Introduction Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a rare, self-limiting lymphoproliferative disorder often seen in immunosuppressed individuals, including the elderly. It can involve the oral mucosa and mimic malignant lesions clinically and histologically. While solitary lesions are most commonly reported, multifocal presentations are exceedingly rare, with only two previously documented oral cases. This series highlights one multifocal and three solitary oral EBV-MCU cases, focusing on clinical features, diagnostic challenges, and management strategies. Materials and Methods We conducted a retrospective analysis of cases submitted to the Oral Pathology Clinic and Laboratory at the University of Iowa, diagnosed as EBV-positive mucocutaneous ulcers. Results An 80-year-old patient presented with multiple oral ulcers. Histopathological analysis revealed ulceration with granulation tissue, atypical lymphoid cells positive for CD20 (IHC) and PAX5 (IHC). Epstein-Barr virus was confirmed by EBV-encoded RNA (EBER) in situ hybridization. One month later, the patient was diagnosed with diffuse large B-cell lymphoma (DLBCL), underscoring the importance of immune status evaluation. Three additional cases were identified presenting as solitary oral ulcers at different sites, with no immunosuppression reported, and sharing similar histopathological findings. In these 3 patients, medical work-up did not reveal any underlying immunosuppressive diseases and the patients experienced resolution of EBV-MCU with supportive care. Conclusions This case series underscores the rarity of multifocal EBV-MCU and its potential association with underlying conditions. Awareness among clinicians and pathologists is essential to recognize this benign lesion, particularly in the elderly, that can mimic malignancy. While EBV-MCU typically resolves spontaneously with a favorable prognosis, thorough evaluation for potential immune dysregulation or systemic disease is critical, particularly in multifocal lesions.

Background Pemphigus vulgaris is an autoimmune disease that causes blisters on skin and/or the mucous membrane. It is the most common suprabasilar splitting disease in the oral cavity, with the oral cavity often showing the first signs of this condition. Though still a serious disease, pemphigus vulgaris can usually be treated with modern medical advances. In clinical practice, pemphigus vulgaris is most often seen in middle-aged female. We describe three cases of pemphigus vulgaris in male patients. Case description 25-year-old, 30-year-old, and 50-year-old healthy male patients presented with multifocal painful erosions and ulcerations in the oral cavity. The second and third patients also had blisters and ulcers on their skin. The lesions appeared a few weeks following the injection of the COVID-19 vaccine. Biopsies were performed from either the oral lesions or skin lesions. All specimens displayed suprabasilar epithelial separation with acantholysis. Further investigation with direct immunofluorescence testing, and anti-desmoglein ELISA were conducted. These tests confirmed the diagnosis of pemphigus vulgaris. The treatment included topical steroids, systemic steroids, and Rituximab (anti-CD20 monoclonal antibody, IV). Conclusion There may be a rise in immune-mediated diseases in previously healthy patients of atypical age and gender demographics. If pemphigus vulgaris is diagnosed, further clinical history to include asking about COVID-19 infection/vaccination may be of interest to further evaluate any possible connection.

Hematolymphoid neoplasms originating in the periapical region of a tooth are rare occurrences. Their signs, symptoms, and radiographic findings can also mimic lesions of endodontic origin. History-taking and clinical examination provide clues to determine the possibility of a non-endodontic lesion, although the definitive diagnosis can only be rendered based on histologic examination.In our case series, we present four cases of hematolymphoid neoplasms that radiographically mimicked endodontic lesions. All the cases initially underwent endodontic treatment, but the lesions failed to resolve. In one case, the clinician suspected a diagnosis of lymphoma based on the patient's history. In the other cases, the clinicians' impression was that the lesions originated from endodontic issues. We present two cases of diffuse large B-cell lymphoma, a case of a plasma cell neoplasm, and a case of Langerhans cell histiocytosis, along with a literature review of three entities when found in the oral cavity as well as review of hematolymphoid neoplasm mimicking endodontic lesion previously reported in literature.

Introduction: Radiographic findings in periradicular areas are repeatedly associated with infected root canal systems. Although non-odontogenic lesions in teeth are reported to be low, they often mimic periapical pathoses, and consequently, histopathologic examinations after surgical revisions are nurtured. Methods: Biopsies submitted to the College of Dentistry between 2003 and 2021 were reviewed. Clinicopathologic characteristics were collected, including age, sex, medical history, location, sensibility tests, and clinic impressions from each specimen. Histopathologic diagnosis and gross description were also part of our database. Results: A total of 72,055 pathology reports were reviewed, of which 10,031 lesions (13.9%) met the criterion of being intraosseous lesions at the periradicular area. Among those 10,031 lesions, 7.94% (n = 796) were of non-endodontic origin, 7153 were documented as non-vital, and 2.36% (n = 169) of these non-vital teeth were diagnosed with a non-endodontic origin. A total of 5707 lesions were obtained from surgeries within the periapical tissues, primarily performed by endodontists (94.02%). Non-endodontic lesions were reported in 1.09% of the cases. Odontogenic keratocyst was the most common non-endodontic diagnosis, followed by nasopalatine duct cyst and benign fibro-osseous lesion, respectively. Conclusions: Pathologic findings of the periradicular tissues are not always from endodontic origin. The probability of encountering non-endodontic lesions is almost 8%. Even in clinically reported teeth with pulp necrosis, 1%-3% of biopsies were confirmed as non-endodontic lesions. (J Endod 2023;49:1457-1463.)

90 Background: Premalignant lesions within the oral cavity demonstrate varied degrees of dysplasia. Oral stratified squamous epithelium is sensitive to carcinogenic insults and lesions progress to cancer at variable rates. The current diagnostic standard involves visual and tactile inspection followed by a biopsy. However, thus far, there is clinical ambiguity about which lesions may progress to carcinoma and there are insufficient prognostic tools available to guide clinical decision-making for follow-up. Deep learning is a form of artificial intelligence which can be applied to images. Self-supervised learning (SSL) and attention-based multiple instance learning (aMIL), are deep learning extensions which eliminate the need for pathologist annotations of histology and are more generalizable as the model learns general representations of unlabeled data, compared to traditional tile-based methods. We developed a novel artificial intelligence pipeline to predict progression to oral carcinoma using histological images from oral premalignant lesions. Methods: Digital histopathology images and clinical data cohorts were obtained from the US National Cancer Institute (n=561) and the University of Iowa (n=193) for training, and from the University of Chicago (n=214) for external validation. Patients were defined as progressing if initially non-malignant lesions had documented progression to carcinoma within 12 months of follow-up. Model training and evaluation was done in Python using our publicly available open-source Slideflow platform. We developed a deep learning pipeline utilizing SimCLR as an SSL method for feature extraction paired with an aMIL head for classification. The SimCLR feature generator was trained on only the training cohort, then used to generate features for both training and validation data. The aMIL model was trained on SimCLR-generated features. Trained model performance was evaluated on the external University of Chicago cohort and measured via areas under the receiver operating characteristic curve and precision recall curve (AUROC and AUPRC, respectively). During training and validation, model reliability was interpreted using Class Activation Mapping (Grad-CAM) and generative adversarial network (GAN) methods. Results: On training data, the model achieved average 3-fold cross validation AUROC of 0.86 with AUPRC of 0.83. In the external validation data from UC, the model achieved an AUROC of 0.80 with an AUPRC of 0.79. Deployed as a “rule-in” test for early progression prediction, the model achieved a validation data set specificity of 91% with a sensitivity of 40%. Conclusions: We developed a deep learning model to automatically predict cancer progression from premalignant lesions histopathology using a multi-institutional cohort, with promising external validation performance.

Abstract: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children. This lesion is classically included in the generic group of “small round blue cell tumors” along with other entities that share similar microscopic features. Although the head and neck region is a frequent site for primary tumors, cutaneous metastases of RMS involving this anatomical location are rare in the pediatric population. We report a case of a 12-year old girl previously diagnosed with a primary alveolar RMS involving the left maxillary sinus, presenting with a metastatic lesion on the skin of the left temple area. Along with a brief review of the previous case reports on the topic, we highlight the initial immunohistochemistry panel useful for diagnosing this tumor.

A 58-year-old white female was referred to the oral and maxillofacial surgeon for evaluation of a soft tissue lesion on the left lower lip with a clinical impression of mucocele. At the time of the appointment, the lesion had significantly decreased in size. The clinical diagnosis of a resolving mucocele was established, and the patient decided to monitor the lesion. Extraoral and intraoral examination failed to reveal any significant asymmetry or mass effect besides the referred area on the lower lip. The patient had all 4 third molars extracted at age 19 with no complications. The patient's medical history was significant for hypertension and atrial fibrillation (managed with amlodipine, valsartan, furosemide, rivaroxaban, and carvedilol), hyperglycinemia (managed with simvastatin), and obstructive sleep apnea syndrome (managed with the use of a CPAP machine at bedtime). The patient also had a breast fibroadenoma excised in 2012 with no complications. She reported allergies to penicillin and codeine and was regularly taking vitamin D and potassium supplements. The remaining social, familial, and dental history were noncontributory.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.

I found the June case report “Oral Adverse Reactions Associated With Etoricoxib, a Common Pain Mediation” (Edel J, Vered M, Osnat Grinstein-Koren, O, et al. JADA. 2019;150[6]:556-561) to be well-written and insightful. The lack of recognition of harmful intraoral effects of drugs is responsible for a great deal of patient suffering. Oral adverse reactions associated with etoricoxib, a common pain medicationThe Journal of the American Dental AssociationVol. 150Issue 6PreviewThere have been reports of cutaneous adverse reactions to etoricoxib, a frequently used anti-inflammatory and antipain medication. In this report, the authors describe the first series of patients with adverse reactions to etoricoxib restricted to the oral mucosa. Full-Text PDF Editor’s responseThe Journal of the American Dental AssociationVol. 150Issue 9PreviewI would like to thank Drs. Wenckus, Marek, and Hellstein for taking the time to correspond with us about their concerns with the June JADA article titled “Oral Adverse Reactions Associated With Etoricoxib, a Common Pain Medication” (Edel J, Vered M, Grinstein-Koren O, et al. JADA. 2019;150[6]:556-561). Full-Text PDF

Candidiasis is a very common malady in the head neck region. This review will concentrate on intraoral, pharyngeal and perioral manifestations and treatment. A history of the origins associated with candidiasis will be introduced. In addition, oral conditions associated with candidiasis will be mentioned and considered. The various forms of oral and maxillofacial candidiasis will be reviewed to include pseudomembranous, acute, chronic, median rhomboid glossitis, perioral dermatitis, and angular cheilitis. At the end of this review the clinician will be better able to diagnose and especially treat candidal overgrowth of the oral facial region. Of particular interest to the clinician are the various treatment modalities with appropriate considerations for side effects.

Dental implants have become increasingly common. The maxillary arch has anatomical structures that can pose a challenge when sinus augmentation and/or sinus bone graft are required. Although rare, fungal infection is a potential complication in an immunocompetent patient.

OBJECTIVES:To retrospectively study the prevalence of perineural invasion (PNI) in cases of mucoepidermoid carcinoma (MEC). The study evaluated if previously assessed PNI would be increased by re-review of the original hematoxylin and eosin-stained (H&E) slides and also review of slides reacted immunohistochemically with S100 to enhance nerve visualization and whether this is associated with clinical outcome.STUDY DESIGN:Thirty-one cases were reviewed for PNI with H&E-stained slides as well as S-100-reacted slides. These results were compared with the original pathology report's PNI status when available (13 of 31). Subject demographic characteristics and clinical outcome were collected from electronic medical records.RESULTS:PNI was identified in 23% (3 of 13) of tumors in the original reports, 13% (4 of 31) of the authors' re-review of the slides, and 29% (9 of 31) by immunohistochemical assessment for S100. PNI and larger-diameter nerve involvement were significantly associated with death at 5-year follow-up.CONCLUSIONS:Immunohistochemical assessment for S100 improves the accuracy of PNI determination. PNI is a significant factor in the survival outcome of cases of MEC.

The aim of this study was to compare the immunoexpression of epithelial mucins (MUCs) in salivary duct cysts, papillary cystadenomas, and mucoepidermoid carcinomas and to evaluate if any of these markers could be useful for differentiating between mucoepidermoid carcinoma and papillary cystadenoma. We also sought to validate the p63 expression pattern found to differentiate between mucoepidermoid carcinoma and papillary cystadenoma. Immunoexpression of MUC1, MUC2, MUC4, MUC7, and p63 was studied and quantified in 22 mucoepidermoid carcinomas, 12 papillary cystadenomas, and 3 salivary duct cysts. The immunohistochemical evaluation was collectively performed by 3 oral pathologists. Scores and trends in proportions were assessed using the nonparametric Wilcoxon–Mann–Whitney rank sum test. Mucoepidermoid carcinomas, papillary cystadenomas, and salivary duct cysts demonstrated variable MUC expression patterns. All tumors were positive for p63 immunoexpression with p63 labeling in salivary duct cysts and papillary cystadenomas (15/15) limited to the basal layers of the cystic spaces, whereas in mucoepidermoid carcinomas (22/22) the p63 labeling extended throughout the suprabasal layers (p < 0.001). This study adds more confirmatory data to validate that the reactivity pattern of p63 protein can be used in distinguishing between papillary cystadenoma and low-grade mucoepidermoid carcinoma. Although positive reactivity in a tumor with MUC1 and MUC4 was inconclusive, negative reactivity suggests the diagnosis of a benign PC or SDC.

A 59-year-old man was transferred from an outside hospital to the emergency department (ED) at the University of Iowa Hospital and Clinics with the chief complaint “my mouth is swollen on the inside.” He reported that the swelling started a couple of days before the ED presentation, but the tooth in the area had been fractured for weeks. The patient presented with a maxillofacial computed tomography (CT) scan with contrast from the outside hospital, demonstrating a periapical radiolucent area associated with the maxillary left first molar, a soft tissue mass on the facial and palatal aspects in the area, and a soft tissue mass in the left maxillary sinus. These findings were initially interpreted by the outside hospital as a left maxillary dental infection and maxillary sinusitis. The ED contacted the hospital dentistry department, who ordered a panoramic radiograph (Figure 1), which revealed a well-defined, poorly corticated, radiolucent lesion associated with the apices of the grossly destroyed maxillary left first molar. There was evidence of soft tissue enlargement in the region and complete soft tissue opacification of the left maxillary sinus. Hospital dentistry extracted the referenced tooth and debrided the area. The patient was instructed to finish the antibiotic course (amoxicillin/clavulanic acid) previously prescribed by the outside hospital and was given analgesic medications. Six days later, he presented again to the ED with no relief of his symptoms and increased pain. The clinical presentation revealed an expansile mass of the left hard palate and alveolar ridge displaying surface ulcerations (Figure 2). The patient was transferred to the oral surgery department. The prior imaging was reviewed and a new CT scan was made (Figure 3). An oroantral communication was noted in the region of the extracted maxillary left first molar, as well as ill-defined periapical radiolucent areas associated with the maxillary left second molar and the mandibular right first molar. The soft tissue mass covering the alveolar process in the left posterior maxilla was also seen. Progression of the soft tissue mass in the left maxillary sinus was noted, and now it was extending into the nasal cavity, obliterating the left maxillary infundibulum. There appeared to be discrete bone destruction in the region (Figure 3). The maxillary left second molar was extracted, along with incision and drainage of the palatal space, and incisional biopsies of palatal soft tissues and alveolar bone were done due to concern for possible malignancy.Fig. 2Clinical photograph showing an ulcerated expansile lesion of the left hard palate and alveolar process with displacement of the second molar.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 3Coronal slices of multidetector computed tomography (CT) scans dated a month apart. Initial presentation (top row): A, Bone and B, soft tissue windows demonstrating a periapical radiolucent area associated with the maxillary left first molar and a soft tissue mass on the facial and palatal aspects in the area (white arrows). A soft tissue mass was also noted in the left maxillary sinus. Current presentation (bottom row): C, Bone and D, soft tissue windows demonstrating an oroantral communication in the region of the extracted maxillary left first molar. The soft tissue mass covering the alveolar process is still seen in the area. A progression of the soft tissue mass in the left maxillary sinus is also noted, and now it is extending into the nasal cavity and obliterating the left maxillary infundibulum (black arrows). There appears to be discrete bone destruction in the region.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In patients with expansile, destructive sinonasal lesions with palatal extension and ulceration, aggressive lesions such as vasculitic diseases, deep fungal or bacterial infections, and malignant neoplasms should be considered.1Batsakis J.G. Luna M.A. Midfacial necrotizing lesions.Semin Diagn Pathol. 1987; 4: 90-116PubMed Google Scholar, 2Parker N.P. Pearlman A.N. Conley D.B. Kern R.C. Chandra R.K. The dilemma of midline destructive lesions: A case series and diagnostic review.Am J Otolaryngol. 2010; 31: 104-109Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Based on the location of the present case, malignant neoplasms to consider would include sinonasal carcinomas, non-Hodgkin lymphoma (NHL), and high-grade salivary gland neoplasms.2Parker N.P. Pearlman A.N. Conley D.B. Kern R.C. Chandra R.K. The dilemma of midline destructive lesions: A case series and diagnostic review.Am J Otolaryngol. 2010; 31: 104-109Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Even though granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) has been classified as the most common vasculitic disease to classically present with a destructive, ulcerated, upper respiratory lesion,3Allen C.M. Camisa C. Salewski C. Weiland J.E. Wegener’s granulomatosis: Report of three cases with oral lesions.J Oral Maxillofac Surg. 1991; 49: 294-298Abstract Full Text PDF PubMed Scopus (35) Google Scholar, 4Eufinger H. Machtens E. Akuamoa-Boateng E. Oral manifestations of Wegener’s granulomatosis. Review of the literature and report of a case.Int J Oral Maxillofac Surg. 1992; 21: 50-53Abstract Full Text PDF PubMed Scopus (36) Google Scholar, 5Ponniah I. Shaheen A. Shankar K.A. Kumaran M.G. Wegener’s granulomatosis: The current understanding.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005; 100: 265-270Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 6Grindler D. Cannady S. Batra P.S. Computed tomography findings in sinonasal Wegener’s granulomatosis.Am J Rhinol Allergy. 2009; 23: 497-501Crossref PubMed Scopus (33) Google Scholar the described case presented very few similarities with such condition. Deep fungal infections of the head and neck, on the other hand, involve the sinuses primarily, followed by the nasal cavity, as seen in the current case. Invasive fungal sinusitis with Aspergillus and mucormycosis with the subphylum Mucormycotina would present similarly and would most likely be seen an immunocompromised host. With maxillary sinus involvement, intraoral swelling of the maxillary alveolar process and palate is often present, with surface ulceration not uncommon.7deShazo R.D. O’Brien M. Chapin K. et al.A new classification and diagnostic criteria for invasive fungal sinusitis.Arch Otolaryngol Head Neck Surg. 1997; 123: 1181-1188Crossref PubMed Scopus (252) Google Scholar, 8Jones A.C. Bentsen T.Y. Freedman P.D. Mucormycosis of the oral cavity.Oral Surg Oral Med Oral Pathol. 1993; 75: 455-460Abstract Full Text PDF PubMed Scopus (62) Google Scholar Radiographically, sinus opacification is seen, with bone erosion and adjacent soft tissue infiltration of an ill-defined or mass-like soft tissue lesion, an appearance that can mimic that of a malignant process.9Aribandi M. McCoy V.A. Bazan 3rd, C. Imaging features of invasive and noninvasive fungal sinusitis: A review.Radiographics. 2007; 27: 1283-1296Crossref PubMed Scopus (260) Google Scholar Among sinonasal carcinomas, squamous cell carcinoma arising from the maxillary sinus is the most common. The next most frequent site of occurrence is the lateral wall of the nasal cavity. Clinically, early symptoms are often similar to sinusitis, with progression of the disease displaying nasal obstruction, epistaxis, oral ulceration, swelling, and/or paresthesia.10Harbo G. Grau C. Bundgaard T. et al.Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.Acta Oncol. 1997; 36: 45-50Crossref PubMed Scopus (137) Google Scholar, 11Weber A.L. Tumors of the paranasal sinuses.Otolaryngol Clin North Am. 1988; 21: 439-454Abstract Full Text PDF PubMed Google Scholar Other sinonasal carcinomas that could present similarly and should be included in the differential diagnosis are NUT midline carcinoma, sinonasal undifferentiated carcinoma, lymphoepithelial carcinoma, and sinonasal adenocarcinoma. NHL is the second most common craniofacial malignancy and includes a large group of hematopoietic cancers, most likely arising from B cells. Tumors with a T cell origin are less common.12Kemp S. Gallagher G. Kabani S. Noonan V. O’Hara C. Oral non-Hodgkin’s lymphoma: Review of the literature and World Health Organization classification with reference to 40 cases.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 105: 194-201Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Although less common, similar to granulomatosis with polyangiitis (GPA), extranodal natural killer (NK)/T cell lymphoma, nasal type, is known as a midline lethal granuloma due to its clinical presentation as an aggressive tumor that destroys the structures of the palate and nasal fossa. Swelling of the soft and/or hard palate is often seen, followed by the formation of a deep, necrotic ulceration.1Batsakis J.G. Luna M.A. Midfacial necrotizing lesions.Semin Diagn Pathol. 1987; 4: 90-116PubMed Google Scholar, 13Meng W. Zhou Y. Zhang H. et al.Nasal-type NK/T-cell lymphoma with palatal ulcer as the earliest clinical manifestation: A case report with literature review.Pathol Oncol Res. 2010; 16: 133-137Crossref PubMed Scopus (15) Google Scholar, 14Li S. Feng X. Li T. et al.Extranodal NK/T-cell lymphoma, nasal type: A report of 73 cases at MD Anderson Cancer Center.Am J Surg Pathol. 2013; 37: 14-23Crossref PubMed Scopus (155) Google Scholar, 15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar, 16Al-Hakeem D.A. Fedele S. Carlos R. Porter S. Extranodal NK/T-cell lymphoma, nasal type.Oral Oncol. 2007; 43: 4-14Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Systemic signs and symptoms such as fever, weight loss, visceral pain, anemia, and lymphadenopathy that are often present in NHL and not in the other entities considered in our differential diagnosis were not present in our current case.17Mawardi H. Cutler C. Treister N. Medical management update: Non-Hodgkin lymphoma.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009; 107: e19-e33Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Although any high-grade salivary gland neoplasm could be considered, the majority of salivary-type carcinomas of the sinonasal tract are adenoid cystic carcinomas (ACCs).18Tran L. Sidrys J. Horton D. Sadeghi A. Parker R.G. Malignant salivary gland tumors of the paranasal sinuses and nasal cavity. The UCLA experience.Am J Clin Oncol. 1989; 12: 387-392Crossref PubMed Scopus (43) Google Scholar These tumors arise from the seromucinous glands of the nasal cavity and paranasal sinuses and the overlying surface epithelium. Like ACC of the salivary glands, sinonasal ACC shows a more aggressive course when the histologic architecture is solid.19Goepfert H. Luna M.A. Lindberg R.D. White A.K. Malignant salivary gland tumors of the paranasal sinuses and nasal cavity.Arch Otolaryngol. 1983; 109: 662-668Crossref PubMed Scopus (99) Google Scholar These aggressive ACCs often present like our current case, as a fast-growing, destructive soft tissue mass. The incisional biopsy showed normal overlying squamous mucosa with an underlying submucosal infiltrate of atypical large cells with irregular nuclei and prominent nucleoli in a background of small lymphocytes. Immunohistochemistry was performed and showed the large atypical cells to be reactive with CD3, CD8, Granzyme B, and CD56 (weak). The cells were negative for CD4, CD5, CD30, TDT, CD34, CD20, CD10, CD1a, CD68, CD31, FLI1, pankeratin, and Melan-A. Acid-fast bacillus was negative, gram stain was negative for bacteria, and Grocott's methenamine silver stain was negative for fungi. Epstein-Barr encoding region in situ hybridization was positive in the large cells as well. Polymerase chain reaction analysis for clonal T cell receptor gamma gene rearrangement was performed and detected an oligoclonal T cell population. These findings led to the final diagnosis of an Epstein-Barr virus (EBV)-driven T cell lymphoproliferative neoplasm, favor extranodal NK/T cell lymphoma, nasal type (Figure 4). The patient was subsequently sent for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT imaging and bone marrow biopsy. The bone marrow biopsy showed no evidence of involvement on either routine morphologic assessment or flow cytometry immunophenotyping. The PET-CT (Figure 5) revealed marked FDG uptake in the left maxillary sinus involving the left alveolar ridge, middle turbinate, and tooth extraction site. A marked FDG uptake in the left adrenal gland and moderate uptake in the right adrenal gland were also noted. Spreading to the left and right adrenal glands was confirmed with a CT-guided core biopsy. The treatment recommended was the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen.20Kwong Y.L. Kim W.S. Lim S.T. et al.SMILE for natural killer/T-cell lymphoma: Analysis of safety and efficacy from the Asia Lymphoma Study Group.Blood. 2012; 120: 2973-2980Crossref PubMed Scopus (300) Google Scholar However, due to the increased risk of infection with this regimen, the patient elected to undergo treatment with L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen).21Jaccard A. Gachard N. Marin B. et al.Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study.Blood. 2011; 117: 1834-1839Crossref PubMed Scopus (299) Google Scholar The patient is currently scheduled to undergo 4-6 cycles of AspaMetDex regimen every 3 weeks. Extranodal NK/T-cell lymphoma, nasal type (ENKTCL), is a rare subtype of non-Hodgkin lymphoma characterized by its aggressive destruction of the palate and nasal fossa. ENKTCL has a strong association with EBV infection. ENKTCL most commonly occurs in adults, with a male predilection. It is seen more frequently in Asian and South American populations than North American or European populations.14Li S. Feng X. Li T. et al.Extranodal NK/T-cell lymphoma, nasal type: A report of 73 cases at MD Anderson Cancer Center.Am J Surg Pathol. 2013; 37: 14-23Crossref PubMed Scopus (155) Google Scholar, 16Al-Hakeem D.A. Fedele S. Carlos R. Porter S. Extranodal NK/T-cell lymphoma, nasal type.Oral Oncol. 2007; 43: 4-14Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Clinically, the initial presentation is often localized to the nasal region and includes nasal obstruction and/or epistaxis. Eventually, progressive ulceration and necrosis of the midfacial tissues ensues.15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar, 22Harabuchi Y. Imai S. Wakashima J. et al.Nasal T-cell lymphoma causally associated with Epstein-Barr virus: Clinicopathologic, phenotypic, and genotypic studies.Cancer. 1996; 77: 2137-2149Crossref PubMed Scopus (151) Google Scholar Systemic symptoms such as fever and weight loss are not uncommon. The majority of cases at the time of diagnosis are categorized as being in the early stages (Ann Arbor classification I or II). However, when widespread dissemination does occur, it is often to the bone marrow and gastrointestinal tract.15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar The present case was classified as stage IV with dissemination to the adrenal glands. The histopathologic findings of ENKTCL show diffuse infiltrates of a variety of inflammatory cells, often in an angiocentric pattern with widespread ischemic necrosis. Medium to large angular pleomorphic cells with an atypical appearance and frequent mitosis comprise the lymphoma cells that are seen as a component of the cellular infiltrate.15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar, 23Swerdlow S.H. Campo E. Pileri S.A. et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood. 2016; 127: 2375-2390Crossref PubMed Scopus (4468) Google Scholar Immunohistochemical evaluation shows the atypical cells marking with pan-T antigens such as CD2 and CD3, as well as the NK-cell marker CD56. In situ hybridization evidence of EBV in the lesional cells is required to make the diagnosis.15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar Without treatment, ENKTCL eventually leads to death due to secondary infection, massive hemorrhage, or infiltration of vital structures. Radiation therapy with 40-50 Gy followed by concurrent or sequential treatment with multidrug chemotherapy is recommended for localized lesions. Five-year survival rates are reported in the range of 70-80%. For cases with widespread dissemination, as in the present case, combination chemotherapy is the treatment of choice. In such cases, a 30-50% 5-year survival is expected.14Li S. Feng X. Li T. et al.Extranodal NK/T-cell lymphoma, nasal type: A report of 73 cases at MD Anderson Cancer Center.Am J Surg Pathol. 2013; 37: 14-23Crossref PubMed Scopus (155) Google Scholar, 15Harabuchi Y. Takahara M. Kishibe K. et al.Nasal natural killer (NK)/T-cell lymphoma: Clinical, histological, virological, and genetic features.Int J Clin Oncol. 2009; 14: 181-190Crossref PubMed Scopus (56) Google Scholar, 20Kwong Y.L. Kim W.S. Lim S.T. et al.SMILE for natural killer/T-cell lymphoma: Analysis of safety and efficacy from the Asia Lymphoma Study Group.Blood. 2012; 120: 2973-2980Crossref PubMed Scopus (300) Google Scholar, 21Jaccard A. Gachard N. Marin B. et al.Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study.Blood. 2011; 117: 1834-1839Crossref PubMed Scopus (299) Google Scholar, 24Kwong Y.L. The diagnosis and management of extranodal NK/T-cell lymphoma, nasal-type and aggressive NK-cell leukemia.J Clin Exp Hematop. 2011; 51: 21-28Crossref PubMed Scopus (63) Google Scholar, 25Yamaguchi M. Current and future management of NK/T-cell lymphoma based on clinical trials.Int J Hematol. 2012; 96: 562-571Crossref PubMed Scopus (33) Google Scholar

GKA (GPEH) appear histopathologically indistinguishable from reported cases of juvenile gingival squamous cell carcinoma (SCC) and their C15ORF48 and Krt9 gene expressions, as shown by multiplex qRT-PCR, are more similar to cutaneous SCC than PEH. Although this molecular method distinguishes GKA from PEH, the possibility of these tumors to have a profile similar to cutaneous KA cannot be excluded. Cutaneous KA differ significantly from SCC arising in actinic damaged skin as shown by microarrays. Also, there is known association of at least some cutaneous KA with HPV. Aim: 1) To compare GKA to cutaneous KA and SCC by using microarrays and 2) to investigate the presence of HPV by PCR.

ABSTRACT Zoonotic anatrichosomiasis in a mother and daughter is reported. Both presented with a 10-week history of multiple painful oral ulcers. Biopsy specimens revealed the presence of small, coiled trichuroid nematodes with distinctive morphological features, including stichocytes and paired bacillary bands. This represents an unusual infection by a zoonotic Anatrichosoma species.

Osteonecrosis of the jaw to a certain extent has been with us for many years. But recently the advent of various medications such as bisphosphonates, VEGF inhibitors, tyrosine kinase inhibitors and humanized antibodies to osteoclastic action have resulted in thousands of cases. While the bisphosphonates continue to be the most common medication associated with osteochemonecrosis antibodies such as denosumab which irreversibly act on osteoclastic action are also being reported. This narrative review will serve as an update with a focus on some of the histopathologic features discussed and reviewed. Perhaps even more uncommonly seen in past reports a discussion of features possibly observed while grossing specimens will be discussed. At the end of this report is hoped that the pathologist will have a better understanding of the historical features, clinical settings, gross examination features as well as histopathologic features associated with osteochemonecrosis.