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Originally described exclusively orally in HIV-infected patients, plasmablastic lymphoma (PBL) is increasingly described extra orally and in non-HIV-infected persons. The study comparatively analysed the clinico-pathologic features of oral PBLs (n = 55) to previously published extra-oral PBLs (n = 45 + 1) diagnosed over a seven-year period at the same institution in an HIV prevalent setting in South Africa in order to clarify any distinction between oral and extra-oral PBLs.Tumours were assessed histologically and immunohistochemically with CD45 (LCA), CD3, CD20, CD79a, PAX5, CD138, MUM1, BLIMP1, VS38c, Ki-67, BCL6 and CD10 using standard protocols. Age ranged from 22 to 76 years (oral) and 9 and 59 years (extra-oral). Most PBL patients were HIV positive [oral (84%); extra-oral (65%)]. Male:female ratio was 2.7:1 for oral and 1.4:1 for extra-oral PBLs. Favoured oral and extra-oral sites were the maxilla and anus. PBLs displayed an indistinguishable immunohistochemical profile with unusually high CD45 expression (oral: 98%, extra-oral: 84%). EBV assessed by chromogenic in situ hybridisation (ISH) showed positivity in all oral PBLs and 95% extra-oral PBLs. MYC rearrangements (fluorescence ISH MYC break-apart probe) were similar in all the PBLs.Extra-oral PBL is identical to its oral counterpart in gender and age distribution, HIV status, morphological appearances, immunophenotypic profile and EBV association. PBL should be regarded as the same tumour irrespective of oral or extra-oral site of origin.

Ectomesenchymal chondromyxoid tumor (ECT) is a rare oral lesion first described by Smith et al. in 1995 . These tumors are typically painless, slow growing and benign masses occurring predominantly on the anterior tongue dorsum. Prior to this seminal report, many ECTs may have been misdiagnosed due to the histological similarities with other lesions. Immunohistochemical stains aid in definitive diagnosis of an ECT. A total of 39 papers since published have reported 96 patients with ECT. Most lesions involve the anterior aspect of the tongue, with only 6 occurring in the posterior tongue and 2 involving the hard palate. ECTs are considered to develop from ectomesenchymal cells of neural crest cells that have migrated to the tongue during embryological development. This paper is of a rare case of ECT of the posterolateral tongue occurring in association with an unusual asymmetrical soft palate cleft. It is postulated that since the tongue develops before the formation of the soft palate, an ECT lesion occurring on the posterior aspect may have a causal contribution to the development of the soft palate cleft.

Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole-exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK–STAT signaling pathway, including STAT3 (42%), JAK1 (14%), and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches. Significance: Plasmablastic lymphoma is a poorly studied and extremely aggressive tumor. Here we define the genomic landscape of this lymphoma in HIV-positive individuals from South Africa and identify pervasive mutations in JAK–STAT3 and RAS–MAPK signaling pathways. These data offer a genomic framework for the design of improved treatment strategies targeting these circuits. See related commentary by Küppers, p. 23. This article is highlighted in the In This Issue feature, p. 5

Background Extragonodal germ cell tumors (GCTs) primarily affect the sacrococcygeal region. Head and neck GCT is rare and accounts for 3% of pediatric neoplasms. Only isolated cases of metastatic GCT have been reported. Objective To report a unique case of a metastatic nonseminomatous GCT of mixed phenotype with yolk sac tumor, embryonal carcinoma, and immature teratoma components. Clinical Findings A 13-year-old male patient presented with a rapidly enlarging, painless right maxillary tuberosity mass, present for 4 months. The tumor was on the buccal gingiva extending to the hard and soft palate posteriorly. Ipsilateral submandibular lymphadenopathy was evident. No pathology was noted on the panelipse and periapical radiographs. The clinical impression was that of a lymphoma or Kaposi sarcoma. Pathologic Findings The histology showed an extensively infiltrative high-grade malignancy composed of small, round, blue discohesive tumor cells demonstrating a solid growth pattern, with areas of adenocarcinoma and squamous differentiation with keratinization. Surface dysplasia was not present. Brisk mitotic activity was noted. Immunohistochemistry revealed positivity with for AE1/AE3, SALL4, Glyplican 3, and OCT3/4, confirming the diagnosis of a metastatic nonseminomatous GCT of mixed phenotype. Summary Benign teratomas are the most common childhood extragonodal tumors, followed by yolk sac tumors, which frequently arise in the ovaries and testis. Yolk sac tumors that frequently arise in the ovaries and testis have been reported but continue to be a rare extragonodal tumor and are difficult to diagnose. This report reviews germ cell tumors in the spectrum of metastatic disease to the oral cavity.

Background Originally thought to be exclusive to the oral cavity in human immunodeficiency virus (HIV)-infected persons, plasmablastic lymphoma (PBL) is increasingly described extraorally, and in non-HIV-infected patients. Demographic data are often dependent on case reports, case series, and systemic reviews. Objective This is an epidemiological, morphological, and immunological comparison of oral and extraoral PBLs in a high HIV endemic setting. Methods This retrospective study of extraoral and oral PBLs diagnosed over a 5-year period analyzed patients’ age, sex, HIV status, and tumor site. Histologic diagnosis was confirmed and tumors were assessed immunohistochemically with CD45 (LCA), CD20, CD79a, PAX5, CD138, MUM1, BLIMP1, VS38c, Ki-67, BCL6, CD10, and HHV8 using the manufacturers’ protocols. The presence of Epstein-Barr virus (EBV) was assessed by chromogenic in situ hybridization. Ethics clearance: M10750. Results There were 46 extraoral and 54 oral PBLs. Patient age ranged from 9 to 59 years (extraoral) and from 22 to 78 years (oral). In known HIV cases, 95% of extraoral and 97% of oral cases were HIV-positive. None had systemic disease at presentation. The male:female ratio was 1.4:1 for extraoral and 2.7:1 for oral PBLs. The favored extraoral and oral sites were the anus (28%) and maxilla (29%). Immunohistochemical profiles recapitulated that previously reported, except for CD45 expression, which was higher (85.7% extraoral, 97% oral). EBV was positive by in situ hybridization in 96% of PBLs, 93% of extraoral PBLs, and all oral PBLs. Conclusions Extraoral and oral PBLs are identical in sex and age distribution, HIV status, morphological appearance, immunophenotypic profile, and EBV association. PBL should be regarded as the same tumor irrespective of oral or extraoral site of origin.

Objectives Non-Hodgkin lymphoma occurs with increasing frequency in HIV/AIDS. As South Africa has the highest incidence of HIV/AIDS worldwide, an epidemiologic study of this nature provides insight into head and neck lymphomas in a defined South African population. This retrospective review evaluated frequency and clinico-pathologic characteristics of patients diagnosed with head and neck lymphoma at the Oral Pathology Department, University of Witwatersrand between 1993 and 2012. Materials and methods Histopathology reports of patients with head and neck lymphomas ( n = 504) were reviewed. Demographic (age, gender), clinical (site and size of tumour), laboratory and histological parameters were recorded. Results There were 504 patients with head and neck lymphomas. The mean age was 40.4 years. The male:female ratio was 1.1:1. The cervical lymph node was the most common anatomic site (115 cases) and the maxilla (60 cases) the most common extranodal site. Plasmablastic lymphoma (159 cases) was the most common histologic subtype, seen more frequently as a result of its strong association with HIV/AIDS. The most common Hodgkin’s lymphoma was the nodular sclerosing variant (21 cases). Of the head and neck lymphomas in patients with a known HIV status, 56% had plasmablastic lymphoma, 43.9% diffuse large B cell lymphoma and 25% Burkitt lymphoma. Conclusion There is an increase in head and neck lymphoma frequency, contrary to that found in Western countries. The high HIV prevalence in certain lymphomas provides strong indication of the role of HIV/AIDS in pathogenesis of lymphomas. This study serves as a baseline for future studies, especially in South Africa.

Minor salivary gland tumours represent 9–25% of all salivary gland tumours. South African epidemiological reports on minor salivary gland tumours are lacking. This study aims to evaluate the frequency, epidemiology and histology of minor salivary gland tumours in a defined South African population from 1997 to 2016. This cross sectional retrospective review of epithelial minor salivary gland neoplasms recorded patient demographic data: prevalence, age, gender, site, histology. There were 553 benign (57%) and malignant (43%) minor salivary gland tumours, in patients between the ages of 9 and 93 years. There was no significant age (p = 0.64) or gender (p = 0.18) difference between males and females. Common histologic types of salivary gland tumours in the continually evolving spectrum were pleomorphic adenoma (52%), adenoid cystic carcinoma (12%) and mucoepidermoid carcinoma (10%). Common sites were the palate (56%), cheek (11%), lip (9%) and paranasal sinuses (7%). Minor salivary gland tumours represent 2.3% of head and neck pathology. Although this prevalence is higher than reported, there is no overall increase in number diagnosed per year. Minor salivary gland tumours were more prevalent in females. Benign tumours occurred at a younger age than malignant tumours. This study serves as a baseline for future studies, especially in South Africa.

Aims Plasmablastic lymphoma (PBL) occurs mainly in immunocompromised individuals, usually secondary to human immunodeficiency virus (HIV) infection. It classically occurs intraorally, but has been described in extraoral locations. The aim of this study was to define the immunophenotype and Epstein-Barr virus (EBV) status in a large single-centre cohort of extraoral PBL (EPBL) in South Africa, a high-prevalence HIV setting. Methods and results This retrospective study of 45 EPBLs included patients' age, gender, race, HIV status, and site. Cases were reviewed histologically, and classified morphologically as pure plasmablastic or plasmablastic with plasmacytic differentiation, and assessed immunohistochemically with antibodies against CD45, CD20, CD79a, PAX5, CD138, MUM1/IRF4, BLIMP1, VS38c, Ki67, bcl-6, CD10, cyclin D1, and human herpesvirus-8, by the use of standard automated procedures. EBV was assessed by the use of chromogenic in-situ hybridisation. Tumours were assessed with a fluorescence in-situ hybridisation (FISH) MYC break-apart probe. Twenty-seven PBLs showed pure plasmablastic morphology, and 18 showed plasmacytic differentiation. The male/female ratio was 1.5:1. The anus was the favoured extraoral site (31.1%), followed by lymph nodes (15.6%). All 29 patients with known HIV status were HIV-positive. The immunohistochemical profile recapitulated that reported for oral PBLs and EPBLs in HIV-positive and HIV-negative patients. EBV was positive in 92.5% of PBLs. FISH analysis showed MYC rearrangement in 48% of cases. Conclusion This study showed a strong association of EPBLs with HIV and EBV infection, similarly to the previously described oral PBL. The strong EBV association together with other clinicopathological parameters and an immunohistochemical profile that includes CD45, CD20, MUM1/IRF4, CD138 and Ki67 may be used in distinguishing PBL from diffuse large B-cell lymphoma and plasma cell myeloma.

Professor Mervyn Shear made immense contributions to the discipline of Oral Pathology and indeed was the founder of the speciality in South Africa, holding the first Chair of Oral Pathology in the country. He graduated BDS from Wits in 1964, Neil to MDS (Oral Pathology) in 1961 and to the FRC (Pathology) from the Royal College of Pathologists in 1965. His passion for the discipline motivated his determination that Oral Pathology should be affiliated to Anatomical Pathology, a relationship which has ensured maximum exposure for South African registrars in Oral Pathology.

Salivary gland disease is a common manifestation of human immunodeficiency virus (HIV) infection, with a significant increase in prevalence over the last two decades. This review summarizes contemporary knowledge of non-neoplastic salivary gland disease in HIV infection. The aim is to update information on and bring attention to those lesions, which are almost exclusive to the salivary glands in the HIV setting. The associated conditions include xerostomia or salivary gland hypofunction; Sjogren syndrome-like illness; salivary gland enlargements, including benign lymphoepithelial cysts (cystic lymphoid hyperplasia); diffuse infiltrative CD8+ lymphocytosis syndrome; and mucous extravasation phenomena, especially ranula. Many of these conditions show considerable overlap, and thus, the term HIV-associated salivary gland disease is used to designate HIV infection with xerostomia or salivary gland hypofunction, enlargement of one or more of the major salivary glands, or both. These manifestations may be related to HIV infection, and therefore, prompt recognition is invaluable in the diagnosis and treatment of both the salivary gland disease and HIV infection.

AIMS AND OBJECTIVES: To determine the frequency and histomorphology of secondary Candida infection in oral HIV-associated Kaposi sarcoma (HIV-KS) and to describe the demographics of patients with oral HIV-KS with and without secondary Candida infection. MATERIALS AND METHODS: Haematoxylin and eosin, and periodic acid-Schiff stains of 32 oral HIV- KS were examined histologically for intensity and morphology of Candida colonisation, depth of invasion, number of organisms, epithelial reactions and inflammatory response. Depth of Candida invasion and severity of infection were correlated with CD4 T-cell counts of HIV-positive patients. RESULTS: Forty-one percent of oral HIV-KS were secondarily infected with Candida (n=13). Intensity varied from an isolated single pseudohyphus to matted colonies. Whilst in most cases, organisms did not invade beyond the parakeratin layer, pseudohyphae extended into stratum spinosum in two cases, and a single case showed a pseudohyphus within the lamina propria. Two cases showed pseudohyphae in the pyogenic membrane. Neutrophilic permeation of epithelium, commonly associated with Candida infection was frequently present even in absence of Candida infection CONCLUSION: Oral HIV-KS is commonly secondarily infected with large numbers of Candida organisms. Morphological characteristics of secondary Candida infection in surface epithelium of HIV-KS suggest an altered pathogenetic pathway. Further studies are indicated.

Objectives: The purpose of this retrospective study was to investigate differences between black and white persons with oral squamous cell carcinoma (OSCC) with regard to age, gender, oral site affected, and histopathological degree of differentiation; and to compare these clinicopathological parameters between persons younger and older than 40 years in a South African population sample from the greater Johannesburg area. Material and Methods: The histopathological reports of 510 cases of OSCC during the period 1995-2002 were retrospectively evaluated, and the data regarding age, gender, ethnicity/race, oral site affected, and degree of histopathological differentiation were recorded and statistically analyzed for differences between black and white persons, and between persons younger and older than 40 years of age. Results: Statistically significantly, black persons were diagnosed with OSCC at a younger mean age (57 years) than white persons (61 years) (P = 0.0086). The difference between male: female (M: F) ratio in black (3.74:1) and white persons (1.96:1) was statistically significant (P = 0.0041). White persons had a significantly higher proportion of SCC of the lower lip than black persons (P < 0.0001). Conclusion: OSCC was diagnosed at a younger age in black than in white persons; the proportion of black males in the black population group was greater than that of white males in the white population group; and the proportion of SCC of the lips was higher in younger than in older persons.

Our aim was to evaluate the histological association of mandibular solid and multicystic ameloblastoma with the inferior alveolar nerve, both in situ and in segments of the nerve that had been removed separately, to assess the feasibility of preserving the nerve during resection of mandibular ameloblastomas. In this prospective histological examination of 13 resected hemimandibulectomy specimens, we studied the proximity of tumour cells to the inferior alveolar nerve. In group 1 (n=8) this association was examined with the nerve still within the mandibular segment after resection, while in group 2 (n=5) the nerve was removed from the resected tumour and examined separately. Perineural and intraneural involvement of the ameloblastoma with the nerve was confirmed in 5 cases in group 1 and 2 cases in group 2. Tumour cells abutted the nerve directly in group 1. In group 2 tumour was removed with, and found within, the nerve. On this evidence we cannot recommend preservation of the inferior alveolar nerve during operation for large, advanced, mandibular ameloblastomas.

Human papillomavirus (HPV) infection, most commonly genotype 16 of the alpha-9 family, is implicated in the etiology of a subset of oropharyngeal squamous cell carcinomas (OPSC) worldwide. Data are scarce regarding OPSC in South Africans, and three prior studies suggest no significant etiologic role for HPV. We aimed to investigate for evidence of HPV etiology in OPSCs from black South Africans by polymerase chain reaction (PCR) methodologies with determination of HPV subtype by sequencing, in situ hybridization (ISH), and p16INK4a immunohistochemistry (IHC), as a surrogate marker for an HPV-driven tumor. It was hypothesized that HPV-driven tumors would be positive by PCR plus IHC and/or ISH whereas OPSCs with HPV background infections (HPV-passenger) would be positive by PCR alone. Formalin-fixed, paraffin embedded tissues from 51 OPSCs collected between 2005 and 2010 from 41 patients were analyzed for HPV by GP5?6? PCR (targeting the HPV L1 region), pU-1M/pU- 2R PCR (targeting the HPV E6/E7 region) and HPV-31 specific PCR (targeting the E5 region), chromogenic ISH, and p16INK4a IHC. All cases positive by PCR were subject to sequencing to determine HPV genotype. The patient mean age was 58.0 years and 88 % were male. Of the 51 evaluable tumors, 48 (94.1 %) were positive for HPV DNA by PCR: 25 (49.1 %) met criteria for an HPV-driven tumor, 23 (45.1 %) for HPV-passenger, and 3 (5.9 %) were HPV unrelated. Sequencing of the PCR-positive cases revealed the following genotypes: combined HPV-16 and 31 (41.7 %), HPV-31 (25.0 %), HPV-16 (22.9 %), combined HPV-16 and 18 (6.3 %), and a single case each of HPV 18 and HPV 33. Studies via ISH were negative in all cases. In accordance with worldwide trends but contrary to prior South African data, HPV likely plays an etiologic role in a significant subset (at least 49.1 %) of OPSC in black South Africans. We found that the alpha-9 HPV family, particularly HPV-16 and 31 either in combination or separately, to predominate in our sample tumors. The use of multiple PCR primers increased sensitivity of viral detection, and a HPV-31 specific primer confirmed the presence of this genotype in many samples. Further studies including HPV E6/E7 mRNA assays are needed to better elucidate the pathogenic role of HPV in black South African OPSCs.

Aims Cystic lymphoid hyperplasia (CLH) frequently affects the parotid gland in human immunodeficiency virus (HIV)-infected patients. This clinicopathological study, comprising 167 cases, aims to define the clinical–pathological parameters of CLH in order to elucidate the aetiopathogenesis. Methods and results This retrospective study of 167 archival cases of CLH recorded patients' age, race and gender, and the nature, site and symptoms of CLH. A total of 109 cases were reviewed histologically and analyzed for HIV-1 p24 antigen immunopositivity using standard procedures. CLH of the parotid gland showed a male predominance, whereas submandibular gland (P = 0.27) and bilateral parotid involvement favoured females (2:1). CLH occurred at a younger mean age in females than males in the parotid gland (P = 0.0035) and in the submandibular gland (P = 0.0032). Intra-lymph nodal origin was favoured, with 76.1% of cases occurring within entrapped salivary gland remnants. P24 staining revealed ~90% sensitivity in HIV-associated CLH. Conclusion CLH should be used preferentially to describe parotid enlargement in HIV-infected patients. This study strongly supports the hypothesis that CLH develops following ductal ectasia of entrapped salivary gland inclusions arising within lymph nodes. CLH should be classified as an orofacial lesion associated strongly with HIV and AIDS.

Context: Langerhans cells (LCs) are effective antigen-presenting cells that function as “custodians” of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections. Aims: To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection. Materials and Methods: Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals. Results: LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247). Conclusion: LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.

Objective The role of human papillomavirus (HPV) in keratinizing odontogenic cysts (OC) has only rarely been studied. We describe the clinicopathologic findings in a series of OCs that had unusual keratinization patterns and were investigated for a possible HPV etiology. Study Design Tissue samples from 29 patients with keratinizing OCs were studied for light microscopic features suggestive of HPV infection and by an HPV DNA polymerase chain reaction assay. Results The mean age at presentation was 31.1 years; 79.3% of the OCs occurred in the mandible and 46.4% were associated with an impacted tooth. The phenotypic characteristics koilocytes, hypergranulosis, and a verrucous pattern of the cyst-lining epithelium were observed in 69%, 62.1%, and 17.2% of cases, respectively. These histomorphologic features did not, however, correlate with HPV infection. Conclusions HPV does not appear to play a role in keratinizing OCs and is not responsible for the wart-like histomorphologic features that may be seen in these lesions.

Background Primary intraosseous salivary-type adenocarcinomas are rare neoplasms of uncertain histogenesis. The prevailing theories suggest origin from heterotopic salivary glands, odontogenic rests, or cystic epithelium. Methods A case of central adenoid cystic carcinoma is reported in a 53-year-old woman who presented with a painless swelling in the anterior segment of her lower jaw. Radiographic examination confirmed the presence of an expansile, radiolucent lesion within the mandible with a multilocular appearance. On light microscopy analysis, areas showing cribriform and tubular growth patterns; admixed cysts, some of which were characterized by the presence of localized plaque-like thickenings of their epithelial linings; and the formation of aberrant dental hard tissue were observed. Results The radiographic and histomorphologic findings highlight the potential misdiagnosis of this rare tumor. The findings also draw attention to an embryologic histogenetic concept for some central salivary neoplasms. Conclusion The divergent salivary and odontogenic differentiation evident in this tumor signifies the pluripotential nature of derivatives of oral ectoderm. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Superficial angiomyxoma is an unusual benign myxoid tumor of the trunk, head and neck, extremities, and genitalia. We report the third case of intraoral superficial angiomyxoma, which occurred within the buccal mucosa of a 37-year-old woman. The symptomless slow-growing mass was present for 2 years. The lobulated, paucicellular myxoid tumor showed prominent vascularity, stromal inflammation, including neutrophils, and immunopositivity for CD34, vimentin, and muscle-specific actin. Cure is effected by localized excision, with follow-up, owing to the high recurrence rate of the cutaneous tumors, which has not been substantiated for the few reported intraoral cases. Superficial angiomyxoma does indeed occur intraorally and should be included in the differential diagnosis of myxoid intraoral soft tissue neoplasms.

The introduction of bisphosphonates has increased in the last decade following their indication for metastatic bone diseases, osteoporosis, hypercalcaemia of malignancy and Paget’s disease. Although bisphosphonates have been used clinically for more than three decades there have been no documented long-term complications of their effects on the jaws until recently, where there is now growing evidence of the influence of bisphosphonates on osteonecrosis of the jaws. The aim of this paper is to report a case of this newly described complication, to review this phenomenon, including the clinical implications and to reiterate current clinical guidelines for management of patients in which bisphosphonate therapy is indicated. To the best of our knowledge this is the first reported case of bisphosphonate-induced necrosis of the jaw in South Africa.

The follicular variant of the adenomatoid odontogenic tumor (AOT) is thought to originate from the reduced enamel epithelium of the dental follicle. The origin of the extra-follicular variant however, remains less clear. This paper presents a case of an extra-follicular AOT, which we believe originated from the epithelial lining of a unicystic ameloblastoma, and reviews the literature. The available evidence seems to indicate that some extra-follicular AOTs might arise as secondary phenomena within pre-existing odontogenic cysts or cystic tumors.

BACKGROUND: Adenomatoid odontogenic tumour (AOT) is a benign odontogenic jaw lesion. The aim of this study was to update the biological profile of AOT. MATERIAL AND METHODS: Cases published in the literature and cases in files of co-authors were included. RESULTS: 550 new cases were retrieved, and of a total of 1082 cases analysed, 87.2% were found in the second and third decades. The M:F ratio was 1:1.9. 70.8% were of the follicular variant (extrafollicular: 26.9%, peripheral: 2.3%). 64.3% occurred in the maxilla. 60% of follicular AOTs were associated with unerupted canines. Nineteen cases of AOT (2.8%, M:F ratio was 1:1.4) were associated with embedded third molars. Twenty-two peripheral AOTs (2.3%, M:F ratio was 1:5.3) were recorded. The relative frequency (RF) of AOT ranged between 0.6% and 38.5%, revealing a considerably wider AOT/RF range than hitherto reported (2.2–7.1%). CONCLUSIONS: This updated review based on the largest number of AOT cases ever presented, confirms the distinctive, although not pathognomonic clinicopathological profile of the AOT, its worldwide occurrence, and its consistently benign behaviour.

Central granular cell odontogenic tumors are rare, with only 30 cases having been reported. The tumors usually occur in the mandibular molar area and are seen as localized painless swellings in patients older than 40 years. We report an additional case that occurred in the posterior mandible of an elderly black woman. All reported cases of this tumor are benign, and cure is effected by localized surgical excision. Ultrastructurally, the cells contain numerous lysosomes and phagocytic vacuoles. Immunohistochemically, the granular cells were positive for vimentin, CD68, muramidase, carcinogenic embryonic antigen, and bcl-2. These features support a mesenchymal origin with a possible histiocytic lineage for the granular cells. Awareness of the occurrence of this neoplasm is important to promote detection and differentiation from other intraoral granular cell lesions.

The head and neck region constitutes the second most common site of involvement for synovial sarcoma, accounting for up to 10% of all cases. Intraoral synovial sarcoma is rare; in fact, only 29 cases have been reported. We describe 2 additional cases occurring in the floor of the mouth and the retromolar area. In addition, we have reviewed the clinicopathologic features of the previously reported cases. Our findings indicate that intraoral lesions differ from lesions occurring in other sites only in that intraoral cases show a greater male predilection and a generally painless initial presentation. In the oral cavity, the possible earlier detection, easy accessibility, and small size render these tumors more likely to be amenable to surgical excision, but their biologic behavior remains aggressive, with a poor long-term prognosis. Awareness of the potential for the occurrence of this neoplasm in the oral cavity is important for effective histopathologic diagnosis of intraoral spindle cell malignancies.

Perineurioma is a rare benign peripheral nerve sheath tumour that occurs as an intraneural or extraneural form. To the best of our knowledge, this is the second reported case of an intraoral submucosal extraneural perineurioma. The tumour was symptomless, measured 2 cm in diameter and occurred in the nasolabial fold of a 46-year-old black female. Awareness of the occurrence of this neoplasm in the oral cavity is important to promote detection and differentiation from other benign spindle tumours, which occur intraorally. All reported cases of perineurioma have been benign and cure is effected by localized surgical excision.

Accessory salivary gland tissue is found in many sites throughout the head and neck region, including centrally within the maxilla and mandible. 1,2 Neoplastic transformation of the salivary gland tissues in particular is a known, albeit uncommon, phenomenon. 3-9 A comprehensive literature review by Bouquot et al 10 of salivary gland tumors within the jaw yielded 224 cases, which comprised mainly mucoepidermoid carcinomas (76.7%). In the latter study, benign and malignant pleomorphic adenomas accounted for 12 cases (5.4%), but neither myoepitheliomas nor myoepithelial carcinomas were diagnosed. The mandible is the most common anatomic site for intraosseous salivary neoplasia, accounting for 75% of all cases. 11 Myoepithelial cells may be found as a component of several different salivary gland tumors. These include adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and epimyoepithelial carcinoma. However, they assume a dominant role in the development of myoepitheliomas, myoepithelial carcinomas, and pleomorphic adenomas. The goal of this paper is to report 5 cases of intraosseous maxillary myoepithelial cell-derived neoplasms, because they pose special diagnostic and therapeutic considerations. These cases include 3 cases of intraosseous myoepitheliomas and 2 cases of myoepithelial cell-predominant pleomorphic adenoma. Myoepitheliomas have not been reported in an intraosseous location. A single case of myoepithelial carcinoma was documented in the maxilla, but in that case the tumor actually arose in the maxillary sinus. 12 .

Background: Cystic lymphoid hyperplasia (CLH) describes benign salivary lymphoepithelial cysts with a strong link to human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The pathogenesis is related to ductal dilatation of entrapped salivary elements due to intranodal HIV-associated atypical lymphoid hyperplasia. Very little is known about the immunophenotypic profile of this entity. Aim: This study aims to describe the immunopathological features of a series of CLH cases in HIV-positive patients to clarify the etiopathogenesis. Materials and Methods: Paraffin-embedded tissue from 25 cases of parotid CLH in HIV seropositive patients was immunohistochemically analyzed with CD3, CD20, CD4, CD8, and p24 using standard procedures. Statistical Analysis: The data are mostly descriptive and were analyzed using EpiInfo (3.5.1) (CDC, Atlanta, USA); significant differences were analyzed using the Student's t-test and the Chi-square test with a statistical significance level of P < 0.05 being used. Results: Immunostaining showed a CD8:CD4 of ~1:1 except in selected cases with decreased CD4 and increased CD8 expression in the interfollicular (IF) areas. p24 staining revealed 100% specificity in HIV-associated CLH. Conclusion: The immunohistochemical description of CD20, CD3, CD4, and CD8 provides an understanding of CLH pathogenesis. CLH of parotid lymph nodes in confirmed HIV-positive patients with 100% specificity with HIV p24 antibody validates the strong association of CLH with HIV and AIDS. The CD4:CD8 ratio was ~1:1; however, increased CD8 expression within IF areas may indicate possible HIV-related CLH as compared to other cystic parotid lesions.

Background:Oral mucosal melanoma (OMM) is relatively rare, runs an aggressive course, affects most frequently the hard palate and the maxillary gingiva, and may be multifocal. The aetiological factors and the chain of molecular events that give rise to OMM and to its growth and metastasis are largely unknown.Objectives:The purpose of this retrospective study was to characterize some clinical and histopathological features of OMM in a South African sample.Materials and Methods:The histopathological reports and histological sections of 17 cases with OMM during the period 1968–2013 were retrospectively evaluated, and the data regarding age, gender, ethnicity/race and the histopathological patterns were recorded. c-Kit immunohistochemical staining was performed.Results:OMM most frequently affected the palate and the maxillary gingiva of black persons without gender predilection. The age of the patients ranged from 20 to 78 years with the mean age at diagnosis being 56 years. Most tumours were nodular comprisi...

OBJECTIVE: This study analysed differences in clinicopathological features of oral leukoplakia in different racial groups in the greater Johannesburg area of South Africa, with emphasis on the black population. MATERIAL AND METHODS: The retrospective review included cases diagnosed clinically as oral leukoplakia and histologically as hyperkeratosis without dysplasia, hyperkeratosis with mild, moderate or severe dysplasia, and carcinoma in situ from 1990 to 2010. Age, gender, ethnicity, clinical appearance, site of lesion and tobacco smoking habit were recorded. RESULTS: Fourteen per cent of oral leukoplakia occurred in black South Africans compared with 80% in white South Africans. In contrast to whites, blacks were diagnosed with oral leukoplakia at a younger age; there were more men affected than women; and the proportion of idiopathic leukoplakia was greater. There were significantly more blacks (23%) than whites (13%) with non-homogenous leukoplakia and significantly more whites (51%) than blacks (23%) with dysplastic oral leukoplakia. CONCLUSION: This study suggests that oral leukoplakia, especially non-homogenous and idiopathic forms affects South African blacks less frequently than white South Africans; and in the former, it occurs more in men and at a younger age. These findings may provide some guidance in establishing screening policies for oral cancer, particularly suited for blacks. Oral Diseases (2012) doi:10.1111/odi.12040

Aims. To evaluate the immunohistochemical expression of bcl-2 and c-kit proteins in the salivary gland tumors, adenoid cystic carcinoma, and polymorphous low-grade adenocarcinoma with a view to tumor differentiation. Methods. Immunohistochemical studies were performed on 29 adenoid cystic carcinoma and 23 polymorphous low-grade adenocarcinoma archival cases with bcl-2 and c-kit antibodies using standard procedures, and the data were statistically analyzed. Results. The difference in bcl-2 expression in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma was not statistically significant. Whilst the difference in c-kit expression was statistically significant (), the difference proved small so as to be of no practical or diagnostic importance. Moderate to strong immunostaining was noted in adenoid cystic carcinoma with c-kit, the pattern and intensity varying within different histological subtypes, being greater the more aggressive the tumor subtype. Conclusions. Bcl-2 and c-kit are not useful as immunohistochemical markers in differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma.

Clinical PresentationA 31-year-old female patient presented with a swollen eye(Fig. 1). Intraoral examination showed a necrotic ulceratedlesion extending from the midline involving the buccalsulcus over the right central and lateral incisors (teeth 7 and8) (Fig. 2). The CT scan showed an erosive mass anteriorto the ethmoid cells and an opacified maxillary sinus. Thepatient is HIV negative.Differential DiagnosisImportant clinical features from the clinical photos (Figs. 1and 2) and history include:• an ulcerated intraoral tumor in the right anterior maxillaextending to the right buccal sulcus• an avascular, possibly necrotic socket of the rightmaxillary central incisor (tooth 8) with no evidence ofalveolar bone destruction, features suggestive ofischemic change and exfoliation of the central incisor(tooth 8)• tumor tissue in the maxillary and ethmoidal sinuses• periorbital swelling around the left eye suggestive oftumor infiltration or cavernous sinus thrombosis• skin ulceration suggestive of ischemic changesThese features are suggestive of an infective or neo-plastic process affecting a large area of the maxilla,crossing the midline, with bone and soft tissue involve-ment, and showing an affinity for blood vessels. Theclinical differential diagnosis includes mid-facial necro-tizing granulomatous diseases, deep fungal infections,primary intraoral neoplasms, maxillary sinus neoplasmsand the so-called midline tumors.Mid-facial necrotising granulomatous diseases includediseases such as Wegener’s granulomatosis, leprosy, sar-coidosis and tuberculosis. These conditions may presentwith skin lesions and oral ulceration but are seldom asso-ciated with ulcerative ‘‘tumors’’ or periorbital swelling.Deep fungal infections such as zygomycosis, aspergil-losis and histoplasmosis must be excluded. Zygomycosisremains a prime consideration as it has a known affinity forblood vessels resulting in thrombus formation and associ-ated ischemic necrosis. Oral ulceration and periorbitalswelling are common features. Patients frequently presentwith a short history of symptoms and are often uncon-trolled diabetics. Intraoral tumor formation however is nota common presentation.The clinical presentation of intraoral necrotic ulcerationaccompanied by paranasal sinus involvement and perior-bital swelling are highly indicative of malignant disease.Of the wide spectrum of primary intraoral malignancies,squamous cell carcinoma or salivary gland carcinomasshould be foremost considered. This patient is relativelyyoung and furthermore the hard palate is a relativelyuncommon site for a squamous cell carcinoma. The intra-oral site is more compatible for a salivary gland

Sclerosing polycystic adenosis (SPA) is a rare lesion of salivary glands with a striking resemblance to fibrocystic disease of the breast. Most of the 47 reported cases have occurred within the parotid gland, with only a single case being described within the buccal mucosa. We report an additional case of SPA of the buccal mucosa. The exact nature of this entity is unknown, but has up until recently believed to be a pseudoneoplastic reactive and inflammatory sclerosing process. Even though SPA has satisfied the criteria for monoclonality, the debate as to whether SPA represents a true neoplasm or a pseudoneoplastic inflammatory sclerosing process, with low-grade neoplastic potential continues. Awareness of the occurrence of this lesion in both major and minor salivary glands is important to promote its differentiation from other more sinister salivary gland pathology. Cure is effected by localized surgical excision and all reported cases of SPA show an excellent prognosis with no true recurrence or metastasis.

Adenomatoid odontogenic tumour (AOT) is a benign odontogenic jaw lesion. The aim of this study was to update the biological profile of AOT.Cases published in the literature and cases in files of co-authors were included.550 new cases were retrieved, and of a total of 1082 cases analysed, 87.2% were found in the second and third decades. The M:F ratio was 1:1.9. 70.8% were of the follicular variant (extrafollicular: 26.9%, peripheral: 2.3%). 64.3% occurred in the maxilla. 60% of follicular AOTs were associated with unerupted canines. Nineteen cases of AOT (2.8%, M:F ratio was 1:1.4) were associated with embedded third molars. Twenty-two peripheral AOTs (2.3%, M:F ratio was 1:5.3) were recorded. The relative frequency (RF) of AOT ranged between 0.6% and 38.5%, revealing a considerably wider AOT/RF range than hitherto reported (2.2-7.1%).This updated review based on the largest number of AOT cases ever presented, confirms the distinctive, although not pathognomonic clinicopathological profile of the AOT, its worldwide occurrence, and its consistently benign behaviour.

Aims: To evaluate cytokeratin (CK) 7/20 expression patterns in salivary gland neoplasia. Methods and results: Formalin-fixed paraffin embedded tissue from 153 salivary gland tumours were evaluated for CK7/20 immunoreactivity. The tumours included pleomorphic adenoma (n = 24), myoepithelioma (n = 9), papillary cystadenoma (n = 3), oncocytoma (n = 2), adenoid cystic carcinoma (n = 22), mucoepidermoid carcinoma (n = 21), polymorphous low-grade adenocarcinoma (n = 21), carcinoma ex-pleomorphic adenoma (n = 11), acinic cell carcinoma (n = 17), epimyoepithelial carcinoma (n = 7), oncocytic carcinoma (n = 3), hyalinizing clear cell carcinoma (n = 1), papillary cystadenocarcinoma (n = 1), salivary duct carcinoma (n = 3), adenocarcinoma (not otherwise specified) (n = 4) and squamous carcinoma (n = 4). Immunohistochemical procedures were performed using monoclonal antibodies CK7 (OV-TL 12/30), CK20 (Ks 20.8) and M3515 cytokeratin (AE1/AE3) in the presence of appropriate controls. The results were expressed semiquantitatively, according to the estimated percentage of positive tumour cells: 1+, 5–25%; 2+, 26–75%; and 3+, 76–100%. All salivary gland neoplasms showed a CK7+/CK20– immunoprofile ranging from 5 to 100%. Squamous carcinoma showed negative CK7/20 immunoexpression. Conclusions: Although the CK7/20 immunoprofile is not useful in distinguishing the various types of salivary gland neoplasms or between benign and malignant salivary gland tumours, it may facilitate differentiation of primary salivary gland neoplasia from metastatic tumours and squamous carcinoma, and the diagnosis of metastatic salivary gland tumours.

Objectives: The aim of this study was to investigate the potential use of E-cadherin, a tumour-suppressor gene product involved in establishing cell–cell adhesion and one of its associated proteins, β-catenin, as markers of nodal metastasis in oral squamous cell carcinoma (OSCC). Materials and methods: Thirty invasive OSCCs in patients with (n = 19) and without (n = 11) nodal metastases, as confirmed on histopathologic examination of the resected regional lymph nodes (n = 30), were examined for E-cadherin and β-catenin expression by immunohistochemistry. Results: There was a highly significant association (P

Information on histopathological changes within sinus mucosa is lacking, both in the general population, and in subjects with specific facial morphology and chronic respiratory obstruction.To provide baseline data of the frequency and nature of pathological changes in the maxillary sinus in a specified group of patients.119 patients undergoing elective maxillary osteotomies were selected. These included patients with (70) and without (49) vertical maxillary excess (VME), and mouth and nasal breathers. The frequency and nature of the histopathological changes within the maxillary antral lining were recorded.Patients ranged from 13 to 47 years, with a M:F ratio of 1:2.4. The findings included congestion (95%), submucosal oedema (90%), retention cysts (26%), true polyps (4.6%) and inflammation. There was eosinophilia (68%), basement membrane thickening (28%), goblet cell hyperplasia (95%) and dystrophic calcification (59%).A significant degree of sinus pathology was found in this specified group of patients. This was probably due to their living in a polluted urban environment. In the presence of such widespread pathological changes and the virtual impossibility of obtaining "normal" control tissue, investigators may find it impossible to correlate maxillary sinus pathology with either facial form or breathing pattern.

Herpes zoster is a common viral infection, the oral soft tissue manifestations of which are widely known and recognized. Reports of spontaneous tooth exfoliation and jaw osteonecrosis following herpes zoster infection in the distribution of the trigeminal nerve are extremely infrequent and sporadic, with only 39 cases being reported in the literature. We report an additional case of mandibular osteomyelitis and spontaneous tooth exfoliation following herpes zoster infection, which occurred in the left mandible of a 70-year-old diabetic man; however, our case also showed CMV co-infection. The role of CMV in the pathogenesis of the osteonecrosis remains uncertain. Awareness of the possibility of CMV co-infection in various oral diseases including oral ulcers, Kaposi's sarcoma, and herpes zoster infections especially in immunocompromised patients is important, since spread of the CMV can easily occur to other sites with potentially fatal consequences. Early diagnosis can lead to effective treatment and prevention of complications.

Objective. This study used proliferating cell nuclear antigen (PCNA) and Ki67 to evaluate and compare the in situ proliferative activity of (1) solid and multicystic and (2) unicystic ameloblastomas in an attempt to provide a scientific basis for any differences in biologic behavior that exists between these 2 groups of lesions. Study design. Twenty archival tissue sections, 10 of primary unicystic and 10 of solid and multicystic ameloblastomas, were immunohistochemically stained with PCNA and Ki67 antisera. Immunoreactivity was evaluated by the counting of cells, and the data obtained were statistically analyzed. Results. The results showed that cellular proliferative activity varied within the ameloblastoma types. The unicystic ameloblastomas showed statistically significantly higher PCNA and Ki67 labeling indices than the solid and multicystic variant. Conclusion. There appears, therefore, to be no correlation between proliferative activity as shown by these proteins and reported biologic behavior. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:213-21)