Sachin C. Sarode

Plasmablastic lymphoma of the oral cavity: A review

Plasmablastic lymphoma (PBL) is a rare AIDS associated non-Hodgkins lymphoma (NHL), with predilection for the mucosa of oral cavity. It usually has a plasmablastic morphology, expressing plasma cell-associated antigens with weak or no expression of B-cell associated markers. The tumor cells also show monoclonal rearrangement of the immunoglobulin heavy chain gene (IgH) and/or clonal restriction of Ig light chain (IgL) gene expression in most of the cases. An etiological role for EBV seems likely but the association with HHV8 is questionable. The treatment guidelines for PBL are not well defined and patients have been treated heterogeneously with chemo and/or radiotherapy, although the prognosis is poor. The present article discusses the 68 cases reported in English medical literature with comprehensive review on PBL involving the oral cavity.

Abfraction: A review

Abfraction (AF) is the pathological loss of tooth substance caused by biomechanical loading forces that result in flexure and failure of enamel and dentin at a location away from the loading. The theory of AF is based primarily on engineering analyses that demonstrate theoretical stress concentration at the cervical areas of the teeth. However, the theory is not yet proven and there are explanations against it. AF lesions present primarily at the cervical region of the dentition and are typically wedge-shaped, with sharp internal and external line angles. Diagnosis of AF plays a very important role in the management of patients. The aim of the present narrative review is to comprehensively discuss the historical, etiopathogenetic, clinical, and diagnostic and treatment aspects of AF.

Complex cannibalism: an unusual finding in oral squamous cell carcinoma.

Cellular cannibalism, defined as a large cell enclosing a slightly smaller one within its cytoplasm is a characteristic morphologic feature exclusively seen in aggressive malignancies. It was first described by Leyden in 1904 and he called them ‘‘bird-eye cells’’. They were also called as ‘‘signet-ring cells’’, owing to their appearance. This phenomenon of ‘‘tumor cell within a tumor cell’’ is frequently seen in vivo in different types of cancers; it has, for instance, been referred to as ‘‘cellular phagocytosis’’, ‘‘cell phagocytosis’’, ‘‘cell in cell appearance’’, ‘‘cell in cell pattern’’, ‘‘one cell delicately wrapped around the next’’, ‘‘phagocytosis of tumor cell by tumor cell’’, and ‘‘tumor cell embraced by another tumor cell’’. The fact, although often ignored, that ‘‘cannibalism’’ is commonly observed in vivo suggests that this phenomenon may represent a general growth behavior of tumor cells. The acidic microenvironment which is created in carcinogenesis due to a shift in the metabolic pathway encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. These selected malignant cells are highly virulent and cannibalize/engulf their siblings as well as cells from the immune system in order to sustain and progress in adverse conditions within the microenvironment such as hypoxia, starvation (low nutrient supply) and acidity. The mechanism underlying cannibalism involves a complex framework, wherein lysosomal proteases, cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function have a role to play. Cannibalism, as an indicator of reverse evolution of cancer, represents an additional tool of spite (adaptive strategy) of the malignant cells. Other forms of cell eating such as phagocytosis, entosis, emperipoleosis and autophagy may mimic malignant cannibalism. Hence, proper interpretation skills are required for the detection of cannibalism. Cell cannibalism is an important morphologic feature to distinguish benign from malignant lesions. Cannibalism has been described previously in breast carcinoma, giant cell carcinoma of lung, gall bladder carcinoma, endometrial stromal carcinoma, malignant thymoma, malignant melanoma etc. and is correlated well with the aggressiveness, degree of anaplasia, invasiveness and metastatic potential of the malignancy. Demonstration of an increased number of cannibalistic cells may also be helpful in grading breast carcinoma. In oral squamous cell carcinoma (OSCC), there are several wellrecognized histological prognosticators like grade of the tumor, histological subtyping/categorization, tumor border being either infiltrative or more pushing, perineural invasion, lymphovascular invasion, bone involvement, sialoadenotropism/ductal invasion etc. Similarly, cannibalism could also be a significant histopathological prognosticator which will aid in predicting the grading,

Plasmablastic lymphoma of the oral cavity in an HIV-positive patient: a case report and review of literature

Plasmablastic lymphoma (PBL) of the oral cavity is an uncommon, recently described B-cell derived lymphoma that is most commonly seen in patients with human immunodeficiency virus (HIV) infections. The authors report a rare case of PBL in the oral cavity of a 40-year-old man with HIV. The lymphoma cells were positive for leukocyte common antigen, CD79a, CD138, Epstein-Barr virus (EBV) and kappa light chain restriction and negative for CD20, CD3, S100, HMB45 and cytokeratins. The lesion regressed after treatment with local radiotherapy and systemic chemotherapy. The features of this rare disease are summarized based on a comprehensive review of the epidemiological, clinical and immunohistochemical findings of previously reported cases.

Better grade of tumor differentiation of oral squamous cell carcinoma arising in background of oral submucous fibrosis

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. Most of the people affected by OSMF are betel quid chewers. It is characterized by epithelial atrophy and progressive accumulation of collagen fibers in lamina propria and submucosa of the oral mucosa. 7.6% of OSMF cases undergo oral squamous cell carcinoma (OSCC) transformation of which majority display low grade of tumor differentiation. In the present paper, a hypothesis has been proposed to correlate atrophy, turnover rate and surface keratization in OSMF with degree of tumor differentiation in OSCC. A novel hypothesis for epithelial atrophy in OSMF has also been emphasized. High proliferative activity and basal cell hyperplasia in conjunction with rapid exfoliation of superficial cells and epithelial atrophy suggest that epithelial turnover rate is very high in OSMF. Presence of surface keratinized layer in this situation suggests faster maturation or differentiation of epithelium in OSMF. Thus, the epithelial cells are genetically programmed for high turnover rate and faster differentiation or maturation to form keratin. During malignant transformation of OSMF, the transformed epithelial cells may retain the genetic memory of faster differentiation and maturation resulting in better grade of tumor differentiation. The well differentiated OSCC has good prognosis, better survival rate and less chances of recurrence of regional and distant metastasis. Studies are needed to explore the biomarkers or molecular markers associated with carcinogenesis like genetic instability, oncogenes, tumor suppressor genes and angiogenesis in OSCC associated with OSMF. If investigated in the suggested direction, it might provide some important clues about the pathogenesis of OSCC arising in background of OSMF and for the future development of treatment strategies.

Cellular cannibalism in central and peripheral giant cell granuloma of the oral cavity can predict biological behavior of the lesion

BACKGROUND Cancer cannibalism is used to differentiate benign tumors from malignant, but recently the phenomenon has been demonstrated in giant cell tumor of tendon sheath (localized type). Microscopically and pathogenetically, this tumor is similar to central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG) of oral cavity. Hence, attempt has been made to study the cannibalistic giant cells (GCs) in CGCG and PGCG with their correlation with the biological behavior. METHODS Surgically treated 16 CGCG and 23 PGCG cases with adequate clinical and radiographic documentation were selected. Quantification of cannibalistic GCs was performed using routine HE stain. Hundred GCs were examined in each section, and number of cannibalistic cells was expressed in percentage. Ten cases were randomly selected for further immunohistochemical analysis with CD68 and bcl-2. RESULTS Cannibalism was found in all the cases (100%). The frequency of occurrence of cannibalistic GCs ranged from 20% to 56% with a mean of 33.62 ± 8.9. CGCG showed significantly higher mean cannibalistic GC frequency (38.06 ± 10.15) than PGCG (30.04 ± 5.63). In aggressive CGCG, mean cannibalistic GC frequency was significantly higher (42.20 ± 10.4) than non-aggressive type (31.17 ± 6.014). Similarly, recurrent cases showed significantly higher mean cannibalistic cell frequency (43 ± 6.26) than non-recurrent cases (30.81 ± 6.66). Immunohistochemistry results showed histiocytic nature of GCs as well as mononuclear cells. The internalized cells did not expressed bcl-2, suggesting that the internalization induces apoptotic cell death. CONCLUSION Assessment of frequency of cannibalistic cells in CGCG and PCGC could help in predicting the biological behavior of the tumor.

Why only areca nut chewing cannot cause oral submucous fibrosis

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral cavity. Most of the affected people are betel quid chewers. Although, betel quid is consumed in various forms, only areca nut chewing habit has become very rare. We came across 34 such cases with 32 showing no evidence of OSF. Therefore, we hypothesize that only areca nut chewing cannot cause OSF and presence of other factors like slaked lime and inflammation is necessary. Keeping in mind the composition of areca nut, hypothesis is comprehensively discussed at molecular level in the present paper with special emphasis on the role of TGF-beta and lysyl oxidase enzyme in OSF. If investigated in the suggested direction, it might provide an important clue about the pathogenesis of OSF and thus can help in the future development of treatment strategies.

Oral potentially malignant disorders: A proposal for terminology and definition with review of literature.

Several attempts to produce internationally accepted terminologies and definitions of ‘oral precancer’ have appeared in the literature. World Health Organizations (WHO) in 1972 subdivided ‘precancer’ into ‘lesions’ and ‘conditions’ with their definitions. Recent working group of WHO is not in favor of such subdivision and recommended the use of the term ‘oral potentially malignant disorder (OPMD)’. This is mainly attributed to the recent advancement in molecular and genetic aspects of ‘oral precancer’. But efforts to define OPMDs are few in the literature. ‘Oral precancer’ is ultimately colligated to oral squamous cell carcinoma (OSCC). With this semantics in mind, different OPMD and related terminologies in the literature used till date with their lexicographic analysis have been reviewed in the present paper. Attempt has also been made to propose desirable terminology and definition which suits to the current concept of OPMD. The proposed terminology and definition is based on the authors’ opinions with a hope for further suggestions from readers.

Neutrophil-tumor cell cannibalism in oral squamous cell carcinoma

BACKGROUND Cannibalism was recognized as a phenomenon seen mainly with the tumor cells ingesting other tumor cells. Recent reports have shown tumor cell engulfing other cells (xeno-cannibalism) as well, such as neutrophils, lymphocytes and erythrocytes. But no such finding has been reported in oral squamous cell carcinoma (OSCC) in the literature till date. OBJECTIVE Retrospective histopathological analysis of OSCC for identification of neutrophil-tumor cell cannibalism (NTCC) and its correlation with clinico-pathological parameters. METHODS The hematoxylin and eosin stained tissue sections of 500 OSCC cases were thoroughly screened at high power magnification (400X) for NTCC. Cases showing only frank NTCC were selected. Cases were subjected to immunohistochemical analysis using CD68 and lysozyme. RESULTS Seven (1.4%) cases of OSCC which showed classical features of extreme NTCC on histopathological examination. Seventeen Cases (3.4%) showing occasional isolated NTCC were excluded. All the cases were poorly differentiated and showed cervical lymph node metastasis. Immunohistochemical analysis showed mild (+) to moderate (++) positivity in tumor cells for CD68 and lysozyme markers. CONCLUSION NTCC in OSCC can predict the biological behavior and could serve as a useful prognostic marker in future. Tumor cell displaying macrophage phenotype and cell digestion could be mediated through lysosomal enzyme activity.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinico‐pathological entity with better prognosis

BACKGROUND The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). METHODS A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. RESULTS The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. CONCLUSION The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients.