classification. We identified BRAF V600E mutations (via PCR and/or immunohistochemistry) in five ceruminous syringocystadenomas papilliferum. We also identified HMGA2::WIF1 fusions (via RNA sequencing) in five ceruminous adenomas NOS and one ceruminous pleomorphic adenoma. Tumors with HMGA2::WIF1 fusion did not display the canalicular adenoma-like morphology seen in salivary gland pleomorphic adenomas with this fusion. Overall, these findings suggest that the three subtypes of ceruminous adenoma represent two biologically distinct groups. Recurrent BRAF V600E mutations in ceruminous syringocystadenoma papilliferum are parallel to those in cutaneous syringocystadenoma papilliferum. Histologic and molecular concordance suggests that ceruminous syringocystadenoma papilliferum should be part of the broader syringocystadenoma papilliferum category rather than a subtype of ceruminous adenoma. Conversely, HMGA2::WIF1 fusions in ceruminous adenoma NOS and ceruminous pleomorphic adenoma suggest that a stromal component may not be an essential point of distinction between these groups. These residual true ceruminous adenomas all likely represent a specialized form of mixed tumor unique to the external ear.

Teratocarcinosarcoma is rare malignant sinonasal neoplasm with immature and malignant endodermal, mesodermal, and neuroepithelial elements resembling immature teratoma, commonly with SMARCA4 loss or activating CTNNB1 mutation. The carcinoma component may be either squamous or adenocarcinoma and the mesenchymal component may be composed of spindle cells, cartilage, bone, smooth muscle, or skeletal muscle. Due to the uncommon nature of this malignancy, there are frequently diagnostic difficulties that result in management problems. Herein we report a teratocarcinosarcoma arising in the nasal cavity of a 13-year-old boy with CTNNB1 activating mutation and copy number variations by next-generation sequencing along with an abnormal karyotype. This tumor must be included in the differential of neoplasms with immature elements, more likely seen in pediatric patients.

Ghost cell odontogenic carcinoma (GCOC) is rare. These tumors can arise from odontogenic precursors or de novo, displaying a spectrum of clinical behaviors with potential for rapid local recurrence, distant metastasis, and death from disease. Considering limited data, we present two cases of GCOC in female patients and perform a comprehensive review of the literature related to GCOC with a focus on adjuvant therapies. The first case, a de novo occurrence, had an aggressive course, while the second, arising from an ameloblastoma, was more indolent. A review of 65 previously published cases revealed that 82% of GCOCs occurred in males. Recurrence rates were higher in cases arising from precursor lesions (64%) compared with de novo lesions (26%). Of the 59 patients who had documented follow-up, 37% had an isolated local recurrence, 3% had an isolated distant metastasis, and 5% had both a local recurrence and distant metastasis. Overall, GCOC is a rare but aggressive odontogenic carcinoma requiring a multidisciplinary approach. Radical surgical excision with clear margins remains the primary treatment. Adjuvant therapies, such as radiotherapy, are indicated for aggressive features like rapid growth, positive margins, and local recurrence. While both local and distant recurrences are a risk, local recurrence is the most common mode of treatment failure. Further research into prognostic markers such as CTNNB1, p53, and Ki-67 may lead to more personalized therapies and improved outcomes. Additional research should also focus on intensifying adjuvant therapies to improve outcomes.

Despite decades of progress, laryngeal squamous cell carcinoma (SCC) is still associated with significant morbidity and mortality worldwide. Additional biomarkers are needed to apply precision medicine and predict the clinical course. We reviewed and summarised routinely reported histopathologic features (e.g. subtypes of laryngeal SCC) along with promising potential biomarkers not yet routinely assessed using international guidelines. These include extra- vs intratumoural vascular and perineural invasion, tumour budding, depth of invasion, and tumour-infiltrating lymphocytes. We also address the problem of specimen quality and type (open approach vs endoscopic surgery) and the related limitations. High-risk human papillomavirus infection is another controversial issue to be discussed, being rare in laryngeal SCC, with an indeterminate prognostic significance and less reliable p16 overexpression as a surrogate marker of HPV infection. Further studies are warranted to address the applicability and to see which of the described parameters may help to better stratify patients with laryngeal SCC and should therefore be included in the pathology report.

Cervical lymph node metastasis significantly influence prognosis in oral squamous cell carcinoma (OSCC), guiding staging, treatment decisions, and overall survival. Sentinel lymph node biopsy (SLNB) offers a minimally invasive approach for early detection of subclinical nodal metastasis, including micrometastases (0.2–2 mm) and isolated tumor cells (ITCs, < 0.2 mm). Despite its success in melanoma and breast cancer, the clinical relevance of micrometastases and ITCs in OSCC remains incompletely defined. This narrative review explores the biological significance, diagnostic challenges, and emerging strategies for detecting micrometastasis and ITCs in OSCC, aiming to inform their potential role in refining staging systems and treatment algorithms. We performed a comprehensive literature review of SLNB in OSCC, examining data on histopathological detection techniques, molecular markers, artificial intelligence (AI), and radiomics-based tools that enhance diagnostic sensitivity and specificity for occult metastases. While current guidelines in some countries endorse SLNB for early-stage OSCC, integration of micrometastasis and ITC data into staging remains inconsistent. Studies suggest that ITCs represent early metastatic events with variable prognostic significance. Advanced techniques such as step-serial sectioning, immunohistochemistry, and molecular diagnostics—including ctDNA, gene-expression profiling, and AI-assisted pathology—have shown promise in improving detection accuracy. However, robust prospective data are lacking, and a consensus on the management of minimal nodal disease is yet to be reached. Accurate identification and interpretation of micrometastasis and ITCs in OSCC represent an evolving frontier in head and neck oncology. Future staging systems should incorporate these elements supported by standardized protocols and high-level evidence. The integration of AI, molecular diagnostics, and radiomics holds the potential to enhance risk stratification and personalize surgical decision-making, reducing overtreatment while ensuring oncologic safety.

The International Collaboration on Cancer Reporting is a not-for-profit organization whose goal is to develop evidence-based, internationally agreed standardized data sets for each anatomic site to be used throughout the world. To update the changes in the 2nd edition of the data set suite, including carcinomas of the hypopharynx, larynx and trachea, major salivary glands, nasal cavity and paranasal sinuses, oropharynx and nasopharynx, and oral cavity, and ear and temporal bone tumors, malignant odontogenic tumors, mucosal melanomas of the head and neck, and nodal excisions and neck dissection specimens. International consensus by expert data set authoring committees, especially authors of the World Health Organization head and neck tumor classification. The unique features have been updated based on current research and developments in histologic classification and standardized reporting guidelines. Separation between core and noncore elements is based on data meaningful to prognosis and stratification. The changes are in conjunction with publication of the 5th edition of the World Health Organization head and neck tumor classification. Increased harmonization of reporting and benchmarking improves patient outcomes and international collaborative research.

Objective Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.Methods A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.Results We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m(2)/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.Conclusions The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

BackgroundMitotane is employed as adjuvant therapy in managing adrenocortical carcinoma in pediatric patients. While various adverse effects, such as estrogen-like manifestations, are well-documented in adults, there is limited knowledge regarding pediatric-specific toxicity. This report details an uncommon case of isosexual precocious pseudopuberty induced during childhood due to the estrogen-like effects of mitotane.Case reportA 2.8-year-old female diagnosed with adrenocortical carcinoma (pT4 pN0 M0) underwent adjuvant treatment with mitotane and cytotoxic chemotherapy following incomplete resection (tumor stage III). Approximately eight months into mitotane treatment, she exhibited signs of puberty (Tanner stage 2), including progressive breast development, uterine enlargement, vaginal discharge, and an advancement of bone age by nearly two years. Gonadotrophin-dependent puberty and endogenous estrogen production were ruled out. The precocious pseudopuberty was attributed to previously reported estrogen-like effects of mitotane therapy. Subsequent administration of the aromatase inhibitor anastrozole in combination with mitotane led to a reduction in clinical signs of puberty.ConclusionMonitoring for estrogen-like effects of mitotane is crucial, particularly in pre-pubertal children, to avert potentially irreversible changes associated with precocious pseudopuberty. Aromatase inhibitors may serve as a prompt therapeutic option, enabling the continuation of mitotane treatment.

Primary 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.

Physicians and dentists have a very limited exposure to personal financial management and yet find themselves in the top 10% of earners in the United States of America. Education loans, practice expenses, and high standards of living obligate them to be good financial stewards to succeed financially. Anecdotal personal experience and review. The article establishes seven steps to implement as medical/dental students, interns, residents, or practicing doctors to move towards financial health and security. The steps include (1) saving enough; (2) good debt management; (3) being tax savvy; (4) obtaining the correct insurance; (5) making wise investments; (6) if choosing to marry, avoid divorce; and (7) keeping track with periodic progress assessment. Each of these steps contains several components that can aid and guide physicians and dentists in their financial arc of development over their professional career and into retirement, considering generational wealth transfer or charitable donation as ultimate goals. This brief guide is based on my own financial journey to achieve long-term financial independence: start early, use simple tax deferred investments without chasing trends while keeping fees down, live within your means, and adequately insure your income.

Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Fifteen lesions (3–42 mm) were identified, predominantly in male (87