Breast osteosarcoma originating from a malignant phyllodes tumor: A case report of a rare neoplasm.

RATIONALE: Malignant phyllodes tumors with osteosarcomatous transformation are exceedingly rare. The clinical manifestations are similar to those associated with benign giant calcification, resulting in nonspecific and complex clinical symptoms. PATIENT CONCERNS: A 59-year-old woman presented with a firm, painless, movable, 5.0 × 4.0 cm lump in the lower inner quadrant of the left breast that she had detected 1 month prior. DIAGNOSES: Breast osteosarcoma originating from a malignant phyllodes tumor was confirmed by histopathologic and immunohistochemical evaluation. INTERVENTIONS: The patient underwent a wide local excision. OUTCOMES: The patient recovered uneventfully and was discharged after the operation. The 6-month postoperative follow-up assessment revealed no evidence of recurrence. LESSONS: Diagnosing malignant phyllodes tumors with osteosarcomatous transformation requires a high level of suspicion and awareness by both surgeons and pathologists. They should be aware of the extent of such disease, which might be mistaken as benign giant calcification. Medical history and imaging findings are important for accurate diagnosis. Phyllodes tumor with an osteosarcomatous component is an aggressive neoplasm associated with distant metastasis. Delayed diagnosis and insufficient excision might negatively impact both treatment and survival.

Malignant adenomyoepithelioma of the breast: A case report.

RATIONALE: Adenomyoepithelioma (AME) is a rare biphasic tumor consisting of epithelial and Myoepithelial cell. Most of the AME is benign, and only a few will progress to malignancy, Here, we report a case of low-grade malignant adenomyoepithelioma, and review the related literature, in a bid to investigate its clinical and pathological features and thus, enhance our understanding of this tumor. PATIENT CONCERNS: A 64-year-old woman visited our hospital with a 1-year history of a painless mass in her left breast. Physical examination revealed a palpable painless mass, measuring approximately 4.5 cm, in the left breast. DIAGNOSIS: Histological examination confirmed the diagnosis of malignant adenomyoepithelioma. INTERVENTIONS: The patient underwent local excision of the mass, with frozen section analysis revealing ductal carcinoma in situ. Mastectomy and sentinel lymph node biopsy were then performed. OUTCOMES: We conducted a one-year follow-up, and relapse was not observed. LESSONS: Treatment of AME remains controversial owing to the lack of high volume data and absence of prospective studies. Simple mastectomy is an acceptable treatment of this tumor.

Higher efficacy and reduced adverse reactions in neoadjuvant chemotherapy for breast cancer by using pegylated liposomal doxorubicin compared with pirarubicin.

The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.

Metastatic serous borderline tumor with micro-invasive ovarian carcinoma presenting as a breast lump: A case report.

RATIONALE: Breast metastasis from serous borderline tumor with micro-invasive carcinoma of ovary is a very rare condition. The breast lump as the only clinical presentation is rarely seen in ovarian carcinoma, which may lead to be misdiagnosed, and the mechanism of breast metastasis from ovarian tumors in early stage still needs to be explored. Differentiation from primary breast cancer and extramammary malignancy is crucial because the treatment and prognosis are significantly different. PATIENT CONCERNS: A 33-year-old female presented with a painless, movable, 1.0 × 1.0 cm lump in the upper outer quadrant of the right breast for a month. DIAGNOSES: Breast metastasis of serous borderline tumor with micro-invasive ovarian carcinoma confirmed by pathology and immunohistochemistry. INTERVENTIONS: The patient underwent lumpectomy, bilateral ovarian tumor stripping operation and prophylactic chemotherapy. OUTCOMES: No signs of recurrence have been detected in 1.5 years of follow-up. LESSONS: Distant metastasis may occur in early stage of ovarian carcinoma. It is important to determine the origin of the primary tumor and develop an effective treatment strategy for patients. Imaging findings and pathological diagnostic criteria are important to accurately differentiate between metastasis and primary breast lesions, which may improve the patient's outcomes.

Laryngeal adenoid cystic carcinoma: Three cases reports.

INTRODUCTION: Laryngeal adenoid cystic carcinoma (LACC) is an extremely rare malignant neoplasm. The etiology of LACC remains unknown, and it is characterized by multiple recurrences, slow progression, and late distant metastasis. This study aimed to provide more information regarding the characteristics, diagnosis, and treatment of LACC by analyzing 3 clinical cases and reviewing the literature on this topic. PATIENT CONCERNS: Here, we present all 3 cases of LACC within the period between 2010 and 2019. Dyspnea was the most commonly observed symptom in these patients, followed by hoarseness, pharyngeal paresthesia, and difficulty swallowing. DIAGNOSIS: All patients were pathologically confirmed as LACC. INTERVENTIONS: All the patients underwent a combined therapy of surgical resection plus external irradiation. OUTCOMES: The follow-up time was between 2 and 6 years; no local recurrence occurred in any of the 3 patients. Lung metastasis was found in 1 patient 6 years after surgery. CONCLUSION: LACC is usually a slowly progressing cancer; the main treatment methods are surgery and radiotherapy, and the adequate radiotherapy dose should usually be greater than 60 Gy. The 5-year disease-specific survival rate is high; however, distant metastasis may still occur in patients with LACC even beyond 5 years after treatment. Therefore, patients with LACC require long-term surveillance.

Cystic metastasis of prostate cancer: A case report.

RATIONALE: Prostate cancer often metastasizes (most commonly to the pelvic lymph nodes and axial skeleton); however, metastases to the pelvic cavity as a solitary mass are unusual. While metastatic prostate cancer is unconventional in pelvic cavity, cystic pelvic lesions are even more scarce. Accurate identification of cystic metastasis can be helpful in management of prostate cancer. PATIENT CONCERNS: A 64-year-old male was admitted to our hospital due to urethral irritation symptom and dysuria. DIAGNOSIS: In addition to prostate cancer, abdominal computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the prostate revealed that a cystic mass was located at right pelvic cavity. Histopathological examination diagnosed the pelvic cystic mass as metastasis from prostatic cancer. Immunohistochemistry results demonstrated Calretinin (+), D2-40 (-), Ki-67 (10%+), Vimentin (-), CK-pan (+), CK5/6 (-), WT-1 (-), PSA (+), SALL4 (-), Villin (-), CK20 (-), CK7 (-), PAX-8 (-), and TTF-1 (-). INTERVENTIONS: The cystic mass was removed. Primary cancer of the prostate was reserved as well. After discharge, the patient underwent in a two-year androgen deprivation therapy (ADT) treatment. OUTCOMES: After 13 months of discharge, no disease progression was found in the patient. LESSONS: Although cystic prostate cancer is rare, the occurrence possibility should be considered when cystic lesions are accompanied with prostate cancer.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.

Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy.

The aim of this study was to find the differences and relationships between normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) lesions of the breast based on biochemical characteristics determined by Raman spectroscopy (RS). After collecting 39 frozen sections from patients who underwent surgical resection or mammotome biopsy, nine normal tissues, seven ADH, eight DCIS, and 15 IDC lesions were detected using confocal RS. We then used leave-one-out cross-validation (LOOCV) and radial basis function (RBF) to build a support vector machine (SVM) diagnosis model. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS, and IDC tissues. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The major spectra differences in ADH, DCIS, and IDC spectrograms were evidenced by a red shift with a broad peak of CH2 (1301 cm-1), the intensity of the stretching vibration peak of carotenoids (1526 cm-1), a relatively strong band of amide-I (1656 cm-1), and the nuclear (882 cm-1) acid peak. Atypical ductal hyperplasia tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The overall accuracy of SVM model is 74.39%. The sensitivities of normal tissue, ADH, DCIS, and IDC are 62.5%, 50%, 90%, and 66.7%, respectively. The specificities of normal tissue, ADH, DCIS, and IDC are 100%, 100%, 66.7%, and 89.06%, respectively. Atypical ductal hyperplasia shows significant differences and the relationship between normal tissue and malignant disease. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH converts to DCIS and to IDC.

Salt-inducible Kinase (SIK1) regulates HCC progression and WNT/ß-catenin activation.

BACKGROUND & AIMS: In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). METHODS: Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the ß-catenin signaling pathway. RESULTS: SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of ß-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of ß-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of ß-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/ß-catenin pathway. However, SMRT-T1391A reverses the phenotype of SIK1 and promotes ß-catenin transactivation. Twist1 is identified as a critical factor downstream of SIK1/ß-catenin axis, and Twist1 knockdown (Twist1(KD)) reverses SIK1(KD)-mediated changes, whereas SIK1(KD)/Twist1(KD) double knockdown cells were less efficient in establishing tumor growth and metastasis than SIK1(KD) cells. The promoter activity of SIK1 were negatively regulated by Twist1, indicating that a double-negative feedback loop exists. Importantly, levels of SIK1 inversely correlate with Twist1 expression in human HCC specimens. CONCLUSIONS: Our findings highlight the critical roles of SIK1 and its targets in the regulation of HCC development and provides potential new candidates for HCC therapy.

Breast infarction during pregnancy and lactation: A case report.

Spontaneous infarction is a rare condition associated with the physiological hyperplasia of breast tissue associated with pregnancy and lactation. The causes of and mechanism underlying the occurrence of this complication remain largely unknown. The present study describes a rare case of breast infarction occurring during pregnancy and lactation in a 20-year-old woman. At 2 months of gestation, the patient noticed a soft and painless lump (size, ~5×4 cm) in the right breast. The lump grew to eventually occupy the entire breast. The patient was hospitalized 1 month after delivery and underwent a mastectomy. Histopathological study of the resected breast tissue revealed that 90% of the breast tissue had undergone infarction, with the infarct located centrally, under the areola. Involution of the breast tissue and small focal hemorrhages were noted, along with acute or chronic inflammatory cell infiltration in the interstitial tissue. Some breast ducts showed cystic dilatation, while some small blood vessels showed dilatation and congestion. Postoperative recovery of the patient was uneventful. This was a case of breast infarction with irregular, high-grade fever. The findings of core-biopsy were inconclusive, which highlights the importance of Mammotome™ biopsy or surgical excision in the diagnosis in such cases.

Pursuing shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) for concomitant detection of breast lesions and microcalcifications.

Although tissue staining followed by morphologic identification remains the gold standard for diagnosis of most cancers, such determinations relying solely on morphology are often hampered by inter- and intra-observer variability. Vibrational spectroscopic techniques, in contrast, offer objective markers for diagnoses and can afford disease detection prior to alterations in cellular and extracellular architecture by furnishing a rapid "omics"-like view of the biochemical status of the probed specimen. Here, we report a classification approach to concomitantly detect microcalcification status and local pathological state in breast tissue, featuring a combination of vibrational spectroscopy that focuses on the tumor and its microenvironment, and multivariate data analysis of spectral markers reflecting molecular expression. We employ the unprecedented sensitivity and exquisite molecular specificity offered by Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) to probe the presence of calcified deposits and distinguish between normal breast tissues, fibroadenoma, atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). By correlating the spectra with the corresponding histologic assessment, we developed partial least squares-discriminant analysis derived decision algorithm that provides excellent diagnostic power in the fresh frozen sections (overall accuracy of 99.4% and 93.6% using SHINs for breast lesions with and without microcalcifications, respectively). The performance of this decision algorithm is competitive with or supersedes that of analogous algorithms employing spontaneous Raman spectroscopy while enabling facile detection due to the considerably higher intensity of SHINERS. Our results pave the way for rapid tissue spectral pathology measurements using SHINERS that can offer a novel stain-free route to accurate and economical diagnoses without human interpretation.

The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia.

Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other--they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5.

[Two cases of synovial sarcoma in the head and neck].

Synovial sarcoma is a malignant soft tissue with unknown origin. Although head and neck region is the second common site of involvement, rare cases have been reported in Para nasal sinus and larynx. We presented two cases of synovial sarcoma, one of which arised from maxillary sinus and the other from laryx, and re- view the literature to sum up the diagnosis and treatment strategies. The conclusion is that synovial sarcoma in the head and neck still raises diagnostic and therapeutic issues. Surgical excision with wide margins is essential and necessary, usually associated radiotherapy. The effect of chemotherapy remains to explored.

Fabrication and Characterization of a Novel Anticancer Drug Delivery System: Salecan/Poly(methacrylic acid) Semi-interpenetrating Polymer Network Hydrogel.

Salecan is a novel linear extracellular polysaccharide with a linear backbone of 1-3-linked glucopyranosyl units. Salecan is suitable for preparing hydrogels for biomedical applications due to its prominent physicochemical and biological profiles. In this contribution, a variety of innovative semi-interpenetrating polymer network (semi-IPN) hydrogels consisting of Salecan and poly(methacrylic acid) (PMAA) were developed via free radical polymerization for controlled drug delivery. The successful fabrication of the semi-IPNs was verified by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric (TGA) measurements. Scanning electron microscopy (SEM) and rheology analyses demonstrated that the morphological and mechanical behaviors of the resultant hydrogels were strongly affected by the contents of Salecan and cross-linker N,N'-methylenebis(acrylamide) (BIS). Moreover, the swelling properties of these hydrogels were systematically investigated, and the results indicated that they exhibited pH sensitivity. The drug delivery applications of such fabricated hydrogels were further evaluated from which doxorubicin (Dox) was chosen as a model drug for in vitro release and cell viability studies. It was found that the Dox release from the Dox-loaded hydrogels was significantly accelerated when the pH of the release media decreased from 7.4 to 5.0. Toxicity assays confirmed that the blank hydrogels had negligible toxicity to normal cells, whereas the Dox-loaded hydrogels remained high in cytotoxicity for A549 and HepG2 cancer cells. All of these attributes implied that the new proposed semi-IPNs serve as potential drug delivery platforms for cancer therapy.

Exploring type II microcalcifications in benign and premalignant breast lesions by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS).

The characteristics of type II microcalcifications in fibroadenoma (FB), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) breast tissues has been analyzed by the fingerprint features of Raman spectroscopy. Fresh breast tissues were first handled to frozen sections and then they were measured by normal Raman spectroscopy. Due to inherently low sensitivity of Raman scattering, Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was utilized. A total number of 71 Raman spectra and 70 SHINERS spectra were obtained from the microcalcifications in benign and premalignant breast tissues. Principal component analysis (PCA) was used to distinguish the type II microcalcifications between these tissues. This is the first time to detect type II microcalcifications in premalignant (ADH and DCIS) breast tissue frozen sections, and also the first time SHINERS has been utilized for breast cancer detection. Conclusions demonstrated in this paper confirm that SHINERS has great potentials to be applied to the identification of breast lesions as an auxiliary method to mammography in the early diagnosis of breast cancer.

The use of Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy for human breast cancer detection.

This study uses the powerful fingerprint features of Raman spectroscopy to distinguish different types of breast tissues including normal breast tissues (NB), fibroadenoma (FD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Thin frozen tissue sections of fresh breast tissues were measured by Raman spectroscopy. Due to the inherent low sensitivity of Raman spectra, Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was utilized to provide supplementary and more informative spectral features. A total of 619 Raman spectra were acquired and compared to 654 SHINERS spectra. The maximum enhancement effect of distinct and specific bands was characterized for different tissue types. When applying the new criteria, excellent separation of FD, DCIS, and IDC was obtained for all tissue types. Most importantly, we were able to distinguish ADH from DCIS. Although only a preliminary distinction was characterized between ADH and NB, the results provided a good foundation of criteria to further discriminate ADH from NB and shed more light toward a better understanding of the mechanism of ADH formation. This is the first report to detect the premalignant (ADH and DCIS) breast tissue frozen sections and also the first report exploiting SHINERS to detect and distinguish breast tissues. The results presented in this study show that SHINERS can be applied to accurately and efficiently identify breast lesions. Further, the spectra can be acquired in a minimally invasive procedure and analyzed rapidly facilitating early and accurate diagnosis in vivo/in situ.

Abnormal expression of an ADAR2 alternative splicing variant in gliomas downregulates adenosine-to-inosine RNA editing.

BACKGROUND: RNA editing is catalyzed by adenosine deaminases acting on RNA (ADARs). ADAR2 is the main enzyme responsible for recoding editing in humans. Adenosine-to-inosine (A-to-I) editing at the Q/R site is reported to be decreased in gliomas; however, the expression of ADAR2 mRNA was not greatly affected. METHODS: We determined ADAR2 mRNA expression in human glioblastoma cell lines and in normal human glial cells by real-time RT-PCR. We also determined ADAR2 mRNA expression in 44 glioma tissues and normal white matter. After identifying an alternative splicing variant (ASV) of ADAR2 in gliomas, we performed sequencing. We then classified glioblastomas based on the presence (+) or absence (-) of the ASV to determine the correlations between ASV + and malignant features of glioblastomas, such as invasion, peritumoral brain edema, and survival time. RESULTS: There were no significant differences in ADAR2 mRNA expression among human glioblastoma cell lines or in gliomas compared with normal white matter (all p > 0.05). The ASV, which contained a 47-nucleotide insertion in the ADAR2 mRNA transcript, was detected in the U251 and BT325 cell lines, and in some glioma tissues. The expression rate of ASV differed among gliomas of different grades. ASV + glioblastomas were more malignant than ASV - glioblastomas. CONCLUSIONS: ADAR2 is a family of enzymes in which ASVs result in differences in enzymatic activity. The ADAR2 ASV may be correlated with the invasiveness of gliomas. Identification of the mechanistic characterization of ADAR2 ASV may have future potential for individualized molecular targeted-therapy for glioma.