{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:27:32Z","timestamp":1773368852473,"version":"3.50.1"},"reference-count":626,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4]]},"abstract":"\n Context.\u2014<\/jats:italic>\n Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems with a variety of benign (more common) as well as other malignant mimics, the latter setting often being represented by secondary involvement by endometrioid endometrial carcinoma especially in small samplings.\n <\/jats:p>\n \n Objective.\u2014<\/jats:italic>\n To highlight key histologic features and immunohistochemical markers that may be helpful in the distinction of in situ endocervical carcinoma from benign glandular proliferations, and those that separate different subtypes of invasive endocervical carcinoma, as well as invasive carcinoma from other carcinomas secondarily involving the cervix and nonneoplastic proliferations of the cervix.\n <\/jats:p>\n \n Conclusions.\u2014<\/jats:italic>\n Clinical and morphologic features as well as immunohistochemistry results should be used in conjunction in the differential diagnosis of glandular proliferations of the cervix, as correct interpretation has major clinical consequences for the patient in most instances (especially benign versus malignant). Immunohistochemical markers should be used as part of a panel of antibodies, as exceptions may occur to the usual pattern of staining, and if used singly, they may mislead the pathologist to establish a wrong diagnosis.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0493-ra","type":"journal-article","created":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T21:18:38Z","timestamp":1396041518000},"page":"453-483","source":"Crossref","is-referenced-by-count":63,"title":["The Spectrum of Cervical Glandular Neoplasia and Issues in Differential Diagnosis"],"prefix":"10.5858","volume":"138","author":[{"given":"Joana","family":"Loureiro","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Instituto Portugu\u00eas de Oncologia, Porto, Portugal (Dr Loureiro); and the Department of Pathology, Massachusetts General Hospital, Boston (Dr Oliva)."}]},{"given":"Esther","family":"Oliva","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Instituto Portugu\u00eas de Oncologia, Porto, Portugal (Dr Loureiro); and the Department of Pathology, Massachusetts General Hospital, Boston (Dr Oliva)."}]}],"member":"3906","reference":[{"issue":"5","key":"i1543-2165-138-4-453-b01","series-title":"Cancer","first-page":"887","article-title":"Adenocarcinoma in situ of the endocervix","volume":"6","author":"Friedell\n GH,","year":"1953","unstructured":"Friedell\n GH, \n \n McKay\n DG. \n \n Adenocarcinoma in situ of the endocervix. 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Gynecol Oncol. 1994;53(2):256\u2013264."},{"issue":"1","key":"i1543-2165-138-4-453-b233","series-title":"Am J Pathol","first-page":"339","article-title":"Somatic mutations in the STK11\/LKB1 gene are uncommon in rare gynecological tumor types associated with Peutz-Jegher's syndrome","volume":"156","author":"Connolly\n DC,","year":"2000","unstructured":"Connolly\n DC, \n \n Katabuchi\n H, \n \n Cliby\n WA, \n \n Cho\n KR. \n \n Somatic mutations in the STK11\/LKB1 gene are uncommon in rare gynecological tumor types associated with Peutz-Jegher's syndrome. Am J Pathol. 2000;156(1):339\u2013345."},{"issue":"6","key":"i1543-2165-138-4-453-b234","series-title":"Cancer Res","first-page":"1140","article-title":"A distinct region of chromosome 19p13.3 associated with the sporadic form of adenoma malignum of the uterine cervix","volume":"58","author":"Lee\n JY,","year":"1998","unstructured":"Lee\n JY, \n \n Dong\n SM, \n \n Kim\n HS, \n et al\n . 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Histopathology. 2008;53(4):487\u2013490."},{"issue":"2","key":"i1543-2165-138-4-453-b240","series-title":"Int J Gynecol Pathol","first-page":"187","article-title":"p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia","volume":"25","author":"Hashi\n A,","year":"2006","unstructured":"Hashi\n A, \n \n Xu\n JY, \n \n Kondo\n T, \n et al\n . p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia. Int J Gynecol Pathol. 2006;25(2):187\u2013194."},{"issue":"2","key":"i1543-2165-138-4-453-b241","series-title":"Histopathology","first-page":"184","article-title":"Reappraisal of synchronous and multifocal mucinous lesions of the female genital tract: a close association with gastric metaplasia","volume":"54","author":"Mikami\n Y,","year":"2009","unstructured":"Mikami\n Y, \n \n Kiyokawa\n T, \n \n Sasajima\n Y, \n et al\n . 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APMIS. 2001;109(7\u20138):546\u2013550."},{"issue":"2","key":"i1543-2165-138-4-453-b252","series-title":"Histopathology","first-page":"130","article-title":"Immunophenotypic alteration of the stromal component in minimal deviation adenocarcinoma (\u2018adenoma malignum') and endocervical glandular hyperplasia: a study using oestrogen receptor and alpha-smooth muscle actin double immunostaining","volume":"46","author":"Mikami\n Y,","year":"2005","unstructured":"Mikami\n Y, \n \n Kiyokawa\n T, \n \n Moriya\n T, \n \n Sasano\n H. \n \n Immunophenotypic alteration of the stromal component in minimal deviation adenocarcinoma (\u2018adenoma malignum') and endocervical glandular hyperplasia: a study using oestrogen receptor and alpha-smooth muscle actin double immunostaining. 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Int J Gynecol Pathol. 2007;26(1):71\u201375."},{"issue":"2","key":"i1543-2165-138-4-453-b75","series-title":"Am J Surg Pathol","first-page":"137","article-title":"PAX2 distinguishes benign mesonephric and mullerian glandular lesions of the cervix from endocervical adenocarcinoma, including minimal deviation adenocarcinoma","volume":"34","author":"Rabban\n JT,","year":"2010","unstructured":"Rabban\n JT, \n \n McAlhany\n S, \n \n Lerwill\n MF, \n \n Grenert\n JP, \n \n Zaloudek\n CJ. \n \n PAX2 distinguishes benign mesonephric and mullerian glandular lesions of the cervix from endocervical adenocarcinoma, including minimal deviation adenocarcinoma. 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Histopathology. 2008;53(4):487\u2013490."},{"issue":"2","key":"i1543-2165-138-4-453-b240","series-title":"Int J Gynecol Pathol","first-page":"187","article-title":"p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia","volume":"25","author":"Hashi\n A,","year":"2006","unstructured":"Hashi\n A, \n \n Xu\n JY, \n \n Kondo\n T, \n et al\n . p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia. Int J Gynecol Pathol. 2006;25(2):187\u2013194."},{"issue":"2","key":"i1543-2165-138-4-453-b241","series-title":"Histopathology","first-page":"184","article-title":"Reappraisal of synchronous and multifocal mucinous lesions of the female genital tract: a close association with gastric metaplasia","volume":"54","author":"Mikami\n Y,","year":"2009","unstructured":"Mikami\n Y, \n \n Kiyokawa\n T, \n \n Sasajima\n Y, \n et al\n . 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Histopathology. 2005;46(2):130\u2013136."},{"issue":"4","key":"i1543-2165-138-4-453-b253","series-title":"Am J Surg Pathol","first-page":"559","article-title":"Reappraisal of orthodox histochemistry for the diagnosis of minimal deviation adenocarcinoma of the cervix","volume":"24","author":"Hayashi\n I,","year":"2000","unstructured":"Hayashi\n I, \n \n Tsuda\n H, \n \n Shimoda\n T. \n \n Reappraisal of orthodox histochemistry for the diagnosis of minimal deviation adenocarcinoma of the cervix. Am J Surg Pathol. 2000;24(4):559\u2013562."},{"issue":"2","key":"i1543-2165-138-4-453-b254","series-title":"Histopathology","first-page":"167","article-title":"Enteric tumours of the lower female genital tract: a report of three cases","volume":"12","author":"Fox\n H,","year":"1988","unstructured":"Fox\n H, \n \n Wells\n M, \n \n Harris\n M, \n \n McWilliam\n LJ, \n \n Anderson\n GS. \n \n Enteric tumours of the lower female genital tract: a report of three cases. 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Primary signet-ring cell carcinoma of the uterine cervix with long term follow-up: case report","volume":"28","author":"Insabato\n L,","year":"2007","unstructured":"Insabato\n L, \n \n Simonetti\n S, \n \n De Cecio\n R, \n \n Di Tuoro\n S, \n \n Bifulco\n G, \n \n Di Spiezio Sardo A. Primary signet-ring cell carcinoma of the uterine cervix with long term follow-up: case report. Eur J Gynaecol Oncol. 2007;28(5):411\u2013414."},{"issue":"12","key":"i1543-2165-138-4-453-b259","series-title":"Arch Pathol Lab Med","first-page":"1586","article-title":"Primary cervical adenocarcinoma with intestinal differentiation and colonic carcinoma metastatic to cervix: an investigation using Cdx-2 and a limited immunohistochemical panel","volume":"127","author":"Raspollini\n MR,","year":"2003","unstructured":"Raspollini\n MR, \n \n Baroni\n G, \n \n Taddei\n A, \n \n Taddei\n GL. \n \n Primary cervical adenocarcinoma with intestinal differentiation and colonic carcinoma metastatic to cervix: an investigation using Cdx-2 and a limited immunohistochemical panel. 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Diagn Pathol. 2012;7:9."},{"issue":"3","key":"i1543-2165-138-4-453-b265","series-title":"Pathol Res Pract","first-page":"156","article-title":"Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas","volume":"207","author":"Bayrak\n R,","year":"2011","unstructured":"Bayrak\n R, \n \n Yenidunya\n S, \n \n Haltas\n H. \n \n Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract. 2011;207(3):156\u2013160."},{"issue":"3","key":"i1543-2165-138-4-453-b266","series-title":"Pathol Res Pract","first-page":"163","article-title":"Aberrant pattern of the cytokeratin 7\/cytokeratin 20 immunophenotype in colorectal adenocarcinomas with BRAF mutations","volume":"208","author":"Gurzu\n S,","year":"2012","unstructured":"Gurzu\n S, \n \n Jung\n I. \n \n Aberrant pattern of the cytokeratin 7\/cytokeratin 20 immunophenotype in colorectal adenocarcinomas with BRAF mutations. Pathol Res Pract. 2012;208(3):163\u2013166."},{"issue":"3","key":"i1543-2165-138-4-453-b267","series-title":"Am J Surg Pathol","first-page":"303","article-title":"CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas","volume":"27","author":"Werling\n RW,","year":"2003","unstructured":"Werling\n RW, \n \n Yaziji\n H, \n \n Bacchi\n CE, \n \n Gown\n AM. \n \n CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27(3):303\u2013310."},{"issue":"6","key":"i1543-2165-138-4-453-b268","series-title":"Appl Immunohistochem Mol Morphol","first-page":"562","article-title":"Expression of p16INK4a, alone or combined with p53, is predictive of better prognosis in colorectal adenocarcinoma in Tunisian patients","volume":"19","author":"Miladi-Abdennadher\n I,","year":"2011","unstructured":"Miladi-Abdennadher\n I, \n \n Abdelmaksoud-Damak\n R, \n \n Ayadi\n L, \n et al\n . Expression of p16INK4a, alone or combined with p53, is predictive of better prognosis in colorectal adenocarcinoma in Tunisian patients. Appl Immunohistochem Mol Morphol. 2011;19(6):562\u2013568."},{"issue":"1","key":"i1543-2165-138-4-453-b269","series-title":"Am J Clin Pathol","first-page":"12","article-title":"Immunohistochemical identification of tumor markers in metastatic adenocarcinoma: a diagnostic adjunct in the determination of primary site","volume":"107","author":"Brown\n RW,","year":"1997","unstructured":"Brown\n RW, \n \n Campagna\n LB, \n \n Dunn\n JK, \n \n Cagle\n PT. \n \n Immunohistochemical identification of tumor markers in metastatic adenocarcinoma: a diagnostic adjunct in the determination of primary site. 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Gastric Cancer. 2005;8(1):47\u201349."},{"issue":"10","key":"i1543-2165-138-4-453-b272","series-title":"Pathol Int","first-page":"787","article-title":"Combined signet ring cell and glassy cell carcinoma of the uterine cervix arising in a young Japanese woman: a case report with immunohistochemical and histochemical analyses","volume":"54","author":"Moritani\n S,","year":"2004","unstructured":"Moritani\n S, \n \n Ichihara\n S, \n \n Kushima\n R, \n \n Sugiura\n F, \n \n Mushika\n M, \n \n Silverberg\n SG. \n \n Combined signet ring cell and glassy cell carcinoma of the uterine cervix arising in a young Japanese woman: a case report with immunohistochemical and histochemical analyses. 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Acta Cytol. 2000;44(5):824\u2013830."},{"issue":"2","key":"i1543-2165-138-4-453-b274","series-title":"Gynecol Oncol","first-page":"147","article-title":"Behavior of estrogen-associated female genital tract cancer and its relation to neoplasia following intrauterine exposure to diethylstilbestrol (DES)","volume":"76","author":"Herbst\n AL.","year":"2000","unstructured":"Herbst\n AL. \n \n Behavior of estrogen-associated female genital tract cancer and its relation to neoplasia following intrauterine exposure to diethylstilbestrol (DES). Gynecol Oncol. 2000;76(2):147\u2013156."},{"issue":"6","key":"i1543-2165-138-4-453-b275","series-title":"Obstet Gynecol","first-page":"720","article-title":"Clear cell adenocarcinoma of the cervix unrelated to diethylstilbestrol exposure","volume":"62","author":"Kaminski\n PF,","year":"1983","unstructured":"Kaminski\n PF, \n \n Maier\n RC. \n \n Clear cell adenocarcinoma of the cervix unrelated to diethylstilbestrol exposure. Obstet Gynecol. 1983;62(6):720\u2013727."},{"issue":"3","key":"i1543-2165-138-4-453-b276","series-title":"Gynecol Oncol","first-page":"331","article-title":"Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB-IIB disease in women not exposed in utero to diethylstilbestrol","volume":"76","author":"Reich\n O,","year":"2000","unstructured":"Reich\n O, \n \n Tamussino\n K, \n \n Lahousen\n M, \n \n Pickel\n H, \n \n Haas\n J, \n \n Winter\n R. \n \n Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB-IIB disease in women not exposed in utero to diethylstilbestrol. Gynecol Oncol. 2000;76(3):331\u2013335."},{"issue":"1","key":"i1543-2165-138-4-453-b277","series-title":"Cancer Causes Control","first-page":"207","article-title":"Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States","volume":"23","author":"Smith\n EK,","year":"2012","unstructured":"Smith\n EK, \n \n White\n MC, \n \n Weir\n HK, \n \n Peipins\n LA, \n \n Thompson\n TD. \n \n Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States. Cancer Causes Control. 2012;23(1):207\u2013211."},{"issue":"3","key":"i1543-2165-138-4-453-b278","series-title":"Gynecol Oncol","first-page":"335","article-title":"Clear cell carcinoma of the cervix: a multi-institutional review in the post-DES era","volume":"109","author":"Thomas\n MB,","year":"2008","unstructured":"Thomas\n MB, \n \n Wright\n JD, \n \n Leiser\n AL, \n et al\n . Clear cell carcinoma of the cervix: a multi-institutional review in the post-DES era. Gynecol Oncol. 2008;109(3):335\u2013339."},{"issue":"2","key":"i1543-2165-138-4-453-b279","series-title":"Gynecol Oncol","first-page":"297","article-title":"High-risk human papillomavirus seems not involved in DES-related and of limited importance in nonDES related clear-cell carcinoma of the cervix","volume":"122","author":"Kocken\n M,","year":"2011","unstructured":"Kocken\n M, \n \n Baalbergen\n A, \n \n Snijders\n PJ, \n et al\n . High-risk human papillomavirus seems not involved in DES-related and of limited importance in nonDES related clear-cell carcinoma of the cervix. 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