MGR - case R2. 김슬기 / Prof. 백선경

Case 1

Chief complaint sore throat o/s) 5 개월전 Present illness 63/M, 5 개월 전부터 sore throat, oral & gingival ulcer 있어 conservative Mx 하던 중 4 개월 전부터 sore throat aggravation 되고 foreign body sensation 동반되어 5 월 26 일 본원 ENT 에서 시행한 Lt tonsil Bx 결과 NK/T cell lymphoma 나와 stage W/U 및 Mx 위해 내원함 이 O 영 M/63 Adm date:

Past medical history DM / HTN / Tb / Hepatitis (-/+/-/-) HTN: 10 년전진단 Hypothyroidism 7 년전 Medication Hx Omega mg, Levothyroxine 0.1mg, Astrix 100mg, Pitavastatin 2mg, Benidipine 8mg, Carvediolol 12.5mg, Indapamide 2,5mg OP Hx (+) : Lt clavicle internal fixation d/t clavicle Fx 30 년전 Personal History Smoking (-) : 과거흡연 1 pack/day x 13 years Alcohol (-) : 과거 음주 ( 소주 1 병, 주 2~3 회 ) Occupation: 자영업 Family History Unremarkable

Review of system General generalized weakness (-) fever (-) fatigue(-) wt change (+) : -4kg/3mo Skin rash (-) Itching (-) pigmentation (-) Head / Neck headache (-) hoarseness (+) sore throat (+) hearing disturbance (-) Respiratory cough (-) sputum (-) dyspnea (-) hemoptysis (-) Cardiac chest pain (-) DOE(-) palpitation (-) GI A/N/V/D/C (-/-/-/-) hematochezia(-) hematemesis(-) bowel habit change(-) abdominal pain (-) Urinary dysuria(-) hematuria(-) nocturia(-) Musculoskeletal pain(-) swelling(-) tenderness(-)

Physical examination Vital sign 130/80 mmHg – 64 회 /min - 20 회 /min °C 169.5cm – 67.4 kg – 23.5 kg/m 2 General alert mentality acutely ill looking appearance Head & Neck isocoric pupil c PLR (++/++) cervical LN enlargement (-) no neck vein engorgement PI (-) PTH (+/+) : Lt. tonsil ulcer, inflammation Thorax symmetrical chest expansion clear breathing sounds s rale or wheezing regular heart beat without murmur

Abdomen soft & flat abdomen normoactive bowel sound tenderness (-) rebound tenderness (-) no palpable mass no hepatomegaly Back & Extremity CVA Td (-/-) no pretibial pitting edema Neurology Motor V V Sensory V V

Initial lab finding CBC/DC 8020/mm² g/dl – 47.7 %- 228K (seg : 43%) aPTT 35.5 sec PT(INR) 12.7 (1.12) ESR 28 mm/h Chemistry AST / ALT 31 / 26 U/L BUN / Cr 8 / 0.7 mg/dL TB / DB 0.46/ 0.13 mg/dL Na / K / Cl 134 / 4.0/ 94 mmol/L ALP / GGT 89 / 44 U/L Ca / P / Mg 8.6 / 3.3 / 1.8 mg/dL Protein / Alb 6.3/ 3.2 g/dL Uric acid 5.9 mg/dL CRP 2.83 mg/dL LD 391 IU/L UA RBC 0~1 WBC 0~1/HPF Protein (-) Nitrite (-) Glucose (-)

Chest X-ray

EKG

Lt tonsil biopsy (5/26)

CD3+ CD20- EBER + CD56+ Ki67+

Initial problem list #1. NK/T cell lymphoma #2. HTN #3. Hypothyroidism

Initial assessment & plan #1. NK/T cell lymphoma diagnostic plan) neck CT, chest CT, abd CT, PET CT, BM biopsy for staging EGD for evaluation of lymphoma extent EBV evaluation →VCA Ig M-Ab, EA-D Ab, EA-R Ab, EBNA Ab, DNA PCR ENT consult for nasopharynx involvement

Initial assessment & plan #2. HTN → 현 medication 유지 #3. Hypothyroidism → TFT 후 medication 결정

Neck CT (6/2)

PET CT (6/3)

EGD (6/2) duodenal biopsy: chronic ulcer

BM examination (6/7) Bone Marrow Finding Differential Finding : (Total count : 500) Blast: 0.6 % Eosinophil: 2.4 % Histiocyte: 0 % Promyelocyte: 0.6 % Basophil: 0 % Plasma cell: 1.8 % Myelocyte: 7.8 % Pronormoblast: 0.8 % Lymphocyte: 29.2 % Metamyelocyte: 8.2 % Baso. normoblast: 0.6 % Monocyte: 0.8 % Band neutrophil: 11.2 % Poly. normoblast: 1.6 % Atypical lym : 0 % Seg. neutrophil: 12.4 % Ortho. normoblast: 22.0 % Others: 0 % BM Aspiration : The aspiration smears show hypocellualr marrow particles. The granulocytic series and erythroid both decreased in number showing normal maturation sequences. Lymphocytes show an increase in number. The estimated M:E ratio is approximately 1.7:1. Clot Section & Biopsy Section : The estimated cellularity is approximately 10-20% at most. Special Stain : Iron stain : decreased storage iron in marrow particles (Grade 1) Cytogenetic Study : Chromosome : 46,XY[20] Hematologic Diagnosis 1. No evidence of bone marrow involvement of malignant lymphoma (S NK/T cell lymphoma, nasal type) 2. Hypocellular marrow, slightly No evidence of involvement of malignant lymphoma

EBV specific Ab 6/2 VCA Ab(IgM)- VCA Ab(IgG)+ EA-D Ab- EA-R Ab- EBNA Ab(IgG)+ EBV DNA PCRPositive (970,000 copies/ml)

Staging Stage II

Staging Low intermediate risk

TFT (6/2) T3: 127 ng/dL fT4: 1.47 ng/dL TSH: 3.48 μU/Ml → 현 synthyroxine 용량 유지

Final diagnosis #1. NK/T cell lymphoma, stage II low intermediate risk #2. HTN #3. Hypothyroidism

Bx: NK Tcell lymphoma Dx CDDP #1 CCRT Total 540cGy(3 회 ) CDDP #2 CCRT Total 1440cGy (8 회 ) CDDP #3 CCRT Total 2340cGy (13 회 ) CDDP #4 CCRT Total 3240cGy (18 회 ) RTx 만 지속 Total 3960cGy(22 회 )

Skin lesion r/o herpes simplex -> antiviral agent, skin biopsy

skin biopsy (7/13)

skin biopsy CD20- CD3+ CD56+EBER+ Ki67+

F/U Neck CT (7/21)

F/U PET CT (7/20)

Clinical course LD CCRT #1CCRT #2CCRT #3CCRT #4 RT 만 지속 Skin Bx Acyclovir regimen change (smile) 고려 중 SMC 로 전원

Case 2

Chief complaint Nasal obstruction o/s) remote: 2 년 전 recent: 일주일전 Present illness 상기 43/M 특이 병력 없는 자로 2 년전부터 nasal obstruction 있고, rhinorhea, cough 동반되어 local ENT 에서 allergic rhinitis 치료 받았으나 증상 호전없어 본원 ENT 방문하여 Biopsy 시행 (5/20) 후 Extranodal NK/T-cell lymphoma 진단받아 F/E 및 Mx 위해 adm 전 O 경 M/43 Adm date:

Past medical history DM / HTN / Tb / Hepatitis (-/-/-/-) Medication Hx : allergin rhinitis for 7 days levofloxacin 100mg tid, mucosta 100mg tid, loxonin 60mg tid OP Hx (-) Personal History Smoking (-) Alcohol (-) Occupation: 목사 Family History Unremarkable

Review of system General generalized weakness (-) fever (+) fatigue(+) wt change (+) : -5kg/5mo Skin rash (-) itching (-) pigmentation (-) Head / Neck headache (-) hoarseness (-) sore throat (+) hearing disturbance (-) nasal obstruction (+) : Rt>Lt Respiratory cough (+) sputum (+) dyspnea (-) hemoptysis (-) Cardiac chest pain (-) DOE(-) palpitation (-) GI A/N/V/D/C (-/-/-/-) hematochezia(-) hematemesis(-) bowel habit change(-) abdominal pain (-) Urinary dysuria(-) hematuria(-) nocturia(-) Musculoskeletal pain(-) swelling(-) tenderness(-) whitish

Physical examination Vital sign 110/70 mmHg – 80 회 /min - 20 회 /min °C cm – 46kg – 15.4 kg/m 2 General alert mentality acutely ill looking appearance Head & Neck isocoric pupil c PLR (++/++) cervical LN enlargement (-) no neck vein engorgement PI (-) PTH (+/+) Rt nose 근처 swelling (+) tenderness (+) redness (-) Thorax symmetrical chest expansion clear breathing sounds s rale or wheezing regular heart beat without murmur

Abdomen soft & flat abdomen normoactive bowel sound tenderness (-) rebound tenderness (-) no palpable mass no hepatomegaly Back & Extremity CVA Td (-/-) no pretibial pitting edema Neurology Motor V V Sensory V V

Initial lab finding CBC/DC 4750/mm² g/dl – 30.6 %- 230K (seg : 74.5%) aPTT 42.3sec PT(INR) 12.0 (0.92) Chemistry AST / ALT 20 / 11 U/L BUN / Cr 15 / 0.8 mg/dL TB 0.89 mg/dL Na / K / Cl 138 / 3.4 / 98 mmol/L ALP / GGT 62 / 22 U/L Ca / P / Mg 8.3 / 2.8 / 1.9 mg/dL Protein / Alb 8.0 / 4.0 g/dL Uric acid 4.8 mg/dL CRP 2.98 mg/dL LD 328 IU/L UA RBC (-) WBC 0~1/HPF Protein (-) Nitrite (-) Glucose (-)

Chest X-ray

EKG

nasal cavity biopsy (5/20) CD20 - CD3+ CD56+EBER+ H&E

Initial problem list #1. extranodal NK/T cell lymphoma

Initial assessment & plan #1. NK/T cell lymphoma diagnostic plan) neck CT, chest CT, abd CT, PET CT, BM biopsy for staging EGD for evaluation of lymphoma extent EBV evaluation →VCA Ig M-Ab, EA-D Ab, EA-R Ab, EBNA Ab, DNA PCR ENT consult for nasopharynx involvement

EGD (5/31)

PNS CT (5/12)

NECK CT (5/31)

PET CT (6/1)

BM biopsy (5/30) Bone Marrow Finding Differential Finding : (Total count : 500) Blast: 1.0% Eosinophil: 8.0% Histiocyte: 0.0% Promyelocyte: 0.0% Basophil: 0.0% Plasma cell: 1.2% Myelocyte: 20.0% Pronormoblast: 0.0% Lymphocyte: 7.6% Metamyelocyte: 6.0% Baso. normoblast: 0.6% Monocyte: 0.0% Band neutrophil: 15.8% Poly. normoblast: 7.6% Atypical lym : 0.0% Seg. neutrophil: 16.8% Ortho. normoblast: 15.8% Others: 0.0% BM Aspiration : normocellualr marrow particles. granulocytic series and erythroid elements are normal in number and show good maturation sequences. The estimated M:E ratio is approximately 2.75:1. Clot Section & Biopsy Section : The estimated cellularity is approximately 40-50% (Lt.) and 10-20% (Rt). Cytogenetic Study : 46,XY[20] Hematologic Diagnosis 1.No evidence of involvement of malignant lymphoma (S : Extranodal NK/T-cell lymphoma) 2. Hypocellular marrow (Rt/Lt) No evidence of involvement of malignant lymphoma

EBV specific Ab 5/29 VCA Ab(IgM)+ VCA Ab(IgG)+ EA-D Ab- EA-R Ab- EBNA Ab(IgG)+ EBV DNA PCR-

Staging Stage IIE

Staging High intermediate risk

Final diagnosis #1. NK/T cell lymphoma, stage IIE c high intermediate risk

Treatment: systemic chemotherapy EPOCH –etoposide –prednisone –oncovin(vincristine) –cyclophosphamide –hydroxydaunorubicin

Clinical course - EPOCH #1(6/2~6/6) Etoposide 90mgitraconazole Solondo 110mg Doxorubicin 18mg Vincristine 0.7mg Cyclophosphamide 1400mg Allopurinol 200mg Levofloxacin cefepime LD

Clinical course - EPOCH #2(6/28~7/3) Etoposide 75mg Solondo 90mg Doxorubicin 15mg Vincristine 0.6mg Cyclophosphamide 1150mg Allopurinol 200mg LD Nasal swelling aggravation

F/U NECK CT (7/12) Nasal cavity lateral, septum: 7.57 → 13.21mm 7.58 → 7.37mm Rt internal jugular chain LN: 14.3 → 12.7mm 9.38mm → 9.66mm Both submandibular LN: 11.5 → mm 11.57→ mm 6.89 → 8.53mmm

F/U PET-CT (7/20)

MTX 2900mg D1 Etoposide150mg D2-4 LV 80mg D2-4 IFX 2200mg D2-4 Mesna 1200mg D2-4 Dexa 40mg D2-4Amphotericin D11(7/28~8/8) Teicoplanin (7/18~8/8) LD Clinical course - SMILE #1(7/20~8/8) Pip/taz (7/18~8/8) L-asparaginase 8700unit EOD D8~D20

MTX 2200mg D1G-CSF (8/22~29) Etoposide110mg D2-4 LV 80mg D2-4 IFX 1650mg D2-4 Mesna 990mg D2-4 Dexa 40mg D2-4 Metronidazole (8/18~8/24) Clinical course - SMILE #2(8/17~9/5) L-asparaginase 5600unit EOD D8~D LD

F/U NECK CT (9/6) Nasal cavity lateral, septum: → 8.59mm 7.37 → 6.55mm Rt internal jugular chain LN: 12.7 → 11.36mm Both submandibular LN: → mm 9.96→ 7.14 mm → 13.30mm

Bx: NK Tcell lymphoma Dx ~06.06 EPOCH # ~07.03 EPOCH # ~08.08 SMILE # ~09.05 SMILE #2CDDP #1 CCRT daily dose 200cGy CDDP #2 CCRT daily dose 200cGy