Sinonasal teratocarcinosarcoma with yolk sac elements: a neoplasm of somatic or germ cell origin?

Sinonasal teratocarcinosarcoma is an uncommon, aggressive, morphologically heterogenous tumor composed of cells derived from the 3 somatic layers. A histogenetic origin from a multipotential adult somatic stem cell with divergent differentiation has been favored over a germ cell origin. This assumption has been based on the lack of germ cell elements and, until recently, the absence of demonstrable amplification of 12p. We report a case that exhibited foci of yolk sac elements with papillary structures and intracytoplasmic periodic acid-Schiff-positive, diastase-resistant, α-fetoprotein-positive, hyaline globules. An expanded area of undifferentiated cells, likely precursor cells, in the basal layer of the overlying mucosal epithelium transitions into and merges with the immature epithelial, neuroepithelial, and mesenchymal components. These previously unreported histomorphological features support the hypothesis that this tumor is a teratomatous tumor arising from pluripotent embryonic stem cells in the basal layer of the sinonasal epithelium. That notion is further supported by fluorescence in situ hybridization cytogenetic analysis, which showed a distinct subpopulation of the tumor cells with an extra copy of chromosome 12p13.     

Cervical embryonal rhabdomyosarcoma and ovarian Sertoli-Leydig cell tumour: a more than coincidental association of two rare neoplasms?

A case in which an embryonal rhabdomyosarcoma of the cervix and an ovarian Sertoli-Leydig cell tumour of intermediate differentiation occurred in a 13-year-old girl is described. Although initially considered as a chance association, a review of the literature showed the co-occurrence of these two uncommon neoplasms in three previous cases. The reason for this association, which is thought to be more than coincidental, is not known, although an underlying genetic abnormality is a possibility. The ovarian tumour in this case was characterised by the presence of foci of cells with extremely pleomorphic nuclei, which initially raised the possibility of metastatic rhabdomyosarcoma. These were interpreted as foci of bizarre nuclei within the Sertoli-Leydig cell tumour.     

The expression of heterochromatin protein 1α/β in the kidney tumors: a microarray immunohistochemical study

Kidney tumors of various types may behave differently and have different prognosis. Due to some overlapping morphological features and immunohistochemical staining pattern, they may pose diagnostic challenge. Therefore, it is necessary to explore additional immunohistochemical stains to help in subclassifying these epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell carcinomas (RCC) of clear cell, chromophobe, and papillary variants and oncocytoma were constructed and used to test the heterochromatin-associated protein (HP) 1α/β expression. HP-1α/β showed strong nuclear staining. Expression of HP-1α/β was found mostly in papillary RCC (79%) and oncocytoma (75%) but less in chromophobe (30%) and clear cell RCCs (35%). HP-1α/β may be useful in the differential diagnosis of renal tumors, especially in the differentiation of chromophobe RCC and oncocytoma.     

Lung cancer and urban air-pollution in Dublin: a temporal association?

In 1990, the sale, marketing and distribution of bituminous coal, primarily used for domestic heating, were banned across Dublin. This study exploits the potential of a 'natural experiment' to assess a temporal association between adjusted annual lung cancer death rates and the changing annual mean urban air-pollution concentrations in Dublin from 1981 to 2000. Annual mean 'black smoke' (BS) concentration was used as an indicator variable for the urban air-pollution mixture. Log-linear Poisson regression model (with an offset) was used to estimate adjusted rate ratios of lung cancer death rates between two periods (1981-1990 and 1991-2000) relative to the year 1990. A significant (p<0.0001) two-third decline in BS concentration (28.2 microg/m(3)) was seen between the two periods [pre-ban (46.4 microg/m(3)) vs. post-ban (18.2 microg/m(3))]. Relative to 1990 (rate ratio= 1 ), a slightly greater decline (2%) in death rates was achieved in the pre-ban period (1981-1990) when mean annual BS concentrations were very high, but a lower decline (1%) was seen in the post-ban period (1991-2000) corresponding to very low mean annual BS concentrations. In other words, a further fall in adjusted rates in lung cancer was achievable both in the pre-ban and the post-ban periods when simultaneously controlling for BS and smoking. A temporal association thus observed between lung cancer death rates and the changing BS concentrations suggests that control of particulate air-pollution could further reduce lung cancer rates, irrespective of smoking patterns.     

Heme oxygenase-1 in tumors: is it a false friend?

Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to biologically active products: carbon monoxide (CO), biliverdin, and ferrous iron. It participates in maintaining cellular homeostasis and plays an important protective role in the tissues by reducing oxidative injury, attenuating the inflammatory response, inhibiting cell apoptosis, and regulating cell proliferation. HO-1 is also an important proangiogenic mediator. Most studies have focused on the role of HO-1 in cardiovascular diseases, in which its significant, beneficial activity is well recognized. A growing body of evidence indicates, however, that HO-1 activation may play a role in carcinogenesis and can potently influence the growth and metastasis of tumors. HO-1 is very often upregulated in tumor tissues, and its expression is further increased in response to therapies. Although the exact effect can be tissue specific, HO-1 can be regarded as an enzyme facilitating tumor progression. Accordingly, inhibition of HO-1 can be suggested as a potential therapeutic approach sensitizing tumors to radiation, chemotherapy, or photodynamic therapy.     

Isolation and genome characterization of a novel duck Tembusu virus with a 74 nucleotide insertion in the 3′ non-translated region

During investigations into the outbreak of duck Tembusu virus (DTMUV) infection in 2011 in China, a DTMUV strain (DTMUV-AH2011) was isolated from the affected ducks. The length of the genome of the DTMUV-AH2011 strain was found to be 11,064 nucleotides and to possess 10,278 nucleotides of one open reading frame (ORF), flanked by 94 nucleotides of the 5′ non-translated region (NTR) and 692 nucleotides of the 3′ NTR. In comparison with five fully sequenced TMUV genomes, the genome of DTMUV-AH2011 had a 74 nucleotide insertion in the 3′ NTR. Comparison of the DTMUV-AH2011 fully deduced amino acid sequences with those of other Tembusu virus strains reported recently in China showed they had a highly conserved polyprotein precursor, sharing 98.9% amino acid identities, at least. The overall divergences of amino acid substitutions were randomly distributed among viral proteins except for the protein NS4B, the protein NS4B was unchanged. Knowledge of the biological characters of DTMUV and the potential role of the insertion in the 3′ NTR in RNA replication will be useful for further studies of the mechanisms of virus replication and pathogenesis.     

Germ cell tumours in neonates and infants: a distinct subgroup?

Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological and cytogenetical aspects of these infantile GCTs. The primordial germ cell (PGC) has been suggested to be the cell of origin for GCTs. Infantile GCTs, however, have been suggested to originate from PGCs at a different stage of maturation than adult GCTs. The cytogenetic constitution of infantile GCTs also appears to differ from the adult GCTs and includes recurrent losses of lp and 6q. Recently, two cases of infantile GCT were detected with constitutional 12q13 translocations. These exceptional cases may be instrumental in the search for candidate genes related to infantile and/or adult GCT development.     

Late relapse of primary hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation: a consequence of low-level chimerism from a carrier donor?

Immunologic Research -     

Myo‐Inositol: a marker of reactive astrogliosis in glial tumors?

In a prospective study, two-dimensional (1)H-MRS with TE of 30 ms was performed before surgery in 56 patients with glial brain tumors. Concentrations of myo-inositol (MI), trimethylamine (TMA) and creatine/phosphocreatine (tCr) were evaluated for the whole tumor and scaled to the normal-appearing contralateral brain tissue. To assign changes in MI to specific tissue pathology, the normalized peak and mean concentrations of MI were correlated with TMA and tCr concentrations. TMA is accepted as a marker of proliferating tumor tissue, and tCr might be a marker of reactive astrogliosis. The mean and peak concentrations of MI and tCr correlated positively (r = 0.7), but not the concentrations of MI and TMA. The absolute concentration of MI was significantly increased in all tumor tissues (5.55 +/- 2.92 mM; mean +/- SD) compared with the normal-appearing white matter (4.33 +/- 1.22 mM, p = 0.005), with the highest concentrations for gliomatoses (n = 10) and grade II oligoastrocytomas (n = 3). Significant differences (P = 0.004) between low- and high-grade astrocytomas were found for TMA (1.67 +/- 0.32 mM and 2.65 +/- 0.86 mM, respectively), but not for MI (5.92 +/- 1.98 mM and 5.49 +/- 3.27 mM, respectively). As increased MI and tCr concentrations were found in gliomatosis and other cerebral diseases associated with marked astrogliosis, this process may also be responsible for the observed changes in MI in other glial tumors.     

Expression of cancer stem cell markers in basal and penta-negative breast carcinomas – A study of a series of triple-negative tumors

Purpose

Breast cancer is a heterogeneous disease. Immunohistochemistry has given rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of neoplasia and its heterogeneity has been strongly debated in cancer stem cells (CSC) theme. This study investigates the prevalence of basal (BCC) and penta-negative carcinomas (5NC) in TNC and establishes associations with CSC (CD44CD24).

Materials and methods

94 TNC were tested for CK5/6, HER1, CD44 and CD24, evaluated by a simple immunohistochemistry score and correlated with clinicopathological and survival data.

Results

BCC had higher tumor grades than 5NC (p = 0.004). CD44 negativity (p = 0.007) and CD44⁻CD24⁺ phenotype (p = 0.013) were associated with less vascular invasion amongst TNC. CD44 expression was associated with BCC (p = 0.007). CD44⁻CD24^−/low phenotype was associated with 5NC. None of the variables were associated with clinical outcome.

Conclusion

BCC and 5NC are closely related tumor subtypes. CD44⁻CD24^−/low phenotype was associated with 5NC and CD44⁻CD24⁺ phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.     

Carcinoembryonic antigen–related cell adhesion molecule 1 is expressed and as a function histotype in ovarian tumors

Carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma (P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern (P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis.     

Atypical cell clusters expressing both neuronal and oligodendrocytic markers: Novel histological pattern of glioneuronal tumors?

Glioneuronal tumors are a group of brain tumors that consist of both neuronal and glial cells. The spectrum of glioneuronal tumors is currently expanding, and many atypical glioneuronal tumors require further characterization. Two patients are described who had an atypical glioneuronal tumor with peculiar pathological features. One patient was a 7-year-old girl with a tumor in the right cerebellar hemisphere. This patient had no recurrence after total resection. The other was a 37-year-old man with a tumor in the spinal cord. He suffered incessant recurrence and received operative treatment four times. Although the clinical features (age at diagnosis, tumor location, and recurrence) were very different in these patients, the tumors had a characteristic common feature of atypical cell clusters. Intriguingly, the tumor cells in the clusters expressed both neuronal and oligodendroglial markers, indicating aberrant differentiation. Furthermore, the cluster-forming cells had modest proliferative indices and CD133 expression, indicating their role in the growth of the tumor. It is believed that these atypical cell clusters are a novel pattern of differentiation of glioneuronal tumors and that they need further investigation.     

The association of an adenine insertion variant in the 5’UTR of the endothelin-1 gene with hypertension and orthostatic hypotension

Introduction

An adenine insertion polymorphism in the 5’ untranslated region of the endothelin-1 gene is functional and increases the expression of endothelin mRNA and protein in the insertion homozygote. In the present study we hypothesized that this functional polymorphism might be associated with hypertension and/or orthostatic hypotension.

Material and methods

The adenine insertion polymorphism was genotyped in 381 untreated hypertensive patients and 298 normotensive subjects, all of whom underwent an upright posture study for orthostatic blood pressure measurements. Orthostatic hypotension was defined as a drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the upright posture.

Results

The allele frequency of the adenine insertion was similar in hypertensive and normotensive subjects (15.2% vs. 15.3%, p > 0.05). After adjustment for age, sex and body mass index, blood pressure levels did not differ significantly among the genotypes in both hypertensives and normotensives. No associations were found between the distribution of the adenine insertion genotypes and the risk of orthostatic hypotension in both hypertensive patients and normotensive subjects even after adjustment for demographic parameters and supine systolic or diastolic blood pressure. Neither hypertensive nor normotensive subjects showed significant differences in orthostatic systolic or diastolic blood pressure changes among the genotype groups (all p > 0.05).

Conclusions

We concluded that the functional adenine insertion polymorphism in the endothelin-1 gene is not associated with either hypertension or orthostatic hypotension risk in Chinese.     

Lesions resembling Langerhans cell histiocytosis in association with other lymphoproliferative disorders: a reactive or neoplastic phenomenon?

Langerhans cell histiocytosis (LCH) has been described in association with a variety of neoplasms preceding, after, or synchronous with the other tumor. In some cases, a neoplasm may arise as a complication of therapy for LCH, and in others, the association may be coincidental. Synchronous occurrence has been reported most commonly in association with malignant lymphoma in which discrete proliferations of Langerhans cells (LCs) histologically indistinguishable from LCH are seen. In most cases, these LCs are closely related to or intermingling with the primary pathology. The nature of LCs in this context remains elusive with debate as to whether they represent a true clonal neoplasm or an exaggerated reactive phenomenon. The lack of evidence for LCH progression or disease elsewhere strongly supports the latter. We have encountered 5 examples of LCH-like proliferations occurring in the context of other lymphoproliferative disorders. These include 2 cases of mycosis fungoides and 1 of cutaneous B-cell pseudolymphoma, associations that to our knowledge have not been described before. Two patients were female, and the clonality of the LC proliferation was assessed using laser capture microdissection and the human androgen receptor. The results showed that the LCs forming discrete nodules in a case of cutaneous B-cell pseudolymphoma and a case of Hodgkin's lymphoma were polyclonal. This suggests that, at least in a proportion of cases, the aggregates of LCs occasionally identified within other lymphoproliferative lesions represent a reactive proliferation rather than a potentially aggressive second neoplasm.