Head & Neck Pathology最新文献

Jaw osteosarcoma (JOS) is a rare, distinct variant that differ from long bone osteosarcoma (LBOS) in several aspects. JOS typically appears about twenty years later than LBOS, displays a lower propensity for metastasis to other organs, and exhibits better survival rates. The dissimilarities in clinical and biological behavior between JOS and LBOS are likely due, at least in part, to variations in their respective microenvironments. In this report, we present a case of OS affecting the mandible in a young patient. This case displayed classic radiographic features but a unique histopathological presentation, posing a diagnostic challenge for pathologists, especially if encountered in small biopsies.

Purpose: A major problem in establishing treatment strategies for salivary gland carcinomas is the difficulty of preoperative histologic subtyping. Core needle biopsy (CNB) allows the collection of a small, intact specimens from the tumor center for detailed analysis. We evaluated the efficacy and limitations of preoperative diagnosis with CNB specimens collected using a newly developed 20-gauge needle designed to popularize its use.

Methods: Paired preoperative CNB and surgical specimens from 41 patients with malignant salivary gland tumors were retrospectively reviewed. A histologic typing platform, including morphologic and immunohistochemical evaluation and fluorescence in situ hybridization, was evaluated using CNB specimens. Biopsy specimen quality, diagnostic accuracy, and immunohistochemistry concordance rates between biopsy and surgical specimens were analyzed.

Results: In 39 of the 41 patients, CNB provided high-quality specimens, enabling adequate morphologic, immunohistologic, and genomic analyses. In two patients, high-quality CNB specimens could not be obtained due to cystic fluid and tumor firmness. The overall accuracy of correct preoperative diagnosis was 75%. The success rate of histologic subtyping and HER2 immunostaining concordance between CNB and surgical specimens was lower in carcinoma ex-pleomorphic adenoma (CXPA) than in de novo carcinoma (histologic subtyping; CXPA vs de novo carcinoma 50% vs 89%, p = 0.016, HER2 concordance; salivary duct carcinoma [SDC] ex-PA vs de novo SDC 16% vs 100%, p = 4.66E-03). No recurrence occurred due to tumor seeding after CNB.

Conclusions: Highly accurate histologic subtyping of salivary gland carcinomas can be performed by preoperative CNB; however, specificity can be more challenging in pathologically heterogenous tumors.

Purpose: Adenoid cystic carcinoma (AdCC) of the head and neck harbors MYB/MYBL1::NFIB fusions in around 60% of cases, with unfavorable long-term survival due to frequent recurrences and metastases, currently lacking effective targeted therapy. The study aims to identify actionable alterations and to elucidate the molecular underpinnings of MYB/MYBL1::NFIB-negative AdCC using a large targeted RNA sequencing panel.

Methods and results: We retrospectively searched our MSK-Solid Fusion clinical sequencing database for head and neck AdCC sequenced between 2016 and 2023. Of a total of 55 cases, 28 showed MYB::NFIB, 7 showed MYBL1::NFIB, and one case each harbored MYB::MPDZ (case 1) and FUS::MYB (case 2). One base of tongue tumor expressed both MYB::NFIB fusion and MET exon 14 skipping transcripts due to concurrent MET splice site mutation, D1010N (case 3). One parotid tumor lacked MYB/MYBL1 rearrangement but instead showed an in-frame SEC16A::NOTCH1 fusion that preserved the secretase cleavage site (case 4). Clinical records on 4 cases with non-canonical sequencing findings were reviewed. Distant metastases were present at the initial diagnosis (case 2) or at recurrence (cases 1, 3, and 4). Disease-related mortality occurred in cases 2 and 4 despite radiotherapy and immunotherapy.

Conclusions: The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1 fusions in AdCC.

Purpose: Salivary gland malignancies may have overlapping architectural patterns, tumor morphology, and immunohistochemical phenotypes, presenting challenges in precise classification. Molecular phenotyping has become quite useful for providing an additional diagnostic modality, and potential drug targets. Here we reported a young female patient with salivary gland tumor of the tongue base harboring genetic alterations by next generation sequencing (NGS).

Methods: The morphological, immunohistochemical and molecular features of this case were described, and related literature was reviewed.

Results: The tumor showed an epithelial myoepithelial architecture arranged in cords and tubules interwoven with a chondromyxoid stroma, along with perineural invasion and adjacent striated muscle infiltration. Myoepithelial cells were positive for CK5/6, partially positive for P63 and CK7, and sporadically positive for S100. Immunoprofiling revealed a low density of infiltrating lymphocytes and macrophages and the absence of programmed death ligand 1 (PD-L1). Notably, RNA-based NGS showed EWSR1::BEND2 gene fusion in this tumor, and EWSR1 break-apart was confirmed by fluorescence in situ hybridization. This led to a final diagnosis of a minor salivary gland malignancy with EWSR1::BEND2 fusion. Only two other cases of salivary gland tumors with EWSR1::BEND2 fusion had been previously reported, which were also detected via RNA-based NGS.

Conclusion: This study emphasized that EWSR1::BEND2 fusion may drive the carcinogenesis in salivary glands neoplasia. In clinic RNA-based NGS could be essential for precise genotyping of EWSR1 fusion in this rare disease.

Eosinophils are often encountered in the stroma and peritumoral microenvironment of squamous cell carcinomas. Because eosinophils are readily identified on routine hematoxylin and eosin stained sections, researchers have explored multiple ways in which identifying the extent of eosinophil infiltration on routine biopsy and excisional specimens might provide diagnostic and prognostic information. We review the literature on this evolving topic.

Objective: This study aimed to implement and evaluate a Deep Convolutional Neural Network for classifying myofibroblastic lesions into benign and malignant categories based on patch-based images.

Methods: A Residual Neural Network (ResNet50) model, pre-trained with weights from ImageNet, was fine-tuned to classify a cohort of 20 patients (11 benign and 9 malignant cases). Following annotation of tumor regions, the whole-slide images (WSIs) were fragmented into smaller patches (224 × 224 pixels). These patches were non-randomly divided into training (308,843 patches), validation (43,268 patches), and test (42,061 patches) subsets, maintaining a 78:11:11 ratio. The CNN training was caried out for 75 epochs utilizing a batch size of 4, the Adam optimizer, and a learning rate of 0.00001.

Results: ResNet50 achieved an accuracy of 98.97%, precision of 99.91%, sensitivity of 97.98%, specificity of 99.91%, F1 score of 98.94%, and AUC of 0.99.

Conclusions: The ResNet50 model developed exhibited high accuracy during training and robust generalization capabilities in unseen data, indicating nearly flawless performance in distinguishing between benign and malignant myofibroblastic tumors, despite the small sample size. The excellent performance of the AI model in separating such histologically similar classes could be attributed to its ability to identify hidden discriminative features, as well as to use a wide range of features and benefit from proper data preprocessing.

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.