Metastasis of adenoid cystic carcinoma from a submandibular gland to the larynx.

The present article discusses the first reported case of adenoid cystic carcinoma (ACC) metastasis from a submandibular gland to the larynx. Both treatments of distant metastasis of ACC and secondary laryngeal tumor are challenging. Despite its slow progression, ACC is associated with high rates of local recurrence, distant metastasis, and poor prognosis. Patients with secondary laryngeal cancer often have other concurrent metastatic lesions. Therefore, treatment selection should consider the biological behavior of the tumor and characteristics of the laryngeal lesion, along with the general condition and quality of life of the patient. The patient (55-year-old female) had a history of ACC of the right submandibular gland, removed surgically 9 years prior to the present consultation. Follow-up showed multiple pulmonary metastases. The patient complained of dysphonia lasting 3 months. Following the diagnosis of ACC metastasis to the larynx (supraglottic) and a neck lymph node via biopsy, we performed partial laryngectomy, left neck dissection, and tracheotomy. Histopathological examination showed an increase in the tumor grade over time. Two months after discharge, there was no obvious local recurrence or increase in lung metastasis.

Gastric cancer metastatic to neck lipoma: a case report with imaging consideration.

A 71-year-old man visited our hospital for examination of a soft neck mass. Computed tomography and magnetic resonance imaging scans showed a well-circumscribed large lipomatous tumor with multiple nodules inside. Atypical lipomatous tumor or lipoma involving the lymph nodes was considered. Pathological examination of the surgical specimen suggested typical lipoma including multiple metastatic foci from gastric cancer. Subsequent endoscopy revealed a gastric tumor, which was histologically proven to be signet-ring cell carcinoma. Considering these findings, this case was diagnosed as tumor-to-tumor metastasis to lipoma. We present the first such case with imaging and clinical characteristics.

Carcinoma ex pleomorphic adenoma of the parotid gland: a multi-institutional retrospective analysis in the Northern Japan Head and Neck Cancer Society.

CONCLUSION: The 3-year progression-free survival rate of non-invasive salivary duct carcinoma (SDC) or adenocarcinoma not otherwise specified (NOS) was significantly better than that of invasive SDC or adenocarcinoma NOS in Carcinoma ex pleomorphic adenoma (CXPA). The presence of invasion is an important prognostic factor for SDC and adenocarcinoma NOS in CXPA. OBJECTIVES: CXPA is a rare parotid gland malignant tumor for which therapy is not yet standardized. The purpose of this study was to review the characteristics of CXPA patients and to analyze their outcomes in the Northern Japan Head and Neck Cancer Society. METHOD: The medical records of 33 patients who had been provided initial treatment in 12 institutes of northern Japan from 2002-2011 were reviewed as a multi-institutional retrospective study. RESULTS: The 3-year overall and progression-free survival rate of all patients was 79.9% and 76.8%, respectively. Both the 3-year overall and progression-free survival rates were 87.5% for patients with non-invasive SDC or adenocarcinoma NOS. The 3-year overall and progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS were 60.4% and 30.5%, respectively. The progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS was significantly poor (p < 0.05).

Transcanal endoscopic resection for leiomyoma of the external auditory canal and a review of the literature.

Leiomyoma usually originates from the uterus and alimentary tract, but in extremely rare cases leiomyoma can appear in the external auditory canal. Here we present a 37-year-old man with right auricular fullness. Preoperative findings suggested benign tumor or cholesteatoma in the right external auditory canal. We performed total resection using an endoauricular approach with transcanal endoscopic ear surgery. Histopathological and immunohistochemistry examination confirmed the diagnosis of leiomyoma of external auditory canal. Leiomyoma arising from soft tissue, including that in the external auditory canal, is classified into two types: that from the arrectores pilorum muscles and that from the muscle coats of blood vessels. Only four cases of leiomyoma of external auditor canal have been published in the English literature. The other four cases demonstrated vascular leiomyomas. This is the first report of leiomyoma of the EAC arising from arrectores pilorum muscles.

Extraosseous chondroma of anterior neck in pediatric patient.

Extraosseous chondroma (EC) is uncommon soft tissue tumor composed of hyaline cartilage without connection to bone or periosteum. The frequent sites of EC are the hands and feet and rarely reported in the pediatric population and anterior neck lesion. We present an extremely rare case of anterior neck mass in a 5-year-old male who underwent total resection, with the final diagnosis of EC. The review of the literature showed that all cases of EC in anterior neck lesion have been found in young age and preoperative diagnosis was difficult.

Differences between oral cancer and cancers of the pharynx and larynx on a molecular level.

In order to elucidate differences between oral cancers and cancers of the pharynx and larynx, we investigated the genetic and epigenetic changes in these tumors using molecular biology methods. Methylation of the promoter region of the p16 tumor suppressor gene was examined using methylation-specific polymerase chain reaction in specimens from 47 oral, 39 pharyngeal and 35 laryngeal squamous cell carcinomas. These specimens were also characterized for allelic loss of certain areas of the genome, i.e., 3p22, 9p21 and 17p13 (TP53). The frequency of methylation of the promoter region of the p16 gene in tongue cancers (35.3%) was significantly higher than in pharyngeal (12.8%) and laryngeal cancers (11.4%) (p=0.046 and p=0.039, respectively). The frequency of methylation in tumors of female patients (47.1%) was significantly higher compared to tumors of male patients (15.4%) (p=0.0067). In contrast, the frequency of the loss of heterozygosity (LOH) at 3p21 in pharyngeal cancers (66.7%) was significantly higher than in oral cancers (20.0%) (p=0.0006). The frequencies of LOH at 17p13 in pharyngeal (71.0%) and laryngeal cancers (73.1%) were also significantly higher than in oral cancers (36.1%) (p=0.009 and p=0.009, respectively). Our results indicate that there are marked differences in the frequencies of the hypermethylation of genes and allelic loss between oral cancers and cancer of the pharynx and larynx. Although all of these tumors were diagnosed as squamous cell carcinomas, the process of carcinogenesis may be different in tumors located in various parts of the head and neck. Loss of function of tumor suppressor genes by allelic loss gives rise to tumors in the pharynx and larynx, while loss of function due to methylation of the promoter regions of those genes is related to carcinogenesis in the oral cavity.

Distinct features of second primary malignancies in head and neck cancer patients in Japan.

Second primary malignancies (SPMs) are one of the most critical problems in treating head and neck cancer patients. Our hospital had 742 patients with a diagnosis of malignant head and neck tumors during the five-year period from 2002 to 2006. In this study, we analyzed 360 of those patients who were assumed to have risk factors such as alcohol and tobacco use: 106 oral, 120 laryngeal, 50 oropharyngeal and 84 hypopharyngeal cancer patients. Synchronous SPMs are defined as second cancers diagnosed at the same time or within 6 months of the diagnosis of the index head and neck cancers. There were 4 (3.8%) and 11 (10.4%) oral cancer patients, 11 (8.3%) and 8 (5.8%) laryngeal cancer patients, 7 (14.0%) and 4 (8.0%) oropharyngeal cancer patients, and 30 (28.6%) and 7 (8.3%) hypopharyngeal cancer patients with synchronous and metachronous SPMs, respectively. The number of metachronous patients with synchronous SPMs tended to increase during this time period. The frequencies of SPMs in oropharyngeal and hypopharyngeal cancer patients are similar to those in oral and laryngeal cancer patients. Notably, the most frequent SPMs are upper gastrointestinal tract cancers in Japan, compared to lung cancers in Europe. The five-year overall survival rate of patients with synchronous SPMs was significantly poorer than that of patients without any other tumor except for the index cancer, according to the Kaplan-Meier analysis. In conclusion, searching for SPMs in the upper gastrointestinal tract is a critical issue in head and neck cancer patients in Japan.

Melanoma-associated retinopathy associated with intranasal melanoma.

PURPOSE: To present a case of melanoma-associated retinopathy (MAR) associated with an intranasal melanoma. CASE REPORT: A 77-year-old Japanese man visited us complaining of night blindness, blurred vision, and color vision difficulties in both eyes. His best-corrected visual acuity was 0.7 in the right and 1.0 in the left eyes. The rod response of the electroretinogram (ERG) was abolished, and the maximum response had a negative waveform. The a-wave of the single-flash cone response was square shaped, and the b-wave was delayed. The ON-response of the long-flash cone ERG was absent, but the OFF-response was preserved. A severe loss of retinal sensitivity was detected by static perimetry. Positron emission tomography showed no abnormal signs. Six months after the initial examination, an intranasal tumor was detected and surgically removed. The final diagnosis based on histopathology was malignant melanoma. CONCLUSION: Our case demonstrates that MAR can be associated with an intranasal mucosal melanoma. Thus, in cases where the primary lesion cannot be identified in patients with MAR-like symptoms and signs, we recommend that preferential sites of mucosal melanomas be examined.

Surgical treatment is recommended for advanced oral squamous cell carcinoma.

Oral squamous cell carcinoma is one of the most frequent types of head and neck cancers in Japan. Although recent reports have shown positive results of non-surgical treatment for advanced head and neck squamous cell carcinoma, including tongue cancer, no clear treatment strategies have been established for oral cancers, except for tongue cancer. To assess appropriate therapies, we conducted a retrospective chart review of 114 Japanese patients with oral cancers that were pathologically diagnosed as squamous cell carcinoma, excluding tongue cancers. The overall and the disease specific 5-year survival rates were 53% and 61%, respectively. Univariate and multivariate analyses revealed a lower stage (I, II, or III) and non-surgical treatment as good and poor prognostic factors of oral squamous cell carcinoma, respectively, based on their hazard ratios of 0.17 (95% CI 0.045-0.60, p = 0.0061) and 5.3 (95% CI 2.7-11, p < 0.0001). Furthermore, impact of surgery was well documented in the operable stage IVa cancers (p = 0.00015). The surgical treatment consisted of the wide resection of the primary tumor and the neck dissection for stage III or IV tumors. The present data also suggest that adjunctive therapy, such as post-operative radiation therapy or post-operative chemo-radiation therapy, shows no survival benefit compared to the surgery alone. We therefore recommend the surgical treatment for advanced oral squamous cell carcinoma in Japanese patients. These results would be helpful in future clinical trials, especially in non-surgical treatment studies of oral squamous cell carcinoma in Japan.

Nonrecurrent inferior laryngeal nerve without vascular anomaly as a genuine entity.

Inferior laryngeal nerve (ILN), which usually arises from vagus nerve, runs recurrent course and is called recurrent ILN (RILN). Intimate knowledge of normal and anatomic variants of the ILN reduces the risk of nerve injury and vocal cord paralysis in thyroid and parathyroid surgery. The nonrecurrent ILN (NRILN) is a rare nerve anomaly that is associated with a right aberrant subclavian artery. We encountered 2 patients with NRILN during thyroid surgery. Patient 1, a 57-year-old woman, had mediastinal thyroid tumor without vascular anomaly. Patient 2, a 47-year-old woman with a history of esophageal foreign body (fish bone), was suspected to have NRILN with vascular anomaly before surgery, as judged by preoperative enhanced CT. In the patient 1, we verified laryngeal mobility function of the NRILN by nerve stimulation, and confirmed the absence of RILN in usual recurrent course. The findings in the patient 1 indicate that NRILN without subclavian artery anomaly is a genuine entity. In both patients we performed thyroid surgery safely and fast by expectation and identification of NRILN by use of nerve stimulator. In conclusion, we confirm the existence of NRILN without vascular anomaly and show effectiveness of preoperative enhanced CT and valuable use of nerve stimulator for nerve preservation in the patients with NRILN.

Retropharyngeal abscess complicated with torticollis: case report and review of the literature.

Retropharyngeal abscess commonly develops among infants and small children, and is associated with the severe inflammation of the retropharyngeal lymph nodes located in the retropharyngeal space. Retropharyngeal abscess causes cervical pain, swelling, contracture of the neck, and in rare cases inflammatory torticollis, all of which result from an inflammatory process that irritates the cervical muscles, nerves or vertebrae. Here we report a rare case of retropharyngeal abscess with a complication of torticollis. A 4-year-old girl suffered from severe retropharyngeal abscess spreading through the deep cervical fascia, as judged by magnetic resonance imaging of the neck. Blood analysis showed high degree of inflammatory reactions, and so the patient was transferred to our hospital ward. The inflammation caused spasms of the prevertebral muscles, eventually leading to torticollis. The surgical drainage was performed immediately under general anesthesia, and an anti-inflammation therapy with intravenously administered meropenem trihydrate and clindamycin was used together with traction therapy to relieve the symptoms of the patient. We must be careful about the existence of epidural abscess and infectious spondylitis when the retropharyngeal abscess causes torticollis. In conclusion, an anti-inflammation therapy using antibiotics, along with traction therapy, was effective to relieve the symptoms. In addition to repeated clinical examinations, cooperation with orthopedists and careful follow-up are necessary. We also discussed the relationship between acute torticollis and retropharyngeal abscess.

[Management of cervical tuberculous lymphadenitis: evaluation of 6 cases].

Unlike other advanced nations, secondary spread of tuberculosis still occurs in Japan. Cervical tuberculous lymphadenitis is still an important disease of the neck, and between 2001 to 2005, we treated 6 patients with cervical tuberculous lymphadenitis. All 6 patients were females, and their ages ranged from 28 to 77 years old (average: 62 years). One patient had received antitubercular chemotherapy for pulmonary tuberculosis 40 years earlier. Two patients had a family history of pulmonary tuberculosis. One patient was an immigrant from Thailand. Three patients underwent open biopsy of the cervical lymph node, and were diagnosed with tuberculosis histologically. The remaining three patients had an abscess, and fine-needle aspiration (FNA) biopsy was performed. The diagnosis of tuberculosis was made by detection of acid-fast bacilli, MTD (Mycobacterium tuberculosis direct test), PCR (polymerase chain reaction), and culture. All six patients were treated with antitubercular chemotherapy for 6-9 months and recovered. MTD and PCR of the FNA sample seemed to enable early treatment. Attention needs to be paid to countries around Japan where tuberculosis is spreading. We suggest that treatment should be performed while at the same time making an effort to grasp the trend of spread in other countries as well as Japan.

Combined therapy after superselective arterial cisplatin infusion to treat maxillary squamous cell carcinoma.

OBJECTIVE: We sought to assess the efficacy of combined therapy after superselective arterial cisplatin infusion (SACI) therapy to treat the maxillary squamous cell carcinoma. STUDY DESIGN: We conducted a retrospective chart review of 50 patients. After completion of two courses of SACI, 25 of the patients were successively treated by concurrent SACI and radiotherapy (AR), while the other 25 patients were treated by surgery with postoperative radiotherapy (ASR). RESULTS: Patients with surgery (ASR) had an 88% local control rate with 75% disease-free survival rate at 60 months by Kaplan-Meier analysis, compared with 62% disease-free survival rate for patients with AR treatment. A particularly good outcome was obtained in T4 cases of the ASR group (n=8) whose 5-year survival rate was 87% and local control rate was 100%. CONCLUSION/SIGNIFICANCE: Combined SACI therapy is very effective for the treatment of maxillary squamous cell carcinomas and contributes to the improving prognoses of patients and organ preservation rates.

Management of the patients with hypopharyngeal cancer: eight-year experience of Miyagi Cancer Center in Japan.

The aim of this study is to evaluate the results of treatment for hypopharyngeal cancer and indicate the future prospect of the treatment. Seventy-four patients with squamous cell carcinoma of the hypopharynx admitted to Miyagi Cancer Center from 1993 through 2000 are reviewed. Sixty-four patients received radical treatment, and 10 patients received palliative treatment or no treatment. The cancer was advanced (stages III and IV) in 82% of all the patients. The overall 5-year survival rate of all the patients was 38%. The overall 5-year survival rate of 64 patients received radical treatment was 43%. The ten patients who received palliative treatment or no treatment died of cancer within 16 months. Fifty-two out of the 74 patients underwent neck dissection for the neck lymph node involvement; forty of the 52 patients underwent ipsilateral neck dissection and 12 underwent bilateral neck dissection. Four out of the 40 patients, who underwent ipsilateral neck dissection alone, developed late contralateral regional recurrence but were successfully treated by contralateral neck dissection at the time of recurrence. Twenty-three out of 74 patients had multiple primary cancers synchronously or metachronously (31%). Cause of the death of six patients out of 74 patients was confirmed to be primary cancers other than hypopharyngeal cancer, as judged by physicians in other department or other hospitals. Most of the patients died due to distant metastasis from hypopharyngeal cancer or other primary cancers. We therefore conclude that contralateral elective neck dissection which is frequently chosen for the treatment of hypopharyngeal cancer surgery is unnecessary. Even if locoregional control is accomplished, distant metastasis or multiple primary cancers emerge and make prognosis poor. To improve the prognosis, we should develop some strategy against hypopharyngeal cancer for each patient. New strategies including chemoprevention and surgery against distant metasistasis are necessary.

Allelic loss correlated with tissue specificity in head and neck squamous cell carcinomas and the clinical features of patients.

Head and neck squamous cell carcinomas (HNSCC) manifest various clinical behaviors according to their origin, i.e., from various parts of the head and neck mucosa. However, genetic factors involved in the carcinogenesis of HNSCC in different tissues have not yet been studied and evaluated. Three hundred and two specimens of HNSCC were characterized for allelic loss of certain areas of the genome, i.e., 3p21, 9p21 and 17p13, and were examined for genetic factors that might correlate with the tissue specificity of HNSCC and influence their clinical features. Loss of heterozygosity (LOH) at 3p21, 9p21 and 17p13 was detected in 54.5%, 57.4% and 57.1% of the informative cases, respectively. The frequencies of LOH in hypopharyngeal and in laryngeal cancers were significantly higher than in oral cancers. There were significant correlations between LOH at 3p21 and lymph node involvement and between LOH at 17p13 and tumor size, resulting in positive correlations with clinical stage of HNSCC in the patients. These results indicate that not only the functions of tumor suppressor genes differ among HNSCC in various regions, but also that allelic loss plays a key role in the acquisition of a malignant phenotype of these tumors.

Multiple squamous cell carcinomas of the head and neck show different phenotypes of allelic loss patterns suggesting different clonal origin of carcinogenesis.

BACKGROUND: Multiple squamous cell carcinomas in the head and neck are not such a rare phenomenon in patients. To examine if these tumors have the same genetic basis or not, we investigated genetic alterations such as allelic loss in such multiple tumors to see if they showed identical patterns. MATERIALS AND METHODS: Patterns of the loss of heterozygosity at 3p, 9p and 17p loci were analyzed in multiple head and neck squamous cell carcinomas of the same patient. RESULTS: Metachronous laryngeal and tongue tumors of a patient were found to have identical patterns of allelic loss, while synchronous tumors of three other patients had different patterns of such loss. CONCLUSION: Our data support the idea that field carcinogenesis caused by exposure of oral, laryngeal and pharyngeal mucosa to carcinogens may lead to the independent development of synchronous non-related tumors at different sites of the upper aerodigestive tract.

Protein expression of p53 and Bcl-2 has a strong correlation with radiation resistance of laryngeal squamous cell carcinoma but does not predict the radiation failure before treatment.

To examine what factors can precisely predict the radio-sensitivity or radio-resistance of early stage laryngeal squamous cell carcinomas (LSCC), protein expression of p53, Bcl-2 and Bax and loss of heterozygosity (LOH) at 3p and 9p loci were investigated. From June 1994 through June 1999, specimens of primary tumors were obtained by biopsy from 21 patients diagnosed as early stage LSCC at Miyagi Cancer Center Hospital under approved protocol. Labeling indexes of p53 and Bcl-2 were markedly increased in the recurrent tumors (n=8) and the differences were significant by statistical analysis (p=0.043 and p=0.015). However, when labeling indexes of the samples before treatment from non-recurrent cases were compared with those of the samples before treatment from recurrent tumors (n=13), no significant difference was observed. When LOH was examined, 16 out of these 21 cases were acceptable for evaluation, 4 of which (25%) had a relapse. Allelic loss at the 9p21 and 3p21 loci was found in 6 of 13 cases (46%) and 10 of 16 cases (63%), respectively. The frequency of LOH at the 3p21 locus in the recurrent cases was 100% (4 out of 4) and that in non-recurrent cases was 50% (6 out of 12). The frequency of LOH in recurrent tumors was apparently higher than that in non-recurrent tumors. Preservation rates of the larynx of the patients with 3p21 LOH negative tumors was very high (100%) and that of the patients with 3p21 LOH positive tumors was low. These results indicate that although expression of p53 and Bcl-2 had a strong correlation with recurrent LSCC treated by irradiation, immunohistochemical analysis of p53 and Bcl-2 in the sample before treatment was not able to predict the radiation failure. Moreover, our results also indicated that molecular research on genetic instability such as allelic loss may be more sensitive for the detection of radio-resistant tumor cells.

[A case report of epithelioid hemangioendothelioma metastasizing to the tonsil].

Epithelioid hemangioendothelioma is an extremely rare, difficult-to-diagnose vascular tumor mainly originating from the lung or liver. Primary tumors in the head and neck are very rare. A 40-year-old man admitted for right throat pain had been found in biopsy elsewhere to have squamous cell carcinoma. Based on a diagnosis of mesopharyngeal cancer, he underwent radical surgery, reporting cough, sputum, and hemosputum postoperatively. Epithelioid hemangioendothelioma was first diagnosed histopathologically from a biopsy of scalp tumors. Lung specimens at open biopsy 4 years earlier showed the same histological features indicating he had had epithelioid hemangioendothelioma lesion since that time. We assumed this epithelioid hemangioendothelioma had originated in the lung and metastasized to the right tonsil. These tumors are typically progressive and aggressive, and this patient had a poor prognosis. We discuss tumor features and review them clinically and histologically.

Complication-free laryngeal surgery after irradiation failure with prostaglandin E1 administration.

To examine the usefulness and efficacy of administration of prostaglandin E1 (PGE1) after laryngeal surgery in patients who were previously treated with radiotherapy, we retrospectively examined the clinical data of 12 patients who had undergone partial laryngectomy and 21 patients who had undergone total laryngectomy. Complications were observed in 5 of the 7 cases treated with partial laryngectomy without PGE1 administration, while no complications were observed in the 5 cases treated with PGE1 after operation. Also, complications, including major leakage, were observed in 6 of the 15 patients who underwent total laryngectomy without PGE1, and no complications were observed in the 6 patients who received PGE1. The hospital stay was shorter for the patients treated with PGE1 than for those not receiving such treatment. Although this study was a small, nonrandomized pilot trial, the results indicated that PGE1 administration may be useful and effective for patients who undergo laryngeal surgery after irradiation failure, in decreasing the risk of postoperative complications and increasing the quality of life of the patients.