{"paper_id":"47d7b3b1-b12c-4440-ae16-38f7f9d355a7","body_text":"More than 90% of colorectal cancer (CRC) is well-to-moderately differentiated\nadenocarcinoma. Primary adenosquamous carcinoma (ASC) of the colon is extremely rare. It has\nhigh malignant potential and its long-term prognosis is usually unfavorable. 1  Here, we report a rare case of cecal ASC with good\nprognosis.\n\nA 63-year-old woman was admitted to our hospital with a right lower abdominal mass.\nShe had no relevant previous medical or family history. On admission, her height and body weight\nwere 145 cm and 40 kg, respectively. Her initial laboratory data showed severe anemia,\nwith hemoglobin levels of 5.6 g/dL, red blood cell count of 3.888×10 6 /μL,\nand platelet count of 69.4×10 4 /μL, as well as slight transaminitis and\nproteinemia. Marker antigen levels were carcinoembryonic antigen (CEA): 1.9 ng (normal:\n<5.0); carbohydrate antigen 19-9 (CA19-9): 0.1 U/mL (normal: <37); and squamous cell\ncarcinoma (SCC) antigen: 0.6 ng/mL (normal: <1.5).\nAbdominopelvic contrast-enhanced computed tomography (CT) showed a large mass\ninvolving the cecum and the right ovary, with well-contrasted circumference vessels. The tumor\nsize was 100×80×70 mm, and was of suspected cecal origin, with swelling of the\nmesenteric lymph nodes ( Figure 1 ). Barium enema findings\nshowed cecal wall thickness and obstruction with a “apple core sign”; however, barium flow to\nthe ileum was good ( Figure 2 ).\nColonoscopy and biopsy could not be performed as the patient refused; therefore,\nhistological diagnosis was not possible. Surgery was performed with a pre-operative diagnosis of\ncarcinoma with the suspected origin in cecum or right ovary. During surgery, we identified the\norigin of this tumor as a cecal carcinoma, with invasion to the retroperitoneum and right ovary,\nas well as the right external iliac artery. We performed an ileocecal resection with bilateral\noophorectomy, partial resection of iliopsoas muscle, and D3 lymph node resection. We observed no\nevidence of peritoneum dissemination or hepatic metastases.\nPathological findings showed a type 2 tumor, measuring 10 cm in diameter at the\ncecum, that had invaded to the right ovary and iliopsoas muscle. The tumor was pathologically\ndiagnosed as adenosquamous cell carcinoma, T4b (retroperitoneum), int, INFβ, ly2, v1, n1(2/11),\n 2RAS -wild type. Immunohistochemical examination showed it to be MLH1+, PMS2+,\nand MSH6+ ( Figures 3 ,  4 ). 2\nThe patient had no postoperative complications. She received eight courses of\nadjuvant chemotherapy with CapeOX (capecitabine 2000 mg/m 2  PO d1–14, oxaliplatin\n130 mg/m 2  civ d1) over 6 months. A colonoscopy performed 18 months after the\ninitial surgery found an Isp polyp at the sigmoid colon, for which an endoscopic mucosal\nresection was performed. Pathological findings of the polyp revealed a well-differentiated\nadenocarcinoma, depth 500 μm, ly0, v0. A follow-up CT 7 years after the initial surgery\nrevealed a tumor of the right breast, diagnosed as invasive ductal carcinoma, and resected. The\npatient is currently receiving postoperative adjuvant hormonal therapy and is alive 8 years\nafter the first surgery, with no recurrence of colonic ASC.\n\nJapanese clinical guidelines for colon cancer define ASC of the colon as a neoplasm\nthat comprises adenocarcinoma and SCC. The histogenesis of ASC of the colon is not clearly\nunderstood, but three hypotheses have been suggested: (1) undifferentiated or reverse cells in\nthe colonic epithelium may change directly into SCC; (2) secondary ASC derived from\nadenocarcinoma (currently, the most widely accepted explanation); and (3) ectopic squamous cells\nin the colonic mucosa may be directly transformed into squamous malignant cells. 3 , 4  ASC of the\ncolon is rare, with an incidence of 0.1%−0.2% among all CRCs. 5  Masoomi et al. reported a population-based evaluation of ASC of the colon\nin the California Cancer Registry from 1994 to 2004; they found that out of 111,263 cases of\nCRC, ASC was identified in only 99 cases (0.09%). 6  The most common location was the proximal colon and the median age was 67\nyears, which is similar to our present case. As colorectal ASC tends to form both regional and\ndistant metastases, its long-term prognosis is often unfavorable, with an overall 5-year\nsurvival rate of only 31%. A study of 576 patients with ASC in Taiwan showed 27 had colorectal\nASC (0.04%); it found that colorectal ASC was most likely to affect the respiratory system\n(73.8%), followed by the alimentary canal (16.2%), and the female reproductive tract (10%), and\nthat prognosis for ASC of the colon was much worse than for other primary ASCs. 7 , 8  Data from the\nNational Institutes of Health also showed a poor prognosis, which Hijikawa et al. suggested\nwas due to the very rapid growth of secondary ASC derived from adenocarcinoma. 4  Our present patient had no distant metastases, but as\nshe had lymph node metastases and T4b tumor depth, she had a high risk of recurrence. She\nreceived adjuvant chemotherapy using CapeOX for colon adenocarcinoma; however, the exact role of\nadjuvant chemotherapy remains unclear. 9\nIn the present case, the patient developed early sigmoid colon cancer at 1 year\nafter the first surgery and advanced breast cancer at 7 years after. Metachronous colon cancer\nis a criterion for Lynch syndrome in the Revised Bethesda guidelines. Raymond et al.\nreported the possibility of Lynch syndrome-associated breast and prostate cancers. 10  In the present case, the specimen was immunopositive\nfor MLH1, PMS2, and MSH6; however, these proteins are not clearly described in the criteria and\nwe conclude this case is not Lynch syndrome. Recently, Duncan et al. reported high\nmicrosatellite instability in ASC and ASC with Lynch syndrome. 11 – 13\nAs no biomarkers for diagnosis and prognosis are currently known, we should treat\nASC as conventional adenocarcinoma. In the future, we expect genetic analysis using\nnext-generation sequencing to assist in drug and treatment choice. Erik et al. reported\nmolecular profiling of lung ASC. 14  Because of\nthe rarity of colonic ASC, countrywide registry database systems and gene analysis programs are\nrequired.","source_license":"CC-BY-4.0","license_restricted":false}