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Table 1 Differential Diagnosis of TUGSE

From: Traumatic ulcerative granuloma with stromal eosinophilia — clinical case report, literature review, and differential diagnosis

ParameterTraumatic ulcerative granuloma with stromal eosinophilia (TUGSE)Squamous cell carcinoma (SCC)CD30 positive lymphoprolipherative disorder (LPD)Lues (syn. Syphilis)Epstein-Barr virus (EBV) mucocutaneous ulcerAphthous stomatitis
Location in the oral cavityTongue, buccal and vestibular mucosa, palatal mucosa, retromolar area, gingiva, floor of the mouthBottom of the oral cavity, lateral side and tip of the tongue, lower lip, retromolar areaRarely in the oral cavity, often recurring lesionsLips, tongue, pharynxOropharyngeal mucosaNon-keratinizing epithelial surfaces in the mouth (labial and buccal mucosa, soft palate, lower side of the tongue); in patients with Severe aphthous stomatitis, the keratinized mucosa can also be affected
EtiopathogenesisUnknown, causal connection with repeated traumaCausal connection with chronic tobacco and alcohol consumption and poor oral hygieneTypically in patients with an impaired immune systemMost commonly spread through unprotected (oral) sexual intercourse or congenital infectionAssociated with immunosuppressionStress, trauma, hormonal fluctuations, allergic reaction (certain foods, drinks, toothpastes and mouth rinses)
Peak ageTwo peaks of life incidence: one during the first two years of life and another between the 5th and 7th decadeMost commonly after the 5th decade of life (men more frequently affected than women)Elderly (> 75 years)Most commonly between the 3rd and the 4th decade of life (men more frequently affected than women)Primarily elderly (> 75 y), any ageAny age but the frequency increases later in life
Clinical featuresUlcer with elevated and indurated margins and yellowish fibrinous baseEndophytic growth, nodose and shallow ulcer with elevated margins, often covered by a non-strippable reddish, whitish or mixed focus growing infiltrative and destructiveNodules or ulceration, indolent clinical behavior, primary cutaneous manifestation possibleStage I (primary syphilis): after an incubation period of 2–3 weeks, the papule at the portal of entry converts into a indolent and superficial ulcers with indurated margins (also called primary chancre) multifocal, aphthous enanthemaSharply circumscribed indolent ulcerationNonspecific shallow round or oval painful ulcer, covered by a grayish-white fibrin pseudomembrane with a sharply defined erythematous border
HistopathologyGranulomatous tissue with a dense, diffuse, polymorphic, inflammatory infiltrate predominately of eosinophils and histiocytes, often extending into the submucosa, deeper muscle fibers and salivary glandsEpithelial differentiated structures with cornification (hyperkeratosis, parakeratosis, horn beads and multiple dyskeratotic keratinocytes) and peritumoral inflammatory reaction composed of a mixed cellular infiltrate, which is rich in plasma cellsInfiltrate of atypical lymphoid cells admixed with eosinophils involving the oral epithelium and the deep soft tissuesSignificant plasmacytosis, plasmacell phlebitis, vague granulomas, detectable spirochetes (Warthin-Starry, immunohistochemistry)Polymorphous infiltrate with inflammatory cells and atypical large B-cells blasts often with Hodgkin/Reed-Sternberg (HRS) cell-like morphology, sharply demarcated towards deeper structures (assessible only on excisional biopsies)Nonspecific ulcer, inflammatory cells, predominately T-cells, with high local levels of TNF-α
ImmunohistochemistryMixture of phenotypically regular T-lymphocytes, occasionally CD30+CK5/6+, CK19+, p63+, p40+MUM1p+, MYC+, CD30+ T-cells with antigenic loss of T-cell markersDetection of Treponema pallidum by the following tests: TPPA test (Treponema pallidum particle agglutination assay test), FTA-ABS test (fluorescent treponemal antibody absorption test)EBER+ (EBV encoded small nuclear RNA), CD30+Nonspecific