Signet Ring Cell Differentiation Research Articles

The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas: a clinicopathologic and immunohistochemical analysis of tumors often misinterpreted as primary ovarian tumors or metastatic tumors from other gastrointestinal sites.

Twenty cases of ovarian metastases derived from appendiceal adenocarcinomas were analyzed. The most common presentation was a pelvic mass. The appendiceal and ovarian tumors were diagnosed concurrently in 15 cases; in the remaining five, the ovarian tumors were diagnosed before the appendiceal tumor. The appendiceal adenocarcinomas demonstrated four morphologic patterns: 1) signet ring cell type, with or without glandular or goblet cell differentiation (14 cases); 2) mixed signet ring cell and intestinal type (two cases); 3) intestinal type (two cases); and 4) typical colorectal type (two cases). The ovarian tumors were bilateral in 16 cases and were histologically similar to the associated appendiceal tumor in each case. Ovarian metastases that demonstrate signet ring cell, glandular, and goblet cell differentiation mimic metastases from gastric adenocarcinoma. Those that are derived from well-differentiated mucinous appendiceal adenocarcinomas mimic primary ovarian mucinous tumors and metastases from the pancreas and biliary tract. Metastases of appendiceal adenocarcinomas of colorectal type simulate both metastatic colorectal carcinoma and primary ovarian endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically identical in each case. Approximately 50% of the appendiceal and ovarian tumors were positive for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK 20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal origin; CK 7 positivity does not confirm ovarian origin, because appendiceal carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma should be considered in the differential diagnosis of mucinous ovarian tumors with signet ring cell, goblet cell, or intestinal type differentiation, especially when these tumors are associated with extraovarian disease and are bilateral.

Signet-ring cell differentiation in primary cutaneous neoplasms

17th Colloquium of the International Society of Dermatopathology (ISD) and Swiss Group of Dermatopathology (SGDP) of the Swiss Society of Dermatology and Venerology

Adenocarcinoma of the Uterine Cervix with Massive Signet-Ring Cell Differentiation

Primary signetring cell adenocarcinoma of the cervix is very rare and less common than metastatic signet-ring cell adenocarcinoma. To the best of the authors' knowldge only one genuine case has been reported to date. Tvvo cases of primary signeting cell adenocarcinoma of the uterine cervix in patients aged 68 and 74 years are presented. The tumors were in stage IB. The light microscopic findings were conirmed by histochemical and immunohistochemical study. DNA nuclear analysis by flow cytometry of the neoplasms revealed an aneuploid (tetraploid) pattern. The paients had no evidence of recurrent or metastatic disease 35 and 25 months after a radical hysterectomy with bilateral salpingo-oophorectomy and lymph node dissecion respectively. Primary signet-ring cell adenocarcinoma of the cervix should be diferentiated from metastatic adenocarcinoma, endocervical involvement by signeting cell carcinoma of the endometrium, benign mucinfilled signet-ring cell aggregates that may accumulate in mucosal folds, microglandular hyperplasia, muciarminophilic histiocytosis, and other malignant neoplasms that may have signet ringlike cells and deserve consideration such as squamous cell carcinoma, maligant lymphoma, myeloma, and malignant melanoma. Although very rare, signeting cell adenocarcinoma of the cervix can exist as a primary tumor. Distinction beween a primary neoplasm and a metastasis to the cervix is decisive for treatment and prognosis.

Subtyping and prognostic assessment of invasive lobular breast carcinoma

Invasive lobular carcinoma (ILC) is recognized in its classical form and as variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell differentiation. The most common classical form differs from invasive ductal carcinoma (IDC) by its slower tumor proliferation and less common axillary metastases. When compared stage by stage, long term prognosis is similar to IDC, however. Prognostic subtyping of ILC can be achieved by the recognition of variant forms and mitotic counting. The combination of these factors may be used for tumor grading (5-year survival 100% with grade 1 vs. 82% with grade 2, and 57% with grade 3, n = 241). The detailed histopathologic diagnosis therefore permits prognostic assessment also in ILC.

Pseudomyxoma peritonei in women: A clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis, and relationship to ovarian mucinous tumors of low malignant potential

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by the accumulation of abundant mucinous material within the peritoneal cavity and associated with a mucinous tumor of the gastrointestinal tract or ovaries. Recently there has been considerable debate over the primary site of origin of the tumor associated with PMP in women. Some investigators have proposed a primary site in the ovaries, whereas others favor the gastrointestinal tract or the peritoneum. Another confusing issue has been the nature of the ovarian mucinous tumors associated with PMP. Although these neoplasms may be frankly malignant, more often they show minimal cytologic atypia and epithelial proliferation and have been classified as borderline or low malignant potential tumors. In order to address the issues of site of origin and nature of the associated ovarian mucinous tumors, we studied 68 cases of PMP in women, 30 of whom had mucinous tumors involving the ovaries. All 30 of these cases had an associated mucinous appendiceal or intestinal tumor. The PMP cases with ovarian tumors were compared with 30 ovarian mucinous tumors of low malignant potential (LMP). Based on the analysis of the primary ovarian mucinous LMP tumors, a set of criteria was formulated and used to determine the probable site of origin of PMP in the 30 women with mucinous tumors involving the ovaries. The following gross and microscopic features of the ovarian tumor were considered to be inconsistent with a primary ovarian origin: (1) surface involvement with or without superficial stromal involvement only; (2) adenocarcinoma with signet ring cell differentiation, with a previously diagnosed or concurrent appendiceal tumor of similar morphology; (3) bilateral adenocarcinoma consistent with colonic or appendiceal morphology; and (4) unilateral adenocarcinoma consistent with colonic or appendiceal morphology with a history of a co-. Ionic or appendiceal adenocarcinoma. When any one of these features was present the ovarian tumor was diagnosed as secondary. The following additional features also were considered to be more typical of secondary ovarian involvement: (1) normal or only slightly enlarged ovaries; (2) bilateral ovarian involvement; (3) simple or only focally proliferative mucinous epithelium with abundant extracellular mucin in cases with predominantly surface involvement of the ovaries, with or without a history of/or concurrent appendiceal adenoma; (4) multifocal or extensive pseudomyxoma ovarii in cases with stromal involvement, with or without a history of/or concurrent appendiceal adenoma; (5) ruptured appendiceal adenoma and unruptured ovarian tumor of similar histology; and (6) presence of an associated mucinous intestinal tumor. If at least three of the above features were present, the ovarian tumor also was diagnosed as secondary. When classified according to all of these criteria 28 of the 30 cases of PMP (93.3%) were attributed to primary mucinous appendiceal or colonic tumors, and the remaining two were compatible with either intestinal or ovarian origin. No cases were of unequivocal ovarian origin. Analysis of multiple histologic features of the ovarian, intestinal, and peritoneal mucinous tumors showed that the PMP cases could be separated into two pathologically and prognostically distinct groups based on the associated intestinal tumor diagnosis. Appendiceal adenomaassociated cases showed a significantly better prognosis than appendiceal or intestinal carcinoma-associated cases ( P < .0001). Nearly all appendiceal adenoma-associated cases were characterized by appendiceal, ovarian, and peritoneal tumors with no significant atypia or epithelial proliferation and absence of lymph node involvement and parenchymal organ invasion. In contrast, the carcinoma-associated cases displayed significant atypia and epithelial proliferation in the intestinal, ovarian, and peritoneal tumors. In addition, these tumors were frequently associated with lymph node and parenchymal organ metastases. Accordingly, we recommend that the term PMP be restricted to those cases that have the features of appendiceal adenoma-associated cases. The carcinoma-associated cases should be classified as mucinous carcinomas and not included in the category of PMP. Finally, the conclusion that PMP is virtually always of appendiceal origin provides the basis for reassessing the entire concept of ovarian mucinous LMP tumors because malignant behavior associated with the latter tumors has virtually always been confined to women with PMP.

Signet ring cell differentiation in adenocarcinoma of the prostate: a study of five cases.

Signet ring cell differentiation in adenocarcinoma of the prostate is uncommon. In a review of 200 cases of prostatic carcinoma, we identified five cases with this change, all in moderately to poorly differentiated prostatic carcinomas. The signet ring cells in prostatic carcinoma contain an intracytoplasmic lumen, shown on electronmicroscopy to be lined by microvilli. Transition stages were seen from solid to acinar to signet ring cells to mucinous variants. We believe that this change is part of the spectrum of appearances of prostatic carcinoma and should not be regarded as a subtype of specific significance.

Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors.

A retrospective immunoperoxidase staining study for a glycoprotein isolated from human breast gross cystic disease fluid (GCDFP-15) in 562 primary breast carcinomas in 539 patients was conducted to correlate its immunohistochemistry with pathologic and clinical factors. Overall, 55% of the carcinomas studied stained positively for GCDFP-15. In certain histologic subtypes, the percentage of carcinomas that stained positively was greater: those subtypes with apocrine histologic features (75%), intraductal carcinoma (70%), and infiltrating lobular carcinoma with signet-ring cell differentiation (90%). In contrast, only 5% of medullary carcinomas exhibited positive staining. Only 23% of breast carcinomas without apocrine features stained positively for GCDFP-15. Carcinomas that stained positively were more likely to have involved axillary lymph nodes (P less than 0.054). The staining was independent of nuclear grade, mitotic index, tumor size, and estrogen receptor status. Positive staining was related to a history of gross cystic disease but not to age, parity, menopausal status, or age at first birth. A positive stain was not related to risk of recurrence or survival.

Primary carcinoma of the cecum with uterine metastases

We report an unusual case of a poorly differentiated signet ring cell type of adenocarcinoma of the cecum, rare in its own right, that had metastasized to the endometrium. The diagnosis was made on the basis of fractional uterine curettage. It is believed that this is the first case of such an unusual cecal carcinoma metastatic to the endometrium.

Invasive lobular carcinoma of the breast: incidence and variants

The criteria for the separation of invasive lobular and ductal carcinomas are analysed. Lobular tumours account for 14% of invasive cancers in our material. The widely differing figures given in the literature are mainly attributable to intrinsic difficulties of classification. In addition to the classical dissociated-cell patterns with single filing, a tragetoid appearance and related features, variants with trabecular, loose alveolar and tubular features are recognized; a 'solid' variant requires further investigation. The variants either represent better differentiated forms, or in some cases, an 'earlier' phase in the production of the more traditional Indian file formations and dartboard patterns. Focal signet-ring cell differentiation is another newly-recognized feature. The theoretical and practical implications of these variants are considered. The division into invasive lobular and ductal carcinomas is not as easy as most of the literature implies. Five per cent of cases could not be so classified and, in some of these unclassified cases, both ductal and lobular differentiation may be present. In the diagnosis of problem cases, no single parameter proved reliable but a combination of several parameters enables one to make an objective diagnosis in about 95% of cases.