1. 경희대학교병원 혈액종양내과 R2 문정락 / Prof 백선경 2014.5.22 Medical Ground Round 악성종양 환자에서 발생한 간종괴의 감별진단

2. Case 1 C.C. 간 종괴 검사 P.I. 2011 년 6 월 위암 (stage IIA, adenocarcinoma) 으로 원위부 위부분절 제술 시행한자, 2012 년 3 월 간전이 발견되어 고주파 열치료 및 고식 적 항암화학요법 (Xelox #5, SD) 받았음. 2012 년 10 월 간전이 여러 군 데 재발하여 항암용법 변경 (PTx #6, PR) 시행 중 환자 힘들어 하여 2013 년 4 월 부터 항암치료 휴식기 가짐. 2013 년 10 월 시행한 영상검 사상 간 종괴 이상 소견보여 이에 대한 검사 위해 입원함. 12203302 노희갑 69/M

3. History 과거력 -DM/HTN/Hepatitis/TBc (+/-/-/-) DM: since 2003 -Magliancy Hx (+) 2011/6: AGC (Stage IIA, pT3N0M0, L/V -/-, adenocarcinoma) 2003: rectal cancer ( 송도병원 ) -Op Hx (+) : 2011/6/16 LADG c Billroth I 2003 rectal cancer operation 개인력 -Smoking (+) : past smoker, 20 pack-years -Alcohol (-)

4. 2011/6 Stage IIA Adenoca. Surgery AGC ’12/2 C.C. Hematochezia C.C. Regular f/u Abd CT: Two hepatic metastases at segment 4 and lateral segment Doxyfluridine

5. 2012/2/10 Abdomen CT

6. 2012/2/21 Liver MRI Two hepatic metastases at segment 4 and lateral segment

7. 2011/6 Stage IIA Adenoca. Surgery RFA ’12/3/6 AGC ’12/2 C.C. Hematochezia C.C. Regular f/u Abd CT: Two hepatic metastases at segment 4 and lateral segment Liver MRI F/U: (2012/3/21) Slightly decreased size of hepatic metastasis Liver MRI F/U: (2012/5/21) new metastatic lesion at segment 2 Doxyfluridine

8. 2012/3/21 Liver MRI 1.Slightly decreased size of hepatic metastasis at left lateral segment (1cm → 0.7cm) 2.RFA associated necrotic lesion at S4

9. 2012/5/21 Liver MRI Suggested new metastatic lesion at segment 2

10. Serial Abdomen Imaging 1) 12/2/21 2) 12/3/21 3)-A 12/5/21 3)-B 12/5/21

11. 2011/6 Stage IIA Adenoca. Surgery RFA ’12/3 Xelox #5 ‘12/5 – ’12/8 AGC ’12/2 C.C. Hematochezia C.C. Regular f/u Abd CT: Two hepatic metastases at segment 4 and lateral segment Liver MRI: (2012/9) New two metastatic nodules on segment 5 Liver MRI F/U: (2012/5/21) new metastatic lesion at segment 2 Doxyflurid ine

12. 2012/9/19 Liver MRI New two metastatic nodules on segment 5

13. 2011/6 Stage IIA Adenoca. Surgery RFA ’12/3 Xelox #5 ‘12/5 – ’12/8 PTx #6 ‘12/10 – ’13/3 AGC ’12/2 C.C. Hematochezia ’12/10’13/10’13/4 C.C. Regular f/u Abd CT: Two hepatic metastases at segment 4 and lateral segment Liver MRI: (2012/9) New two metastatic nodules on segment 5 Liver MRI: (2013/10) Suggestive of hemorrhagic hepatic infarction at S4 Chemo- holiday Liver MRI F/U: (2012/5/21) new metastatic lesion at segment 2 Doxyflurid ine

14. Serial Abdomen Imaging 1) 12/9/19 2) 13/3/29 3)-A 13/10/14 3)-B 13/10/14

15. Review of system Physical examination Vital sign 130/80mmHg - 70/min - 20/min - 36.1°C (BMI: 25.4 kg/m 2 ) General Not so ill-looking appearance Chest Clear breathing sound without rales/crackles Abdomen Soft abdomen Abdominal Td/rTd(-/-) Muscle guarding(-) General febrile sensation(-) chills(-) body weight loss(-) GI A/N/V/D/C(-/-/-/-/-)abdominal pain(-) hematochezia(-) melena(-)hematemesis(-)

16. Initial Lab Findings CBC/DC 6470/mm² - 13.7g/dL – 39.7% - 295K (seg. 52.4%) Chemistry Prot/Alb7.1/4.0 g/dL TB0.62 mg/dL AST/ALT29/15 IU/L ALP/GGT99/100 IU/L BUN/Cr13/0.6 mg/dL Na/K/Cl141/4.5/105 mEq/L Ca/P8.7/3.7 mg/dL LD485 U/L CRP<0.3 mg/dl Viral marker HBsAg/ Anti-HBs/ Anti-HBc/ Anti-HCV/anti-HIV (-/+/+/-/-)

17. Problem list #1. Newly developed hepatic lesion #2. AGC c known hepatic metastasis (adenoca, stage IV) s/p distal gastrectomy c Billroth I (2011/6) s/p RFA (2012/3) s/p Xelox #5, SD (2012/5 ~ 2012/8) s/p PTx #6, PR (2012/10 ~ 2013/3) #3. h/o rectal cancer, cured #4. DM, known

18. Initial Assessment & Plan #1-3 A) Aggravated liver metastasis of AGC r/o hemorrhagic abscess r/o colon cancer recur, least likely P) Liver biopsy

19. 2011/6 Stage IIA Adenoca. Surgery RFA ’12/3 Xelox #5 ‘12/5 – ’12/8 PTx #6 ‘12/10 – ’13/3 AGC ’12/2 C.C. Hematochezia ’12/10’13/10’13/4 C.C. Regular f/u Abd CT: Two hepatic metastases at segment 4 and lateral segment Liver MRI: (2012/9) New two metastatic nodules on segment 5 Liver MRI: (2013/10) Suggestive of hemorrhagic hepatic infarction at S4 Chemo- holiday Liver MRI F/U: (2012/5/21) new metastatic lesion at segment 2 Doxyflurid ine Liver Biopsy: (2013/10/22) Adenocarcinoma, metastatic Clinical course

20. Liver Biopsy (2013/10/22)

22. CD19

23. Final Diagnosis #1. Aggravated liver metastasis #2. AGC c known hepatic metastasis (adenoca, stage IV) s/p distal gastrectomy c Billroth I (2011/6) s/p RFA (2012/3) s/p Xelox #5, SD (2012/5 ~ 2012/8) s/p PTx #6, PR (2012/10 ~ 2013/3) #3. h/o rectal cancer, cured #4. DM, known

24. 2 blood supply sources –hepatic artery –portal vein Metastatic Liver Cancer Synchronous: metastatic lesion identified at the same time as the original cancer Metachronous: metastatic lesion discovered later, after the original cancer has been treated or surgically removed ∴ Liver is the most common site for metastasis from gastrointestinal cancers

25. Metastatic Liver Cancer Diagnosis 1.Blood work: LFT, CBC/DC 2.Imaging ① CT ② MRI ③ PET-CT 3. Liver biopsy Treatment 1.Systemic chemotherapy 2.Transarterial Chemoembolization (TACE) 3.Radiofrequency Ablation 4.Surgery

26. Case 2 C.C. 유방암 치료 P.I. 2009 년 1 월 16 일 오른쪽 유방암 (stage IIB, ER/PR/HER2 +/+/-) 으로 고대안암병원에서 유방 보존술시행후 보조항암화학요법 (AC → PTx) 및 방사선치료 받던중 추적 소실 된 자임. 2012 년 등쪽 통증으로 시행 한 검사상 뼈전이 진단되어 아로마타제 억제제 (letrozole) 복용중 본 원 진료원하여 전원됨. 11296313 이순자 66/F

27. History 과거력 -DM/HTN/Hepatitis/TBc (-/-/-/+) TBc: pulmonary & lymphadenitis, 40 years ago -Magliancy Hx (+) 2009/1/2: Invasive ductal carcinoma, Rt breast (Stage IIB, pT2N1M0, ER/PR/HER2 +/+/-) -Op Hx (+) : 2009/1/16 BCS, Rt c axillary LN dissection 개인력 -Smoking / Alcohol (-/-) -Occupation: housewife

28. 2009/1 Stage IIB (ER/PR/HER2 +/+/-) Surgery Adjuvant AC #4 Paclitaxel #5 RTx + Tamoxifene IDC, Rt ‘12 ‘14/2 T4 spine, sternal mets Stage IV C.C. Palpable breast mass C.C. Back pain Aromatase inhibitor (letrozole)

29. Review of system Physical examination Vital sign 140/85mmHg - 88/min - 20/min - 36.5°C (BMI: 25.4 kg/m 2 ) General Chronically ill-looking appearance Chest Breast discharge (-)Skin lesion (-) Symmetric chest expansion Clear breathing sound without rales/crackles General febrile sensation(-) chills(-) body weight loss(-) Musculoskeletal weakness(-)myalgia (-)numbness(-)

30. Initial Lab Findings CBC/DC 6470/mm² - 13.7g/dL – 39.7% - 295K (seg. 52.4%) Chemistry Prot/Alb7.1/3.9g/dL TB0.66 mg/dL AST/ALT24/14 IU/L ALP/GGT58/10 IU/L BUN/Cr18/0.5 mg/dL Na/K/Cl139/4.5/103 mEq/L Ca/P8.3/2.8 mg/dL LD588 U/L CRP<0.3 mg/dl Viral marker HBsAg/ Anti-HBs/ Anti-HCV/anti-HIV (-/-/-/-)

31. Initial Abdomen CT (2014/2/7) 2) 14/02/072) 13/11/06 New ill-defined low attenuated lesion on segment 5 (1.6cm)

32. Problem list #1. Newly developed hepatic mass #2. Relapsed breast cancer, Rt c spine & sternum metastasis (stage IV, ER/PR/HER2 +/+/-) s/p BCS, Rt c axillary LN dissection (2009/1) s/p adjuvant AC #4 → PTx #4 s/p RTx & tamoxifene on letrozole (since 2012) #3. Treated tuberculosis

33. Initial Assessment & Plan Initial Abdomen CT Newly developed a low attenuated lesion at S5 of liver, liver metastasis cannot be excluded YES Annals of Oncology 22: 2227–2233, 2011 Annals of Oncology 20: 1499–1504, 2009 NO

34. 1.Substantial discordance in receptor status between primary tumor and metastases (40% in hormone receptor status, 8% in HER2 status)→ altered management in 20% of cases 2.Therefore, tissue confirmation should be considered in patients with clinical or radiological suspicion of metastatic recurrence Annals of Oncology 20: 1499–1504, 2009

35. Annals of Oncology 22: 2227–2233, 2011 1.Significant changes in receptor status (ER : 14.5%, PR : 48.6%, HER2 : 13.9%)→ change in therapy in 12.1% 2.Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out

36. Initial Assessment & Plan YES Annals of Oncology 22: 2227–2233, 2011 Annals of Oncology 20: 1499–1504, 2009 NO LAB REVISION Eosinophilia 12.3% Do additional imaging studies first Liver MRI PET-CT

37. 2009/1 Stage IIB (ER/PR/HER2 +/+/-) Surgery Adjuvant AC #4 Paclitaxel #5 RTx + Tamoxifene IDC, Rt ‘12‘14/2 T4 spine, sternal mets Stage IV C.C. Palpable breast mass C.C. Back pain ‘13/11 Abd CT Aromatase inhibitor (letrozole) Clinical course PET-CT (2014/02/18) Focal Hypermetabolic lesion (segment 5) Suggestive of metastasis Eosinophil count : 12.3%

38. Focal hypermetabolic lesion (segment 5) Metastasis? 2014/2/18 PET-CT

39. 2009/1 Stage IIB (ER/PR/HER2 +/+/-) Surgery Adjuvant AC #4 Paclitaxel #5 RTx + Tamoxifene IDC, Rt ‘12‘14/2 T4 spine, sternal mets Stage IV C.C. Palpable breast mass C.C. Back pain ‘13/11 Abd CT Aromatase inhibitor (letrozole) Clinical course PET-CT (2014/02/18) Focal Hypermetabolic lesion (segment 5) Eosinophil count : 12.3% ‘14/4 Abdomen-CT (2014/04/07) Disappeared previous low attenuated lesion at S5

40. Serial Abdomen Imaging 2) 14/02/07 3) 14/04/07 Disappeared previous low attenuated lesion at segment 5 2014/4/07 Abdomen CT 1) 13/11/06

41. Final Diagnosis #1. Eosinophilic infiltration of Liver #2. Relapsed breast cancer, Rt c spine & sternum metastasis (stage IV, ER/PR/HER2 +/+/-) s/p BCS, Rt c axillary LN dissection (2009/1) s/p adjuvant AC #4 → PTx #4 s/p RTx & tamoxifene on letrozole (since 2012) #3. Treated tuberculosis

42. Eosinophilic Infiltration of Liver Focal eosinophilic infitration, focal eosinophilic necrosis, focal eosinophilic abscess, eosinophilic granuloma, foci of eosinophil-related necrosis → not a disease entity, but a histopathological findings Focal eosinophilic infiltration in the lungs and liver: Parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseases, hypereosinophilic syndrome Neoplastic diseases (tumor associated eosinophiliotactic factor) Relatively common in Korean patients -Usually self-limiting -Associated with parasitic infection in Koreans -Somewhat characteristic radiologic findings on USG and CT Eosinophilia: presence of more than 500 eosinophils/ uL in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues Korean J Radiol 7(1), March 2006 Abdom Imaging 28:326–332 (2003), The Korean Journal of Hepatology 2010 ; 16 : 95 - 99

43. Eosinophilic Infiltration of Liver 59/M C.C. jaundice PMHx: none Lab: obstructive jaundice, eosinophilia (1343/mm 3 ), hypergammaglobulinemia Imaging (CT, MRCP, ERCP): dilatation of the intrahepatic bile duct, stenosis of the common bile duct with diffuse wall thickening, gallbladder wall thickening, irregular narrowing of the pancreatic duct, and swelling of the pancreatic parenchyma Biopsy: lymphocytes, histiocytes, plasma cells, and a number of eosinophils Diagnosis: inflammatory pseudotumor Impression: pancreatic cancer with liver metastasis Tx: prednisolone Px: liver masses disappeared; swelling of the pancreatic head improved; peripheral eosinophil count normalized. BUT!

44. Case 3 C.C. 간 조직검사 P.I. 2012 년 12 월 28 일 성바오로 병원에서 위내시경 검사상 위암 진단 후 2013 년 1 월 15 일 본원 외과에서 원위부 위부분절제술 시행 받았음. 이후 보조적 항암 요법 (XELOX) 시행중 2013 년 5 월 14 일 시행한 복 부 전산화 단층촬영상 간종괴 발견되어 간조직검사 시행 위해 입원 함. 12319727 김옥점 53/F

45. History 과거력 -DM/HTN/Hepatitis/TBc (-/-/-/-) -Magliancy Hx (+) 2012/12: AGC (Stage IIIC, pT4N3aM0, L/V -/-, adenocarcinoma) -Op Hx (+) : 2013/1/15 Open DG c R-en-Y anastomosis 개인력 -Smoking (-) -Alcohol (-)

46. 2013/01 Stage IIIC Adenoca. Surgery AGC ’13/05 C.C. Epigastric pain C.C. Regular f/u Abd CT: three low attenuated lesions at S4, 5 and S5/8 Adjuvant Xelox #1 ~ #4 (13/2~13/5)

47. Review of system Physical examination Vital sign 110/70mmHg - 60/min - 20/min - 36.0°C (BMI: 18.2 kg/m 2 ) General Chronically ill-looking appearance Chest Clear breathing sound without rales/crackles Abdomen Soft abdomen Abdominal Td/rTd(-/-) Muscle guarding(-) General febrile sensation(-) chills(-) body weight loss(-) GI A/N/V/D/C(-/-/-/-/-)abdominal pain(-) hematochezia(-) melena(-)hematemesis(-)

48. Initial Abdomen CT (2013/5/14) 2) 14/02/072) 13/11/06 Three low attenuated lesions at S4, S5 and S8

49. Problem list #1. Newly developed hepatic lesions #2. AGC (adenoca, stage IIIc) s/p open DG c Roux-en-Y anastomosis (2013/1) on adjuvant Xelox #4 (2013/2~)

50. Initial Assessment & Plan #1-2 A) r/o hepatic metastasis of AGC P) Liver biopsy

51. Clinical course 2013/01 Stage IIIC Adenoca. Surgery ’13/05 C.C. Epigastric pain C.C. Regular f/u Abd CT: three low attenuated lesions at S4, S5 and S8 Liver Biopsy: (2013/5/21) Result: Cholestasis Adjuvant Xelox #1 ~ #4 (13/2~13/5)

52. Liver Biopsy (2013/05/21)

54. Clinical course 2013/01 Stage IIIC Adenoca. Surgery ’13/05 C.C. Epigastric pain C.C. Regular f/u Abd CT: three low attenuated lesions at S4, S5 and S8 Adjuvant Xelox #1 ~ #4 (13/2~13/5) Liver Biopsy: (2013/5/21) Result: Cholestasis Abd CT F/U: (2013/9/27) Decreased size of 2 low attenuated lesions at S5, disappeared low attenuated lesion at S4 Adjuvant Xelox #5 ~ #7 (13/5~13/7)

55. F/U Abdomen CT (2013/9/27) Decreased size of 2 low attenuated lesions at S5, disappeared low attenuated lesion at S4

56. Final Diagnosis #1. Fatty infiltration of liver #2. AGC (adenoca, stage IIIc) s/p Open DG c R-en-Y anastomosis (2013/1) s/p adjuvant Xelox #7 (2013/2 ~ 2013/7) 17

57. Fatty Infiltration of Liver Why the interest? Its hypodense appearance on CT scan may make it difficult to distinguish from metastatic disease, especially in individuals with a history of malignancy Prevalence, etiology, natural history, and treatment Unknown Diagnosis 1.MRI, using combination of in-phase and opposed- phase gradient-echo imaging 2.Contrast- enhanced ultrasound 3.Judicious use of liver biopsy Gastroenterology & Hepatology Volume 3, Issue 3 March 2007 AJR 145:79-80, July 1985 0361-803X/85/1451-0079 Postgrad Med J (1990) 66, 290 – 291 Eur Radiol. 2000;10:1095-1100

58. Fatty Infiltration of Liver Dx: recurred cancer at liver 2 nd opinion: same diagnosis Tx: immune tx with a Mycobacterium tuberculosis–derived arabinomannan Clinical Course: LFT elevation → follow imaging shows atypical findings USG- guided needle biopsy of the liver: focal fatty infiltration 57/F PMHx: At age 47, cancer of the uterine cervix → radical hysterectomy & postoperative radiation therapy 5 years after the operation: small multinodular lesions were detected in the liver on CT and sonography