Mucosal Melanomas of the Head and Neck Histopathology Reporting Guide. 2nd edition.

Head & Neck, Staging
Williams MD, Fitzpatrick S, Franchi A, Kakkar A, Patel S, Yamazaki N, Helliwell T, Thompson LDR
International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-922324-48-1.
The dataset has been developed for the reporting of resection and biopsy specimens of mucosal melanoma arising in the nasal cavity and paranasal sinuses, oral cavity, nasopharynx, oropharynx, larynx and hypopharynx. All other malignancies are dealt with in separate ICCR datasets, specifically cutaneous melanoma is separately reported.
Direct extension of a cutaneous primary into a mucosal site should be excluded and would not be reported in this dataset. Metastatic melanoma to a head and neck mucosal site is also excluded. If there are overlapping sites, clinical centring of the tumour should determine the dataset to be completed. If a primary tumour extends to involve the contralateral side, the tumour is still considered a unifocal tumour, but involving multiple, contiguous sites. It should be noted that for limited biopsies the pathologist may not be able to complete all of the elements in the ICCR dataset.
Neck lymph node dissections and excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable.
This dataset is intended for use for primary cancer resections. For resections of recurrent disease, the reporting guide may be used pragmatically although some data elements may be not applicable nor assessable.
PubMed ID: n/a
Article Size: <1 MB

Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumours Histopathology Reporting Guide. 2nd edition.

Head & Neck, Staging
Bullock M, Carlson DL, Fonseca I, Katabi N, Taylor SM, Thavaraj S, Williams MD, Helliwell T, Thompson LDR.
International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-922324-49-8.
The dataset has been developed for the reporting of lymph node resections from patients with primary carcinomas and mucosal melanomas of the head and neck. This excludes nodal resections for lymphoma and sarcomas. It is not intended for use in reporting lymph node core biopsy or fine needle aspirations. Carcinomas covered by the dataset include sinonasal tract, nasopharnx, oral cavity, oropharynx, hypopharynx, larynx and trachea, salivary glands (major and minor), and ear and temporal bone. Neuroendocrine tumours (grade 1, 2 and 3) and neuroendocrine carcinomas are also included in this dataset, along with musical melanoma and cutaneous carcinomas (except Merkel cell carcinoma). For resections of recurrent disease, the reporting guide may be used pragmatically although some data elements may be not applicable nor assessable. This dataset is to be used in conjunction with other ICCR datasets in the Head and Neck Series. Lymph node excisional biopsies or neck dissections may precede, accompany, or follow the biopsy or resection of a primary tumour. Concurrent reporting of the lymph node and primary tumour dataset elements – ideally in the same report – is preferable, as it provides clinicians with the most comprehensive information for tumour stage categorisation.
PubMed ID: n/a
Article Size: 1 MB

Meaningful Value Added by Standardized, Internationally Validated, and Evidence-Based Pathology Data Sets for Cancer Reporting of Head and Neck Sites Coordinated by the International Collaboration on Cancer Reporting.

Head & Neck, Staging
Thompson LDR.
Arch Pathol Lab Med. 2019 Apr;143(4):422-423. doi: 10.5858/arpa.2018-0489-ED.
This is an introduction to the Special Section–Structured Reporting Data Sets for Head and Neck Tumors From the International Collaboration on Cancer Reporting, Part I
PubMed ID: 30920861
Article Size: <1 MB

Ghost Cell Odontogenic Carcinoma: Case Series and Literature Review.

Head & Neck, Oral Cavity/Gnathic (Jaw)
Parks D, Zhou NJ, Vazquez DA, Fisher M, Budhathoki S, Chen J, Iganej S, Bhattasali O, Thompson LDR.
Head Neck Pathol. 2025 Dec 2;19(1):133. doi: 10.1007/s12105-025-01861-4.
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.
PubMed ID: 41329303
Article Size: 2.6 MB

Data Sets for the Reporting of Head and Neck Tumors (2nd Edition)

Head & Neck, Staging
Thompson LDR, Bishop JA, Bullock M, Chernock RD, Faquin WC, Müller S, Odell EW, Williams MD, Zidar N, Webster F.
Arch Pathol Lab Med. 2025 Nov 28. doi: 10.5858/arpa.2025-0335-OA. Online ahead of print.
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.
PubMed ID: 41321292
Article Size: 1.9 MB

Targeted molecular profiling uncovers true ceruminous adenomas with HMGA2::WIF1 and ceruminous syringocystadenoma papilliferum with BRAF V600E.

Ear & Temporal Bone, Head & Neck
Rooper LM, Thompson LDR, Sangoi AR, Oliver D, Gagan J, Bishop JA.
Virchows Arch. 2025 Nov 20. doi: 10.1007/s00428-025-04256-6. Online ahead of print.
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.
PubMed ID: 41266927
Article Size: 3.44 MB

Comprehensive next generation sequencing of middle ear neuroendocrine tumors

Ear & Temporal Bone, Head & Neck
Bishop JA, Xu J, Thompson LDR.
Ann Diagn Pathol. 2026 Feb 1:82:152620. doi: 10.1016/j.anndiagpath.2026.152620. Online ahead of print.
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.
PubMed ID: 41650632
Article Size: 12.5 MB

Barnaculate Carcinoma in Four Patients: Verrucoid Squamous Cell Carcinoma Subtype with TERT and HRAS Oncogenic Variants

Head & Neck, Oral Cavity/Gnathic (Jaw)
Liang Y, Afkhami M, Thompson LDR, Gao H, Maghami EG, D’Apuzzo M, Chang S, Bell D, Telatar M, Gernon TJ, Wu H.
Head Neck Pathol. 2026 Jan 5;20(1):6. doi: 10.1007/s12105-025-01870-3.
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.
PubMed ID: 41489678
Article Size: 1 MB

International Consensus Guidelines for Diagnostic Criteria and Checklist for Future Studies for Minimally Invasive Carcinoma ex Pleomorphic Adenoma: An HN CLEAR Initiative

Head & Neck, Salivary Gland
Beadle BM, Benzerdjeb N, Cho J, Costes-Martineau V, Faquin WC, Gomez RS, Gupta R, Kholová I, Nagao T, Rane SU, Rito M, Thompson LDR, Samra S, Luk PP, Chiosea SI.
Head Neck Pathol. 2026 Mar 18;20(1):33. doi: 10.1007/s12105-026-01898-z.
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.
PubMed ID: 41848802
Article Size: 1.4 MB

Recent developments in salivary gland pathology after the WHO 2024 classification

Head & Neck, Salivary Gland
Skálová A, Laco J, Thompson LDR, Bradová M, Vander Poorten V, Araújo ALD, Stenman G, Leivo I, Agaimy A, Ferlito A.
Virchows Arch. 2026 Apr 25. doi: 10.1007/s00428-026-04532-z. Online ahead of print.
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.
PubMed ID: 42032135
Article Size: 4.62 MB