Methylation Abnormality in Body Fluid Cytology: A Supplemental Molecular Marker for the Diagnosis of Malignant Mesothelioma

송준선,정진경,강지혜,황일선,장세진,Song, Joon-Seon,Jung, Jin-Kyung,Kang, Ji-Hye,Hwang, Il-Seon,Jang, Se-Jin The Korean Society for Cytopathology 2008 대한세포병리학회지 Vol.19 No.2

Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only $32{\sim}79%$ of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1 % (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

증례 : 호흡기 ; 낭종성 폐병변으로 내원하여 진단된 Birt-Hogg-Dube 증후군 2예

서명숙 ( Myeong Sook Seo ),임두호 ( Doo Ho Lim ),송준선 ( Joon Seon Song ),박찬식 ( Chan Sik Park ),채은진 ( Eun Jin Chae ),송진우 ( Jin Woo Song ) 대한내과학회 2014 대한내과학회지 Vol.87 No.4

Birt-Hogg-Dube (BHD) syndrome is a rare autosomal-dominant disease caused by germline folliculin (FLCN) mutations, characterized by fibrofolliculoma or trichodiscoma, renal tumors, and multiple lung cysts with or without spontaneous pneumothorax. Here, we report two cases of BHD syndrome that presented with bilateral pulmonary cysts. One patient was a 39-year-old woman who had a history of pneumothorax, multiple papules on her cheeks, and a family history of the same skin lesions and renal cell carcinoma in her father. BHD syndrome was confirmed by molecular tests that revealed a missense mutation in FLCN gene (exon 4, c.31T > C). The other patient was a 56-year-old man who showed FCLN gene polymorphism and typical radiopathological features of multiple cysts in the lung, but apparently no other manifestation. (Korean J Med 2014;87:477-483)

증례 : 혈액종양 ; 위에 발생한 투명세포육종 1예

김좌훈 ( Jwa Hoon Kim ),김범수 ( Beom Su Kim ),송준선 ( Joon Seon Song ),조형우 ( Hyungwoo Cho ),김종관 ( Jongkwan Kim ),이주희 ( Joohee Lee ),류민희 ( Min Hee Ryu ) 대한내과학회 2015 대한내과학회지 Vol.89 No.4

위에 발생한 투명세포육종은 매우 드물며 국내에서 첫 증례를 보고하는 바이다. 투명세포육종의 진단은 어렵지만 충분한 조직 검체를 이용하여 면역조직화학 검사 및 분자학적 검사를 하면 진단할 수 있고, 특히 EWS 유전자 전좌를 확인하는 것이 중요하다. 문헌 보고에 따르면 투명세포육종의 치료로서 항암화학요법의 효과는 미미하였고 아직까지 항암화학요법에 대해 일치된 의견이 없어 현재까지 수술적 절제가 권장된다. 본 증례에서 초기 유잉 육종 진단하에 항암화학요법을 적용하였는데 치료 경과가 유잉 육종과 일치하지 않아투명세포육종을 의심하에 수술적 절제로 진단 및 치료를 하였다. 수술적 절제 이후에 부종양 증후군이 호전되는 것을 확인하였고 재발 없이 추적관찰 중이다. Clear-cell sarcoma (CCS) is a rare soft tissue sarcoma that usually develops in the lower extremities of young adults. CCS of the gastrointestinal tract is extremely rare. We report here the first case of CCS of the stomach in Korea. A 28-year-old female developed a large tumor of the stomach that was initially considered Ewing sarcoma, based on the results of a needle biopsy. She had paraneoplastic syndrome; fever, anemia, and hyperglycemia. Follow-up abdominal computed tomography after four-cycles of chemotherapy with vincristine-doxorubicin-cyclophosphamide or ifosfamide-etoposide showed no tumor shrinkage and revealed a fistula between the tumor and the gastric lumen. The infected tumor prompted debulking surgery, which resulted in improvement of her symptoms. The pathologic findings were consistent with CCS, and fluorescence in situ hybridization for EWS gene rearrangement was positive, confirming the diagnosis. This case highlights the importance of clinical suspicion for CCS in chemotherapy-refractory Ewing sarcoma. (Korean J Med 2015;89:465-469)

증례 : 호흡기 ; 비특이적 간질성 폐렴의 양상으로 발생한 IgG4 연관 폐 질환의 1예

조동희 ( Dong Hui Cho ),안지환 ( Ji Hwan An ),강유미 ( Yu Mi Kang ),채은진 ( Eun Jin Chae ),송준선 ( Joon Seon Song ),송진우 ( Jin Woo Song ) 대한내과학회 2015 대한내과학회지 Vol.88 No.3

특발성 비특이적 간질성 폐 질환과 IgG4 related lung disease는 증상, 폐기능 검사, 영상의학 소견만으로는 감별이 어려운 질환이다. 하지만 IgG4 related lung disease는 steroid 치료에 좋은 치료 반응을 보이는 것으로 알려져 있어 이들의 감별은 매우 중요하다고 할 수 있다. 본 증례는 특발성 간질성 폐 질환, 특히 비특이적 간질성 폐렴에서 혈청 IgG4의 증가 혹은 조직 소견상 lymphoplasmacytic infiltration이 다수 관찰되고 obliterative phlebitis, storiform fibrosis 등이 관찰된다면 IgG4 연관 질환의 폐 침범 가능성을 고려해야 함을 시사해 준다. Immunoglobulin (Ig) G4-related disease is a recently described systemic inflammatory disease characterized by high serum IgG4 concentrations and sclerosing inflammation of numerous IgG4-positive plasma cells that responds favorably to steroid treatment. Although initial description of this disorder focused on its pancreatic presentation, it has become apparent that it is a systemic disease. In this report, we describe a case of IgG4-related lung disease presenting as non-specific interstitial pneumonia in a 78-year-old male with interstitial lung disease. Pathological examination through video-assisted thoracic surgery showed a non-specific interstitial pneumonia pattern and numerous (> 50/high-power field) infiltrating IgG4-positive plasma cells. Laboratory tests also revealed a high serum IgG4 concentration. Prednisolone therapy was initiated and his symptoms and reticular opacity improved after two months of treatment.(Korean J Med 2015;88:308-312)

Mucormycosis에 의한 척추골수염 1예

오경환 ( Kyunghwan Oh ),권오찬 ( Oh Chan Kwon ),박형준 ( Hyung Jun Park ),이민기 ( Mingee Lee ),조상철 ( Sang-cheol Cho ),송준선 ( Joon Seon Song ),김성한 ( Sung-han Kim ) 대한내과학회 2017 대한내과학회지 Vol.92 No.1

털곰팡이에 의한 척추 골수염 증례보고가 국내에서는 아직 없었으며, 전 세계적으로도 매우 드물다. 저자들은 급성백혈병으로 3년 전 항암 치료를 받고 재발이 없는 상태로 지내던 환자에서 발생한 털곰팡이에 의한 척추 골수염을 조직형태학적 방법 및 면역조직화학염색 방법으로 진단하였기에 보고하는 바이다. Mucormycosis is a rare but fatal disease and usually affects the rhinocerebrum, lungs, traumatic wounds or surgical sites. Vertebral osteomyelitis due to mucormycosis is very rare, with only three cases caused by mucormycosis since 1970 being reported, and none in Korea. Here, we present a case of vertebral osteomyelitis caused by mucormycosis in a 67-year-old woman, having type 2 diabetes mellitus for 10 years, who was in complete remission from acute leukemia after chemotherapy 3 years previously. (Korean J Med 2017;92:84-88)

증례 : 혈액종양 ; 간 전이를 동반한 VIPoma에서 간동맥 색전술을 이용한 현저한 증상 호전

최윤숙 ( Yun Suk Choi ),고기영 ( Gi Young Ko ),류민희 ( Min Hee Ryu ),강신광 ( Shin Kwang Khang ),김정은 ( Jeong Eun Kim ),송준선 ( Joon Seon Song ),강윤구 ( Yoon Koo Kang ) 대한내과학회 2014 대한내과학회지 Vol.87 No.3

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) cause VIPoma syndrome, which is characterized by watery diarrhea, hypokalemia, and achlorhydria. The treatment options for metastatic VIPomas include somatostatin analogs, cytoreductive surgery, and chemotherapy. We report the case of a 54-year-old male who presented with a peripancreatic mass with multiple hepatic metastases on computed tomography. After resection, the peripancreatic mass was demonstrated pathologically to be a neuroendocrine tumor. Although the patient received systemic chemotherapy and somatostatin analogs for the hepatic metastatic masses, the tumor increased in size. The patient then experienced severe diarrhea, despite treatment with the somatostatin analogs. Elevated serum VIP levels (3,260 pg/mL) and typical symptoms confirmed the diagnosis of VIPoma. We performed hepatic artery embolization (HAE) to reduce the tumor volume and control his symptoms, which led to a very rapid symptomatic response. The patient has remained symptom-free for 18 months with repeated HAE. (Korean J Med 2014;87:363-368)