Delayed adverse reaction to a natural dermal filler mimicking salivary gland neoplasia.

Background: Cosmetic dermal fillers are a sought-after procedure globally. However, despite the safety claims of filler materials by the manufacturers, adverse reactions still occur. Case presentation: This case report is of a 66-year-old female who presented with a late-onset complication of a hyaluronic acid dermal filler that clinically mimicked a salivary gland neoplasm. The patient presented with firm peri-oral swellings of short duration that clinically mimicked a pleomorphic adenoma and mucoepidermoid carcinoma. The diagnosis was that of a foreign-body granulomatous response to dermal fillers. Although other mimics of a similar nature are reported a knowledgeable clinician, careful choice of filler material, knowledge of the product, thorough pre-procedural history taking and post-procedural patient follow-up can drastically minimize a possible misdiagnosis. The reaction was treated with a combination of hyaluronidase, betamethasone and 5-flurouracil intra-lesional injections monthly for 11 consecutive months, with total clinical resolution. Conclusions: Patient education of the procedure, product name and the possibility of an adverse reaction occurring, even years later or at a site distant to the initial site of placement, is vital. Further, we review the recent reported adverse association of the new mRNA COVID-19 vaccines and dermal filler placement.

Ectomesenchymal Chondromyxoid Tumor: A Rare Association With an Asymmetrical Soft Palate Cleft.

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.

Oral versus extra-oral plasmablastic lymphoma: A comparative analysis of 101 cases.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Genomic characterization of HIV-associated plasmablastic lymphoma identifies pervasive mutations in the JAK-STAT pathway.

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.

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area.

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.

Primary Epithelial Minor Salivary Gland Tumors in South Africa: A 20-Year Review.

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.

Human immunodeficiency virus and salivary gland pathology: an update.

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; Sjögren 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.

Human immunodeficiency virus-associated cystic lymphoid hyperplasia: An immunohistochemical description.

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.

Head and neck lymphomas: A 20-year review in an Oral Pathology Unit, Johannesburg, South Africa, a country with the highest global incidence of HIV/AIDS.

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 40.4years. 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.

Keratinizing odontogenic cysts with a spectrum of verrucoid morphology: investigation of a potential role of human papillomavirus.

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.

Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis.

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.

Evidence that alpha-9 human papillomavirus infections are a major etiologic factor for oropharyngeal carcinoma in black South Africans.

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.

Cystic lymphoid hyperplasia: an orofacial lesion strongly associated with HIV and AIDS.

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.

Perineural infiltration of the inferior alveolar nerve in mandibular ameloblastomas.

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.

Central adenoid cystic carcinoma of the mandible with odontogenic features: Report of a case.

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.

Intraoral superficial angiomyxoma.

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.

Sclerosing polycystic adenosis of the buccal mucosa.

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.

An updated clinical and epidemiological profile of the adenomatoid odontogenic tumour: a collaborative retrospective study.

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.