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Background: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). Methods: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. Results: Forty‐eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty‐nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). Conclusion: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Ossified cartilage is much more susceptible to cancer infiltration, but the reason remains unknown, and the relationship between the ossification pattern and cancer infiltration has not been studied. Methods: The presence of thyroid cartilage ossification, cancer infiltration, ossification pattern (usual: direction from inferior to superior; unusual: other than the usual pattern), and distance between cancer and ossified cartilage were evaluated in laryngectomy specimens. Results: There were 28 and 27 cases of usual and unusual patterns, respectively. There was no association between ossification pattern and cancer infiltration. However, the distance between the ossified area and cancer cells was greater in the usual pattern than in the unusual pattern (p = 0.006). And the usual pattern was more frequently observed in cases with a distance >1 mm than in cases with cancer infiltration or a distance ≤1 mm (p = 0.004). Conclusion: These results suggest the possibility of an active ossification due to tumor progression. [ABSTRACT FROM AUTHOR]

Background: This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC). Methods: This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease‐free survival (DFS). Results: In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P <.05). Our new N classification proposed three categories: N0 (0 LN+), N1 (1 LN+), and N2 (≥2 LN+ or ENE). The C‐index of our N classification showed improvement in OS prediction (0.768) compared with the AJCC seventh (0.743) and eighth (0.756) edition N classifications. Conclusions: Our proposed N classification incorporating LN+ number and ENE may improve prediction of post‐treatment survival and recurrence in patients with SGC. [ABSTRACT FROM AUTHOR]

Background: Primary cutaneous mucinous carcinoma (PCMC) is a rare epithelial tumor with unclear histogenesis. Methods: We evaluated the immunohistochemical expression of the estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) in six cases of PCMC. The immunoreactivity of adipophilin and gross cystic disease fluid protein (GCDFP)‐15 was investigated to determine the origin of the tumor. Results: The study included five males and one female aged 50 to 69 years who presented with a cutaneous mass in the face. Immunoreactivity for ER, PR, and AR was observed in all cases, and all cases were negative for adipophilin but positive for GCDFP‐15. Conclusions: This report is the first to show AR expression in PCMC. All of followed cases manifested indolent clinical course, and the prognostic significance of hormone receptors in PCMC remains unclear. The negative immunoreactivity of PCMC for adipophilin and positivity for GCDFP‐15 suggests a more likely relationship to apocrine than to sebaceous glands. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the expression of CD44 and cystine‐glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival. Methods: Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence‐free survival (RFS), disease‐specific survival (DSS), and overall survival (OS). Results: Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P <.05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P <.01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P <.05 each). Conclusion: Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16 and Epstein-Barr virus (EBV), in metastatic lymph nodes vs. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16 and EBV analyses of lymph node fine-needle aspirates and 18F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and 18F-FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of 18F-FDG PET/CT ( p < 0.05). The area under the ROC curve of HPV was higher than that of 18F-FDG PET/CT (0.857 vs. 0.666, p = 0.007). The disease-free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients ( p < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment and predict patient survival. [ABSTRACT FROM AUTHOR]

Background We examined the prognostic value of lymph node density in predicting cancer-specific mortality (CSM) for patients with lymph nodes positive (pN+) laryngeal squamous cell carcinoma (SCC) after laryngectomy. Methods The records of 156 patients with laryngeal SCC who initially underwent curative resection of the primary tumor combined with neck dissection were reviewed. Results The 5-year cumulative incidence of CSM was 20.4%. N classification and extralaryngeal spread (ELS) were independent variables for CSM in all patients. Univariate analyses in 71 pN+ patients showed that ELS, number of positive lymph nodes >4, and lymph node density >0.044 were significantly associated with increased CSM, whereas pN classification was not ( p = .218). On multivariate analysis, lymph node density ≥0.044 remained an independent predictor of CSM ( p = .001). Conclusion Among the pN+ patients with laryngeal SCC, no pN classification but lymph node density was noted to have an independent impact on CSM. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1319-1325, 2015 [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is generally an indolent tumor indicative of favorable prognosis. However, post-treatment recurrences may be problematic, and management strategies for recurrent disease have not been established. This study investigated risk factors associated with re-recurrence of PTC after reoperative surgery. Materials and methods: This study included 151 patients with pathologically confirmed recurrent/persistent PTC who underwent reoperation. Clinical factors, operative and pathologic findings, serum thyroglobulin levels, postoperative complications, and recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with re-recurrence-free survival (RFS) after reoperative surgery. Results: Recurrent tumors were found in thyroid remnants or previous resection bed ( n = 28), central nodes ( n = 48), and lateral neck nodes ( n = 102). Biochemical complete remission (stimulated thyroglobulin <1 ng/mL) was achieved in 69 (51.5 %) patients after reoperative surgery. Permanent vocal fold paralysis and hypoparathyroidism developed in 6 (4.1 %) and 4 (2.8 %) patients, respectively. Vocal fold paralysis occurred primarily due to intentional nerve resection following tumor invasion. During a median follow-up of 57.5 months, 41 (27.2 %) patients had re-recurrences. Univariate analyses showed that extranodal extension ( p = 0.028), recurrent laryngeal nerve invasion ( p = 0.037), as well as stimulated ( p = 0.001) and unstimulated ( p = 0.015) serum thyroglobulin were significant predictors of RFS. Multivariate analyses showed that postoperative biochemical remission independently predicted RFS ( p = 0.014). Conclusions: Postoperative thyroglobulin after reoperative surgery predicted re-recurrence. Careful follow-up of these patients after reoperation is recommended. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is associated with an excellent prognosis but frequently spreads to regional lymph nodes. The extent of neck dissection, particularly routine level II or V lymphadenectomy, is still controversial as it may lead to spinal accessory nerve injury and associated postoperative morbidities. We assessed the diagnostic value of preoperative ultrasonography (US) plus computed tomography (CT) for detecting metastatic lymph nodes and for identifying predictors of level II or V metastasis in patients with PTC. Methods: The results of US and CT were compared with histopathologic findings at various neck levels in 209 previously untreated PTC patients with lateral cervical nodal metastases who underwent total thyroidectomy with central and lateral neck dissection. Clinicopathologic predictors for level II or V metastases were identified. Results: Pathologic metastases to level II and V were observed in 53.6 and 25.4 % of patients, respectively. Occult metastases were found in 34.5 and 16.8 %, respectively. The sensitivities of US plus CT for levels II and V were 64.6 and 50.9 %, respectively. Image-based, isolated lateral level IV involvement and macroscopic extranodal extension were independently associated with level II metastasis or either level II or V metastasis ( p < 0.01). Macroscopic extranodal extension was also independently associated with level V metastasis ( p = 0.001). Conclusions: Patients with image-based, isolated lateral level IV involvement and no macroscopic extranodal extension are potential candidates for limited level III-IV dissection or prophylactic level II lymphadenectomy omission. Level V lymphadenectomy may be omitted in patients without macroscopic extranodal extension. [ABSTRACT FROM AUTHOR]

Background We compared clinical outcomes between patients with salivary gland carcinomas preoperatively misdiagnosed as benign lesion and properly diagnosed as malignant lesion. Methods The outcomes were compared between patients with benign lesion and malignant lesion (44 each) on preoperative fine-needle aspiration cytology diagnosis who underwent conservative or radical surgery. Results Five-year lesion-free survival (DFS) rates were 86.8% for benign lesion and 76.3% for malignant lesion ( p = .128). Surgical extent did not significantly affect locoregional recurrence and DFS ( p = .360). Univariate analysis showed that sublingual gland tumor, positive resection margin, and extraparenchymal extension (EPE) were significantly associated with DFS ( p < .05 each). On multivariate analysis, EPE remained an independent variable ( p = .047, hazard ratio = 6.621, 95% confidence interval = 1.393-31.474). Conclusions The clinical outcomes of patients with salivary gland carcinomas misdiagnosed as benign are relatively favorable. Conservative surgery may be sufficient for patients with low-grade and T1-2 salivary gland carcinomas. © 2013 Wiley Periodicals, Inc. Head Neck 35: 1764-1770, 2013 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis This study was intended to evaluate prognostic factors and the role of postoperative radiotherapy (RT) in patients with adenoid cystic carcinoma (ACC) of the head and neck (ACCHN). Study Design Retrospective study. Methods Eighty-eight patients with ACCHN who underwent curative intent surgery with or without RT between 1991 and 2009 at a single institute were retrospectively analyzed. Results Patients with ACC of the sinonasal area ( P=.005) and those with diabetes mellitus (DM; P=.027) showed a significantly higher risk of local recurrence. Age (<40 or >60 years, P=.028) and tumor stage III or IV ( P=.022) were significant adverse factors predicting distant metastasis. High-grade histology ( P=.014) and DM ( P=.027) were independently associated with shorter disease-free survival (DFS). In addition, postoperative RT (≥59 Gy) significantly enhanced local control ( P=.025) and DFS ( P=.001) in both univariate and multivariate analyses. Conclusions Age, DM, tumor site, histologic grade, and stage were independently significant prognostic factors for ACCHN. In addition, an adequate dose of postoperative radiotherapy can improve local control and DFS of patients with ACCHN. Level of Evidence 2b. [ABSTRACT FROM AUTHOR]

Background To determine whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) could serve as a useful technique predicting tumor hypoxia and prognosis in tongue cancer, we assessed the relationship between FDG uptake and the levels of hypoxia-related markers. Methods Tumor uptake of FDG in 33 patients with T2 tongue cancer was assessed by measuring maximum standardized uptake values (SUVmax). Expression of hypoxia-inducible factor (HIF)-1α, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR), was determined by immunohistochemical staining. Correlation between SUVmax and the expression of hypoxia-related markers was assessed and multivariate analysis was performed to determine what parameters affected clinical outcomes. Results We observed strong correlations between SUVmax and expression of HIF-1α ( p < .05), CA-9 ( p < .01), and GLUT-1 ( p < .01). SUVmax, HIF-1α expression, and tumor grade were significant independent predictors of disease-free survival (DFS). Conclusion SUVmax may be a good noninvasive biomarker for prediction of hypoxic status and prognosis of patients with T2 tongue cancer. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Primary extragonadal germ cell tumors are rare and mostly occur in young men with predominance of nonseminomatous histology. We report an undescribed case of primary retroperitoneal dysgerminoma presenting as an adrenal tumor in a 17-year-old girl. Surgery was performed on a 10 × 9.5 cm sized adrenal gland tumor and the resected tumor showed unequivocal histological features of dysgerminoma. The diagnosis was confirmed by the tumor's germ cell immunophenotype. Postoperative ultrasonography, CT and PET over a 6-month period revealed no evidence of ovarian lesion. The patient is stable, but with a suspicious residual tumor after adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39: 722-727 Background: Zinc is known to play an important role for growth and development, the immune response, neurological function, and reproduction. Although the etiology of burning mouth syndrome (BMS) is unknown, zinc deficiency may be implicated in the pathogenesis of BMS. The aim of this study was to demonstrate a causal relationship between zinc deficiency and BMS and to assess whether zinc replacement is an effective therapy for BMS. Methods: Serum zinc level was evaluated in 276 patients with BMS. To assess the therapeutic effect of zinc replacement, patients with zinc deficiency were administered a zinc supplement (14.1 mg/day). Pain intensity 6 months after zinc replacement was evaluated using an 11-point numerical scale. We also developed an animal model of zinc deficiency to assess the effects of zinc deficiency on the oral mucosa. Results: Of the 276 patients with BMS, 74 (26.8%) had low serum zinc levels. Zinc replacement therapy lowered the mean numerical pain scale in these patients from 8.1 to 4.1, compared with a mean decrease from 7.7 to 6.7 in a control group ( P = 0.004). In our animal model of zinc deficiency, the main pathologic findings were hyperkeratinization and increased mitosis on the dorsum of the tongue, although there were no gross oral mucosal lesions. Conclusions: Zinc deficiency might play a role in some patients with BMS. In such patients, appropriate zinc replacement therapy is effective in relieving symptoms. [ABSTRACT FROM AUTHOR]

ABSTRACT Primary extracranial meningiomas are rare disease entities, occurring primarily in the head and neck. We herein present a very rare case of primary extracranial meningioma of the retroperitoneum, observed in a 56-year-old man who presented with a retroperitoneal mass measuring 11 cm in its greatest dimension. Histological examination revealed sheets of spindle cells with frequent whorling patterns. The neoplastic cells had abundant light eosinophilic cytoplasm with minimal mitosis or cellular atypism. Immunohistochemical analysis demonstrated diffuse and strong positivity for vimentin and epithelial membrane antigen. Ultrastructural findings revealed abundant intermediate filaments, complex interdigitating cellular processes, and desmosome-like intercellular junctions, all of which are characteristic ultrastructural features of meningiomas. The patient was free of recurrence or metastasis 11 months after surgery. To the best of our knowledge, this is only the second reported case of primary retroperitoneal meningioma. [ABSTRACT FROM AUTHOR]

Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is important to distinguish it from metastases of clinically undetected thyroid carcinoma because metastatic papillary thyroid carcinoma is often so well differentiated, simulating normal thyroid tissue. Described herein are histological findings of heterotopic intrathymic thyroid tissue that was incidentally identified in a woman with papillary thyroid carcinoma during histological examination of a radical neck dissection specimen. These findings emphasize that this rare incidence may occur and should be differentiated from metastatic papillary carcinoma. Histologically, the patient’s intrathymic thyroid follicles were identical to the normal thyroid follicles, having flat cuboidal cells with uniformly small nuclei without nuclear grooves or inclusions. The follicular cells had a low Ki-67 labeling index close to zero, and immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the tumor cells in primary papillary thyroid carcinoma of the patient. To the authors’ knowledge this is the first case report of intrathymic heterotopic thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

ABSTRACT The present paper reports a rare case of granulocytic sarcoma (GS) with plasmacytoid features occurring in the maxillary sinus of a 63-year-old man. The diagnosis of GS has always been difficult, and diagnosis in the present case was made more difficult by the tumor's manifestation as longstanding maxillary sinusitis, the late development of leukemia, unusual location of the tumor, and the plasmacytoid features of the tumor cells. The potential for any lesion of any organ to be GS should be considered in a patient with hematologic abnormalities. [ABSTRACT FROM AUTHOR]

Ameloblastic fibrosarcoma (AFS) is a rare malignant tumor of the jaw. The malignant mesenchymal component of AFS has been described as‘fibroblast-like’, although little is known about the immunophenotype, except for vimentin expression. Here, we present a case of AFS in a 62-year-old woman. The mesenchymal component displayed the features of either dermatofibrosarcoma protuberans or fibrosarcoma, and was positive for CD34. This is the first reported case of CD34 expressing AFS in the maxilla.J Oral Pathol Med(2005)34:318–20 [ABSTRACT FROM AUTHOR]

Objective: To determine the significance of beta1 integrin expression as a prediction marker for the response to radiotherapy in patients with early glottic carcinoma., Study Design: Retrospective study in a tertiary referral center., Methods: Among the T1/T2 glottic carcinoma patients treated with radiotherapy from 1992 to 2002, 52 had more than 2 years of follow-up and available pretreatment biopsy specimens. The immunohistochemical staining was performed for the assay of beta1 integrin expression, and the staining pattern of each was classified as diffuse, localized, or negative. The associations between the patterns of beta1 integrin expression and clinicopathologic parameters, including response to radiotherapy, involvement of the anterior commissure, and grade of histologic differentiation, were evaluated., Results: After radiotherapy, 42 patients remained tumor free, and 10 patients had recurrent or persistent disease. Six (12%) specimens were negative for beta1 integrin expression, 39 (75%) had a localized staining pattern, and 7 (13%) had a diffuse staining pattern. Recurrence rate was significantly higher in the diffuse group (53%) than in the localized (13%) or negative (17%) groups (P=.023). The pattern of beta1 integrin expression was also closely related to histologic differentiation (P=.008), although the association between response to radiotherapy and histologic differentiation was not significant, Conclusion: The pattern of expression of beta1 integrin, which has been known as a stem cell marker of the epidermis, may be helpful in predicting the response to radiation in patients with early glottic carcinoma.

Objectives/hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist., Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells., Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells., Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin., Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC.