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RARE INTRAORAL CONGENITAL MELANOTIC NEVUS - A CASE REPORT
ORAL AND MAXILLOFACIAL PATHOLOGY e220 Abstracts cytological examination, buccal squamous cells demonstrated binucleation (89%), micronuclei (86%), prominent nucleoli (67%), karyorrhexis (45%), karyolysis (47%), pleomorphism (28%) and anucleated squames in (42%). Mild acute and chronic inflammation (59%) with inflammatory (24%) and non-inflammatory (4%) atypical changes in keratocytes were observed. However, only one patient had fungal hyphae on cytology. Glossitis was associated with nuclear pleomorphism (p¼0.059), prominent nucleoli (0.000) and inflammatory atypia (p¼0.006). However, no statistical association was observed between duration of disease and these variables. Conclusions: Immune mediated diseases cause various changes on tongue ranging from inflammation to atypical epithelial morphology. However these changes were not significantly associated as the disease process advances.
PROGNOSTIC VALUE OF MX1 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA. C. DONNELLY, L. DONNELLY, Y. XIE, OKEMOS E. BELLILE, G. WOLF, Y. LEI. UNIVERSITY OF MICHIGAN, ANN ARBOR AND MICHIGAN STATE UNIVERSITY. Objectives: Evidence gleaned from recent clinical studies suggests that an intact anti-tumor immune response is indispensable for patient response to adjuvant therapy. Type I Interferon (IFN-I) signatures have rapidly emerged as central regulators of the immune microenvironment of cancer. Hence, we explored whether an IFN-I signature MX1 can be utilized to predict patient clinical outcome. Materials: Primary Head and Neck Squamous Cell Carcinoma (HNSCC) specimens were procured from 74 patients with a maximal follow-up of 85.9 months. We produced an HNSCC tissue microarray with 3 cores per specimen. We then stained sections of 5mm thickness with an anti-MX1 antibody. MX1 staining densities within cancer cells were quantitated using Aperio ImageScope. Conclusion: Among the enrolled patients, 28% had early stage (I-II) cancer, and 72% presented with stage III or IV cancer. HNSCC exhibited a spectrum of MX1 staining density. We observed a statistically significant association between MX1 immunohistochemical staining scores and overall patient survival, using the median MX1 score to separate the patients into two groups (p ¼ 0.003). This finding suggests that cancer autonomous IFN-I signaling plays a critical role in the patient clinical outcome. Our ongoing multivariate analysis will provide insight into the mechanism underpinning the MX1-mediated difference in patient survival.
PSEUDOSARCOMATOUS MYOFIBROBLASTIC LESIONS OF THE ORAL CAVITY. S. WETZEL, S. BUDNICK, S. MULLER. ATLANTA ORAL PATHOLOGY, ATLANTA, GA. Myofibroblastic lesions of the oral cavity can vary greatly in their histologic appearance. Occasionally, lesions of myofibroblastic origin can exhibit aggressive histologic features such as brisk mitotic activity and extension into underlying skeletal muscle and adipose tissue. Such cases can present a diagnostic challenge and can be aided by immunohistochemical (IHC) studies along with key morphological features to arrive at the appropriate diagnosis. The following is a discussion of two such cases. The first example presented as an exophytic lesion
OOOO September 2017 of the left dorsum of the tongue in a 73-year-old male. Histologically, the lesion was highly cellular, exhibited a moderate mitotic rate and showed extension into underlying skeletal muscle and adipose tissue. The lesional cells were focally positive for smooth muscle actin (SMA) and desmin by IHC, showed retention staining for retinoblastoma 1 (RB1) and was negative for CD34. The lesion was classified as a cellular fibrous histiocytoma. The second case also occurred on the tongue and presented in a 23-year-old female patient. Microscopically, this lesion was composed of mitotically active myofibroblasts set in a myxoinflammatory stroma. By IHC the lesion was positive for ALK and SMA but negative for keratin markers. Based on the histologic and IHC findings the lesion was diagnosed as a pseudosarcomatous myofibroblastic proliferation. Reactive and benign neoplastic myofibroblastic lesions can exhibit features suggesting malignancy, which can lead to misdiagnosis and mismanagement. The aim of this study was to examine and provide a discussion of two such cases and to illustrate how the IHC profile along with the overall morphology of the lesion can lead to the appropriate diagnosis of these challenging cases.
RARE INTRAORAL CONGENITAL MELANOTIC NEVUS - A CASE REPORT. A. SALCINES, S.B. WOO, V. NOONAN, M. MANSFIELD, C.C. LI. HARVARD SCHOOL OF DENTAL MEDICINE, BOSTON, MA; CENTER FOR ORAL PATHOLOGY, STRATADX, LEXINGTON, MA; AND PRIVATE PRACTICE, GLENDALE, AZ. Objective: Congenital melanocytic nevus (CMN) consists of a benign proliferation of melanocytes at birth or shortly after birth. CMN is not an uncommon entity on the skin, and it possesses increased risk of developing melanoma. While the cutaneous counterpart is common, intraoral CMN is extremely rare. There are only five well-documented case reports in the English literature, and here we present one case of an intraoral CMN. Clinical Presentation: A 9-year-old Caucasian female presented with a rapidly expanding mass on the right hard and soft palate, measuring 2 1.5 0.3 cm. The lesion was covered by normal oral mucosa, and presented as a well-circumscribed, non-tender, firm mass. There was no gross pigmentation and no palpable lymphadenopathy. Computed topography images showed no bone involvement. Intervention and Outcome: The mass was removed and evaluated histopathologically; margins were positive. Three years after the excision, there was a recurrence; re-excision was performed. Both specimens showed a dense diffuse infiltrate of small epithelioid melanocytes in the lamina propria with involvement of the vessel walls. The melanocytes arranged in clusters, theques or bands, streaming through collagen bundles with occasional melanin deposition. Cellular atypia or mitosis was not identified. The overlying oral mucosa exhibited slight papillomatosis with junctional activity. The majority of the melanocytes in the lamina propria were positive for MART-1 and p16, with a small population of HMB-45 positive cells within the superficial and junctional components. MIB-1 positivity was low (< 5%). No recurrence was reported at 1 year follow-up.
OOOO Volume 124, Number 3 Conclusion: This report of an intraoral CMN, with a unique clinical presentation, adds to the literature of this rare entity.
REGULATION OF ENDOPLASMIC RETICULUM STRESS BY DENTIN SIALOPHOSPHOPROTEIN IN ORAL CANCER CELLS. I. GKOUVERIS, N. NIKITAKIS, K. OGBUREKE, J. ASEERVATHAM. DEPARTMENT OF DIAGNOSTIC AND BIOMEDICAL SCIENCES, SCHOOL OF DENTISTRY, UNIVERSITY OF TEXAS, HEALTH SCIENCE CENTER AT HOUSTON, TX; AND THE DEPARTMENT OF ORAL PATHOLOGY AND MEDICINE, SCHOOL OF DENTISTRY, NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS, GREECE. Objectives: Dentin sialophosphoprotein (DSPP) has been recently related with development, invasion and metastasis of oral squamous cell carcinoma. Cancer cells are commonly found under constant endoplasmic reticulum (ER) stress showing increased levels of misfolded proteins because of mutations and stressful microenvironment. This study examined the effects of DSPP modulation on ER regulating mechanisms and unfolded protein response (UPR) in oral cancer cells. Methods: DSPP shRNA silenced and scrambled OSC2 cells were used. mRNA levels of ER-related molecules were assayed by RT-PCR, while Bcl-2, Bax, PCNA and Cytochrome C protein levels were analyzed by Western blot. Cell viability, apoptosis and migration capacity were monitored by MTT, Annexin V/FITC flow cytometry and wound-healing assay, respectively. Results: DSPP silencing significantly downregulated mRNA levels of major ER stress regulator GRP78, as well as ER stress-related molecules SERCA2b, PERK, IRE1 and ATF6, accompanied by decreases in cell viability and migration and increases in apoptotic rate of OSC2 cells. Further, Bcl-2 and PCNA protein levels were reduced and Bax and cytochrome c were upregulated. Puromycin treatment ameliorated without reversing DSPP silencing effects on ER stress-related molecules and increased migration capacity, while it enhanced cell viability reduction and apoptosis induction in DSPP silenced cells. Conclusions: DSPP-silencing in OSC2 cells perturbed ER stress homeostasis, deregulated UPR and decreased critical hallmarks of oral tumorigenesis. Puromycin treatment weakened DSPP silencing effects on ER stress-related molecules and triggered a proper UPR. DSPP function may correlate with GRP78, leading to interactions with important proteins of ER stress homeostasis and UPR.
STEM CELL MARKER BMI-1 INCREASED EXPRESSION IN CARCINOMA EX PLEOMORPHIC ADENOMA PROGRESSION: AN ASSOCIATION WITH THE DEVELOPMENT OF DISTANT METASTASIS. B. SEDASSARI, M. RODRIGUES, R. CARMO, F. NUNES, A. ALTEMANI, S.M. DE SOUSA. UNIVERSITY OF SÃO PAULO. Objective: Pleomorphic adenoma (PA) is the most common salivary gland neoplasm and its malignant transformation into a carcinoma ex pleomorphic adenoma (CXPA) is a well-recognized event. CXPAs are typically high-grade and widely infiltrative malignancies at the diagnosis, often associated
ABSTRACTS Abstracts e221 with adverse outcome. However, if the carcinoma is diagnosed at a non-invasive phase of progression (intracapsular CXPA), the prognosis is excellent. We evaluated the immunoexpression of the stem cell marker Bmi-1 in the stepwise progression from pleomorphic adenoma (PA) to invasive carcinoma ex pleomorphic adenoma (CXPA), correlating it with clinicopathological aspects. Methods: 30 PAs, 27 CXPAs (8 intracapsular and 19 invasive) and 25 residual PA areas were evaluated immunohistochemically for Bmi-1 expression. Results: Twenty CXPAs (7 intracapsular and 13 invasive, 74%) were positive to Bmi-1. Residual PA and PA without malignant transformation were negative. High Bmi-1 expression levels (>50% of positive cells) was correlated with the development of distant metastasis in invasive CXPA (p¼0.005, Ç2 test), but no associations were found with histological grade, mitotic index, tumor-associated necrosis, perineural and angiolymphatic invasion, tumor recurrence, nodal metastasis and disease-related death. Conclusion: These results suggest that Bmi-1 may play an important role in carcinogenesis and progression of CXPA. Although direct therapeutic intervention in Bmi-1 may result in unwanted complications because of its constitutive functions, strategic approach to Bmi-1-related pathways may provide new therapeutic opportunities for patients with invasive CXPA.
THE COMPARISON OF P53 EXPRESSION PATTERNS IN NORMAL AND DYSPLASTIC ORAL MUCOSA. E. SIDO, C.C. LI, S.B. WOO. HARVARD SCHOOL OF DENTAL MEDICINE, BOSTON, MA; AND DIVISION OF ORAL MEDICINE AND DENTISTRY, BRIGHAM AND WOMENS HOSPITAL, BOSTON, MA. Objective: Current diagnostic criteria for oral epithelial dysplasia (OED) mostly rely on cytologic and architectural alterations, and these sometimes are not sufficient to distinguish reactive atypia from mild OED. Wild-type p53 protein has been shown to be present in approximately 25% of the basal cell nuclei in normal oral mucosa. In OED, basal and suprabasal p53 overexpression has been noted. We hypothesize that p53 may help to differentiate OED and reactive keratoses, and improve the accuracy of histopathologic diagnosis. Methods: One hundred and twenty-three archived human oral mucosa specimens were reviewed by two board certified oral pathologists, consisting of 20 cases of reactive keratosis, 76 OED and 27 oral squamous cell carcinoma (OSCC). Nuclear positivity for p53 was recorded as follows: intensity (low, intermediate and high) and percentage of positive basal cells (< 25%, 25%-50%, 50%-75% and > 75%). Results: In reactive keratosis, p53 expression was confined to the basal cell layer with low intensity and less than 5% nuclear positivity. In OED and OSCC, basal and suprabasal cells exhibited intermediate to high intensity positivity for p53, and the percentage of p53 positive basal and suprabasal cells ranged from 25%-100% with a continuous distribution. In addition, the percentage and intensity of p53 positive cells were higher in moderate/severe OED (50%-75%) and OSCC (> 75%) than mild OED (25%-50%) (p < 0.05). Interestingly, in 1.5% of cases, OED and OSCC were completely negative for p53.
PROGNOSTIC VALUE OF MX1 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA. C. DONNELLY, L. DONNELLY, Y. XIE, OKEMOS E. BELLILE, G. WOLF, Y. LEI. UNIVERSITY OF MICHIGAN, ANN ARBOR AND MICHIGAN STATE UNIVERSITY. Objectives: Evidence gleaned from recent clinical studies suggests that an intact anti-tumor immune response is indispensable for patient response to adjuvant therapy. Type I Interferon (IFN-I) signatures have rapidly emerged as central regulators of the immune microenvironment of cancer. Hence, we explored whether an IFN-I signature MX1 can be utilized to predict patient clinical outcome. Materials: Primary Head and Neck Squamous Cell Carcinoma (HNSCC) specimens were procured from 74 patients with a maximal follow-up of 85.9 months. We produced an HNSCC tissue microarray with 3 cores per specimen. We then stained sections of 5mm thickness with an anti-MX1 antibody. MX1 staining densities within cancer cells were quantitated using Aperio ImageScope. Conclusion: Among the enrolled patients, 28% had early stage (I-II) cancer, and 72% presented with stage III or IV cancer. HNSCC exhibited a spectrum of MX1 staining density. We observed a statistically significant association between MX1 immunohistochemical staining scores and overall patient survival, using the median MX1 score to separate the patients into two groups (p ¼ 0.003). This finding suggests that cancer autonomous IFN-I signaling plays a critical role in the patient clinical outcome. Our ongoing multivariate analysis will provide insight into the mechanism underpinning the MX1-mediated difference in patient survival.
PSEUDOSARCOMATOUS MYOFIBROBLASTIC LESIONS OF THE ORAL CAVITY. S. WETZEL, S. BUDNICK, S. MULLER. ATLANTA ORAL PATHOLOGY, ATLANTA, GA. Myofibroblastic lesions of the oral cavity can vary greatly in their histologic appearance. Occasionally, lesions of myofibroblastic origin can exhibit aggressive histologic features such as brisk mitotic activity and extension into underlying skeletal muscle and adipose tissue. Such cases can present a diagnostic challenge and can be aided by immunohistochemical (IHC) studies along with key morphological features to arrive at the appropriate diagnosis. The following is a discussion of two such cases. The first example presented as an exophytic lesion
OOOO September 2017 of the left dorsum of the tongue in a 73-year-old male. Histologically, the lesion was highly cellular, exhibited a moderate mitotic rate and showed extension into underlying skeletal muscle and adipose tissue. The lesional cells were focally positive for smooth muscle actin (SMA) and desmin by IHC, showed retention staining for retinoblastoma 1 (RB1) and was negative for CD34. The lesion was classified as a cellular fibrous histiocytoma. The second case also occurred on the tongue and presented in a 23-year-old female patient. Microscopically, this lesion was composed of mitotically active myofibroblasts set in a myxoinflammatory stroma. By IHC the lesion was positive for ALK and SMA but negative for keratin markers. Based on the histologic and IHC findings the lesion was diagnosed as a pseudosarcomatous myofibroblastic proliferation. Reactive and benign neoplastic myofibroblastic lesions can exhibit features suggesting malignancy, which can lead to misdiagnosis and mismanagement. The aim of this study was to examine and provide a discussion of two such cases and to illustrate how the IHC profile along with the overall morphology of the lesion can lead to the appropriate diagnosis of these challenging cases.
RARE INTRAORAL CONGENITAL MELANOTIC NEVUS - A CASE REPORT. A. SALCINES, S.B. WOO, V. NOONAN, M. MANSFIELD, C.C. LI. HARVARD SCHOOL OF DENTAL MEDICINE, BOSTON, MA; CENTER FOR ORAL PATHOLOGY, STRATADX, LEXINGTON, MA; AND PRIVATE PRACTICE, GLENDALE, AZ. Objective: Congenital melanocytic nevus (CMN) consists of a benign proliferation of melanocytes at birth or shortly after birth. CMN is not an uncommon entity on the skin, and it possesses increased risk of developing melanoma. While the cutaneous counterpart is common, intraoral CMN is extremely rare. There are only five well-documented case reports in the English literature, and here we present one case of an intraoral CMN. Clinical Presentation: A 9-year-old Caucasian female presented with a rapidly expanding mass on the right hard and soft palate, measuring 2 1.5 0.3 cm. The lesion was covered by normal oral mucosa, and presented as a well-circumscribed, non-tender, firm mass. There was no gross pigmentation and no palpable lymphadenopathy. Computed topography images showed no bone involvement. Intervention and Outcome: The mass was removed and evaluated histopathologically; margins were positive. Three years after the excision, there was a recurrence; re-excision was performed. Both specimens showed a dense diffuse infiltrate of small epithelioid melanocytes in the lamina propria with involvement of the vessel walls. The melanocytes arranged in clusters, theques or bands, streaming through collagen bundles with occasional melanin deposition. Cellular atypia or mitosis was not identified. The overlying oral mucosa exhibited slight papillomatosis with junctional activity. The majority of the melanocytes in the lamina propria were positive for MART-1 and p16, with a small population of HMB-45 positive cells within the superficial and junctional components. MIB-1 positivity was low (< 5%). No recurrence was reported at 1 year follow-up.
OOOO Volume 124, Number 3 Conclusion: This report of an intraoral CMN, with a unique clinical presentation, adds to the literature of this rare entity.
REGULATION OF ENDOPLASMIC RETICULUM STRESS BY DENTIN SIALOPHOSPHOPROTEIN IN ORAL CANCER CELLS. I. GKOUVERIS, N. NIKITAKIS, K. OGBUREKE, J. ASEERVATHAM. DEPARTMENT OF DIAGNOSTIC AND BIOMEDICAL SCIENCES, SCHOOL OF DENTISTRY, UNIVERSITY OF TEXAS, HEALTH SCIENCE CENTER AT HOUSTON, TX; AND THE DEPARTMENT OF ORAL PATHOLOGY AND MEDICINE, SCHOOL OF DENTISTRY, NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS, GREECE. Objectives: Dentin sialophosphoprotein (DSPP) has been recently related with development, invasion and metastasis of oral squamous cell carcinoma. Cancer cells are commonly found under constant endoplasmic reticulum (ER) stress showing increased levels of misfolded proteins because of mutations and stressful microenvironment. This study examined the effects of DSPP modulation on ER regulating mechanisms and unfolded protein response (UPR) in oral cancer cells. Methods: DSPP shRNA silenced and scrambled OSC2 cells were used. mRNA levels of ER-related molecules were assayed by RT-PCR, while Bcl-2, Bax, PCNA and Cytochrome C protein levels were analyzed by Western blot. Cell viability, apoptosis and migration capacity were monitored by MTT, Annexin V/FITC flow cytometry and wound-healing assay, respectively. Results: DSPP silencing significantly downregulated mRNA levels of major ER stress regulator GRP78, as well as ER stress-related molecules SERCA2b, PERK, IRE1 and ATF6, accompanied by decreases in cell viability and migration and increases in apoptotic rate of OSC2 cells. Further, Bcl-2 and PCNA protein levels were reduced and Bax and cytochrome c were upregulated. Puromycin treatment ameliorated without reversing DSPP silencing effects on ER stress-related molecules and increased migration capacity, while it enhanced cell viability reduction and apoptosis induction in DSPP silenced cells. Conclusions: DSPP-silencing in OSC2 cells perturbed ER stress homeostasis, deregulated UPR and decreased critical hallmarks of oral tumorigenesis. Puromycin treatment weakened DSPP silencing effects on ER stress-related molecules and triggered a proper UPR. DSPP function may correlate with GRP78, leading to interactions with important proteins of ER stress homeostasis and UPR.
STEM CELL MARKER BMI-1 INCREASED EXPRESSION IN CARCINOMA EX PLEOMORPHIC ADENOMA PROGRESSION: AN ASSOCIATION WITH THE DEVELOPMENT OF DISTANT METASTASIS. B. SEDASSARI, M. RODRIGUES, R. CARMO, F. NUNES, A. ALTEMANI, S.M. DE SOUSA. UNIVERSITY OF SÃO PAULO. Objective: Pleomorphic adenoma (PA) is the most common salivary gland neoplasm and its malignant transformation into a carcinoma ex pleomorphic adenoma (CXPA) is a well-recognized event. CXPAs are typically high-grade and widely infiltrative malignancies at the diagnosis, often associated
ABSTRACTS Abstracts e221 with adverse outcome. However, if the carcinoma is diagnosed at a non-invasive phase of progression (intracapsular CXPA), the prognosis is excellent. We evaluated the immunoexpression of the stem cell marker Bmi-1 in the stepwise progression from pleomorphic adenoma (PA) to invasive carcinoma ex pleomorphic adenoma (CXPA), correlating it with clinicopathological aspects. Methods: 30 PAs, 27 CXPAs (8 intracapsular and 19 invasive) and 25 residual PA areas were evaluated immunohistochemically for Bmi-1 expression. Results: Twenty CXPAs (7 intracapsular and 13 invasive, 74%) were positive to Bmi-1. Residual PA and PA without malignant transformation were negative. High Bmi-1 expression levels (>50% of positive cells) was correlated with the development of distant metastasis in invasive CXPA (p¼0.005, Ç2 test), but no associations were found with histological grade, mitotic index, tumor-associated necrosis, perineural and angiolymphatic invasion, tumor recurrence, nodal metastasis and disease-related death. Conclusion: These results suggest that Bmi-1 may play an important role in carcinogenesis and progression of CXPA. Although direct therapeutic intervention in Bmi-1 may result in unwanted complications because of its constitutive functions, strategic approach to Bmi-1-related pathways may provide new therapeutic opportunities for patients with invasive CXPA.
THE COMPARISON OF P53 EXPRESSION PATTERNS IN NORMAL AND DYSPLASTIC ORAL MUCOSA. E. SIDO, C.C. LI, S.B. WOO. HARVARD SCHOOL OF DENTAL MEDICINE, BOSTON, MA; AND DIVISION OF ORAL MEDICINE AND DENTISTRY, BRIGHAM AND WOMENS HOSPITAL, BOSTON, MA. Objective: Current diagnostic criteria for oral epithelial dysplasia (OED) mostly rely on cytologic and architectural alterations, and these sometimes are not sufficient to distinguish reactive atypia from mild OED. Wild-type p53 protein has been shown to be present in approximately 25% of the basal cell nuclei in normal oral mucosa. In OED, basal and suprabasal p53 overexpression has been noted. We hypothesize that p53 may help to differentiate OED and reactive keratoses, and improve the accuracy of histopathologic diagnosis. Methods: One hundred and twenty-three archived human oral mucosa specimens were reviewed by two board certified oral pathologists, consisting of 20 cases of reactive keratosis, 76 OED and 27 oral squamous cell carcinoma (OSCC). Nuclear positivity for p53 was recorded as follows: intensity (low, intermediate and high) and percentage of positive basal cells (< 25%, 25%-50%, 50%-75% and > 75%). Results: In reactive keratosis, p53 expression was confined to the basal cell layer with low intensity and less than 5% nuclear positivity. In OED and OSCC, basal and suprabasal cells exhibited intermediate to high intensity positivity for p53, and the percentage of p53 positive basal and suprabasal cells ranged from 25%-100% with a continuous distribution. In addition, the percentage and intensity of p53 positive cells were higher in moderate/severe OED (50%-75%) and OSCC (> 75%) than mild OED (25%-50%) (p < 0.05). Interestingly, in 1.5% of cases, OED and OSCC were completely negative for p53.