Journal of Pathology and Translational Medicine

Review

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists: Yosep Chong, Dae Cheol Kim, Chan Kwon Jung, Dong-chul Kim, Sang Yong Song, Hee Jae Joo, Sang-Yeop Yi; J Pathol Transl Med. 2020;54(6):437-452. Published online October 8, 2020; DOI: https://doi.org/10.4132/jptm.2020.08.27

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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.

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Original Articles

Extrapulmonary Lymphangioleiomyoma: Clinicopathological Analysis of 4 Cases: Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Yoon-La Choi, Kee-Taek Jang, Sang Yong Song, Chin A Yi, Joungho Han; Korean J Pathol. 2014;48(3):188-192. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.188

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Abstract PDF

Background

Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease that predominantly affects females. Usually, LAM affects the lung; it can also affect extrapulmonary sites, such as the mediastinum, the retroperitoneum, or the lymph nodes, although these locations are rare. A localized form of LAM can manifest as extrapulmonary lesions; this form is referred to as extrapulmonary lymphangioleiomyoma (E-LAM). Due to the rare occurrence of E-LAM and its variable, atypical location, E-LAM is often difficult to diagnose. Herein, we report the clinicopathological information from four E-LAM cases, and also review previous articles investigating this disease.

Methods

Four patients with E-LAM were identified at the Samsung Medical Center (Seoul, Korea) from 1995 to 2012. All E-LAM lesions underwent surgical excision.

Results

All patients were females within the age range of 43 to 47 years. Two patients had para-aortic retroperitoneal masses, while the other two patients had pelvic lesions; two out of the four patients also had accompanying pulmonary LAM. In addition, no patient displayed any evidence of tuberous sclerosis. Histologically, two patients exhibited nuclear atypism with cytologic degeneration.

Conclusions

E-LAM should be considered in the differential diagnosis of patients presenting with pelvic or para-aortic masses. We also conclude that further clinical and pathological evaluation is needed in patients with E-LAM and nuclear atypism.

Citations

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Pathologic Characteristics of Korean Prostatic Adenocarcinoma: A Mapping Analysis of 60 Cases.: Yoon La Choi, Sung Rim Kim, Sang Yong Song, Han Yong Choi; Korean J Pathol. 2001;35(1):35-40.

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Abstract PDF: BACKGROUND
Pathologic characteristics of the prostatic adenocarcinoma in Korean patients are not clear. We studied 60 cases of radical prostatectomy specimens using mapping analysis in an effort to discover the pathologic characteristics of the Korean prostatic adenocarcinoma.
METHODS
A resected prostate was sectioned serially and embedded near-totally. Gleason score, tumor volume or size, capsular extension, involvement of lateral margin, seminal vesicle, vas, apex and base, presence of lymphatic and neural invasion, and presence of high grade prostatic intraepithelial neoplasm (HGPIN) were examined. DNA ploidy and proliferative index were evaluated.
RESULTS
Mean values were as follows: age, 63.6 years; serum prostate specific antigen level (sPSA), 24.0 ng/ml; tumor amount (volume, 29.1%; size, 2.4 cm); Gleason score, 7.3; aneuploidy, 23.3%; proliferative index, 14.2%. Involvement rates of apex, base, seminal vesicle, resection margin, nerve and lymphatics were 5.2%, 39.0%, 23.7%, 31.7%, 56.7% and 16.7%, respectively. Rates of multifocal tumors and HGPIN were 43.3% and 63.3%, respectively. The Gleason score was correlated with tumor amount (volume%, p<0.001; size, p<0.01) and tumor extent (T) (p<0.005). Tumor amount was correlated with sPSA (p<0.05) and T (p<0.005). T was correlated with sPSA (p<0.05).
CONCLUSION
Korean prostatic adenocarcinomas showed higher Gleason scores, lower HGPIN rates and multifocalities in comparison to western prostatic adenocarcinomas, suggestive of the Korean prostatic adenocarcinomas' late detection.

Case Reports

Giant Multilocular Cystadenoma of the Prostate: A Case Report.: Chang Ohk Sung, Jinwon Seo, Sang Yong Song; Korean J Pathol. 2004;38(2):106-108.

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Abstract PDF: Large multilocular cysts and cystic neoplasms of the prostate are very rare. A healthy 52-year-old man presented with acute urinary retension. Physical examination revealed a large abdominal mass. Pelvic MRI showed a 15x10x9 cm, lobulated, and multiseptated cystic mass in the pelvic cavity. Exploration laparotomy revealed a large cytic mass that compressd and displaced the urinary bladder antero-laterally, and adhered to the prostate and the sigmoid colon. Macroscopically, the mass was grayish white colored, multilocular cysts containing reddish-brown serous fluid. Microscopically, the tumor was composed of glands and cysts lined by the prostatic-type epithelium in the fibrous stroma. The prostatic nature of the lesion was confirmed by the lining epithelium expressing prostate-specific antigen.

Atypical (Bizarre) Leiomyoma of the Prostate: A Case Report.: Sung Rim Kim, Sang Yong Song, Geunghwan Ahn, Han Yong Choi; Korean J Pathol. 2001;35(2):172-175.

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Abstract PDF: Atypical (bizarre) leiomyoma of the prostate is a very rare neoplasm. Five cases have been reported in English medical literature. A 60-year-old Korean man with a history of prostatism and slightly elevated serum prostate specific antigen was presented. Microscopically, the transurethral resection specimen consisted of a proliferation of hypercellular spindle cells with intersecting bundles. The nuclei of the tumor cells showed marked pleomorphism and hyperchromasia with occasional multinucleated giant cells. Mitoses were seen in areas of up to 2 per 10 high power fields, but there was no evidence of atypical ones. The tumor cells were immunoreactive against anti-smooth muscle actin and desmin antibodies. The proliferative index (10.0%) of the atypical leiomyoma lay between that of a benign smooth muscle and that of a leiomyosarcoma of the prostate. Flow cytometry showed a diploid pattern with an elevated S phase fraction. To the best of our knowledge, this is the first demonstration of atypical leiomyoma of the prostate in a Korean man.

Original Articles

Expression of nm23 Protein in Breast Carcinoma: An immunohistochemical study.: Sang Yong Song, Je G Chi, Se Hwan Han, Kuk Jin Choe; Korean J Pathol. 1995;29(4):469-477.

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Abstract PDF: To elucidate a possible prognostic factor, we studied 91 cases of breast carcinoma for the expression of n-tn23 protein using an immunohistochemical method, and compared these results with the known prognostic parameters of the breast carcinoma. The mn23 protein was intensely stained in the cytoplasm and/or the nucleus of carcinoma cells in 82 cases(90.1%). There were two patterns of cytoplasmic staining; heterogeneous pattern and homogeneous pattern. Among the positive cases, 43 cases(47.2%) were heterogeneous while 39 cases(42.8%) were homogeneous. Axillary lymph node metastases(p<0.005) was found more frequently in the heterogeneous pattern group(79.0%) than in the homogeneous pattern group(41.0%). There was no significant correlation between nm23 protein expression and other parameters such as patient age, tumor size, estrogen receptor, histopathologic grade, and p53 overexpression. Although axillary lymph node metastasis was correlated with the disease free status(p<0.0005) and patient survival (p<0.05), they showed no correlation with nin23 expression. Multivariate analysis showed that axillary lymph node metastasis was the only prognostic indicator(p<0.05), and the expression of nm23 protein was of borderline significance. The results suggest that the homogeneous and/or granular cytoplasmic expression of mn23 protein plays a role in the suppression of nodal metastasis in breast carcinoma and might contribute in predicting patient survival.

Evaluation of Self-collected Pad Sampling for the Detection of HPV In Cervicovaginal Secretion.: Seong Rim Kim, Sang Yong Song, Dae Shick Kim, Jung Won Lee, Chang Soo Park, Duk Soo Bae, Hyen Ji Lee, Kyung Tae Kim, Oh Joong Kwon, Eun Seop Song, Hee Jae Joo, Gheungwhan Ahn; Korean J Pathol. 2004;38(4):258-264.

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Abstract PDF: BACKGROUND
Self-collection of secretion samples for HPV testing is a feasible alternative method for women who would decline to participate in population based cervical cancer programs. The purpose of this study was to determine the sensitivity and specificity of self-sampling for HPV in determining high grade squamous intraepithelial lesion (HSIL) using the pad, and we also wished to compare the results from samples collected by women themselves and those results from samples collected by physicians.
METHODS
Fifty patients voluntarily participated in the sensitivity and specificity study at the university hospitals and 290 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers for the direct sequencing of the pad samples.
RESULTS
For the detection of HSIL, self-collected pad sampling showed good sensitivity (75.0%) and excellent specificity (100%). Two hundreds eighty-six samples from the pads and concurrent physicians?samples showed the agreement at 98.6% with the Kappa, 0.9622 (p=0.0000).
CONCLUSIONS
A self-sampling method using the pad for the detection of HPV DNA is suggested to be an efficient method to access many women for screening easily, rapidly and conveniently. Testing the pad method? utility for a country- or large area-based mass screening study will be necessary in the future.

Case Report

Congenital Neuroblastoma of the Adrenal with Metastasis to Liver, Contralateral Adrenal and Pituitary: Report of an autopsy case.: Na Hye Myong, Sang Yong Song, Je G Chi; Korean J Pathol. 1993;27(2):169-174.

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Abstract PDF: Neoplasms presenting at birth or within the first month of life are defined as congenital tumors. The principal components of this congenital tumors are neuroblastoma, leukemia, brain tumors and sarcomas. The neuroblastoma is the most common accounting for 15~50% of all tumors in this group. It most often presents with an abdominal mass due to adrenal-retroperitoneal primary or hepatomegaly resulting from extensive metastasis. Most often the primary site is adrenal but other loci include the retroperitoneum, mediastinum, pelvis, etc. This 2-day-old female presented with hepatomegaly and a left adrenal mass at birth, first detected by ultrasonography. On the first day, she suffered from hematemesis and bradycardia. She died on the second day. Postmortem examination revealed massive metastatic tumor nodules in the liver and a well-demarcated round mass, 4 cm, in the left adrenal, with necrosis and hemorrhage. Microscopic findings revealed largely undifferentiated neuroblastoma with focal neuronal differentiation and areas of necrosis and calcification in the background of fine fibrovascular stroma. Other metastatic foci were detected in the right adrenal and pituitary gland.

Original Article

Grading System for Gastric Epithelial Proliferative Diseases Standardized Guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.: Hoguen Kim, So Young Jin, Ja June Jang, Woo Ho Kim, Sang Yong Song, Kyu Rae Kim, Eun Sil Yu, Hyung Sik Shin, Han Kyeom Kim, Jin Hee Sohn, Eun Kyung Hong, Youn Wha Kim, Jin Sook Jeong, Chang Jin Kim, Shin Eun Choi, In Suh Park, Chan Il Park, Yong Il Kim; Korean J Pathol. 1997;31(5):389-400.

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Abstract PDF: The assessment of epithelial changes in gastric mucosal biopsies has been one of the major problems caused by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, members of the Study Group for Pathology of Digestive Diseases reviewed microslides of 50 gastric lesions showing varying degrees of mucosal abnormality and reached the following consensus; 1) the proliferating gastric epithelium can be divided into hyperplastic and neoplastic; 2) the term "dysplasia" is reserved for the microscopic epithelial changes that are unequivocally neoplastic; 3) Biopsy specimens can be categorized as regenerative(negative for dysplasia), indefinite(questionable dysplasia), positive(positive for dysplasia) and overt carcinoma; 4) The positive category can be divided into two subgroups, high grade dysplasia and low grade dysplasia. Criteria for each grade are presented and discussed. We offer these guidelines for establishing the correct diagnosis of the gastric mucosal biopsy specimens and for prospective studies.

Case Report

Neuroendocrine Differentiation in Adrenal Cortical Tumor of Chidhood: A case report.: Sang Yong Song, Seung Sook Lee, Na Hye Myung, Je G Chi; Korean J Pathol. 1993;27(2):175-180.

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Abstract PDF: Although neuroendocrine differentiation is a characteristic feature of tumors of the adrenal medulla, cortical tumors may also rarely be differentiated into medullary element. Recently we experienced such a case of adrenal cortical tumor having features of both cortical and medullary tumor. The patient was an 11-year-old girl who was incidentally found to have a left adrenal mass. Laboratory results showed elevated serum cortisol, aldosterone, renin, and epinephrine with high excretion of urinary metanephrine. Urine vanillyl mandelic acid and 17-ketosteroid remained within normal limits. Histologic featuresof a 6 cm round yellowish tumor were ambiguous to decide the orgin of this neoplasm. Cortical element predominated in the tumor with minor areas of pheochromocytomatous feature. Immunohistochemically, the tumor cells were positive for vimentin, neuron specific enolase, and epithelial membrane antigen. Ultrastructural examination revealed scattered membrane bound dense core granules in the tumor cells of medullary differentiation, measuring 150~500 nm in average diameter. Cortical tumor element showed corresponding ultrastructural features. These results indicate that this is a case of adrenal cortical tumor with features of neuroendocrine differentiation.

Original Articles

Dedifferentiated Chordoma: Report of a case.: Sang Yong Song, Mi Kyung Kim, Yong Il Kim; Korean J Pathol. 1993;27(3):256-262.

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Abstract PDF: Dedifferentiated chordoma is a rare pathologic entity presenting an additional sarcomatous component in otherwise classical chordoma. It has been also emphasized that this neoplasm is classified as a distinct entity because of its different clinical settings and aggressive behavior. Dedifferentiation is a peculiar phenomenon but its histogenesis has remained controversial. A 50-yera-old man developed a huge tumor mass in the retrorectal, presacral area, featured with two histological components. The one was a typical chordoma accounted for approximately 60% of the mass and the other was made up of highly cellular, plemorphic, undifferentiated tumor cells, reminiscent partly to the cells of plemorphic malignant fibrous histiocytoma. Ultrastructural features and immunoreactivity against cytokeratin, S-100 protein and alpha-1-antichymotrypsin in both portions support that histologically different components of this neoplasm derive from the same origin. To our knowledge, this is the first case of dedifferentiated chordoma in Korea.

Nephroblastomatosis Associated with Wilms' Tumor.: Kyeong Cheon Jung, Sang Yong Song, Yeon Lim Suh, Je G Chi, Hwang Choi; Korean J Pathol. 1993;27(3):274-278.

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Abstract PDF: In contrast to the nodular renal blastema which is defined by nests of primitive metanephric cells after 36 weeks of gestation, the nephroblastomatosis is characterized by neoplastic proliferation of the primitive cells. This lesion is presumed to be closely related to the development of Wilms' tumor. We report a case of bilateral nephroblastomatosis associated with Wilms' tumor in a child. This 4 1/2 year-old girl was admitted because of a 10 cm-sized round mass in the right kidney, and smaller nodules in the left kidney and the lung. After three cycles of chemotherapy and subsequent disappearance of the nodules in the left kidney and lung, she underwent a right nephrectomy and a wedge resection of the left kidney. A round Wilms' tumor mass was seen in the lower pole of the right kidney. Remaining right renal cortex showed multiple, slightly depressed gray-white nodules associated with multiple samll cysts. They were comprised of multifocal subcapsular nests of primitive nephrogenic cells with focal tubular or glomerular differentiation. They resembled fetal renal tissue. In the left kidney, similar nests of primitive cells were also noted. These lesions were interpreted as multifocal perilobar type of nephroblastomatosis.

Case Reports

Iris Cyst: A case report.: Sang Yong Song, Je G Chi, Jin Hak Lee; Korean J Pathol. 1993;27(4):427-429.

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Abstract PDF: Cysts of the iris may be primary lesions of either epithelial or stromal in origin, or secondary lesions after trauma or surgery. The stromal cyst is usually of primary lesion, although it could be secondary as shown in our case. We report a case of recurrent iris cyst after trauma. The patient was an 8-year-old girl. She had a penetrating injury of the involved eye three years ago. She had a similar iris cyst removed two years before this surgery. Histologically, the cyst was lined by non-keratinizing stratified squamous epithelia and subjacent fibrovascular tissue. Islands of melanin-containing epithelial cells and acellular basophilic degenerating materials were also seen in the lesion. This case represents a stromal epithelial cyst that by history appears to be of post-traumatic etiology.

Primary Oxalosis: A case report.: Sang Yong Song, Je G Chi, Yong Choi, Sang Jun Kim; Korean J Pathol. 1993;27(5):509-513.

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Abstract PDF: Primary oxalosis is a rare genetic disorder caused by a deficiency of the peroxisomal enzyme alanine-glyoxylate aminotransferase(type I) and D-glyceric dehydrogenase(type II). It is characterized by the triad of radiopaque urolithiasis, nephrocalcinosis, and latered renal function. We report a case of primary oxalosis in a 10-year-old Korean girl. She presented with chronic renal failure at 9 years of age. Ultrasonographic examination revealed bilateral, multiple renal and ureteral stones. Removed stones were chemically analysed to be composed of calcium oxalate. She underwent renal transplantation after prolonged period of dialysis. Removed kidneys were firm and gritty. Cut sections showed numerous tiny yellow sandy stones and a large staghorn stone. Specimen X-ray also exhibited disseminated fine granular and often coalescent radiopaque materials throughout the cortex and medulla. Microscopically numerous varying-sized crystals were noted in the kidney in globular or rhomboid appearance. The crystals were semitranslucent and doubly refractile under the polarized light. Diffuse interstitial fibrosis and chronic inflammation as well as glomerular obsolescence were also noted. The oxalate deposit was diffuse and marked, and was thought to be intimately related to the parenchymal damage and fibrosis.

Sex Cord Tumor with Annular Tubules and Serous Surface Papillary Carcinoma of the Ovary: A case report.: Dae su Kim, Sang Yong Song, Geung hwan Ahn; Korean J Pathol. 1999;33(8):627-630.

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Abstract PDF: Sex cord tumor with annular tubules (SCTAT) is a rare ovarian neoplasm which usually occurs in two forms. In patients associated with Peutz-Jeghers syndrome, the tumors are usually small, bilateral or multifocal, and show benign clinical course. However, tumors from patients without the syndrome are often large, usually unilateral, and rarely show malignant behavior. Serous surface papillary carcinoma (SSPC) is an aggressive neoplasm which involves peritoneal linings, including ovarian surface. Recently, we encountered a case of an unusual combination of SCTAT and SSPC in the ovary of a 55-year-old Korean woman presented with abdominal distention for one year. Systemic review and physical examination were within normal limit, except for abdominal discomfort and distention. There was no stigmata of Peutz-Jeghers syndrome in all diagnostic examinations, including gastroscopy and colonoscopy. Pelvic computed tomography showed adnexal mass with multiple peritoneal nodules. Exploration revealed uterine and ovarian surfaces covered with multiple, yellow-white papillary nodules. However, the sizes of both ovaries were within normal limit. Typical serous papillary carcinomas were identified in nodules from peritoneum and ovarian surfaces. Well-circumscribed columnar epithelial cell nests composed of ring-shaped tubules encircling hyalinized basement membrane-like materials were found in the ovary away from serous surface papillary carcinoma.

Original Article

Expression of p27kip1, Cyclin D1 and p53 Protein in Ductal Carcinoma In Situ of the Breast.: Young Lyun Oh, Sang Yong Song, Jong Sun Choi, Young Hyeh Ko, Hwoe J Ree, Geung Hwan Ahn; Korean J Pathol. 1999;33(9):709-716.

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Abstract PDF: p27(kip1) protein, a cyclin-dependent kinase inhibitor, has been reported to be a powerful negative prognostic marker in patients with breast carcinoma. However, to this day, studies on p27(kip1) protein expression in ductal carcinoma in situ (DCIS) have been extremely limited. We studied the immunohistochemical expression of p27(kip1) protein in 49 cases of the DCIS and compared the findings to the clinicopathologic parameters, cyclin D1, p53 and estrogen receptor (ER). Positive nuclear staining of p27(kip1) protein was identified in 23 (46.9%) cases. The p27(kip1) protein expression correlated positively with the cyclin D1 immunopositivity (p<0.005) and ER expression (p<0.005). No significant associations were seen in the p27(kip1) protein expression and clinicopathologic parameters. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with ER expression (p<0.001). The p53 protein expression was identified in 30.6% and seemed to be correlated inversely with ER expression (p=0.06). The DCISs with high grade nuclei were more likely to be p53-positive (p<0.05). Our data suggest that the expression of p27(kip1) protein as well as cyclin D1 and p53 protein may be influenced by the ER status in DCIS. The significantly positive correlation of p27(kip1) protein and cyclin D1 expression (p<0.005) supports the theory that the balance of the two opposing signals is important in determining the cell proliferation in breast cancers. Therefore, a comprehensive understanding of loop reaction of p27(kip1)-cyclin D1-ER may be necessary for the treatment of DCIS.

Case Report

Malignant Melanoma Arising in Giant Congenital Melanocytic Nevus: A case report.: Jung Sun Kim, Sang Yong Song, Kye Yong Song, Je G Chi; Korean J Pathol. 1993;27(6):650-655.

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Abstract PDF: Giant congenital melanocytic nevus is found in 0.1% of live born infants. If present, this lesion has a 6.3% chance to develop malignant melanoma. We report such a case in a 22-year-old woman who had multiple pigmented skin lesions since birth. Rapidly growing masses were recently detected in the 19 cm-sized occipital pigmented lesion. Removed scalp lesion revealed yellowish white lobulated soft nodules in the background of pigmented nevus. Microscopically, the nodules consisted of epithelioid cells with prominent nucleoli, and pleomorphic cells including signetring cells. These cells seldom contained melanin pigment. There were metastatic aggregates of tumor cells in the cervical lymph node, which were reminiscent of germinal centers of lymph nodes. S-100 protein immunostaining was helpful to distinguish them. Incidentally, focally scattered pigmented spindle cells were seen in the capsule of a lymph node

Original Article

Gastrointestinal Cytomegalovirus Infection: A clinicopathologic analysis of 8 cases.: Yun Kyung Kang, Sang Yong Song, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1994;28(1):22-29.

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Abstract PDF: We analysed 8 cases of gastrointestinal cytomegalovirus(CMV) infection including one autopsy, three surgically resected and four endoscopic biopsy cases. Involved sites were colon in four,stomach in three and small intestine in one. Three of them were associated with immu-nosuppressed condition but others had no clinical evidence of immune deficiency. Multiple aphthous mucosal ulceration was a common presentation, but one revealed a mucosal ulcer with segmental narrowing and thickening of wall. Microscopically, six showed cytomegalic inclusions in endothelial cells and fibroblasts, one in mucosal epithelial cells and the remaining one in both endothelial cells and mucosal epithelial cells. Immunohistochemical staining using monoclonal antibody against CMV confirmed postive result in seven cases. Serum IgM anti-CMV antibody was elevated in one case. We conclude that gastrointestinal CMV infection is currently not a rare condition and frequently associated with non-immunosuppressed condition, and thus a thorough histologic examination is required especially in the gastrointestinal ulcerative lesion. Once cytomegalic inclusion is suspected, immunohistochemical identification of CMV seems essential for specific diagnosis.

Case Report

Teratoid Wilms' Tumor: A Case Report.: Seong Rim Kim, Sang Yong Song, Yeon Lim Suh, Ki Woong Sung, Suk Koo Lee; Korean J Pathol. 2002;36(3):187-190.

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Abstract PDF: Teratoid Wilms' tumor is a rare renal tumor. Fourteen cases have been reported. A 14-month-old girl was presented to us. She had a right renal mass which was diagnosed as a Wilms' tumor in another hospital. She had been treated with chemotherapy but failed to respond to it. The nephrectomy specimen revealed an encapsulated mass of which the cut surface was solid, firm, gray to yellow tan. Microscopically, the stromal elements were predominant, especially comparing with few blastemal element, but the degree of heterologous differentiation was sufficient to warrant the diagnosis of teratoid Wilms' tumor.

Original Articles

Carcinoid Tumors of the Gastrointestinal Tract: Analysis of 36 Cases.: Kyeong Cheon Jung, Hee Sung Kim, Sang Yong Song, Ghee Young Choe, Yong Il Kim; Korean J Pathol. 1996;30(5):396-407.

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Abstract PDF: We reviewed a total of 36 cases of gastrointestinal carcinoid tumors during a period of ten and a half years at Seoul National University Hospital, looking at their histologic and ultrastructural features, as well as immunohistochemical results, then we correlated these with location. The primary sites of carcinoid tumors were rectum(39%), stomach(25%), appendix(22%), small intestine(8%) and colon(6%), in order of frequency. The predominant histologic types by organ were mixed and solid(A) types in all location, the solid type(type A) in the stomach, and tubular type(type C) in the rectum. Six out of 8 cases of appendiceal carcinoid were type A and the other two cases were mucinous carcinoid. Tubular adenoma or adenocarcinoma was associated with 36% of the rectal carcinoids, with one case of carcinoid in the small intestine, and one(11%) of the gastric carcinoids was found near an adenocarcinoma. Metastasis was found in one case of ileal carcinoid(100%), one case of cecal carcinoid, 3 of gastric carcinoid(33%) and 2 of rectal carcinoid(14%). Primary tumor size ranged from 1 to 7 cm. Tumor necrosis and endolymphatic tumor emboli were found in 57% and 43% of the metastatic carcinoids, respectively. PCNA index showed a borderline significant difference between metastatic and nonmetastatic groups(P value=0.063). The low prevalence of appendiceal carcinoid and the relatively high prevalence of gastric-rectal carcinoid may reflect a low chance of incidental appendectomy and frequent detection of gastrointestinal endoscopy.

Quality Assurance of Frozen Section Diagnosis An analysis of 5,273 consecutive cases .: Sang Yong Song, Geunghwan Ahn; Korean J Pathol. 1999;33(12):1182-1190.

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Abstract PDF: Quality assurance analysis of frozen section diagnosis is very important for the pathologists to improve the diagnostic ability and the quality of medical service. We analysed 5,273 consecutive cases of frozen section diagnosis which were done in Samsung Medical Center during 10 months from June 1, 1998 to March 31. 1999 with special reference to the discordance between frozen section diagnosis and final diagnosis. The concordance rate was 97.65%, discordance rate 1.34%, and deferred diagnosis (type 1) rate 1.01%. Category A (discordant diagnosis without any effect on the patients) was 53 cases (1.01%), category B (discordant diagnosis with minimal but no serious effect on the patients) was 10 cases (0.19%), and category C (discordant diagnosis with serious effect on the patients) was 8 cases (0.15%). Type 2 (discordant diagnosis by extra-pathologist problem) was 22 cases (0.42%) and type 3 (discordant diagnosis by pathologist problem) was 49 cases (0.93%). The most frequent causes of type 2 and 3 discordant diagnosis were presence of new lesions on deeper sections and the misinterpretation of lesions. Discordant diagnosis was noted in lymphoreticular system, central nervous system, thyroid, gastric resection margin, breast, female genital organs, intestine, hepatobiliary system, upper aerodigestive tract, urinary tract, lung, and soft tissue in descending order of frequency. Frozen section diagnosis was deferred in central nervous system, lymphoreticular system, gastric resection margin, female genital organs, thyroid, intestine, upper aerodigestive tract, lung, and soft tissue in descending order of frequency. The most important cause of discordant diagnosis was a misinterpretation of the lesions. Based on our results, a continuous and careful follow-up of quality assurance analysis of frozen section diagnosis and a share of experience of problematic cases are mandatory for the pathologists to improve the quality of medical services.

Case Report

Primitive Neuroectodermal Tumor of the Kidney: A case report .: Sang Yong Song, Eun Youn Cho, Jung Won Lee, Jai Hyang Go, Mi Kyung Kim, Dae Shick Kim, Young Hyeh Ko; Korean J Pathol. 1998;32(3):231-236.

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Abstract PDF: Peripheral primitive neuroectodermal tumor (pPNET), a rare, highly aggressive neoplasm of indetermined histogenesis, occurs typically in the soft tissues of the chest wall and the paraspinal region. Comprehensive diagnostic studies including histological, ultrastructural, immunohistochemical and molecular analyses have been stressed to diagnose this entity. We report a case of primary renal PNET which was incidentally found in a 59-year-old man who presented with generalized weakness for 4 months. He was diagnosed as a non-insulin dependent diabetes mellitus 15 years ago and has been made well by oral therapy. An ill-defined mass, measuring 3.5 3 cm, located in the left kidney and perirenal fat, was incidentally found by ultrasonogram during a renal diabetic examination. The mass was resected because of the unresponsiveness against one-year chemotherapy and radiation therapy. Grossly, a homogeneously solid, gray-white mass, measuring 2.8 1.8 cm, was noted in the mid portion of renal cortex. The mass showed severe adhesion to the perirenal fatty tissue. Microscopically, tumor cells were rather uniform, small round with scanty cytoplasm and often showed rosette formation. Ultrastructurally, they showed membrane-bound dense core granules, measuring 125~150 nm, intercellular junctions and microvillous cytoplasmic projections. The tumor cells were uniformly immunoreactive for neuron-specific enolase and were focally immunoreactive for CD99 (013), chromogranin, synaptophysin and cytokeratin. They were not reactive for S-100 protein, vimentin, Leu-7, leukocyte common antigen, desmin and smooth muscle actin. To our knowledge, this is the smallest renal PNET in literature.

Original Articles

Cyclin D1 Expression in 101 Cases of Breast Carcinoma.: Duck Hwan Kim, Eun Sook Nam, Hyung Sik Shin, Jin Woo Ryu, Jai Hyang Go, Young Lyun Oh, Sang Yong Song, Dae Shick Kim, Min Chul Lee; Korean J Pathol. 1998;32(4):266-272.

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Abstract PDF: Cyclin D1, a cell cycle regulator essential for G1 phase progression, is a candidate proto-oncogene implicated in pathogenesis of several human carcinomas including breast carcinoma. We studied the cyclin D1 expression in 101 cases of primary breast carcinoma tissues. The overexpression of cyclin D1 was immunohistochemically demonstrated in 34 (37.8%) of 90 cases of invasive breast carcinoma. Positive cyclin D1 staining was seen in 32 of 79 invasive ductal carcinomas, and 2 of 3 mucinous carcinomas. All 5 medullary carcinomas, 2 invasive lobular carcinomas, and 1 metaplastic carcinoma were negative. Cyclin D1 overexpression was observed in 9 of 11 ductal carcinoma in situ (DCIS). Normal epithelial components, either ductal or lobular, were not immunoreactive for cyclin D1. No significant correlations were observed between cyclin D1 immunoreactivity and other parameters including tumor size, clinical stage, nuclear or histologic grades, lymphatic or angioinvasion, lymph node metastasis, and immunohistochemical status of progesterone receptor, p53 and c-erbB-2. The overexpression of cyclin D1 was positively correlated with estrogen receptor status (p=0.025). Based on our results, the cyclin D1 protein aberration may play a role in tumorigenesis of breast carcinoma, but does not seem to have prognostic value in invasive breast carcinoma without hormonal treatment.

Small Hepatocellular Carcinoma: Pathologic Features of 39 Cases A Comparison with Large Hepatocellular Carcinoma.: Yong Il Kim, Geon Kook Lee, Sang Yong Song; Korean J Pathol. 1992;26(2):103-116.

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Abstract PDF: With advance of diagnostic imaging technics, the detection rate of small hepatocellular carcinoma (HCC) has become much increased, but the questions whether the growth pattern and histologic nature of the HCC keep maintain the original gross and microscopic features with its advancement of tumor size remain still unclear. We reviewed 39 surgically resected hepatocellular carcinomas(HCCs) with a tumor size less than or equal to 3 cm in diameter(s-HCC), and their gross and microscopic features were compared with the HCCs bigger than 3 cm (i-HCC, 199 cases). Single nodular type(SN) was the most common gross type(60%) in s-HCCs, and was followed by single nodular type with perinodular extension(SNPE; 15.4%), multinodular-discrete type(10.3%) and multinodular-confluent type(5.1%). These figures contrasted to SNPE(42.2%) and SN(20.6%) in the i-HCCs. Of the 39 s-HCCs, 25 cases(64.1%) were encapsulated, and 14 cases(36%) demonstrated intratumoral fibrous septations, being contrasted to the i-HCCs in which fibrous septa formation was mord prominent but complete capsule formation was found only in 40.2% of the larger ones. Microscopically, the trabecular type was the most frequent one(53.9%), and increased with their size while the compact type transformed into trabecular one. Thirty three cases(84.6%) were associated with macronodular cirrhosis. Seropositivity for HBsAg was found in 26 cases(66.6%), and high serum alpha-fetoprotein level over 500 IU/L was found in 15 s-HCC cases(38.4%), while 53.3% in i-HCC. The above results suggest that HCCs change their pathologic features by increase of their size, and a comparison of the details with regard to the possible mechanisms involved is discussed.

Case Report

Multiple Fibromuscular Dysplasia of Arteries with Aneurysm Formation: A case report.: Soo Min Kang, Sang Yong Song, Yong Il Kim, Sung Kwon Kim, Jung Sang Lee, Sang Joon Kim; Korean J Pathol. 1992;26(3):288-292.

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Abstract PDF: Multiple involvement of arterial fibromuscular dysplasia is unusal and such a case is quite limited in the literature. We present a case of multiple arterial fibromuscular dysplasia with aneurysm formation in a 38-year-old non-hypertensive man. Angiographic study showed multiple aneurysmal dilatations of the right renal, superior mesenteric, celiac axis, and left colic arteries. The resected right kidney demonstrated an aneurysm of the main renal artery and extensive infarction in the midportion of the renal parenchyma. The segmentally resected superior mesenteric artery disclosed a similar nature of aneurysm occluded by recent thrombi. Microscopically, all the resected arterial walls showed both intimal and medial fibroplasia together with periadventitial fibrosis resulting in marked narrowing of the lumen and subsequent thrombus formation.

Original Articles

Primary Central Nervous System Lymphomas; A Clinicopathologic Study of 18 Cases.: Yu Kyung Jeong, Young Hyeh Ko, Dong Kyu Na, Yeon Lim Suh, Sang Yong Song, Dae Shik Kim, Mi Kyung Kim, Howe Jung Ree; Korean J Pathol. 1998;32(9):670-679.

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Abstract: The incidence of a primary central nervous system (CNS) lymphoma in western countries is about 1% of all the intracranial tumors and has increased 2.2% over the last decade. A similar pattern of increased frequency is observed in Korea. Although most CNS lymphomas in western countries are high grade tumors carrying poor prognosis, the clinicopathologic features of the Korean CNS lymphoma have not been well studied. We report clinicopathological features of 18 cases of histologically proven primary brain lymphoma. The mean age of the patients was 50 years and there was no sex difference. The clinical and radiological characteristics included multiple site of occurrence, infrequent extracranial spread, and frequent seeding via cerebrospinal fluid. No patients were immune-compromised host. Of 18 cases, 15 cases were of B-lineage and 2 cases were of T-lineage. According to REAL classification, there were 12 cases of diffuse large B cell lymphoma, two cases of B cell lymphomas of small lymphoid cell, and two cases of peripheral T cell lymphoma, unspecified. The remaining subtypes were not subclassified because of inadequate material. Pleomorphic cytologic features and necrosis of varying extent were frequent in the cases of diffuse large B-cell lymphoma. These results suggest that overall clinicopathologic features of primary malignant lymphomas of the central nervous system in Korea are similar to those of western countries.

Liver Cell Dysplasia: Analysis of 141 cases with reference to histopathologic Characterization and proliferative activity.: Sang Yong Song, Yong Il Kim; Korean J Pathol. 1992;26(4):338-347.

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Abstract PDF: Liver cell dysplasia of Anthony(LCD) is a common association in hepatocellular carcinoma(HCC)-bearing liver and has been regarded as a premalignant condition with strong linkage to hepatitis B virus infection and cirrhosis. A total of 189 surgically resected livers [HCC(168 cases), cholangiocarcinoma(3 cases), metastatic carcinoma(3 cases), and non-neoplastic lesions(15 cases)] were reviewed to elucidate the nature of LCD by means of light microscopic examination, in situ hybridization method for HBV DNA and expression of proliferatin cell nuclear antigen(PCNA) using immunohistochemical technique. LCD was present in 141 cases(74.6%), and its prevalence rate was independently significant in HCCs with or without cirrhosis than other groups. There was no difference in mean age, although LCD-positive group was younger than its negative counterpart. Association rate of LCD in HCC-cirrhosis group was statistically significant than the non-cirrhotic group, and higher histological grading of LCD was correlated well with wider distribution pattern and clustering. Seropositivity of HBsAg was not correlated with presence of LCD or with histological grading. In situ hybridization techique using HBV DNA probe demonstrated fine granular stainable particles even in LCD cells. Immunohistochemical study for PCNA revealed that the proliferative activity of LCD was lower than that of the cirrhotic cell. With the above results it is concluded that LCD reflects neither a regenerating condition nor a premalignant lesion but suggest a reactive change.

Elastofibroma.: Sang Yong Song, In Ae Park, Yong Il Kim; Korean J Pathol. 1992;26(4):420-422.

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Abstract PDF: Elastofibroma is a rare benign tumorous growth presenting as a slowly growing ill-defined mass of fibroblastic tissue occurring in elderly persons and arising mainly form the connective tissue between the lower portion of the scapula and the chest wall. Its pathogenesis is not well established but it may be the result of nonneoplastic reactive hyperplasia taking place with constitutional predisposition in the background. A case of elastofibroma occurring in the subscapular area of a 65-year-old female cook is presented. The mass, 6x5x3 cm in maximum dimensions, was poorly circumscribed, solid, hard, pale fleshy and pray-white fibrous tumor. Microscopically, it was composed of numerous small globular and linear elastic fibers embedded in collagenous matrix. To our knowledge, it is the first case of elastofibroma in Korea.

Significance of the Expression of Cyclin-Dependent Kinase Inhibitor, p27Kip1, in Human Breast Cancer.: Sang Yong Song, Duck Hwan Kim, Yeon Lim Suh, Young Hyeh Ko, Dae Shick Kim, Seok Jin Nam, Jung Hyun Yang; Korean J Pathol. 1998;32(12):1081-1088.

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Abstract: p27Kip1 protein, a negative cell cycle regulator in G1 progression, has been reported to be related with human cancers including colon, breast and non-small cell lung carcinomas. To elucidate a possible prognostic indicator, we studied 49 cases of human breast carcinoma for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of the breast cancer. p27Kip1 protein was intensely stained in nuclei of carcinoma cells in 26 cases (53.1%). The expression rate of p27Kip1 protein was significantly higher in higher nuclear grade (p<0.05), lower histologic grade (p<0.01), lower N classification (p<0.001) and lower clinical stage (p<0.05) than in lower nuclear grade, higher histologic grade, higher N classification and higher clinical stage, respectively. p27Kip1 protein expression was significantly correlated with progesterone receptor status (p<0.05) or cyclin D expression (p<0.05). No statistical correlations were found between expression of p27Kip1 protein and other parameters including tumor size, estrogen receptor status, p53 overexpression and c-erbB-2 expression. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of breast carcinoma and might contribute in predicting breast cancer patient's survival.

Case Reports

Cavernous Hemangioma of Lymph node: A case report with the review of literature.: Seong Nam Kim, Sang Yong Song, Yong Il Kim; Korean J Pathol. 1992;26(5):496-499.

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Abstract PDF: Primary hemangioma of the lymph node is an extremely rare vascular neoplasm, and only four cases on the subject have been reported in the literature. We describe a case of cavernous hemangioma in an axillary lymph node that was incidentally found in 70-year-old woman who underwent a modified radical mastectomy for infiltrating duct carcinoma of the left breast. Brief review of the literature regarding vasoformative lesions occupying lymph node is made with special regard to differential diagnosis from reactive-proliferative processes and other true neoplasms.

Primary Necrotizing Granulomatous Vasculitis of the Stomach.: Myeong Cherl Kook, Sang Yong Song, Yong Il Kim, In Sung Song, Keun Wook Lee; Korean J Pathol. 1997;31(1):68-74.

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Abstract PDF: A 55-year-old woman suffered from upper abdominal pain for two months and remained refractile against the anti-ulcer regimen. The palliative gastrectomy specimen revealed multiple shallow ulcerations on the thickened mucosal folds mainly in the antrum and body along the greater curvature where multiple, whitish nodules were found in the submucosa. Microscopically, individual submucosal nodules clearly corresponded to the necrotizing granulomatous vasculitis which were featured with diffuse fibrinoid necrosis of arterial walls accompanying granuloma formation and heavy infiltration of neutrophils, eosinophils, histiocytes and giant cells. Similar vasculitic lesions involved venules and arterioles. There were scattered vasculitic changes in the liver biopsy specimens and omentum. There were no clinical presentations or serological support of systemic involvement including systemic lupus erythematosus, Henoch-Schoenlein purpura, cryoglobulinemia or Churg-Strauss granulomatous vasculitis. We conclude that this is a hitherto undescribed primary necrotizing granulomatous vasculitis predominantly involving the stomach.

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