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Current data advocate that oropharyngeal squamous cell carcinoma (OPSCC) should be divided into subsites when evaluating the presence of human papillomavirus (HPV) and prognosis. More specifically, tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have much higher HPV prevalence compared to other OPSCC. Moreover, patients with HPV positive (HPV+) TSCC and BOTSCC have a better prognosis as compared to patients with HPV negative (HPV-) corresponding tumors, while the prognostic role of HPV in other OPSCC is unclear. Furthermore, in a recent report from Denmark, TSCC was further subclassified into specified TSCC (STSCC) and nonspecified TSCC (NSTSCC), with HPV significantly more prevalent in STSCC. In this study, the histopathological influence of HPV prevalence and survival in TSCC was analyzed in a TSCC cohort with known HPV status, of patients diagnosed 1970-2002 in Stockholm. In total, 139 TSCC biopsies with both tumor and adjacent normal tissue were separated into STSCC and NSTSCC. HPV was significantly more commonly found in STSCC than in NSTSCC. Patients with HPV+ STSCC had a better disease-specific and overall survival as compared to patients with HPV+ NSTSCC, but no survival differences were observed in patients with HPV- STSCC and NSTCC. These findings confirm previous reports and suggest that TSCC subsite may also be of relevance for clinical outcome and should be further followed up in future studies.

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The present study aimed to define the natural history, World Health Organization (WHO) classification, prognostic factors, and treatment outcome of 87 patients with primary lymphoma of the palatine tonsil and literature review and analysis. Between 1990 and March 2008, 87 consecutive patients diagnosed with primary lymphoid malignancy of the palatine tonsil. All pathologic specimens were reviewed and reclassified according to the recent WHO classification. To investigate the association of tonsillar lymphomas with Epstein-Barr virus (EBV), in situ hybridization was performed for 24 tonsillar lymphomas (23 diffuse large B-cell lymphoma (DLBC) and one classic Hodgkin's disease) and ten normal tonsils as control group. In literature review, we found 26 major related series including 1,602 patients with primary tonsillar lymphoma. The median age of our patients was 52 years (range 11-86 years). There were 39 women and 48 men with a median follow-up of 67 months for living patients. The vast majority (95%) of patients had B-cell phenotype. DLBC was the most frequent histology. In situ hybridization revealed none of 23 DLBC to be positive for EBV. The 5-year disease-free and overall survival rates were 78.9% and 86%, respectively. In the literature review and by analyzing the data collection from 26 major reported series, the median age was 55 years and male/female ratio was 1.3:1. Intermediate grade tumors consisted of 72% of all tonsillar lymphomas and B-cell lymphomas constituted 82% of all cell immunophenotypes. The 5-year disease-free and overall survival rates were 61% and 67%, respectively. The vast majority of tonsillar lymphomas are of B-cell origin and with intermediate to high-grade histology. These neoplasms tend to present in early stage disease and to have favorable outcome. WHO classification predicts more accurately treatment outcome of patients with tonsillar lymphoma. The association of DLBC in the palatine tonsil with EBV infection is infrequent.

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BACKGROUND: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region. METHODS: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced. The authors identified or derived a measure for each criterion and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). Data were from a retrospective chart review on 642 cases of carcinoma of the tonsillar region treated with radiotherapy for cure at the Princess Margaret Hospital from 1970-1991. None of the patients had distant metastases. RESULTS: The scheme proposed by Synderman and Wagner, which was published in Otolaryngology Head and Neck Surgery in 1995 (vol.112, pages 691-4), scored best at 1.2. The UICC/AJCC scheme scored worst at 6.1. The hazard consistency ranged from a 3.1% average survival difference to 6.7% across the 8 schemes. The hazard discrimination measure varied by 28% from the best to worst scheme. Prediction varied by up to almost twofold across the schemes assessed. The distribution of patients varied from expected by between 0.13% and 0.57%. CONCLUSION: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically-derived schemes the authors evaluated. The results of the current study suggest that the usefulness of the TNM system can be enhanced by optimizing the design of stage groupings through empirical investigation.

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Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing squamous cell carcinomas (SCC). Their cervical lymph node metastases are not uncommonly cystic and filled with necrotic tumor cells. Some cysts, however, contain clear fluid. During the investigation of SCC producing "fluid-filled" cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90 primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of primary and metastatic carcinoma with special focus on the expression of CK7, a putative marker for ductal differentiation. CK7 was expressed in submucosal minor salivary gland acini and ducts, but not in the squamous surface epithelium of the Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts of submucosal minor salivary glands, and showed only insignificant surface involvement. They were characterized by a solid infiltrative growth pattern of basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7-positive carcinomas produced CK7-positive cystic nodal metastases, most of which contained paucicellular fluid. No solid CK7-positive nodal metastases were identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring area appear to arise from large excretory ducts of submucosal minor salivary glands with only limited surface involvement, express CK7, and produce CK7-positive cystic "fluid-filled" nodal metastases. The histomorphology and immunophenotype suggest that these carcinomas represent basaloid SCC arising from excretory ducts of the submucosal minor salivary glands.

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A prospective study on the value of ultrasound (US) for the staging of 70 cases of cancer of the tongue and tonsil was performed. A real-time, high-frequency transducer was used, and the examination was often coupled with endobuccal palpation. US did not visualize the tumor in nine of 42 cases of tongue cancer (seven stage T1 and two anterior stage T2 tumors); US accurately defined tumor size in 33 cases. The degree of in-depth extension and the location with respect to the median line (only four false results) were evaluated correctly. With regard to 28 tonsil cancers, US depicted extension from the tonsillar fossa to the tongue in all cases but one (13 of 14 cases). US is valuable for the detection of cervical lymph nodes associated with both tongue and tonsil tumors and is a safe and helpful technique for the follow-up of medium-size lesions. The major limitations of US include the nonvisualization of superficial lesions, reduced accuracy for evaluation of the extension of large tumors, and analysis of posterior pharyngeal extension.

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In a retrospective review of 170 cases of malignancies of the tonsil the authors report on 81 malignant epithelial tumors. In 56 cases (69.1%), the tumor (squamous cell carcinoma) was composed of solid epithelial nests with different degrees of keratinization. In 24 cases (29.6%) the tumor (undifferentiated carcinoma of nasopharyngeal type) had histologic characteristics similar to the undifferentiated carcinomas observed in the nasopharynx. Only one case was unclassifiable. Squamous cell carcinomas occurred more frequently in males (6:1), in older age, with more frequent extratonsillar and nodal extension and a poorer prognosis. Undifferentiated carcinoma had a similar incidence in both sexes, occurred also at an early age, and more often seemed to be limited to the tonsil. The 10-year disease-free survival rate was 30% for undifferentiated carcinoma; all the patients affected by squamous cell carcinoma had a recurrence within 6 years of the diagnosis.

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The clinicopathologic data of 97 patients with non-Hodgkin's lymphomas involving Waldeyer's ring were retrospectively reviewed. Age, sex, the site of involvement within Waldeyer's ring, and Rappaport's histological classification played little role in the prognosis. Although the Ann Arbor staging classification was the only factor that correlated with the patients' prognoses (stage I vs stage II, p less than 0.01; stage II vs stage III + IV, p less than 0.02), it is not considered the ideal classification. The survival rates of stage II patients, who comprised about 60% of the entire group, was quite different due to their cervical node status. That is, 33 patients with bulky cervical nodes (4 cm in diameter or more) or bilateral cervical nodes had significantly poorer survival rates than 24 patients with small unilateral cervical nodes (p less than 0.001). The survival curve of the former group was similar to that of the stage III and IV patients, whereas the survival curve of the latter group was similar to that of the stage I patients. Lymphography, which was performed for 72 patients in this series, is not considered essential. From these results, we recommend the categorization of patients with malignant lymphomas involving Waldeyer's ring into two major groups according to cervical and inguinal node status in order to assess treatment methods. That is, patients with bulky or bilateral cervical lymph nodes or those with inguinal lymphadenopathy and patients without any lymphadenopathy or those with minimal unilateral cervical nodes alone.

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A diffuse, large cell lymphoma of palatine tonsil was found to contain a considerable number of enlarged tumor cells with prominent, hyaline, Russell body-type cytoplasmic inclusions displacing the nucleus peripherally and, thus, the morphologic features of signet-ring cell lymphoma. Immunoperoxidase staining revealed that the contents of the signet-ring cells were strongly positive for mu heavy chains and kappa light chains. Ultrastructurally, Russell body-type inclusions consisted of multiple, angulated, electron-dense crystalloids enclosed within expanded segments of rough endoplasmic reticulum.

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In the present study a re-classification of 96 lymphomas of the epipharynx and the mesopharynx including tonsils, paranasal sinuses and neck region was performed using the Kiel-classification. The histological criteria employed for this procedure were described briefly. 33 cases could be diagnosed as lymphomas of low grade malignancy, 50 cases belonged to the group of high grade malignancy and 13 cases remained unclassifiable. There was a light preponderance of male patients in the whole lymphoma group. The most frequent tumors were immunoblastic lymphomas, followed by immunocytomas, lymphoblastic lymphomas, centroblastic lymphomas, centroblastic/centrocytic and centrocytic lymphomas. Examples of transitions of one lymphoma type into another were demonstrated. The fact must be mentioned that lymphomas of the paranasal sinuses were nearly completely of the immunocytic or immunoblastic type.

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The Rappaport classification of the non-Hodgkin's lymphomata was applied to 460 cases at the Princess Margaret Hospital. Statistically significant differences in the numerical incidence between the nodular and diffuse patterns was found for the entire series and for the lymphocytic, "histiocytic" and mixed cell types individually. All of the undifferentiated types were diffuse. These differences were sustained for the degrees of differentiation within the lymphocytic group. The "histiocytic" group was not subclassified by differentiation. The cell types differed in the numerical distribution of the patterns. The lymphocytics were predominantly diffuse but their nodular forms constituted a higher proportion of the nodular pattern than did their diffuse types of the diffuse group. More of the well differentiated lymphocytics were nodular than were diffuse and they formed a higher proportion of the nodular group than they did of the diffuse. On the other hand, the poorly differentiated lymphocytics were predominantly diffuse and these were less well represented in the nodular group than in the diffuse tumours. The intermediate differentiated types were usually diffuse but slightly better represented in the nodular group. Most tumours of the "histiocytic" type were diffuse and these constituted a higher proportion of diffuse than the nodular tumours. The mixed cell lesions were predominantly nodular and comprised a much higher proportion of nodular lesions than diffuse. No real differences were identified amongst the histological types according to age or sex distributions. The crude survival to 4 years differed significantly for the histological types. For the entire series and for each cellular type, the nodular patterns were superior to the diffuse, although, in the lymphocytic well differentiated types, pattern made no real difference to survival.

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