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Intraoral basal cell carcinoma (IOBCC) is an extremely rare entity that is often confused with the peripheral ameloblastoma (PA). Basal cell carcinomas are thought to arise from pluripotential basal cells present within surface epithelium and adnexal structures, so theoretically they can arise within the oral cavity. Most of the well-documented cases arise from the gingiva. Many of the early cases reported as IOBCC actually represent PA. We present 2 cases displaying histologic, immunohistochemical, and clinical features characteristic of an IOBCC. The histologic features of IOBCC that help separate it from a PA include prominent retraction artifact, tumor arising from surface epithelium, scattered mitotic figures and apoptotic cells, presence of mucoid ground substance, and tumor infiltrating widely throughout the connective tissue. Clinically, IOBCCs resemble carcinomas, compared with the benign and innocuous appearance of the PA. IOBCCs typically present as surface ulcerations varying from rodent ulcer to an ulcerated erythroplakic appearance. This contrasts with the classic “bump on the gum” appearance of PAs, with usually intact surface and appearing as small, discrete, sessile, exophytic lesions. In the more recent literature, Del Rosario et al. and Koutlas et al. described IOBCC with positive immunoreactivity of only the neoplastic basal cells for the antiepithelial antibody Ber-EP4, a cell surface glycoprotein. Normal skin or oral epithelium, PA, and squamous cell carcinomas do not stain with Ber-EP4, a very important distinguishing factor separating these entities.
Glandular odontogenic cysts (GOCs) are relatively uncommon, developmentally distinct odontogenic cysts with unusual histopathologic features. Due to the overlap of key microscopic features with other developmental cysts, particularly dentigerous cysts, it is imperative that stringent criteria and specific markers be identified. Immunohistochemistry has been studied to aid differentiation of GOCs from other cysts. Tosios et al., with a very limited sample size, reported increased expression of bcl-2 in GOCs compared with dentigerous cysts.
SOX2 (sex determining region Y-box 2), originally identified as a pivotal transcription factor for epithelial renewal, is found to be overexpressed in a spectrum of epithelial malignancies. As an odontogenic epithelium-derived cancer, ameloblastic carcinoma (AC) often poses diagnostic challenges, especially in its separation from benign ameloblastoma with atypical cytologic features or unusual clinical course. In our previous publication, we identified SOX2 as a marker for high-grade transformation in ameloblastic neoplasms with only 2 stained AC cases. Here we include an additional 8 AC cases to provide a more comprehensive interpretation. SOX2 marks the basal proliferative zone of epithelium in dentigerous cysts. It is negative in mature epithelium and in ameloblastic neoplasms without high-grade transformation. The diffuse strong nuclear staining pattern has 100% specificity to indicate the presence of high-grade features (7/7), and 70% sensitivity (7/10) in comparison with other benign ameloblastic neoplasms (P = .039). Although previously shown as a promising marker for ameloblastic neoplasms, calretinin is weakly positive in a few cells in 50% (5/10) of AC and 43% (3/7) of benign ameloblastic neoplasms, with little value in highlighting the high-grade change (P = .36). A diffuse nuclear stain pattern of SOX2 is suggestive of a high-grade process in ameloblastic neoplasms. Focal aggregates of cells harboring dense nuclear stain should raise caution for a malignancy arising in ameloblastoma with otherwise classical benign features. This is conceptually consistent with recent studies that show that increased SOX2 expression is associated with a poorer prognosis in oral cancer, sinonasal cancer, and urothelial cancer.
Mammary analog secretory carcinoma (MASC) is a newly recognized salivary gland tumor with a unique histologic appearance, immunohistochemical profile, and chromosomal translocation. In the seminal paper, these tumors are described as circumscribed, lobulated masses with microcystic, tubular, and solid structures. To date, 89 cases of MASC have been reported. Of those cases, only 21 were located intraorally. We present an additional 20 cases of MASC involving the minor salivary glands. Microscopically, these tumors are locally infiltrative and composed of mildly pleomorphic cells with abundant eosinophilic and granular cytoplasm. The majority of the minor salivary gland tumors are arranged in solid, microcystic, and tubular growth patterns. However, 8 of the 20 cases in this series consisted of one or more cysts lined by tumor cells with papillary projections extending into the cyst lumen. These tumors are described as having a papillary cystic morphology. Immunohistochemistry shows these tumors to be positive for proteins S-100, mammaglobin, and vimentin, with variable positivity for GCDFP-15. This is similar to the staining pattern of secretory carcinoma of the breast, which is consistently positive for S-100 and mammaglobin. Although fluorescence in situ hybridization reveals consistent t(12;15), this may not be practical for routine diagnosis in most laboratories. A recent publication suggests the use of histopathologic features along with strong immunohistochemical positivity for S-100 and mammaglobin as diagnostic criteria. These additional cases help to further refine the histologic spectrum of mammary analog secretory carcinoma.
In recent years cementum protein (CEMP-1) has been isolated from human cementoblastoma. CEMP-1 is considered as a specific marker of cementoblasts, periodontal progenitor cells, and mineralization processes such as octacalcium phosphate crystal nucleation of hydroxyapatite precursor. Also, CEMP-1 has been observed to induce phenotype differentiation of periodontal ligament cells toward the cementoblastic/osteoblastic and chondroblastic. The aim of this study was to identify the presence of CEMP-1 in a lower right first molar cementoblastoma in a 26-year-old man. An orthopanoramic radiograph showed a well-defined radiopaque lesion in the lower right first molar region. The excisional biopsy showed cementum-like tissue, prominent basophilic reversal lines, and fibrous connective tissue as a capsule. An immunofluorescence study was performed with the use of polyclonal antibody against CEMP-1 at a 1:100 concentration diluted with bovine serum albumin. Subsequently, a secondary goat anti-rabbit antibody labeled with fluorescein isothiocyanate (FITC; Santa Cruz Biotechnology, Inc) in a 1:75 concentration was incubated according to the manufacturer's instructions and with phosphate-buffered saline (PBS) 1× diluted for 2 hours at room temperature. At the end, 2 more washes with PBS 1× were performed. As a negative control, the same procedure was done but with the absence of the primary antibody. The expression of CEMP-1 was positive in subpopulations of cementoblasts and mineralized tissue. CEMP-1 could help to identify and standardize tumoral lesions like cementoblastoma.
Papillary cystadenoma (PCA) and its malignant counterpart papillary cystadenocarcinoma (PCAC) are both rare neoplasms in sublingual salivary glands. There is considerable overlap in microscopic characteristics, with PCA being encapsulated whereas PCAC was infiltrative. Atypia, necrosis, or increased mitotic activity may not be present. We report a sublingual tumor in a 78-year-old woman, present for several years and stable in size, presenting gradual growth for 4 months. A multilobulated, nonulcerated, bluish submucosal mass of 4-cm diameter occupied the floor of the mouth. Magnetic resonance imaging identified a well-circumscribed, multicystic mass, located above the mylohyoid and replacing the sublingual gland. Biopsy exhibited multiluminal cystic architecture. The lining epithelium was thin, composed of uniform cuboidal cells creating delicate luminal papillary projections. The cytology was bland, lacking atypia, prominent mitotic activity, or necrosis, and the diagnosis was PCA. During surgery the lesion seemed to present a distinct capsule and separated easily by extracapsular dissection. However, in the most posterior region, firm attachment to the submandibular gland area was observed. The microscopic analysis of the resection specimen showed features identical to those of the biopsy, with a clear capsule in the majority of the periphery, except for the posterior aspect, where a clear infiltrative pattern was observed. The final diagnosis was reversed to PCAC. The history of a long duration with a recent increase in size, the encapsulation of most of the tumor periphery, and the localized front of invasion all suggest transformation from PCA to PCAC. This has never been described before in this particular tumor type, although it is well recognized in long-standing pleomorphic adenoma.
Dendritic cell neurofibroma with pseudorosettes (DCNP) is a rare benign peripheral nerve sheath tumor first described in 2001 by Michal et al. Only 25 cases (26 lesions) have been published in the English-language literature, with no intraoral lesions reported to date. DCNP has been reported in adults with no gender predilection; the mean age was 46.5 years (range, 24-73). DCNPs commonly present as well-circumscribed, dome-shaped, firm nodules in the dermis of the trunk (40%), extremities (32%), or the head and neck region (28%). DCNP is characterized by a biphasic population of neural cells with S-100 and CD57 positivity. Type I cells are small and lymphocyte-like with dark nuclei; type II cells are large and neural ganglion–like with pale, vesicular nuclei showing intranuclear pseudoinclusions. Type I cells are generally arranged concentrically around centrally located type II cells, forming pseudorosettes. The tumor cells are negative for neuroendocrine, muscular, and epithelial markers. There is no reported tendency for lesional recurrence or malignant transformation after complete excision. We present a series of 5 cases of DCNP, the first report of intraoral lesions. The lesions presented in 2 men and 3 women, with a mean age of 53.4 years (range, 36-73). Three presented on the buccal mucosa and 2 on the tongue. Each tumor demonstrated all the characteristic features of DCNP. Both cell populations exhibited strong S-100 positivity. Strong CD57 positivity was consistently demonstrated in type II cells and was variable among type I cells. Pathologists should consider DCNP in their differential diagnoses when confronted with unusual neural lesions that do not exhibit classic features of neurofibromas, schwannomas, or other benign peripheral nerve sheath tumors.
Ewing sarcoma and primitive neuroectodermal tumor (ES/PNET) represent opposite ends of a spectrum of malignant round-cell neoplasms that show variable degrees of neuroectodermal differentiation. Initial presentation of ES/PNET in the oral cavity is exceedingly rare, and involvement of the gnathic or craniofacial region occurs in approximately 1% to 2% of cases. We contribute 2 cases of ES/PNET presenting as enlarging mandibular radiolucencies from a 5-year-old boy and a 34-year-old man. Although ES/PNET may involve any site, it predominantly affects bone, representing the third most common primary malignancy of bone following osteosarcoma and chondrosarcoma. It is most common in children and young adults, with 80% of cases occurring before 20 years of age. This malignancy has a slight male predilection and affects white people with a much greater frequency than African Americans. The histopathology is variable but typically includes a population of monomorphous, round, blue, undifferentiated cells (ES) or cells with neuroectodermal features (PNET) arranged in sheets or nests. Immunohistochemical analysis shows the majority of cases are positive for proteins CD99 (95%) and FLI-1 (90%), and a minority of cases highlight neuroendocrine markers. A translocation involving EWS on chromosome 22 and FLI-1 on chromosome 11 is seen in 90% of cases. The treatment for ES/PNET is surgery and chemotherapy with or without local radiation therapy. The prognosis of this family of malignant neoplasms is reported to be 65% survival at 5 years. Here, we describe 2 unusual cases with initial presentation in the gnathic bones prompting a diagnosis of ES/PNET.
Crohn disease (CD) is an immune-mediated disorder of the gastrointestinal tract; CD and ulcerative colitis comprise the 2 major types of inflammatory bowel disease. The underlying etiology has been attributed to defects in mucosal immunity and the intestinal epithelial barrier in a genetically susceptible host, resulting in an inappropriate inflammatory response to intestinal microbes. The lesions of CD can affect any region of the alimentary tract, as well as extraintestinal sites such as the skin, joints, and eyes. The most common presenting symptoms are periumbilical pain and diarrhea associated with fevers, malaise, and anemia. Oral involvement has been termed oral CD and may manifest as lip swelling, cobblestoned mucosa, mucogingivitis, and linear ulcerations and fissures. Oral lesions may precede gastrointestinal involvement and can serve as early markers of CD. We describe a 6-year-old boy who presented for evaluation of multifocal gingival erythema and swellings. His medical history was unremarkable for gastrointestinal disorders or distress. Histopathologic examination showed multiple well-formed granulomas that were negative for special stains and foreign body material. A diagnosis of granulomatous gingivitis was rendered. The patient and his parents were advised to seek consultation with a pediatric gastroenterologist, and following colonoscopy the boy was diagnosed with early-stage CD. Timely recognition of the oral manifestations of CD is critical, because only a minority of patients will continue to exhibit CD-specific oral lesions at follow-up. This places the dental practitioner in a unique position to detect occult CD in an otherwise asymptomatic patient, which may ultimately lead to early diagnosis and treatment.
Sjögren syndrome (SS) is an autoimmune disease that affects the exocrine glands, causing dry mouth. Local moisturizers, immunosuppressants, and antimuscarinic medications are commonly prescribed. However, there are few studies addressing the influence of eating habits caused by dry mouth on the quality of life of patients with this disease. In the present study, we evaluated the nutritional status and eating habits in patients with SS and made adjustments to their diet by adding moisture and soft textures that avoid damaging the oral mucosa. We studied 25 patients with SS through nutritional interviews to inquire about their eating habits. (Patients were diagnosed with SS according to the criteria established by the Sjögren International Clinical Collaborative Alliance [SICCA].) Of these 25, 22 (90%) reported having to limit their food selection because certain foods caused them discomfort. Nutritional status was assessed based on body mass index, laboratory assays, and asking about changes in weight since disease onset. Based on the results, each patient's diet was modified, focusing on changes in the consistency and moisture of foods. Each patient was given a healthy eating plan and a guide to the selection and preparation of foods for patients with dry mouth, designed by our Nutrition Service, that ensure the inclusion of all necessary nutrients. With this help, 85% of the patients self-reported improvements in their diet and ability to swallow foods and therefore in quality of life. These results show the importance of the creation of a personalized eating plan that is consistent with the patient's degree of oral dryness and that ensures the nutritional value is maintained. This study was supported by National Institutes of Health contract NOI-DE-32636.
We report a case of pseudoxanthoma elasticum involving the oral cavity in a 65-year-old woman. Pseudoxanthoma elasticum is a heritable multisystem disorder with cutaneous, ophthalmologic, and cardiovascular manifestations. The disorder is caused by mutations in the ABCC6 gene located on chromosome 16p13.1. A recent study found an association of oral mucosal lesions and cardiovascular disease. Our patient presented with 2 areas of leukoplakia on the soft palate. Both lesions were excised and submitted for histopathologic diagnosis to rule out epithelial dysplasia. One lesion was diagnosed as hyperkeratosis and mild acanthosis, whereas the other was consistent with pseudoxanthoma elasticum.
Amalgam lichenoid reaction (ALR) presents clinical and histologic features of oral lichen planus (OLP); however, each is a different example of lesion evolution and of evidence of hypersensitivity to amalgam. Langerhans cells (LCs) are cells of the innate immune system and are responsible for initiating adaptive immune response. The aim of this study was to measure the number of LCs in specimens of ALR, OLP, and normal oral mucosa (NOM). LCs were identified by immunohistochemistry for the CD1a protein in 21 samples of OLP, ALR, and NOM in oral epithelium and lamina propria. The inflammatory cells were evaluated in subepithelial region (RS) and in below region of subepithelial region (BRS) for samples of OLP and ALR. Density of LCs (cells/mm2) was determined using the AxioVision 2.4 software (Microsoft and Carl Zeiss Vision GmbH, Göttingen, Germany). Samples were obtained from the files of the Service of Maxillofacial Pathology, School of Dentistry, Universidade Federal de Minas Gerais (1965 to 2010). Significantly higher density was observed for CD1a+ LCs in RS (95.73 cells/mm2) and OLP (87.04 cells/mm2) with the OLP when compared with RS (44.71 cells/mm2), OLP-ALR (42.12 cells/mm2), and OLP-NOM (29.82 cells/mm2). The densities of LCs were correlated with the density of inflammatory cells, and there were strong and positive correlations between oral epithelium cells, RS, BRS, and OLP, when compared with inflammatory infiltrate in OLP (P > .05). A strong positive correlation was also observed in the BRS in ALR (P < .05). Higher densities of inflammatory cells were observed in the OLP and ALR when compared with NOM (P < .05). Our results suggest that different immunologic mechanisms can be associated with the pathogenesis of OLP and ALR. This study was supported by the Brazilian National Council for Scientific and Technological Development (CNPq); the Foundation for Research Support of the State of Minas Gerais (Fapemig); and the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES).
To report a case of allergic contact stomatitis, initially presenting clinically as oral bullae. Allergic contact stomatitis is a delayed-type hypersensitivity reaction (type IV). Its oral manifestations include inflammation followed by erosions, and it can present as bullae, occasionally resembling lesions of pemphigoid or pemphigus. These manifestations usually occur within 24 to 72 hours of contact with the antigen.
This retrospective clinical study documented common orofacial lesions in infants with cleft lip and palate (CL/P), who were managed using a nasoalveolar molding appliance (NAMA).
Intravascular fasciitis is a rare variant of nodular fasciitis involving arteries or veins, typically in an extremity. However, approximately 10% of published cases involve the head and neck.
Kaposi sarcoma (KS) is a multifocal vascular tumor that occurs most commonly in patients who have immunosuppression caused by HIV. KS-associated herpesvirus, also called human herpesvirus 8 (HHV8), has been identified as the causative agent. KS growth involves the upregulation of many key HHV8 gene products, such as the latency-associated nuclear antigen (LANA-1 or LNA-1). Frequently, the oral cavity may be the initial site of KS, and the discovery there of KS is often also the first clinical indication of HIV infection in previously undiagnosed individuals. Due to the great variability of morphologic aspects, it may be necessary to assess the positivity to HHV8 in order to differentiate KS from other vascular lesions. In our biopsy service, the main problem can be the small size of most biopsies, which sometimes creates difficulties in the detection of HHV8. Thus, in the present study we aimed to compare immunohistochemistry (IHC) and polymerase chain reaction (PCR) techniques to detect HHV8 in oral biopsies of supposed KS. Sixteen cases diagnosed in the last 5 years were retrieved from the files of the Oral Pathology Department at the University of São Paulo. The biopsies measured an average of 2.5 mm in diameter. For IHC, the material was submitted to the streptavidin-biotin method, and the antibody used was anti-HHV8-LNA (Novocastra, Leica Biosystems). For PCR, DNA from the lesions was isolated using the phenol-chloroform extraction protocol. Primers were obtained from the National Center for Biotechnology Information GenBank databases. Real-time PCR was performed on DNA using Jumpstart SYBR green mastermix (Sigma-Aldrich) on a thermocycler (Applied Biosystems 7500 Real-Time PCR System). Fifteen samples, which were HHV8-IHC positive, were positive to HHV8-DNA detection.
Echinococcosis is a zoonosis caused by a canine tapeworm. Although dogs are the definitive target for this parasite, humans can serve as an intermediate host when eggs from the organism are ingested. Infection results in formation of a hydatid cyst. Echinococcal infections are endemic to the Middle East, Europe, and parts of Africa. However, there is an increase in cases arising outside of these regions. The most common sites for hydatid cyst formation are the liver and lungs. Only 1% to 2% of cases are seen in the head and neck region. The current case is that of an African man that presented with an enlarged tongue. Imaging studies revealed a cystic lesion involving the deep musculature. Histologic examination of the excision specimen showed an echinococcal organism residing within the hydatid cyst. This case represents an unusual anatomic location for this occurrence, as well as an uncommon geographic location. For these reasons, a parasitic infection did not enter into the differential diagnosis. Failure to recognize this condition can lead to complications during the excision process. These risks include anaphylaxis and secondary infection from removal of the cyst. This case represents the significance of proper recognition and treatment for this condition.
NK/T cell lymphoma of the nasal type is an aggressive lymphoma commonly presenting as a destructive process of the facial midline, often demonstrating clinical and histologic features of necrosis and angioinvasion. It was initially categorized as an angiocentric lymphoma in the Revised European-American Lymphoma (REAL) classification. It has been recategorized as extranodal NK/T cell lymphoma in the World Health Organization classification of lymphoid neoplasms. Historically these tumors were considered part of “midline lethal granuloma.” This entity frequently arises in extranodal regions, especially the nasal or paranasal sinuses. Other extranodal sites include the palate, trachea, skin, and gastrointestinal tract. In most instances, Epstein-Barr virus (EBV) genomes are detectable in the tumor cells, and immunohistochemistry detects CD56 positivity. The pathologic diagnosis of nasal-type NK/T cell lymphoma is based on expression of cytoplasmic CD3 and CD56 and positivity for EBV in situ hybridization. If EBV in situ hybridization is negative, the immunophenotype studies should demonstrate cytoplasmic CD3 expression and positive cytotoxic molecules such as TIA-1. Nasal-type NK/T cell lymphoma is known to be one of the most aggressive lymphomas, so it is imperative to offer an appropriately aggressive treatment at an early stage of disease. We present the clinical and therapeutic treatment course and outcome of a 60-year-old white man diagnosed with NK/T cell lymphoma. This includes a clinicopathologic review, approaches to diagnosis, and surgical and prosthetic treatment strategies for patient optimization throughout oncologic therapies.
CD30 (Ki-1) is a surface differentiation protein that is demonstrable in 1% of bone marrow cells and is a member of the tumor necrosis superfamily 8. This glycoprotein is expressed on Reed-Sternberg immunoblasts in Hodgkin lymphoma and other lymphoblastic lesions of the skin and internal organ sites. CD30-positive lymphoproliferative diseases are rare in the oral cavity and may be seen in conjunction with systemic and cutaneous counterparts.
A 5-year-old boy presented clinically with a subgingival supraperiosteal expansile mass associated with the mandibular anterior central incisors. There was no obvious clinical intraosseous involvement. The oral mucosal epithelium did not reveal any clinical changes suggestive of a process originating from the surface. Histopathologic evaluation revealed soft tissue fragments that were surfaced or lined by hyperkeratinizing and acanthotic stratified squamous epithelium exhibiting cytologic variations that include irregular rete pegs, loss of polarity, individual cell keratinization, increased nuclear/cytoplasmic ratio, and prominent nucleoli. Areas of prominent endophytic epithelial proliferation comprising cords and islands that showed cytologic atypia were also present. The differential diagnosis was between a well-differentiated squamous cell carcinoma and an atypical epithelial proliferation of uncertain biologic behavior. Review of the literature revealed a similar lesion reported by Elzay and O’Keefe (Oral Surg Oral Med Oral Pathol 1979;47:436) who also discussed the unusual presentation of their case and the inability to completely exclude well-differentiated squamous cell carcinoma. External consultation with 3 senior oral pathologists resulted in the diagnoses of atypical epithelial proliferation (2 pathologists) and squamous cell carcinoma (1 pathologist), further underscoring the difficulty in obtaining a definitive diagnosis. No additional treatment was performed, and the patient remained lesion-free in a 10-month follow-up.