New Clinicopathologic Scenarios of EBV+ Inflammatory Follicular Dendritic Cell Sarcoma: Report of 9 Extrahepatosplenic Cases.

EBV+ inflammatory follicular dendritic cell (FDC) sarcoma is an indolent malignant neoplasm of spindled FDCs with a rich lymphoplasmacytic infiltrate and a consistent association with Epstein-Barr virus (EBV). It occurs exclusively in the liver and spleen, with the exception of a few colonic examples. In this study, we report 9 extrahepatosplenic cases, including 4 occurring in previously undescribed sites, but all apparently anatomically related to the aerodigestive tract. The cases included 5 gastrointestinal tumors all presenting as colonic pedunculated polyps, 2 presenting as mesocolon mass, and 2 involving the palatine or nasopharyngeal tonsils. One patient with a colonic tumor was complicated by paraneoplastic pemphigus. The patients had a median age of 58 years, with female predominance (female:male=7:2). A favorable outcome was observed in 7 patients. Histologically, EBV+ inflammatory FDC sarcomas arising from these anatomic sites were similar to their hepatosplenic counterparts. Spindled to oval neoplastic cells with ill-defined cell borders were dispersed or formed loose whorled fascicles in a dense lymphoplasmacytic background. They had vesicular nuclei with distinct nucleoli and typically exhibited a range of nuclear atypia in the same case. The neoplastic cells showed variable expression of FDC markers and were labeled for Epstein-Barr virus-encoded RNA on in situ hybridization. These 9 cases thus broaden the clinicopathologic scenarios of EBV+ inflammatory FDC sarcoma. Recognition of the potential existence of this tumor type in extrahepatosplenic sites permits a correct diagnosis to be made.

[Clinicopathologic characteristics and prognositic indicators of tonsillar mantle cell lymphoma].

Objective: To investigate clinicopathological features and prognosis of tonsillar mantle cell lymphoma(TMCL). Methods: Clinical data of 25 patients with TMCL at Beijing Friendship Hospital, Capital Medical University from 2002 to 2016 were included. All the cases were reviewed microscopically. Various immunohistochemical stains were performed using the MaxVision two-step method. IgH/CCND1 gene fusion was detected by fluorescent in situ hybridization(FISH). Additionally, randomly selected 40 cases of non-tonsil MCL of the same period were compared. Results: Among all mantle cell lymphomas (MCL), TMCL accounted for 5.6%(25/449). The median age of the patients was 60 years(range: 44-82 years) with a M∶F ratio of 5.3 to 1.0. The main symptoms were sore throat and foreign body sensation and patients usually presented with enlargement or mass of tonsil. At the early stage of the disease, 18 cases(72.0%) were clinically misdiagnosed as tonsillitis. Lymph node involvement was present in 76.0%(19/25) of the patients. There were 4 cases(16.0%)with current splenic involvement, 11 cases(44.0%) with pharyngeal focal recidivism, and 3 cases(12.0%) with involvement of other non-lymphoid organs. Morphologically, tonsillar architectures were effaced at various degrees. Eighteen MCL cases showed classical type and 7 cases were blastoid variant. All tumors were positive for CD20 and cyclin D1. 92.0%(23/25) tumors showed weakly positive or positive expression for CD5. FISH test that IgH/CCND1 gene fusion was positive in two CD5 negative classical cases. 18 patients(72.0%) had a median follow-up time of 26 months(range: 6-81 months). The difference of survival rate between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients was not statistically significant(P>0.05). Compared with NTMCL, TMCL was found to have higher proportion of stage Ⅰ-Ⅱ disease (χ(2)=12.789, P<0.01), lower the proportion of non-lymphatic organ involvement (χ(2)=8.125, P<0.01), and better prognosis (χ(2)=4.351, P=0.037). Conclusion: The incidence of TMCL is low and prone to be misdiagnosed as tonsillitis. Patients with TMCL are more likely at stage Ⅰ-Ⅱ at presentation and the prognosis is better than that of NTMCL.

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation.

BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. METHODS: The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS-PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. RESULTS: Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and α-1-antichymotrypsin, as well as complement C1q. CONCLUSIONS: Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis.

Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure.

Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma.

BACKGROUND: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. METHODS: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. RESULTS: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. CONCLUSION: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.

Long-term Tumor-free Survival With Untreated Primary Diffuse Large B-cell Lymphoma of the Tonsil: A Report of 9 Cases.

In some cases, long-term tumor-free survival might be possible for untreated primary diffuse large B-cell lymphoma (DLBCL) of the tonsil. Here, we report of 9 untreated patients who had primary tonsil DLBCL with long-term tumor-free survival. All these patients were children or young adults (4 male and 5 female individuals; ages: 6 to 38 y, median age: 25 y) with clinically evident swollen tonsils or papillary neoplasms. Tonsillectomy and biopsies indicated partial structural destruction of the tonsils with diffuse infiltration of large lymphoid cells. The large cells expressed CD20 with a Ki-67 proliferative index >50%. All samples were negative for CD5, Epstein-Barr virus-encoded RNA, and t(14;18) translocation. Except for cases 2 and 4, all samples showed monoclonal immunoglobulin gene rearrangements. Although chemotherapy and radiotherapy had not been administered after tonsillectomy (for various reasons), periodic imaging and clinical evaluation showed that none of the 9 patients developed or died of lymphoma (median follow-up: 40 mo). In conclusion, primary tonsil DLBCL does not always behave in a malignant manner, and some patients can achieve long-term tumor-free survival without chemotherapy or radiotherapy. On the basis of this case series, we concluded that close follow-up and observation might be possible for pediatric and young-adult patients who have undergone complete tonsillectomy for primary tonsil DLBCL with the following features: short disease course, morphologically early lesions, negativity for Epstein-Barr virus-encoded RNA and t(14;18) translocation, and no involvement of any other sites, after careful clinical evaluation.

Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

OBJECTIVE: To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS: Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS: Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION: The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

Human papillomavirus-related cell cycle markers can predict survival outcomes following a transoral lateral oropharyngectomy for tonsillar squamous cell carcinoma.

OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)-related cell cycle marker profiles in patients who have received a transoral lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV-related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA status of 42 consecutive TSCC patients who underwent TLO-based treatments were analyzed. The prognostic value of each marker was evaluated. RESULTS: Univariate analysis indicated that high p16, low pRb, and low p53 expression levels are significantly associated with a good disease-free and overall survival outcome. Clinicopathological parameters and the HPV DNA status did not show prognostic significance. When adjusted for age, overall stage and treatment strategy, a high p16 and low pRb level remained an effective prognostic marker for good survival outcomes. A high p16/low pRb combination showed superior survival prediction ability over high p16 or low pRb alone. CONCLUSION: HPV-related cell cycle markers may also be good indicators for predicting survival after TLO for TSCC. The de-escalation TLO surgery approach would be more effective if performed under the stringent guidance of these markers.

Primary small cell neuroendocrine carcinoma of the tonsil: a case report and review of the literature.

Small cell neuroendocrine carcinoma (NEC) that originates in the tonsil is extremely rare and carries a poor prognosis. Only a few cases of this tumor have been reported so far and the standard treatment protocol remains uncertain. Here we describe a 74-year-old woman presented with throat pain for about 2 months. Computed tomography (CT) scan revealed a 3.4×1.8 cm tumor with moderate enhancement in the left tonsil and a 1.3×1.0 cm neck mass in left level II. A biopsy of the tonsillar mass was performed and histologic examination revealed small round to oval tumor cells were arranged in cords or nests, containing hyperchromatic nuclei and scant cytoplasm. Mitotic figures were readily identified. Immunohistochemical staining showed that tumor cells were strongly positive for CD56, focally positive for PCK and negative for LCA. A diagnosis of primary small cell NEC of the left tonsil was obtained. The patient was treated by six cycles of cisplatin combined with etoposide and the masses showed initial complete response. But recurrence in the left neck was found 9 months after initial diagnosis and the patient refused any further treatment. With a review of the literature, the nomenclature, clinicopathological characteristics and treatment modalities of this rare tumor are discussed.

Possible role of nano-sized particles in chronic tonsillitis and tonsillar carcinoma: a pilot study.

This study aimed to evaluate the palatine tonsils of patients with chronic tonsillitis and spinocellular carcinoma to determine the presence of nano-sized particles. Tonsil samples from adult patients with chronic tonsillitis and spinocellular carcinoma of the palatine tonsil were dried and analyzed using a scanning electron microscope with the X-ray microprobe of an energy-dispersive spectroscope. Demographic data and smoking histories were obtained. The principal metals found in almost all tissues analyzed were iron, chromium, nickel, aluminum, zinc, and copper. No significant difference in elemental composition was found between the group of patients with chronic tonsillitis and the group with spinocellular carcinoma of the palatine tonsil. Likewise, no significant difference was found between the group of smokers and the group of nonsmokers. The presence of various micro- and nano-sized metallic particles in human tonsils was confirmed. These particles may potentially cause an inflammatory response as well as neoplastic changes in human palatine tonsils similar to those occurring in the lungs. Further and more detailed studies addressing this issue, including studies designed to determine the chemical form of the metals detected, studies devoted to quantitative analysis, biokinetics, and to the degradation and elimination of nanoparticles are needed for a more detailed prediction of the relation between the diagnosis and the presence of specific metal nanoparticles in tonsillar tissue.

Unlocking pathology archives for microRNA-profiling.

BACKGROUND: MicroRNAs (miRNAs) are approximately 22 nucleotide long, non-coding RNAs that regulate gene expression by binding to the 3'-untranslated region of target mRNAs and also a variety of cellular processes. It has recently been established that dysregulation of miRNA expression can be detected in the majority of human cancers. A variety of high-throughput screening methods has been developed to identify dysregulated miRNA species in tumours. For retrospective clinical studies formalin-fixed, paraffin-embedded (FFPE) tissue is the most widely used material. MATERIALS AND METHODS: The miRNA expression profiles of freshly frozen (CRYO) and FFPE tissues of seven tonsil and four liver samples were compared, using a qPCR-based assay, profiling 157 miRNA species. RESULTS: The significance of miRNA-profiles was barely influenced by FFPE treatment in both tissues and the variance induced by FFPE treatment was much smaller than the variance caused by biologically based differential expression. CONCLUSION: FFPE material is well suited for miRNA profiling.

Marginal zone B-Cell lymphoma among primary B-Cell lymphoma of Waldeyer's ring: histopathologic and immunohistochemical study of 16 tonsillectomy specimens.

Two subtypes of marginal zone B-cell lymphoma (eg, mucosa-associated lymphoid tissue [MALT] type and splenic type) have been reported in the lymph node. To determine the presence or absence of marginal zone B-cell lymphoma of MALT type and the splenic type among Waldeyer's ring (WR) lymphomas, 16 tonsillectomy specimens were studied. Ten cases (63%) were marginal zone B-cell lymphoma. Among marginal zone B-cell lymphoma, 7 were the MALT type and the remaining 3 cases of marginal zone B-cell lymphoma were the splenic type. Moreover, 4 cases of 7 MALT-type lymphomas contained numerous large cells (diffuse large B-cell lymphoma arising from a low-grade marginal zone B-cell lymphoma of MALT type). The low incidence of primary mucosa-associated lymphoid tissue type lymphoma of WR in previous reports may be because it is difficult to correctly identify the characteristic histologic findings of MALT-type lymphoma because of the small biopsy size.

Extramedullary plasmacytoma of the tonsil diagnosed by fine-needle aspiration cytology.

A case of tonsillar extramedullary plasmacytoma in a 53-year-old man with a complaint of lump sensation in the throat is presented. Examination of the oral cavity showed enlargement of the left tonsil. Magnetic resonance imaging demonstrated a solid mass, measuring 3.2 x 2.0 x 3.8 cm, in the left tonsil. Cytologic smear obtained by fine-needle aspiration biopsy appeared highly cellular and was composed of clusters of plasma cells with varying maturity. Atypical plasma cells had prominent eccentric nuclei with nucleoli and finely granular cytoplasm. Binucleated cells and mitotic figures were also identified. The cytoplasm of mature-looking small plasma cells was also finely granular without a perinuclear halo. A cytologic diagnosis of plasmacytoma was made. Excisional biopsy showed sheets of plasmacytoid cells with abundant eosinophilic granular cytoplasm. Occasional binucleated and pleomorphic cells with giant nuclei and prominent nucleoli were observed. These plasmacytoid cells were diffusely immunoreactive for lambda light chain and IgG, partially positive for epithelial membrane antigen. Metastatic examination finding was negative for multiple myeloma, and the patient was diagnosed as having extramedullary plasmacytoma. Although the diagnosis of plasmacytoma on cytologic smear may be difficult, in the current case, fine-needle aspiration cytology provided a rapid and accurate diagnosis.

Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome.

To determine whether human papillomaviruses (HPV) positive tonsillar squamous cell carcinoma (SCC) represent a specific entity, we studied the prevalence of HPV association and of tobacco/alcohol exposure in a series of 52 cases of tonsillar SCC cases. p53, p16, and pRb levels, deregulated by viral oncoproteins were assessed. Forty patients reported tobacco/alcohol exposure, 10 reported no exposure. HPV DNA was found in 32/52 (62%) cases, (HPV16 genotype in 27). All patients with no history of tobacco-alcohol exposure presented HPV positive tumor (p=0.0008). A strong correlation was observed between positive HPV status, decrease in pRB and increase in p16 expression level. 5 year overall survival rate was higher in HPV16 positive patients than in HPV negative (71% versus 36%; p=0.023). HPV status remained a significant prognostic factor in multivariate analysis. Tonsillar SCC can thus be divided in HPV positive and negative subgroups with different oncogenesis and response to treatment.

Solitary fibrous tumor with atypical histological features occurring in the palatine tonsil: an uncommon neoplasm in an uncommon site.

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleura. Although this tumor has been described in other sites, including the head and neck area, in the oropharynx it is extremely rare. We report the first case of a SFT arising from the palatine tonsil of a 62-year-old man. The tumor consisted of spindle-shaped cells distributed in a haphazard pattern and presented atypical histological features such as hypercellular areas and high mitotic count. Immunohistochemical studies showed strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100 protein and cytokeratines were negative. The patient was well without disease 1 year after surgery.

Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular lymphoma with diffuse areas or follicular colonization.

Focal follicular features in diffuse large B-cell lymphomas (DLBCLs) are bound to raise the question of follicular lymphoma (FL) with diffuse areas, because the diagnosis of FL is based on the presence of follicular areas, even though focal. We report 7 cases of primary tonsillar DLBCLs with focal follicular features that presented with morphologic, immunohistochemical, and biological features distinct from those of FL. Histologically, these tumors were characterized by involvement of pericryptal follicles with adjacent dominant diffuse areas. Monomorphous large tumor cells were evenly spaced with abundant, often clear cytoplasm, and blastoid nuclei often with a delicate nuclear membrane. Importantly, residual germinal centers (GCs) were present in the form of either an intrafollicular GC remnant or an isolated GC in the midst of diffuse tumor. An extrafollicular and/or parafollicular growth pattern was also observed. Bcl-6 staining revealed a predominantly sporadic occurrence of Bcl-6(+) cells, comprising <50% of tumor cells, and none displayed diffusely dense collections (>75%) of Bcl-6(+) tumor cells characteristic of the GC or FL. Staining for CD10 was negative in 6 cases. Five of 7 patients were younger than 60, the median age of other patients with primary tonsillar DLBCL. No extratonsillar involvement was seen at 18 months after diagnosis. After chemotherapy or radiotherapy, complete remission was achieved with ease in all patients, but 2 patients who were treated with chemotherapy alone relapsed at 24 and 30 months. In conclusion, tonsillar DLBCL includes a small (10%) but distinct subgroup that warrants distinction from FL with predominant diffuse areas or de novo DLBCL. It appears that the focal follicular features in tonsillar DLBCL likely represent follicular colonization of marginal zone B-cell lymphoma, probably high-grade, if the possibility of FL is excluded.

Extranodal follicular dendritic cell sarcoma of the head and neck region: three new cases, with a review of the literature.

Extranodal follicular dendritic cell (FDC) sarcoma of the head and neck region is uncommon, with 16 well-documented cases previously reported (four in the tonsil, four in the pharynx, two in the palate, five in the soft tissue, and one in the thyroid). We here report an additional three cases of extranodal FDC sarcoma in the tonsil (two cases) and pharynx (one case). In these new cases, the neoplastic cells were arranged in diffuse, fascicular, and vaguely whorled growth patterns. A background lymphocytic infiltrate was sprinkled throughout the neoplasms, with focal prominent perivascular cuffing. Scattered multinucleated giant cells were present. Immunohistochemically, tumor cells were strongly and diffusely positive for follicular dendritic cell markers CD21 and CD35. Tumor cells were diffusely positive for fascin and negative for leukocyte common antigen, S-100 protein, cytokeratin, and Epstein-Barr virus (EBV) latent membrane protein-1 (EBV-LMP). EBV was also not detected in the tumor cells by in situ hybridization for EBV-encoded RNAs. FDC sarcomas are probably an underrecognized neoplasm, especially when they occur in extranodal sites in the head and neck region. Two of the three new cases we report were initially misdiagnosed, and five cases of extranodal FDC sarcoma in the head and neck region reported in the recent literature were initially misdiagnosed. Our aim is to complement the current understanding of this neoplasm and alert pathologists to this rare entity in this region to avoid misdiagnosis. Recognition of extranodal FDC sarcoma requires a high index of suspicion, but this tumor has numerous distinctive histological features that should bring the neoplasm into the differential diagnosis. Confirmatory immunohistochemical staining with follicular dendritic cell markers such as CD21 and/or CD35 is essential for the diagnosis. Correct characterization of this neoplasm is imperative given its potential for recurrence and metastasis.

Epstein-Barr virus DNA is not increased in tonsillar carcinoma.

Epstein-Barr virus (EBV) is a known oncogenic virus associated with a wide variety of cancers, including nasopharyngeal carcinoma. Waldeyer's ring, a collection of lymphoid tissues, includes the nasopharynx, pharyngeal, and lingual tonsils. To determine if EBV plays a causative role in carcinomas arising from other tissues in Waldeyer's ring, we examined pharyngeal tonsillar carcinomas for evidence of EBV infection. As previously reported, DNA was extracted from 53 consecutive tonsil cancers, as well as from age- and gender-matched non-cancerous tonsillectomy specimens. Three different sets of primers for discrete exons of EBV were then used to determine if active or latent EBV infection was expressed in the extracted DNA using the polymerase chain reaction (PCR). All positive bands were then sequenced to confirm the presence of amplified EBV fragments. None of the samples showed evidence for active EBV infection. In primers demonstrating latent infection, 1 of 53 (1.9%) of tumors were positive, versus 6 of 53 (11.3%) of the controls. These results indicate that EBV expression is not increased in DNA from tonsil cancers and that EBV infection does not have a causal relationship with tonsil cancer.

Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival.

BACKGROUND: Human papilloma virus (HPV), which is frequently present in tonsillar carcinoma seems to be a prognostically favourable factor for patient survival and also for low risk of relapse. Since HPV may abrogate the function of wild type p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53 status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and patient survival. MATERIALS AND METHODS: Pre-treatment primary tonsillar carcinoma specimens were obtained retrospectively from 40 patients, 21 complete responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage III and IV tumours. The paraffin-embedded biopsies were analysed for presence of HPV DNA, by general and type specific PCR, and for p53 overexpression by immunohistochemical staining with the murine Mab DO-1. RESULTS: It was possible to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53 immunostaining (p53+) were not correlated with response to RT, since 8/18 CR patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR patients were p53+. A tendency towards a survival benefit in patients with HPV+ tumours was observed and this tendency was significant for patients with stage IV HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A difference in survival between patients with p53+ cancer as compared to patients with p53- lesions was not demonstrated. In conclusion, although presence of HPV and p53 immunoreactivity in tonsillar carcinoma could not be related to RT response, determination of HPV and p53 status may still prove useful as predictive/prognostic markers.

Immunohistochemical analysis of small cell carcinoma of the head and neck: a report of four patients and a review of sixteen patients in the literature with ectopic hormone production.

Small cell carcinoma (SCC) occurs mostly in the lung, and in some patients is accompanied by production of ectopic hormones. Small cell carcinoma of the head and neck is very rare. We report 4 patients with SCC of the head and neck (larynx, tonsil, maxillary sinus, and parotid gland). The patient with SCC of the maxillary sinus demonstrated a high level of plasma serotonin and overexpression of parathyroid hormone; however, he did not show any related symptoms. The patient with SCC of the tonsil showed the syndrome of inappropriate secretion of antidiuretic hormone associated with antidiuretic hormone hyperproduction at the terminal stage. In the literature, 16 patients with SCC of the head and neck with ectopic hormone production have been reported. Antidiuretic hormone and adrenocorticotropic hormone were the hormones that caused clinical symptoms (paraneoplastic syndromes). We believe that the evaluation of hormonal syndromes is valuable for diagnosis and treatment.