Rapidly growing adenosquamous carcinoma in the pancreatic tail discovered upon its resection for cervical tuberculous lymphadenitis: A case report

Rapidly growing adenosquamous carcinoma in the pancreatic tail discovered upon its resection for cervical tuberculous lymphadenitis: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Rapidly growing adenosquamous carcinoma in the pancreatic tail discovered upon its resection for cervical tuberculous lymphadenitis: A case report Hideo Ota, Hiromitsu Hoshino, Kyohei Ogisu, ryu Jokoji, Shinya Yamashita, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4023615/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cancer (including pancreatic adenocarcinoma) can develop within one year of tuberculosis infection. However, it is unclear whether tuberculosis infection increases the risk of developing pancreatic adenosquamous carcinoma (ASCP), an extremely rare cancer with a poorer prognosis than pancreatic ductal adenocarcinoma (PDAC). Herein, we report a resected, rapidly growing adenosquamous carcinoma case of the pancreatic tail associated with cervical tuberculous lymphadenitis. The patient is a 57-year-old woman. An excisional biopsy of the swollen right cervical lymph nodes revealed tuberculous lymphadenitis. One month after the biopsy, an abdominal computed tomography scan showed a 2.0 cm (diameter) ischemic tumor in the pancreatic tail. The tissue obtained using endoscopic ultrasonography-guided fine-needle aspiration led to the pathological diagnosis of ASCP. Two months after the biopsy, the tumor had grown to 3.5 cm (diameter), and invasion of the stomach and colon was suspected. A distal pancreatectomy, splenectomy, partial gastrectomy, and transverse colectomy were performed. The final diagnosis was ASCP (4.7 cm, pT3, pN0, cM0, and p Stage IIA). Postoperative adjuvant combination chemotherapy combined with antituberculosis drugs was administered orally. We report the first case of a rapidly growing adenosquamous carcinoma resected from the pancreatic tail in association with cervical tuberculous lymphadenitis. Additional evidence is required to confirm that tuberculosis infection increases the risk of developing pancreatic adenosquamous cell carcinoma because its involvement in squamous cell metaplasia has not been proven. Patients with ASCP who underwent resection and adjuvant chemotherapy without early recurrence may have a 5-year survival rate similar to that of patients with PDAC. Hepatobiliary & Transplant Surgery adenosquamous carcinoma pancreas tuberculous lymphadenitis metaplasia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Cancer and tuberculosis are two of the most common diseases affecting human health worldwide. According to the World Health Organization, tuberculosis is among the infectious diseases with the highest mortality rates worldwide, causing 1.5 million deaths in 2018 [ 1 ] and 155 million survivors in 2020 [ 2 , 3 ]. Infectious pathogens are carcinogens, causing 2.2 million cancers globally each year [ 4 ]. Recent systematic reviews have shown an association between tuberculosis and pulmonary [ 5 ] and non-pulmonary [ 6 ] cancers. However, guidelines for cancer screening in patients with TB are absent. Luczynski et al. [ 7 ] showed that tuberculosis was associated with an increased pooled standard incidence ratio (SIR) of pancreatic cancer (Relative risk [RR]: 1.58, 95% confidence interval [CI]: 1.29–1.93, I 2 = 0%). Additionally, Leung et al. [ 6 ], in a meta-analysis, found that tuberculosis was associated with an increased risk for ten cancer types: head and neck, hepatobiliary, lung, gastrointestinal, pancreatic, kidney and bladder, and ovarian cancer, along with Hodgkin and non-Hodgkin lymphoma, and leukemia. Moreover, Luczynski et al. [ 7 ] indicated that the SIR of all cancers was highest within the first year following tuberculosis infection (SIR: 4.70, 95% CI: 1.80–12.27, I 2 = 99%). Thus, it is crucial to monitor carcinogenesis and cancer development, including pancreatic cancer, within the first year of tuberculosis infection. Adenosquamous carcinoma of the pancreas (ASCP) is an extremely rare subtype of pancreatic neoplasia [ 8 ], accounting for approximately 1–4% of exocrine pancreatic malignancies [ 9 ]. Histologically, ASCP comprises at least 30% of malignant squamous cell carcinomas with coexisting ductal adenocarcinomas [ 10 , 11 ]. The prognosis of ASCP is poor, with a reported median survival of 4 months [ 10 ]. However, no treatment guidelines have been established. Furthermore, ASCP occurring consequently to tuberculosis is not reported. Moreover, an association of tuberculosis infection with adenosquamous carcinoma development remains uncleart. Herein, we present a case of rapidly growing adenosquamous carcinoma of the pancreatic tail discovered sequentially after cervical tuberculous lymphadenitis. Case Presentation A 57-year-old woman underwent lymphadenectomy for a swollen right cervical lymph node. Pathological examination revealed an epithelioid granuloma with caseous necrosis. Ziehl-Neelsen staining revealed acid-fast bacterial cells, leading to the tuberculous lymphadenitis diagnosis (Fig. 1 ). Three months later, abdominal enhanced computed tomography (CT) revealed a 20-mm-in-diameter hypovascular lesion adjacent to the stomach in the pancreatic tail, which was not apparent at the onset of tuberculous lymphadenitis (Fig. 2 (a)(c)). Positron emission tomography/CT confirmed significant uptake in the tumor region despite no initial uptake in this area during tuberculous lymphadenitis onset (Fig. 2 (b)(d)). The patient was referred to our hospital for further investigations. Laboratory tests revealed no peripheral blood abnormalities. Serological results suggested a latent hepatitis B infection (hepatitis B surface antigen (HBsAg) (-) < 0.001 [0–0.004], HBs antibody (HBsAb) (+) 341 [0–9], and hepatitis B core antibody (HBcAb) (+) 163.7 [0–0.9]) and were negative for hepatitis C and syphilis. T-cell spot test for tuberculosis infection (T-SPOT TB) was positive. However, the multiplex polymerase chain reaction was negative for Mycobacterium tuberculosis , Mycobacterium avium , and intracellular bacteria in three consecutive sputum samples. Based on these findings, preexisting tuberculosis infection was suspected. Carbohydrate antigen 19 − 9 (CA19-9) and squamous cell carcinoma (SCC) antigen levels were above normal limits: CA19-9, 318 [0–37]; SCC, 3.0 [0–2.5]. Carcinoembryonic antigen (CEA), duke pancreatic monoclonal antigen type 1, and serum pancreatic antigen type 1 levels were within normal limits. Abdominal enhanced CT revealed a 20-mm-in-diameter hypovascular lesion adjacent to the stomach in the pancreatic tail (Fig. 3 ). Endoscopic ultrasonography (EUS) showed a 20-mm-in-diameter circular hypoechoic mass in the pancreatic tail. Specimens obtained from EUS-guided fine-needle aspiration (EUS-FNA) revealed a poorly differentiated adenocarcinoma with differentiation into squamous epithelium (Fig. 4 ). One month after the first visit, abdominal enhanced CT showed a 35-mm-in-diameter hypovascular enlarged lesion in the pancreatic tail in contact with the stomach and adjacent to the transverse colon (Fig. 5 ). Based on these findings, a preoperative diagnosis of adenosquamous cell carcinoma of the pancreatic tail with suspected invasion of the stomach and transverse colon was made. Therefore, we performed distal pancreatectomy and splenectomy with partial gastric and transverse colon resections (Fig. 6 ). Pathological examination revealed squamous cell carcinoma with extensive keratinization, adenocarcinoma forming a ductal structure, and transition from adenocarcinoma to squamous cell carcinoma. Squamous cell carcinoma cells accounted for over 90% of all tumor cells (Fig. 7 [a-c]). The Ki-67 labeling index was approximately 80–90% (Fig. 7 [d]). Based on these findings, the final diagnosis was ASCP with the following characteristics: Pt (Pancreatic tail), ACS, nodular type, pTS3 (4.7 cm), pT3, int, INF-beta, ly1, v1, ne1, mpd0, pS1 (transverse mesocolon), pRP1, pPV0, pA0, pPL0, pOO1 (stomach), pPCM0, pDPM1, pN0(0/38), cM0, and pStage IIA. The patient received a combination of anti-tuberculous agents with isoniazid, rifampicin, ethambutol, and pyrazinamide, and adjuvant chemotherapy with tegafur/gimeracil/oteracil (Taiho Pharmaceutical Company, Tokyo, Japan). The patient was alive 15 months after distal pancreatectomy and splenectomy. Discussion Individuals with tuberculosis have an increased risk of both pulmonary and non-pulmonary cancer [ 7 ]. Although the pathogenesis underlying the increased risk of malignancy following Mycobacterium tuberculosis infection remains unknown, several hypotheses have been made. Tuberculosis may promote oncogenesis through chronic inflammation, particularly by increasing circulating tumor necrosis factor-alpha (TNF-ɑ) levels. This factor improves tumor-cell survival via anti-apoptotic intracellular signaling pathways, angiogenesis, and mutagenesis [ 12 ]. Tuberculosis leads to fibrous scar formation in the lungs and is associated with an increased incidence of cancer over time [ 13 ]. This is partly due to the impaired lymphatic flow, which causes decreased immune surveillance and increased deposition of metastatic cells [ 14 ]. These hypotheses are likely to apply not only to lung cancer but also to other types of cancer. Leung et al. [ 6 ] and Luczynski et al. [ 7 ] reported that tuberculosis is associated with an increased risk of pancreatic cancer. However, the factors contributing to the development of adenosquamous carcinoma after Mycobacterium tuberculosis infection remain unclear. Nalbandian et al. [ 15 ] showed that squamous cell aggregates consistently appeared within the lung tissue associated with chronic tuberculous lesions and, in some cases, resembled SCC. Chronic tuberculous infection induced lung-specific cell dysplasia and resulted in SCC formation in an experimental model. Tuberculosis may result in the reactivation of permanent tuberculous infection, severe tissue damage, and the appearance of squamous metaplasia in the lung and several other tissues. However, further evidence is required to confirm clinically the findings from this experimental model. Hypotheses regarding the developmental mechanism of adenosquamous cell carcinoma include its origin from cells capable of differentiating into columnar and squamous epithelium [ 16 ], the possibility of ectopic squamous epithelium or normal pancreatic duct metaplasia becoming cancerous [ 17 , 18 ], and the transformation of adenocarcinoma into squamous cell carcinoma (squamous metaplasia of adenocarcinoma) [ 19 , 20 ]. These three hypotheses support the squamous metaplasia theory of adenocarcinomas, indicating that pancreatic adenocarcinoma develops first, followed by squamous cell metaplasia of adenocarcinoma cells. Pathological findings in our case showed a transitional area between adenocarcinoma cells and squamous epithelium, which could indicate squamous metaplasia of the adenocarcinoma. Evidence from previous studies indicates that tuberculosis infection increases the risk of developing pancreatic adenocarcinoma, while adenocarcinoma cells can undergo squamous metaplasia favored by factors such as the infection and the existence of adenosquamous cell carcinoma per se . However, this evidence is insufficient, and further studies are required to determine whether tuberculosis infection affects the transition of pancreatic adenocarcinoma into squamous metaplasia. Charbit et al. demonstrated that the doubling time of squamous cell carcinoma is approximately 80 days, which is half that of adenocarcinoma [ 21 ]. Borazanci et al. reported that tumor cell necrosis is frequently observed in patients with adenosquamous carcinomas [ 22 ]. Necrosis of tumor cells may lead to expansive growth. The area of squamous metaplasia probably increased rapidly due to expansive growth. According to the matched pair analysis for treatment and prognosis of ASCP compared to pancreatic ductal adenocarcinoma (PDAC) by Kaiser et al. [ 23 ], the 5-year overall survival (OS) rates were comparable, with 18.2% in the ASCP group (n = 91) and 17.5% in the PDAC group (n = 2653); however, the median OS was significantly poorer in patients with ASCP than in the unmatched cohort of patients with PDAC. Moreover, the OS of all patients with resected ASCP (n = 83) was significantly longer than that of the patients who did not undergo resection (n = 6). Furthermore, the median survival of patients who received adjuvant chemotherapy (n = 52) was significantly longer than that of patients who did not receive adjuvant chemotherapy (n = 24). Patients who did not experience early recurrence after resection and adjuvant chemotherapy for the treatment of ASCP may have a 5-year survival rate similar to that of patients with PDAC. In conclusion, we report the first case of a rapidly growing adenosquamous carcinoma that developed in the pancreatic tail sequentially to the development of cervical tuberculous lymphadenitis. Patients with tuberculosis are more likely to develop cancer within one year of infection diagnosis. Although tuberculosis may induce the development of pancreatic adenosquamous cell carcinoma, its effect on squamous metaplasia is demonstrated only at an experimental level and has not been fully elucidated; thus, further evidence is needed. Abbreviations ASCP, adenosquamous carcinoma of pancreas; PDAC, pancreatic ductal adenocarcinoma; CT, computed tomography; EUS, endoscopic ultrasonography; EUS-FNA, EUS-guided fine-needle aspiration; HBsAg, Hepatitis B surface antigen; Ab, antibody; HBcAb, Hepatitis B core antibody; T-SPOT TB, T-cell spot test for tuberculosis infection; CA19-9, Carbohydrate antigen 19-9; SCC, Squamous cell carcinoma; CEA, Carcinoembryonic antigen; PET, Positron emission tomography. Declarations Acknowledgements This manuscript was proofread by a professional editor who is a native English speaker at Editage, a division of Cactus Communications (https://www.editage.jp). Authors’ contributions All authors have read and approved the final manuscript. Funding No funding. Consent for publication Written informed consent was obtained from all patients involved in this study and their accompanying images. A copy of this written consent form is available for review by the journal’s editor-in-chief. Availability of data and materials All data generated or analyzed in this case report are included in this published article and its supplementary information files. Conflict of interest The authors declare that they have no conflict of interest. References Harding E (2020) WHO global report on tuberculosis elimination. Lancer Respir Med 8:30418–30417 Dodd PJ, Yuen CM, Jayasooriya SM et al (2021) Quantifying the global number of tuberculosis survivors: a modelling study. Lancet Infect Dis 21:984–992 World Health Organization (2021) Global tuberculosis report. 2021. Geneva: World Health Organization; 2021. https://iris.who.int/bitstream/handle/10665/346387/9789240037021-eng.pdf?sequence=1 accessed 14 October 2021 De Martel C, Georges D, Bray F et al (2020) Global burden of cancer attributable infections in 2018: a worldwide incidence analysis. Lancer Glob Heal 8:e180–e190 Abdeahad H, Salehi M, Yaghoubi A et al (2022) Pervious pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis. Infect Dis (Lond) 54:255–268 Leung CY, Huang HL, Rahman MM et al (2020) Cancer incidence attributable to tuberculosis in 2015: global, regional, and national estimates. BMC Cancer 20:412 Luczynski P, Poulin P, Romanowski K et al (2022) Tuberculosis and risk of cancer: A systematic review and meta-analysis. PLoS ONE 17:e0278661 Nagtegaal ID, Odze RD, Klimstra D et al (2020) The 2019 WHO classification of tumours of the digestive system. Histopathology 76:182–188 Madura JA, Jarman BT, Doherty MG et al (1999) Adenosquamous carcinoma of the pancreas. Arch Surg 134:599–603 Boyd CA, Benarroch-Gampel J, Sheffield KM et al (2012) 415 patients with adenosquamous carcinoma of the pancreas: a population-based analysis of prognosis and survival. J Surg Res 174:12–19 Okabayashi T, Hanazaki K (2008) Surgical outcomes of adenosquamous carcinoma of the pancreas. World J Gastroenterol 14:6765–6770 Hussain SP, Hofseth LJ, Harris CC (2003) Radical causes of cancer. Nat Rev Cancer 3:276–285 Yu YY, Pinsky PF, Caporaso NE et al (2008) Lung cancer risk following detection of pulmonary scarring by chest radiography in the prostate, lung, colorectal, and ovarian cancer screening trial. Arch Intern Med 168:2326–2332 Ardies CM (2003) Inflammation as cause for scar cancers of the lung. Integr Cancer Ther 2:238–246 Nalbandian A, Yan B-S, Pichugin A et al (2009) Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control. Oncogene 28:1928–1938 Wood DA (1943) Adenoacanthoma of the pyloric end of the stomach: a consideration of its histogenesis and a report of two cases. Arch Pathol 36:177–189 Boswell JT, Helwig EB (1965) Squamous cell carcinoma and adenoacanthoa of the stomach. A clinicopathologic study. Cancer 18:181–192 Cook CB, Klickstein GD (1958) Adenoacanthomas of the colon. AMA Arch Pathol 65:681–687 Barr RJ, Hancock DE (1975) Adenosquamous carcinoma of the liver. Gastroenterology 69:1326–1330 Straus R, Heschel S, Fortmann DJ (1969) Primary adenosquamous carcinoma of the stomach. A case report and review. Cancer 24:985–995 Charbit A, Malaise EP, Tubiana M (1971) Relation between the pathological nature and the growth rate of human tumors. Eur J Cancer 7:307–315 Borazanci E, Millis SZ, Korn R et al (2015) Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review. World J Gastrointest Oncol 7:132–140 Kaiser J, Hinz U, Mayer P et al (2021) Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas - Matched-pair analysis with pancreatic ductal adenocarcinoma. Eur J Surg Oncol 47:1734–1741 Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4023615","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":276935009,"identity":"1275a815-9242-4be8-aa9c-a1743aad1baf","order_by":0,"name":"Hideo Ota","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYBACAzBZwZDA2IAsLIFfC1DxGYYE5gZkxQS1MLYxJLCjaMEHzBmYjz/4Oa8uj7eB/eEDxh02dQzSzQcYLHfg1mLZwJbY2LuNrViygcfYgPFMmgSDzLEEBskzeBx2/41hA+82nsSNDTxs0n/bDkswSOQYMEi24dFygMew8e8cicT9B9ifSTC2/Qdqyf9AUEszb4NBYmMDgxlQywGQLQwEtLAlzga6vpixGeSXtmTJNok0gwN4/XKA+cDHNzV1eYzt7cAQa7Pj55dIfvhYEk+IIQAzlGYD4sOSDcRoQQaMH0nWMgpGwSgYBcMYAADwzUlFal8b1AAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Gastroenterological Surgery,Nippon Life Hosptal","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hideo","middleName":"","lastName":"Ota","suffix":""},{"id":276935010,"identity":"05b780da-619a-4e1b-9f2c-6a5ac3bd4874","order_by":1,"name":"Hiromitsu Hoshino","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiromitsu","middleName":"","lastName":"Hoshino","suffix":""},{"id":276936046,"identity":"da9baa02-e76e-449f-bf7a-08015da08f37","order_by":2,"name":"Kyohei Ogisu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kyohei","middleName":"","lastName":"Ogisu","suffix":""},{"id":276936047,"identity":"8d1f4acc-32f1-41d5-b878-af2aeebfabae","order_by":3,"name":"ryu Jokoji","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"ryu","middleName":"","lastName":"Jokoji","suffix":""},{"id":276936048,"identity":"9af5bff6-ab4f-4915-ba44-964df858c1f1","order_by":4,"name":"Shinya Yamashita","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shinya","middleName":"","lastName":"Yamashita","suffix":""},{"id":276936049,"identity":"c75e44be-af15-4857-a9c5-7c2a4aecf989","order_by":5,"name":"Hirofumi Ikushima","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hirofumi","middleName":"","lastName":"Ikushima","suffix":""},{"id":276936050,"identity":"ab9875fb-defb-407e-ac72-6a86d2bd17cb","order_by":6,"name":"Yoshifumi Arisaka","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yoshifumi","middleName":"","lastName":"Arisaka","suffix":""},{"id":276936051,"identity":"b9b16da9-dcde-43d0-a0e2-ef434e7a365e","order_by":7,"name":"Hitoshi Mizuno","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hitoshi","middleName":"","lastName":"Mizuno","suffix":""}],"badges":[],"createdAt":"2024-03-07 08:41:16","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":true,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-4023615/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4023615/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52302746,"identity":"5ba3858a-7990-4e0e-8611-c2f9d981b088","added_by":"auto","created_at":"2024-03-08 18:48:13","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":348346,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCervical tuberculous lymphadenitis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Cervical enhanced computer tomography (CT) findings reveal a 10-mm (in diameter) hypovascular lesion in the swollen right cervical area (arrow); (b) positron-emission tomography/CT shows tumor uptake; (c)-(e) pathological examination of resected cervical lymph nodes showing epithelioid granuloma with caseation necrosis; (f) Ziehl-Neelsen staining depicts a small number of acid-fast bacterial cells (arrow), establishing diagnosis of tuberculous lymphadenitis\u003c/p\u003e","description":"","filename":"1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/22c59b7f0d241d9b5e0cb3e8.jpeg"},{"id":52302750,"identity":"0b7063a6-aaf0-45e0-808b-555bcd29c932","added_by":"auto","created_at":"2024-03-08 18:48:13","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":189115,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAbdominal plain computed tomography (CT) and positron-emission tomography (PET)/CT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a)(b) At the onset of tuberculous lymphadenitis\u003c/p\u003e\n\u003cp\u003e(c)(d) Three months after the onset of lymphadenitis (during the first visit to our department)\u003c/p\u003e\n\u003cp\u003e(a)(c) Abdominal CT (b)(d) Positron emission tomography (PET)/CT\u003c/p\u003e\n\u003cp\u003eThree months after the onset of lymphadenitis, plain abdominal CT reveals an enlarged area in the pancreatic tail, and PET/CT confirms increased uptake in this area\u003c/p\u003e","description":"","filename":"2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/806cda70fb1ad28471df72ac.jpeg"},{"id":52302751,"identity":"d5d10581-5b9f-4986-95ba-17a696b28706","added_by":"auto","created_at":"2024-03-08 18:48:13","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":165266,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAbdominal contrast-enhanced computed tomography (CT) (during the first visit to our department)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Arterial phase; (b)(d) portal phase; (c) equilibrium phase\u003c/p\u003e\n\u003cp\u003e(a-c) Abdominal enhanced CT shows a 20-mm-in-diameter hypovascular lesion (tumor, circled area)\u003c/p\u003e\n\u003cp\u003e(d) Lesions adjacent to the stomach in the pancreatic tail (tumor, circled area)\u003c/p\u003e","description":"","filename":"3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/6a0b8191d9dc535bafcb0b4d.jpeg"},{"id":52302748,"identity":"2acba652-42b9-44e9-abc5-e10b3182e0ac","added_by":"auto","created_at":"2024-03-08 18:48:13","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":172952,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEndoscopic ultrasonography (EUS)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) EUS showing a 20 mm-in-diameter circular hypoechoic mass in the pancreatic tail (arrow)\u003c/p\u003e\n\u003cp\u003e(b) Hypovascular lesion is observed (arrow)\u003c/p\u003e\n\u003cp\u003e(c) EUS-guided fine-needle aspiration reveals a poorly differentiated adenocarcinoma with differentiation into the squamous epithelium (arrow)\u003c/p\u003e","description":"","filename":"4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/b4ed9cd49c99739245155948.jpeg"},{"id":52303134,"identity":"0a0adfe3-2bab-4782-b60d-a90e2aaa4455","added_by":"auto","created_at":"2024-03-08 18:56:13","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":258003,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAbdominal contrast-enhanced computed tomography (CT) (one month after the first visit to our department)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a)(d) Plain; (b)(e) arterial phase; (c)(f)(g) portal phase\u003c/p\u003e\n\u003cp\u003e(a-f) Axial section; (g) coronal section\u003c/p\u003e\n\u003cp\u003eAbdominal enhanced CT shows a 35-mm-in-diameter hypovascular enlarged lesion in the pancreatic tail in contact with the stomach [(a-c), (g), circled area] and adjacent to the transverse colon [(d-g), circled area]\u003c/p\u003e","description":"","filename":"5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/bf556ab42a6f1d84a3febe41.jpeg"},{"id":52304492,"identity":"93f5b9c9-445e-4b70-af4a-71876721d3d4","added_by":"auto","created_at":"2024-03-08 19:04:13","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":375238,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntraoperative and macroscopic findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDistal pancreatectomy with splenectomy with partial gastric and transverse colon resections.\u003c/p\u003e\n\u003cp\u003e(a) Intraoperative findings indicating tumor invasion of the gastric serosa; (b) macroscopic examination revealing tumor invasion of the gastric mucosa; (c) macroscopically suspected tumor invasion of the transverse colon serosa; (d) cross-section of the macroscopic findings showing tumor invasion in the transverse mesocolon without invasion of the transverse colonic serosa\u003c/p\u003e","description":"","filename":"6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/a9b26b1a2593d610dd1a8b36.jpeg"},{"id":52303133,"identity":"4e8a3fa0-72e6-40c0-8ec0-41cf8aaec851","added_by":"auto","created_at":"2024-03-08 18:56:13","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":658682,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMicroscopic findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Atypical cells with high degree nuclear atypia forming alveolar structures that grow invasively, indicating squamous cell carcinoma with extensive keratinization\u003c/p\u003e\n\u003cp\u003e(b) Adenocarcinoma forming ductal structures in certain areas\u003c/p\u003e\n\u003cp\u003e(c) Transition from adenocarcinoma to squamous cell carcinoma observed in some regions. Squamous cell carcinoma cells account for over 90% of all tumor cells\u003c/p\u003e\n\u003cp\u003e(d) Ki-67 labeling index at approximately 80–90%\u003c/p\u003e","description":"","filename":"7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/7b264fb3cf8d32a4cd678f6b.jpeg"},{"id":52304794,"identity":"a4791b76-4a89-414e-888b-eabb10048a7a","added_by":"auto","created_at":"2024-03-08 19:12:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1012091,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4023615/v1/000aa711-e711-4cb6-97bb-31f210f90801.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eRapidly growing adenosquamous carcinoma in the pancreatic tail discovered upon its resection for cervical tuberculous lymphadenitis: A case report\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCancer and tuberculosis are two of the most common diseases affecting human health worldwide. According to the World Health Organization, tuberculosis is among the infectious diseases with the highest mortality rates worldwide, causing 1.5\u0026nbsp;million deaths in 2018 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and 155\u0026nbsp;million survivors in 2020 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Infectious pathogens are carcinogens, causing 2.2\u0026nbsp;million cancers globally each year [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recent systematic reviews have shown an association between tuberculosis and pulmonary [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and non-pulmonary [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] cancers. However, guidelines for cancer screening in patients with TB are absent.\u003c/p\u003e \u003cp\u003eLuczynski et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] showed that tuberculosis was associated with an increased pooled standard incidence ratio (SIR) of pancreatic cancer (Relative risk [RR]: 1.58, 95% confidence interval [CI]: 1.29\u0026ndash;1.93, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%). Additionally, Leung et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], in a meta-analysis, found that tuberculosis was associated with an increased risk for ten cancer types: head and neck, hepatobiliary, lung, gastrointestinal, pancreatic, kidney and bladder, and ovarian cancer, along with Hodgkin and non-Hodgkin lymphoma, and leukemia. Moreover, Luczynski et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] indicated that the SIR of all cancers was highest within the first year following tuberculosis infection (SIR: 4.70, 95% CI: 1.80\u0026ndash;12.27, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;99%). Thus, it is crucial to monitor carcinogenesis and cancer development, including pancreatic cancer, within the first year of tuberculosis infection.\u003c/p\u003e \u003cp\u003eAdenosquamous carcinoma of the pancreas (ASCP) is an extremely rare subtype of pancreatic neoplasia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], accounting for approximately 1\u0026ndash;4% of exocrine pancreatic malignancies [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Histologically, ASCP comprises at least 30% of malignant squamous cell carcinomas with coexisting ductal adenocarcinomas [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The prognosis of ASCP is poor, with a reported median survival of 4 months [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, no treatment guidelines have been established.\u003c/p\u003e \u003cp\u003eFurthermore, ASCP occurring consequently to tuberculosis is not reported. Moreover, an association of tuberculosis infection with adenosquamous carcinoma development remains uncleart. Herein, we present a case of rapidly growing adenosquamous carcinoma of the pancreatic tail discovered sequentially after cervical tuberculous lymphadenitis.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 57-year-old woman underwent lymphadenectomy for a swollen right cervical lymph node. Pathological examination revealed an epithelioid granuloma with caseous necrosis. Ziehl-Neelsen staining revealed acid-fast bacterial cells, leading to the tuberculous lymphadenitis diagnosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Three months later, abdominal enhanced computed tomography (CT) revealed a 20-mm-in-diameter hypovascular lesion adjacent to the stomach in the pancreatic tail, which was not apparent at the onset of tuberculous lymphadenitis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e(a)(c)). Positron emission tomography/CT confirmed significant uptake in the tumor region despite no initial uptake in this area during tuberculous lymphadenitis onset (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e(b)(d)). The patient was referred to our hospital for further investigations. Laboratory tests revealed no peripheral blood abnormalities. Serological results suggested a latent hepatitis B infection (hepatitis B surface antigen (HBsAg) (-)\u0026thinsp;\u0026lt;\u0026thinsp;0.001 [0\u0026ndash;0.004], HBs antibody (HBsAb) (+) 341 [0\u0026ndash;9], and hepatitis B core antibody (HBcAb) (+) 163.7 [0\u0026ndash;0.9]) and were negative for hepatitis C and syphilis. T-cell spot test for tuberculosis infection (T-SPOT TB) was positive. However, the multiplex polymerase chain reaction was negative for \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, \u003cem\u003eMycobacterium avium\u003c/em\u003e, and intracellular bacteria in three consecutive sputum samples. Based on these findings, preexisting tuberculosis infection was suspected. Carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA19-9) and squamous cell carcinoma (SCC) antigen levels were above normal limits: CA19-9, 318 [0\u0026ndash;37]; SCC, 3.0 [0\u0026ndash;2.5]. Carcinoembryonic antigen (CEA), duke pancreatic monoclonal antigen type 1, and serum pancreatic antigen type 1 levels were within normal limits. Abdominal enhanced CT revealed a 20-mm-in-diameter hypovascular lesion adjacent to the stomach in the pancreatic tail (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Endoscopic ultrasonography (EUS) showed a 20-mm-in-diameter circular hypoechoic mass in the pancreatic tail. Specimens obtained from EUS-guided fine-needle aspiration (EUS-FNA) revealed a poorly differentiated adenocarcinoma with differentiation into squamous epithelium (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). One month after the first visit, abdominal enhanced CT showed a 35-mm-in-diameter hypovascular enlarged lesion in the pancreatic tail in contact with the stomach and adjacent to the transverse colon (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Based on these findings, a preoperative diagnosis of adenosquamous cell carcinoma of the pancreatic tail with suspected invasion of the stomach and transverse colon was made. Therefore, we performed distal pancreatectomy and splenectomy with partial gastric and transverse colon resections (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Pathological examination revealed squamous cell carcinoma with extensive keratinization, adenocarcinoma forming a ductal structure, and transition from adenocarcinoma to squamous cell carcinoma. Squamous cell carcinoma cells accounted for over 90% of all tumor cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e[a-c]). The Ki-67 labeling index was approximately 80\u0026ndash;90% (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e[d]). Based on these findings, the final diagnosis was ASCP with the following characteristics: Pt (Pancreatic tail), ACS, nodular type, pTS3 (4.7 cm), pT3, int, INF-beta, ly1, v1, ne1, mpd0, pS1 (transverse mesocolon), pRP1, pPV0, pA0, pPL0, pOO1 (stomach), pPCM0, pDPM1, pN0(0/38), cM0, and pStage IIA. The patient received a combination of anti-tuberculous agents with isoniazid, rifampicin, ethambutol, and pyrazinamide, and adjuvant chemotherapy with tegafur/gimeracil/oteracil (Taiho Pharmaceutical Company, Tokyo, Japan). The patient was alive 15 months after distal pancreatectomy and splenectomy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIndividuals with tuberculosis have an increased risk of both pulmonary and non-pulmonary cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the pathogenesis underlying the increased risk of malignancy following \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e infection remains unknown, several hypotheses have been made. Tuberculosis may promote oncogenesis through chronic inflammation, particularly by increasing circulating tumor necrosis factor-alpha (TNF-ɑ) levels. This factor improves tumor-cell survival via anti-apoptotic intracellular signaling pathways, angiogenesis, and mutagenesis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Tuberculosis leads to fibrous scar formation in the lungs and is associated with an increased incidence of cancer over time [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This is partly due to the impaired lymphatic flow, which causes decreased immune surveillance and increased deposition of metastatic cells [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These hypotheses are likely to apply not only to lung cancer but also to other types of cancer.\u003c/p\u003e \u003cp\u003eLeung et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and Luczynski et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] reported that tuberculosis is associated with an increased risk of pancreatic cancer. However, the factors contributing to the development of adenosquamous carcinoma after \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e infection remain unclear.\u003c/p\u003e \u003cp\u003eNalbandian et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] showed that squamous cell aggregates consistently appeared within the lung tissue associated with chronic tuberculous lesions and, in some cases, resembled SCC. Chronic tuberculous infection induced lung-specific cell dysplasia and resulted in SCC formation in an experimental model. Tuberculosis may result in the reactivation of permanent tuberculous infection, severe tissue damage, and the appearance of squamous metaplasia in the lung and several other tissues. However, further evidence is required to confirm clinically the findings from this experimental model.\u003c/p\u003e \u003cp\u003eHypotheses regarding the developmental mechanism of adenosquamous cell carcinoma include its origin from cells capable of differentiating into columnar and squamous epithelium [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], the possibility of ectopic squamous epithelium or normal pancreatic duct metaplasia becoming cancerous [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and the transformation of adenocarcinoma into squamous cell carcinoma (squamous metaplasia of adenocarcinoma) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These three hypotheses support the squamous metaplasia theory of adenocarcinomas, indicating that pancreatic adenocarcinoma develops first, followed by squamous cell metaplasia of adenocarcinoma cells. Pathological findings in our case showed a transitional area between adenocarcinoma cells and squamous epithelium, which could indicate squamous metaplasia of the adenocarcinoma.\u003c/p\u003e \u003cp\u003eEvidence from previous studies indicates that tuberculosis infection increases the risk of developing pancreatic adenocarcinoma, while adenocarcinoma cells can undergo squamous metaplasia favored by factors such as the infection and the existence of adenosquamous cell carcinoma \u003cem\u003eper se\u003c/em\u003e. However, this evidence is insufficient, and further studies are required to determine whether tuberculosis infection affects the transition of pancreatic adenocarcinoma into squamous metaplasia.\u003c/p\u003e \u003cp\u003eCharbit et al. demonstrated that the doubling time of squamous cell carcinoma is approximately 80 days, which is half that of adenocarcinoma [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Borazanci et al. reported that tumor cell necrosis is frequently observed in patients with adenosquamous carcinomas [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Necrosis of tumor cells may lead to expansive growth. The area of squamous metaplasia probably increased rapidly due to expansive growth.\u003c/p\u003e \u003cp\u003eAccording to the matched pair analysis for treatment and prognosis of ASCP compared to pancreatic ductal adenocarcinoma (PDAC) by Kaiser et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], the 5-year overall survival (OS) rates were comparable, with 18.2% in the ASCP group (n\u0026thinsp;=\u0026thinsp;91) and 17.5% in the PDAC group (n\u0026thinsp;=\u0026thinsp;2653); however, the median OS was significantly poorer in patients with ASCP than in the unmatched cohort of patients with PDAC. Moreover, the OS of all patients with resected ASCP (n\u0026thinsp;=\u0026thinsp;83) was significantly longer than that of the patients who did not undergo resection (n\u0026thinsp;=\u0026thinsp;6). Furthermore, the median survival of patients who received adjuvant chemotherapy (n\u0026thinsp;=\u0026thinsp;52) was significantly longer than that of patients who did not receive adjuvant chemotherapy (n\u0026thinsp;=\u0026thinsp;24). Patients who did not experience early recurrence after resection and adjuvant chemotherapy for the treatment of ASCP may have a 5-year survival rate similar to that of patients with PDAC.\u003c/p\u003e \u003cp\u003eIn conclusion, we report the first case of a rapidly growing adenosquamous carcinoma that developed in the pancreatic tail sequentially to the development of cervical tuberculous lymphadenitis. Patients with tuberculosis are more likely to develop cancer within one year of infection diagnosis. Although tuberculosis may induce the development of pancreatic adenosquamous cell carcinoma, its effect on squamous metaplasia is demonstrated only at an experimental level and has not been fully elucidated; thus, further evidence is needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASCP, adenosquamous carcinoma of pancreas; PDAC, pancreatic ductal adenocarcinoma; CT, computed tomography; EUS, endoscopic ultrasonography; EUS-FNA, EUS-guided fine-needle aspiration; HBsAg, Hepatitis B surface antigen; Ab, antibody; HBcAb, Hepatitis B core antibody; T-SPOT TB, T-cell spot test for tuberculosis infection; CA19-9, Carbohydrate antigen 19-9; SCC, Squamous cell carcinoma; CEA, Carcinoembryonic antigen; PET, Positron emission tomography.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript was proofread by a professional editor who is a native English speaker at Editage, a division of Cactus Communications (https://www.editage.jp).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all patients involved in this\u0026nbsp;study and their accompanying images. A copy of this written consent form is available for review by the journal\u0026rsquo;s editor-in-chief.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed in this case report are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHarding E (2020) WHO global report on tuberculosis elimination. Lancer Respir Med 8:30418\u0026ndash;30417\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDodd PJ, Yuen CM, Jayasooriya SM et al (2021) Quantifying the global number of tuberculosis survivors: a modelling study. 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Histopathology 76:182\u0026ndash;188\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadura JA, Jarman BT, Doherty MG et al (1999) Adenosquamous carcinoma of the pancreas. Arch Surg 134:599\u0026ndash;603\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoyd CA, Benarroch-Gampel J, Sheffield KM et al (2012) 415 patients with adenosquamous carcinoma of the pancreas: a population-based analysis of prognosis and survival. J Surg Res 174:12\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkabayashi T, Hanazaki K (2008) Surgical outcomes of adenosquamous carcinoma of the pancreas. World J Gastroenterol 14:6765\u0026ndash;6770\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussain SP, Hofseth LJ, Harris CC (2003) Radical causes of cancer. 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Eur J Surg Oncol 47:1734\u0026ndash;1741\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Nippon Life Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"adenosquamous carcinoma, pancreas, tuberculous lymphadenitis, metaplasia","lastPublishedDoi":"10.21203/rs.3.rs-4023615/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4023615/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCancer (including pancreatic adenocarcinoma) can develop within one year of tuberculosis infection. However, it is unclear whether tuberculosis infection increases the risk of developing pancreatic adenosquamous carcinoma (ASCP), an extremely rare cancer with a poorer prognosis than pancreatic ductal adenocarcinoma (PDAC). Herein, we report a resected, rapidly growing adenosquamous carcinoma case of the pancreatic tail associated with cervical tuberculous lymphadenitis. The patient is a 57-year-old woman. An excisional biopsy of the swollen right cervical lymph nodes revealed tuberculous lymphadenitis. One month after the biopsy, an abdominal computed tomography scan showed a 2.0 cm (diameter) ischemic tumor in the pancreatic tail. The tissue obtained using endoscopic ultrasonography-guided fine-needle aspiration led to the pathological diagnosis of ASCP. Two months after the biopsy, the tumor had grown to 3.5 cm (diameter), and invasion of the stomach and colon was suspected. A distal pancreatectomy, splenectomy, partial gastrectomy, and transverse colectomy were performed. The final diagnosis was ASCP (4.7 cm, pT3, pN0, cM0, and p Stage IIA). Postoperative adjuvant combination chemotherapy combined with antituberculosis drugs was administered orally. We report the first case of a rapidly growing adenosquamous carcinoma resected from the pancreatic tail in association with cervical tuberculous lymphadenitis. Additional evidence is required to confirm that tuberculosis infection increases the risk of developing pancreatic adenosquamous cell carcinoma because its involvement in squamous cell metaplasia has not been proven. Patients with ASCP who underwent resection and adjuvant chemotherapy without early recurrence may have a 5-year survival rate similar to that of patients with PDAC.\u003c/p\u003e","manuscriptTitle":"Rapidly growing adenosquamous carcinoma in the pancreatic tail discovered upon its resection for cervical tuberculous lymphadenitis: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-08 18:48:08","doi":"10.21203/rs.3.rs-4023615/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1d54993-3631-4ba0-8e23-7bf1f258f02a","owner":[],"postedDate":"March 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29187915,"name":"Hepatobiliary \u0026 Transplant Surgery"}],"tags":[],"updatedAt":"2024-03-08T18:48:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-08 18:48:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4023615","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4023615","identity":"rs-4023615","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}