Amyloid and hyaline globules in undifferentiated nasopharyngeal carcinoma

We characterize the clinicopathological features of two patients (one 38 year old woman and one 42 year old man, both of Chinese ethnicity) with Epstein Barr Virus positive non-keratinizing nasopharyngeal carcinoma from an endemic region with prominent presence of amyloid and one case with both amyloid and abundant intracytoplasmic hyaline globules. The amyloid material was positive for Congo red and showed apple green birefringence when examined under polarized light. The amyloid was immunoreactive for cytokeratins and was located both intra- and extracellularly. Frequently the amyloid had a light microscopical spherical appearance and displayed peripheral radiating fibrils from a central homogenous core. One of the patients had a unique presentation of nasopharyngeal carcinoma with perceived hemoptysis and coughing up two pieces of tumor tissue. In reality, the nasopharyngeal tumor was polypoid and the two fragments were pinched of from the main tumor mass.     

Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma

Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases.     

Prekeratin immunohistochemistry in the diagnosis of undifferentiated carcinoma of the nasopharyngeal type

We investigated the value of prekeratin immunostaining in establishing the diagnosis of undifferentiated carcinoma of the nasopharyngeal type (lymphoepithelioma). As in squamous cell carcinoma of the nasopharynx, all seven lymphoepithelial carcinomas stained for prekeratin whereas other look-alike but histogenetically different neoplasms (malignant lymphoma, esthesioneuroblastoma, and small round cell sarcomas) did not stain. In addition to confirming the squamous epithelial nature of lymphoepithelioma, our findings indicated that immunoperoxidase staining for prekeratin is a useful diagnostic tool in the differential diagnosis of nasopharyngeal carcinomas in general and lymphoepithelioma in particular.     

New BZLF1 sequence variations in EBV-associated undifferentiated nasopharyngeal carcinoma in southern China

The viral lytic gene BZLF1 triggers replication of the Epstein–Barr virus (EBV), which is commonly found in nasopharyngeal carcinoma (NPC). Here, RT-PCR revealed five new BZLF1 variants in 8 of 12 NPC and 4 of 12 non-NPC nasopharyngeal biopsies from an NPC-endemic area in southern China. The deduced peptide sequence of the dominant BZLF1 variant differed by 11 amino acids from that of the prototypical strain B95.8 (V01555). Anti-ZEBRA antibody levels were higher in NPC than that in non-NPC patients (P < 0.001). These findings demonstrated a dominant BZLF1 variant in southern Chinese EBV-associated NPC and non-NPC patients.     

Serum antibody response to lytic and latent Epstein-Barr virus antigens in undifferentiated nasopharyngeal carcinoma patients from an area of nonendemicity

Epstein-Barr virus (EBV)-associated undifferentiated carcinoma of the nasopharyngeal type (UCNT) is highly prevalent in southeast China, where immunoglobulin A (IgA) antibodies to viral capsid antigen and early antigen (EA) represent important markers, routinely used to assist in diagnosing this malignancy. Our study aimed at determining the EBV serological profiles of 78 UCNT patients from Italy, an area of nonendemicity for this tumor, using different assays specific for both lytic and latent EBV antigens. Serum IgA against both EA and EBNA1 and IgG and IgA to the latent membrane protein 1 (LMP1), to EA, and to the EBV transactivator ZEBRA protein were assessed. These serological responses were then evaluated according to the clinicopathologic parameters at diagnosis. The sensitivities of the IgG assays were 37.7% for LMP1, 73.6% for EA, and 61.0% for ZEBRA. EA/EBNA1 IgA reactivity was 84.4%, and a high association (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7 to 4.0) with UCNT was observed. When EBV serological reactivities were analyzed according to the tumor, node, and metastasis staging system (TNM), a statistically significant association was found between N stage and IgG antibody rates for EA (OR, 3.6; 95% CI, 1.2 to 10.9) and ZEBRA (OR, 2.6; 95% CI, 1.2 to 5.5) and between M stage and IgG antibody rates for ZEBRA (OR, 7.1; 95% CI, 3.2 to 16.0) and LMP1 (OR, 14.0; 95% CI, 1.8 to 110.9). Our results show that no single serological marker allows the detection of all UCNT cases. EA/EBNA1 IgA represents a reliable marker for diagnosis, with a high predictive value also in areas where UCNT is not endemic, such as Italy. The analysis of serological results according to TNM classification is consistent with a progressive impairment of humoral immune response to EBV as the disease advances and may be used to improve the accuracy of diagnosis.     

A20 RNA expression is associated with undifferentiated nasopharyngeal carcinoma and poorly differentiated head and neck squamous cell carcinoma

A20 is an anti-apoptotic gene that can be induced in human epithelial cell lines in response to expression of the Epstein–Barr virus (EBV) gene product latent membrane protein 1 (LMP1). EBV is a ubiquitous, persistent human herpesvirus that is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC), in which antigen expression includes LMP1. Consistent with a potential role in the development of NPC, LMP1 has profound effects on epithelial cell growth. A20 may be a key downstream effector of LMP1 in NPC, as LMP1-induced A20 blocks p53-mediated apoptosis in H1299 epithelial cells and most NPCs have wild-type p53. Moreover, the potential role of A20 in the development of epithelial malignancies may extend to tumours not associated with EBV. The purpose of this study was to develop an in situ hybridization assay to assess expression of A20 RNA in undifferentiated NPC and in non-EBV-associated poorly differentiated head and neck squamous cell carcinomas (SCCs) and well-differentiated SCCs of the skin. A20 RNA expression was also examined in normal samples of oral mucosa and skin. Expression of A20 was demonstrated in 76 per cent of undifferentiated NPCs and in 80 per cent of poorly differentiated head and neck SCCs, suggesting a role for A20 in the pathogenesis of these epithelial malignancies. By contrast, A20 RNA was not detected in well-differentiated SCCs of the skin, or in any normal samples of squamous epithelial tissue. The pathway leading to A20 expression in non-EBV-associated poorly differentiated head and neck SCCs is clearly LMP1-independent. LMP1 expression was demonstrated in 29 per cent of NPC biopsies, suggesting an LMP1-independent pathway to A20 induction in undifferentiated NPC. Copyright © 1999 John Wiley & Sons, Ltd.     

Immune response to the terminal repeat protein of epstein-barr virus in patients with undifferentiated nasopharyngeal carcinoma

Screening of 205 patients suffering from various diseases and healthy donors for the presence of serum antibodies to terminal repeat protein (TP) of Epstein-Barr virus was carried out using the indirect immunofluorescence technique. TP antibodies were detected exclusively in patients with undifferentiated nasopharyngeal carcinoma (in 30–40% of patients within this group). Evaluation of TP antibody titers before and after treatment revealed a correlation between the dynamics of these antibodies and the clinical prognosis of patients. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, No. 3, pp. 311–314, March, 1995 Presented by Yu. N. Solov'ev, Member of the Russian Academy of Medical Sciences     

Assessing for primary oropharyngeal or nasopharyngeal squamous cell carcinoma from fine needle aspiration of cervical lymph node metastases

In fine needle aspirates of cervical lymph nodes with metastatic squamous cell carcinoma (SCC), the site of origin may not be clinically evident. The distinction between oropharyngeal and nasopharyngeal primary SCC has important management consequences. In the current study, we evaluated metastatic SCC for HPV types 16, 18, 31, 33, 51 (by in situ hybridization[ISH]), p16 and ProExC (surrogate HPV markers), and Epstein Barr Virus reported in nasopharyngeal SCC. Forty patients diagnosed between 2004 and 2008, with adequate cell block material were identified. ISH for high risk HPV and EBV (EBER), and immunohistochemistry for p16 and ProExC were performed. Primary site was designated in 31 cases with 26 head and neck including 11 oropharyngeal and 2 nasopharyngeal, and 5 other sites. High risk HPV was detected in 9 cases (22.5%), p16 in 16 (40%), ProExC in 35 (87.5%), and EBER in 2 (5%). All cases with high risk HPV ISH also showed overexpression of p16. The sensitivity for HPV infection by both surrogate markers was 100%; specificity for p16 and ProExC was 78.7 and 16.1%, respectively. Seven (63.6%) oropharyngeal SCC were positive for HPV ISH and negative for EBV; one nasopharyngeal SCC (50%) was EBER positive and HPV negative. HPV and EBER detection can serve as indicators for oropharyngeal and nasopharyngeal primary SCC, respectively, however our data show that only a subset (63.6%) of oropharyngeal SCC are high risk HPV‐related. Additionally, despite their high sensitivity for HPV infection, surrogate markers, especially ProExC, lack specificity. Diagn. Cytopathol. 2010;38:795‐800. © 2009 Wiley‐Liss, Inc.     

Pineal gland metastases from mammary carcinoma

Breast carcinomas often metastasize into various organs, most commonly into the lung and rather infrequently into the pineal gland. There were only 20 cases of the latter recorded until 1950. Currently, the total number of reported cases, including this report, is 74. At Sunnybrook Health Science Centre, between 1984 and 1992, 27 patients died of disseminated breast cancer; 2 patients had metastases to the pineal gland. Five patients had metastatic deposits in the pituitary and J had metastases in both organs. Average survival time from diagnosis of breast tumor to death was nearly 3 years. In contrast, the 2 patients with pineal metastasis lived for 1 and 7 months, respectively, after diagnosis. The significance of pineal metastases with regard to short survival may be related to the fact that destruction of the pineal parenchyma reduced melatonin production, thereby decreasing the nonspecific oncostatic effect normally exerted by pineal gland secretions.     

Endocrine organ metastases from breast carcinoma.

Breast carcinoma frequently metastasizes to endocrine organs, a behavior which may have prognostic or therapeutic relevance. Whether endocrine organ involvement represents a trophic influence on some carcinomas or is simply a "mass effect" of tumor dissemination is uncertain. To investigate this question, the authors reviewed the clinical and pathologic features of 187 subjects with metastatic breast carcinoma, all of whom had been subjected to complete autopsy at The Johns Hopkins Hospital. Metastases to primary endocrine organs, ie, the anterior pituitary, thyroid, parathyroid, or adrenal cortex, occurred in 57%, and metastases to secondary endocrine organs, ie, the pineal, posterior pituitary, thymus, adrenal medulla, or pancreas, occurred in 62% of patients. In general, patients with endocrine organ metastases were significantly younger and had significantly greater numbers of metastases and greater overall tumor burden than those without endocrine organ metastases (all P less than 0.001). There was no correlation between endocrine organ metastases and survival, therapy, histologic type of tumor, or grade of anaplasia or desmoplasia. Metastases to primary endocrine organs were correlated with one another and with metastases in secondary endocrine organs. Metastases in secondary endocrine organs were intercorrelated and also correlated with several nonendocrine organs, chiefly the heart, liver, and gut (all P less than 0.005). These findings indicate that metastases of breast carcinoma to endocrine organs occur in a setting of widely disseminated tumor. However, the observed correlations among metastatic sites suggest that the distributions are nonrandom; these distributions may reflect fundamental properties of some breast carcinomas with respect to hormone receptors, biologic behavior, or environmental growth requirements.     

Familial nasopharyngeal carcinoma

We report 3 cases of nasopharyngeal carcinoma occurring in a single family group. All 3 patients are male, caucasian, born in Australia and of Greek origin. Two of the patients are brothers, the third their first cousin.     

Detection of Epstein-Barr virus in a case of undifferentiated nasopharyngeal carcinoma by in situ hybridization with digoxigenin-labelled PCR-generated probes

A case of nasopharyngeal carcinoma is presented. Epstein-Barr viral genome was identified in the neoplastic cells by in situ hybridization with digoxigeninlabelled polymerase chain reaction-generated probes. We report the development of this technique in paraffinembedded sections and propose that such identification may prove valuable for the diagnosis of this tumour in routine material.P. Delvenne is a research associate of the National Fund for Scientific Research (Belgium)     

Chest wall metastases from unknown primary hepatocellular carcinoma

Metastases of hepatocellular carcinoma (HCC) to the bones are common but bone metastases of hepatocellular carcinoma in the presence of a normal liver are an uncommon entity. A 50-year-old male patient presented with a rapidly growing tumour on the sternum. Biopsy of the lesion showed metastatic sternal tumour from a primary hepatocellular carcinoma. Radiological evaluation however, failed to detect a primary lesion in the liver. Bone metastases of hepatocellular carcinoma localized to the chest wall in the presence of a normal liver are scarcely reported as anecdotal case reports in the literature.