Ki67 Index Is the Most Powerful Factor for Predicting the Recurrence in Atypical Meningioma : Retrospective Analysis of 99 Patients in Two Institutes

Objective@#: The primary objective of this study was to identify predicting factors for local control (LC) of atypical meningioma, and we validated them with comparing the predicting factors for recurrence-free survival (RFS). We also examined the rate of LC after surgical resection with or without adjuvant treatment and RFS. @*Methods@#: Clinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. @*Results@#: Of the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean, 83.3 months; range, 12–232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7%, respectively. The mean time-to-recurrence was 49.4 months (range, 12–150). The mean RFS was 149.3 months (95% confidence interval, 128.8–169.8 months) during the mean follow-up duration of 83.3 months (range, 12–232 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (hazard ratio [HR], 4.761; p=0.013), Ki67 index (HR, 8.541; p=0.004), mitotic index (HR, 3.275; p=0.044), and tumor size (HR, 3.228; p=0.041) were independently associated with LC. These factors were also statistically associated with RFS. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. @*Conclusion@#: The present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, and tumor size are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials to overcome the inborn bias of retrospective nature of the study design.

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

Prognostic Role of Methylation Status of the MGMT Promoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients

OBJECTIVE: This study investigated whether pyrosequencing can be used to determine the methylation status of the MGMT promoter as a clinical biomarker using relatively old archival tissue samples of glioblastoma. We also examined other prognostic factors for survival of glioblastoma patients. METHODS: The available study set included formalin-fixed paraffin-embedded (FFPE) tissue from 104 patients at two institutes from 1997 to 2012, all of which were diagnosed histopathologically as glioblastoma. Clinicopathologic data were collected by review of medical records. For pyrosequencing analysis, the PyroMark Q96 CpG MGMT kit (Qiagen, Hilden, Germany) was used to detect the level of methylation at exon 1 positions 17-39 of the MGMT gene, which contains 5 CpGs. RESULTS: Methylation of the MGMT promoter was detected in 43 (41.3%) of 104 samples. The average percentage methylation was 14.0+/-16.8% overall and 39.0+/-14.7% for methylated cases. There was no significant pattern of linear increase or decrease according to the age of the FFPE block (p=0.687). In multivariate analysis, age, performance status, extent of surgery, method of adjuvant therapy, and methylation status estimated by pyrosequencing were independently associated with overall survival. Additionally, patients with a high level of methylation survived longer than those with low methylation (p=0.016). CONCLUSION: In this study, the status and extent of methylation of the MGMT promoter analyzed by pyrosequencing were associated with overall survival in glioblastoma patients. Pyrosequencing is a quantitative method that overcomes the problems of MSP and a simple technique for accurate analysis of DNA sequences.

Pleomorphic Adenoma with Sarcomatous Change in a Lacrimal Gland

A 69-year-old man was referred with left exophthalmos. Computed tomographic (CT) findings detected a well-circumscribed mass in the left side of the intraorbital cavity. At that time, he refused the further evaluation and treatment. About three years later, the size of the mass had enlarged, and the patient's symptoms were getting worse. The mass was completely removed with frontotemporal craniotomy and superolateral orbitotomy. In operative findings, the mass had originated in the lacrimal gland and was well-encapsulated without invasion to the surrounding tissue. In the pathologic findings, the tumor consisted of pleomorphic adenoma with osteosarcomatous change of stromal components. Postoperatively, the adjuvant radiotherapy was done four weeks later. The patient's symptoms were improved. The pleomorphic adenoma with osteosarcomatous change is extremely rare and appropriate treatment is not clearly established. We would like to report this rare case with a review of the literature.

Expression Patterns of Gli-1, Pleckstrin Homology-Like Domain, Family A, Member 1, Transforming Growth Factor-beta1/beta2, and p63 in Sebaceous and Follicular Tumors

BACKGROUND: Certain epidermal appendage tumors, including hyperplasias (hamartomas), adenomas, benign epitheliomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-beta1, TGF-beta2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood. OBJECTIVE: The aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-beta1/beta2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation. METHODS: Immunohistochemistry was performed in follicular and sebaceous tumors using antibodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF-beta1, and TGF-beta2. RESULTS: Gli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differentiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-beta1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation. CONCLUSION: We propose that p63 and/or TGF-beta1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma.

Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral Lentiginous Melanoma in Korean Patients: A Preliminary Study

BACKGROUND: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway is constitutively activated, due to oncogenic mutations in the BRAF and NRAS genes. The BRAF mutation has been mainly described in Caucasian melanomas. However, there is a lack of study evaluating the status, and the clinical significance, of BRAF mutation in the Asian population. OBJECTIVE: This study was aimed to determine the frequency of BRAF mutation, and to evaluate the correlation of BRAF status with clinicopathologic features and outcomes, in Korean primary acral lentiginous melanoma (ALM) patients. METHODS: ALM samples (n=36) were analyzed for the BRAF V600E mutation, by dual-priming oligonucleotide (DPO) based real-time polymerase chain reaction. The clinicopathologic features and prognosis of the patients were analyzed with BRAF mutation status. RESULTS: The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated with clinicopathologic features, except for the age factor. All of the BRAF-mutant patients survived without recurrence or metastasis, and have a better clinical outcome than BRAF wild-type patients. CONCLUSION: In Korean primary ALM, a low frequency of BRAF mutation was shown; and BRAF mutation presented with a favorable prognosis. These results indicate that other distinctive genetic mechanisms may have more important roles in the development and progression of disease. Further multicenter study with large sample size is firmly needed, to confirm the results of our preliminary study.

Oculomotor Nerve Schwannoma: A Case Report

Schwannomas account for about 8% of intracranial tumors and 90% are vestibular schwannomas. Oculomotor schwannoma without neurofibromatosis is extremely rare. A 41-year-old female presented with complaints of blurred vision, and the neurologic examination revealed afferent pupillary defect and decreased visual acuity of the left side. Brain magnetic resonance image showed an extra axial mass in the left superior orbital fissure. The patient underwent major surgery via the fronto-temporal approach. The tumor originated from the oculomotor nerve and was subtotally removed under microscopic surgery. The pathological findings confirmed the tumor as a schwannoma. After surgery, ptosis and medial gaze limitation of the left eye was detected, but the symptoms improved gradually.

A Case of Temporomandibular Joint Disorder Accompanied with Ear Bleeding / 대한이비인후과학회지

Temporomandibular joint disorder (TMD) is a generic term used for any problem concerning the jaw joint. The clinical signs of TMD are crepitus associated with movement, restriction of jaw movements, and pain within the joint cavity. But ear bleeding and an external auditory canal (EAC) mass as presenting symptoms are rare. We report the case of 78-year-old man with TMD, whose initial symptoms were ear bleeding, and temporomandibular pain intensifying when he is chewing, accompanied by an EAC mass. Physical examination revealed a reddish mass that originated from the anterior wall of EAC and bled when touched. Computed tomography showed a mass with soft tissue density and a bony defect in the anterior EAC wall. After conducting arthrocentesis and lavage repetitively, the wound was healed completely. It is likely that the patient's ear bleeding was due to patent foramen of Huschke or erosion of the anterior wall of EAC due to temporomandibular joint inflammation.

Factors associated with serum vitamin D levels in children with recurrent wheezing less than 3 years old

PURPOSE: We evaluated the relationship between laboratory/clinical factors and vitamin D levels in recurrent wheezers less than 3 years old. METHODS: We retrospectively analyzed clinical data and laboratory factors (25-hydroxyvitamin D, complete blood count, C-reactive protein, glutamic oxaloacetic transaminase, glutamyl purovic transaminase, alkaline phosphatase [ALP], eosinophil counts, and serum IgE IgG, IgA, IgM) of 84 children less than 3 years who had experienced wheezing episodes at least 3 times. RESULTS: Children in the normal group (1.4+/-0.9 years) were younger than those in the deficient (2.2+/-1.2 years) and insuffient (2.3+/-1.0 years) groups (P=0.010). Glutamyl purovic transaminase were higher in the normal group (24.5+/-19.4 IU/L) than in the deficient (16.0+/-4.7 IU/L) and insufficient (15.3+/-4.5 IU/L) groups (P=0.009). ALP were higher in the deficient (791.4+/-180.8 IU/L) and insufficient (770.4+/-251.2 IU/L) groups than in the normal group (631.9+/-127.0 IU/L, P=0.034). Total IgE levels were higher in the deficient group (171.9+/-212.1 kU/L) than in the normal group (43.7+/-58.3 kU/L, P<0.05), and the rate of sensitization to aeroallergens was higher in the insufficient group (36.1%) than in the normal group (10%, P<0.05). CONCLUSION: Among children with recurrent wheezing less than 3 years old, low vitamin D levels may be associated with older age, total IgE, ALP level, glutamic pyruvate transaminase level, and rate of sensitization to aeroallergens.

Adenomyoepithelioma Located Over the Tibial Tuberosity

Adenomyoepithelioma is a rarely occurring tumor and its generation in the limbs is extremely rare. We report a case of an adenomyoepithelioma over the proximal tibial tuberosity that was treated without any complications after an excisional biopsy with a literature review.

A Case of Epidermolysis Bullosa Simplex (Other Generalized Type) / 대한피부과학회지

The other generalized type of epidermolysis bullosa simplex (EBS) is a genetic blistering skin disease, caused by a mutation of the genes encoding keratin 5 and 14. EBS starts at birth and is characterized by generalized blisters following a minor trauma that heals with hyperpigmentation. A 19-year-old man presented with 19-year history of multiple erythematous vesicles in a herpetiform arrangement on the trunk, axilla, and thigh with post-inflammatory hyper-pigmentations. On light and electron microscopy, the biopsy specimen showed intraepidermal blisters that formed within the basal keratinocyte. The serum from a patient with bullous pemphigoid antibody and laminin 5 antibody showed the linear deposition at the floor of the blister on immunofluorescence mapping study. On the basis of our clinical, microscopic, and immunofluorescence findings, we diagnosed the patient as having a generalized type of EBS. Herein, we report on an interesting case of the other generalized type of EBS.

Epidermal Growth Factor Receptor Is Related to Poor Survival in Glioblastomas: Single-Institution Experience

PURPOSE: There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy. MATERIALS AND METHODS: Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. RESULTS: EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent. CONCLUSION: The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.

A Case of Synchronous Esophagus and Stomach Cancer Successfully Treated by Combined Chemotherapy / 대한소화기학회지

Although cases of simultaneous esophagus and stomach cancer have been reported sporadically, there are rare reports of successful treatment using chemotherapy. We report a case of synchronous esophageal and gastric cancer successfully treated using docetaxel and cis-diammineedichloro-platinum (CDDP) combination chemotherapy instead of surgery. A 82-years-old man with anorexia and progressive weight loss was diagnosed with synchronous esophageal and gastric cancer by endoscopy. Both cancers were diagnosed as resectable by the preoperative clinical staging. However, surgery was contraindicated because of severe lung dysfunction. Moreover, he actively refused radiotherapy and endoscopic management. Therefore, the patient was given combined chemotherapy with docetaxel (65 mg/m2) and CDDP (60 mg/m2). The esophageal and gastric lesion completely disappeared on endoscopy, and there were no residual tumor cells on endoscopic biopsy after three cycles of chemotherapy. Metastatic lymph nodes also completely disappeared on the CT scan. The patient received a total of ten cycles of chemotherapy, without severe adverse effects. The patient remained asymptomatic for 18 months after discontinuation of the chemotherapy, without evidence of local recurrence or distant metastasis. Surgery or endoscopic treatment of both esophageal and gastric cancers is desirable, but, if medically inoperable, chemotherapy can be alternative treatment option.

Detection of BRAF(V600E) Mutation using Peptide Nucleic Acid-Mediated PCR Clamping Method in Fine Needle Aspiration Cytology / 대한내분비외과학회지

PURPOSE: The aim of this study was to evaluate the diagnostic value of a peptide nucleic acid (PNA)-mediated PCR clamping method for the detection of BRAFV600E mutations in fine needle aspiration cytology (FNAC). METHODS: One hundred sixty four patients underwent FNAC to evaluate BRAFV600E mutations between April 2011 and November 2011. Among them, forty-two patients were diagnosed with papillary thyroid carcinoma in a permanent pathologic specimen. A PNA-mediated PCR clamping method and a Dual-Priming Oligonucleotide (DPO)-based Real-time PCR method were used to detect the BRAFV600E mutation. We compared the result of mutation between the two methods. RESULTS: A BRAF mutation was found in 31 samples created by the PNA-mediated PCR clamping method, and in 28 samples in the DPO-based Real-time PCR method. The rate of BRAF mutation was 73.8% in association with the PNA-mediated PCR clamping method, and 66.7% in association with the DPO-based Real-time PCR method. There was no statistical differences between the two methods (P>0.05). CONCLUSION: The PNA-mediated PCR clamping method may be an alternative to the DPO-based Real-Time PCR method for detection of BRAF mutations in thyroid nodules.

Reliability of Reconstructed Breast Flap after Chemotherapy and Radiotherapy in Immediate Breast Reconstruction

BACKGROUND: Postmastectomy adjuvant therapy is used to prevent locoregional recurrence and improve overall breast cancer specific survival rates. However, it can adversely affect the cosmetic results of reconstruction. Therefore, the authors examined flap stability and patients' satisfaction with immediate breast reconstruction after adjuvant therapy. METHODS: We retrospectively reviewed the medical records of 204 patients from January 2006 to November 2011. For complication rates, the authors categorized the patients who underwent the immediate breast reconstruction into 4 groups: adjuvant chemotherapy and radiotherapy group, adjuvant chemotherapy only group, adjuvant radiotherapy only group, and the group that did not undergo adjuvant therapy. For comparison of patients' satisfaction, the study was performed with an additional 16 patients who had undergone delayed breast reconstruction. RESULTS: Regarding complication rates, the group that had undergone adjuvant therapy showed no significant difference compared to the group that did not undergo adjuvant therapy. In evaluating the patients' satisfaction, there was no significant difference. CONCLUSIONS: Even after adjuvant therapy, immediate breast reconstruction showed good results with respect to flap stability and patients' satisfaction. Immediate breast reconstruction and adjuvant therapy is a safe and useful option for breast cancer patients.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

A Case of Aggressive Digital Papillary Adenoma of the Fifth Finger / 대한정형외과학회잡지

Aggressive digital papillary adenoma is a rare neoplasm of eccrine sweat gland origin. We report a case of aggressive digital papillary adenoma of the fifth finger, together with a literature review.

MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour

BACKGROUND: The aim of this study was to determine whether pyrosequencing (PSQ) might be useful to achieve O6-methyl guanine methyltransferase (MGMT) promoter methylation using 1- to 13-year-old archival tissues as a clinical biomarker in routine practice. METHODS: The study included 141 formalin-fixed paraffin-embedded (FFPE) glial tumors from the archives of the Pathology Department from 1997-2010. RESULTS: The average percentage of methylation (MP) of the 141 cases was 14.0+/-16.8%, and methylated cases were 32.3+/-14.9%. The average MP of each year did not show a linear increasing or decreasing pattern according to the age of the FFPE block (p=0.771). The average MP of methylated glioblastomas was 35.8+/-14.7%, 31.8+/-15.5% for anaplastic astrocytomas, and 22.4+/-15.1% for astrocytoma. A tendency was observed toward an increasing pattern of average MP with World Health Organization (WHO) grade (p=0.063) in astrocytic tumors. A correlation was observed between average MP and WHO grade (p=0.038) and a bimodal distribution was observed between the methylated and unmethylated cases, using a 9% cut-off value (p<0.001). CONCLUSIONS: The results showed that a quantitative approach for MGMT promoter methylation yielded a 100% success rate for FFPE tissues from archives. PSQ can be used in a retrospective trial, but the cut-off value and calculation method should be further validated.