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1.

Background

Breast metastases from extramammary tumors are extremely rare, the most common primary tumors being contralateral breast carcinoma, followed by lung, gynecological, gastrointestinal, melanoma, and hematological cancers. Only a few cases deriving from head and neck squamous cell carcinoma have been reported in the literature to date.

Case presentation

We report a case of a 47-year-old Caucasian woman who presented to our hospital with a solitary breast lesion in the right upper external quadrant associated with multiple bone and visceral metastases. Two years before, she had undergone radical resection of a squamous cell carcinoma of the oropharynx (stage pT2, pN1), which was followed by adjuvant radiotherapy. Breast ultrasound showed a hypoechogenic tumor lesion of 4 cm in the right upper external quadrant that was associated with multiple axillary and infra-/supraclavicular adenopathies. A positron emission tomographic scan documented multiple visceral and bone metastases with a single hypermetabolic lesion of the right breast. The results of histology and immunohistochemistry were consistent with a metastasis from a squamous cell carcinoma. The patient died of acute respiratory insufficiency 1 month after her breast metastasis diagnosis and before starting any systemic antitumoral treatment.

Conclusions

Although breast metastases are extremely rare, they should be considered in any patient with a history of cancer and confirmed by histology and immunohistochemistry because they are very difficult to distinguish from other primary breast tumors based only on clinical and radiological features. There are no standardized treatment guidelines for breast metastasis management. Surgery and radiotherapy can play a role in symptom palliation, but they do not have any relevant impact on survival, the prognosis being poor, with an estimated overall survival less than 1 year from diagnosis.
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2.

Background

Choroidal metastases from gynaecological primary are extremely rare. There is no documented case in the literature of choroid metastasis in a patient with primary peritoneal carcinoma (PPC).

Methods & Results

We describe the first case of a 54-year-old woman with a history of borderline mucinous tumour who presented 17 months later with PPC and 21 months after with recurrent disease metastatic to the eye, and review pertinent literature.

Conclusion

High index of suspicion is warranted when patients with history of primary peritoneal carcinoma present with visual complaints in order to treat and/or relieve symptomatology from metastatic eye disease.
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3.

Background

Renal cell carcinoma most commonly metastasizes to the lungs, skeleton or liver. Metastatic renal cell carcinoma to the breast is very rare, especially for clear cell carcinoma, and few cases regarding this condition have been reported.

Case Presentation

The case we presented was a 68-year-old Chinese female with metastatic renal clear cell carcinoma of the left breast 10 years after a nephrectomy. Identification of the metastatic renal clear cell carcinoma in the breast required multiple breast imaging modalities. Imaging showed a single, ovary-shaped, well-defined hypo-echoic mass, with abundant blood flow on ultrasound images. The mass was enhanced early on MRI, and it was hypointense on a T1-weighted image and hyperintense on a fat-saturated T2-weighted image. Following surgical excision of the tumor, a routine immunohistochemistry antibody panel on the tumor cells revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2). Strong positive staining for the cluster of differentiation 10 (CD10) and vimentin was present.

Conclusion

This case is unusual because of the site of metastatic progression. It is important for physicians to be aware of this progression so early diagnoses can be made, and appropriate therapeutic planning can be initiated.
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4.
5.

Background

Knockdown of Akt1 promotes Epithelial-to-Mesenchymal Transition in breast cancer cells. However, the mechanisms are not completely understood.

Methods

Western blotting, immunofluorescence, luciferase assay, real time PCR, ELISA and Matrigel invasion assay were used to investigate how Akt1 inhibition promotes breast cancer cell invasion in vitro. Mouse model of lung metastasis was used to measure in vivo efficacy of Akt inhibitor MK2206 and its combination with Gefitinib.

Results

Knockdown of Akt1 stimulated β-catenin nuclear accumulation, resulting in breast cancer cell invasion. β-catenin nuclear accumulation induced by Akt1 inhibition depended on the prolonged activation of EGFR signaling pathway in breast cancer cells. Mechanistic experiments documented that knockdown of Akt1 inactivates PIKfyve via dephosphorylating of PIKfyve at Ser318 site, resulting in a decreased degradation of EGFR signaling pathway. Inhibition of Akt1 using MK2206 could induce an increase in the expression of EGFR and β-catenin in breast cancer cells. In addition, MK2206 at a low dosage enhance breast cancer metastasis in a mouse model of lung metastasis, while an inhibitor of EGFR tyrosine kinase Gefitinib could potentially suppress breast cancer metastasis induced by Akt1 inhibition.

Conclusion

EGFR-mediated β-catenin nuclear accumulation is critical for Akt1 inhibition-induced breast cancer metastasis.
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6.

Background

Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low malignant tumor arising in the sinonasal tract, with histological mimicry of renal cell carcinoma.

Case presentation

We present a case of sinonasal renal cell-like carcinoma in a 63-year-old male patient. Computer tomography(CT) scanning revealed a soft tissue mass at the left nasal cavity and choana. Histologically, the predominant tumor architecture was follicular to glandular with intervening fibrous septa. The tumor cells were uniform cuboidal to polyhedral with abundant clear or eosinophilic cytoplasm. Immunohistochemically, the tumor cells were strongly positive for CK7, EMA, vimentin, SOX10, S-100, and focally positive for CA9. During 6 months of follow-up, there was no clinical or radiological evidence of recurrence or metastasis.

Conclusion

SRCLC has microscopic features which overlap with tumors that contain clear cells. Thus, several other tumors must be considered in the differential diagnosis of a tumor of the sinonasal region with clear cells, especially metastatic renal clear cell carcinoma. SRCLC is an indolent tumor and none of the reported SRCLC patients had metastatic disease.
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7.

Introduction

Hypoxia commonly occurs in cancers and is highly related with the occurrence, development and metastasis of cancer. Treatment of triple negative breast cancer remains challenge. Knowledge about the metabolic status of triple negative breast cancer cell lines in hypoxia is valuable for the understanding of molecular mechanisms of this tumor subtype to develop effective therapeutics.

Objectives

Comprehensively characterize the metabolic profiles of triple negative breast cancer cell line MDA-MB-231 in normoxia and hypoxia and the pathways involved in metabolic changes in hypoxia.

Methods

Differences in metabolic profiles affected pathways of MDA-MB-231 cells in normoxia and hypoxia were characterized using GC–MS based untargeted and stable isotope assisted metabolomic techniques.

Results

Thirty-three metabolites were significantly changed in hypoxia and nine pathways were involved. Hypoxia increased glycolysis, inhibited TCA cycle, pentose phosphate pathway and pyruvate carboxylation, while increased glutaminolysis in MDA-MB-231 cells.

Conclusion

The current results provide metabolic differences of MDA-MB-231 cells in normoxia and hypoxia conditions as well as the involved metabolic pathways, demonstrating the power of combined use of untargeted and stable isotope-assisted metabolomic methods in comprehensive metabolomic analysis.
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8.
9.

Background

Pagets disease of the nipple presents as an eczematous lesion, occurs in 1 – 4% of all female breast carcinoma cases and is invariably associated with underlying malignancy either overt or occult. The majority of these cases are invasive disease although 40–45% are associated with DCIS.

Case presentation

A 39 year old lady presented to our unit with a palpable lump in the right breast. Radiological and histological investigation proved this to be an extensive area of Ductal Carcinoma in Situ (DCIS) for which she underwent a simple mastectomy and immediate latissimus dorsi flap reconstruction. Histology revealed high grade DCIS with 2 small foci of invasive carcinoma. At 1 year the patient represented with a nodule adjacent to the reconstruction scar which was proved on biopsy to be consistent with Paget's disease. This was proved on formal excision.

Conclusion

In the absence of underlying breast or apocrine tissue this case details a case of Paget's disease of uncertain origin.
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10.

Background

Renal cell carcinoma is well known for its frequency to metastasise, particularly to lungs, liver, bones and brain. Metastasis to the skin is much less common. Presentation as a result of the skin lesion is even more unusual, with only 14 previously reported cases in the English literature. The majority of these cases have been reported in patients with recurrent disease or with other metastases.

Case presentation

We present only the second case of non-recurrent renal cell carcinoma with a solitary cutaneous facial metastasis reported in the English literature.

Conclusion

Clinicians should conduct a careful inspection of the skin in patients with renal cell carcinoma and also have a high index of suspicion of primary internal organ malignancy in patients presenting with a skin lesion.
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11.

Background

Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research.

Objective

To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells.

Method and Result

In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) phenotypes are associated with the metastatic cascade.

Conclusion

In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.
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12.

Introduction

Metastatic disease in the sinonasal region occurs rarely and the primary site may be elusive. This case highlights the possibility of an occult renal tumor manifesting with nasal symptoms and the risk of severe bleeding following nasal biopsy.

Case presentation

We report the case of a 79-year-old Caucasian woman who presented with a six-week history of intermittent left-sided nosebleeds. She was fit, without previous surgery or anticoagulation. Nasal endoscopy and computed tomography showed a hemorrhagic mass occupying her left ethmoid cells and middle meatus. After a highly hemorrhagic biopsy, the lesion was histologically confirmed as clear cell carcinoma. Screening revealed a right kidney mass with widespread metastases. Palliative radiotherapy to the sinonasal metastasis and systemic treatment rendered her free of symptoms nine months after initial presentation.

Conclusions

General practitioners and ear, nose and throat (ENT) doctors are very often confronted with epistaxis. A small minority of patients with epistaxis show a primary or metastatic nasal mass. Detection of the origin of secondary sinonasal masses requires a high index of suspicion and examination of infraclavicular sites by a multidisciplinary team. Renal cell carcinoma metastases are prone to severe bleeding during any surgical intervention, therefore, preoperative embolization is recommended. Resection or radiotherapy to the sinonasal metastasis of renal origin is justified in order to prevent recurrent nosebleeds.
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13.

Background

This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males.

Methods

We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995–2008.

Results

Median age at presentation was 66,7 ± 10,9 years. Average follow-up was 63 ± 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ýnvasive ductal carcinoma was the most frequent pathologic type (70% of cases).

Conclusion

Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.
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14.

Background

We report a new case of small bowel metastases from primary lung cancer. Such metastases are not exceptional, but their clinical manifestations are rare.

Case presentation

The case involved a 56-year-old man with a squamous cell carcinoma of the lung (stage IV) that had been treated with chemotherapy. He presented fourteen months after diagnosis with an acute abdominal pain. Abdominal CT-scan demonstrated a perforated jejunum and he underwent emergency surgery. Postoperative pathologic analysis confirmed the diagnosis of metastatic pulmonary carcinoma. The patient was discharged after ten days, but died 8 weeks after surgery at home on tumor progression.

Conclusion

We were able to find 58 documented similar cases in the literature. Most cases presented with bowel perforation or obstruction. Squamous cell carcinoma was the most common histological cell type followed by large cell carcinoma. Other metastases are often present, and the prognosis is mostly fatal at short term.
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15.

Background

Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited.

Material and method

In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K.

Results

A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis.

Conclusions

The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.
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16.

Objective

To investigate the roles of miR-145 in lung adenocarcinoma (LAC) and to clarify the regulation of N-cadherin by miR-145.

Results

In 57 paired clinical LAC tissues, diminished miR-145 was significantly correlated with the lymph node metastasis and was negatively correlated with N-cadherin mRNA level expression. Wound healing and transwell assays revealed a reduced capability of tumor metastasis induced by miR-145 in LAC. miR-145 negatively regulated the invasion of cell lines through targeting N-cadherin by directly binding to its 3′-untranslated region. Silencing of N-cadherin inhibited invasion and migration of LAC cell lines similar to miR-145 overexpression.

Conclusions

MiR-145 could inhibit invasion and migration of lung adenocarcinoma cell lines by directly targeting N-cadherin.
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17.

Background

TER measurements across confluent cellular monolayers provide a useful indication of TJ strength between epithelial and endothelial cells in culture. Having a reliable and accurate method of measuring cell-to-cell adhesion is critical to studies in pathophysiology and cancer metastasis. However, the use of different technical approaches to measure TER has reportedly yielded inconsistent measurements within the same cell lines.

Methods

In the current study, we compared the peak TER values for the MDCK (canine kidney) and MCF-7 (human breast cancer) epithelial cell lines using two common approaches (Chopstick and Endohm) and two types of polymer inserts (PC and PET).

Results

Both cell lines demonstrated a statistically significant difference in the peak TERs obtained using the two different approaches. Further, the MDCK (but not the MCF-7) cells demonstrated a statistically significant difference between the peak TERs when using the same approach but different inserts.

Conclusion

Our study indicates the importance of using a single approach when seeking to measure and compare the TER values of cultured cell lines.
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18.

Background

It has been widely accepted that hepatitis B virus X protein (HBx) plays an important role in hepatocellular carcinoma (HCC). This study aimed to explore the function of long non-coding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) induced by HBx.

Methods

The association between HBx and EMT markers was detected using immunohistochemistry in HCC tissues. The effect of HBx on HCC EMT was assessed through morphological analysis, transwell assay, metastatic in vivo study and detection of EMT markers. LncRNA microarray was used to screen the differently expressed lncRNAs. Small interfering RNA and Western blot were used to analyse the function and mechanism of the locked lncRNA.

Results

HBx was negatively correlated with the epithelial marker E-cadherin but positively correlated with the mesenchymal marker vimentin in HCC tissues. HBx induced the mesenchymal phenotype and improved the metastatic ability of HCC cells. Meanwhile, HBx down-regulated E-cadherin, whereas it up-regulated vimentin. In HCC cells, HBx altered the expression of 2002 lncRNAs by more than 2-fold. One of them was ZEB2-AS1. Inhibition of ZEB2-AS1 can compensate for the EMT phenotype and reverse the expression of EMT markers regulated by HBx. Additionally, HBx affected the Wnt signalling pathway.

Conclusions

HBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.
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19.
20.

Objectives

To investigate the biological functions of microRNA-144-3p with respect to proliferation and apoptosis of human salivary adenoid carcinoma cell lines via mTOR.

Results

After transfection of microRNA-144-3p agomir, cell viability assays confirmed that the salivary adenoid carcinoma cell (SACC) proliferation was inhibited and apoptosis was induced. Dual luciferase reporter assay validated that the mammalian target of rapamycin (mTOR) was a direct target of miR-144-3p. Western blot, immunofluorescent analysis and a xenograft mouse model of adenoid cystic carcinoma indicated that miR-144-3p was a tumor suppressor and repressed mTOR expression and signaling in SACCs.

Conclusions

MicroRNA-144-3p inhibits proliferation and induces apoptosis of human salivary adenoid carcinoma cells by downregulating mTOR expression in vitro and in vivo.
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