Current state of cytopathology residency training: a Korean national survey of pathologists

Background@#Although the Korean Society for Cytopathology has developed educational goals as guidelines for cytopathology education in Korea, there is still no systematic approach to cytopathology education status for pathology residents. Furthermore, satisfaction with cytopathology education and with the outcome of the current training/educational program has not been investigated in Korea. This study aimed to obtain comprehensive data on the current state of cytopathology education for residents and evaluate education outcomes. @*Methods@#An online survey was conducted in December 2020 for the board-certified pathologists and training residents registered as members of the Korean Society for Cytopathology. The questionnaire comprised questions that investigated the current status of cytopathology at each training institution, the degree of satisfaction with the work and education related to cytopathology, outcomes of cytopathology training, and educational accomplishments. @*Results@#Of the participants surveyed, 12.3% (132/1,075) completed the questionnaire, and 36.8% (32/87) of cytopathology residents participated. The mean overall satisfaction with cytopathology education was 3.1 points (on a 1- to 5-point scale, 5: very satisfied). The most frequent suggestion among the free description format responses was to expand educational opportunities, such as online education opportunities, outside of the individual institutions. @*Conclusions@#Our results showed that cytopathology training in Korea needs further improvement. We expect that this study will inform systematic training of competent medical personnel armed with broad cytopathology knowledge and strong problem-solving abilities.

Evaluation of PostNeoadjuvant Chemotherapy Pathologic Complete Response and Residual Tumor Size of Breast Cancer: Analysis on Accuracy of MRI and Affecting Factors

Purpose@#To evaluate the accuracy of MRI in predicting the pathological complete response (pCR) and the residual tumor size of breast cancer after neoadjucant chemotherapy (NAC), and to determine the factors affecting the accuarcy. @*Materials and Methods@#Eighty-eight breast cancer patients who underwent surgery after NAC at our center between 2010 and 2017 were included in this study. pCR was defined as the absence of invasive cancer on pathological evaluation. The maximum diameter of the residual tumor on post-NAC MRI was compared with the tumor size of the surgical specimen measured pathologically. Statistical analysis was performed to elucidate the factors affecting pCR and the residual tumor size-discrepancy between the MRI and the pathological measurements. @*Results@#The pCR rate was 10%. The diagnostic accuracy of MRI and the area under the curve for predicting pCR were 90.91% and 0.8017, respectively. The residual tumor sizes obtained using MRI and pathological measurements showed a strong correlation (r = 0.9, p < 0.001), especially in patients with a single mass lesion (p = 0.047). The size discrepancy between MRI and the pathological measurements was significantly greater in patients with the luminal type (p = 0.023) and multifocal tumorson-mass enhancement on pre-NAC MRI (p = 0.047). @*Conclusion@#MRI is an accurate tool for evaluating pCR and residual tumor size in breast cancer patients who receive NAC. Tumor subtype and initial MRI features affect the accuracy of MRI.

Evaluation of PostNeoadjuvant Chemotherapy Pathologic Complete Response and Residual Tumor Size of Breast Cancer: Analysis on Accuracy of MRI and Affecting Factors

Purpose@#To evaluate the accuracy of MRI in predicting the pathological complete response (pCR) and the residual tumor size of breast cancer after neoadjucant chemotherapy (NAC), and to determine the factors affecting the accuarcy. @*Materials and Methods@#Eighty-eight breast cancer patients who underwent surgery after NAC at our center between 2010 and 2017 were included in this study. pCR was defined as the absence of invasive cancer on pathological evaluation. The maximum diameter of the residual tumor on post-NAC MRI was compared with the tumor size of the surgical specimen measured pathologically. Statistical analysis was performed to elucidate the factors affecting pCR and the residual tumor size-discrepancy between the MRI and the pathological measurements. @*Results@#The pCR rate was 10%. The diagnostic accuracy of MRI and the area under the curve for predicting pCR were 90.91% and 0.8017, respectively. The residual tumor sizes obtained using MRI and pathological measurements showed a strong correlation (r = 0.9, p < 0.001), especially in patients with a single mass lesion (p = 0.047). The size discrepancy between MRI and the pathological measurements was significantly greater in patients with the luminal type (p = 0.023) and multifocal tumorson-mass enhancement on pre-NAC MRI (p = 0.047). @*Conclusion@#MRI is an accurate tool for evaluating pCR and residual tumor size in breast cancer patients who receive NAC. Tumor subtype and initial MRI features affect the accuracy of MRI.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Early-Onset Breast Cancer in a Family with Neurofibromatosis Type 1 Associated with a Germline Mutation in BRCA1 / 한국유방암학회지

Neurofibromatosis type 1 (NF1), which may occur as an autosom-al dominant disorder, is caused by the absence of neurofibromin protein due to somatic mutations in the NF1 gene, and it has been associated with an increased risk of breast cancer. Herein we describe a family with two women affected by both NF1 and early-onset breast cancer. We evaluated whether the concomitance of NF1 and early-onset breast cancer could be due to disease-causing mutations in both NF1 and BRCA1 gene in a Korean family with clinical features of both NF1 and hereditary breast cancer. Mutation analyses identified nonsense mutations in NF1 and BRCA1 genes. Our findings indicate that an awareness of the possible concomitance of NF1 and BRCA1 gene mutations is important for identifying the genetic origin of early-onset breast cancer in patients with NF1 to achieve early detection of cancers and decrease breast cancer-associated morbidity and mortality in these patients.

Spontaneous Pneumomediastinum, Pneumopericardium, and Pneumothorax with Respiratory Failure in a Patient with AIDS and Pneumocystis jirovecii Pneumonia

Spontaneous pneumothorax occurs in up to 35% of patients with Pneumocystis jirovecii pneumonia. However, spontaneous pneumomediastinum and pneumopericardium are uncommon complications in patients infected with human immunodeficiency virus, with no reported incidence rates, even among patients with acquired immunodeficiency syndrome (AIDS) and P. jirovecii pneumonia. We report a case of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax with respiratory failure during treatment of P. jirovecii pneumonia in a patient with AIDS; the P. jirovecii infection was confirmed by performing methenamine silver staining of bronchoalveolar lavage specimens. This case suggests that spontaneous pneumomediastinum and pneumopericardium should be considered in patients with AIDS and P. jirovecii pneumonia.

Microtubule-Associated Protein Tau, alpha-Tubulin and betaIII-Tubulin Expression in Breast Cancer

BACKGROUND: The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, alpha-tubulin, and betaIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment. METHODS: Immunohistochemical expressions of Tau, alpha-tubulin, and betaIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival. RESULTS: Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of alpha-tubulin was significantly correlated with distant metastasis (p=.034). Loss of betaIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of alpha-tubulin and betaIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049). CONCLUSIONS: Tau expression and loss of alpha-tubulin and betaIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, alpha-tubulin and betaIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival

BACKGROUND: The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. METHODS: Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. RESULTS: The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012). CONCLUSIONS: Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy

BACKGROUND: This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC. METHODS: Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case. RESULTS: Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%. CONCLUSIONS: This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

A Case of Steroid Dependent Eosinophilic Gastroenteritis Presenting as a Huge Gastric Ulcer

Eosinophilic gastroenteritis is defined as primary eosinophilic infiltration of the gastrointestinal tract. Endoscopic findings of this disease entity are non-specific, and huge gastric ulceration as initial presentation is extremely rare. We experienced a case of eosinophilic gastroenteritis presenting with abdominal pain in a 38 year-old-woman. Deep and huge ulceration in gastric antrum and body looked like advanced gastric cancer. Surgical resection was performed and histopathological examination showed dense infiltration of eosinophil without malignant cells. 5 years after surgery, diffuse abdominal pain and generalized edema developed and computed tomography showed entire wall thickening of the gastrointestinal tract. Random mucosal biopsy of the remnant stomach and terminal ileum showed mucosal eosinophilic infiltrations. She was treated with steroids and azathioprine but experienced frequent relapses and was dependent on steroids to maintain remissions. After 3 years, she died from infective endocarditis due to the prolonged use of immunosuppressive agents.

A Case of Severe Gingival Overgrowth Caused by Long-Term Amlodipine Treatment / 대한내과학회지

Amlodipine is one of the most commonly used calcium-channel blockers for the management of hypertension in Korea. Gingival overgrowth is an infrequent complication in patients receiving amlodipine treatment. A 52-year-old man on an amlodipine regimen of 10 mg/day for 25 months sought medical attention because of gradually progressive gingival enlargement. Examination of the oral cavity revealed severe gingival overgrowth. We stopped the amlodipine treatment and recommended the maintenance of good oral hygiene and a gingivectomy. Histological findings of the gingivectomy were typical of drug-induced gingival overgrowth, including epithelial thickening with proliferation, acanthosis with elongated rete ridges, and focal parakeratosis. A marked reduction in gingival overgrowth was evident 1 month after the gingivectomy and cessation of amlodipine. This report describes the case of a 52-year-old man who developed severe and histologically confirmed amlodipine-induced gingival overgrowth.

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

A Case of Severe Gingival Overgrowth Caused by Long-Term Amlodipine Treatment / 대한내과학회지

Amlodipine is one of the most commonly used calcium-channel blockers for the management of hypertension in Korea. Gingival overgrowth is an infrequent complication in patients receiving amlodipine treatment. A 52-year-old man on an amlodipine regimen of 10 mg/day for 25 months sought medical attention because of gradually progressive gingival enlargement. Examination of the oral cavity revealed severe gingival overgrowth. We stopped the amlodipine treatment and recommended the maintenance of good oral hygiene and a gingivectomy. Histological findings of the gingivectomy were typical of drug-induced gingival overgrowth, including epithelial thickening with proliferation, acanthosis with elongated rete ridges, and focal parakeratosis. A marked reduction in gingival overgrowth was evident 1 month after the gingivectomy and cessation of amlodipine. This report describes the case of a 52-year-old man who developed severe and histologically confirmed amlodipine-induced gingival overgrowth.

Review of atypical cytology of thyroid nodule according to the Bethesda system and its beneficial effect in the surgical treatment of papillary carcinoma / 대한외과학회지

PURPOSE: For the atypical cases of fine needle aspiration (FNA) cytology of thyroid nodules, ultrasonographic findings are a primary guideline for the surgical treatment. However, they have the intrinsic risk of overtreatment, as well. In this study we examined whether the Bethesda system could provide a real effect on the diagnostic rate of atypical cytology, and thereby reduce the number of cases diagnosed as atypical from FNA cytology. METHODS: We reviewed 166 cases diagnosed as atypical by FNA cytology at this institute between the years 2005 to 2010. We classified these cases on the basis of ultrasonographic and cytological findings and compared them with the histological results. RESULTS: Ultrasonographically, findings suspicious for malignancy and indeterminate were associated with 83.7% and 47.2% of malignancy rates, respectively. Cytopathologically, the malignancy rates varied according to the main cytological features and the highest malignancy rate was 77.3%. Based on the Bethesda system, 39.2% of the cases diagnosed as atypical could be grouped into the category of suspicious for malignancy and yielded a malignancy rate of 76.9%. CONCLUSION: Although ultrasonography provides an excellent guideline for the surgical treatment of atypical cases, it also showed considerable risk of overtreatment. The Bethesda system did not offer definitive effects on the rate of atypical cytology, but this system seemed to provide stricter boundaries for the atypical cytology and to aid in reducing the rates thereof. This in turn may permit that more limited cases are allotted to ultrasonographic decision making.

A Rare Case of Recurrent Myoid Hamartoma Mimicking Malignancy: Imaging Appearances

Myoid hamartoma is an uncommon type of breast hamartoma and its recurrence is very rare. We report the imaging appearance of an unusual case of recurrent myoid hamartoma of the breast mimicking malignancy in a 43-year-old woman. Although the mammographic and ultrasonographic findings have long been described in the literature, MR finding with a dynamic study has not, to the best of our knowledge, been reported previously.

Malignant Fibrous Histiocytoma Arising in a Mature Cystic Teratoma of the Ovary: A Case Report

A 50-year-old female patient presented with anorexia and weight loss. Pelvic computed tomography revealed a 12.5 x 7.3 cm heterogeneous mass in the left ovary. About 30% of the tumor was occupied by a mature cystic teratoma. The remaining solid portion was composed of fibrous and histiocytic elements, arranged in storiform patterns admixed with bizarre giant cells. The mitotic index was 8 per 10 high power fields, including atypical mitoses. The only immunopositivity was for vimentin. The tumor was diagnosed as a malignant fibrous histiocytoma arising in a mature cystic teratoma. To the best of our knowledge, this is only the third such case in the English language literature.

Painless Posterior Thigh Mass as a Presentation of Metastatic Breast Cancer / 한국유방암학회지

Soft tissue metastasis clinically presenting as either painless subcutaneous or painful intramuscular nodules is extremely rare and may lead to an errant clinical suspicion of sarcoma. In general, most soft tissue metastasis comes from lung carcinoma; however, to date, there have been no reports of a posterior thigh mass just beneath the skin metastasizing from breast cancer. Here, we report a case of distant soft tissue metastasis presenting as a painless solitary left posterior thigh mass measuring 1.5 cm in diameter, which was later shown by positron emission tomography-computed tomography (PET-CT) to have multiple simultaneous mediastinal lymph node metastases. Eleven months ago, the patient had undergone curative breast-conserving surgery (BCS) for cancer of her left breast. At that time, her tumor showed a triple negative phenotype. Initial PET-CT right before the BCS had shown no metastasis. After histological and radiologic evaluation for the metastases, she decided to have systemic chemotherapy.

Alteration of G1/S Cell Cycle Regulatory Proteins in Carcinogenesis of Cutaneous Squamous Cell Carcinomas

BACKGROUND: Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. METHODS: We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen's disease (BD; n=37), keratoacanthoma (KA; n=23), and squamous cell carcinoma (SCC; n=22). RESULTS: The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. CONCLUSIONS: The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.

Severe preeclampsia at 16 weeks' gestation associated with a partial hydatidiform mole and bilateral theca-lutein cysts / 대한산부인과학회지

We present an unusual case in which a patient was diagnosed with the preeclampsia associated with a partial hydatidiform mole and bilateral theca-lutein cysts. The patient newly developed proteinuric hypertension at 16 weeks' gestation. Ultrasound findings showed small multiple cystic spaces in the placenta and a live singleton fetus. Triploid 69, XXX was confirmed at karyotype analysis. Intrauterine fetal death was found at 18 weeks' gestation and termination of pregnancy was performed, and a partial hydatidiform mole was confirmed at pathologic examination. Torsion of bilateral theca-lutein cysts was developed at postpartum one week. Detorsion and aspiration of the bilateral theca-lutein cysts were performed under the laparoscopy.

Expression of p73 in Non-small Cell Lung Carcinomas

BACKGROUND: The p73 is a recently identified homologue of the tumor suppressor gene, p53, and it has been found to induce apoptosis and inhibit cell proliferation. However, its role in the development of tumors is unclear. This study examined the expression of p73 in patients with non-small cell lung carcinomas (NSCLCs) to determine its clinical significance and association with the expressions of p53, pRb, and mdm2. METHODS: A total of 183 NSCLCs were analyzed immunohistochemically using a tissue microarray. RESULTS: The p73 protein was expressed in the cell nuclei in 156 (85.2%) out of the 183 cases. There was no correlation between the p73 expression and the clinicopathological variables. However, there was a correlation between the p73 expression and the mdm2 and pRb expressions. Multivariate Cox survival analysis identified tumor size and lymph node metastasis to be independent prognostic factors, but the p73 expression was not found to be associated with the patients' survival. CONCLUSIONS: p73 is commonly expressed in NSCLC and it might, in conjunction with pRb and mdm2, be involved in the development of these tumors.