Oral Surgery Oral Medicine Oral Pathology Oral Radiology最新文献

Introduction

Methotrexate is used to treat a variety of conditions, including cancer, rheumatoid arthritis, and psoriasis. It has been strongly associated with oral mucositis, especially in the setting of folate deficiency and has been reported to cause atypical changes in the oral epithelium. Its cytotoxic effects are dose-dependent and mediated by folate antagonism. We present two cases in which patients presented with methotrexate-induced mucositis and whose biopsies also demonstrated cytologic atypia.

Materials and Methods

Two cases of methotrexate induced ulcerations were seen by the Oral Pathology Laboratory Inc. at New York Presbyterian Queens. One was submitted with clinical images and biopsy material by an outside surgeon. The second was seen by the Oral Pathology Service at NYPQ.

Case Report

Both patients were females in their seventies who had medical histories requiring methotrexate use. One patient was taking folic acid. They both presented with widespread painful oral ulcerations. Biopsies were performed on both patients. Both cases demonstrated ulcerated, atrophic stratified squamous epithelium exhibiting scattered mitotic activity and cells with variously sized nuclei with a sparse underlying neutrophilic and lymphocytic infiltrate. In one case, a diagnosis of ulcer with epithelial atypia and sparse inflammatory infiltrate was made. In the other, a diagnosis of mucositis with cytologic atypia was rendered. A note stating that these findings are consistent with methotrexate mucositis was included with each. The lesions completely resolved upon discontinuation of methotrexate use.

Conclusion

Methotrexate has been strongly associated with oral mucositis. In patients receiving methotrexate therapy with new onset painful oral ulcerations the clinician should consider methotrexate-associated mucositis in their differential diagnosis. Pathologists should be aware that methotrexate can induce mucositis as well as atypical changes that can mimic dysplasia. These lesions should not be treated as dysplasia, but rather as methotrexate-induced mucositis, which will resolve upon discontinuation of methotrexate use.

Introduction

Human papillomavirus (HPV)-associated oral epithelial dysplasia (OED) and squamous cell carcinoma of the oral cavity (OSCC) are uncommon. They are known to present with distinct histomorphology and diffuse block-like p16 immunohistochemistry (IHC). We recently described a novel OED classification system using p53 and p16 IHC and encountered several cases of OED with both diffuse p16 expression and aberrant p53 expression (“double-positive”). We hereby report five cases of “double-positive” p53 and p16 OED and OSCC with their unique morphology and results of high-risk (HR) HPV in situ hybridization (ISH) and TP53 mutation analysis.

Materials and Methods

Five cases of “double-positive” OED and/or OSCC with basaloid morphology were identified from the British Columbia Oral Biopsy Service, Vancouver General Hospital and Pathology and Laboratory Medicine, Foothills Medical Centre, University of Calgary. HR HPV ISH was performed on all cases. TP53mutation analysis by targeted Next-Generation Sequencing (NGS) was performed on four of the five cases.

Results

All five cases showed abundant karyorrhectic cells, apoptotic keratinocytes, and basaloid or “Bowenoid” morphology. All five cases demonstrated p16 diffuse block-like positivity and p53 abnormal staining patterns (3 overexpression, 2 null). HR HPV RNA ISH was negative in all five cases. Three of the four cases sent for targeted NGS demonstrated pathogenic TP53 mutations.

Conclusion

Our results suggest these “double-positive” cases should be classified as p53 abnormal-OED and p53 abnormal-OSCC, instead of HPV-associated OED and HPV-associated OSCC, to accurately reflect their underlying pathophysiology. Interpretation of p16 IHC in OED and OSCC with basaloid histomorphology should be done with extreme caution. Confirmation with p53 IHC, with consideration for HR HPV ISH is highly recommended to prevent misdiagnosis and misclassification of these oral lesions.

Leiomyosarcoma (LMS) is a soft tissue sarcoma arising from the embryonic mesoderm of smooth muscle lineage. LMS of the oral cavity is exceedingly rare, accounting for less than 1% of smooth muscle malignancies. We describe a 60-year-old female who presented for evaluation of a rapidly expanding mass in her lower left mandibular quadrant of three weeks duration. The patient reported a one-year history of sporadic pain in the area. The patient's medical history was significant for a lesion involving the same quadrant three months prior that was diagnosed as a myofibroma. Clinical examination revealed a large, exophytic, fleshy, erythematous mass extruding from the left posterior mandible. Cone beam computed tomography demonstrated a multilobulated hypodensity involving the left mandibular body and ramus. The lesion had perforated the buccal and lingual cortices, displaced tooth #19 in an anterior-buccal direction, and inverted its vertical orientation. A left hemimandibulectomy was performed, and histopathologic examination of the resection specimen showed an infiltrative hypercellular proliferation of atypical spindle cells with distinctly eosinophilic cytoplasm, cigar-shaped nuclei, and a fascicular growth pattern. The spindle cells demonstrated immunoreactivity to desmin and caldesmon, supporting a diagnosis of LMS. Immunohistochemical staining was also positive for ER, PR, and patchy WT1, suggesting the possibility of a gynecological origin. A uterine primary was discovered on subsequent medical evaluation. The patient is currently undergoing chemotherapy for the management of metastatic uterine LMS. Less than twenty cases of metastatic LMS have been reported in the literature to date. Knowledge of the morphological and immunohistochemical hallmarks of this malignancy can aid in directing the diagnostic workup, thereby facilitating timely management. Furthermore, this challenging case highlights the importance of effective interdisciplinary communication in reconciling discrepancies that arise between the histologic diagnosis and clinical behavior of a lesion.

Introduction

Ameloblastomas, a type of odontogenic tumor, exhibit the BRAF V600E mutation in more than 65% of cases. This study aims to explore the potential correlation between the BRAF V600E mutation, the biological behavior of conventional ameloblastomas, and Disease-Free Survival in patients.

Materials and Methods

This retrospective cohort study, following STROBE recommendations, involved individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF V600E mutation analyses were conducted. Bivariate statistical analysis employed chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression identified disease-free survival predictors at a 5% significance level.

The study included 41 individuals, with a male-to-female ratio of 1.15:1. The BRAF V600E mutation was present in 75.6% of tumors. No significant associations were found between BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables. Univariate (p = 0.008) and multivariate (p = 0.030) analyses revealed that the initial treatment modality significantly influenced prognosis, favoring radical treatment with a Hazard Ratio of 9.60 (95%IC = 1.24 – 73.89).

Conclusions

BRAF V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, and disease-free survival outcomes.

Introduction

Osteosarcoma is the most common malignancy of bone when excluding hematopoietic neoplasms. The vast majority occur in the long bones of adolescents with a second, lesser peak in patients sixty years or older; only approximately 6% arise in the jaws, with an average age of 35-40 years. Distribution is relatively equal between the maxilla and mandible. Osteosarcomas are classified based on anatomic location within the bone (central, surface, or extraskeletal), predominant histopathologic subtype (osteoblastic, chondroblastic, fibroblastic, etc), and by grade (low-, intermediate-, and high). Most gnathic lesions are located centrally. Surface osteosarcomas, especially those that exhibit high-grade features, are extremely rare in the gnathic bones.

Materials and Methods

A well-documented case of high-grade surface chondroblastic osteosarcoma of the anterior maxilla is presented with clinical photographs, radiographic images, and photomicrographs.

Results

A painless, rapidly enlarging nodular lesion extending from the anterior maxillary alveolus was noted in a 28-year-old male, measuring approximately 3.5 × 3.5 × 2.0 cm. The patient reported that the lesion appeared approximately 1 year prior after being hit in the face while playing with his child. The clinical differential diagnosis provided by the clinician included peripheral ossifying fibroma and peripheral giant cell granuloma. Radiographic images showed hyperostosis associated with the root of #9 and mild surface erosion. Microscopic examination exhibited cellular rays of abnormal neoplastic bone running perpendicularly toward the surface with extensive cartilaginous differentiation in a vague nodular arrangement. Delicate lacy osteoid was present at the base of the specimen and scattered within the cartilaginous component. Numerous large atypical chondroid neoplastic cells with moderate atypia and primitive-appearing stellate-to-spindled chondroid mesenchymal cells were also noted. FISH did not demonstrate an MDM2 amplification; however, monosomy 12 was detected in 17.5% of cells.

Conclusions

This case represents a valuable addition to the literature in light of its extreme rarity.

Introduction

Sinonasal neuroendocrine malignancies are subclassified into small cell and large cell neuroendocrine carcinoma and olfactory neuroblastoma (ONB). Recently, neoplasms that display histomorphologic similarities to ONB but additionally reveal overt epithelial features have been designated as olfactory carcinoma (OCA). Herein, we report the clinicopathologic characteristics of two cases of OCA.

Material and methods

The archives of the OSU Department of Pathology were searched for tumors diagnosed as or displaying features suggestive of OCA. Information regarding patient age and gender, location, radiographic, histopathologic and immunohistochemical features of the lesion, treatment and follow-up was retrieved.

Results

Two cases, arising in 48 and 55-year-old males, met the diagnostic criteria for OCA. Both presented as destructive, midline, sinonasal tumors (4.3 and 7.0cm) that caused erosion of the cribriform plate and nasal septum, extending into the ethmoid, sphenoid and maxillary sinuses, with intracranial and, in one case, orbital involvement. Histopathologically, the tumors exhibited solid or ribbon-like areas with prominent rosette formation, or organoid and trabecular arrangements lacking identifiable neural-type rosettes. Neoplastic cells were small with rounded, ovoid and/or angulated, hyperchromatic nuclei, coarse nucleoplasm, nuclear molding, and minimal cytoplasm with indistinct cell borders. Geographic necrosis, apoptosis and mitoses were plentiful. Immunohistochemically, lesional cells featured focal-to-diffuse reactivity for pancytokeratin, CAM 5.2, EMA and p40, in addition to variable positivity for synaptophysin, chromogranin, CD56 and INSM1. S100 focally highlighted sustentacular cells, while SMARCB1 expression was retained. Both tumors were classified as Stage IVb and treated with surgery and chemoradiation therapy. Patients remained disease-free after 7 and 60 months of follow-up.

Conclusions

OCAs are exceedingly rare sinonasal malignancies with aggressive biologic behavior and overt neuroepithelial attributes. Such diagnosis, however, may be challenging due to lack of well-established criteria and occasional absence of glandular or rosette-like structures. Therefore, proper diagnosis relies heavily on immunohistochemical recognition of the combined neuroepithelial differentiation.

Introduction

Oral squamous cell carcinoma (OSCC) is the most common neoplasm in the oral and maxillofacial region and is commonly preceded by tissue alterations in the form of oral epithelial dysplasia (OED). OEDs are clinically and histologically heterogeneous, with unique cellular, stromal, and signaling components. The dysplasia immune microenvironment (DIME) and the study of this complex interplay of its various cellular and non-cellular components remain a knowledge gap in the field of OSCC immune-oncology. In our study, we propose a high-throughput multi-dimensional analysis to visualize the complex interactions of the tumor microenvironment in progressing and non-progressing oral epithelial dysplasia. This study highlights the vast potential of multiplex single-cell technology to quantify and understand spatial interactions within the microenvironment as a tool to understand dysplasia progression and oral cancer behaviour.

Materials and Methods

In this retrospective study, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously examine the expression of 21 protein markers in the DIME including cellular and non-cellular components. We analyzed 11 progressing oral epithelial dysplasia, 11 non-progressing oral epithelial dysplasia, and 9 inflamed mucosa and 2 non-inflamed mucosa controls, resulting in 693 high-dimensional pathology images. Deconvolution, t-SNE, UMAP, cytometry analyses were performed using FlowJo, HistoCat, and ImaCyte.

Results

Qualitative, quantitative, and spatial interactions were characterized in both progressing and non-progressing oral epithelial dysplasias. We found that within progressing and carcinoma groups, there is a reduction in the cytotoxic immune response, and upregulation of inflammatory phenotypes, and stromal markers that promote a favorable microenvironment for cell growth and proliferation.

Conclusion

Our study highlights that spatially resolved, single-cell analysis can characterize pre-malignant and malignant OSCC heterogeneity in cellular architecture and cellular composition, which provides a basis for future studies on how better understanding of the microenvironment can influence disease outcomes.

Introduction

Neuroendocrine and nonneuroendocrine neoplasms can rarely coexist in the same epithelial malignancy as a mixed neuroendocrine and nonneuroendocrine neoplasms (MiNEN). The most common neuroendocrine component in MiNEN is small cell carcinoma (SmCC) and the most common nonneuroendocrine component is squamous cell carcinoma (SqCC). Head and neck MiNEN neoplasms are rare with only twenty-one cases reported. Of these, only eight arose in the oropharynx and had SqCC as the nonneuroendocrine component. Herein we present the first case of an oropharyngeal MiNEN containing an HPV-associated adenocarcinoma as the nonneuroendocrine component.

Case Description

A 56-year-old male smoker (30-pack-years) presented with a four-month history of a progressively growing painless right neck mass. Computed tomography scan revealed an ill-defined heterogeneously enhancing soft tissue lesion in the right palatine tonsil. Histopathologic examination showed two intermixed morphologically distinct neoplastic components. One component, accounting for 90% of the tumor on biopsy, had typical histologic and immunophenotypic features of SmCC. The other component, comprising 10% of the tumor on biopsy, was a gland forming epithelial neoplasm. These tumor cells were positive for CK AE1/AE3, MOC31, CK20, and CDX2. Both components were negative for squamous markers (CK5/6 and p63) as well as CK7, TTF1, GATA3 and SOX10. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components. A diagnosis of oropharyngeal HPV-associated MiNEN with SmCC and adenocarcinoma components was rendered.

Discussion

The presence of two adjacent components with distinct morphologies should always alarm the pathologist to consider MiNEN in their case work up, and HPV testing should be performed for all oropharyngeal carcinomas, not just SqCC. Careful morphologic and immunohistochemical examination is necessary to identify and correctly diagnose these neoplasms.

Introduction

The proper preservation of biopsy specimens is crucial for maintaining cellular integrity during histological processing, significantly influencing the quality of immunohistochemical (IHC) and histological analyses. Despite recommendations for 10% buffered formalin as the ideal fixative, pathology labs often receive materials in various solutions. This study assesses the effects of different solutions and temperatures on histological and immunostaining outcomes in IHC reactions, a pivotal diagnostic tool for detecting specific proteins in tissue samples.

Materials and Methods

Skin samples from euthanized Wistar rats were collected and fixed in different solutions (buffered and unbuffered formaldehyde, alcohol, and saline), stored for 24 hours, 7 days, and 30 days. Staining involved Hematoxylin and Eosin, along with Monoclonal Mouse Anti-Human Muscle Actin antibody (Code HHF-35, Dako Denmark). Qualitative and quantitative assessments were conducted.

Results

Histological analysis revealed that samples fixed in formalin at room temperature exhibited higher immunostaining and more homogeneous tissue structures than those stored in the refrigerator. Fragments stored in alcohol and saline exhibited reduced immunostaining and tissue autolysis, respectively.

Conclusions

Rat skin samples fixed with 10% formalin at room temperature for up to 7 days yielded superior histological and immunohistochemical results, considering cellular expression and integrity. Refrigerated storage increased the incidence of tissue artifacts. This study underscores the importance of optimal storage conditions for preserving tissue quality in histopathological investigations. Valuable insights are provided for pathology laboratories handling diverse fixative solutions, emphasizing the need for adherence to recommended protocols.