Focal Benign Disorders of the Pediatric Mandible With Radiologic-Histopathologic Correlation: Mandibular Development and Lucent Lesions.

OBJECTIVE: Lucent lesions of the pediatric mandible may present variably. Cysts, neoplasms, and developmental and inflammatory conditions have a host of possible causes. There is also substantial overlap in the imaging appearance of cysts and that of benign but locally aggressive tumors that need to undergo resection. CONCLUSION: The purpose of this article is to present common and uncommon lucent lesions of the mandible in children, with an emphasis on benign abnormalities. Discussions of imaging and histopathologic features are provided.

PRAME immunohistochemistry is useful in the diagnosis of oral malignant melanoma.

OBJECTIVES: While the incidence of cutaneous melanoma has dramatically increased in recent years, oral malignant melanoma (OMM) remains a rare form of noncutaneous melanoma with poor survival. PRAME (PReferentially expressed Antigen in MElanoma) is reported to have diagnostic and some prognostic utility in cutaneous melanomas and some head and neck malignancies. We sought to explore the diagnostic utility of PRAME in OMM. METHODS: A total of ten specimens from eight unique cases of OMM were identified from the Oral Pathology Biopsy Service (OPBS) at University of Washington School of Dentistry between 2005 and 2019. For all cases, standard histology and immunohistochemistry stains were performed, including a stain against PRAME. The diagnoses were reviewed and confirmed by two pathologists. Clinical and epidemiologic features were described. RESULTS: Patient ages ranged from 55 to 82. The group consisted of five males and three females. All eight cases were located on the hard palate. Six cases represented invasive melanoma while two were early melanoma in situ. PRAME immunohistochemistry was successfully performed on seven of eight cases: six were positive (86%), one was negative (14%) and one case lacked sufficient tissue for staining. CONCLUSIONS: Our results suggest that PRAME immunohistochemistry may be useful in the diagnosis of OMM, including early melanoma in situ. Further studies with clinical follow-up and a larger number of cases are needed to explore prognostic value as well as the ability to distinguish between benign, intermediate and malignant melanocytic proliferations of the oral cavity.

Osteoblastoma and Osteoid Osteoma of the Mandible: Review of the Literature and Report of Two Cases.

Osteoblastoma and osteoid osteoma are rare benign neoplasms of the jaws. We reviewed current literature surrounding the ongoing debate over similarities and differences of osteoblastoma and osteoid osteoma and present two cases. Both cases are well-demarcated mixed radiodensity mandibular lesions with histological features of osteoblastoma. They exhibit, however, distinctly unique and contrasting clinical and imaging characteristics suggesting that the first case is osteoblastoma and the second is osteoid osteoma. The first case of a 37-year-old male presents with a large, expansile lesion at posterior mandible, surrounded by a thick sclerotic band. Unusual features include significant buccal/lingual expansion, extensive new bone apposition, and soft tissue edema in the masseter muscle. This is in contrast to the second case of a much smaller lesion in a 17-year-old male with history of recent third molar extraction in the left posterior mandible. In this case, CT imaging revealed a circular, nonexpansile lesion with a sclerotic border surrounded by a radiolucent rim. Both patients underwent surgical excision of the lesion with extraction of the adjacent tooth. We discuss herein the distinct clinical and imaging features.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

Adenomatoid odontogenic tumor: Case series of 14 with wide range of clinical presentation.

BACKGROUND: To present 14 cases of adenomatoid odontogenic tumor (AOT), highlighting their clinical, radiographic, and histologic characteristics. MATERIAL AND METHODS: Fourteen cases of AOT were retrieved from the archives of the Oral Pathology Biopsy Service (OPBS). Clinical, radiologic, and histologic findings are described. RESULTS: Fourteen AOT cases were reviewed, of which 12 were intraosseous and two were peripheral (gingiva). The cases came from eight females and six males with an age range of 11-30. Of the 12 intraosseous cases, nine were follicular (associated with impacted teeth), while three were extra-follicular (present between teeth). Six of the 12 cases were in the maxilla, and the other six were in the mandible. The two peripheral cases presented as nodules on the buccal gingiva of the anterior maxillary teeth. Radiographically, all 12 follicular and extra-follicular cases were unilocular radiolucencies; of those, only one had specks of radiopacity. Histologically, all specimens were similar in morphology, demonstrating a varied degree of duct-like structures, epithelial spheres, spindle-shaped epithelial cells, calcifications, and a thick capsule. The two peripheral cases had no capsule. CONCLUSIONS: AOT usually affects patients under 20 years of age, with a female to male ratio close to 2:1. Presentation in the anterior maxilla is almost twice as common as in the anterior mandible. Radiographically, AOT presents as a unilocular radiolucency more commonly associated with impacted teeth, simulating a dentigerous cyst. We present 14 new cases of AOT (nine follicular, three extra-follicular, and two peripheral) with discussions of their clinical, radiographic, and histological features. Key words:Adenomatoid, odontogenic, tumor.

Glandular odontogenic cyst associated with ameloblastoma: Case report and review of the literature.

Glandular odontogenic cyst (GOC) associated with ameloblastoma is an exceedingly rare histologic presentation with no known clinical significance or treatment applications. Four cases have been reported, three in the mandible and one in the maxilla. The age range is 14-65 and with male predilection. All four presented with swellings and two with pain. We add one more case to the literature of a 58-year old male presenting with an expansile multilocular radiolucency between teeth #19-23. The ameloblastomatous changes in this case are consistent with those of a unicystic ameloblastoma-mural subtype. Although the histologic changes are those of a unicystic ameloblastoma, the clinical and radiographic findings are not. This case therefore presents a clinical challenge with regards to treatment planning for recurrence and prognosis. We conclude that treatment for GOC therefore be based on individual clinical presentation. Key words:Glandular odontogenic cyst, GOC, ameloblastoma, unicystic ameloblastoma, mural unicystic ameloblastoma.

A case series of intraosseous hemangioma of the jaws: Various presentations of a rare entity.

BACKGROUND: Hemangiomas of the soft tissue are common in the head and neck area, especially in the tongue and in children under ten years of age. Intraosseous hemangiomas of the mandible and maxilla (IHM), on the other hand, are exceedingly rare and are not well characterized. This study presents six IHM cases focusing on the clinical, radiographic, and histologic characteristics. MATERIAL AND METHODS: Six cases of IHM were retrieved from the archives of the Biopsy Services at the University of Washington. Clinical, radiologic, and histologic findings are described. RESULTS: A total of six cases of IHM were reviewed. The patient age range was 16 to 65; the group comprised three females and three males. All six cases presented as swellings, two caused tooth resorption, and one was associated with pain and numbness. Three of the six IHM were present in the body of the mandible, two in the area of the extracted right mandibular third molar, and one in the anterior maxilla between the right canine and lateral incisor. Radiographically, five were radiolucent and one was radiopaque. Of the five radiolucent, two were unilocular and three multilocular. The one radiopaque case was exophytic, simulating a large osteoma. Histologic features ranged from cavernous to a mix of venous and arterial types. Follow-up is available for all six cases ranging between one to seven years; only one case recurred within the first year post-surgery. CONCLUSIONS: IHM are exceedingly rare; IHM do not present in a consistent manner both clinically and radiographically. It is therefore important to recognize the wide spectrum of IHM's clinical, radiographic, and histological presentations. Key words:Hemangioma, Vascular Malformation, mandible, maxilla.

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases.

Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington. Radiologic findings and clinical history, as well as pathologic findings from hematoxylin and eosin slides and immunohistochemistry for myogenic markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal, three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged from 18 to 57 years (median 21 years). Classic and unique histologic features for each subtype, including post-treatment morphologic changes, were identified. Clinical follow-up information was available for 4 patients. 3 of 4 patients experienced recurrence, including two with distant metastasis. One patient died of disease progression 41 months after presentation. Head and neck rhabdomyosarcoma in adults can manifest both classic and unique histologic features for each subtype. In addition, recurrence and distant metastasis were observed, suggesting aggressive clinical behavior regardless of subtype.

Oral manifestations as the first presenting sign of Crohn's disease in a pediatric patient.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal (GI) tract. Although the GI tract is the primary site of involvement, many patients, particularly in pediatric cases, first present with non-intestinal manifestations, including oral lesions. Oral manifestations of CD in children occur in around 50-80% of cases, and about 30% of CD cases in children occur first in the mouth. Recognizing such oral lesions in the pediatric population, and requesting a biopsy, may expedite the diagnosis of CD. We describe a 15 year old male who presented with oral findings of multiple aphthous ulcers and plaques of pink papules of the buccal vestibule. We highlight the initial pathology findings, including non-caseating granulomas, sialadenitis, and a notable plasmacytosis, from biopsy of the left retromolar pad area, which triggered further testing for CD. We provide discussion of how CD was eventually diagnosed and treated and highlight the significance of the pathological findings in this case as they relate to the pathogenesis of CD. Key words:Crohn's disease, Inflammatory bowel disease, Oral manifestations, Pediatric, Granulomatous inflammation, Monotypic plasma cells.

Diagnosis and Clinical Management of Human Papilloma Virus-Related Gingival Squamous Cell Carcinoma in a Patient With Leukemia: A Case Report.

INTRODUCTION: Close clinical inspection for intraoral lesions in patients with leukemia that develop chronic graft-versus-host disease (cGVHD) is critical. Additionally, neoplasias developing in bone marrow transplant patients after treatment for leukemia represent a significant obstacle for long-term patient survival, necessitating lifetime follow-up by health care providers. This case report describes the identification, diagnosis, and treatment of gingival squamous cell carcinoma (SCC) in a patient with leukemia who was treated previously with a stem cell transplant and referred for routine periodontal care. CASE PRESENTATION: A 53-year-old male was referred to the Department of Periodontics for an assessment of tooth #10 with 2+ mobility and associated cross-bite occlusion. The patient was diagnosed with acute myeloid leukemia at age 39 years, received hematopoietic stem cell transplantation (HSCT), and later developed cGVHD followed by human papilloma virus (HPV) infections. During the periodontal evaluation, a large, non-painful, exophytic, alveolar gingival mass was identified and later diagnosed as SCC. It is unusual that oral SCC presents as an exophytic, gingival swelling. The patient received comprehensive periodontal management in coordination with his otolaryngology team before and during the diagnosis of SCC secondary to cGVHD and HPV infection. CONCLUSIONS: Patients with a history of HSCT treatment for leukemia and subsequent cGVHD are at a high risk of developing second primary oral malignancies, including SCC. Exposure to oncogenic HPV infection may compound this risk. Therefore, it is important for dentists to be aware of special treatment concerns and to frequently screen these patients to achieve early diagnosis and treatment of these neoplasms.

Soft-tissue lesions in children.

This article reviews some of the benign and malignant oral soft-tissue swellings that occur in children, with an emphasis on their clinical presentation, etiology, histopathology, and treatment. These lesions include single and multiple nodules, reactive lesions, and benign and malignant neoplasms. Diseases discussed include reactive gingival swelling, generalized gingival fibromatosis, melanotic neuroectodermal tumor of infancy, fibromas, vascular lesions, salivary gland lesions, and infantile rhabdomyomas. Also covered are lesions that may present in multiples, such as neuromas, multiple endocrine neoplasia type 2b, neurofibromatosis, and human papilloma virus-related benign epithelial lesions. Benign but locally aggressive and malignant neoplasms are discussed, such as aggressive fibromatosis, myofibromatosis, fibrosarcoma, and rhabdomyosarcoma.

Artemisinin: an alternative treatment for oral squamous cell carcinoma.

Artemisinin (AR) is a widely used antimalarial drug. Recently, additional uses for AR as an anticancer drug were discovered. Using TUNEL, immunohistochemistry (IHS) markers and flow cytometry techniques, we evaluated the effect of AR and 5-FU on HPV 16 immortalized and transformed human gingival epithelial (IHGK) cells. The results of TUNEL showed that AR-treated IHGK cells consisted of 82% positive cells, while 5-FU-treated cells consisted of 18% positive cells. The IHS markers demonstrated positive staining with Bax p53, CD40 and CD40L in AR-treated cells and negative staining with Bcl-2. 5-FU-treated cells demonstrated a profile similar to AR but with less intensity. Cell cycle by flow cytometry results showed that only 5-FU-treated cells demonstrated a significant S-phase rate increase to 45%. In conclusion, our results indicate that AR is cytotoxic to transformed oral epithelial cells through apoptosis, while 5-FU is cytotoxic primarily through cell toxicity.

Primary lesion of multiple myeloma presenting as gingival swelling.

It is rare that multiple myeloma (MM) occurs as a primary lesion in the jaws; we report such a case in an elderly patient involving the gingiva of the left posterior mandible. Multiple myeloma is a monoclonal malignant neoplasm of plasma cell origin which occurs in the bone marrow and may result in extensive destruction of skeletal structures. If the jaws are involved, it usually indicates an advanced stage of the disease.Thi s makes our case very unique due to the fact no other osteolytic lesions were identified at the time of the diagnosis of multiple myeloma. We report a rare case of multiple myeloma which was diagnosed from an intraoral gingival lesion on the lower left mandible.

Detection of Cytochrome P450 mRNA in Tissue Sections and Cell Lines Using Enzyme-Labeled Fluorescence In Situ Hybridization.

Cytochrome P450s (P450s) constitute a superfamily of enzymes that metabolize a broad array of xenobiotics. The ability to measure basal and induced levels of P450 mRNA in specific cells and tissues should provide valuable insight regarding the functional role and heterogeneous expression of these enzymes in chemically related diseases. Methodologies for detecting cell-specific mRNA expression patterns typically rely on radiolabeled probes and photographic emulsions, often coupled with long exposure times. These studies were conducted to evaluate an enzyme-labeled fluorescence (ELF) in situ hybridization technique to detect specific P450 mRNA. Deparaffinized, formalin-fixed tissue sections and cells from culture were incubated for 12 hours with 5'-biotinylated 20-base DNA oligomer probes (20-mer). Specific hybridization was detected using a streptavidin alkaline-phosphatase conjugate followed by incubation with the ELF substrate, yielding a bright, yellow-green fluorescent signal. In this study, utility of the technique was demonstrated using cultured rat hepatorna cells, and tissue sections from rat liver and human oral epithelium. Ribonuclease A pretreatment of the sample, omission of the probe, competition with a nonbiotinylated oligomer, and the use of only partially homologous probes served as negative controls to demonstrate the specificity of the hybridization signal. Our results clearly demonstrated the ability of ELF in situ hybridization to discriminately detect cell-specific P450 mRNA in tissue sections and cultured cells. This technique eliminates the use of radioactivity and enables in situ detection of mRNAs with relative ease, efficiency, specificity, and high sensitivity.