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1 The Korean Journal of Gastrointestinal Endoscopy Case Report 구불결장의동일부위에발생한선암과결핵성림프절염 1 예 류성호ㆍ신운건ㆍ이승민ㆍ박소연ㆍ김성준ㆍ유종진ㆍ조성진 * ㆍ김학양 한림대학교의과대학내과학교실, * 병리학교실 Adenocarcinoma and Tuberculous Lymphadenitis on the Same Site of the Sigmoid Colon: A Case Report and Literature Review Sung Ho Ryu, M.D., Woon Geon Shin, M.D., Seung Min Lee, M.D., So Yeon Park, M.D., Sung Jun Kim, M.D., Jong Jin Yoo, M.D., Seoung Jin Cho, M.D.* and Hak Yang Kim, M.D. Departments of Internal Medicine and *Pathology, Hallym University College of Medicine, Seoul, Korea Inflammatory bowel disease can progress to cancer. However, there is not much of a causal relationship between intestinal tuberculosis and cancer. There have been a few case reports of intestinal tuberculosis in association with cancer. We experienced a 59-year-old man who had the collision-like pathology of adenocarcinoma and tuberculous lymphadenitis on the sigmoid. He visitied our hospital because of abdominal pain and hematochezia. Colonoscopy showed a mass on the sigmoid that was causing luminal obstruction. Therefore, sigmoidectomy was performed and the resected specimen revealed a collision-like appearance; the mass was composed of adenocarcinoma invading the proper muscle layer and caseating granuloma in the serosa and lymph nodes. We report here on a case of collision-like pathology that was composed of adenocarcinoma and tuberculosis on the sigmoid, and we review the relevant literature. (Korean J Gastrointest Endosc 2009;39: ) Key Words: Collision pathology, Colon cancer, Tuberculosis colitis, Sigmoid 교신저자. 신운건강동성심병원내과 ( ), 서울시강동구길 1 동 445 전화 : 팩스 : 이메일 : sgun91@hallym.or.kr 접수 년 6 월 26 일승인 년 10 월 20 일 서론 궤양성대장염이나크론병과같은만성염증성장질환이장기간지속된환자에서대장암발생의위험이정상인에비해높은것으로알려져있다. 1 반면에, 대장의결핵과악성종양은임상적으로잘알려져왔으나이두질환이대장에합병되는경우는드문데, 1810년이후외국에서꾸준히보고되어왔고, 2-8 국내에서도 1988년에첫보고가있은후모두 7차례유사사례가보고되었다 대장결핵과악성종양의공존시, 선행질환과합병질환사이의병인적인과관계가불분명하지만일부보고들에서는선행된결핵병소에서의대장암의발생가능성을시사한바있다. 2-8 한편, 조직학적으로다른두병변이나란히위치하거나한병변위에다른병변이얹혀있는형태로나타나는충돌병변 (collision pathology) 은대장에서는매우드물게보고되었는데, 16 기존의증례보고와는달리, 저자들은좌하복부통증, 혈 변으로내원한 59세남자환자에서염증성병변인장결핵과, 선암종인대장암이대장의동일부위, 동일병변에충돌하는듯한모양 (collision-like appearance) 으로나타난 1예를경험하여문헌고찰과함께보고한다. 증례 59세남자가 9개월전부터발생한좌하복부통증, 변비, 혈변, 8 kg의체중감소가있어내원하였다. 복부촉진시좌하복부에약 6 6 cm 크기의단단하고고정된종양이만져지고압통이있었다. 내원당시활력징후는, 혈압 120/80 mmhg, 맥박수 82/ 분, 호흡수 20/ 분, 체온 36.6 C였고, 검사실검사에서말초혈액검사는, 혈색소 8.8 gm/dl, 적혈구용적율 21% 였으며, CEA는 35.7 ng/ml ( 정상범위 : 0 8 ng/ml), 대변잠혈검사양성이었다. 흉부방사선촬영에서는우상엽에오래된결핵병변이있었다. 대장내시경검사에서구불결장에관강을막고있는, 쉽게 Vol. 39, No. 5 November, 2009 ( ) 285

(A) Abdominalpelvic CT shows mass-like lesion, distal descending and

invasion. (B) PET-CT shows no distant metastasis. Figure 3.

(A) On low magnititude power, the mucosal part of operated specimen

The Left area in this figure, which is not involved by the tumor, shows

2 Figure 1. Sigmoidscopic finding. The bowel lumen has been obstructed by a mass of which mucosa is bled easily by endoscopic touch. Figure 2. Abdominalpelvic CT and PET-CT findings. (A) Abdominalpelvic CT shows mass-like lesion, distal descending and proximal sigmoid, LLQ pericolic infiltration - cancer with serosa invasion. (B) PET-CT shows no distant metastasis. Figure 3. Microscopic findings. (A) On low magnititude power, the mucosal part of operated specimen shows irregularly infiltrating tumor glands through the muscle proper. The Left area in this figure, which is not involved by the tumor, shows exuberant active inflammation at the serosa and subserosa (H&E stain, 40). (B) On medium magnititude power, aberrant glandular architecture and pleomorphic carcinoma cells are noted (H&E stain, 200). 286 The Korean Journal of Gastrointestinal Endoscopy

Figure 4. Microscopic findings. (A) There are typical caseating granulomas and severe active inflammation of the serosa of the operated specimen (H&E stain, 40).

Follow up oscopy and PET-CT findings. (A) One year later, oscopy shows normal finding after sigmoidectomy and antituberculous.

이때시행한조직검사에서보통수준으로분화된선암종이진단되었고, 복부전산화단층촬영및양전자방출컴퓨터단층촬영에서는원위부하행결장, 근위부구불결장에종양이관찰되며장막의침범이의심되었으나주변조직및간, 폐전이소견은없었다 (Fig. 2).

조직학적인검사에서종양은고유근육층까지침범한보통수준으로분화된선암종이었고림프절전이는없었다 (Fig. 3). 선암종의아래장막층에서는특징적인결핵병변인건락성괴사가있는만성육아종이관찰되었으며 (Fig. 4), 주위 대부분의림프절에서도결핵병소가발견되었고, 결핵균에대한중합효소연쇄반응 (PCR) 도양성소견을보였다.

3 Figure 4. Microscopic findings. (A) There are typical caseating granulomas and severe active inflammation of the serosa of the operated specimen (H&E stain, 40). (B) There are typical caseating granulomas and severe active inflammation of the lymph node of the operated specimen (H&E stain 100). Figure 5. Follow up oscopy and PET-CT findings. (A) One year later, oscopy shows normal finding after sigmoidectomy and antituberculous. (B) PET-CT shows no evidence of local recurrence or distant metastasis after s. 출혈하는종양이있어내시경이근위부로진행되지않았다 (Fig. 1). 이때시행한조직검사에서보통수준으로분화된선암종이진단되었고, 복부전산화단층촬영및양전자방출컴퓨터단층촬영에서는원위부하행결장, 근위부구불결장에종양이관찰되며장막의침범이의심되었으나주변조직및간, 폐전이소견은없었다 (Fig. 2). 구불결장절제술을시행했고, 당시복강내에복수는없었으며, 장간막의비후는관찰되지않았으나병변주위에있는다수의림프절이커져있었고림프절과장막은서로복합된 (Conglomerization) 소견을보였다. 절제된구불결장의육안적소견은 10 6 cm의종양이관강을둘러싸고있는폐쇄소견을보였다. 조직학적인검사에서종양은고유근육층까지침범한보통수준으로분화된선암종이었고림프절전이는없었다 (Fig. 3). 선암종의아래장막층에서는특징적인결핵병변인건락성괴사가있는만성육아종이관찰되었으며 (Fig. 4), 주위 대부분의림프절에서도결핵병소가발견되었고, 결핵균에대한중합효소연쇄반응 (PCR) 도양성소견을보였다. 수술후최종병기는 AJCC (American Joint Committee on Cancer) 기준으로 T 2N 0M 0, 1기에해당하였다. 수술 4개월후시행한대장내시경에서다른부위에결핵병변은없었다. 환자는 9개월간항결핵제를복용하였고, 수술 1 년후에시행한대장내시경 (Fig. 5A), 복부전산화단층촬영및양전자방출컴퓨터단층촬영에서도재발및전이된소견은발견되지않았고 (Fig. 5B), 태아성암항원 (CEA) 도정상이었다. 현재환자는재발없이 24개월째외래에서추적관찰중이다. 고찰본증례의경우염증성병변인건락성육아종이장막과주위림프절에위치하고선암종이고유근육층까지침범하며, 병변 Vol. 39, No. 5 November, 2009 ( ) 287

4 Table 1. Cases of Coexisting Tuberculosis and Carcinoma of Colon in the Different Sites Year of publication Nation Age Sex Site of tuberculosis Site of carcinoma Stage Chest x-ray Treatment Follow up India 6 35 F Proximal transverse Caecum III Rt.hemicolectomy Died (2.5 years) India 6 47 F Caecum Distal transverse I Extended Rt. hemicolectomy (1.5 years) Korea M Ileocecal portion Descending I Old Tb* Total colectomy & ileo-rectal anastomosis (11 months) Korea F Transverse Ascending, transverse III Rt.hemicolectomy Chemotherapy Korea M Ileocecal portion Descending I Old Tb* Lt, hemicolectomy & end to end anastomosis *Old tuberculosis. 이외의구불결장부위, 복막등에는이상소견없이두병변이경계를분명히하며얹혀있는형태로관찰된점이매우흥미롭다. 잘알려진바와같이선암종에는그전암성병변인선종이혼재하는경우가흔한데, 결핵병변에선암종이경계가분명한충돌형태로관찰된경우는보고된바가없다. 충돌병변 (collision pathology) 은근접한위치에서두병변이각각발생하여겹쳐져서존재하지만혼재하지않는형태로, 조직학적으로근원이다른두가지병변이서로근접하거나하나의병변위에다른한가지또는두가지병변이얹혀서발생하는것을말한다. 16 이러한충돌병변의특징으로미루어볼때본증례의두조직학적인병변은근접한위치에서각각발생하여겹쳐진것으로, 본증례의대장결핵과대장암병변은서로의발생에관계가없음을조심스럽게추측해볼수있다. 물론, 결핵병변이장막과주위림프절에서로복합된소견을보이고있어대장장막을침범한결핵성림프절염과대장암이우연히같은부위에동반되었을가능성을배제할수는없다. 궤양성대장염이나크론병과같이염증성병변이오래지속될경우대장암의발생이증가한다는사실을잘알려져있으나결핵성대장염의경우는논란이많다. 실제로 1810년 Bayle이처음결핵과암의공존을보고한이후꾸준히보고하고있어두병변의연관관계를완전히배제할수는없다. 결핵과악성종양이공존하게되는기전에관하여 Randall 및 Tanaka의보고에서는두질환의합병이결핵의호발병소인회맹부에서주로발견된다는점등을들어대장결핵과대장암사이에병인적상호관계가있음을시사한바있으나실제로결핵병소혹은그반흔으로부터악성종양이진행되는지에대해아직입증된바는없다. 2-8 그동안대장에암과결핵이공존할수있는기전으로제기된여러가지가능성으로는대장암으로인해장폐쇄가 합병되어면역력이약해진악성종양점막에결핵균이이차적감염을일으킬수있다는가능성과우연히두병변이공존하거나결핵병소에타장기로부터암이전이되었을가능성을들수있다. 또다른가설로는결핵으로인해장기간지속된염증부위에궤양성대장염에서와같이침윤성대장암이병발하였다는가설인데결핵성장염에서대장암이빈발한다는역학적증거가없고림프절내석회화병변이나병변주위의섬유화가관찰되지않아이러한가설은가능성이적어보인다. 12 따라서, 충돌병변처럼발생한본증례의경우, 우연히두병변이공존할수있다는가설이가장설득력이있어보인다. 그러나결핵병변이대장벽에는관찰되지않고장막및림프절에만관찰되면서, 결핵성복막염의증거가없어대장암이복강내결핵에병발한것인지대장결핵에병발한것인지에대한구분은명확하지가않다. 지금까지발표된대장결핵과대장암이공존했던기존보고들의임상적, 병리학적특징을비교해보았다 (Table 1, 2) 내용을살펴보면, 대장암과대장결핵이합병되는경우에서로다른위치에서발생하거나아니면같은위치에서발생하는데나이는 35세에서 81세까지다양하게분포하였고평균나이는 58세였으며, 여자가우세하게많았다 (10/15). 암과결핵병변이서로다른위치에서발생한경우에는횡행결장, 상행결장, 맹장, 회맹부빈도순으로나타났으며, 서로같은위치에서발생한경우에는대장결핵의호발부위인맹장, 상행결장, 회맹부, 횡행결장의순으로나타났다. 전체적으로살펴보면결핵의호발병소로알려진회맹부와상행결장에주로우세하게발견되었고, 본증례처럼대장암의호발부위인구불결장에서발생하는예는외국에서드물게보고된적이있었으나, 6 국내에는아직보고된예가없었고, 더욱이충돌병변처럼보고된경우 288 The Korean Journal of Gastrointestinal Endoscopy

5 Table 2. Cases of Coexisting Tuberculosis and Carcinoma of Colon in the Same Site Year of publication Nation Age Sex Site of tuberculosis India 5 65 F Caecum, ascending Site of carcinoma Stage Chestx ray Treatment Follow up (years) Caecum, ascending IV Rt.hemicolectomy Died, peritoneum (5 days) Korea 9 53 F Ascending Ascending I Old Tb* Colectomy India 6 50 F Proximal transverse Proximal transverse I Segmental resection (2.5 years) India 6 62 F Terminal ileum, caecum, ascending Caecum I Rt.hemicolectomy (2.5 years) Korea M Transverse Transverse IV Discharge against medical authority Europe 7 81 F Caecum, Ileocecal Caecum, Rt. hemicolectomy portion Ileocecal portion Korea F Caecum, ascending Caecum, ascending I Rt.hemicolectomy India 8 50 M Ascending Ascending I Rt.hemicolectomy Korea F Caecum, appendix Caecum II Rt.hemicolectomy Korea (present case) *Old tuberculosis. 59 M Sigmoid (collision lesion) Died Died (7 months) I Old Tb* Sigmoidectomy (24 months) 는본증례가처음이다. 폐에오래된결핵병변이있는경우는 15예중에 4명 (27%) 이었다. 대장암의병기를평가할수있었던 14예중에 9예 (64.2%) 가 1기였고대장내시경의진입이불가능한장폐쇄를보였던경우가 3예였다. 11,13 결핵과동반된대장암의경우에진단당시 1기가많은이유가확실하지는않지만두가지의가설을생각할수있겠다. 첫째, 대장암에의한증상이나타나기전에결핵에의한체중감소, 복통, 설사, 발열등의증상이대장암초기에나타나서검사하는과정에서대장암이우연히발견되었을가능성이다. 둘째, 림프종이나다른악성종양에서유육종반응 (Sarcoid reaction) 이동반될수있는데이반응은조직학적으로비건락성육아종을특징으로하며림프종또는종양의국소림프절에분포하여면역학적인기전을통하여향후악성종양의예후에유리하게작용한다. 17 대장결핵은결핵균이포함된객담을삼키거나또는혈행성림프성전이에의해발생하는것으로알려져있는데, 일단결핵균이항원제공세포에의해탐식된후결핵균의단백이 T림프구에노출되면세포가증식하고대식세포가활성화된다. 이후점막내에서는항원자극에의한 Th1세포의활성화가일어나며대식세 포와주위조직의괴사가발생하게되는것이다. 대장결핵의주병변이주로점막하에존재하는것도장의점막하층에존재하는많은림프구에밀접한연관이있는것으로알려져있다. 18 건락성괴사가있고없고의차이를제외하면유육종반응과대장결핵발생의면역학적기전이동일하다는점을고려할때대장암과대장결핵이동반된경우대장결핵이대장암의림프절전이의면역학적방어역할을할수도있다는가설을세워볼수있겠다. 결론적으로, 궤양성대장염이나크론병과는달리대장결핵이대장암의위험인자인지는아직까지명확하지않다. 그러나현재까지의보고와본증례를검토해보았을때, 대장암과대장결핵은서로다른질환으로, 우연히동시에발견되는것일가능성이있으며대장결핵은대장암과공존할경우대장암의림프절전이에대한면역학적방어역할을할가능성이있음을제시해본다. 본증례에서는좌하복부동통, 복부팽만감및체중감소를보이던남자환자에서구불결장에대장암과결핵병소가충돌형태로나타났고수술후항결핵제를투여하여양호한경과를 Vol. 39, No. 5 November, 2009 ( ) 289

6 보인한예를경험하여문헌고찰과함께보고한다. 요약 선암종에는그전암성병변인선종이혼재하는경우가흔한데염증성병변인건락성육아종위에선암종이경계를분명히하며얹혀있는형태의충돌병변은매우흥미로운경우로, 결핵과대장암의공존의기존보고는대장결핵의호발부위인회맹부, 상행결장에우세하게발견되었으나대장암의호발부위인구불결장에충돌병변모양으로보고된예는아직까지없었다. 본증례는좌하복부동통, 복부팽만감, 체중감소를보이던남자에서구불결장의동일한위치에대장암과결핵병소가경계를분명히하면서충돌형태로나타나수술후항결핵제투여하여치료한예를경험하여보고한다. 색인단어 : 충돌병변, 대장암, 대장결핵, 구불결장 참고문헌 1. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with ic involvement. Lancet 1990;336: Jain BK. Ileocaecal tuberculosis associated with adenocarcinoma of the caecum and. J Indian Med Assoc 1996;94: Sheikh MY, Yousuf AH, Khalid TR, Islam MU, Ahmed MN. Coexistent tuberculosis and carcinoma of the. J Pak Med Assoc 1995;45: Maheshwari V, Alam K, Indu, Tyagi SP. Ileocaecal tuberculosis associated with adenocarcinoma of the caecum and. J Indian Med Assoc 1995;93: Sane SY, Nimbkar SA. Carcinoma with tuberculosis. J Postgrad Med 1980;26:199A-200A. 6. Jain BK, Chandra SS, Narasimhan R, Ananthakrishnan N, Mehta RB. Coexisting tuberculosis and carcinoma of the. Aust N Z J Surg 1991;61: Isaacs P, Zissis M. Colonic tuberculosis and adenocarcinoma: an unusual presentation. Eur J Gastroenterol Hapatol 1997; 9: Gopal SV, Panda S, Kadambari D, Srinivasan K. Carcinoma associated with tuberculosis: an unusual presentation. Int J Colorectal Dis 2007;22: Ahn TH, Kim JW, Kang DH, Ryu SK, Hyun JH. Colon cancer associated with tuberculosis colitis, report of a case. Korean J Gastroenterol 1988;20: Seong SG, Ryu CS, Kim DK, Park KH, Cho BS, Choi HS. A case of cancer associated with tuberculous colitis. Korean J Gastroenterol 1996;28: Ha CY, Jung HK, Ryu JH, et al. A case of diffuse infiltrative cancer coexisting with ic tuberculosis. Korean J Gastrointest Endosc 2004;29: Han MS, Kim JS, Kim WS, Jang HJ, Kang GH. Colon cancer and polyposis associated with ic tuberculosis. J Korean Soc Coloproctol 2000;16: Hwang LS, Nam SW, Lee SE, et al. A case of pancreatiocobiliary duct obstruction due to pancreatic tuberculosis combined with a adenocarcinoma and tuberculosis colitis. Korean J Gastrointest Endoc 2007;35: Yun SC, Shin EJ, Song OP, et al. A case of cancer associated with ic tuberculosis. J Korean Soc Coloproctol 2007;23: Kim CH, Han HS, Kim JH, Kim BK, Jang SH. A case of cancer coexisting with ic tuberculosis and this presented as bowel perforation. Korean J Gastrointest Endosc 2009;38: Brahmania M, Kanthan CS, Kanthan R. Collision tumor of the -ic adenocarcinoma and ovarian granulosa cell tumor. World J Surg Oncolo 2007;5: Brincker H. Sarcoid reactions in malignant tumors. Cancer Treatment Review 1986;13: Orme IM, Andersen P, Boom H. T cell response to mycobacterium tuberculosis. J Infect Dis 1993;167: The Korean Journal of Gastrointestinal Endoscopy

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untitled 대한소화기내시경학회지 2008;37:369-373 장결핵에동반된대장암 1 예 경희대학교의과대학내과학교실, * 외과학교실 차재명ㆍ이정일ㆍ최재원ㆍ주광로ㆍ정성원ㆍ신현필ㆍ허우영ㆍ이석환 * A Case of Colon Cancer Coexisting with Colonic Tuberculosis Jae Myung Cha, M.D., Joung Il Lee, M.D.,