The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer.

BACKGROUND: Sex-determining region Y-box 2 (SOX2) is a transcriptional factor that drives embryonic stem cells to neuroendocrine cells in lung development and is highly expressed in small-cell lung cancer (SCLC). However, the prognostic role of SOX2 and its relationship with tumor-infiltrating lymphocytes (TILs) has not been determined in SCLC. Herein, we assessed the expression of SOX2 and CD8+ TILs to obtain insights into the prognostic role of SOX2 and CD8+ TILs in limited-stage (LS)-SCLC. METHODS: A total of 75 patients with LS-SCLC was enrolled. The SOX2 expression and CD8+ TILs were evaluated by immunohistochemistry. RESULTS: High SOX2 and CD8+ TIL levels were identified in 52 (69.3%) and 40 (53.3%) patients, respectively. High SOX2 expression was correlated with increased density of CD8+ TILs (p = 0.041). Unlike SOX2, high CD8+ TIL numbers were associated with significantly longer progression-free survival (PFS; 13.9 vs. 8.0 months, p = 0.014). Patients with both high SOX2 expression and CD8+ TIL numbers (n = 29, 38.7%) had significantly longer PFS and overall survival (OS) compared to those from the other groups (median PFS 19.3 vs. 8.4 months; p = 0.002 and median OS 35.7 vs. 17.4 months; p = 0.004, respectively). Multivariate Cox regression analysis showed that the combination of high SOX2 expression and CD8+ TIL levels was an independent good prognostic factor for OS (HR = 0.471, 95% CI, 0.250-0.887, p = 0.02) and PFS (HR = 0.447, 95% CI, 0.250-0.801, p = 0.007) in SCLC. CONCLUSIONS: Evaluation of the combination of SOX2 and CD8+ TIL levels may be of a prognostic value in LS-SCLC.

Sonographic appearance of an eccrine spiradenoma: A case report.

Eccrine spiradenoma is a rare, benign, adnexal skin tumor of the sweat gland, which may manifest in any part of the body. It is typically located in the dermal or the subcutaneous fat layer. Eccrine spiradenomas rarely progress to malignant transformation and only a few cases of malignant transformation have been reported. Due to its rarity, there have been few reports about the sonographic appearances of eccrine spiradenoma. We report the sonographic findings in one case of eccrine spiradenoma, located in the subcutaneous fat and the deep dermal layers of the upper arm in a middle-aged woman.

Imaging sonographic findings of in a case of proliferating trichilemmal tumor of a finger: A case report.

Proliferating trichilemmal tumor (PTT) is a rare tumor that originates from the outer root sheath of a hair follicle. About 90% of PTTs occur on the scalp. The sonographic findings of PTT in the subungual region have not been reported previously. In our case, sonography showed a heterogeneous mass containing echogenic foci with no detectable intratumoral vascularity. These echogenic foci probably represent keratin and cholesterol. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:215-217, 2018.

Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer.

Cancer-associated fibroblasts (CAFs) play key roles in tumor microenvironment; they are thought to originate from adipocytes. This study aimed to evaluate CAF-related protein expression and its implications in breast cancer. Of the 939 enrolled breast cancer patients, 642 had fibrous and 297 had adipose stroma. The status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER-2), Ki-67, podoplanin, prolyl 4-hydroxylase, fibroblast activation protein α (FAPα), S100A4, platelet-derived growth factor receptor α (PDGFRα), PDGFRß, and chondroitin sulfate proteoglycan (NG2) was evaluated via tissue microarrays. Tumors were divided into luminal A, luminal B, HER-2, or triple-negative breast cancer subtypes according to their molecular status. Luminal A subtype was more prevalent in breast cancer of adipose stroma type, whereas other molecular subtypes were more common in fibrous stroma type (p < 0.001). Tumor cell expression of podoplanin and FAPα was higher in adipose stroma type, while higher expression of prolyl 4-hydroxylase and PDGFRα was observed in fibrous stroma type. Furthermore, adipose stroma type exhibited higher stromal expression of podoplanin, FAPα, PDGFRß, and NG2, whereas fibrous stroma type had higher prolyl 4-hydroxylase and S100A4 expression. In adipose stroma type, tumor positivity (p = 0.034) and stromal positivity (p = 0.005) of prolyl 4-hydroxylase were associated with shorter disease-free survival, and stromal prolyl 4-hydroxylase positivity was with shorter overall survival (p < 0.001). In conclusion, expression of CAF-related proteins was observed in breast cancer, with different profiles between adipose and fibrous stroma types. Prolyl 4-hydrolase status might be of prognostic value in adipose stroma type.

Comparison of Clinicopathological and Prognostic Characteristics Between Minimal Deviation Adenocarcinoma and Gastric-type Endocervical Adenocarcinoma.

BACKGROUND/AIM: Minimal deviation adenocarcinoma (MDA) is an extremely well-differentiated variant of gastric-type endocervical adenocarcinoma (GEA). This study compared the clinicopathological and prognostic characteristics of MDA to those of GEA. PATIENTS AND METHODS: Nine MDAs and 22 GEAs were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological and prognostic information. RESULTS: GEA showed significantly higher stage at presentation, more frequent parametrial extension and lymphovascular space invasion, and recurrence than MDA. Patients with GEA had significantly lower survival rates than those with MDA. None of the cases with MDA exhibited singly dispersed or clustered tumor cells, diffuse stromal desmoplasia, severe nuclear pleomorphism, loss of nuclear polarity, or coarse chromatin, all of which were frequently observed in GEA. CONCLUSION: Significant differences were observed in the clinicopathological characteristics and patient outcomes between MDA and GEA. Further investigations using a larger cohort are warranted to determine the clinical behavior and aggressiveness of MDA.

Imaging Findings of Primary Acinic Cell Carcinoma of the Breast: A Case Report.

Acinic cell carcinoma is a rare malignant tumor that accounts for 2%-3% of salivary gland tumors. Acinic cell carcinoma arising from the breast is extremely rare, with only approximately 70 cases reported to date. Owing to its rarity, previous studies have primarily focused on pathological findings. Herein, we present the clinical and radiological features of acinic cell carcinoma of the breast in a 33-year-old woman.

A pilot study evaluating liquid-based fine needle aspiration cytology of breast lesions: a cytomorphological comparison of SurePath® liquid-based preparations and conventional smears.

OBJECTIVE: Fine needle aspiration cytology (FNAC) is recommended by the World Health Organization as a diagnostic method for breast lesions. The morphological interpretation of liquid-based preparations (LBPs) remains a diagnostic challenge due to considerably altered cytomorphology. The aim of the current study was to compare cytomorphological characteristics of SurePath® (SP)-based LBP and conventional smear (CS) in breast FNACs. STUDY DESIGN: The study included 77 benign and 60 malignant breast FNACs obtained by both SP and CS, all with tissue confirmation. Cases analyzed with both preparations were reviewed and compared, focusing on 10 cytomorphological features. RESULTS: SP aspirates demonstrated notable cytomorphological alterations. Among them, a prominent three-dimensional configuration of cell clusters and frequent and conspicuous nucleoli were the most prominent characteristics of SP compared with CS. Overall diagnostic performances were comparable but were slightly lower for SP than CS (diagnostic accuracy of two reviewers; 87.6 and 90.5% for SP vs. 91.2 and 92.7% for CS, respectively). CONCLUSION: Although the reviewer should be aware of distinctive cytomorphological alterations, the SP technique is reliable for the evaluation of breast lesions with the advantage of easy interpretation and a diagnostic accuracy equivalent to CS.

Application of chemokine CXC motif ligand 12 as a novel diagnostic marker in preoperative fine-needle aspiration biopsy for papillary thyroid carcinoma.

OBJECTIVES: A panel composed of three immunomarkers, cytokeratin 19, HBME-1 and galectin-3, is recommended for improving the accuracy of diagnosing papillary thyroid carcinoma (PTC), but the results are sometimes inconsistent and difficult to interpret. We used immunocytochemistry to assess the utility of chemokine CXC ligand 12 (CXCL12) as a novel diagnostic marker for PTC employing paraffin-embedded cell blocks. METHODS: We analyzed the expression of CXCL12 using immunocytochemical staining in 82 cases of thyroid lesions (47 PTCs and 35 thyroid lesions other than PTC). To determine the optimal cut-off value for the assessment of CXCL12 positivity, we used receiver operating characteristics (ROC). RESULTS: ROC curves showed that the optimum diagnostic cut-off was 10% (area under the curve 0.950, 95% confidence interval 0.891-1.008), with exclusive CXCL12 expression in PTC compared to other thyroid lesions (p < 0.001). In total, more than 90% of the PTCs were associated with CXCL12 immunohistochemical staining, while only up to 11.4% of thyroid lesions other than PTC were positive for CXCL12. The follicular variant PTC showed 90% CXCL12 expression compared to 10.5% positivity in follicular neoplasm. CONCLUSION: Our findings indicate that CXCL12 may be an effective supplementary diagnostic marker for PTC in preoperative fine-needle aspiration cytology using the cell block method.

The unique liquid-based cytologic findings of thyroid signet-ring follicular adenoma: a report of two cases with fine needle aspiration cytology.

BACKGROUND: Signet-ring follicular adenoma is a rare variant of follicular neoplasm, which has only been described using the conventional smear cytologic preparation. Here we report the unique cytologic findings of two cases of signet-ring follicular adenoma using liquid-based samples and corresponding histologic features and results of ancillary tests. CASES: Case 1: A 65-year-old man presented with a solitary nodule in the right lobe of the thyroid. Ultrasound-guided fine needle aspiration (FNA) yielded several groups of microfollicles containing colloid or mucin-like globules. The tumor cells had eccentrically located nuclei compressed by distended luminal globules. Case 2: A 51-year-old woman presented with a nodule in the left lobe of the thyroid. On liquid-based cytology, cord-like arrangements of microfollicules were noted. The tumor cells had large, clear vacuoles, but the nuclei maintained their round shape and central location. CONCLUSION: The liquid-based cytologic characteristics are quite different from those encountered in the conventional smear of FNA; therefore, pathologists must also be familiar with the cytomorphologic characteristics of liquid-based preparations. In addition, given the distinctive cytological and histological appearance and the benign clinical course, signet-ring follicular adenoma should be distinguished from other metastatic neoplasms displaying signet-ring cell features.

Protective effect of phosphatidylcholine on lipopolysaccharide-induced acute inflammation in multiple organ injury.

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-α, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-α and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

Rare Manifestation of the Cutaneous and Cervical Lymph Node Metastases of Urothelial Carcinoma of Urinary Bladder: A Case Report.

Lymph node metastasis from bladder cancer mainly involves the external/internal iliac and obturator nodes as the primary lymphatic drainage sites of the bladder, and common iliac sites as the secondary drainage. Lymph node involvement above the diaphragm is rare. Metastasis to the head and neck region is associated with poor prognosis and low survival rate. Herein, we report a case of cervical cutaneous and lymph node metastases in a patient with bladder cancer. This is a rare case of advanced urothelial carcinoma presenting as an aggressive inflammatory process with extensive lymph node involvement, without bony or visceral metastasis.

Dissecting Gonadoblastoma of the Ovary Coexistent with an Atypical Endometriotic Cyst: Incidental Detection in Cystectomy Specimen of a Woman with 46,XX Karyotype.

Dissecting gonadoblastoma (DGB) of the ovary, a recently described terminology, defines a unique distribution of neoplastic germ cells. Here, we report a case of incidental DGB coexistent with an atypical endometriotic cyst occurring in a 23-year-old woman. The ovarian cyst was lined by endometrial-like glands and stroma. Some glands displayed nuclear enlargement and hyperchromasia, and abundant eosinophilic cytoplasm with occasional intracytoplasmic hemosiderin and mucin vacuoles. The neoplastic germ cells resembled those of ovarian dysgerminoma and were diffusely distributed within the ovarian stroma, which was stretched around the wall of the endometriotic cyst. These cells were arranged in nests and cords, possessing clear cytoplasm and centrally located round nuclei with prominent nucleoli and occasional mitoses. Chromosomal analysis revealed a 46,XX karyotype. We describe the clinical, histological, immunophenotypical, and genetic features of ovarian DGB incidentally detected in the ovarian cystectomy specimen of a woman with normal female karyotype.

Ultrasonographic Findings of a Chondrolipoma Arising from the Left Supraclavicular Region: A Case Report.

Chondrolipomas, which are lipomas with chondroid metaplasia, are rare benign soft tissue tumors with no relevant epidemiological reports or radiological information. A limited number of lipomas with osteo/chondroid differentiation have been reported in the literature between 1960 and 2008. Moreover, only few studies have described the radiologic findings of chondrolipomas. Herein, we present a case of chrondrolipoma arising from the left supraclavicular region in a 77-year-old female.

Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation.

We present herein a rare case of uterine serous carcinoma with mesonephric-like differentiation (SC-MLD) initially misdiagnosed as mesonephric-like adenocarcinoma (MLA). A 51-year-old woman underwent total hysterectomy for a uterine tumor. Histologically, the tumor exhibited various architectures, including papillary, glandular, tubular, cribriform, and cystic. On the basis of this architectural diversity accompanied by intraluminal eosinophilic secretions and intermediate-grade nuclear atypia, the initial diagnosis was MLA. However, the tumor was diffusely and strongly positive for the expression of p16 and negative for the expression of GATA-binding protein 3 (GATA3). Furthermore, we identified a pathogenic tumor protein 53 (TP53) mutation affecting an acceptor splice site in intron 9, despite a wild-type p53 immunostaining pattern. The observations of diffuse and strong p16 expression, lack of GATA3 expression, pathogenic TP53 mutation, and wild-type Kirsten rat sarcoma viral oncogene homolog indicate that this tumor was not an MLA but an SC-MLD. Both uterine SC and MLA can exhibit various histological growth patterns. Our comprehensive clinicopathological and molecular analyses can serve to improve the understanding of this rare condition and help pathologists in making an accurate diagnosis.

Clinicopathological Characteristics of Gastric-type Endocervical Adenocarcinoma Misdiagnosed as an Endometrial, Ovarian or Extragenital Malignancy, or Mistyped as Usual-type Endocervical Adenocarcinoma.

BACKGROUND/AIM: The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors. PATIENTS AND METHODS: We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases. RESULTS: Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma. CONCLUSION: The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results.

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma.

BACKGROUND/AIM: We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC). CASE REPORT: A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA. CONCLUSION: Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.

A Rare Case of Pituicytoma Presenting Cystic Formation.

Pituicytoma is a rare solid benign tumor of the sellar and/or suprasellar region originating from the pituicytes of the neurohypophysis or infundibulum, which is not differentiated from a pituitary adenoma that is diagnosed mostly in the sellar and/or suprasellar region. In addition, cystic tumors are very rare and have not been reported due to their solid and hypervascular natures. A 33-year-old man presented with a chronic headache which exacerbated recently. MRI was performed and revealed a cystic tumor in the sellar and suprasellar regions with a small parenchymal island in the cyst compressing the optic chiasm. The endoscopic endonasal transsphenoidal approach was used to remove the tumor. Immunohistochemical staining was positive for thyroid transcription factor 1, S-100 protein, and glial fibrillary acidic protein. The pituicytoma was diagnosed based on histologic findings. The authors review herein the literature on clinical presentation, diagnosis, surgical management, and outcome.

Targeted Genomic Sequencing Reveals Novel TP53 In-frame Deletion Mutations Leading to p53 Overexpression in High-grade Serous Tubo-ovarian Carcinoma.

BACKGROUND/AIM: High-grade serous carcinoma (HGSC) is the most common histological subtype of ovarian carcinoma. Somatic mutation of tumor protein 53 (TP53) is a hallmark of tubo-ovarian HGSC and is observed in almost all such cases. Highly sensitive targeted genomic sequencing can be used to identify novel mutations that may become potential druggable targets and aid in therapeutic decisions. The aim of this study was to describe the clinicopathological and molecular characteristics of HGSCs with novel somatic TP53 mutations identified by next-generation sequencing (NGS). MATERIALS AND METHODS: A commercial NGS panel comprising 170 genes, including TP53, was used to analyze the genetic profiles of 132 ovarian carcinoma cases. The clinicopathological characteristics and p53 immunostaining results of two HGSCs exhibiting novel TP53 mutations were investigated. RESULTS: Eighty-eight (66.7%) out of 132 ovarian carcinoma cases were diagnosed as HGSC. Novel TP53 in-frame deletion mutations c.719_727delGTTCCTGCA (p53 p.Ser240_Cys242del) and c.634_642delTTTCGACAT (p53 p.F212_H214del) were detected in a single case of HGSC each. Both patients were postmenopausal women. Imaging and laboratory studies revealed peritoneal carcinomatosis and elevated levels of serum tumor markers. The patients underwent primary debulking surgery and were diagnosed as having stage IIIC HGSC. In both cases, p53 immunostaining revealed uniform nuclear immunoreactivity in 90% or more of tumor cells at a very strong intensity. CONCLUSION: Targeted genomic sequencing revealed novel in-frame deletion mutations of TP53 leading to p53 overexpression in tubo-ovarian HGSC. This discovery of previously unreported somatic TP53 mutations provides insight into the translation of NGS technology into personalized medicine and identifies new potential targets for therapeutic applications.

Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma.

BACKGROUND/AIM: Mucinous metaplasia of the endometrium occurs as a spectrum of epithelial alterations ranging from the formation of simple, tubular glands to architecturally complex glandular proliferation with intraglandular papillary projection and cellular tufts. Endometrial mucinous metaplasia often presents a diagnostic challenge in endometrial curettage. MATERIALS AND METHODS: We analyzed the clinicopathological characteristics and the mutation status for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) of 11 cases of endometrial mucinous metaplasia. Electronic medical record review and histopathological examination were performed. KRAS mutation status was analyzed using a pyrosequencing technique. RESULTS: Cases were classified histopathologically into simple (5/11) or papillary (6/11) mucinous metaplasias. All (6/6) papillary mucinous metaplasias were associated with atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN; 1/6) or carcinoma (5/6), whereas in a single patient with simple mucinous metaplasia, grade 1 endometrioid carcinoma was incidentally detected. The difference in frequency of association of the metaplasia with AH/EIN or carcinoma was significant (p=0.015). KRAS mutations were identified in five out of six cases of papillary mucinous metaplasias, comprising three cases with G12D and two with G12V mutations; the frequency of KRAS mutation was significantly higher (p=0.015) than in cases of simple mucinous metaplasia (0/5). CONCLUSION: Papillary mucinous metaplasia is frequently associated with endometrial neoplastic lesions. The high incidence of KRAS mutations in papillary mucinous metaplasia suggests that papillary mucinous metaplasia may be a precancerous lesion of a certain subset of mucinous carcinomas of the endometrium.

Down-regulation of B-Cell Translocation Gene 1 by Promoter Methylation in Colorectal Carcinoma.

BACKGROUND: B-cell translocation gene 1 (BTG1) acts as a tumour suppressor in human malignancies. However, the precise mechanism of BTG1 down-regulation in colorectal carcinoma (CRC) remains unclear. We analyzed BTG1 expression in CRC cell lines and tissues and investigated the mechanism underlying the observed alterations. MATERIALS AND METHODS: Real-time polymerase chain reaction (PCR) and western blot analyses were performed to analyze BTG1 expression in CRC cell lines. The methylation status of the BTG1 promoter region in cell lines was determined by methylation-specific PCR, and the effect of demethylation on BTG1 expression was explored with 5-aza-deoxycytidine treatment. BTG1 protein expression in CRC tissue samples was evaluated using immunostaining. RESULTS: CRC cell lines and tissue samples expressed lower levels of BTG1 compared to controls, and BTG1 levels were significantly lower in metastatic than primary CRC. In BTG1-down-regulated CRC cell lines, the BTG1 promoter was highly methylated, and 5-aza-deoxycytidine significantly restored BTG1 expression. CONCLUSION: BTG1 down-regulation in CRC occurs through epigenetic repression, which is involved in the development and progression of CRC.