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.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder

PURPOSE: To evaluate the prognostic significance of the depth of lamina propria invasion in primary T1 transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 183 patients with primary T1 TCC of the bladder who had undergone transurethral resection (TUR) at our institution. Substaging was defined according to the depth of lamina propria invasion as follows: T1a, superficial invasion of lamina propria; T1b, invasion into the muscularis mucosa (MM); T1c, invasion beyond the MM but not to the muscularis propria. The prognostic significance of various clinicopathological variables for recurrence and progression was analyzed. RESULTS: Of the 183 patients, substaging was T1a in 119, T1b in 57, and T1c in 7 patients. The recurrence rate was 32.8% for T1a and 40.6% for T1b/c, but there was no significant difference between the two groups. The progression rate was significantly different between the two groups: 5.8% in T1a and 21.9% in T1b/c (p=0.003). The cancer-specific mortality rate was also significantly different: 4.2% in T1a and 14.0% in T1b/c (p=0.036). In the univariate analysis, microscopic tumor architecture was the only significant prognostic factor for recurrence. In the univariate and multivariate analysis concerning progression, depth of lamina propria invasion and concomitant carcinoma in situ were significant prognostic factors. CONCLUSIONS: Substaging according to the depth of lamina propria invasion in primary T1 TCC of the bladder was an independent prognostic factor for progression. This suggests that substaging would be helpful for guiding decisions about adjuvant therapies and follow-up strategies.

Comparison of Conventional Smear, Cell Block and Liquid-based Preparation in the Evaluation of Bronchial Washing Specimen in Lung Cancer Patients

BACKGROUND: The preparation of conventional smears (CS) from mucoid samples, despite mucolysis, can pose difficulties for cytotechnologists or cytopathologists. In recent years, liquid-based cytology (LBC) devices have been developed in attempts to improve the cytopreparation process. LBC improves both sample collection and sample preparation. Cell block preparations (CB) can be made from residual tissue fluids, and are a useful adjunct to smears. METHODS: We retrospectively reviewed 3 preparations from 209 patients whose diagnosis was later confirmed via bronchoscopic biopsy, fine needle aspiration, gun biopsy or operation. Each case was categorized into one of three groups: "negative," "atypical or suspicious" and "malignant." RESULTS: When conflating the "atypical" and "malignant" categories into a "positive" category, the sensitivity of each preparation was 74.4% in LBC, 72.9% in CS, and 76.5% in CB preparations. Specificity was 98.7%, 94.7% and 98.7%, respectively. By combining LBC and CB, the sensitivity is 78.2%. CONCLUSIONS: Among three different preparation methods, sensitivity is highest in the CB method. LBC has many advantages in evaluating cell morphology and by combining CB method, the sensitivity can be improved slightly. The application of all three methods may prove helpful when one or another method proves diagnostically inconclusive.

Extensive Systemic Sarcoidosis with Testicular Involvement Mimicking Metastatic Testicular Cancer

Sarcoidosis is an idiopathic, multisystem disease that rarely involves the genitourinary tract. Here we present an unusual case of testicular sarcoidosis with extensive lymphadenopathy that mimicked a metastatic testicular tumor. A 27-year-old male presented with a palpable right testicular mass accompanied by multiple palpable inguinal lymph nodes. The scrotal ultrasound showed a hypoechoic lesion at the inferior portion of the right testis. Extensive enlarged lymph nodes were noted in multiple areas on the abdominal computed tomography. Preoperative testicular tumor markers were within the normal range. Exploration of the right testis with a frozen section analysis of the right testicular mass and of a palpable right inguinal lymph node showed granulomatous inflammation. The testis was salvaged and the final pathological diagnosis was sarcoidosis. Treatment with high-dose corticosteroids resulted in complete resolution of the intratesticular mass and a significant decrease in the extent of the lymphadenopathy.

Premenopausal early-stage endometrial carcinoma patients with low CA-125 levels and low tumor grade may undergo ovary-saving surgery / 부인종양

OBJECTIVE: The purpose of this study was to determine the possible predicting factors of coexisting adnexal malignancies, and to evaluate the safety of ovary-saving surgery for early-stage endometrial carcinoma in premenopausal patients. METHODS: A retrospective review of 107 patients with endometrial carcinoma who underwent surgical treatment at our institution was conducted. All patients were younger than 50 years of age and premenopausal status. Statistical analysis was performed. RESULTS: Of the 107 patients, 78 patients had stage I to II disease and both preoperative CA-125 levels were measured and tumor grades evaluated. On multivariate analysis, preoperative CA-125 levels (p=0.018) and preoperative tumor grade (p=0.029) were independent predicting factors of adnexal diseases. The risk of coexisting ovarian malignancy was 1.8% in patients with preoperative CA-125 levels less than or equal to 34.5 U/ml and preoperative tumor grade 1 or 2. The risk increases to 20% for low CA-125 and grade 3, 13.3% for high CA-125 and grade 1 or 2, and 100% for high CA-125 and grade 3. Between patients who underwent unilateral salpingo-oophorectomy and those who underwent bilateral salpingo-oophorectomy, there was no statistically significant difference in terms of BMI, preoperative CA-125 levels, FIGO stage, histology, tumor grade, lymphadenectomy, and adjuvant treatment. CONCLUSION: Ovary-saving surgery for premenopausal, early-stage endometrial cancer patients may be considered as a treatment option in those with low preoperative CA-125 and low tumor grade.

Basal Cell Carcinoma of the Prostate

Basal cell carcinoma (BCC) of the prostate, a rare variant of prostate cancer, is derived from the basal cells of prostatic ducts and acini. BCC generally occurs in elderly men with obstructive voiding symptoms and levels of serum prostate-specific antigen within the normal range. In most cases, diagnosis is made through transurethral resection or simple enucleation. Most cases are indolent, but local recurrence and metastasis have been reported in a few cases. Thus, radical surgery and long-term follow-up are recommended. We report a case of a 54-year-old man who underwent radical retropubic prostatectomy after being diagnosed with BCC during a transurethral resection performed for lower urinary tract symptoms. The patient has remained free of disease for 4 months after surgery.

A case of bladder rhabdomyosarcoma in an adult / 대한내과학회지

Rhabdomyosarcomas, malignant neoplasms exhibiting skeletal muscle differentiation, are the most common childhood sarcomas. Embryonal rhabdomyosarcomas of the genitourinary tract also occur in children but are rare in adults. We report a case of embryonal rhabdomyosarcoma arising in the bladder of a 29-year-old man who presented with dysuria and microscopic hematuria. A partial cystectomy was performed, and he received chemotherapy with vincristine and actinomycin.

A case of bladder rhabdomyosarcoma in an adult / 대한내과학회지

Rhabdomyosarcomas, malignant neoplasms exhibiting skeletal muscle differentiation, are the most common childhood sarcomas. Embryonal rhabdomyosarcomas of the genitourinary tract also occur in children but are rare in adults. We report a case of embryonal rhabdomyosarcoma arising in the bladder of a 29-year-old man who presented with dysuria and microscopic hematuria. A partial cystectomy was performed, and he received chemotherapy with vincristine and actinomycin.

A case of leiomyomatosis peritonealis disseminata arising after laparoscopic myomectomy / 대한산부인과학회지

Leiomyomatosis peritonealis disseminata (LPD) is rare, typically benign condition characterized by multiple smooth muscle, myofibroblasticand fibroblastic nodules arising in the pelvic and abdominal cavities in women. LPD is observed in reproductive age group especially and often mimics carcinomatosis grossly but has benign histologic feature and good prognosis. We report a case of leiomyomatosis peritonealis disseminata arising after laparoscopic myomectomy with review of literature.

Sonohysterography-Guided Biopsy of Focal Endometrial Lesions: Value of Four-dimensional Ultrasonography

PURPOSE: To assess the usefulness of four-dimensional (4D) ultrasonographic guidance in sonohysterographyguided biopsy of focal endometrial lesions. MATERIALS AND METHODS: Endometrial biopsies were performed prospectively under 4D ultrasound guidance in 24 consecutive patients with focal endometrial lesions detected on baseline sonohysterography. A single slice view in three orthogonal planes, a sagittal surface-rendered image, and multislice views in the sagittal plane were used for real-time guidance during the procedure. We evaluated feasibility based on the technical success rates and the number of "diagnostic" specimens obtained for histological diagnosis, and we correlated the biopsy results with the pathological diagnosis determined through the surgical procedure. RESULTS: Four-dimensional sonohysterography-guided biopsy was successfully performed in 21 (87.5%) of 24 patients without any significant complication. The biopsy specimens were diagnostic in 19 (90.5%) of 21 patients. Thirteen of 19 patients (68.4%) patients underwent surgery, and the diagnoses obtained using cytology correlated well with the pathology. CONCLUSION: Four-dimensional ultrasonography-guided biopsy is technically feasible and may be useful in the diagnosis of focal endometrial lesions.

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma

BACKGROUND: The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC). METHODS: Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists. RESULTS: There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3. CONCLUSIONS: The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.

Mixed Epithelial and Stromal Tumor of the Kidney / 대한비뇨기과학회지

Mixed epithelial and stromal tumor of the kidney(MEST) is a rare, recently described benign renal neoplasm that predominantly affects perimenopausal women. It is composed of dual components of epithelial and stromal cells, and the tumor is characterized by admixed cystic and solid growth patterns. Herein, we report on a case of MEST in a 35-year-old woman who presented with an incidentally found renal tumor. The patient has had no evidence of disease 4 years after the surgery.

Sonohysterography-Guided Biopsy of Focal Endometrial Abnormalities: Technical Feasibility and Diagnostic Accuracy

PURPOSE: To assess the feasibility and diagnostic accuracy of a sononohysterography-guided biopsy in an evaluation of focal endometrial lesions. MATERIALS AND METHODS: Sixty-five consecutive patients with focal endometrial lesions detected on baseline sonohysterography were enrolled prospectively. The biopsy was performed under real-time sonohysterography guidance, using a 3.1 mm Pipelle endometrial sampler as the primary biopsy device. The feasibility was evaluated from the technical success rates and the number of "diagnostic" specimen for the histological diagnosis. The diagnostic accuracy was assessed by comparing the biopsy results with the final pathological diagnosis obtained by the surgical procedure. RESULTS: Sonohysterography-guided biopsy was performed successfully in 59(90.8%) out of 65 patients. The reasons for failure in 6 patients were a failure to pass through the cervix (n=3); failure to target a focal lesion (n=2); and inadequate uterine distension (n=1). The biopsy specimen was "diagnostic" in 49 (83.1%) out of 50 patients, and "non-diagnostic" in 10 patients with insufficient tissue (n=6) and indeterminate cellular features for a histological diagnosis (n=4). The cytology results of the sonohysterographically-guided biopsy correlated well with the pathological diagnosis in 35 (92.1%) out of 38 patients who underwent subsequent surgical procedures. CONCLUSION: Sonohysterography-guided biopsy is technically feasible and can be an accurate method for diagnosing focal endometrial lesions. It could be considered to be a reliable office triage as an alternative to hysteroscopic biopsy in patients with focal endometrial abnormalities.

Correlation of Caveolin-1 Expression on Tissue Microarray with Prognosis in Renal Cell Carcinoma / 대한비뇨기과학회지

PURPOSE: We investigated the relationship between the expression of caveolin-1, using a tissue microarray (TMA), and the prognosis of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: TMA sections of formalin-fixed, paraffin-embedded tissues of RCC from 82 patients, who had undergone radical nephrectomy, were stained immunohistochemically with specific antibodies against caveolin-1. The caveolin-1 immunostaining was semi-quantitatively estimated based on intensity. The expression pattern of caveolin-1 was compared with the clinicopathological variables. RESULTS: The expression of caveolin-1 was significantly correlated with tumor size (p=0.002), TNM stage (p<0.001), T stage (p=0.001), M stage (p=0.004), grade (p=0.028) and metastasis (p<0.001), and was also significantly higher in clear cell than non-clear cell RCC (p<0.001). The survival of patients with higher caveolin-1 expression was significantly worse than that of patients with lower caveolin-1 expression (p=0.001). Univariate analyses were able to identify all variables, including caveolin-1 expression as significant prognostic factors for cancer-specific survival; multivariate analyses indicated that TNM stage, M stage and grade were independent prognostic factors. Caveolin-1 expression was not an independent factor. CONCLUSIONS: The increased expression of caveolin-1 is associated with tumor size, stage, grade, metastasis and a worse prognosis in RCC, which suggests that caveolin-1 may be important in the progression of RCC.

A case of malignant mesothelioma of the uterus / 부인종양

Malignant mesothelioma of the uterus is a rare mesenchymal neoplasm originating from the mesothelial surface cell lining of the uterus. It is known to have very poor prognosis with median survival period of 4-18 months. We report a rare case of primary malignant mesothelioma of the uterus showing no evidence of recurrence for 2 years, after management with operation and adjuvant chemotherapy.

A case of malignant mesothelioma of the uterus / 부인종양

Malignant mesothelioma of the uterus is a rare mesenchymal neoplasm originating from the mesothelial surface cell lining of the uterus. It is known to have very poor prognosis with median survival period of 4-18 months. We report a rare case of primary malignant mesothelioma of the uterus showing no evidence of recurrence for 2 years, after management with operation and adjuvant chemotherapy.

Primary Actinomycosis of the Urinary Bladder Associated with Intrauterine Contraceptive Device / 대한비뇨기과학회지

Actinomycosis is a chronic suppurative infectious disease usually caused by the anaerobic bacterium Actinomyces israelii. Pelvic actinomycosis is rare, and usually associated with the use of intrauterine contraceptive devices. Primary vesical actinomycosis is extremely rare. Herein, a case of a 42-year-old woman, who presented with bladder irritative symptoms and had a 13 year history of intrauterine device insertion, is reported. With the presumptive diagnosis of bladder tumor or abscess, partial cystectomy was performed. Pathological examination revealed a primary vesical actinomycosis.

Cyclooxygenase-2 and p53 Expression as Prognostic Indicators in Conventional Renal Cell Carcinoma

The aim of this study was to investigate the relationship of cyclooxygenase (COX) -2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p= 0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p < 0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.