A standardized pathology report for gastric cancer: 2nd edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Diagnostic Test Accuracy Review of Cytology for Squamous Intraepithelial Lesion and Squamous Cell Carcinoma of Uterine Cervix

BACKGROUND: Even though cervico-vaginal smears have been used as a primary screening test for cervical carcinoma, the diagnostic accuracy has been controversial. The present study aimed to evaluate the diagnostic accuracy of cytology for squamous intraepithelial lesion (SIL) and squamous cell carcinoma (SqCC) of the uterine cervix through a diagnostic test accuracy (DTA) review. METHODS: A DTA review was performed using 38 eligible studies that showed concordance between cytology and histology. In the DTA review, sensitivity, specificity, diagnostic odds ratio (OR), and the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve were calculated. RESULTS: In the comparison between abnormal cytology and histology, the pooled sensitivity and specificity were 93.9% (95% confidence interval [CI], 93.7%–94.1%) and 77.6% (95% CI, 77.4–77.8%), respectively. The diagnostic OR and AUC on the SROC curve were 8.90 (95% CI, 5.57–14.23) and 0.8148, respectively. High-grade squamous intraepithelial lesion (HSIL) cytology had a higher sensitivity (97.6%; 95% CI, 94.7%–97.8%) for predicting HSIL or worse histology. In the comparison between SqCC identified on cytology and on histological analysis, the pooled sensitivity and specificity, diagnostic OR, and AUC were 92.7% (95% CI, 87.3%–96.3%), 87.5% (95% CI, 87.2%–87.8%), 865.81 (95% CI, 68.61–10,925.12), and 0.9855, respectively. Geographic locations with well-organized screening programs had higher sensitivity than areas with insufficient screening programs. CONCLUSION: These results indicate that cytology had a higher sensitivity and specificity for detecting SIL and SqCC of the uterine cervix during primary screening.

Extranasopharyngeal Angiofibroma of the Nasal Septum: A Case Report

Angiofibroma is benign hypervascular tumor that usually occurs in the nasopharynx of adolescent male patient and rarely originates from outside of the nasopharynx, called extranasopharyngeal angiofibroma. The clinical and radiologic findings of extranasopharyngeal angiofibroma are similar to other hypervascular tumors, which may delay diagnosis and treatment. We present a case of extranasopharyngeal angiofibroma arising from nasal septum of a 43-year-old male who complained of right nasal obstruction. Contrast enhancement CT revealed a hypervascular tumor of the nasal septum and the tumor was removed by endoscopic resection. Histopathologic examination confirmed the diagnosis of angiofibroma.

Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

BACKGROUND: Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. METHODS: A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). RESULTS: The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). CONCLUSIONS: In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.

Clinicopathological Significance and Diagnostic Accuracy of c-MET Expression by Immunohistochemistry in Gastric Cancer: A Meta-Analysis

PURPOSE: The aim of the present study was to elucidate the clinicopathological significance and diagnostic accuracy of immunohistochemistry (IHC) for determining the mesenchymal epidermal transition (c-MET) expression in patients with gastric cancer (GC). MATERIALS AND METHODS: The present meta-analysis investigated the correlation between c-MET expression as determined by IHC and the clinicopathological parameters in 8,395 GC patients from 37 studies that satisfied the eligibility criteria. In addition, a concordance analysis was performed between c-MET expression as determined by IHC and c-MET amplification, and the diagnostic test accuracy was reviewed. RESULTS: The estimated rate of c-MET overexpression was 0.403 (95% confidence interval [CI], 0.327~0.484) and it was significantly correlated with male patients, poor differentiation, lymph node metastasis, higher TNM stage, and human epidermal growth factor receptor 2 (HER2) positivity in IHC analysis. There was a significant correlation between c-MET expression and worse overall survival rate (hazard ratio, 1.588; 95% CI, 1.266~1.992). The concordance rates between c-MET expression and c-MET amplification were 0.967 (95% CI, 0.916~0.987) and 0.270 (95% CI, 0.173~0.395) for cases with non-overexpressed and overexpressed c-MET, respectively. In the diagnostic test accuracy review, the pooled sensitivity and specificity were 0.56 (95% CI, 0.50~0.63) and 0.79 (95% CI, 0.77~0.81), respectively. CONCLUSIONS: The c-MET overexpression as determined by IHC was significantly correlated with aggressive tumor behavior and positive IHC status for HER2 in patients with GC. In addition, the c-MET expression status could be useful in the screening of c-MET amplification in patients with GC.

Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis

BACKGROUND: The clinicopathological characteristics and conclusive treatment modality for multifocal papillary thyroid microcarcinoma (mPTMC) have not been fully established. METHODS: A retrospective study, systematic review, and meta-analysis were conducted to elucidate the clinicopathological significance of mPTMC. We investigated the multiplicity of 383 classical papillary thyroid microcarcinomas (PTMCs) and the clinicopathological significance of incidental mPTMCs. Correlation between tumor recurrence and multifocality in PTMCs was evaluated through a systematic review and meta-analysis. RESULTS: Tumor multifocality was identified in 103 of 383 PTMCs (26.9%). On linear regression analysis, primary tumor diameter was significantly correlated with tumor number (R2=0.014, p=.021) and supplemental tumor diameter (R2=0.117, p=.023). Of 103 mPTMCs, 61 (59.2%) were non-incidental, with tumor detected on preoperative ultrasonography, and 42 (40.8%) were diagnosed (incidental mPTMCs) on pathological examination. Lymph node metastasis and higher tumor stage were significantly correlated with tumor multifocality. However, there was no difference in nodal metastasis or tumor stage between incidental and non-incidental mPTMCs. On meta-analysis, tumor multifocality was significantly correlated with tumor recurrence in PTMCs (odds ratio, 2.002; 95% confidence interval, 1.475 to 2.719, p<.001). CONCLUSIONS: Our results show that tumor multifocality in PTMC, regardless of manner of detection, is significantly correlated with aggressive tumor behavior.

Core Needle Biopsy Is a More Conclusive Follow-up Method Than Repeat Fine Needle Aspiration for Thyroid Nodules with Initially Inconclusive Results: A Systematic Review and Meta-Analysis

BACKGROUND: This study investigated the appropriate management of thyroid nodules with prior non-diagnostic or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) through a systematic review and meta-analysis. METHODS: This study included 4,235 thyroid nodules from 26 eligible studies. We investigated the conclusive rate of follow-up core needle biopsy (CNB) or repeat fine needle aspiration (rFNA) after initial fine needle aspiration (FNA) with non-diagnostic or AUS/FLUS results. A diagnostic test accuracy (DTA) review was performed to determine the diagnostic role of the follow-up CNB and to calculate the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve. RESULTS: The conclusive rates of follow-up CNB and rFNA after initial FNA were 0.879 (95% confidence interval [CI], 0.801 to 0.929) and 0.684 (95% CI, 0.627 to 0.736), respectively. In comparison of the odds ratios of CNB and rFNA, CNB had more frequent conclusive results than rFNA (odds ratio, 5.707; 95% CI, 2.530 to 12.875). Upon subgroup analysis, follow-up CNB showed a higher conclusive rate than rFNA in both initial non-diagnostic and AUS/FLUS subgroups. In DTA review of followup CNB, the pooled sensitivity and specificity were 0.94 (95% CI, 0.88 to 0.97) and 0.88 (95% CI, 0.84 to 0.91), respectively. The AUC for the SROC curve was 0.981, nearing 1. CONCLUSIONS: Our results show that CNB has a higher conclusive rate than rFNA when the initial FNA produced inconclusive results. Further prospective studies with more detailed criteria are necessary before follow-up CNB can be applied in daily practice.

Predictors of Recurrent Ductal Carcinoma In Situ after Breast-Conserving Surgery / 한국유방암학회지

PURPOSE: Local recurrence is a major concern in patients who have undergone surgery for ductal carcinoma in situ (DCIS). The present study assessed whether the expression levels of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as resection margin status, tumor grade, age at diagnosis, and adjuvant hormonal therapy and radiotherapy (RT) are associated with recurrence in women with DCIS. METHODS: In total, 111 patients with DCIS were included in the present study. The invasive and noninvasive recurrence events were recorded. The clinicopathological features; resection margins; administration of hormonal therapy and RT; expression statuses of estrogen receptor (ER), progesterone receptor (PR), and HER2; Ki-67 expression; and molecular subtypes were evaluated. Logistic regression analysis was performed to examine the risk factors for recurrence. RESULTS: Recurrence was noted in 27 of 111 cases (24.3%). Involvement of resection margins, low tumor grade, high Ki-67 expression, and RT were independently associated with an increase in the recurrence rate (p<0.05, Pearson chi-square test). The recurrence rate was not significantly associated with patient age; ER, PR, and HER2 statuses; molecular subtype; and hormonal therapy. CONCLUSION: The results of the present study suggested that the involvement of resection margins, low tumor grade, high Ki-67 index, and the absence of adjuvant RT were independently associated with increased recurrence in patients with DCIS. Future studies should be conducted in a larger cohort of patients to further improve the identification of patients at high-risk for DCIS recurrence.

Total Surface Area Is Useful for Differentiating between Aggressive and Favorable Multifocal Papillary Thyroid Carcinomas

PURPOSE: The purpose of the present study was to identify more useful parameters for predicting behaviors of multifocal papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: We investigated dominant tumor diameter (TD), total tumor diameter (TTD), and total surface area (TSA) in tumors from 588 patients and evaluated their usefulness as parameters for assessment of tumor behaviors in multifocal PTCs. RESULTS: In 588 PTCs, tumor multifocality was found in 179 PTCs (30.4%). Multifocal tumors were significantly associated with extrathyroidal extension, lymph node metastasis, and higher tumor stage grouping (p3.14 cm2 had higher rates of nodal metastasis than mPMCs with TSA 1.0 cm and with TTD 3.14 cm2 than in unifocal papillary thyroid microcarcinomas (uPMCs) (TD 1.0 cm) (p=0.244). CONCLUSION: Our results suggest that mPMCs with TSA >3.14 cm2 show more aggressive behavior than uPMCs and mPMCs with TSA < or =3.14 cm2. TSA could be useful in distinguishing aggressive mPMCs from favorable cases.

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

BACKGROUND: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). METHODS: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. RESULTS: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren's classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren's classification, pN stage, or pTNM stage. CONCLUSIONS: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

Carcinosarcoma of the uterine cervix arising from Mullerian ducts

Carcinosarcomas of the uterine cervix are extremely rare. Cervical carcinosarcoma can be characterized by having two different origins: the Mullerian ducts and the mesonephric duct remnants. A 53-year-old Korean woman was admitted to the hospital because of pelvic mass detected on computed tomography scan done at private clinic. A Radical hysterectomy with bilateral salpingooophorectomy and pelvic lymphadenectomy was carried out upon a diagnosis of stage IB2 cervical sarcoma. Immunohistochemically, the epithelial component was positive for pancytokeratin and estrogen receptor, but negative for CD 10 and carletinin. The mesenchymal component was positive for vimentin. The histopathologic diagnosis was a carcinosarcoma of the uterine cervix arising from Mullerian ducts. She underwent chemotherapy. She developed systemic recurrence seven months after operation and died of disease. The origin of cervical carcinosarcoma needs to be verified and immunohistochemical studies using mesonephric marker (CD 10, carletinin, and estrogen receptor) is helpful.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Glomus Tumor of the Stomach: A Clinicopathologic Analysis of 10 Cases and Review of the Literature

BACKGROUND/AIMS: Gastric glomus tumors are extremely rare, and presurgical confirmation is often impossible. The identification of clinical and radiologic characteristics of this tumor type is important for preoperative diagnosis and treatment planning. METHODS: In this study, we analyzed 10 cases of gastric glomus tumors resected at a single institute over 9 years. RESULTS: Eight of the patients were men and 2 were women, with a mean age of 49 years. Five patients presented with abdominal discomfort or pain, 1 presented with anemia, and the remaining 4 cases were found incidentally during endoscopic examinations. The most common location of the tumor was the antrum (n=7), followed by the low (n=2) and high body (n=1). Although the endoscopic ultrasonography findings were variable, contrast-enhanced computed tomography generally showed a strong homogeneous enhancement. The resected tumors were well-demarcated solid masses with sizes ranging from 1.0 to 3.6 cm. Microscopically, the masses were composed of abundant vascular channels with clusters of uniform and round glomus cells. There was no evidence of recurrence after complete surgical resection. CONCLUSIONS: Gastric glomus tumors are unusual, distinct lesions that should be considered in the differential diagnosis of a gastric submucosal mass. Unlike their deep soft tissue counterparts, most glomus tumors in the stomach are benign.

Metaplastic Thymoma: Report of 4 Cases

Metaplastic thymoma (MT), accepted in the World Health Organization 2004 scheme, is a circumscribed tumor of the thymus exhibiting biphasic morphology. We herein describe the clinicopathologic features of four MTs and the differential diagnoses of this unusual tumor. There were three women and one man with mean age of 49.5 years. The patients were found to have mediastinal masses, and underwent surgical excision. One exhibited symptoms of myasthenia gravis, and the serum titer for anti-acetylcholine receptor antibody was positive. Grossly, the tumors were encapsulated, and showed vaguely multinodular, solid, tan-white to yellow cut surfaces. Histologically, they comprised epithelial islands intertwining with bundles of delicate spindle cells. The patients remained well after surgical excision at 5-55 months. Because of the distinctive histological appearance and benign clinical course, MT should be distinguished from other more aggressive mediastinal neoplasms displaying biphasic feature.

Fibrous hamartoma of infancy: an experience of a single institute / 대한외과학회지

PURPOSE: Fibrous hamartoma (FH) of infancy is a distinctive fibrous growth that most frequently occurs at birth and during the postnatal period. It is important for clinicians and pathologists to recognize this entity to avoid an aggressive approach. METHODS: We herein describe the clinicopathologic features of 9 FHs diagnosed at a single institution between 1997 and 2010. RESULTS: There were 7 boys and 2 girls, and the mean age of presentation was 14.7 months. The common locations were the lower back and gluteal region (n = 3) and scrotum (n = 2). They were solitary lesions, and measured 1.0 to 7.0 cm in maximum diameter (mean, 4.9 cm). The excised masses tended to be poorly circumscribed, and consisted of an intimate mixture of firm, gray-white tissue with fat. Histologically, these lesions were composed of 3 components forming a vague, irregular, organoid pattern: well-defined intersecting trabeculae of fibrocollagenous tissue; loosely textured areas of small, rounded, primitive mesenchymal cells; and mature fat. Over a median follow-up of 72 months, no patient showed recurrence. CONCLUSION: FH should be distinguished from other forms of fibromatosis and malignant tumors because it is benign and usually cured by local excision.

IgG4-Related Lung Disease Presenting as a Consolidative Mass: A Case Report

Immunoglobulin G4 (IgG4)-related sclerosing disease involving the lung is a rare condition, and this is characterized by an elevated serum IgG4 level, fibrotic inflammation with numerous IgG4-positive plasma cells and a response to steroid therapy. We present here a case of pulmonary IgG4-related disease in a 75-year-old man who presented with cough and yellowish sputum for the previous 3 months. The chest images showed a consolidative mass in the right lower lobe that suggested mucinous bronchioloalveolar carcinoma. The wedge resected specimen revealed an ill-defined gray-tan, firm lesion. Microscopically, the lesion showed a diffuse lymphoplasmacytic infiltration with irregular fibrosis in the alveolar interstitium and bronchovascular bundles. There were numerous IgG4-positve plasma cells and these cells were diffusely distributed. The serum IgG4 level was elevated on the postoperative check-up (249 mg/dL). After corticosteroid therapy for 7 months, the patient's symptoms and radiologic abnormalities were improved.