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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cytomorphological characteristics of glassy cell carcinoma of the uterine cervix: histopathological correlation and human papillomavirus genotyping.

A retrospective analysis was performed to describe the cytomorphological and histopathological findings and human papillomavirus (HPV) genotypes for glassy cell carcinoma (GCC) of the uterine cervix. Five cases of cervical GCC, in which the glassy cell features constituted at least 95% of the specimen, were included. Four patients had stage IIB GCCs and one had stage IIIB GCC. All patients underwent concurrent chemoradiation therapy. Based on pretreatment cytology, only 1 of the 5 cases was correctly diagnosed as GCC. The remaining cases were diagnosed as carcinoma of undetermined type, adenocarcinoma, poorly differentiated carcinoma, or unsatisfactory for evaluation. Cytological specimens had moderate cellularity and contained small clusters of tumor cells admixed with amphophilic, granular tumor diathesis. The tumor cells possessed large, round to oval nuclei and abundant, granular, ground-glass cytoplasm. The nuclei exhibited prominent eosinophilic nucleoli. The cytoplasm displayed sharp margins and molding, resulting in "intercellular windows" between neighboring attached cells. HPV genotyping revealed that high-risk HPV types 18, 16, and 31 were detected in 3, 1, and 1 cases, respectively. Consistent with this finding, all cases exhibited block p16 positivity, confirming the association of HPV infection with GCC. In conclusion, a distinct cytoplasmic margin, the characteristic histopathological feature of GCC, was observed in liquid-based cytological preparations. We suggest that sharp cytoplasmic outlines with molding and intercellular windows are characteristic cytomorphological features of GCC. Detection of high-risk HPV in all cases strongly supported the notion that high-risk HPV is involved in the pathogenesis of GCC.

Histomorphological Factors Predicting the Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled. The core needle biopsy specimens acquired before NAC were used to analyze the clinicopathologic variables and overall performance of the predictive model for therapeutic response. RESULTS: Independent predictors of pathologic complete response after NAC were found to be higher number of tumor infiltrating lymphocytes (p=0.007), absence of clear cytoplasm (p=0.008), low necrosis (p=0.018), and high histologic grade (p=0.039). In the receiver operating characteristics curve analysis, the area under curve for the combination of these four variables was 0.777. CONCLUSION: The present study demonstrated that a predictive model using the above four variables can predict therapeutic response to single-regimen NAC with the combination of doxorubicin, cyclophosphamide, and docetaxel in TNBC. Therefore, adding these morphologic variables to clinical and genomic signatures might enhance the ability to predict the therapeutic response to NAC in TNBC.

Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer.

The aim of this study is to evaluate the biological role and clinical implications of silent mating type information regulation 2 homolog 1 (SIRT1) as a novel candidate for target therapy in triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of SIRT1 significantly correlated with lymph node metastasis (p = 0.008). In multivariate analysis, SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p < 0.001) were revealed to be independent predictive factors for lymph node metastasis. Combination of these three parameters revealed predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.689 on receiver operating characteristics (ROC) curves analysis. SIRT1 expression correlated with shorter disease-free survival (P = 0.003) but not with overall survival. Inhibition of SIRT1 with small interfering RNA (siRNA) conspicuously suppressed the invasiveness of TNBC cell lines. This study reveals the role of SIRT1 on tumor invasiveness and unfavorable clinical outcomes, and we suggest its potential role as a prognostic indicator as well as a novel therapeutic target in TNBC.

The role of cancer-associated fibroblasts in breast cancer pathobiology.

The role of the tumor microenvironment (TME) is critical in cancer pathobiology. Of the components of the TME, cancer-associated fibroblasts (CAFs) play a major role. Breast cancer is a typical tumor type, forming abundant tumor stroma, and CAFs are involved in various aspects of breast cancer, including carcinogenesis, tumor progression, invasion, metastasis, inflammation, metabolism, therapy resistance, and prognosis. Various factors, such as growth factors, cytokines, hormones secreted from CAFs, paracrine effects promoted by the extracellular matrix (ECM), and mechanical pressure, are involved in cancer development, and there are various crosstalk and signaling pathways among CAFs, cancer cells, epithelial cells, and the ECM. Recent studies have evaluated the potential of CAFs as therapeutic targets in breast cancer. In this review, we discuss the role of CAFs and their clinical implications.

The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer.

INTRODUCTION: Beclin 1 plays a crucial role in autophagy via the Beclin 1 interactome, and is involved in various biological processes such as protein sorting, chemokinesis, and cell death. Via these biologic functions, Beclin 1 contributes to both tumor suppression and tumor progression. AREAS COVERED: Beclin 1 plays a key biologic function on cell homeostasis and affects tumorigenesis. In this review, detailing up-to-date knowledge on the tumorigenic role of Beclin 1, its implication in breast cancer, and its utility as a breast cancer-specific drug target is discussed. EXPERT OPINION: Because Beclin 1 is expressed in breast cancer cells, Beclin 1 could be a unique, effective drug target for the prevention and treatment of breast cancer. However, the expression of Beclin 1 varies according to cancer molecular subtypes, and Beclin 1 is involved in both breast cancer suppression and tumor progression; therefore, the decision of using a Beclin 1 inducer or inhibitor should be made based on breast cancer stage and subtype.

Significance of Subcategory Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Showing Both Cytologic and Architectural Atypia in Thyroid Aspiration Cytology.

OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology is now widely used as the standard reporting system for fine-needle aspiration cytology (FNAC). Recently, several studies have attempted to subcategorize the atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) category. We aimed to analyze the significance of a subcategory of AUS/FLUS showing both cytologic and architectural atypia (AUS/FLUS-C&A). STUDY DESIGN: From April 2011 to May 2014, 18,091 patients underwent FNAC at Samsung Medical Center. For those patients we analyzed the clinical significance of the subcategory AUS/FLUS-C&A. RESULTS: One hundred and sixty-three patients were diagnosed as AUS/FLUS-C&A. Of 71 cases with subsequent histologic confirmation, 47 (66.2%) were diagnosed with papillary thyroid carcinoma (PTC). Of the 47 PTC cases, 32 (68.1%) were follicular variant-PTC. A significant difference in the PTC rate (58.3 vs. 82.6%) and PTC size (average: 1.8 and 0.9 cm) was noted between circumscribed lesions and infiltrative lesions on ultrasonography. CONCLUSION: We demonstrated that the subcategory of AUS/FLUS-C&A has considerable clinical implications and one should be aware of the cytological and ultrasonographic features.