Processing of an ambiguous time phrase in posttraumatic stress disorder: Eye movements suggest a passive, oncoming perception of the future.

Metaphorically, the future can be perceived as approaching us (time-moving metaphor) or as being approached by us (ego-moving metaphor). Also, in line with findings that our eyes look more up when thinking about the future than the past, the future's location can be conceptualized in upwards terms. Eye movements were recorded in 19 participants with PTSD and 20 healthy controls. Participants with PTSD showed downward and healthy controls upward eye movements while processing an ego/time-moving ambiguous phrase, suggesting a passive (time-moving) outlook toward the future. If replicated, our findings may have implications for the conceptualization and treatment of PTSD.

Expression of programmed death-1 (CD279) in primary cutaneous B-cell lymphomas with correlation to lymphoma entities and biological behaviour.

BACKGROUND: Programmed death-1 (PD-1/CD279) is a cell-surface protein expressed in activated T cells and a subset of T lymphocytes including follicular helper T cells (TFH ). The interaction between PD-1 and its ligands plays a role in immune response and evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1-positive lymphocytes is associated with overall survival. OBJECTIVES: To investigate 28 cases of primary cutaneous B-cell lymphoma, including the subtypes PCFCL (n = 10), PCMZL (n = 10) and DLBCL-LT (n = 8) for the number and density of PD-1-positive cells. METHODS: Immunohistochemical staining and a computerized morphometric analysis for evaluation were applied. The results were correlated with the clinical outcome. To distinguish between activated T cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13 staining. Double staining for PD-1 and PAX-5 was used to investigate whether tumour cells were positive for PD-1. RESULTS: The PD-1-positive cells represented tumour-infiltrating T cells (TILs). Only a minor subset was represented by TFH . Patients with DLBCL-LT had a significantly lower number of PD-1-positive TILs than those with PCMZL (P = 0·012) and PCFCL (P = 0·002) or both (P = 0·001). The difference between PCMZL and PCFCL did not reach significance (P = 0·074). The tumour cells were negative for PD-1. CONCLUSIONS: A higher number of PD-1-expressing cells was found in indolent PCMZL and PCFCL than in high-malignant DLBCL-LT. The PD-1-positive cells represented not only TFH , but also other activated T cells as a part of the tumour microenvironment. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression.

Taijin kyofusho and social anxiety and their clinical relevance in indonesia and Switzerland.

BACKGROUND: Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. METHOD: 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears. RESULTS: TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms. DISCUSSION: TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

[Warthin tumor with carcinoma: malignant transformation or metastasis?]. / Warthin-Tumor mit Karzinom: Maligne Transformation oder Metastase?

We present the unusual case of a cytologically diagnosed Warthin tumor (WT) of long standing with sudden enlargement und subsequent resection. Histologically, the diagnosis of WT was confirmed, but the tumor additionally showed diffuse infiltrates of an adenocarcinoma undergoing unrestrained growth. Warthin tumor with malignant transformation was suspected and radiological staging examinations were conducted. PET scans detected a metastasizing carcinoma of the breast, morphologically identical to the WT infiltrates. Care should always be taken when the diagnosis of malignant WT is made to exclude metastatic disease.

MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.

BACKGROUND: Primary cutaneous CD30+ lymphoproliferative disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T-cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ lymphoproliferative disorders. OBJECTIVES: To examine the expression of MUM1 in CD30+ lymphoproliferative disorders and to assess its value as a diagnostic marker. METHODS: Thirty-one formalin-fixed paraffin-embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. RESULTS: Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50-90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1-positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0.002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0.015). CONCLUSIONS: MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders.

Sinonasal tubulopapillary low-grade adenocarcinoma. Histopathological, immunohistochemical and ultrastructural features of poorly recognised entity.

We present the clinicopathological, histological and immunohistochemical findings of six cases of primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract with ultrastructural examination in one case. Due to its unique features, we believe that primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract represents a tumour entity different from any tumours generally recognised in the sinonasal region. Our cases had an equal sex incidence, with an age range of 44-76 years. The tumour has a tendency to recur, but none of our six patients developed metastases. We feel that it is important to separate this tumour entity from other types of sinonasal adenocarcinomas that exhibit a papillary growth pattern, as they frequently pursue a much more aggressive clinical course than the tumours in this study.

Sclerosing polycystic adenosis of parotid gland with dysplasia and ductal carcinoma in situ. Report of three cases with immunohistochemical and ultrastructural examination.

We describe three cases of sclerosing polycystic adenosis (SPA) of the parotid gland, a salivary condition analogous to fibrocystic disease of the breast. For the first time, immunoreactivity for oestrogen and progesterone receptors was demonstrated, suggesting a possible participation of hormone stimulation in its pathogenesis. In addition, all our cases showed foci of dysplasia of the ductal epithelium, which in one case was severe enough to amount to carcinoma in situ. This feature that has not previously been reported in SPA.

Sentinel lymph node evaluation in squamous cell carcinoma of the head and neck.

OBJECTIVE: The aim of our study was to assess the feasibility of sentinel lymph node (SLN) radiolocalization in N0 neck in squamous cell head and neck carcinoma and its predictive value for occult metastasis. STUDY DESIGN: Nineteen patients of an open prospective trial. SETTING: After peritumoral injection of a 99m Tc labeled radiocolloid, the SLN was localized preoperatively by lymphoscintigraphy and intraoperatively through the intact skin by a hand-held gamma-probe. The histology of the SLN and the nodes of the elective neck dissection were compared. RESULTS: Localization of the SLN by lymphoscintigraphy was possible in 18 of 19, and with the hand-held gamma-probe in all 19 patients. Six SLN revealed occult metastatic disease. No skip metastasis were found in the 13 neck specimen with negative SLN. CONCLUSION: SLN evaluation in N0 neck in squamous cell carcinoma of the head and neck is accurately feasible and seems to adequately predict the presence of occult metastasis.

Significance of human papillomavirus in sinonasal papillomas.

Recent investigations have suggested human papillomavirus (HPV) to be involved in the development of sinonasal papillomas (SNP). Forty-three patients operated for SNP were studied to determine the prevalence of HPV-DNA sequences in these tumours and to evaluate their value as a prognostic parameter. The original sections of all cases were reviewed and reclassified according to the WHO. Paraffin blocks available from 37 patients were subjected to in situ hybridization (ISH) and polymerase chain reaction (PCR). Histology revealed 34 cases of inverted papilloma (IP) (79 per cent), five cases of exophytic papilloma (EP) (12 per cent) and four cases of columnar cell papilloma (CCP) (nine per cent). Recurrences developed in seven of 41 patients (17 per cent), and malignancy occurred in four of 43 patients (nine per cent). HPV was detected in four of 37 specimens (11 per cent) both by ISH and PCR. In particular, HPV-11 was found in three lesions (two EP, one IP) (eight per cent), and HPV-6b was detected in one lesion (one EP) (three per cent). Our findings suggest a possible role for HPV in the pathogenesis of exophytic papillomas. As no correlation was found to malignancy and recurrence of disease, screening for HPV seems not to be useful as a prognostic parameter.

[Significance of human papillomaviruses (HPV) in sinonasal papillomas]. / Wertigkeit der humanen Papillomaviren (HPV) bei sinonasalen Papillomen.

The present study comprises 43 patients with sinonasal papillomas operated on between 1990 and 1997 at the ENT Department, University Hospital of Zurich. Histology showed 5 cases of exophytic papilloma (EP) (12%), 34 cases of inverted papilloma (IP) (79%) including 4 cases of associated carcinoma (9%), and 4 cases of columnar cell papilloma (CCP) (9%). Recurrence developed in 6 of 41 patients (2 EP, 4 IP) (15%). HPV was detected in 4 of 37 specimens (11%) both by in situ hybridization (ISH) and polymerase chain reaction (PCR). HPV-11 was found in 3 lesions (2 EP, 1 IP), whereas HPV-6b was detected only in one lesion (1 EP). Altogether 3 of 5 EP (60%), one of 29 IP (3%) and one of 6 recurrent papillomas (1 EP) (17%) tested positive for HPV. Our findings suggest a possible role for HPV in the pathogenesis of exophytic papilloma. As no correlation was found with associated malignancy and recurrence of disease, screening for HPV seems not to be useful as a prognostic parameter.

[Primary small cell carcinomas and metastatic disease in the head and neck]. / Kleinzellige Karzinome. Primärtumoren und Metastasen im Kopf-Hals-Bereich.

Extrapulmonary small cell carcinomas are recognized as a clinicopathologic entity distinct from small cell lung cancer. Such carcinomas as primary tumors have been described in several locations in the head and neck although most cases of metastatic tumor in the neck originate from a pulmonary primary. In this report we present a small cell carcinoma of the larynx, metastasis in the parotid gland as the first manifestation of a small cell lung cancer and a small cell carcinoma of the Merkel cell type in a parotid lymph node. Our review of the current literature shows that most small cell carcinomas in the head and neck are extrapulmonary primary tumors. Since histological criteria are the same, a pulmonary neoplasm has to be excluded in every case. The differentiation between a primary head and neck tumor and metastatic disease as well as the location and staging are essential criteria for therapy and prognosis.

[Basal cell adenocarcinoma of the parotid gland: a rare tumor entity. Case report and review of the literature]. / Basalzelladenokarzinom der Glandula parotis: eine seltene Tumorentität. Fallbericht und Literaturübersicht.

Basal cell adenocarcinoma is a rare entity that was first defined as a malignant salivary gland tumor in 1991. We present another case report and discuss pathology, pathogenesis, differential diagnosis, therapy and prognosis on the basis of currently available literature. Although histomorphologic features of the tumors are similar to basal cell adenomas, proof of an infiltrative and destructive growth is essential for diagnosis. Adenoid cystic carcinoma and basaloid squamous carcinoma must also be considered in any differential diagnosis. Tumor development within a pre-existing basal cell adenoma and de novo development are discussed. Most of the tumors appear to be benign clinically. Facial pain is rare and facial nerve palsy was noted in only one case. Metastases have occurred in less than 10% of patients, with only one involving the lung. Due to their biologic behavior and prognosis, basal cell adenocarcinomas should be classified as low-grade carcinomas. The therapy of choice is parotidectomy with preservation of the facial nerve. Neck dissection has to be added in cases with cervical metastases. Radiation is advisable in patients with recurrent disease. Since there is a nearly 30% local recurrence rate, intensive follow-up is necessary.

[Parotid tumors of non-glandular origin: local and distant metastases in the parotid gland]. / Parotistumoren nicht glandulären Ursprungs: Nah- und Fernmetastasen in der Ohrspeicheldrüse.

BACKGROUND: Secondary involvement of the parotid gland by nonsalivary gland malignancies is relatively common. Especially if the primary site is unknown, distinguishing a primary neoplasm from a metastasis can be difficult. PATIENTS: This text reviews 10 metastatic lesions to the parotid gland from 252 consecutive parotid tumors. Moreover we present the metastasis of an oat cell carcinoma as initial presentation of a lung tumor. RESULTS: The percentage of metastatic tumors of the parotid gland in our study group was 4%, representing 32% of all malignancies. The majority (80%) originate from primary tumors in the head and neck region with skin cancer being the most important primary site (70%). In 40% the parotid gland metastasis was the first manifestation of a malignancy. CONCLUSIONS: The distinction between primary salivary gland tumor and metastasis is of particular importance for therapy and prognosis. The possibility of a metastatic tumor should always be considered when primary salivary gland tumors have histologic features similar to those of tumors occurring in other regions of the body (squamous carcinoma, melanoma, adenocarcinoma, clear cell, oat cell, and undifferentiated carcinoma). The skin of the head and neck is of primary interest during clinical examination, followed by the mucosa of the upper respiratory and digestive tract. Histologic and especially immunohistochemical characteristics can be helpful in identifying the primary tumor. If metastases to the parotid gland are the only manifestation and if they only spread to regional lymph nodes, more aggressive surgical treatment may be beneficial.

CD44 standard and variant isoform expression in normal human skin appendages and epidermis.

CD44 isoforms have been implicated in tumor progression and metastasis formation. This study presents a thorough immunohistochemical analysis of CD44 standard and isoform expression in normal human skin appendages and epidermis applying monoclonal antibodies against CD44s, CD44v3, -v4, -v5, -v6, and -v9. An improved immunohistochemical protocol with microwave-based antigen retrieval in paraffin sections and heavy metal amplification of the diaminobenzidine reaction product provided enhanced resolution and sensitivity as compared to studies on frozen sections. The hair follicle, the seborrheic and eccrine sweat glands were strongly positive for all CD44 isoforms studied. In the latter, the clear cells but not the dark (intercalated) cells were positive. the sudoriferous ducts adjacent to the glands were weakly positive for all CD44 isoforms and strongly positive near the skin surface. In the apocrine glands, the basal cells showed only a moderate positivity. The myoepithelial cells expressed only CD44s. In the epidermis, all CD44 isoforms were detectable, with strongest CD44 immunostaining in the lower third of the stratum spinosum and weaker staining in the stratum basale and the upper two-thirds of the stratum granulosum. The stratum granulosum and corneum were unreactive. Thus, a regional and cell type-specific CD44 expression was revealed.

CD44 standard and variant isoform expression in human epidermal skin tumors is not correlated with tumor aggressiveness but down-regulated during proliferation and tumor de-differentiation.

CD44 isoforms have been reported to be involved in tumor invasion and metastasis formation. Normal human skin expresses high levels of CD44 isoforms, but little is known about their expression in epidermal skin tumors. Expression of CD44 standard (CD44s) and variant exon (CD44v3, -v4, -v5, -v6, -v9)-encoded gene products has been studied in 74 benign, semi-malignant and malignant human epithelial skin tumors using a panel of well-characterized, variant exon-specific monoclonal antibodies (MAbs). Sensitivity and resolution of the immunohistochemical staining in paraffin sections was substantially improved by using microwave-based antigen retrieval and an optimized streptavidin-biotin-peroxidase technique. Immunostaining was evaluated semi-quantitatively and correlated with tumor type and degree of histological differentiation by non-parametric statistical tests. Furthermore, the relationship between CD44 expression and cellular proliferation rate as defined by the Ki-67 antigen was analyzed in basal cell carcinomas. We found a significant correlation between tumor type and CD44 isoform expression. Basal cell carcinomas exhibited the weakest staining and keratoacanthomas the strongest. Squamous cell carcinomas ranged in between, with a tendency to down-regulate CD44 expression upon de-differentiation. In basal cell carcinomas, an inverse relationship between CD44 expression and proliferation rate was directly demonstrated at the cellular level using double immunolabelling. Our data indicate that qualitative and quantitative changes in CD44 splicevariant expression in human skin tumors do not correlate with invasive and metastatic potential but are rather related to the degree of tumor differentiation.

Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma: no evidence for an etiological association.

Epidemiological studies indicate that acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) may be caused by an infectious, preferentially sexually transmitted agent. Herpesviruses infections are common sexually transmitted diseases in homosexual men, who are also the main risk group for developing Kaposi's sarcoma. To evaluate a possible role of human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) in the development of AIDS-associated KS, we investigated cutaneous AIDS-associated KS in 26 AIDS patients using the polymerase chain reaction (PCR) and immunohistochemistry (IHC) to detect the presence of HHV-6 and CMV. Human herpesvirus-6 was detected in nine of 26 Kaposi's sarcoma specimens (all cases were HHV-6 subtype B) and in eight of 27 normal skin specimens from human immunodeficiency virus (HIV) seropositive and HIV seronegative patients (one case was HHV-6 subtype A and seven cases were HHV-6 subtype B). In two of four patients showing HHV-6 in KS of the skin, the virus also was detected in other investigated tissues, such as heart, lung, liver, kidney, and adrenals. Cytomegalovirus was detected only in AIDS-associated KS (seven of 26 KS specimens) and not in normal skin tissues of HIV-seropositive and HIV-seronegative patients. Cytomegalovirus was detected in other organs of those patients showing CMV in Kaposi's sarcoma. Our data indicate that the presence of HHV-6 and CMV in AIDS-associated KS most likely reflects disseminated viral infection. Human herpesvirus-6 and CMV may be cofactors but not the only causative agents for the development of AIDS-associated KS.

Detection of several types of human papilloma viruses in AIDS-associated Kaposi's sarcoma.

Epidemiological studies indicate that acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) may be caused by an infectious, preferentially sexually transmitted agent. Infections with human papilloma viruses are common, sexually transmitted diseases occurring frequently in homosexual men, who are also the main risk group for developing KS. In order to evaluate the possible role of HPV in the development of KS, 24 cutaneous AIDS-associated Kaposi's sarcomas were investigated by the polymerase chain reaction (PCR) and by in situ hybridization for the presence of human papilloma viruses (HPV). HPV DNA sequences were detected in 5 of 24 KS specimens, in 4 of 13 normal skin specimens from AIDS patients without KS and in 5 of 14 skin specimens of HIV-seronegative patients. For the first time, HPV types 6 and 33 were detected by PCR in KS. A higher proportion of HPV types 16/18 was found in AIDS-associated KS specimens, whereas HPV type 33 was seen more often in normal skin specimens of the control group. Apart from the known HPV types 16/18 described in KS, this study demonstrates also the presence of HPV 6 and 33 in this condition.

[Leiomyosarcoma in the thyroid gland--primary tumor or metastasis?]. / Leiomyosarkom in der Schilddrüse--Primärtumor oder Metastase?

In a 69-year-old female patient a moderately pleomorphic spindle-cell thyroid tumour measuring 5 cm in diameter was initially misinterpreted as primary anaplastic thyroid carcinoma. During clinical investigations to elucidate the cause of severe anaemia, 17 months later an ulcerated duodenal leiomyosarcoma was detected and removed by duodenopancreatectomy. Reevaluation of the thyroid nodule led to revision of the initial diagnosis to metastatic leiomyosarcoma. Six months later the patient died from cerebral stroke. Autopsy findings confirmed the diagnosis of primary leiomyosarcoma of the duodenum with initial manifestation as thyroid metastasis.

p53 gene mutations in oropharyngeal carcinomas: a comparison of solitary and multiple primary tumours and lymph-node metastases.

Despite the steadily increasing number of patients suffering from squamous-cell carcinomas of the oropharyngeal region, little is known about the molecular steps involved in the induction of these neoplasms. We investigated oropharyngeal cancers from 38 patients for mutations in the p53 tumour-suppressor gene. The majority of patients (74%) had a history of tobacco and alcohol abuse. Five had lymph-node metastases, 3 had multiple primary carcinomas and 2 presented with multiple primary tumours and lymph-node metastases. Exons 5 through 8 of the p53 gene were screened by single-strand conformation polymorphism analysis followed by direct DNA sequencing. A total of 16 tumours (42%) contained point mutations which were scattered throughout exons 5 to 8. Most mutations (56%) were transitions, predominantly G-->A. Among the transversions, G-->T mutations prevailed; these have also been found in smoking-related lung cancer. One carcinoma of the soft palate showed a mutation which was retained in a lymph-node metastasis. In another patient, 2 primary carcinomas had different mutations, indicating that they had developed independently. Similar results were obtained in a case with a p53 mutation in the third of 3 primary tongue carcinomas which developed over a period of 23 years. One lymph-node metastasis had a 12-bp deletion which was not detected in any of the primary malignancies. The frequent occurrence of p53 mutations in oropharyngeal carcinomas supports the view that they play a role in the initiation or progression of the malignant phenotype.