Reticular Myxoid Odontogenic Neoplasm with Novel STRN::ALK Fusion: Report of 2 Cases in 3-Year-Old Males.

Odontogenic tumors represent a collection of entities ranging from hamartomas to destructive benign and malignant neoplasms. Occasionally, pathologists encounter gnathic lesions which clearly exhibit an odontogenic origin but do not fit within the confines of established diagnoses. Here, we describe two such odontogenic tumors, both affecting 3-year-old males. Each case presented as a destructive, radiolucent mandibular lesion composed of mesenchymal cells, some with unique multi-lobed nuclei, frequently arranged in a reticular pattern and supported by a myxoid stroma with focal laminations. Production of odontogenic hard tissues was also seen. Because of their unique microscopic features, both cases were investigated by next-generation sequencing and found to harbor the same STRN::ALK oncogene fusion. To our knowledge, these cases represent the first report of an odontogenic tumor with a STRN::ALK gene rearrangement. We propose the possibility that this neoplasm could be separate from other known odontogenic tumors. Both patients were treated with surgical resection and reconstruction. The prognosis of patients with this entity is currently uncertain but shall become more apparent over time as more cases are identified and followed.

Pediatric Odontogenic Tumors.

Odontogenic tumors are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. Some odontogenic tumors demonstrate strong predilection for pediatric patients including the unicystic ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma, ameloblastic fibro-odontoma, odontoma, and primordial odontogenic tumor. In this review, we discuss the clinical, radiographic, histopathologic, and molecular characteristics of select odontogenic tumors that demonstrate pediatric predilection and review management.

Acute Immune-Mediated Lesions of the Oral Cavity.

Although acute immune-mediated lesions of the oral cavity (AIML) can have an onset over several months, they often demonstrate rapid onset and can be self-limited. Despite the self-limiting nature of some disorders, patients with AIML can have significant pain and multisystem involvement. It is vital for the oral health care provider to arrive at the proper diagnosis with distinction from overlapping conditions, as the oral manifestations may be harbingers of more serious systemic complications.

Ectomesenchymal chondromyxoid tumor of the oral cavity: a report of 5 new cases with comprehensive review of the literature and clinicohistopathologic features.

OBJECTIVE: An ectomesenchymal chondromyxoid tumor (ECT) is an uncommon soft tissue tumor with an enigmatic histogenesis and striking predilection for the tongue. We present 5 new cases and review the literature. STUDY DESIGN: We performed a retrospective search for ECTs within the University of Kentucky Oral Pathology Biopsy Service and the published literature. RESULTS: Five new cases from the biopsy archives and 103 well-documented ECT cases from the literature were compiled and reviewed. Whereas 89.8% of ECT are found on the anterior/dorsal/lateral/unspecified tongue, 4.6% are on the posterior/base of tongue. Six extralingual cases are reported. The age ranges from 2.3 to 78 years with an average of 40. Most ECT react with GFAP (92.8%) and S-100 protein (91.3%). Whereas 21/23 cases demonstrated a RREB1-MKL2 fusion, EWSR1 gene mutations are identified in 4 cases. CONCLUSIONS: Most ECT are readily diagnosed on routine histopathology in combination with tumor site, immunohistochemical findings, and molecular findings; however, a subset share overlapping features with myoepithelioma of soft parts. As further molecular analysis is performed on this tumor, we may find that a subset of previously diagnosed ECT relate to or represent myoepithelioma or conversely fall under the spectrum of the pluripotent ECT.

Oral Manifestations of Syphilis: a Review of the Clinical and Histopathologic Characteristics of a Reemerging Entity with Report of 19 New Cases.

BACKGROUND: Syphilis is a sexually-transmitted infectious disease caused by Treponema pallidum. Cases of primary and secondary syphilis are on the rise in the United States, with a 14.4% increase in new cases noted from 2017 to 2018 and an escalation of 71% between the years 2014 and 2018. Fulfilling its nickname of "the great imitator," oral manifestations of syphilis may mimic a variety of infectious, neoplastic, or immune-mediated processes, both clinically and histopathologically. This large spectrum of appearances can create a diagnostic challenge to the clinician and/or pathologist, leading to delay in diagnosis or misdiagnosis. METHODS: A database of oral syphilis cases was created from archives at the University of Kentucky, University of Pittsburgh, LIJMC, Columbia University MC, and University of Tennessee. The age, sex, race, location, duration, and clinical description were recorded. Cases without positive reaction upon immunohistochemistry or serologic tests were excluded. RESULTS: We identified 19 new cases of oral syphilis (17 males, one female, and one case unknown sex) and described the clinical and histopathological features of this re-emerging and potentially fatal disease. All cases demonstrated dense lymphoplasmacytic inflammation, often with inflammatory exocytosis or ulceration at the surface, and perivascular inflammation. CONCLUSIONS: Early recognition of the histopathologic and clinical manifestations of oral syphilis is imperative for prompt diagnosis, improved patient outcomes, and disease prevention.

Glomus tumor: a comprehensive review of the clinical and histopathologic features with report of two intraoral cases.

BACKGROUND: Glomus tumors are benign neoplasms that most commonly present in the subungual region. Their occurrence in the oral cavity is exceedingly rare. Here, we present 2 cases from the oral cavity, detail their clinical and histopathologic features, and review the literature for solitary cases involving the oral regions. STUDY DESIGN: The English language literature was queried for cases of benign glomus tumors in/around the oral cavity. Additional citations were cross-referenced from the identified sources. RESULTS: Thirty-one cases of solitary glomus tumor in the oral and paraoral regions have been described, including the present cases. Patient age ranged from 10 to 85 years, with an average age of 47 years. In 12 of the 31 cases, the tumors occurred in the lips, 5 in the palate, 4 in the tongue, 4 in the buccal mucosa, 3 in the gingiva, and 1 each in the parotid, pterygoid fossa, and oropharynx. Only 18 of these cases had accompanying immunohistochemical stains, with 14 expressing positivity for muscle cell markers. CONCLUSIONS: Although glomus tumors have distinct histopathologic features, diagnostic confusion may exist with regard to extradigital locations. Detailed documentation and discussion of the clinical and histopathologic features of rare tumors like these are vital to understanding them.

Radiculomegaly: a case report of this rare dental finding with review of the associated oculo-facio-cardio-dental syndrome.

BACKGROUND: Radiculomegaly, or root gigantism, is a rare dental abnormality with important clinical implications. It is highly specific for oculo-facio-cardio-dental (OFCD) syndrome, which places dentists at the forefront of diagnosis of this syndrome. Only 1 case of nonsyndromic radiculomegaly has been reported in the literature since the description of OFCD syndrome in 1996. We present the second confirmed, nonsyndromic/nonfamilial case and review the literature for dental treatments in patients with this dental finding. STUDY DESIGN: A review of the English language literature was performed in PubMed for patients with radiculomegaly or OFCD syndrome. Teeth affected by radiculomegaly, gender, orodental findings, presence of OFCD syndrome, and dental treatment methods were recorded. RESULTS: Sixty-seven cases of radiculomegaly and 92 cases of OFCD syndrome were found in the literature. Only 1 confirmed case of nonsyndromic/nonfamilial radiculomegaly had been reported previously. Ten reports described dental treatment or treatment plan details, and even fewer included specific methods. CONCLUSIONS: Because dental anomalies, especially radiculomegaly, are a primary feature of OFCD syndrome, dentists should be aware of the clinical and radiographic features. Radiculomegaly poses a distinct challenge to dentists, and reports of dental therapy provided to these patients are sparse. Early diagnosis of the syndrome may prevent dental challenges and improve prognosis.

Segmental odontomaxillary dysplasia: An underrecognized entity.

BACKGROUND AND OVERVIEW: Segmental odontomaxillary dysplasia (SOD) is a characteristic developmental abnormality that demonstrates posterior maxillary enlargement, dental abnormalities, altered bone trabeculation, and possible cutaneous findings. Only 62 cases have been reported in the English-language literature. CASE DESCRIPTION: The authors described 3 newly diagnosed cases of SOD, all found in the left posterior maxilla in adolescent female patients; they reviewed the literature to elucidate this rare entity. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Because of the complexity and variety of associated dental and craniofacial features, patients with SOD may seek diagnosis from various dental and medical providers. The signs of SOD are characteristic, yet the condition is largely underrecognized among health care professionals, which may lead to unnecessary treatment.

Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

Merkel cell carcinoma (MCC) is an uncommon relatively aggressive neuroendocrine dermal neoplasm first described in 1972 as a tumor of the sun exposed skin. Although most MCC affect the skin of the head and neck, rare primarily oral mucosal cases have been documented. Merkel cells are nondendritic neuroendocrine cells that are found not only in the skin but also the oral mucosa and give rise to MCC. Neuroendocrine cells may be found as aggregates in organs or as diffuse or isolated cells within organs and their epithelial lining. They contain peptide hormones and biogenic amines and occur in two forms: dendritic, which are not associated with nerve fibers and non-dendritic, which are associated with nerve fibers. Merkel cells as well as MCC express simple epithelium-type Cytokeratins (8, 18, 19, 20), neurosecretory substances; chromogranin A, synaptophysin, neuron-specific enolase (NSE), adhesion molecules, and villin (intermediate filament). Though weakly, they also express neural markers such as S-100 protein. Cytokeratin 20, and Cluster of differentiation 56, are the two key diagnostic markers for Merkel cells and MCC. Etiology includes UV radiation, the recently described Merkel cell polyomavirus, and long term systemic immunosuppression. The cutaneous and mucosal variants of MCC are considered aggressive tumors with a high risk for local recurrence and metastasis and should be considered in the differential diagnosis of head and neck mucosal lesions. We present two cases of primary Merkel cell carcinoma, one on the buccal mucosa and the other on the lower lip, and discuss the salient histologic, immunohistochemical and clinical features.

STAT6 Reliably Distinguishes Solitary Fibrous Tumors from Myofibromas.

Solitary fibrous tumors (SFT) and myofibromas (MF) historically have belonged to the same morphologic spectrum and have been lumped together under the nonspecific umbrella term, "hemangiopericytoma" along with other pericytic/myoid tumors. While current evidence shows clear distinction between the two entities, they frequently remain in the same histopathologic differential diagnosis. This diagnostic dilemma especially is common for smaller incisional biopsies from the oral cavity. STAT6 immunohistochemistry (IHC) recently was established as a reliable method to detect solitary fibrous tumor; however, the literature is sparse regarding STAT6 reactivity in MFs. The authors report ten new cases of oral solitary fibrous tumor, discuss histopathologic similarities and differences between the two tumors, and list respective STAT6 IHC expressivity. After IRB approval, 10 cases diagnosed as SFT and 24 cases of MF were collected from the University of Florida Oral and Maxillofacial Pathology Biopsy Service between the years 1994 and 2016. The original hematoxylin and eosin slides and related IHC were reviewed. IHC with STAT6 antibody was performed on all 34 samples, and the findings were analyzed. All cases were from the oral cavity or perioral regions. 10/10 SFTs expressed STAT6 nuclear reactivity, while no cases of MF showed nuclear expression of STAT6. STAT6 is a dependable marker to differentiate SFTs from MFs.

Rhabdomyosarcoma, Spindle Cell/Sclerosing Variant: A Clinical and Histopathological Examination of this Rare Variant with Three New Cases from the Oral Cavity.

Spindle cell/sclerosing rhabdomyosarcoma (S-ScRMS) was recently recognized in 2013 by the World Health Organization (WHO) as a stand-alone entity (Parham et al., WHO classification of tumours of soft tissue and bone, IARC Press, Lyon, 2013). Historically, the spindle cell and sclerosing variants were subcategorized under embryonal type rhabdomyosarcoma. Current data supports that certain S-ScRMS cases have a more aggressive clinical course with reduction of long-term survival, and those found in the head and neck region often exhibit extensive local recurrence. Furthermore, due to variable histopathologic appearances and immunohistochemical findings, misdiagnosis is common. We aim to report the variability in histopathologic patterns, immunohistochemical findings, radiographic features, and clinical data on three new cases of S-ScRMS presenting in the oral cavity of young adult males (ages 22, 24, and 39 years). The English-language literature on S-ScRMS is briefly reviewed as well.

An update on myofibromas and myofibromatosis affecting the oral regions with report of 24 new cases.

OBJECTIVES: Myofibromas are uncommon soft tissue tumors exhibiting considerable histopathologic overlap with other benign and malignant entities. The treatment of lesions arising in the oral cavity is controversial. Here, we present 24 new cases and review the literature. STUDY DESIGN: A search for oral myofibromas was performed within the archives of the University of Florida Oral Pathology and Surgical Pathology Services (1994-2015). Demographic information and immunohistochemical results were recorded. MEDLINE and Web of Science were searched for reports of myofibroma of the oral cavity and oropharynx published in the English-language literature between January 1990 and July 2016, and the results were analyzed. RESULTS: In total, 245 cases were identified: 24 from our present series and 221 from the literature. The distribution by gender was 54.6% male and 45.4% female, and the mean age was 23.1 years. Only 7 patients had known multiple lesions. Treatment modalities varied greatly. Of those with follow-up information, only 9 were cases with recurrences. CONCLUSIONS: Myofibromas may resemble several other entities. Because of the potential for multiple (perhaps visceral) lesions and the possibility of overtreatment, accurate diagnosis is of utmost importance. Reports of cases with minimally invasive treatment are sparse, and no standardized treatment protocol has been established. This information should be a priority for future publications.

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics.

Melanoma of the oral cavity is a rare malignancy that carries a poor prognosis. We identified 46 new cases of both primary and metastatic melanoma to the oral cavity. Following IRB approval, these cases were obtained from the Oral Pathology Biopsy Service archives of the UF College of Dentistry (1994-2014), the UK College of Dentistry (1997-2015), and the UM Medical Center (1988-2015). All slides were reviewed. The location, age, race, gender, clinical impression, duration of lesion, histopathologic diagnosis, and histopathologic features were recorded. Cases from the facial skin and those with an ambiguous diagnosis were excluded. Forty-six cases fulfilled the inclusion criteria with 32 primary cases, 11 known metastases, and 3 cases where metastasis could not be excluded. The primary cases included a total of 20 females and 12 males with an average age of 66.7 (range 27-95), and the majority (80 %) of the patients were Caucasian when race was known. Twenty-two of the 32 primary cases (68.8 %) were located in the maxillary mucosa, 5 in the mandibular mucosa or bone, and 5 in other locations. The clinicians' impressions varied from benign fibrous growths to high grade malignancies. The histopathology varied widely among the cases, however two cell types predominated (often in combination): epithelioid cells (50.0 %) and spindle cells (50.0 %). Only 53.1 % demonstrated melanin pigmentation. Oral melanoma remains one of the most diverse clinical and histopathologic diagnoses. Better understanding of this neoplasm may promote earlier diagnosis and may lead to improved outcomes.