Canalicular adenoma with unicystic morphology. A rare entity.

BACKGROUND: Canalicular adenoma (CA) is a benign salivary gland tumor (SGT) almost exclusively affecting the minor salivary glands, predominantly of the upper lip, and exhibiting characteristic histopathologic features. As observed in several other SGTs, a commonly encountered finding is the presence of prominent cystic morphology. Even though a multicystic appearance is usually noticed, solitary cystic CAs may rarely occur. CASE REPORT: Two female patients (74 and 78 years old respectively) presented for the evaluation of submucosal asymptomatic masses of the oral cavity. In the 1st case a solitary nodule was noticed in the upper lip, while the 2nd patient exhibited two symmetrical lesions of the buccal mucosae. All three excised specimens displayed cystic morphology upon gross examination. Histopathologically, a solitary cystic formation lined by monomorphic cuboidal or basaloid cells arranged in solid or trabecular patterns was observed in the 1st case. With a differential diagnosis of CA vs basal cell adenoma immunohistochemical examination was performed. Positivity for S-100, CK7 and CD117 (c-kit) and negative reaction for GFAP, p63 and SMA rendered the diagnosis of CA. In the 2nd case both lesions displayed well-circumscribed proliferations by monotonous cuboidal or columnar cells arranged in single cords and occasionally forming beading patterns, while central solitary areas of marked cystic degeneration were noticed. Diagnosis of multifocal unicystic CA was disclosed. DISCUSSION: To our knowledge, only 11 additional cases of unicystic CA have been reported in the English-language literature. Although the exact clinical significance of unicystic morphology in CA is unknown, a tendency for occurrence within the context of multifocal tumors has been detected. Key words:Canalicular adenoma, monomorphic adenoma, unicystic morphology, multifocal tumors, minor salivary glands.

Localized juvenile spongiotic gingival hyperplasia: Microscopic variations and proposed change to nomenclature.

OBJECTIVES: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a recently described entity with distinct manifestations. Herein we report a comprehensive histopathologic study of 21 lesions and a literature review. Additionally, we propose a new term that we consider more appropriate. STUDY DESIGN: LJSGH cases were retrieved and their clinicopathologic characteristics were assessed. A review of all pertinent literature was also conducted. RESULTS: Eighteen patients with LJSGH (21 biopsied lesions) were identified. Microscopically, surface morphology was classified into exophytic/papillary, flat, and micropapillary (8, 7, and 6 lesions, respectively). Cases with parakeratinization (n = 9), no prominent spongiosis (n = 5), or epithelial atrophy (n = 4) were recorded. Increased vascularity, mixed inflammation with exocytosis, and cytokeratin-19 positivity were uniformly observed. Less frequent findings included pseudoepitheliomatous hyperplasia (n = 8), bacterial colonies (n = 5), acantholysis (n = 3), and dystrophic calcifications (n = 2). The literature review disclosed 201 patients with a mean age of 14.8 years (range, 3-72; 13.6% affecting adults), similar sex distribution (103:98, female:male), and predominance of the anterior maxilla (≈ 80%). Eighteen cases were multifocal (≈ 10%). CONCLUSIONS: Our data suggest that the terminology could be modified, because LJSGH may be multifocal, affect older individuals, or exhibit epithelial atrophy, and the entity's odontogenic origin (as highlighted by the histopathologic and immunohistochemical findings) needs to be emphasized.

Assessment of TLR4 and TLR9 signaling and correlation with human papillomavirus status and histopathologic parameters in oral tongue squamous cell carcinoma.

OBJECTIVES: Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status. STUDY DESIGN: OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-ß (IFN-ß) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined. RESULTS: TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-ß were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels. CONCLUSIONS: TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-ß, may play a role in oral cancer development and progression.

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions.

OBJECTIVES: The aim of this study was to evaluate the expression levels of DNA damage response (DDR) markers in potentially preneoplastic oral epithelial lesions (PPOELs). STUDY DESIGN: Immunohistochemical expression of DDR markers (γΗ2 ΑΧ, pChk2, 53 BP1, p53, and phosphorylated at Ser 15 p53) was assessed in 41 oral leukoplakias, ranging from hyperplasia (H) to dysplasia (D) and in comparison with oral squamous cell carcinoma (OSCC) and normal mucosa (NM). Statistical and receiver operating characteristic curve analysis were performed. RESULTS: γH2 AX immunoexpression demonstrated a gradual increase and upper layer extension from NM to H to higher D degrees to OSCC. pChk2 expression was minimal in NM, relatively low in PPOELs, with an increasing tendency from H to D, and higher in OSCC. 53 BP1 demonstrated higher levels in OSCC than in NM, whereas its expression in PPOELs was heterogeneous, gradually increasing according to D. p53 demonstrated progressively higher levels and upper layer extension from H to D to OSCC. Phosphorylated p53 was absent in NM and relatively low in PPOELs and OSCC. CONCLUSIONS: DDR markers' expression is variable in PPOELs, showing a tendency to increase along with dysplasia. Activated DDR mechanisms may play an important protective role at early stages of oral carcinogenesis, but probably suffer progressive deregulation, eventually failing to suppress malignant transformation.

An unusual microscopic pattern of foreign body reaction as a complication of dry socket management.

Foreign body reactions in the oral cavity are relatively common, frequently resulting from iatrogenic causes. Depending on the nature of the foreign material, various microscopic patterns may be observed, causing diagnostic difficulties. Recognition of the ensuing unusual microscopic pattern, especially for cases in which the possibility of a foreign body reaction is not entertained in the clinical differential diagnosis, necessitates sufficient degree of suspicion, familiarization with the spectrum of microscopic appearances, and careful clinicopathologic correlation. Medicated dressings of various compositions are commonly placed for prevention or management of dry socket (or alveolar osteitis, a common postoperative complication of tooth extraction) and may be a cause of foreign body reaction. Here, we report a foreign body reaction to a medical dressing material in a postextraction socket, with an unusual microscopic pattern bearing resemblance to parasitic infestation.

A preliminary immunohistochemical study of signal transducer and activator of transcription (STAT) proteins in primary oral malignant melanoma.

OBJECTIVE: Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducer and activator of transcription (STAT) proteins in POMM. STUDY DESIGN: Six POMMs were included in the study. Total protein levels of STAT1, STAT3, and STAT5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically. RESULTS: Immunohistochemical evaluation of total STAT3 revealed diffuse and strong cytoplasmic and nuclear expression in the majority of tumor cells of all cases, whereas activated pSTAT3 had mostly mild nuclear expression in 5%-40% of malignant melanocytes in all cases. Evaluation of STAT1 and STAT5a identified mainly mild cytoplasmic expression in the absence of nuclear localization. CONCLUSION: The identification of aberrant STAT3 expression and activation in oral malignant melanocytes supports a possible role of this molecule in POMM. In contrast, STAT5a has only limited cytoplasmic expression, mitigating against its involvement in POMM. Also, STAT1's low levels may have implications for POMM sensitivity to interferon-based therapeutic strategies, considering the role of this molecule in cutaneous melanoma immunotherapy.

Langerhans cell histiocytosis mimicking aggressive periodontitis: Challenges in diagnosis and management.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of Langerhans cells that affects various organs. Oral involvement may simulate periodontal disease and cause significant diagnostic and management difficulties. Here, we present an interesting LCH case with severe periodontal destruction in a young woman in order to facilitate early recognition of this aggressive disease and successful participation of the general practitioner in the management of such patients. CASE PRESENTATION: A 21-year-old woman was referred for evaluation of recurrent episodes of dull pain in the gingiva for the last 9 months, which had not been successfully managed by her general practitioner. Clinical and radiographic examination showed extensive alveolar bone loss. Histopathologic examination revealed diffuse aggregates of Langerhans cells, while a complete work-up did not demonstrate evidence of systemic involvement. A diagnosis of LCH limited to the oral cavity was established. The patient received systemic chemotherapy in combination with appropriate dental care including gingival debridement and tooth immobilization. Following chemotherapy completion, comparative clinical, radiographic, and microscopic evaluation showed complete remission. During an 18-month follow-up period, frequent oral examinations and appropriate dental interventions confirmed the lack of LCH recurrence and guaranteed the stabilization of periodontal tissues. CONCLUSIONS: Oral soft and hard tissue involvement may be the only manifestation of LCH. The present case exemplifies the importance of close collaboration between general dentistry and its disciplines (periodontology, restorative dentistry, oral medicine, oral and maxillofacial pathology, and oral radiology), and hematology-oncology for diagnosis, management, treatment monitoring, and decision-making.