Journal of Pathology and Translational Medicine

Original Article

Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy: Hyeon Jeong Oh, Jung Ho Kim, Jeong Mo Bae, Hyun Jung Kim, Nam-Yun Cho, Gyeong Hoon Kang; J Pathol Transl Med. 2019;53(1):40-49. Published online December 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.29

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Background
This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.
Methods
F. nucleatumDNA was quantitatively measured in a total of 593 CRC tissues retrospectively collectedfrom surgically resected specimens of stage III or high-risk stage II CRC patients who had receivedcurative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative.
Results
No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses accordingto tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal,ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariateanalysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoidcolon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore,the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not ina MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor locationand MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treatedwith adjuvant chemotherapy.
Conclusions
Intratumoral F. nucleatum load is a potential prognosticfactor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treatedwith oxaliplatin-based adjuvant chemotherapy.

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Case Reports

Cystic Nephroma: A Case Report and Comparing Literature Review with Mixed Epithelial and Stromal Tumor of Kidney.: Hyun Jung Kim, Choong Hee Noh, Giyoung Kwon, Eunah Shin, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2011;45:S25-S28.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S25

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Abstract PDF: Cystic nephroma (CN) is a benign cystic neoplasm composed of mixed epithelial and stromal elements. Less than 200 cases have been reported. We had a patient, a 41-year-old woman, who had a huge typical CN. The patient was admitted for a right renal mass that was found incidentally. On laparaoscopic right nephrectomy, there was an encapsulated 7 cm multilocular cystic mass at the upper pole. Microscopically, the cystic wall was lined by a single layer of low cuboidal or hobnail epithelium without a solid area. The thin septa were composed of bland, ovarian type spindle cells. The main differential diagnoses were mixed epithelial and stromal tumor (MEST), low grade multilocular renal cell carcinoma, and tubulocystic carcinoma. The results of immunohistochemical staining were cytokeratin 7/19(+/+) and CD10(-) in lining epithelium, estrogen receptor/progesterone receptor(+/+) in stromal cells. After surgery, she was free of recurrence for 10 months. We report this rare case and compare it with other cystic renal tumors, especially MEST.

Bronchial Brushing Cytologic Finding of Primary Pulmonary Adenoid Cystic Carcinoma Misinterpretated as Small Cell Carcinoma: A Case Report with Literature Review.: Hyun Jung Kim, Sangbong Choi, Jieun Kwon, Jeong Yeon Kim, Kyeongmee Park; Korean J Pathol. 2011;45(4):441-444.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.441

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Abstract PDF

An adenoid cystic carcinoma is a very rare primary pulmonary neoplasm. Bronchial washing and brushing cytological findings of pulmonary adenoid cystic carcinoma have rarely been described. Here, we report the bronchial brushing cytological findings of an adenoid cystic carcinoma, finally diagnosed in a 71-year-old female patient. The low-power view showed moderate cellularity and cohesive clusters of small to medium-sized cells. The high-power view revealed distinct nuclear moldings, a coarse chromatin pattern, and inconspicuous nucleoli, which was favorable to a diagnosis of small cell carcinoma. However, apoptotic bodies, nuclear debris, and mitoses were not seen frequently. The bronchial biopsy showed solid, trabecular, and cribriform patterns in small cells. Periodic acid Schiff staining disclosed globular basement membrane-like materials, and the immunohistochemical staining revealed the presence of myoepithelial cell components, strongly suggestive of a salivary gland type tumor, compatible with an adenoid cystic carcinoma. In this report, we describe the exfoliative cytological features of a pulmonary adenoid cystic carcinoma with emphasis on some diagnostic pitfalls.

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Joanna K.M. Ng, Ka Pang Chan, Gary M. Tse, Joshua J.X. Li
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Original Articles

WHO Classification of Malignant Lymphomas in Korea: Report of the Third Nationwide Study.: Jin Man Kim, Young Hyeh Ko, Seung Sook Lee, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim; Korean J Pathol. 2011;45(3):254-260.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.254

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Abstract PDF

BACKGROUND
The aim of study was to determine the relative frequency of malignant lymphoma according to World Health Organization (WHO) classification in Korea.
METHODS
A total of 3,998 cases diagnosed at 31 institutes between 2005 and 2006 were enrolled. Information including age, gender, pathologic diagnosis, site of involvement and immunophenotypes were obtained.
RESULTS
The relative frequency of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) was 95.4% and 4.6%, respectively. B-cell lymphomas accounted for 77.6% of all NHL, while T/natural killer (T/NK)-cell lymphomas accounted for 22.4%. The most frequent subtypes of NHL were diffuse large B-cell lymphoma (42.7%), extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (19.0%), NK/T-cell lymphoma (6.3%) and peripheral T-cell lymphoma (PTCL), unspecified (6.3%), in decreasing order. The relative frequency of HL was nodular sclerosis (47.4%), mixed cellularity (30.6%), and nodular lymphocyte predominant (12.1%) subtypes. Compared with a previous study in 1998, increase in gastric MZBCL and nodular sclerosis HL, and slight decrease of follicular lymphoma, PTCL, and NK/T-cell lymphoma were observed.
CONCLUSIONS
Korea had lower rates of HL and follicular lymphoma, and higher rates of extranodal NHL, extranodal MZBCL, and NK/T-cell lymphoma of nasal type compared with Western countries. Changes in the relative frequency of lymphoma subtypes are likely ascribed to refined diagnostic criteria and a change in national health care policy.

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Korean Pediatric/Adolescent Lymphoma: Incidence and Pathologic Characteristics.: Seung Sook Lee, Jin Man Kim, Young Hyeh Ko, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim; Korean J Pathol. 2010;44(2):117-124.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.117

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Abstract PDF

BACKGROUND
The Hematopathology Study Group of the Korean Society of Pathologists conducted a nation-wide retrospective analysis of Korean pediatric lymphoma, to provide pathologic data on pediatric/adolescent lymphoma subtypes and features.
METHODS
All lymphoma cases of all age groups were collected during a recent 2 year-period (2005-2006) from 32 institutes in Korea. Among 3,686 lymphoma patients, 142 who were age 18 or less were classified according to the World Health Organization (WHO) classification.
RESULTS
Among 142 pediatric/adolescent lymphoma patients, Hodgkin lymphoma accounted for 21 (14.8%) and non-Hodgkin lymphoma (NHL) for 121 (85.2%). Hodgkin lymphoma appears to be more common in the pediatric/adolescent age group than in the all-ages group (14.8% vs 4.4%). T- and natural killer cell-NHL was more common in the pediatric/adolescent age group than in the all ages group (46.3% vs 22%). The majority of Korean pediatric/adolescent NHL cases was composed of Burkitt lymphoma, T- or B-lymphoblastic lymphoma, anaplastic large-cell lymphoma, and diffuse large B-cell lymphoma. For lymphoma patients under the age of 6 years, most had B-lymphoblastic or Burkitt lymphoma, which commonly presented at extranodal sites.
CONCLUSIONS
The distribution of lymphoma subtypes in the pediatric/adolescent age group is quite different from the distribution of adults, but it was quite similar to distribution in Western countries.

Citations

Citations to this article as recorded by

A Case of Nasal Type Extranodal NK/T Cell Lymphoma Incidentally Detected in a Child
Ha Jin Oh, Sang Hyun Park, Hae In Jang, Dong Hoon Lee, Yoo Duk Choi, Hee Jo Baek, Hoon Kook
Clinical Pediatric Hematology-Oncology.2015; 22(1): 76. CrossRef

Case Reports

Adenoid Basal Carcinoma Associated with Invasive Squamous Cell Carcinoma of Uterine Cervix: A case report.: Hyun Jung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 1996;30(8):739-741.

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Abstract PDF: Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions. Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.

Fine Needle Aspiration Cytology of Salivary Duct Carcinoma: A Case Report.: A Young Park, Hyun Jung Kim, Dong Won Kim, Dong Wha Lee; Korean J Cytopathol. 1997;8(2):143-149.

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Abstract PDF: PURPOSE: To investigate renal toxicity of high-dose intravenous immunoglobulin(IVIG) in children with Kawasaki disease and idiopathic thrombocytopenic purpura. METHODS: 23 children with Kawasaki disease and 7 children with idiopathic thrombocytopenic purpura who were treated with high-dose IVIG(2 g/kg) were evaluated for the change of urine output, blood urea nitrogen(BUN), serum creatinine(Scr), creatinine clearance(Ccr), tubular reabsorption of phosphorus(TRP), fractional excretion of sodium(FENa), 24hour urine b2-microg1obuin/creatinine(b2MG/cr) ratio and urine microalbumin/creatinine(MA/cr) ratio at post-IVIG 1 and 3 day. RESULTS: There was no significant change of urine output, BUN, Scr, Ccr, TRP, 24hour urine b2MG/cr and MA/cr ratio after high-dose IVIG treatment. Transient increase of FENa at post-IVIG 1 day was the only significant change.
CONCLUSION
There was no significant renal toxicity of high-dose IVIG in children with Kawasaki disease and idiopathic thrombocytopenic purpura who had normal renal function.

Original Article

Fine Needle Aspiration Cytology of Matrix Producing Carcinoma of the Breast.: Hyun Jung Kim, Ayoung Park, Dong Won Kim, Dong Wha Lee, Kui Hyang Kwon; Korean J Cytopathol. 1997;8(2):174-178.

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Abstract PDF: Matrix producing carcinoma of the breast is a variant of heterologous metaplastic carcinoma which is defined as "overt carcinoma with direct transition to a cartilagenous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic cells". This tumor is very rare, occuring in less than 0.2% of total breast carcinoma, but the prognosis is better than other metaplastic carcinoma. We experienced a case of fine needle aspiration(FNA) cytologic finding of matrix producing carcinoma of the breast. A 75-year old woman, who presented a right huge breast mass(9x8cm) during 10months, was examined. Mammography reveals right lateral mass with even density without calcification. Breast ultrasonography shows multifocal hypoechogenic cystic change in the huge mass, suggesting resolving hematoma or carcinoma or sarcoma with necrosis. On cytologic finding of FNA, myxoid matrix was the dominant feature and the rest of the material was composed of scanty isolated atypical cells with large irregular nuclei. The histologic finding was moderately differentiated adenocarcinoma with abundant cartilagenous matrix and focal squamous metaplasia.

Case Report

Fine Needle Aspiration Cytology of Metastatic Alveolar Rhabdomyosarcoma Misinterpreted as Carcinoma: A Case Report.: Hyun Jung Kim, Sung Jik Lim, Kyeongmee Park; Korean J Cytopathol. 2005;16(1):52-56.

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Abstract PDF: Fine-needle aspiration cytology(FNAC) has been used extensively in the diagnosis of metastatic malignancies. However, metastatic soft tissue sarcomas are often overlooked, primarily due to the low frequency with which they occur. Here, we report a rare case of metastatic rhabdomyosarcoma in both cervical lymph nodes, which was detected by FNAC. A 45-year-old woman presented with anosmia, postnasal drip, and sneezing, symptoms which had persisted for 1 month. The patient was found to have a tumorous lesion at the upper portion of the mid-turbinate, with multiple enlarged cervical lymph nodes, and this lesion was examined closely at our facility. FNA cytology smears obtained from both cervical lymph nodes revealed a high degree of cellularity, and displayed cohesive clusters with gland-like spaces, as well as single isolated cells with abundant karyorrhectic debris. The tumor cells exhibited round to oval nuclei containing fine chromatin, occasional small nucleoli, and scanty cytoplasm, or a total lack of cytoplasm. Some of the tumor cells were arranged in multinucleated forms and abundant dense eosinophilic cytoplasms, reminiscent of a rhabdomyoblast. The histological findings of the lymph nodes revealed an outstanding sinusoidal infiltration and a prominent alveolar growth pattern, interspersed with occasional typical rhabdomyoblasts. The immunohistochemical results [desmin(+), myoglobin(+), myogenin (+), pan CK(-), synaptophysin(-), neuron specific enolase(-)] supported a confirmative diagnosis of alveolar rhabdomyosarcoma. Alveolar rhabdomyosarcoma is a representative sarcoma, which typically manifests with nodal metastasis and carcinoma-like clustering. The cytopathologist should remain alert upon encountering unusual morphology, so that the possibility of this condition, although somewhat remote, should not be dismissed or overlooked.

Original Article

DNA Copy Number Changes in Thyroid Medullary Carcinomas Determined by Comparative Genomic Hybridization.: Hyun Jung Kim, Kowan Ja Jee, Young Khee Shong, Suck Joon Hong, Gyungyub Gong; Korean J Pathol. 2008;42(1):27-32.

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Abstract PDF: BACKGROUND
A point mutation in the RET proto-oncogene, in medullary thyroid carcinoma (MTC) is well known, but no other genetic causes of MTC have been found. This study was performed to identify the most common DNA copy number changes in MTC by comparative genomic hybridization (CGH).
METHODS
Twenty-nine surgically resected MTC specimens were retrospectively selected from patients operated on between 1996 and 2004 at the Asan Medical Center. A review of the clinical data and pathological findings was performed. Congored staining and immunohistochemical stains (calcitonin, chromogranin A and CEA) were processed by tissue microarray. CGH analysis was performed.
RESULTS
The Congo-red stain was positive in only 12 cases. The immunohistochemical results were positive in 29 cases for chromogranin A, 26 cases for CEA and 25 cases for calcitonin. DNA copy number changes were found in 23 cases (79.3%). The most frequent change was a gain of 19q (65.5%); less frequent changes were gain of 22 (55.2%), 19p (51.7%), 16p (27.58%), 17q (17.24%), and loss of 4q (27.6%) and 3p (17.24%).
CONCLUSIONS
DNA copy number changes of MTC were more common (79.3%) than reported in previous studies. The most frequent changes were gains in 19q, 22 and 19p.

Case Reports

Ki-1 Positive Extranodal NK/T Cell Lymphoma, Nasal Type, Mistaken as Dermatomyositis: A Case Report and Literature Review.: Hyun Jung Kim, Eunah Shin, Jung Yeon Kim, Kyeongmee Park, Young Jin Yoo, Seung Sook Lee; Korean J Pathol. 2007;41(4):278-283.

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Abstract PDF: We report a case of a 38-year-old male with extranodal NK/T-cell lymphoma, nasal type, showing unusual clinical and pathological features. The patient was admitted for soft tissue swelling and tenderness in both legs. The patient had been treated intermittently 8 months prior for repeated muco-cutaneous ulcers. A muscle biopsy showed medium-sized atypical lymphoid cells with bizarre nuclei and plump cytoplasm, infiltrating to the skeletal muscle fibers with angiocentricity. The immunoresults were Ki-1+, CD56+, cytoplasmic CD3+, with EBV-in situ hybridization +. The patient rapidly deteriorated and died of sepsis and respiratory failure shortly after initiation of low-dose chemotherapy. A careful review of previous biopsies revealed scarce atypical lymphoid cells around vessels with similar immunoprofiles without the presence of Ki-1 positive cells. This case emphasizes that an extranodal NK/T-cell lymphoma may have a dermatomyositis-like diffuse presentation. Ki-1 co-expression can be an unexpected event in a process of the disease course; however, this should be validated with future studies.

Synchronous Invasive Ductal Carcinoma and Metastatic Ovarian Serous Papillary Adenocarcinoma in the Same Breast: A Case Report.: Hyun Jung Kim, Sung jig Lim, Sehwan Han, Ji Young Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):66-69.

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Abstract PDF: A 59-year-old woman displayed multiple palpable right breast masses along with ipsilateral cervical and axillary lymphadenopathy. She had a previous history of bilateral salpingo-oopho- rectomy for serous papillary adenocarcinoma two and half years ago. She underwent mastectomy for the lesions located in the upper inner breast quadrant. A 1 cm-sized primary ductal carcinoma was present; however, the other breast lesions and the metastatic axillary lymph nodes were confirmed as showing papillary serous adenocarcinoma, which were similar to the previous ovarian tumor. After the patient underwent postoperative adjuvant chemotherapy, of 8 cycles of doxorubicin and docetaxel, she has been stable during the clinical follow-up for 10 months with decreases in size of the metastatic nodules.

Original Article

Expressions of CD44s Is Associated with the Expression of Cyclooxygenase-2 in Non-Small Cell Lung Cancers.: Sung Jig Lim, Hyun Jung Kim, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):17-23.

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Abstract PDF: BACKGROUND
The overexpression of Cox-2 in tumors is important for tumor invasion, angiogenesis, resistance to apoptosis and the suppression of host immunity. Moreover, a tumor's CD44 expression plays an important role in tumor invasion and metastasis. We examined the expression of COX-2 and also CD44 and its variants as well as the biological implications and relationship between Cox-2 and the CD44 variants in non-small cell lung carcinoma.
METHODS
The expressions of Cox-2 and also CD44s and its variants (CD44v3 and CD44v6) were examined by performing immunohistochemistry on 98 surgical specimens.
RESULTS
The expressions of CD44s, CD44v3 and CD44v6 were significantly more frequent in squamous cell carcinoma specimens than in the adenocarcinoma (CD44s, p=0.033; CD44v3, p=0.007; CD44v6, p=0.022). The loss of CD44s and CD44v3 were significantly correlated with poor tumor differentiation (CD44s, p=0.03; CD44v3, p=0.011). Patients with Cox-2 positive-adenocarcinoma tumors had a significantly worse cumulative survival than did those adenocarcinoma patients without the Cox-2 (p=0.048). The expression of Cox-2 was significantly associated with the CD44s expression in non-small cell lung cancer, and especially in squamous cell carcinoma.
CONCLUSIONS
These findings suggest that expression of CD44s is associated with the expression of Cox-2 in NSCLC, and especially squamous cell carcinoma.

Case Report

Epithelioid Myofibroblastoma of Mammary-type in Chest Wall: A Case Report.: Hyun Jung Kim, Hunkyung Lee, Ok Jun Lee, Kyung Ja Cho, Jae Y Ro; Korean J Pathol. 2005;39(2):130-133.

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Abstract PDF: Mammary-type myofibroblastoma of the soft tissue is a benign mesenchymal tumor, and it is a recently established clinical entity. We report a case of myofibroblastoma of the chest wall with a prominent epithelioid feature, that occurred in a 12-year old female. Although the lesion occurred in the breast area, there was no breast parenchyma in or around the mass, which favored soft tissue of the chest wall origin. The tumor was immunohistochemically identical to the mammary-type myofibroblastoma with diffuse and strong positivity against CD34 and desmin. The myoepithelial differentiation of the tumor was further supported by the electron microscopic analysis. This case indicates that mammary-type myofibroblastoma can occur in a young girl. The mammary-type myofibroblastoma should be considered a differential diagnosis, among epithelioid soft tissue neoplasms in the chest wall when the proper immunohistochemical work-up is done.

Original Article

Differential Expression of Promyelocytic Leukemia Protein in Autoimmune Liver Diseases.: Hyun Jung Kim, Jung Sun Kim, Yong Sang Lee, Young Hwa Chung, Han Joo Lee, Dong Jin Suh, Chong Jai Kim, Eunsil Yu; Korean J Pathol. 2004;38(6):357-363.

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Abstract PDF: BACKGROUND
Promyelocytic leukemia protein (PML) is a primary biliary cirrhosis (PBC)-specific autoantigen. Anti-PML antibody is analyzed using cultured cells with patient sera, however, PML expression has rarely been examined in liver tissues.
METHODS
In the present study, PML expression was examined immunohistochemically in paraffin embedded liver needle biopsy specimens obtained from 20 cases of PBC, 10 cases of autoimmune cholangitis, 36 cases of autoimmune hepatitis and from 5 cases of noninflammatory livers.
RESULTS
Variable PML immunopositivity was detected in the bile duct epithelial cells of 18 (90.0%) of 20 PBC cases and in all 10 cases (100.0%) of autoimmune cholangitis, whereas it was only present in 6 (16.7%) of 36 cases of autoimmune hepatitis (p<0.001). In contrast, hepatocyte PML immunopositivity was higher in autoimmune hepatitis (33/36 cases, 90.8%), than in PBC (10/20 cases, 50.0%) or autoimmune cholangitis (3/10 cases, 30.0%) (p<0.05).
CONCLUSION
Our data indicate that the differential expression of PML is closely related to autoimmune liver diseases type, and suggest that the overexpression of PML protein in bile duct cells is associated with the development of autoantibodies in patients with PBC or autoimmune cholangitis. Furthermore, PML immunoreactivity may be useful for the diagnosis of autoimmune cholangitis and overlap syndrome.

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