Head & Neck Pathology最新文献

Background: Numeric chromosomal imbalance, known as aneuploidy, is linked to both malignant and potentially malignant epithelial lesions. Aneuploidy has also been investigated in oral potentially malignant disorders (OPMDs) due to its high incidence in head and neck cancers, particularly in oral squamous cell carcinoma (OSCC). The study aimed to evaluate the potential of aneuploidy, a marker of chromosomal imbalance, as a prognostic tool for assessing malignant transformation risk in oral lichen planus (OLP) patients.

Methods: Fluorescent in situ hybridization (FISH) analysis targeting centromeric probes for chromosomes 2 and 8 was conducted on samples from 245 patients, with follow-up in 135 cases.

Results: Aneuploid cells (ACs) were detected in 73 patients (29.8%); 24 (32.9%) exhibited non-diploid cells in a normal looking mucosa. Only 2 (0.8%) patients developed OSCC during the follow-up. Among the 135 followed, 11 (8.1%) were positive for Acs in both samples, 15 (11.1%) were were negative initially but positive later. In contrast, 3 patients (2.2%) were initially positive but later negative.

Conclusion: These results indicate a low malignant transformation rate (< 1%), despite a high rate of aneuploidy. These also demonstrate variability in aneuploidy results over time. The dynamic nature of aneuploidy observed suggests that it may not be a reliable predictive tool for malignant transformation in OLP.

Introduction: Pleomorphic adenoma is the most common neoplasm of the salivary glands. While the overall risk of malignancy is relatively low, a distinct molecular sub-group harboring HMGA2 alterations seems to show an increased risk of malignant progression to carcinoma ex pleomorphic adenoma.

Purpose: This study investigates MDM2 amplification in HMGA2-altered pleomorphic adenoma, atypical pleomorphic adenoma, and carcinoma ex pleomorphic adenoma.

Methods: In this multicenter, retrospective case series analysis, we examined 37 cases of HMGA2-altered pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and pleomorphic adenoma with atypical features. A total of 18 cases were included from our institutional archives, with 19 additional cases derived from published literature. The cases from our institutes were analyzed for MDM2 amplification using a stepped approach by immunohistochemistry and FISH.

Results: Collectively, an MDM2 amplification was present in 27% of pleomorphic adenoma (4 of 15), compared to 78% of carcinoma ex pleomorphic adenoma (14 of 18) (p-value = 0.003). In the group of pleomorphic adenomas with atypical features, an MDM2 amplification was present in 50% of cases (2 of 4). These findings indicate an association between MDM2 amplification and malignancy. Strikingly, a mixed control group of 12 benign and malignant PLAG1-altered neoplasms showed no immunohistochemical staining for MDM2.

Conclusion: Immunohistochemical MDM2 expression, including MDM2 amplification, is enriched in the group of HMGA2-altered pleomorphic adenoma, and potentially plays role in malignant progression. This study highlights the importance of recognizing the molecular sub-group of HMGA2-altered pleomorphic adenomas and integrate MDM2 analysis into routine diagnostics to corroborate the cytonuclear atypia in these challenging cases.

Background: DEK::AFF2 fusion squamous cell carcinoma (SCC) is a rare and aggressive subtype of non-keratinizing SCC. Previously reported cases have predominantly involved the sinonasal tract, middle ear, and skull base. To date, only 62 cases have been described, with rare exceptions including a primary lung tumor and a recurrent tumor in the trachea.

Methods: We describe the first documented case of primary laryngeal SCC harboring a DEK::AFF2 fusion in a 64-year-old female who presented with progressive hoarseness and airway obstruction. Clinical, radiologic, histopathologic, immunohistochemical, and molecular analyses were performed to characterize the tumor.

Results: Imaging and laryngoscopic evaluation revealed a transglottic mass. Histopathology demonstrated non-keratinizing SCC composed of monotonous tumor cells with an infiltrative growth pattern. Immunohistochemistry showed diffuse p40 positivity and moderate to strong nuclear AFF2 expression. The DEK::AFF2 fusion was confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction. The patient underwent total laryngectomy followed by adjuvant chemoradiotherapy and remains disease-free at 12 months of follow-up.

Conclusions: This case expands the known anatomical distribution of DEK::AFF2 fusion SCC to include the larynx, suggesting that this rare entity may arise throughout the respiratory tract epithelium. Recognition of this fusion is important in the differential diagnosis of non-keratinizing SCCs across the respiratory tract.

Introduction: This scoping review was conducted to ascertain the loss of heterozygosity (LOH) signatures reported in Oral Potentially Malignant Disorders (OPMD) and Oral Squamous Cell Carcinoma (OSCC), in the literature in the last fifty years.

Methods: The Joanna Briggs Institute recommendations (2023) for scoping review were used to extract, analyze, and present the results. The review was reported according to the PRISMA guidelines for Scoping Reviews (PRISMA-ScR). The most commonly reported genes associated with LOH in OPMD and OSCC are discussed. The Gene Ontology functional enrichment analysis gives the significance of the protein-protein interactions (PPI) of these genes using the STRING database.

Results: An exhaustive database search of the title, abstract, and full-text screening consistent with the eligibility criteria yielded 277 studies. LOH commonly studied in OPMD and OSCC include p53 gene, p16 gene, adenomatous polyposis coli gene, retinoblastoma (Rb) gene, fragile histidine triad (FHIT) gene and phosphatase and tensin homolog (PTEN) gene. Chromosome loci involving 17p, 9p, 5q, 13q, 3p, and 10q were frequently reported in OPMD and OSCC. PPI analysis demonstrated strong evidence of p53 interaction with p16, FHIT, and Rb.

Conclusion: Distinctive signatures of LOH are seen in OPMD and OSCC. The LOH patterns identified in this scoping review underline the significance of advanced molecular techniques and the need for long-term prospective cohorts to understand LOH pathophysiology in oral carcinogenesis to enable their usefulness as biomarkers in early diagnosis, treatment, and prognostication of oral cancer.

Background: Chondrosarcoma is a malignant neoplasm characterized by the production of a cartilaginous matrix.

Case report: We present the case of a 58-year-old male patient referred to the maxillofacial surgery and traumatology service due to swelling in the posterior region of the right maxilla, with a duration of 8 months, and a previous history of a fibro-osseous lesion in the region. Intraoral examination revealed a rounded lesion with ulceration, firm upon palpation, in the area of teeth 17 and 18. The panoramic radiograph revealed a radiopaque lesion with a flocculated pattern in the right maxilla, and computed tomography showed a hyperdense lesion containing hypodense areas. Histopathological analysis revealed the presence of immature cartilage, with rounded neoplastic cells, nuclei of varied sizes, and intense pleomorphism, leading to a diagnosis of chondrosarcoma. The patient underwent surgical resection followed by radiotherapy and, after one year of follow-up, has shown no signs of recurrence.

Conclusions: Although rare in gnathic bones, chondrosarcoma should be considered in the differential diagnosis of osseous enlargement in this region.

Langerhans cell histiocytosis is a rare disease which is more common in the childhood. Clinical presentation may vary ranging from single to multiple organ involvement. Skeleton is often involved and in the maxillofacial region, it affects the mandible more than the maxilla. Radiographically, it may present as a well-defined radiolucency or an ill-defined radiolucency. The presence of Langerhans cells in an inflammatory background with prominent eosinophils gives a clue to the diagnosis. Confirmation is by positive immunohistochemical staining with S100, CD1a and CD207. Here, we report a case of a 7-year-old female patient who presented with a swelling in the left mandibular region which was diagnosed as unifocal Langerhans cell histiocytosis after complete evaluation.

Background: Ghost cell odontogenic carcinoma (GCOC) is a rare malignant neoplasm that has a propensity for the maxilla, with a male predilection, and approximately sixty-four cases reported to date. We herein report the sixty-fifth case in a 38-year-old male patient with maxillary lesion, along with an extensive literature review.

Case presentation: A 38-year-old male patient was referred to the oral and maxillofacial surgery clinic at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, with a nonhealing proliferative growth in the anterior maxilla for two months. Microscopically, the lesion showed ghost cells and dentinoid deposition with ameloblastoma-like epithelial linings and malignant features, including nuclear pleomorphism, increased mitosis, necrosis, perivascular invasion, and invasion into adjacent bone. The tumor cells were reactive to CAM5.2, p63, CK5/6 and CK19, with CK5/6 and CK19 being positive in the peripheral area in a ring-like pattern in the ghost cell region. Additionally, nuclear staining of beta-catenin was detected while next generation sequencing revealed mutations in the CTNNB1 variant c.110 C > G p.(Ser37Cys) and the ARID1A variant c.4420 C > T p. (Gln1474*), respectively, at the high variant allele. The patient was treated with surgical excision and bilateral cervical lymph node dissection followed by adjuvant radiotherapy, and the patient was free of disease after 30 months.

Conclusion: Ghost cell odontogenic carcinoma is a rare aggressive odontogenic tumor that can be challenging to diagnose, especially with incisional biopsy. CTNNB1 is a consistent gene mutation in this tumor; however, ARID1A was reported for the first time in our patient.

Introduction: Oral squamous cell carcinoma is the most prevalent of all the oral cancers. There is no definitive marker available for its early diagnosis and its effective prognosis. YAP serves as a transcriptional regulator in hippo tumor suppressor pathway thereby activating the transcription of genes taking part in cellular proliferation, alteration, migration, and invasion. On the contrary, PARK2 acts as a tumor suppressor and has been widely explored in various malignancies. However, its role in OSCC carcinogenesis is untrodden.

Aim: To evaluate the Immunohistochemical expression of YAP and PARK2 in oral epithelial dysplasia and Oral Squamous Cell Carcinoma and establish them as prognostic markers.

Material and method: The study sample consisted of 70 formalin fixed paraffin embedded tissue sections of normal oral mucosa (10), oral epithelial dysplasia (30) and oral squamous cell carcinoma (30). Immunohistochemical analysis of YAP and PARK2 was done and final scores were calculated. Further, the markers were graded as low and high expression groups. Statistical analysis was done using chi-square test, cox regression analysis and Spearman's correlation. Kaplan Meier plot for survival analysis was also plotted.

Result: Immunohistochemical expression of YAP depicted a gradual incline from normal oral mucosa to oral squamous cell carcinoma while PARK2 showed a reverse trend. Significant difference of YAP and PARK2 expression between three groups was noted. Inverse moderate degree of correlation was observed between both the markers in OSCC group.

Conclusion: Concomitant immunoexpression of YAP and PARK2 with a moderate degree of inverse correlation from normal oral mucosa to oral squamous cell carcinoma could probably serve as diagnostic and prognostic markers as they might act through a common mechanism, probably hippo/YAP signaling, which could be further confirmed by larger sample size, including longer follow up in future studies.

Purpose: Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.

Methods: A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.

Results: GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10^-7), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10^-11). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10^-5).

Conclusion: The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.