Head & Neck Pathology最新文献

Purpose: Salivary gland tumors include numerous subtypes that vary from benign to highly aggressive, with many showing overlapping histopathological features that can make diagnosis challenging. Most subtypes express driver fusion genes that are tumor specific, and detection of such fusions is useful for differentiating amongst specific diagnoses, determining appropriate tumor grading, and guiding effective treatment. Currently, fusions can be detected by FISH, RT-PCR or through next-generation sequencing approaches, all of which are highly effective methodologies but can be costly or time consuming.

Methods: We developed a rapid NanoString nCounter platform-based assay to detect salivary gland tumor fusions using a combination of fusion junction-specific probes and an approach through differential exon expression analysis. The assay includes 68 junction-specific probes and analysis of exon expression across 9 fusion-associated genes in a single multiplex assay.

Results: Out of 55 retrospective and 171 prospective cases assayed, we accurately detected the majority of cases of pleomorphic adenoma, adenoid cystic carcinoma, cribriform adenocarcinoma, clear cell carcinoma, secretory carcinoma and NUT-rearranged carcinoma, including cases of these tumor types arising in non-salivary gland sites, with the major drawback being an inability to detect MAML2-containing mucoepidermoid samples. With mucoepidermoid carcinoma excluded, the assay shows an overall sensitivity of 96.1% and specificity of 100%.

Conclusion: We show that the majority of salivary gland tumor fusions can be effectively detected with a single rapid NanoString based assay, which can serve as a useful adjunctive tool for routine diagnostic head and neck pathology. The assay is low cost with a rapid turnaround time (30 h total assay time per sample batch, with minimal technician input required) compared to alternate detection methods.

Purpose: MYB has been shown to play a central role in oncogenesis in a majority of adenoid cystic carcinomas (ACC). Testing for MYB expression via immunohistochemistry (IHC) or testing for the MYB gene fusion by next-generation sequencing (NGS) have become useful tools for the diagnosis of ACC. In addition, detection of MYB expression may have implications for patient management.

Methods: A cohort of 35 ACC cases was identified from the archival pathology files of the Massachusetts General Hospital. Cases were tested for MYB expression using a panel of 4 different commercially available MYB antibodies and scored using a modified Allred system. RNA-based NGS for MYB gene fusion detection was also performed.

Results: Among 4 different MYB antibodies, the sensitivity for MYB detection ranged from 26 to 97%. When a 30% threshold for determination of MYB immunohistochemical positivity was used, the AB_10900735 IHC clone showed the maximum sensitivity (97%). RNA sequencing revealed 19 (54%) cases positive for MYB fusions, and expression analysis derived from the sequencing data confirmed a significant association between MYB expression and fusion status (p = 0.036). Although less sensitive, the AB_778878 MYB clone showed a significant positive association between IHC staining and MYB RNA expression (R² = 0.15, p = 0.023).

Conclusion: The detection of MYB expression using immunohistochemistry varies significantly depending on the antibody used. Comparison with MYB fusion and transcription levels, as determined by NGS, reveals that MYB has a complex relationship between genetic alterations, transcript levels, and protein abundance.

Squamous odontogenic tumor (SOT) is an exceedingly rare, benign epithelial odontogenic tumor showing squamous differentiation. It is composed of variably sized and shaped islands of cytologically bland, mature squamous epithelium within a fibrous stroma. In this report, we present a rare transformation of a squamous odontogenic tumor (SOT) of the maxilla into a well-differentiated squamous cell carcinoma (SCC) with involvement of the pterygoid plates. To the best of our knowledge, only two cases of malignant transformation of SOT has been reported in the literature. Herein, we seek to report this extremely rare occurrence to raise awareness of oral and maxillofacial surgeons and pathologists of this unusual, but serious event and perform a literature review of squamous odontogenic tumors.

Heterotopia, the occurrence of specific tissues in ectopic sites during embryogenesis, includes the presence of salivary gland tissue in unusual locations. Salivary gland neoplasms arising from heterotopic sites are rare. Secretory Carcinoma (SC) is a rare salivary gland carcinoma characterized by ETV6-NTRK3 fusion gene, very rarely described in salivary gland heterotopia. Here a case of SC originating from salivary gland heterotopia in a neck lymph node is reported, together with a literature review.A 66-year-old male presented with a left neck mass. Imaging and fine needle aspiration cytology indicated a preliminary diagnosis of a benign/low-grade malignancy neoplasm.Following surgery (superficial parotidectomy and mass excision), histological examination revealed SC within an intranodal salivary heterotopia, confirmed by molecular analysis.Heterotopic salivary gland tissue (HSGT) is rare, and its association with neoplasms is even rarer. Tumours arising on HSGT, share histological similarities with those affecting orthotopic salivary glands. This unique case expands the understanding of SC occurrences on HSGT.

Purpose: This PRISMA-guided and PROSPERO-registered systematic review aimed to summarise the current knowledge on the characteristics (clinical, radiographic, and histopathological) and treatment options for segmental odontomaxillary dysplasia (SOD).

Methods: Descriptive studies, case series, and case reports were searched up to May 2024 in PubMed, Embase, Web of Science, SciELO, and the Cochrane Library databases. Statistical association analyses were performed on clinical variables, using chi-square tests.

Results: The 35 included studies detailed 60 SOD cases in patients with a mean age of 12 ± 9.6 years. 11. Males were more frequently affected than females (62% or 1.6:1 ratio). Most cases involved the right maxilla (55%) and presented facial asymmetry and/or unilateral swelling (78%). Three cases involved both maxillae and mandible; Skin alterations were reported in 50% of the cases. Intraoral alterations such as alveolar process enlargement and gingival hyperplasia were also frequently observed (84% and 58%, respectively). All patients presented tooth alterations and 1st and/or 2nd upper premolars were absent in 80% of the cases. Dense bone and altered trabecular patterns were frequently observed in radiographs. Histopathological exams commonly showed dense trabecular bone and hyperplasic gingival tissue. Only 33 cases reported the SOD treatment, which ranged from follow-up without intervention up to surgery and orthodontics. No significant associations were found between sex and facial asymmetry or continuous lesion growth (p > 0.05). Additionally, no associations were found between intraoral alterations or symptoms and continuous lesion growth (p > 0.05).

Conclusion: This review presents SOD epidemiological, clinical, radiographic and histopathological data. Evidence regarding treatment is scarce.

Background: HPV- associated squamous cell carcinoma (SCC) is uncommon in non-oropharynx sites and not well characterized. This study aims to investigate uncommon phenotypes of HPV-associated head and neck carcinoma, the prevalence and morphologic spectrum of HPV-associated SCC in the oral cavity, larynx and hypopharynx.

Method: P16 immunostaining and HPV E6/7 in situ hybridization (ISH) were performed on tissue microarrays comprised of SCCs from different anatomic sites: oropharynx (n = 270), hypopharynx (n = 52), oral cavity (n = 95) and larynx (n = 123). Tumors were classified as HPV-associated based on a positive E6/7 ISH testing. RNA sequencing was performed on several selected cases.

Result: 66% oropharynx SCCs (OPSCCs) were HPV-associated; all were p16/HPV testing concordant except one which was p16 negative. The p16-/HPV + OPSCC resembled similar gene expression signature with p16+/HPV + OPSCCs by transcriptome analysis. 6/95 (6%) oral cavity SCCs were HPV-associated, all from male patients and 5/6 (83%) arose from the floor of mouth. Morphologically, 3/6 (50%) showed keratinizing SCC and 5/6 (83%) demonstrated HPV-associated squamous dysplasia in adjacent mucosa. 1/123 (less than 1%) larynx SCCs and 0/52 hypopharynx SCCs were HPV-associated.

Conclusion: Although uncommon, p16 negative HPV-associated OPSCC can occur, emphasizing the importance of judicious HPV testing. The morphology of HPV-associated oral cavity SCCs may deviate from prototypic nonkeratinizing SCC, making them difficult to recognize. Presence of HPV-associated squamous dysplasia could serve as a morphologic clue.

Background: Papillary thyroid carcinoma (PTC) with fibromatosis/fasciitis-like/desmoid-type stroma is a rare subtype of PTC,characterized by two distinct components: a classic papillary carcinoma component and a spindle cell proliferationresembling fibromatosis or nodular fasciitis. This stromal component adds a unique dimension to the tumor'spathology, making diagnosis more challenging and potentially leading to misclassification.

Case presentation: We present a case of this rare entity which contributes to the growing body of literature by providing additionalmolecular data, which may shed light on the biological behaviour of the fibromatosis-like stroma and its relationshipwith the papillary carcinoma component. This case underscores the importance of recognizing this subtype, as itsspindle cell proliferation could be mistaken for a separate neoplasm or reactive process, resulting in inappropriatemanagement.

Conclusions: Increased awareness of this entity will help pathologists avoid diagnostic pitfalls and guide clinicians in developingmore precise treatment plans, addressing both the malignant papillary component and the unique stromal features.This case further enriches the current understanding of the heterogeneity of PTC and highlights the need fortailored management strategies in rare subtypes.

Mesenchymal neoplasms of the thyroid gland are exceptionally rare accounting for less than 0.5% of all intrathyroidal tumors with hemangiomas comprising merely 6% of them. The clinicopathologic characteristics of two additional examples of thyroid hemangioma together with a thorough review of the pertinent literature are presented. A 62-year-old man and an 18-year-old woman presented with asymptomatic, soft-to-palpation, mobile nodules of the right thyroid lobe classified as TI-RADS 5 and TI-RADS 4, respectively, on ultrasound imaging. Microscopically, lesions featured a circumscribed, unencapsulated, lobular proliferation of variably-sized, congested, vascular channels lined by a single layer of flattened, cytologically bland endothelial cells, together with interspersed residual follicles. Vascular endothelial cells were strongly positive for CD31, CD34 and ERG, and negative for pancytokeratin AE1/AE3, TTF1, and PAX8. A diagnosis of cavernous hemangioma was rendered in the clinical setting of Hashimoto thyroiditis and follicular adenoma, respectively. Following inclusion of the current cases, a total of 53 intrathyroidal hemangiomas were identified in the literature with a patient mean age of 48.9 years (range = 0.17-84) and a slight female predilection (F:M = 1.4:1). A proclivity for the right thyroid lobe (59.6%) was noted with the striking majority of cases exhibiting features of cavernous hemangioma (95.2%). Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.

Acinic cell carcinoma (ACC) is a salivary gland malignancy most commonly arising in the parotid gland. It is the second most common salivary gland carcinoma in children. It is characterised by neoplastic cells with acinar morphology arranged in variably architectural features, including solid, cystic or follicular patterns. Conventional ACC typically has a low-grade clinical pattern, whereas high grade ACC exhibits a more aggressive clinical course with distant metastasis a high mortality rate. Most ACCs are characterised by gene rearrangements in the NR4A3 gene. Here, we present a case of high grade ACC lacking NR4A3 gene translocation but harbouring a hitherto undescribed SYN2::PPARG gene fusion of uncertain clinical significance. Clinical, radiological, histological and genomic features of the case are discussed alongside a brief review of the literature.

Squamous cell carcinoma (SCC) is one of the most common malignancies involving the parotid gland, but it has been recognized that the vast majority of parotid SCC represents metastases, especially from the ipsilateral facial skin. Bona fide primary SCC of the parotid is so rare that it is unclear whether it truly exists at all. We sought to molecularly characterize cases diagnosed as primary parotid gland SCC to see if they possess a unique genetic makeup.We identified cases in our archives which had been diagnosed as primary SCC of the parotid gland. In all cases, metastatic disease was excluded by a thorough history and physical examination. Cases with histologic evidence of a precursor neoplasm (e.g., carcinoma ex-pleomorphic adenoma) were also excluded. Targeted next-generation sequencing (NGS) was attempted on all cases.Six cases diagnosed as primary parotid SCC were identified, arising in 4 males and 2 females ranging from 8 to 73 years (mean, 51.8 years). All cases exhibited keratinization and unequivocal invasion. Four of 6 appeared to be arising from cystically dilated ducts. Five of 6 exhibited well-developed cellular atypia; the remaining case, while cytologically bland, demonstrated perineural invasion. Targeted NGS was successful in 5 of 6 cases. Two SCC harbored several mutations in a mutational profile reminiscent of SCCs seen in other organs. One case harbored YAP1::MAML2, a fusion previously reported in porocarcinoma and other neoplasms. One case harbored IRF2BP2::RUNX2, and presumably represents keratocystoma or SCC ex-keratocystoma. Finally, one case an increase of C > T mutations consistent with ultraviolet damage, suggesting that this case represented a cryptic metastasis from cutaneous SCC.Our analysis did not confirm a unifying genetic signature for purported primary parotid SCC. Indeed, our findings suggest that true primary parotid gland SCC is even rarer than already believed. In our 5 cases with results, NGS findings demonstrated that one was likely a keratocystoma, one a cryptic metastasis from a cutaneous SCC, and one a porocarcinoma, either metastatic or primary. The two remaining cases had complex genotypes reminiscent of SCCs from other sites. This may be the signature of genuine parotid primary SCC, but metastasis from an SCC from another organ cannot be excluded. Accordingly, a diagnosis of primary parotid gland SCC should be viewed with skepticism.