A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification

Background@#Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. @*Methods@#Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). @*Results@#On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. @*Conclusions@#Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media / 부인종양

OBJECTIVE: To validate the efficacy of Seeplex HPV4A ACE for the detection of high-risk (HR) human papillomavirus (HPV) and HPV 16 and/or HPV 18 genotypes as compared to the PCR method and the Cervista HPV assays in cervical swab samples. METHODS: Besides liquid-based cytology, additional 97 cervical swab samples were collected for HPV genotyping by HPV4A ACE, Cervista HPV assays, and PCR method. To check the statistical differences, we also conducted the paired proportion test, Cohen's kappa statistic, and a receiver operating characteristic curve. RESULTS: Seeplex HPV4A ACE and the Cervista HPV HR showed substantial agreement with PCR for detection of HR HPVs (88.3%, kappa=0.767 and 81.7%, kappa=0.636, respectively). Seeplex HPV4A ACE also showed substantial agreement with the Cervista HPV 16/18 test (89.5%, kappa=0.628). Additionally, the sensitivity and specificity of Seeplex HPV4A ACE and Cervista HPV HR were 91.4% vs. 84.5% and 73.4%, vs. 72.7%, respectively, when those higher than low-grade squamous intraepithelial lesions were regarded as abnormalities. HPV genotyping for HPV 16/18 detected cervical intraepithelial neoplasias (CINs) better than HR HPV tests (66.7% vs. 24.6% by HPV4A ACE, 52.6% vs. 25.9% by Cervista HPV assays in CIN II or more, relatively). CONCLUSION: Seeplex HPV4A ACE is an effective method as the PCR and the Cervista HPV assays for the detection of HR HPVs and for genotyping of HPV 16 and 18.

Prevalence and Genotype Distribution of Cervical Human Papillomavirus DNA in Korean Women: A Multicenter Study

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.

A Case of Melanoacanthoma: Immunohistochemical Staining Using VECTOR(R) NovaRED(TM) to Distinguish Melanocytes from the Cutaneous Pigment

Melanoacanthoma is a rare benign mixed tumor of both keratinocytes and melanocytes. Although some authors said that it is a rare variant of seborrheic keratosis, it has clinical and histological features distinct from seborrheic keratosis. It has large dendritic melanin-laden melanocytes throughout all levels of epidermis showing a disruption of melanin transfer from the melanocytes to neighboring keratinocytes. However, it is difficult to distinguish melanocytes clearly from cutaneous pigment in immunohistochemical stain with usually used brown chromogen. We used chromogen with brick-red indicator product (VECTOR(R) NovaRED(TM)) in S-100 and melan-A immunohistochemical staining to distinguish melanocytes from melanin laden keratinocytes. We suggest that the immunohistochemical staining using this novel chromogen may be useful in the diagnosis of melanoacanthoma.

A Case of Superficial Epithelioma with Sebaceous Differentiation / 대한피부과학회지

Superficial epithelioma with sebaceous differentiation (SESD) is a rare benign neoplasm with peculiar histopathologic characteristics. It is characterized by a superficial plate-like proliferation of basaloid to squamoid cells with broad attachments to the overlying epidermis. Keratin-filled cysts and clusters of sebaceous cells are present within the lobules. We herein report an additional case of SESD which developed on a 68-year-old female.

Primitive Neuroectodermal Tumor on the Buttock

Primitive neuroectodermal tumors (PNET) usually arise in the brain and central nervous system, but rarely occur outside of the brain, such as in the limbs, pelvis, paravertebral region or chest wall. Herein, a case of PNET on the buttocks is reported. A 24-year-old female was admitted for evaluation of a mass on her left buttock. An incisional biopsy revealed a primitive neuroectodermal tumor, with focal neural differentiation histologically. Preoperative MRI demonstrated the tumor was located in the subcutaneous layer of the left perineum, and extended to the ischiorectal fossa. The lesion showed an irregular, but well defined border; however, the differentiation from the left posterior wall of anus was focally obliterated. On operation, the tumor was not adhered to the surrounding structure, except for the external anal sphincter. The mass was completely resected. The tumor was about 8 x 9 x 5.8 cm in size, and the pathological evaluation confirmed a PNET, with a free anal sphincter margin. Therefore, chemoradiation therapy was planned, but the tumor recurred two months later. It was recommended the patient undergo a re-resection, but was lost before the procedure could be undertaken.

Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report

We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.

The Survival Analysis of Immunohistochmically Defined Basal and Luminal Subtype of Breast Cancer

PURPOSE: DNA microarray studies of breast cancer have identified distinct subtypes showing different survivals. The results of DNA microarray revealed the HER2 negative and estrogen receptor (ER) negative subtypes, which were designated as basal or basal-like subtype. The basal subtype can not be manipulated by trastuzumab or the selective estrogen receptor modulator (SERM), but DNA microarrays are not perform in clinical practice. We classified invasive ductal carcinoma (IDC) into the luminal, HER2, basal and negative groups using an immunohistochemical method and evaluated the usefulness of the method in clinical practice. METHODS: A retrospective analysis was conducted using the medical records of 295 patients, diagnosed with IDC of the breast, who subsequently underwent a mastectomy between January 1992 and September 2004. A tissue microarray was constructed and immunohistochemical studies performed for HER2, ER, HER1, c-kit and CK5/6. The breast cancers were divided into four subtypes, which included the HER2 positive, luminal, basal and negative subtypes. The basal subtype was characterized by HER2 negative, ER negative and positive for one of HER1, c-kit or CK5/6. Only the ER positive subtype was designated as a luminal subtype. The survival rates were calculated using the Kaplan Meier methods. RESULTS: The 5 year survival rates of the HER2 positive, luminal and basal subtypes were 80.4, 86.8 and 73.8%, respectively (P=0.1274). The basal subtype was predominant among the patients with poorly differentiated carcinomas (P=0.000). The 5 year overall survival of the basal subtype was lower than that of luminal (P=0.049); the prognosis was also poor in those with an age less than 35 years old, premenopausal and lymph node metastasis. CONCLUSION: The basal subtype was associated with a high histologic grade, and also showed significantly worse prognosis then the luminal subtype, especially in those patients with an age less than 35, premenopausal and lymph node metastasis. The immunohistochemical assay for the basal subtype was helpful in detecting patients with a poor prognostic.

Dermatofibroma: Unusual Lesion with Underlying Cutaneous Horn / 대한피부과학회지

Cutaneous horn is a nonspecific clinical description and may arise from a variety of benign and malignant lesions. A 46-year-old Korean man presented with a 1-year history of an extensively hyperkeratotic nodule on his left foot. Following an initial diagnosis of dermatofibroma with underlying cutaneous horn by wedge biopsy, the tumor was completely removed by excision with 5 mm margin. When excisional surgery was performed, the size of the dermal tumor mass was found to be 1.3 cm in length on the axis and 0.6 cm in depth on section. On histopathologic examination, the tumor was characterized by spindle-shaped cells arranged in storiform pattern, epidermal hyperplasia, and an overlying compact hyperkeratotic mass. The tumor cells did not express CD34. Cutaneous horn of dermatofibroma may be the product of epidermis-dermal tumor interaction. Although we performed a wide excision for complete removal of the tumor, Mohs micrographic surgery could have been another option.

The Clinicopathologic Significance of a p63 Expression in Invasive Breast Cancer

PURPOSE: p63 is a recently described as p53 homologue. Despite their structural homologies, they have different activities. p63 is a specific myoepithelial cell marker in normal breast tissue and it is expressed in a minority of breast cancers. The aim of this study was to evaluate the prognostic significance of the p63 expression in breast cancer. METHODS: The expression of p63 in breast cancer was determined by performing immunohistochemistry on 350 patients who underwent mastectomy at the Department of Surgery at Korea University Medical Center between January 1992 and September 2004. A retrospective analysis was conducted using the medical records. A tissue microarray was constructed, and immunohistochemical analysis for p63 was performed according to the usual methods. RESULTS: Among 350 patients, 40 (11.4%) showed a p63 expression. There was a significant correlation between p63 and the histologic grade. There were significant correlations of p63 with p53 and HER2/neu, respectively. In the basal type of breast cancer, the p63 expression was significantly higher than in the luminal type of breast cancer. The 5 year disease free survival rates were 69% in the patients with a p63 expression and 76% in the patients without a p63 expression, but there was no statistical difference. CONCLUSION: The present results indicate that a p63 expression is associated with a high grade tumor, a p53 expression and a HER2/neu expression in breast cancer, which are the known poor prognostic factors of breast cancer. Immunohistochemical subtyping shows that the p63 expression is a useful predictor for the basal type of breast cancer. In addition, this study suggests that the p63 expression in the basal type of breast cancer is associated with a poor prognosis.

A Case of Multiple Dermatofibromas in a Patient with Systemic Lupus Erythematosus / 대한피부과학회지

Dermatofibroma is a common fibrohistiocytic tumor of the skin. It generally occurs as a solitary lesion. However, some cases of multiple dermatofibromas in immune-compromised patients or patients with abnormal immune status have been reported, hence this phenomenon has been thought to be associated with altered immunity. We present a case of multiple dermatofibromas which developed in a patient with systemic lupus erythematosus, plus a review of the literature.

Henoch-Schonlein Purpura Presenting as Hemorrhagic Vesicles and Bullae with Gastrointestinal Hemorrhage / 대한피부과학회지

No abstract available.

Significance of Akt Expression in Node-negative Breast Cancer

BACKGROUND: Patients with lymph node-negative breast cancer show a 10-year recurrence rate of approximately 20%. In node-negative breast cancer, the prognostic factors are age, menopause, tumor size, hormone receptors, p53, DNA ploidy, Ki-67 index (Ki-67) and c-erbB2. Of these, ErbB2 (the protein of the c-erbB2 gene) is a member of the receptor tyrosine kinase family. Overexpression of ErbB2 is known to regulate cell proliferation, differentiation, growth and apoptosis via the ErbB2/Phosphoinositol 3-Kinase (PI 3-K)/Akt signaling pathway. Therefore, it is important to identify high- risk patients that would benefit from adjuvant therapies related with ErB2. For this purpose, the prognostic relevance of the ErbB2/PI 3-K/Akt pathway was examined in node-negative breast cancer. METHODS: A retrospective analysis was performed on the hospital records of all 72 patients diagnosed with breast cancer, and who underwent surgical treatment between January 1996 and December 2003. Clinicopathological data were compared with the results of immunohistochemical staining using the phospho-specific antibody for the expression of Akt. RESULTS: The mean age of the patient's was 48.6 years. Phospho-Akt (pAkt) was expressed in 24 cases (33.3%), but there was no statistical relationship between pAkt expression and the known prognostic factors of breast cancer. There was no statistical significance in the survival rates between the pAkt positive and negative expression groups (P=0.123). In the ErbB2 positive patients, the expression of pAkt was associated with a shorter disease-free survival (P=0.045), and the disease-free survival was shorter in patients whose tumors expressed pAkt and had a high level of Ki-67 (P=0.040). CONCLUSION: The co-expression of ErbB2 and pAkt positivity implied a poor prognosis in node-negative breast cancer patients, and the co-expression of high Ki-67 and pAkt positivity also revealed a poor prognosis in these patients. These results show that the expression of pAkt could be considered a prognostic marker of node-negative breast cancer with ErbB2 positive expression and high levels of Ki-67.

A case of abnormal placental implantation in diamnionic dichorionic twin with one intrauterine fetal death (IUFD) / 대한산부인과학회잡지

In diamnionic dichorionic twins, the type of placenta consists of fused and separate types. The expansion of one twin placenta often occurs in the direction of the other implantation site in fused type. Placental development often leads to collision, and the growth of one or both placentas may be hindered, which can cause intrauterine growth restriction (IUGR). We represent a single case of one placental implantation above the another which caused IUFD in one fetus in diamnionic dichorionic twin pregnancy with a brief review of literatures.

A Case of Adamantinoid Basal Cell Carcinoma / 대한피부과학회지

Basal cell carcinoma(BCC) exists in great variety. Adamantinoid BCC is one of the rare types of BCC. Histologically, the tumor masses are surrounded by a layer of cells in which the nuclei tend to palisade. Inside this layer, the tumor masses consist of cells with elongated nuclei and stellate cytoplasm stretched as thin, connection bridges across empty spaces, producing adamantinoid appearance. We report a case of adamantinoid BCC in a 49 year-old woman who had a single, asymptomatic, dusky erythematous to black colored nodule on her right jaw area.

Clinical Analysis of 28 Multiple Primary Cancers (MPC) Including Breast Cancer

PURPOSE: Due to improving breast cancer screening programs and treatment methods, we can expect improved long-term survival of breast cancer patients. Given the longer survival times, other primary cancers may develop in other organs of breast cancer patients during their long term follow up period. Our purpose was to elucidate the clinical characteristics of multiple primary cancers developed in breast cancer patients. METHODS: We retrospectively investigated 28 patients with multiple primary cancers including breast cancer. However, we excluded contra-lateral breast cancer. We investigated the patients' clinical characteristics including mean age, stage, hormone receptor status, cause of death, time interval between the breast cancer and other cancers, and common cancers which were combined with breast cancer. RESULT: The mean age of the study group was 53+/-2, higher than the 47.7+/-0.4 of our hospital breast cancer patients group. However, other tumor characteristics were not significantly different from other general breast cancer patients. Among the patients 5 were synchronous and 23 were metachronous MPC. The most common cancer combined with breast cancer was gastric cancer (8, 27.6%), followed by cervical cancer (3, 10.7%) and colon cancer (3, 10.7%). The ranks of the other cancer co-occurred with breast cancer were not significantly different than the Korean 1999 Korean women's cancer incidence ranks excluding breast cancer. CONCLUSION: Due to the increasing length of the follow up period for breast cancer patients, primary cancers may develop in other organs. Therefore, physicians should be concerned and increase efforts to detect these other cancers early in these patients. Additionally, it appears that the prevalence ranking of common cancers developing in breast cancer patients is not significantly different than the ranking of other cancer incidence in the general population.

A Case of Plasma Cell Cheilitis / 대한피부과학회지

Plasma cell cheilitis is an idiopathic, benign, inflammatory mucosal condition characterized histologically by a dense band-like infiltrate of plasma cells in the upper dermis of the mucosa. In addition to the lips, the disease can affect the penis, vulva, buccal mucosa, palate, gingiva, tongue, epiglottis, and larynx. Plasma cell cheilitis of the lip appears as a circumscribed, flat to slightly elevated, eroded area, usually on the lower lip of an elderly person. We report a 70-year-old man who had a well-demarcated, erythematous, erosive lesion on his lower lip for 1 year. A biopsy specimen showed an upper dermal infiltrate that consisted mainly of plasma cells. Oral griseofulvin, 500mg/day, was begun, and 8 weeks later the lesion showed marked improvement.

Giant Cell Tumor Originating from the Anterior Arc of the Rib

We report a case of giant cell tumor originating from the anterior arc of the rib. The tumor and the surrounding chest wall were completely resected, and the chest wall defect was covered with Marlex mesh. Giant cell tumor of the bone usually originates from the epiphysis of long bones. Even when the tumor occur in ribs, it usually occur in the posterior aspect. However, giant cell tumor should be included in the differential diagnosis of a tumor originating from the anterior arc of the ribs.

Distribution and Prognostic Effect on Adjuvant Hormone Therapy of Body Mass Index (BMI) in Korean Breast Cancer Patients

PURPOSE: Obesity has been shown to have important effects related to breast cancer. But there have been few data available on the distribution of body mass index (BMI) among Korean breast cancer patients and on the effects of this distribution on patient prognosis. Therefore we investigated the BMI distribution of Korean breast cancer patient's and its relationship with other tumor markers, in order to elucidate the relationship between BMI and patient prognosis. METHODS: We measured the BMI of 266 Korean adult women with breast carcinoma.and divided the subjects into the following subgroups according to BMI; low body weight (BMIor=25). We compared this distribution with that of the general Korean women's population. and investigated the correlation with other prognostic factors and tumor markers. The 5 year overall and disease free survival rates were evaluated for both the total breast cancer patients and the adjuvant hormone treated breast cancer patients, according to BMI subgroup, using the Kaplan-Meier method. RESULTS: Mean BMI for the breast patients was 23.4+/-3.1, and did not differ from that of the general Korean adult women's population ('1994 National Nutrition Survey Report). BMI increased with increasing age and was highest in the 60~69 yr age group. BMI was correlated with tumor size and stage. The survival rates were low in the high BMI group among both total and adjuvant hormone treated breast cancer patients, but in neither was any statistical difference found between BMI subgroups. CONCLUSION: Korean breast cancer patients are not obese as the general population and their BMI increases with increasing age and menopausal status. There was a tendency for higher BMI to be associated with poorer prognosis, although not to a statistically significant degree.

A Case of Invasive Squamous Cell Carcinoma of the Vulva / 대한피부과학회지

Vulvar cancer is uncommon and represents about 4% of malignancies of the female genital tract. Squamous cell carcinomas account for about 90% of the cases. However few cases are reported in dermatologic literatures. Theses lesions are usually characterized by firm, hyperkeratotic papules, plaques or indurated erosions. Human papilloma virus(HPV)DNA has been reported in 20-60% of patients with invasive vulvar cancer. The HPV-positive group has been characterized by a younger mean age, more tobacco use, and simultaneous presence of vulvar intraepitherial neoplasia(VIN) and the invasive component. We report a case of invasive squamous cell carcinoma of the vulva associated with HPV type 16 positive according to polymerase chain reaction.