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Postoperative adjuvant therapy has been indicated by advanced T classification for T3–4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3–4 OSCC remains unclear. Ninety-eight cumulative patients with T3–4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p p = 0.017, and p

Perineural invasion (PNI) has been an established poor prognostic feature for T1-T2 oral squamous cell carcinoma (OSCC). Different presentations and amounts of PNI are commonly observed, but PNI is currently recorded as being present or absent. This study asked whether the quantification of PNI provides additional information for early OSCC.Retrospective cohort study.Tertiary referral medical center.Pathologic reevaluations were performed for 314 patients with T1-T2 OSCC who underwent curative surgery from June 2001 to August 2009. A novel parameter, PNI focus number, was defined for PNI quantification. With 5 PNI foci as the cutoff, patients were categorized into 3 groups: no PNI (0 PNI foci), low PNI (PNI foci, 1-5), and high PNI (PNI foci5). Rate of cervical lymph node metastasis (LN+), 5-year disease-specific survival (DSS), and 5-year overall survival (OS) were analyzed among these groups.PNI focus number independently predicted for LN+, poor DSS, and poor OS in multivariate analysis after controlling for T classification, lymphovascular invasion, differentiation, margin, and tumor thickness. The 5-year DSS demonstrated a dose-dependent decrease among the 3 groups (no PNI, 88.6%; low PNI, 75.2%; high PNI, 33.8%; P.001). Moreover, the 5-year DSS of the high PNI group was significantly worse than that of the low PNI group.PNI focus number can be a novel parameter for PNI quantification in early OSCC. Although optimal quantification methods still require further investigation, this study offers clear clinical support for the nerve-tumor interaction hypothesis and advocates further mechanistic research for the exploration of PNI-related treatment concepts for OSCC.

Aims Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). Methods and results We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. Conclusions This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs.

To investigate the clinicopathologic characteristics of patients with immunoglobulin G4-related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease.Case series with chart review and pathology study.Tertiary care hospital.We evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared.Of the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P.001). Ratio of IgG4-positive plasma cells to IgG-positive plasma cells in IgG4-RCSS tissues was 0.81 ± 0.14. The mean value of serum IgG4 in IgG4-RCSS patients was 918.8 mg/dL.IgG4-RCSS is more common in older male patients and frequently presents with bilateral involvement. Informing head and neck surgeons of the clinical features of IgG4-RCSS and promoting a combined approach of clinical evaluation, imaging, and biopsy can improve the accuracy of preoperative diagnoses.

Acute pharyngitis is a common disease. However, acute pharyngitis caused by Klebsiella pneumoniae with a gross appearance mimicking hypopharyngeal malignancy has never previously been reported. We report the case of a 57-year-old man with a right hypopharyngeal tumor which was disclosed by fiberoptic laryngoscopy and computed tomography scan. However, both the frozen and final pathologies showed no evidence of malignant cells, and a bacterial culture revealed the growth of K. pneumoniae. The hypopharyngeal lesion completely regressed after 2 weeks of antibiotic treatment. Clinicians should perform biopsy along with tissue culture for tumor-like lesions because infectious agents can lead to lesions with malignancy-like appearance.

// Yi-Fen Wang 1,2 , Chun-Ju Chang 3 , Jen-Hwey Chiu 4 , Chin-Ping Lin 5 , Wing-Yin Li 2,6 , Shyue-Yih Chang 1 , Pen-Yuan Chu 1,2 , Shyh-Kuan Tai 1,2 , Yu-Jen Chen 4,5,7 1 Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2 Department of Medicine, National Yang Ming University, Taipei, Taiwan 3 Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan 4 Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan 5 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 6 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan Correspondence: Chun-Ju Chang, email: // Yu-Jen Chen,, email: // Keywords : Head and neck squamous cell carcinoma (HNSCC); NM23-H1; Metastasis; Cisplatin; Prognosis Received : February 20, 2014 Accepted : April 16, 2014 Published : April 18, 2014 Abstract We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients’ prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.

Neck management for cN0 neck remains controversial for T1-2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear.Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1-2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed.Increased tumor thickness (6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI.PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1-2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.

Objectives Perineural invasion (PNI) is an established poor prognostic pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this study was to analyze the role of pretreatment parameters in predicting PNI for OSCC. Materials and methods We prospectively enrolled into our study 102 newly diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before treatment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue scale (VAS) for cancer pain. Pathological examination was performed to ascertain PNI status in all patients. Patients were divided into two groups, those with PNI and without PNI. Pretreatment parameters were compared between the two groups. Results In univariate analysis, clinical T classification ( P P = 0.001), problem with social eating ( P P = 0.002), VAS scores of primary pain ( P P = 0.004) were found to be associated with PNI. Multivariate logistic regression analysis further revealed VAS score of primary pain ( P = 0.001, OR 2.014) and T3-4 classification ( P = 0.014, OR 6.422) were independent predictors of PNI. A regression equation incorporating pretreatment pain was developed to predict the probability of having PNI. Conclusion PNI can be predicted by higher pretreatment VAS score of primary pain, as well as more advanced clinical T classification. Careful evaluation of pretreatment pain of primary tumor can thus be helpful in improving treatment decision making for OSCC.

Background. Recent studies have indicated hedgehog pathway plays a role in carcinogenesis of certain cancers. We investigated the clinical significance of its signal- ing components, including Sonic hedgehog (Shh), Patched (Ptch), and Gli-1, in oral squamous cell carcinoma (OSCC). Methods. By immunohistochemistry, we determined Shh, Ptch, and Gli-1 expression in surgical specimens from 40 patients with OSCC. The relationship between expression of these molecules and clinicopathologic variables were assessed by chi-square analysis. Statistical difference of sur- vival was compared using log-rank test. Results. Ptch overexpression was associated with lym- phatic metastasis (p ¼ .028). Nuclear Gli-1 overexpression cor- related with primary tumor size (p ¼ .001), lymphatic metastasis (p ¼ .011), and tumor recurrence (p ¼ .008). Over- expression of Ptch (p ¼ .020) or Gli-1 (p ¼ .002) in OSCC indi- cated poor prognosis in the univariate survival analysis. Conclusion. Our results suggest sonic hedgehog (Shh) pathway plays an important role in OSCC progression and should be considered a potential therapeutic target. V C 2012 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2012

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.

The function of EZH2 in tumorigenesis and liver metastasis of pancreatic cancer has never been elucidated in vivo. EZH2 was overexpressed in pancreatic carcinomas and its overexpression was associated with tumor differentiation and pT status. Suppression of EZH2 caused a significant growth inhibition of pancreatic cancer cells in vitro and markedly diminished their tumorigenicity in vivo. Knock-down of EZH2 inhibited liver metastasis of pancreatic cancer in vivo. EZH2 has a crucial role in tumor growth and liver metastasis of pancreatic cancer.

Patients with sino-nasal neuro-endocrine carcinoma should be managed by multi-modality treatment that includes surgery and postoperative chemo-radiotherapy as described in our treatment plan. Even though current combined therapy results in good disease control and survival rate, long-term follow-up is necessary.Neuro-endocrine carcinoma is an aggressive and rare malignant tumor of the sino-nasal tract, and its management remains divergent. The aim of this paper is to present our experience in the management of this kind of aggressive tumor and compare different treatment plans in order to draw up an effective strategy. Various treatment strategies were reviewed and assessed.Seven patients with biopsy-proven primary sino-nasal neuro-endocrine carcinoma from July 2004 to December 2006 were evaluated. The staging system was based on the American Joint Committee on Cancer Staging Manual of 2002. All of the patients underwent endoscopic or open surgery with curative intent. Six patients received postoperative chemo-radiotherapy.The median follow-up after surgery was 43.5 months (range 26.9-57.7 months). One patient was T2N0M0, one was T3N0M0, four were T4aN0M0, and one was T4bN0M0. After endoscopic or open surgery and postoperative chemo-radiotherapy, six patients were alive with no evidence of recurrence. One patient had persistent tumor without clinical and imaging changes for 36.9 months. After the whole treatment course, one patient had sino-cutaneous fistula and underwent flap reconstruction. None had regional failure or distant metastasis during follow-up.

A series of 76 cases of gastrointestinal tract endocrine tumors, including 21 poorly differentiated endocrine carcinomas (PDECs, small cell carcinomas) and 55 well-differentiated endocrine neoplasms (WDENs, carcinoids), 18 metastatic and 37 nonmetastatic rectal carcinoids, were examined by immunohistochemical analysis for p16INK4a, cyclin D1, and retinoblastoma protein (pRB) expression. Overexpression of p16INK4a was noted in 16 (76%) of the PDECs and none of the WDENs (P < .0001). Loss of pRB expression was demonstrated in 14 (67%) of the PDECs and 17 (31%) of the WDENs (P = .004). Overexpression of cyclin D1 was noted in 49 (89%) of the WDENs and 3 (14%) of the PDECs (P < .0001). Loss of pRB expression was noted in 11 (61%) of 18 metastatic WDENs and only 6 (16%) of 37 nonmetastatic WDENs (P = .001). The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors, and the loss of expression of pRB may be helpful in identifying patients at high risk of metastasis in rectal WDENs.

The overall prognosis for tongue cancer patients in Taiwan is unpredictable, even when patients are treated following the guidelines according to TNM stages. In order to determine the optimal treatment modality for tongue cancer in Taiwan the authors aimed to correlate histopathological parameters with neck nodal metastasis. A retrospective analysis of 94 patients with different stages of tongue cancer treated in the Taipei Veterans General Hospital was performed. All 94 patients were clinically diagnosed with stage I-IV tongue cancer before surgery and received primary tumor-wide excision and neck dissection. There were 42 (45%) patients with nodal metastasis. Univariate analysis revealed that cases of tongue cancer with moderate or poor differentiation, an invasion depth more than 3 mm and positive perineural invasion or lymphovascular permeation at the time of presentation may be subject to a higher incidence of neck nodal metastasis. An elective neck dissection or neck treatment should be considered if these histopathological risk factors are present. Cases of tongue cancer with these risk factors also warrant close follow-up after surgery.

Objectives: Hypopharyngeal squamous cell carcinoma (HPSCC) usually presents at an advanced stage. Although chemo-radiotherapy has become more popular in treating HPSCC in recent years, surgery with postoperative adjuvant therapy still plays an important role. The purpose of this study was to identify the clinicopathologic factors that predict survival in patients with HPSCC who underwent surgical treatment. Methods: Between 1986 and 1995, 94 previously untreated HPSCC patients who underwent surgery with or without postoperative radiotherapy were enrolled. The surgical specimens were reexamined by a single pathologist. The clinicopathologic parameters and prognostic data were analyzed. Results: With a median follow-up of 50 months, the 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were 47%, 60%, and 58%, respectively. Thirty-seven patients (39%) had tumor recurrence. The level of lymph node metastasis was an independent factor in OS, DSS, and RFS. Neck biopsy before surgery, tumor involvement of more than 1 subsite, and extracapsular spread were independent factors in DSS, as was lymphovascular permeation in RFS. Conclusions: The level of cervical lymph node metastasis is the only independent prognostic factor in OS, DSS, and RFS. The addition of postoperative chemoradiotherapy may benefit high-risk cases.

OBJECTIVE. Basal cell adenoma is a rare benign epithelial tumor of the salivary gland. The objective of this study is to present the CT findings of parotid basal cell adenoma. We also compare CT findings of basal cell adenoma with those of pleomorphic adenoma, the most common parotid tumor, to determine whether any features on CT can help differentiate these two entities.CONCLUSION. Basal cell adenomas of the parotid gland are located chiefly in the superficial lobe. They are generally round, well-circumscribed tumors that show heterogeneous enhancement on CT. The age of the patient and the attenuation on unenhanced and contrast-enhanced CT may help in differentiating basal cell adenoma from pleomorphic adenoma of the parotid gland.

Awoman in her 50s presented with a several-month history of symptoms that included foreign body sensation in her throat, mild odynophagia, and dyspnea. She had a history of adenoid cystic carcinoma of the right submandibular gland and had undergone wide tumor excision and postoperative radiation therapy 20 years previously (60Gy/30 fractions in 1993). She also had a history of hyperthyroidism,whichwas undermedical control (with propylthiouracil, 50mg/d). She stated that she did not have blurred vision, headache, seizures, or trismus. She had no family history of neurofibromatosis. A physical examination revealed a bulge in the floor of mouth, limitation of tongue movement, and no palpable lymphadenopathy. Shehadnosuspicious spotsornoduleson theskin.Noneurological deficits were revealed. Postgadolinium T1-weighted magnetic resonance imaging disclosed a 7.0 × 4.0 × 3.0-cm,well-definedenhancingmass in the right sideof the floorof themouth, extending posteriorly to the tongue base andmedially across the midline (Figure, A). The results of laboratory investigations were normal. Transcervical removal of the tumor was performed. The surgical specimen was a 7.2 × 5.8 × 4.3-cm encapsulated tumor composed of a homogeneous, whitish, rubbery, and glistening content (Figure, B). Microscopic examination demonstrated oval to eel-like spindle nuclei distributed in a backgroundofgenerallywavycollagenous fibers andmucinousmatrix (Figure,C). Thespecimen showed sparse cellularity and no cellular atypia. Neither mitotic figure nor tumor necrosis wasfound.Thespecimenwas immunoreactive forS-100(Figure,D), focallypositive forCD34, but nonreactive for smoothmuscle actin. A B

BackgroundSalivary gland carcinomas of the larynx are rare, and account for

Background Sarcomas of the larynx are rare neoplasms that constitute less than 1% of laryngeal malignancies. A Medline search found no large series focusing on laryngeal sarcomas. We reviewed the cases of laryngeal sarcomas treated in our cancer center and compared our experiences and treatment results with those from other centers. Methods A retrospective review of 10 patients with laryngeal sarcoma treated in our institute between 1980 and 2000 was done to identify tumor characteristics, therapeutic modalities, and treatment outcomes. Results The patients showed a male predominance (9/10) and presented 8 types of pathology. Nine patients underwent surgery, including 2 total laryngectomy, 4 partial laryngectomy, and 3 endoscopic laser cordectomy. During a median follow-up of 92 months, the 5-year overall survival and disease-specific survival were 76% and 90%, respectively. Two patients developed recurrence, including 1 local recurrence and 1 distant metastasis. Conclusion Surgical intervention was the first choice in the treatment of laryngeal sarcomas. The prognosis is relatively good when compared with sarcoma originating from other anatomic sites.

Purpose and Experimental Design: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non–small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme–based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. Results: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). Conclusion: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.

Objectives: Tumor recurrence and metastasis are major causes of treatment failure in esophageal squamous cell carcinoma (ESCC). Recently, nm23, originally considered to be an anti-metastatic gene, has been reported to associate with various roles in different human cancers. We therefore investigated the clinical significance of nm23-H1 expression in ESCC. Methods: Pathological sections were immunohistochemically stained with monoclonal antibody that was specific to nm23-H1. Expression of positive nm23-H1 staining was further confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between nm23-H1 expression and clinicopathological variables was examined by statistical analysis. Except for 11 (7%) surgical morality, the remaining 145 patients entered the prognostic analysis. The cisplatin-based chemotherapy was established for the patients with tumor stages at or beyond IIb, or with tumor recurrence. Survival difference between groups was compared by log rank test. Results: Immunohistochemically, nm23-H1 expression was detected in 39.3% (57/145) of the pathological sections. It was positively correlated with tumor stage ðP ¼ 0:002Þ; evident lymphovascular invasion ðP , 0:001Þ and tumor recurrence ðP ¼ 0:02Þ: Survival of nm23-H1 positive group was statistically superior to nm23-H1 negative group ðP , 0:0001Þ: By multivariate survival analysis, tumor stage, the number of lymph node metastasis and expression of nm23-H1 were the independent prognostic factors for ESCC patients. Conclusions: Our study demonstrated that nm23-H1 expression was associated with disease progression in ESCC. However, survival of nm23-H1 positive group was superior to nm23-H1 negative group. This paradoxical result could suppose that nm23-H1 expression might increase cisplatin chemosensitivity and hence improve survival. Screening for nm23-H1 expression in tumor cells may be a potential therapeutic strategy in ESCC patients. q 2004 Elsevier B.V. All rights reserved.

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.

We present a rare case of oral metastatic epithelioid sarcoma rapidly growing over the mandibular gingivae; the primary lesion occurred on the wrist and was treated 18 months earlier by surgery and radiotherapy. The oral metastatic lesion was resected and controlled by chemotherapy. This case has been followed for 2 years with good control of the resected oral metastatic lesion. Histologically, round to oval-shaped tumour cells with abundant eosinophylic globular cytoplasm and eccentrically localized nuclei, lack of epithelial features by electron microscopic study, and the immunohistochemical and cytologic features of tumour cells led into the diagnosis of epithelioid sarcoma. To our knowledge, no reports have been published of its occurrence in the oral cavity

We investigated the significances of the expressions of dihydrodiol dehydrogenase (DDH) and glutathione-S-transferase (GST) in patients with esophageal squamous cell carcinoma (ESCC). By using immunohistochemistry, we measured expressions of DDH, GST, COX-2, nm23-H1, HER-2/ neu and mdr-1 in 145 patients with ESCC. Expression of DDH was confirmed by immunoblotting and reverse transcription-polymerase chain reaction. Relation between DDH expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log rank test. DDH overexpression was detected in 66.9% of pathological sections (97/ 145) and in 41.6% of metastatic lymph nodes (37/89). The nucleotide sequencing of DNA fragments from 16 tumorous specimens showed that the major isoform was DDH2 for ESCC. GST expression, however, was only detected weakly in 24 patients (16.6%). For patients with ESCC, DDH overexpression was positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX-2 expression, and inversely correlated with GST and nm23-H1 expressions, but not related to mdr-1 or HER-2/neu expressions. As compared to DDH overexpressed group, patients with low DDH expression had significantly lower incidence of tumor recurrences and better survival (p 0.026). Using univariate analysis, prognostic factors included tumor stage, number of metastatic lymph nodes, cell differentiation, lymphovascular invasion and expressions of DDH and nm23-H1. Multivariate analysis showed significant correlation of tumor stage, number of metastatic lymph nodes and nm23-H1 expression with patient’s survival. In conclusion, inverse expressions of DDH and GST may be associated with carcinogenesis and disease progression for ESCC patients, but their biological function and pathophysiological regulation in tumors require additional studies. © 2004 Wiley-Liss, Inc.

Background Esophageal cancer is one of the most aggressive malignancies in the world, and whether multiple therapeutic modalities could improve long-term survival remains controversial. Recent studies have shown an increase of cyclooxygenase-2 (COX-2) expression in various malignancies, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods From 1993 to 1997, tissue samples from 96 patients with ESCC who underwent esophagectomy at our institution were collected for analysis. Cyclooxygenase-2 expression was examined by immunohistochemical staining, and further confirmed by Western blot analysis on six frozen tissues. Clinicopathologic data were analyzed to verify the significance. Results Cyclooxygenase-2 immunoreactivity was detected in 59 of 96 ESCC specimens (61%), and COX-2 overexpression (COX-2 high) was observed in 49% (47 of 96) of ESCCs. Statistical differences between COX-2 high and COX-2 low were found with respect to the status of distant metastasis (M factor) ( p = 0.035) and tumor stage ( p = 0.04). The survival was not significantly different between patients with and without COX-2 overexpression ( p = 0.43). Using the Cox regression analysis, only the N factor ( p = 0.0034) and M factor ( p = 0.0325) were independent prognostic factors. Conclusions Our results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with fewer metastases and less advanced stage, but had no impact on survival. The status of local or distant lymph node metastasis was the most important prognostic factor. The biological role and pathophysiologic regulation of COX-2 overexpression in ESCC deserve further investigation.

Background Recent studies showed that interleukin-6 (IL-6) played a role in tumor development. However, available information about the prognostic significance of IL-6 and IL-6 receptors (IL-6R) for oral squamous cell carcinoma (OSCC) is limited. Methods Eighty-six patients with OSCC were enrolled. Immunohistochemical staining was used to determine IL-6R expression and in-situ hybridization for IL-6 mRNA transcripts in surgical specimens. Clinicopathologic correlation was evaluated by chi-square test and survival by log rank test. Results Expression rates of IL-6R and IL-6 mRNA transcripts in tumor specimens were 73.3% and 54.7%, much higher than those in nontumor mucosa (p < .001). IL-6R overexpression was associated with larger tumors and more advanced histologic grade (p < .05). The presence of IL-6 mRNA transcripts was inversely correlated with distant metastasis, lymph node involvement, and second primary SCC (p < .05) and predicted better survival (p = .007). Conclusions IL-6-IL-6R coexpression was rather high in OSCC, and IL-6 mRNA transcript expression might influence patient survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional investigation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 850–858, 2002

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy. (Otolaryngol Head Neck Surg 1999;121:622-6.)

OBJECTIVE: Recently, an association between viral infection and the development of esophageal carcinoma has been reported, particularly the human papilloma virus (HPV) and Esptein-Bar virus (EBV). However, geographic variation in carcinogenesis is realized. In this study, we investigate the viral carcinogenesis and the biologic effect of viral infection on esophageal squamous cell carcinoma (ESCC) in Taiwan. METHODS: To determine the association of viral infection (EBV and HPV) with ESCC, we applied polymerase chain reaction (PCR), immunohistochemistry, and in situ hybridization (ISH) to examine 119 surgical specimens from different sites of esophagus in 31 ESCC patients. Additionally, an immunoperoxidase method was used to detect EBV latent membrane protein-1 (LMP-1), p53, CD45RO (UCHL-1), Fas ligand (Fas L), and RNA ISH with oligonucleotide sequences was used to detected interleukin-6 (IL-6) mRNA. RESULTS: By PCR, EBV DNA was detected in 11 cases (35.5%). Expression of EBERs in ESCC was further confirmed with ISH. Nonetheless, no LMP-1 expression was detected. On the other hand, human papillomavirus (HPV) was identified in only one case (3.2%) of ESCC. Furthermore, HPV was located by ISH in the distant normal region rather than in tumor cells. In EBV-positive cases, accumulation of p53 protein was detected in 10 lesions (91%); CD45RO+ lymphocytes together with expressions of FasL and IL-6 were respectively identified in 100%, 63.6%, and 54.5% of 11 EBV-positive lesions. Interestingly, in the EBV-negative cases (n = 20), p53 protein was detected in 40% of lesions; CD45RO 30%; FasL 50%, and IL-6 10%. CONCLUSIONS: In this study, no correlation was found between the presence of EBV in ESCC and the patients’ age, sex, as well as survival. Although our results indicate that EBV could be associated with ESCC, the clinical role of EBV in ESCC remains to be determined.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is rather common among the Chinese, but the therapeutic outcome is dismal. Knowledge of the prognostic factors in cancerous patients may influence therapeutic strategy. However, systemic analyses of clinicopathological and biological factors for patients with ESCC are few, and the results are controversial. METHODS: Between 1985 and 1996, 117 patients undergoing en bloc esophagectomy and gastric substitution were enrolled. None had neoadjuvant treatment. Postoperative adjuvant therapy was provided for patients at and beyond stages IIa. Clinical responses were followed routinely. Flow cytometry was used to measure DNA ploidy and synthesis-phase fraction (SPF) of the resected esophageal tissues from all patients. Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen (PCNA), epidermoid growth factor receptor (EGFR), HER-2/neu, and p53 in the pathological sections. Clinical correlation was evaluated by χ2 with Fisher’s exact test, and survival by log-rank test. RESULTS: The overall survival rates were 74% for 1 yr, 48% for 3 yr, and 38% for 5 yr. TNM tumor staging, the number of diseased lymph nodes (N ≤ 3 or N > 3), degree of cell differentiation, DNA ploidy, SPF, and lymphovascular invasion were more useful than biological markers, such as PCNA, EGFR, HER-2/neu, and p53, for the prognosis of ESCC. Multivariate analysis revealed significant correlation of tumor staging and number of diseased lymph nodes with patient survival after surgery. CONCLUSIONS: En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.

OBJECTIVES: Although significant improvement in myasthenic symptoms has been reported following the removal of thymolipomas, information on surgical outcomes among patients with thymolipomatous myasthenia gravis (MG) is limited. METHODS: This was a retrospective review of patients who underwent extended thymectomy for treatment of MG. RESULTS: From 1995 to 2010, 267 patients with MG underwent extended thymectomy, including 104 with thymomatous MG, 151 with non-thymomatous MG and 12 (4.4%) with thymolipoma. The mean duration of myasthenic symptoms before surgery was greatest in the thymolipomatous group (P< 0.001). The lowest mean age (36.1 years old, P< 0.001) and the lowest preoperative serum anti-acetylcholine receptor antibody titre (P= 0.015) occurred in the non-thymomatous group. More thymic and adipose tissue was removed from the thymolipomatous group compared with the non-thymomatous group (P< 0.001). Regarding surgical outcomes, the rate of stable remission was higher in the non-thymomatous (42.3%) and thymolipomatous (41.7%) groups compared with the thymomatous group (28.8%, P= 0.029). No instances of postoperative exacerbation of MG or tumour recurrence were noted during the postoperative follow-up of patients treated for thymolipoma. CONCLUSIONS: Our results suggest that patients with myasthenia thymolipomatous have surgical outcomes similar to those of patients with non-thymomatous MG and have a mean age at the time of surgery similar to that of patients with thymomatous MG.

Among benign tracheobronchial neoplasms, neurofibromas of neurogenic origin are exceedingly rare. In a search of world literature, only 23 cases of endotracheobronchial neurofibromas in 21 series were found. We report another case of a 52-year-old man who presented to our hospital with the symptoms of intermittent productive cough and fever. Bronchoscopy revealed a round tumor obstructing the lumen of the right main bronchus. Right sleeve pneumonectomy was performed, and neurofibroma was confirmed by pathologic examination. The literature is reviewed.

Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.

Background Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated. Methods Pathological features, including PNI, were re-reviewed under regular hematoxylin-eosin staining in 190 patients with T1-2 oral tongue SCC. Results Tumor thickness >5 mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node involvement. PNI(+) and neck observation also independently predicted neck recurrence, but only PNI(+) was associated with a poor disease-specific survival (DSS; p = .003). In patients who were clinically node negative (cN0), elective neck dissection contributed to a better DSS in patients with PNI(+) tumors (p = .046), but not in patients with PNI (-) tumors (p = .809). Additionally, increased tumor thickness predicted the presence of PNI. Conclusion PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57 years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5 years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.

Objective.Sjögren’s syndrome (SS) is an inflammatory autoimmune disease. We investigated important factors associated with the expression of inflammation-related molecules in minor salivary gland (MSG) mononuclear cells in patients with SS.Methods.Thirty-four patients with SS with a MSG biopsy grading of either grade III (10 patients) or grade IV (24 patients) were enrolled. The age, sex, autoantibodies, cell infiltration, and intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or CXCR3 expression were also analyzed.Results.Ten of the 34 patients with SS were diagnosed with secondary SS; in these patients, the diagnosis of rheumatoid arthritis was confirmed in 8 and systemic lupus erythematosus in 2. TRAIL and ICAM-1 were overexpressed in patients with antinuclear antibodies (ANA) > 1:160, compared to those with titer < 1:160 (45.1 ± 4.4 vs 41.2 ± 3.9, p = 0.021, and 15.2 ± 5.7 vs 10.8 ± 3.3, p = 0.018, respectively). Higher erythrocyte sedimentation rate (ESR; ≥ 20) was associated with higher TRAIL expression and CD20 cell infiltration in contrast to lower ESR (< 20; p < 0.05). ICAM-1, TRAIL, and MMP-3 were expressed more predominantly in anti-SSA-positive than in anti-SSA-negative patients with SS. There was a significant difference in CD20 cell infiltration and MMP-3 expression between primary SS and secondary SS. Biopsy of a grade IV showed a significantly increased expression of TRAIL (44.9 ± 4.5 vs 40.8 ± 3.6, p = 0.013) and MMP-3 (62.7 ± 6.3 vs 54.4 ± 7.3, p = 0.003) in mononuclear cells as compared to those of grade III.Conclusion.In our study, pathologic grading with a higher grade (grade IV) and the presence of SSA or a higher titer of ANA were significantly associated with the overexpression of TRAIL, MMP-3, or ICAM-1 in the salivary gland mononuclear cells in patients with SS.

We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens.

This study was designed to determine the expression of p16, p53, and CD117 in gastrointestinal tract endocrine tumors. Immunohistochemical studies of p16, p53, and CD117 were performed in 57 gastrointestinal tract endocrine tumors, including 22 poorly differentiated endocrine carcinomas (PDECs) and 35 well-differentiated endocrine tumors (WDETs). Overexpression of p16 and p53 was observed in 16 (73%) and 10 (45%) of the PDECs, respectively, whereas only 1 WDET showed overexpression of p53 and none showed overexpression of p16. A total of 18 (82%) of the PDECs showed overexpression of p16 or p53 proteins. This is closely associated with PDEC (P < .0001). By using overexpression of p16 or p53 as the criteria for PDEC, the sensitivity and specificity are 81.8% and 97.1%, respectively, with positive and negative predictive values of 94.7% and 89.5%, respectively. CD117 was not detected in any of the 57 gastrointestinal endocrine tumors by immunohistochemical analysis. Endocrine cells are distributed throughout the body and frequently found in the gastrointestinal tract, pancreas, lung, thyroid, adrenal glands, and many other organs. Although the gastrointestinal tract has the largest population of endocrine cells, endocrine carcinomas of the gastrointestinal tract are rare. 1 Endocrine tumors in the gastrointestinal tract are classified as well-differentiated endocrine tumor (WDET), including typical carcinoid and atypical carcinoid, and poorly differentiated endocrine carcinoma (PDEC), including small cell carcinoma and large cell carcinoma. 2 Clinically, WDETs are generally indolent and resistant to chemotherapy, whereas PDECs are more aggressive but may respond transiently to cisplatin-based chemotherapy. 1-3 There are relatively fewer studies on gastrointestinal tract endocrine tumors compared with pulmonary neuroendocrine tumors. Most staging systems and treatment protocols for gastrointestinal tract endocrine tumors are derived from experience in similar lesions of neuroendocrine tumors in the lung based on the presumption that these diseases are similar in many aspects. 1

Pulmonary hamartoma is the most common type of benign lung tumors. We retrospectively reviewed the clinicopathological features of 61 patients with pulmonary hamartomas undergoing surgical resection in our institution.From 1971 to 2002, 61 patients with 62 pulmonary hamartomas underwent surgical resection in the Division of Thoracic Surgery, Taipei Veterans General Hospital. 45 were men and 16 were women (approximately in 3:1 ratio). Their mean age was 56.9 years (range 20 to 77 years). The medical records of these patients were reviewed. The information collected using a standardized data-collection form consisted of the age at presentation, gender, initial manifestations or symptoms, history of tobacco consumption, location of hamartoma, size of the lesions, state of calcification in the hamartoma, the results of preoperative bronchoscopic examination, operative procedures and pathological report of intra-operative frozen section. All available histological slides were reviewed by the same pathologist to reconfirm the diagnosis of pulmonary hamartoma.Of the 61 patients with pulmonary hamartoma, 41 patients were clinically asymptomatic, 16 patients had new onset of respiratory symptoms and 4 patients had chronic cough. One patient had synchronous 2 separate lesions. The hamartomas were equally distributed in the pulmonary lobes with the mean transverse diameter of 1.8 cm measured in operation (range 0.2 to 5.0). No tumor recurrence developed after resection in our series. The mean follow-up was 8.9 years.The vast majority of pulmonary hamartomas represent as solitary pulmonary nodule. Definite diagnosis and the treatment can be achieved by surgical resection with minimal morbidity. No tumor recurrence was encountered in the follow-up period.

Non-squamous cell carcinoma (SCC) is a rare cancer in the larynx. Although atypical carcinoid tumor is the most common one, it is frequently unrecognized. We present a 55-year-old man with laryngeal atypical carcinoid tumor in the supraglottic region with initial manifestation of neck metastases. Two diagnostic biopsies revealed malignancy of different cell origins. The final pathologic report confirmed this diagnosis after the patient received total laryngectomy and radical neck dissection later. He received post-operative radiotherapy and was disease-free after a 19-month follow-up. We discuss this tumor with particular reference to the difficulty in distinguishing this tumor from other tumors of the larynx. The accurate pathological identification of this tumor is essential for treatment and prognosis.

Sclerosing hemangioma is a rare benign lung tumor. Preoperative diagnosis of this tumor is difficult, and sometimes even intraoperative frozen sections cannot differentiate it from malignant tumors. Herein, we present our experiences in investigating its characteristics.The medical records and pathological examinations of patients diagnosed with sclerosing hemangioma from 1982 to 2001 at the Division of Thoracic Surgery in Taipei-VGH were retrospectively reviewed.The incidence of sclerosing hemangioma in benign lung tumors resected during that period was 32.8%. There were 44 patients (7 male and 37 female) aged from 16 to 72 years, with a peak at fifth decade, and 72.7% of them were asymptomatic. Accurate preoperative diagnosis by chest CT could be achieved in only 20% (4/20) of patients, and malignancy could not be ruled out in 40% (8/20) of tumors. Histologically, this tumor exhibits four major patterns: solid, sclerotic, papillary and hemorrhagic. Five patients in this series had predominantly one pattern. At least two patterns existed in the remaining 39 patients, including eight patients who had tumors with all four patterns. There was no operative mortality or tumor recurrence despite that different operative methods were undertaken.Although rare, sclerosing hemangioma still accounts for the second common benign lung tumor in the current series. Chest CT and bronchoscopic examinations could not make accurate diagnosis preoperatively, and thoracotomy is usually indicated for definite diagnosis and treatment. Limited resection is warranted in view of uncommon tumor recurrence. In addition, multiple nodular lesions could not exclude the possibility of sclerosing hemangioma.

Laryngeal amyloidosis is an uncommon disease accounting for 0.68% of benign tumors of the larynx. It can present as a nodular tumor or diffuse subepithelial deposition forming a bulging mass and causing hoarseness, dysphagia or even airway obstruction. We present our experience in the management of laryngeal amyloidosis, and discuss the clinical features and histopathological characteristics of the disease. Reports on benign laryngeal tumor from June 1988 to June 1998 at Taipei VGH were searched to identify and collect amyloid cases for chart review. Five cases of laryngeal amyloidosis were found in the records. The sites of involvement were false cord, ventricle, post-cricoid, and arytenoid-epiglottic fold. No evidence of systemic amyloidosis involvement was observed for any of the five cases. All cases were treated with CO2 laser excision. Recurrence occurred in two patients within one year. More extensive CO2 laser excision was subsequently performed, with no more recurrences noted as of the last follow-ups. Laryngeal amyloidosis is a benign disease; however, surgical management is required when it is symptomatic. Recurrences or large-sized tumors may be a problem; however, advances in laser technology and the cumulative experience of treating benign lesions of the larynx have made CO2 laser endoscopic excision an effective treatment option.

The DNA content in oesophageal carcinoma and in sequential non-tumour mucosa was evaluated in 35 patients with oesophageal carcinoma, to explore the hypotheses that DNA distribution pattern and S-phase fraction can reflect malignant potential and that DNA aneuploidy can provide an early-warning signal of developing cancer. DNA flow cytometry was performed on 129 specimens from the tumours and on 119 specimens from non-tumour mucosa. Control specimens from gastric fundus had normal diploid DNA content and low S-phase fraction. Aneuploidy was found in 94.3% of the carcinoma specimens and intratumoral heterogeneity in 54.3%. Of the non-tumour specimens, 43.7% showed aneuploidy and none multiple aneuploidy. Pattern III distribution was present in 8.6% of the tumour specimens but not in non-tumour mucosa, where the incidence of aneuploidy rose with closeness to the tumour (p < 0.001). S-phase fraction was smaller in non-tumour than in tumour specimens (p < 0.0001). The study indicated that histologically tumour-free oesophageal mucosa may have a high malignant potential in patients with oesophageal carcinoma. The relative instability of such mucosa, with aneuploid cells and low S-phase fraction, may facilitate transition to abnormally proliferating cells in response to environmental signals. Cigarette smoking and alcohol may increase the risk of multicentric cancer development.

We present a case of odontogenic carcinoma with ghost-cell keratinization of the right maxilla, with a history of 23 years after initial treatment. Within this period, multiple local recurrence, as well as metastasis to axilla, brain, and lung, was noted. Several attempts at resection of the primary lesion were unsuccessful at achieving local control, even when supplemented with chemotherapy and radiotherapy. Metastatic tumors were studied histologically, and their morphology coincided with that of the primary tumor. The medical history of the patient and pathologic findings of the tumor are reviewed.

Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan.

Objective To describe the clinical presentations and management of pilomatricoma, formerly known as pilomatrixoma, of the head and neck. Design Retrospective study. Setting Tertiary care center. Patients The study included 179 patients with a diagnosis of pilomatricoma of the head and neck. Intervention All patients underwent surgical excision for pilomatricoma of the head and neck between 1991 and 2002. Results Pilomatricoma occurred at any age (mean age, 29.8 years); 45.3% of the cases occurred in patients younger than 18 years. The female-male ratio was 0.97:1. The average size of the lesion was 1 cm. The most common sites of occurrence were the neck (30.2%), cheeks (16.8%), scalp (16.2%), and brow and periorbital area (14.0%). Multiple occurrence was found in 1 case. Two of 179 tumors recurred after surgical excision. Conclusions Because preoperative diagnosis of pilomatricoma is usually incorrect, careful clinical examination and a high index of suspicion would result in a more accurate diagnosis. Complete surgical excision is the treatment of choice. Otolaryngologists should consider pilomatricoma in the differential diagnosis of neck masses.