Multiple Actinic Keratoses within Vitiliginous Patches in a Patient with Non-segmental Vitiligo / 대한피부과학회지

A 74-year-old man visited our department with complaints of multiple asymptomatic erythematous scaly crusted patches on the scalp. He had non-segmental vitiligo with the extent of over 20% of the body surface area for 30 years. Biopsies showed hyperkeratosis, foci of atypical, pleomorphic keratinocytes along the basal cell layer, and marked solar elastosis, consistent with actinic keratosis (AK). Melan-A and Fontana-Masson staining showed absence of melanin and melanocytes. Despite conflicting data on the prevalence of skin cancers in patients with vitiligo, it is known that vitiligo does not increase nor decrease the risk of skin cancer. Recent studies have reported that patients with vitiligo lesions show increased epidermal expression of wild-type p53 protein than healthy controls. However, a few cases of skin cancer have been reported in patients with vitiligo. Here, we report a case of AK developing in vitiligo lesions. Dermatologists should not overlook the possible occurrence of AK or skin cancers in sun-exposed vitiliginous skin.

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer / 한국유방암학회지

Purpose@#Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications. @*Methods@#In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data. @*Results@#EMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index. @*Conclusion@#EMP2 may be involved in the early stage of tumor development in hormonepositive breast cancer.

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer / 한국유방암학회지

Purpose@#Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications. @*Methods@#In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data. @*Results@#EMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index. @*Conclusion@#EMP2 may be involved in the early stage of tumor development in hormonepositive breast cancer.

External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence

PURPOSE: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. MATERIALS AND METHODS: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of 10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. RESULTS: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. CONCLUSIONS: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.

Feasibility of Charcoal Tattooing of Cytology-Proven Metastatic Axillary Lymph Node at Diagnosis and Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB) can be performed when node-positive disease is converted to node-negative status after neoadjuvant chemotherapy (NCT). Tattooing nodes might improve accuracy but supportive data are limited. This study aimed to investigate the feasibility of charcoal tattooing metastatic axillary lymph node (ALN) at presentation followed by SLNB after NCT in breast cancers. MATERIALS AND METHODS: Twenty patientswith cytology-proven node metastases prospectively underwent charcoal tattooing at diagnosis. SLNB using dual tracers and axillary surgery after NCT were then performed. The detection rate of tattooed node and diagnostic performance of SLNB were analyzed. RESULTS: All patients underwent charcoal tattooingwithout significant morbidity. Sentinel and tattooed nodes could be detected during surgery after NCT. Nodal pathologic complete response was achieved in 10 patients. Overall sensitivity, false-negative rate (FNR), negative predictive value, and accuracy of hot/blue SLNB were 80.0%, 20.0%, 83.3%, and 90.0%, respectively. Retrieving more nodes and favorable nodal response were associated with improved performance. The best accuracy was observed when excised tattooed node was calculated together (FNR, 0.0%). Cold/non-blue tattooed nodes of five patients were removed during non-sentinel axillary surgery but clinicopathological parameters did not differ compared to patients with hot/blue tattooed node detected during SLNB, suggesting the importance of the tattooing procedure itself to improve performance. CONCLUSION: Charcoal tattooing of cytology-confirmed metastatic ALN at presentation is technically feasible and does not limit SLNB after NCT. The tattooing procedure without additional preoperative localization is advantageous for improving the diagnostic performance of SLNB in this setting.

Metastatic renal cell carcinoma in the thyroid gland: ultrasonographic features and the diagnostic role of core needle biopsy

PURPOSE: The aims of this study were to present the ultrasonographic (US) features of metastatic renal cell carcinoma (RCC) in the thyroid gland and to evaluate the diagnostic utility of fineneedle aspiration (FNA) and core needle biopsy (CNB). METHODS: Eight patients with nine metastatic RCC nodules in the thyroid glands who were treated from January 2002 to March 2015 in a single tertiary hospital were consecutively selected and retrospectively reviewed. US features and clinical history were obtained from the institution's medical database. FNA was performed nine times on eight nodules and CNB was performed six times on six nodules. The diagnostic utility of FNA and CNB was evaluated. RESULTS: All nine nodules showed mass formation without diffuse thyroid involvement. On ultrasonography, metastatic RCC nodules were solid (100%), hypoechoic (100%), and oval-shaped nodules with a well-defined smooth margin (88.9%) and increased vascularity (100%, with 55% showing extensive vascularity). No calcifications were noted in any nodules. Lymph node metastasis and direct extension to nearby structures beyond the thyroid gland were not found. One FNA (11%) was able to confirm metastatic RCC, whereas all six CNBs confirmed metastatic RCC. CONCLUSION: Metastatic RCC appears as oval-shaped hypoechoic solid nodules with well-defined smooth margins, no calcifications, and increased vascularity on ultrasonography. Characteristic US features along with a previous history of RCC should raise clinical suspicion, and CNB should be performed to make an accurate diagnosis.

Mucinous Carcinoma with Extensive Signet Ring Cell Differentiation: A Case Report

Breast cancers that present with mucin include mucinous carcinoma and carcinoma with signet ring cell differentiation. The former shows extracellular mucin and the latter shows abundant intracellular mucin. Here, we report a case of breast cancer showing both extracellular mucin and extensive signet ring cell differentiation due to abundant intracellular mucin. Unlike mucinous carcinoma, this case had the features of high-grade nuclear pleomorphism, high mitotic index, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor-2 positivity, and ductal type with positivity for E-cadherin. In a case with signet ring cell differentiation, differential diagnosis with metastatic signet ring cell carcinoma of the stomach and colon is essential. In this case, the presence of accompanied ductal carcinoma in situ component and mammaglobin and gross cystic disease fluid protein-15 positivity were findings that suggested the breast as the origin.

Retroperitoneal Schwannoma Mimicking an Adrenal Mass / 대한내과학회지

A schwannoma is a benign neoplasm originating from the Schwann cells of the neural sheath. The most common type of benign schwannomas is the acoustic neuroma presenting with deafness. We report a rare case of schwannoma mimicking an adrenal mass. A 66-year-old woman was diagnosed with an adrenal incidentaloma measuring 10 cm in length on a health checkup. The hormonal study revealed that the adrenal mass was non-functioning. Due to a high risk of adrenal malignancy, a retroperitoneal mass excision, distal pancreatectomy, splenectomy, wedge resection of stomach, and left adrenalectomy were conducted. The subsequent histopathologic examination revealed it to be a benign schwannoma.

Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy

Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.

Expression of Autophagy and Reactive Oxygen Species-Related Proteins in Lacrimal Gland Adenoid Cystic Carcinoma

PURPOSE: To investigate the difference of expression of autophagy and reactive oxygen species (ROS) related proteins in adenoid cystic carcinoma (ACC) of lacrimal gland in comparison with ACC of salivary gland. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples from patients pathologically diagnosed as lacrimal gland ACC (n=11) and salivary gland ACC (n=64) were used. Immunochemistry was used to measure expression of autophagy related proteins [beclin-1, light chain (LC) 3A, LC3B, p62, and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] and ROS related proteins [catalase, thioredoxinreductase, glutathione S-transferasepi (GSTpi), thioredoxin interacting protein, and manganese superoxide dismutase (MnSOD)]. The prognostic factors related to disease-free and overall survival (OS) in lacrimal gland ACC by log-rank tests, were determined. RESULTS: GSTpi in stromal cells was more highly expressed in lacrimal gland ACC (p=0.006), however, MnSOD in epithelial cells was expressed more in salivary gland ACC (p=0.046). LC3B positivity and BNIP3 positivity in epithelial component were associated with shorter disease-free survival (both p=0.002), and LC3A positivity in stromal component was the factor related to shorter OS (p=0.005). CONCLUSION: This is the first study to demonstrate the expression of autophagy and ROS related proteins in lacrimal gland ACC in comparison with the salivary gland ACC, which would provide a basis for further study of autophagy and ROS mechanism as novel therapeutic targets in lacrimal gland ACC.

Recurred Adenoid Cystic Carcinoma of Lacrimal Gland with Aggressive Local Invasion to the Maxillary Bone Marrow without Increased Uptake in PET-CT

No abstract available.

Expression of Sarcosine Metabolism-Related Proteins in Invasive Lobular Carcinoma: Comparison to Invasive Ductal Carcinoma

PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results. MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)]. RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (plow sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC. CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.

Low-Grade Adenosquamous Carcinoma of the Breast with Diverse Expression Patterns of Myoepithelial Cell Markers on Immunohistochemistry: A Case Study

This paper reports a case of low-grade adenosquamous carcinoma (LGASC) arising in a 69-year-old woman, who presented with a 1-cm palpable mass on her right breast. Core needle biopsy diagnosed the mass as a fibroadenoma. After six months, the mass increased in size, and the patient received subsequent mammotome excision. On microscopic examination, bland-looking small glands were infiltrating into the fibrotic stroma with lymphocytic infiltrates at the periphery. Hematoxylin and eosin staining revealed relatively easily detectable myoepithelial cells along the outside in each of the glandular structures with variable degrees of squamous metaplasia. Based on histologic features, the patient was diagnosed with LGASC. LGASC is a rare variant of metaplastic carcinoma, which is characterized by a favorable prognosis. Due to the bland cytology and presence of myoepithelial cells, LGASC can be misdiagnosed as benign lesion. Additionally, inconsistent expression of myoepithelial markers could aid the diagnosis of LGASC.

Expression of Glycolysis-Related Proteins in Solid Papillary Carcinoma of the Breast According to Basement Membrane Status

PURPOSE: The aim of this study was to investigate the differences of expression in glycolysis-related proteins such as Glut-1, carbonic anhydrase (CA) IX, and monocarboxylate transporter (MCT) 4 according to the myoepithelial cell (MEC) and basement membrane (BM) status in solid papillary carcinoma (SPC) of the breast. MATERIALS AND METHODS: Immunohistochemical evaluation of Glut-1, CAIX, and MCT4, as well as p63 and type IV collagen, were performed on 23 SPC cases. RESULTS: Six and nine cases of SPC showed the presence and absence of myoepithelial cells, respectively, and eight cases belonged to the borderline status (p63-positive MEC on some areas of the outer tumor surface but not in others). BM was partially or completely absent in 14 cases and present in nine cases. SPC lacking BM more frequently showed high expression of CAIX than SPC with BM (p=0.037). CONCLUSION: In SPC of the breast, a strong expression of CAIX seems to be associated with an increasing degree of loss of BM, which can be interpreted as BM degradation due to the induction of extracellular acidity with increasing expression of CAIX.

Cytomorphological Findings and Histological Correlation of Low-Grade Cribriform Cystadenocarcinoma of Salivary Gland in Fine-Needle Aspiration: A Case Study

Low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland is a rare tumor. We report the cytologic features and histologic correlation of a patient with LGCCC. A 57-year-old man had a hardly palpable, nontender mass in the right cheek area followed over nine months. Radiologic analysis revealed a 1.2 cm multiseptated, cystic, solid nodule in an anterior superficial lobe of the right parotid gland. Fine-needle aspiration cytology revealed many irregular overlapping sheets or clusters of ductal epithelial cells forming solid, pseudopapillary, and cribriform architectures. Nuclei of the tumor cells revealed inconspicuous atypia with minimal size variation. On the basis of these findings, we confirmed a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, with uncertain malignant potential. Tumor excision was performed, revealing a tiny multicystic nodule (0.7 cm). Histopathologically, this tumor showed the characteristic morphology of LGCCC. This is the first report of cytomorphological findings of LGCCC in Korea.

The Expression of Glut-1, CAIX, and MCT4 in Mucinous Carcinoma / 한국유방암학회지

PURPOSE: The aim of this study was to assess the expression of metabolism-related proteins including glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX) and monocarboxylate transporter 4 (MCT4) in breast mucinous carcinoma and to evaluate the implications of the results. METHODS: Immunohistochemical staining for Glut-1, CAIX, and MCT4 was performed on tissue sections from 59 cases of mucinous carcinoma to evaluate the association between the expression of metabolism-related proteins and clinicopathologic factors. Mucinous carcinoma was subclassified into type A and type B according to histopathological characteristics. RESULTS: Of the 59 patients, 35 patients (59.3%) were type A mucinous carcinoma and 24 patients (40.7%) were type B mucinous carcinoma. Stromal expression of MCT4 was significantly associated with a high histologic grade (p=0.022) and type B mucinous carcinoma (p=0.016). There were significant positive correlations between the expression of Glut-1, CAIX and tumoral expression of MCT4 (p<0.05). CONCLUSION: We assessed the expression of metabolism-related proteins including Glut-1, CAIX, and MCT4 in breast mucinous carcinoma and found that the stromal expression of MCT4 was higher in type B mucinous carcinoma than in type A, which reflected a difference in the tumor microenvironment.

Immunophenotypes of Glycogen Rich Clear Cell Carcinoma

PURPOSE: Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported. MATERIALS AND METHODS: Here, we present three cases of GRCC and their immunohistochemical profiles. RESULTS: Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%). CONCLUSION: In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.

Histological Analysis of Benign Breast Imaging Reporting and Data System Categories 4c and 5 Breast Lesions in Imaging Study

PURPOSE: The objective of this study was to analyze the histology of breast lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) 4c or 5 breast lesions during the imaging evaluation, but diagnosed as benign during the histological evaluation. MATERIALS AND METHODS: We retrospectively reviewed 71 breast lesions categorized as BI-RADS 4c or 5 during imaging study, but diagnosed as benign upon histological evaluation. RESULTS: Breast lesions were classified into six groups upon histological analysis: intraductal papilloma (18 cases), inflammatory group (15 cases), fibroepithelial tumor (14 cases), clustered microcalcification (10 cases), minimal histological alteration (10 cases), and adenosis (4 cases). Sclerosis and architectural complexity were associated with most of the biopsies that were morphologically similar to malignancy. CONCLUSION: Among 71 cases categorized as 4c or 5 during the imaging study, but diagnosed as benign upon histological examination, intraductal papilloma was the most frequently identified histological lesion. These 71 cases exhibited histological characteristics of sclerosis and/or complex/complicated features that should be histologically differentiated from malignancy during evaluation.

Rosai-Dorfman Disease in the Breast with Increased IgG4 Expressing Plasma Cells: A Case Report

Rosai-Dorfman disease (RDD) can present in any anatomic site, but breast involvement is rarely reported. Recently, a relationship between RDD and IgG4-related sclerosing disease has been suggested. Here we report another case of RDD with overlapping features of IgG4-related sclerosing disease occurring in a right breast of a 62-year-old female. On microscopic examination, the mass demonstrated a characteristic zonal pattern of proliferation of large polygonal histiocytes and lymphoplasma cells with stromal fibrosis. Emperipolesis was observed in histiocytes with abundant cytoplasm, which showed immunoreactivity for S-100 protein and CD68; the diagnosis of RDD was made. Sheets of plasma cells in the fibrotic stroma demonstrated positive reactions for IgG and IgG4. The mean count of IgG4-positive plasma cells was 100.2/high power field, and the ratio of IgG4/IgG was 56.7%. Additional findings of stromal fibrosis and obliteration of preexisting breast lobules suggested overlapping features with IgG4-related sclerosing disease.

Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma

Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.