Primary intestinal-type adenocarcinoma: Report of a rare case involving a young patient.

The aim of this report was to describe a rare example of sporadic intestinal-type adenocarcinoma of the major salivary glands and oral cavity. A 23-year-old female patient presented an asymptomatic, progressive-growing mass involving the floor of mouth and the left submandibular gland. Fine-needle aspiration cytology, imaging exams, and surgical specimen findings were consisted with the diagnosis of primary intestinal-type adenocarcinoma, despite its similar immunohistochemical results with colorectal adenocarcinoma. Adjuvant chemotherapy and radiotherapy were performed, but the patient developed multiple metastatic lesions after one year of initial the intervention and deceased following 13 months of follow-up, despite several therapeutic efforts. We verified that sporadic cases of primary intestinal-type adenocarcinoma still lack information regarding etiology and tumorigenesis, especially in young and females. A complete diagnostic workflow is indispensable to rule out the presence of primary colorectal adenocarcinoma.

Intraoral sebaceous carcinoma: A rare presentation on the tongue and review of the literature.

Intraoral sebaceous carcinoma (SC) is exceedingly rare, especially in the tongue. We reported the clinicopathological and immunohistochemical features of a rare SC case in a 59-year-old male who presented a painful ulcer on the tongue's posterior region. Microscopically, the tumor was composed of atypical basaloid cells with round to oval nuclei and prominent nucleoli arranged in lobes showing prominent sebaceous differentiation and areas of holocrine secretion. Immunohistochemistry showed positivity for pan-cytokeratin AE1/AE3 and epithelial membrane antigen (EMA) and negativity for cytokeratin 7 (CK7). The sebaceous cells were positive for adipophilin and perforin. Wide surgical excision followed by adjuvant chemotherapy and radiotherapy was performed. Careful histopathological analysis of these lesions is crucial to ensure a correct diagnosis. Due to the aggressive behavior of SCs, early diagnosis and treatment are essential to increase the patient's survival time. To the best of our knowledge, this is the second case of SC in the tongue.

Extranodal NK/T cell lymphoma, nasal type: An updated overview.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is an aggressive malignancy associated with Epstein-Barr virus infection, with a geographic and racial predilection for some Asian and Latin American countries. ENKTCL-NT manifests as a necrotic process affecting nasal or upper aerodigestive structures and, rarely, extranasal sites such as skin, and the gastrointestinal tract. ENKTCL-NT was characterized by its poor prognosis irrespective of clinical stage and therapy. However, during the last two decades, advances in its clinicopathologic, genetic and molecular characterization have been achieved, as have changes in the chemotherapy regimens that, in combination with radiotherapy, are significantly improving the survival of these patients, especially in initial stages. For these reasons, we present an overview of the historical background of ENKTCL-NT along with an updated review of its potential etiological factors, clinicopathologic and molecular features, as well as its prognostic models, current treatment protocols, and future directions on potential promising therapeutic approaches.

Mixed odontogenic tumors: A review of the clinicopathological and molecular features and changes in the WHO classification.

BACKGROUND: Ameloblastic fibromas and ameloblastic fibrosarcomas are rare odontogenic tumors, and controversy exists in the classification of cases presenting hard-tissue production: Ameloblastic fibrodentinoma (AFD) and ameloblastic fibro-odontoma (AFO). These cases are currently considered "developing odontomas" (hamartomatous lesions). AIM: To analyze the clinicopathologic features of these lesions and discuss the changes in the 2017 World Health Organization classification. METHODS: An electronic literature search was performed in the PubMed/MEDLINE database. An electronic search of the English language literature was performed and last updated in September 2020 in the PubMed/MEDLINE database using the following terms: "ameloblastic fibroma", "ameloblastic fibrodentinoma", "ameloblastic fibro-odontoma", "ameloblastic sarcoma", "ameloblastic fibrosarcoma", "ameloblastic fibrodentinosarcoma", "ameloblastic fibroodontosarcoma" and "odontogenic carcinosarcoma". The inclusion criteria were odontogenic tumor series, case reports and systematic reviews that provided sufficient clinical, radiological and microscopic documentation to confirm the diagnosis. RESULTS: The database search strategy resulted in 947 papers. Articles focusing on other topics, articles that were not in English, duplicate articles, and articles without fulfilling the inclusion criteria were excluded. Finally, 96 publications were included in this review to describe and discuss the main features of the searched entities. Several aspects of AFO and AFD, such as biological behavior, age of occurrence, amount of hard tissue, and potential for malignant transformation into odontogenic sarcomas, support the neoplastic nature in most of the reported cases. Considering the clinical, radiographic, histopathological and molecular characteristics of odontogenic lesions with hard tissue production, we suggest that these types of lesions should continue to be recognized as odontogenic tumors by maintaining the classically used terms. CONCLUSION: This recommendation will be relevant for future clinical, microscopic, and molecular studies to better understand the biology of these interesting odontogenic tumors.

Hyalinizing clear cell carcinoma-a rare entity in the oral cavity: A case report.

BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) is an uncommon tumor that originates in the salivary glands. This neoplasia constitutes less than 1% of minor salivary gland tumors. CASE SUMMARY: A 67-year-old female visited the maxillofacial surgery department owing to a smooth, slightly yellowish protruding mass on the left side of the floor of the mouth, at the level of the molars; the tumor mass had a soft consistency on palpation and did not adhere to deep planes. The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen. Normal glandular tissue was absent, periodic acid-Schiff with and without diastase stains, and immunohistochemical reactions were performed to confirm the diagnosis. This is the second case reported in the literature of HCCC arising in the floor of the mouth. CONCLUSION: HCCC is a rare salivary gland tumor that has not been studied extensively. Its diagnosis is usually challenging, because clinically, it can be confused with a benign neoplasm.

Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with peripheral and central giant cell lesions

BACKGROUND: Few cases or periimplant peripheral giant cell lesions (PGCL) have been reported in the literature. The aim of this study was to report 13 new cases of peri-implant PGCL and compare the expression of smooth muscle actin, Bcl-2 protein, GLUT-1, CD68, osteoprotegerin, receptor activator of nuclear factor kappa-B, Ki-67 and CD34 in these cases with PGCL and central giant cell lesions (CGCL). MATERIAL AND METHODS: Clinical data were retrieved from the laboratory records and histological analysis was performed using HE-stained slides. Immunohistochemical reactions for the above mentioned antibodies were performed and digitally scored. RESULTS: Peri-implant PGCL mostly affected the posterior mandible of adult females. CD68 and Bcl-2 expressions were higher in conventional PGCL and CGCL than in peri-implant PGCL (p = 0.033 for CD68 and p < 0.0001 for Bcl-2). Microvessel density was higher in conventional peripheral than in central and peri-implant PGCL (p = 0.002). Proliferative index of the mononuclear cells showed no statistically significant differences comparing the three groups but it was higher in peri-implant PGCL. CONCLUSIONS: The current study demonstrated that peri-implant PGCL is more common in the posterior mandible of adult females. There were some differences in microvessel density, proliferative activity and expression of CD68 and Bcl-2 among conventional PGCL, peri-implant and CGCL. Further studies are encouraged to better understand these early findings

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Extranodal NK/T-Cell Lymphoma, Nasal Type in Guatemala: An 86-Case Series Emphasizing Clinical Presentation and Microscopic Characteristics.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a lymphoid malignancy that mainly affects the nasopharynx and is associated with the Epstein-Barr virus (EBV). Increased incidence is seen in some Latin American and Asian countries. In this study, we describe a case series of 86 Guatemalan patients with ENKTCL-NT from a single diagnostic head and neck center. We emphasize the distinctive clinical, microscopic, and immunohistochemical (IHC) features, as well as EBV positivity by in situ hybridization (ISH). Most of the patients (90.6%) were of Mayan descent and low socioeconomic status (SES). Males were more often affected than females, comprising 68.3% of cases. Patient age ranged from 8 to 71, with a mean of 34.7 years. All cases arose in the upper aerodigestive tract and mainly presented as a rapidly progressive, necrotizing midfacial process affecting the nasal, nasopharyngeal, sinonasal, palatal, and oropharyngeal structures. Microscopically, ENKTCL-NT showed a diffuse polymorphic and atypical lymphoid infiltrate. Angiocentric and angiodestructive growth patterns were present with associated necrosis. Peripheral hyaline necrosis of blood vessels was a histologic hallmark. The ISH and IHC profiles included positivity of EBV, LCA, CD3, CD45RO, CD30 (focal in 39.2%), granzyme-B, TIA-1, perforin (in 82.3%), and CD56 (in 83.7%). CD20 was negative, and the Ki-67 index ranged from 70 to 90%. In Guatemala, this lymphoma is strongly associated with people of low SES and indigenous ethnicity. When affected, the palatal mucosa provides the best site to obtain a representative biopsy. Since ENKTCL-NT is highly aggressive, it is extremely important to recognize the spectrum of clinical presentations and microscopic features in order to avoid misdiagnosis and treatment delay.

Oral juvenile xanthogranuloma in a child: Clinical, histological and immunohistochemical profile of a rare entity.

Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis (non-LCH) affecting normolipemic infants and children most frequently in the first year of life, often showing spontaneous regression within 3 to 6 years. Classic JXG is characterized by a yellowish asymptomatic papule or nodule, often located in the skin of the head, neck and upper trunk. Oral JXG has been reported, but is rare. Histologically, JXG is composed mainly of an infiltrate of macrophages with a variable degree of lipidization (foamy macrophages), and (most of the time) scattered Touton-type giant cells. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies. Our review of the English-language literature disclosed 33 cases of oral JXG, including this case report. The purpose of this study is to present a new case of this uncommon entity as well as to review and discuss its main clinicopathologic features and immunohistochemical findings.

Unusual Multinucleated Giant Cell Reaction in a Tongue Squamous Cell Carcinoma: Histopathological and Immunohistochemical Features.

Multinucleated giant cell (MGC) reaction in oral squamous cell carcinoma (OSCC) usually represents a stromal foreign body reaction to keratin from neoplastic epithelial cells. We describe and illustrate by double immunohistochemistry a case of a tongue squamous cell carcinoma (SCC) in a 70-year-old female patient, with a copious MGC reaction not associated to keratin, showing a histopathological pattern not described before. The MGCs were directly associated with neoplastic cells, which are phagocytosed by the MGCs. Immunohistochemistry for CD68, AE1/AE3, CD163, CD11c, RANK, RANK-L, OPG were performed, as well as double staining for CD68 and AE1/AE3 to better illustrate the relationship between MGCs and neoplastic cells. The clinical and biological significance of this pattern of MGC reaction in OSCC needs to be better elucidated.

Phosphorylated Akt1 expression is associated with poor prognosis in cutaneous, oral and sinonasal melanomas.

Melanomas are highly aggressive tumours derived from melanocytes, which occur most commonly in the skin. Occasionally, these tumours may appear in oral and sinonasal mucous membranes. In this study, we performed a comparative analysis of the Phosphorylated Akt1 (p-Akt1) expression in 144 patients affected by cutaneous (CM), 34 oral cavity (OM), and 31 sinonasal melanomas (SNM). Similar to the metastatic cutaneous melanomas, p-Akt1 was overexpressed in 17/34 of the oral cavity and 20/31 of the sinonasal melanomas. In addition, the p-Akt1-nuclear expression was associated with poorer cancer-specific survival in cutaneous (P < .0001), oral (P < .0001), and sinonasal (P = .001) melanomas. Multivariate analysis showed p-Akt1 to be an independent prognostic marker in oral (P = .041) and sinonasal (P < .0001) melanomas patients. In conclusion, p-Akt1 overexpression is an independent prognostic marker in mucosal melanomas and is significantly up-regulated in sinonasal melanomas. As both mucosal and metastatic cutaneous melanomas showed high frequency of p-Akt1 expression, these findings suggest that mucosal melanomas have a biological behaviour, similar to the aggressive cutaneous melanomas.

BRAF-V600E expression correlates with ameloblastoma aggressiveness.

AIMS: The aim of this study was to investigate whether the expression of BRAF-V600E determines an aggressive clinical and molecular presentation of ameloblastoma. METHODS AND RESULTS: Ninety-three cases of solid ameloblastomas were arranged in a 1.0-mm tissue microarray (TMA) block. Immunohistochemistry against a large panel of cytokeratins (CK), epidermal growth factor receptor (EGFR), parathyroid hormone-related peptide (PTHrP), syndecan-1, Ki67, p53 and BRAF-V600E were performed. Clinicopathological parameters, including sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic pattern, vestibular/lingual and basal cortical plates disruption and follow-up data, were obtained from patients' medical records. Immunoexpression of BRAF-V600E was investigated in 73 cases that remained available in TMA sections. Our results indicated that 46.6% (34 cases) demonstrated cytoplasm positivity (six weak and 28 strong positivity). BRAF-V600E expression was associated significantly with the expression of CK8 (P = 0.00077), CK16 (P = 0.05), PTHrP (P = 0.0082) and p53 (P = 0.0087). Additionally, a significant association was seen with the presence of recurrences (P = 0.0008), multilocular radiographic appearance (P = 0.044) and disruption of basal bone cortical (P = 0.05). Univariate analysis showed that BRAF-positive cases (P = 0.001), EGFR-negative/weak positive cases (P = 0.03) and multilocular tumours (P = 0.04) had a significantly lower disease-free survival rate, but these parameters were not considered independent prognostic factors in the multivariate analysis (P > 0.05). CONCLUSIONS: Our findings suggest an association of BRAF-V600E with parameters of a more aggressive behaviour of ameloblastoma, supporting the future use of BRAF inhibitors for targeted therapy of this neoplasm.

Immunohistochemical Expression of GLUT-1 and HIF-1α in Tooth Germ, Ameloblastoma, and Ameloblastic Carcinoma.

Hypoxia-inducible factor-1α (HIF-1α) promotes proteins that enable cell survival during hypoxia, such as glucose transporter 1 (GLUT-1). Their coexpression has been associated with aggressiveness in malignancies and has not been studied in odontogenic tumors. Immunohistochemical expression of HIF-1α and GLUT-1 was analyzed in 13 tooth germs (TGs), 55 ameloblastomas (AMs), and 3 ameloblastic carcinomas (ACs). HIF-1α was negative in all TGs, and just 1 case of AM and 1 of AC had nuclear positivity. GLUT-1 expressed in ameloblastic cells of all TGs, AMs, and ACs, with an increasing intensity, respectively, and was significantly higher in solid AM than in unicystic AM (P = .041). Absence of nuclear HIF-1α in TGs and most AMs suggest that GLUT-1 may be induced by alternative pathways to hypoxia. However, in ACs, HIF-1α may be activated; however, to confirm this, additional cases are needed. GLUT-1 overexpression could be related to aggressiveness in AMs and ACs and must represent a normal metabolite in TGs.

Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas.

AIMS: Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. METHODS AND RESULTS: Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). CONCLUSION: Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.

Oral presentation of 10 patients with Cowden syndrome.

Cowden syndrome (CS) is an autosomal dominant genodermatosis that frequently affects several tissues with hamartomatous growth. The oral cavity is quite commonly involved with papillomatous lesions, which can be crucial to early diagnosis of this disease. In this series, 10 patients with a great diversity of manifestations associated with CS are presented, in whom oral papillomatosis was a constant and relevant finding to establish the diagnosis of CS. The role of the dentist in recognizing the oral lesions, the other diagnostic criteria, the risk for the development of malignancies, and the importance of lifetime follow-up are discussed.

Expression of PROX-1 in oral Kaposi's sarcoma spindle cells.

BACKGROUND: The histogenesis of neoplastic spindle cells of Kaposi's sarcoma is still uncertain, but some studies consider it a lymphatic vessel differentiation. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis, and it has been considered a specific and sensitive lymphatic endothelial cell marker. The aim of this study was to determine the expression of Prox-1 in oral Kaposi's sarcoma comparing the results with oral benign vascular tumors including capillary hemangiomas and pyogenic granulomas. METHODS: Expression of Prox-1 and HHV-8 was evaluated by immunohistochemistry in 30 oral Kaposi's sarcoma, 5 oral capillary hemangiomas, and 10 oral pyogenic granulomas. The labeling index was expressed as the percentage of positive cells for each case studied. Statistical comparison was performed using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: Twenty-eight (93.3%) and 30 oral Kaposi's sarcoma cases were positive for Prox-1 and HHV-8, respectively, while all oral benign vascular tumors were negative for these markers. The number of Prox-1 and HHV-8 oral Kaposi's sarcoma-positive cells increased significantly from patch/plaque to nodular histological stages. CONCLUSION: The expression of Prox-1 in the neoplastic spindle cells supports the view of a lymphatic differentiation in oral Kaposi's sarcoma. Prox-1 may also be involved in the pathogenesis of oral Kaposi's sarcoma as the number of positive spindle cells increased progressively from patch to nodular stages and could be eventually useful as an additional diagnostic tool for differential diagnosis between oral Kaposi's sarcoma and benign oral vascular lesions.

Immunohistochemical expression of Skp2 protein in oral nevi and melanoma

Objective: The aim of this study was to analyze the immunohistochemical expression of Skp2 protein in 38 oralnevi and 11 primary oral melanomas. Study Design: Expression of this ubiquitin protein was evaluated by immunohistochemistry in 49 oral melanocyticlesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index (LI) was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting1000 cells per slide. Results: Skp2 protein was rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showedhigh levels of this protein. Conclusion: These results indicate that Skp2 protein may play a role in the development and progression of oral melanomas, and it also could be useful as an immunohistochemical marker for differential diagnosis of oral benign and malignant melanocytic lesions (AU)

Signet-ring cell change in adenoid cystic carcinoma: a clinicopathological and immunohistochemical study of four cases.

AIMS: Signet-ring cell (SRC) change has not been reported in adenoid cystic carcinoma (ACC). The aim of this study was to describe the clinicopathological and immunohistochemical findings in four cases of ACC with SRCs (ACC-SRC), in which the relative proportion of the SRC component ranged from 25% to 50%. METHODS AND RESULTS: The median age was 58 years (range: 48-81 years), and all patients were women. The involved sites were sinonasal, lip, and submandibular. Two patients developed lung metastasis, and one died of disease 63 months after tumour resection. Neither mucinous nor lipid substances were detected in the SRCs. These showed positive staining for AE1/AE3, cytokeratin 14, and epithelial membrane antigen, which highlighted the intracytoplasmic vacuole borders. The SRC nests were surrounded by myoepithelial cells positive for α-smooth muscle actin and p63. The SRCs showed similar p53 positivity but lower Ki67 and mitotic indices than the conventional component. SRCs were c-Myb-negative. Ultrastructural examination revealed that the intracytoplasmic vacuoles were lumina lined by microvilli. CONCLUSIONS: ACC-SRC is a non-mucin-producing and non-lipid-producing phenomenon, possibly related to disturbed differentiation of ductal/luminal cells. This cellular modification in ACC apparently does not change the biological behaviour of the tumour, but it may cause significant diagnostic problems, particularly in incisional biopsies.