Faculty Bibliography

Importance/UNASSIGNED:Ulceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of β-blocker therapy for IH. Objectives/UNASSIGNED:To examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. Design, Setting, and Participants/UNASSIGNED:A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. Exposures/UNASSIGNED:Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (β-blocker, corticosteroids), and procedural (pulsed-dye laser). Main Outcomes and Measures/UNASSIGNED:The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. Results/UNASSIGNED:Of the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic β-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration. Conclusions and Relevance/UNASSIGNED:Despite the use of β-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (≤1 mg/kg/d) should be considered.

BACKGROUND/OBJECTIVES/OBJECTIVE:Congenital juvenile xanthogranulomas are infrequently described in the medical literature. We report three previously unpublished cases and systematically review the literature to better characterize this variant. METHODS:We surveyed English-language articles indexed in MEDLINE (1951-March 2017) and EMBASE (1974-March 2017) for cases of congenital-onset juvenile xanthogranulomas confirmed on histopathology. Cases were divided into two categories: cutaneous only or cutaneous with systemic involvement. RESULTS:We identified 31 cases of congenital juvenile xanthogranulomas involving only the skin and 16 cases with systemic involvement. Congenital juvenile xanthogranulomas involving only the skin were large (> 3 cm), presented with various clinical morphologies, and showed signs of regression by 1 year of age. Atypical clinical presentations included exophytic tumors, infiltrative plaques, agminated plaques, and subcutaneous tumors. Complications included ulceration and anetodermic scarring. Infants with congenital cutaneous juvenile xanthogranulomas who also had systemic involvement typically had multiple cutaneous tumors and hepatic involvement and showed signs of spontaneous regression independent of treatment. CONCLUSIONS:The medical literature supports that congenital juvenile xanthogranulomas behave in a fashion similar to that of juvenile xanthogranulomas of infancy or childhood. Congenital cutaneous juvenile xanthogranulomas with or without systemic involvement spontaneously regress. The varied clinical presentations in the skin may lead to misdiagnosis, inappropriate examination, and unnecessary treatments. Infants with multiple congenital cutaneous juvenile xanthogranulomas should be evaluated for systemic involvement, with a particular focus on the liver, because 72.2% of these children were found to have hepatic juvenile xanthogranulomas.

Introduction/UNASSIGNED:Salivary gland tumors are relatively common in the junction of the hard and soft palate area of the oral cavity. Pleomorphic adenoma is considered the most common benign salivary gland tumor in this location. Some of the rarer subtypes of this tumor may have a misleading clinical presentation. Recognition of these variants is important since long-standing pleomorphic adenomas have the potential to become malignant. Case Presentation/UNASSIGNED:A healthy 24-year-old male was referred for a painless, large, slowly growing, exophytic swelling of the right hard and soft palate. Interestingly, the lesion was yellowish in color and soft to palpation, suggestive of an innocuous lipoma or cystic lesion. An incisional biopsy was performed and the diagnosis was consistent with pleomorphic adenoma with a significant adipose tissue component. The patient was referred to an oral surgeon and underwent a complete surgical excision. Upon two-year follow-up, the patient is doing well with no recurrences. Conclusion/UNASSIGNED:This case highlights a rare microscopic variant of pleomorphic adenoma with altered clinical presentation that led to an erroneous clinical diagnosis. The importance of taking a biopsy for definitive diagnosis and appropriate management is reinforced.

INTRODUCTION/BACKGROUND:Malignant melanoma is an aggressive form of cancer that commonly affects skin and rarely affects the oral cavity. With poorly understood risk factors and an often-asymptomatic presentation, oral melanoma is difficult to detect until advanced stages of disease. Treatment for oral melanomas has been primarily surgical, and survival rates have been low. However, in recent years, immunotherapy has shown much promise with increased patient survival. CASE PRESENTATION/METHODS:A 49-year-old male was referred by his primary dentist to a periodontal clinic for management of an alleged unresolved periodontal abscess. The patient had completed full-mouth scaling and root planing and consequently developed a large mass in the left posterior maxilla. Incisional biopsies were performed in multiple locations in the maxillary gingivae, and interpretation revealed atypical melanocytic proliferation and primary melanoma. After appropriate work-up, the patient was treated with two different immunotherapy agents: 1) ipilimumab and 2) pembrolizumab. Results after immunotherapy were favorable, and the tumor significantly decreased in size with no major adverse effects. The response was so strikingly positive that the need for surgical removal was almost eliminated. At the present time, it is unknown whether the patient will receive any surgical treatment barring a recurrence. CONCLUSIONS:Oral mucosal pigmentation is a finding commonly encountered by dentists during clinical patient examinations. However, proper diagnosis of pigmented lesions, especially those associated with malignancy, requires investigations that go beyond clinical examination.

AIMS: Ectomesenchymal chondromyxoid tumor (ECT) is a rare, benign intraoral neoplasm showing predilection for the anterior dorsum of the tongue. The World Health Organization (W.H.O.) includes ECT in the pathologic spectrum of soft tissue myoepithelioma. EWSR1 rearrangement is identified in 45% of cutaneous, soft tissue and bone myoepithelial neoplasms, while PLAG1 aberrations are found in 37% of EWSR1-negative soft tissue myoepitheliomas. The aim of this study was to evaluate the presence of EWSR1 and PLAG1 rearrangements in ECTs. METHODS AND RESULTS: Eleven formalin-fixed, paraffin-embedded ECTs were evaluated using FISH probes to EWSR1 (22q12) and PLAG1 (8q12). Among the 11 ECT cases tested, 3 (27.3%) showed EWSR1 rearrangement in >15% of tumor cells, while 8 (72.7%) cases did not show EWSR1 rearrangement. Eight of 9 (89%) ECTs demonstrated gain of EWSR1, likely representing gain of all or part of chromosome 22, in a varying proportion of neoplastic cells ranging between 1.4-27.9%. PLAG1 rearrangement was not detected in the successfully hybridized tissue sections (7/11). No correlation was observed between the molecular and histopathologic findings such as morphology of the neoplastic cells, presence of atypia, and matrical type. CONCLUSIONS: We identified EWSR1 rearrangement in > 25% of ECTs. These results suggest that some ECTs are at least genetically related to myoepithelioma of the soft parts. Finally, PLAG1 aberrations do not appear to be critical in the pathogenesis of ECT of the tongue