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David S. Klimstra - One of the best experts on this subject based on the ideXlab platform.

  • Invasive Carcinoma arising in intraductal papillary mucinous neoplasms of the pancreas: a matched control study with conventional pancreatic ductal adenoCarcinoma.
    Annals of surgery, 2011
    Co-Authors: Adam C. Yopp, David S. Klimstra, Nora Katabi, Maria Janakos, Michael I. D’angelica, Ronald P. Dematteo, Yuman Fong, Murray F. Brennan, William R. Jarnagin, Peter J. Allen
    Abstract:

    Objective: The purpose of this study was to characterize the clinicopathological features of invasive Carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas (IPMN) by histological subtype of the invasive component and to compare the outcomes of these patients to a cohort of matched patients with conventional ductal pancreatic adenoCarcinoma. Background: Two distinct histological subtypes of invasive Carcinomas arising in IPMNs have been described, Colloid Carcinoma and tubular Carcinoma. Previous reports have suggested prognostic differences between these 2 subtypes but a matched comparison of Colloid Carcinoma, tubular Carcinoma, and conventional pancreatic adenoCarcinoma has not been reported. Methods: The clinicopathological variables of 59 patients resected for an invasive component of IPMN were analyzed with detailed pathologic review of histopathologic subtype (Colloid Carcinoma and tubular Carcinoma). Using a postresection pancreatic adenoCarcinoma nomogram, patients with either tubular or Colloid Carcinoma were matched on a 1:1 basis with patients resected for conventional ductal pancreatic adenoCarcinoma. Clinicopathological factors and overall outcome was analyzed between the matched groups. Results: Fifty-nine patients underwent resection for IPMN with an associated invasive Carcinoma (IPMN-INV). The estimated 3- and 5-year survival rates were 76% and 68%, respectively. Tubular Carcinoma was present in 35 patients (59%) and 24 patients (41%) had Colloid Carcinoma. Tubular Carcinoma subtype [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.2–11.6] and the presence of positive regional lymph nodes (HR 3.2 95% CI 1.2–8.2) were clinicopathological factors predictive of decreased survival by multivariate analysis. The 5-year estimated survival rates for tubular Carcinoma and Colloid Carcinoma were 55% and 87%, respectively (P = 0.01). When compared with patients with conventional ductal pancreatic ductal adenoCarcinoma resected during the same time period matched by a prognostic nomogram, patients with Colloid Carcinoma had a significantly longer survival outcome compared with patients with conventional adenoCarcinoma (P = 0.0001). By contrast, survival after resection between patients with the tubular subtype (3-year estimated survival, 61%) and the matched group with conventional adenoCarcinoma (3-year estimated survival, 21%) (P = 0.87) was not statistically different. Conclusions: In this study, the Colloid Carcinoma histological subtype of invasive IPMN had a more statistically favorable survival outcome than the tubular subtype. Patients with invasive tubular IPMN had no statistically significant difference in survival as matched patients with conventional ductal pancreatic Carcinoma.

  • Not all "mucinous Carcinomas" are equal: time to redefine and reinvestigate the biologic significance of mucin types and patterns in the GI tract.
    Virchows Archiv : an international journal of pathology, 2005
    Co-Authors: N. Volkan Adsay, David S. Klimstra
    Abstract:

    We read with great interest the study by Solcia et al. [14], published in the December 2004 issue of Virchows Archives. Their results reaffirm that the muconodular (or Colloid) type of mucinous Carcinoma is associated with a significantly better prognosis than other types of mucinous Carcinomas (or the conventional Carcinomas of the respective organs), not only in the breast [8] and pancreas [2], but in the stomach as well. As such, this study adds another major blow to a long-held dogma that mucinous Carcinomas of any type are particularly aggressive in the gastrointestinal (GI) tract. It has long been known that “pure mucinous” Carcinomas of the breast, also referred to as Colloid Carcinomas [7, 9, 10, 13], are associated with an excellent prognosis, even better than that of some in-situ Carcinomas of this organ [7]. It is also noted that, interestingly, even a small component of the usual ductal Carcinoma negates this survival benefit [4, 8]. The same seems to apply to the pancreas; pancreatic Carcinomas composed almost entirely of the Colloid pattern have a very good prognosis [2], whereas mixed-mucinous Carcinomas are highly aggressive tumors [12]. Why is pure Colloid Carcinoma indolent, but not mixedmucinous Carcinoma? We believe the answer lies in the pathogenesis of the Colloid Carcinoma pattern. It has been speculated that in Colloid Carcinoma, the mucin acts as a containing factor, exerting a function similar to that of the basement membrane in in-situ Carcinomas [1, 7]. Indeed, the survival advantage and indolent behavior of Colloid Carcinomas appear to be most evident when most of the cells are floating within the mucin, without any nonmucinous glands infiltrating into the stroma. What causes the tumor cells to float within the mucin rather than invading the stroma? One characteristic feature of the Colloid pattern is that the cells have reversed polarity (as evidenced by both immunohistochemical and ultrastructural studies) [1], in which the secretory pole of the cells is oriented toward the stroma-facing surface of the cells, leading to the accumulation of mucin in the stroma, which in turn acts as a barrier to the spread of the cells. Furthermore, the mucin secreted by these cells appears to be distinctive, with inhibitory properties [1]. MUC2, which is a tumor suppressor, is highly expressed in this type of mucinous Carcinoma but not others. Why then is it that even a small component of ordinary Carcinoma negates the survival advantage of the Colloid pattern? One can speculate that once the cells of a Colloid Carcinoma acquire the properties that allow them to overcome the mucin and independently invade the stroma, these cells may represent a more aggressive phenotype than even ordinary invasive Carcinomas. Does the Colloid (muconodular) pattern have the same implication in the GI tract as in the breast and pancreas? The studies by Solcia et al. [14] and others [3] show that it probably does. But in fact, there were already several questions regarding the significance of mucin production in the GI tract. First, appendiceal mucinous neoplasms that have a predominantly Colloid pattern are associated with a protracted clinical course even if they give rise to pseudomyxoma peritonei. There are several observations that support this impression [5, 6]. The invasive (disseminated) component of the cases, referred to as “disseminated peritoneal adenomucinosis” by Ronnett et al. [6] or “low-grade mucinous neoplasm” by Misdraji et al. [5], typically shows a predominant Colloid pattern and has a much better prognosis than those with less of a Colloid pattern. There is yet N. V. Adsay (*) Department of Pathology, The Karmanos Cancer Institute and Harper University Hospital, Wayne State University, Detroit, MI, USA e-mail: adsayv@med.wayne.edu Tel.: +1-313-9932965 Fax: +1-313-7459299

  • Colloid Carcinoma of the pancreas
    Current Diagnostic Pathology, 2004
    Co-Authors: Aleodor A. Andea, David S. Klimstra, Jeanette D. Cheng, N. Volkan Adsay
    Abstract:

    Abstract Pancreatic Colloid Carcinoma, also known as mucinous non-cystic Carcinoma or gelatinous Carcinoma, is a Carcinoma of ductal origin, characterized morphologically by well-circumscribed pools of mucin that contain detached floating epithelial elements. Its distinction from conventional ductal adenoCarcinoma is important because beyond the morphological dissimilarities, there are molecular and biologic differences between Colloid and ordinary ductal Carcinoma of the pancreas. Clinically, patients with Colloid Carcinoma often present with abdominal/epigastric pain and diarrhoea. They usually have larger tumours than ordinary ductal adenoCarcinoma at presentation. Often, an associated intraductal papillary mucinous neoplasm is found. Macroscopically, Colloid Carcinoma is frequently well demarcated and characterized by gelatinous appearance. Microscopic examination reveals well-delineated mucin pools that contain detached and scanty malignant epithelial cells. In contrast with the mixed Carcinomas, which may focally exhibit a similar pattern, pure mucinous Carcinomas (those in which most of the tumour is composed of Colloid pattern) seem to have a more indolent course with longer survival rates than conventional adenoCarcinoma. Even in the presence of lymph node metastases, the patients can sometimes attain prolonged survival. There are certain characteristics of Colloid Carcinoma that are being recognized increasingly as the potential reasons for its distinctive clinicopathologic attributes. One distinctive feature of Colloid Carcinoma cells is that they exhibit altered cell polarity in which the secretory activity of the cell is manifested at its stroma-facing surfaces. In addition, it seems that production of MUC2 type mucin, which is specific for Colloid Carcinoma or its precursors, might act as a barrier limiting the growth and spread of the tumor and partially explaining the indolent nature of these cancers. The frequent association of Colloid Carcinoma with intraductal papillary mucinous neoplasms and also the observation that they share a similar profile of MUC1 and MUC2 expression have suggested that these neoplasms may be characterized by a different carcinogenetic pathway than ordinary ductal adenoCarcinoma, which is believed to originate from pancreatic intraepithelial neoplasia.

  • Pathogenesis of Colloid (pure mucinous) Carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of
    The American Journal of Surgical Pathology, 2003
    Co-Authors: N. Volkan Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p

  • pathogenesis of Colloid pure mucinous Carcinoma of exocrine organs coupling of gel forming mucin muc2 production with altered cell polarity and abnormal cell stroma interaction may be the key factor in the morphogenesis and indolent behavior of collo
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Volkan N Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p <0.0001 in both organs). No labeling was detected in normal ducts. In conclusion, it appears that coupling of two factors is important for the distinctive morphologic characteristics and slow growth of CCs: The first one is the alteration in cell orientation as evidenced by the direction of surface glycoproteins and secretory organelles to the stroma-facing surface of the cells and the disruption of cell-stroma interaction as manifested by lack of basal lamina formation. Apparently, this altered polarity allows the CC cells to secrete the mucin toward the stroma. The mucin produced, MUC2 (also called gel-forming mucin), is highly specific for CC and is known to form strong bonds with the stroma, and also was found recently to have tumor suppressor activity. This distinctive mucin, accumulated in the stroma surrounding the CC cells, may act as a containing factor, slackening the spread of the cells.

N. Volkan Adsay - One of the best experts on this subject based on the ideXlab platform.

  • Not all "mucinous Carcinomas" are equal: time to redefine and reinvestigate the biologic significance of mucin types and patterns in the GI tract.
    Virchows Archiv : an international journal of pathology, 2005
    Co-Authors: N. Volkan Adsay, David S. Klimstra
    Abstract:

    We read with great interest the study by Solcia et al. [14], published in the December 2004 issue of Virchows Archives. Their results reaffirm that the muconodular (or Colloid) type of mucinous Carcinoma is associated with a significantly better prognosis than other types of mucinous Carcinomas (or the conventional Carcinomas of the respective organs), not only in the breast [8] and pancreas [2], but in the stomach as well. As such, this study adds another major blow to a long-held dogma that mucinous Carcinomas of any type are particularly aggressive in the gastrointestinal (GI) tract. It has long been known that “pure mucinous” Carcinomas of the breast, also referred to as Colloid Carcinomas [7, 9, 10, 13], are associated with an excellent prognosis, even better than that of some in-situ Carcinomas of this organ [7]. It is also noted that, interestingly, even a small component of the usual ductal Carcinoma negates this survival benefit [4, 8]. The same seems to apply to the pancreas; pancreatic Carcinomas composed almost entirely of the Colloid pattern have a very good prognosis [2], whereas mixed-mucinous Carcinomas are highly aggressive tumors [12]. Why is pure Colloid Carcinoma indolent, but not mixedmucinous Carcinoma? We believe the answer lies in the pathogenesis of the Colloid Carcinoma pattern. It has been speculated that in Colloid Carcinoma, the mucin acts as a containing factor, exerting a function similar to that of the basement membrane in in-situ Carcinomas [1, 7]. Indeed, the survival advantage and indolent behavior of Colloid Carcinomas appear to be most evident when most of the cells are floating within the mucin, without any nonmucinous glands infiltrating into the stroma. What causes the tumor cells to float within the mucin rather than invading the stroma? One characteristic feature of the Colloid pattern is that the cells have reversed polarity (as evidenced by both immunohistochemical and ultrastructural studies) [1], in which the secretory pole of the cells is oriented toward the stroma-facing surface of the cells, leading to the accumulation of mucin in the stroma, which in turn acts as a barrier to the spread of the cells. Furthermore, the mucin secreted by these cells appears to be distinctive, with inhibitory properties [1]. MUC2, which is a tumor suppressor, is highly expressed in this type of mucinous Carcinoma but not others. Why then is it that even a small component of ordinary Carcinoma negates the survival advantage of the Colloid pattern? One can speculate that once the cells of a Colloid Carcinoma acquire the properties that allow them to overcome the mucin and independently invade the stroma, these cells may represent a more aggressive phenotype than even ordinary invasive Carcinomas. Does the Colloid (muconodular) pattern have the same implication in the GI tract as in the breast and pancreas? The studies by Solcia et al. [14] and others [3] show that it probably does. But in fact, there were already several questions regarding the significance of mucin production in the GI tract. First, appendiceal mucinous neoplasms that have a predominantly Colloid pattern are associated with a protracted clinical course even if they give rise to pseudomyxoma peritonei. There are several observations that support this impression [5, 6]. The invasive (disseminated) component of the cases, referred to as “disseminated peritoneal adenomucinosis” by Ronnett et al. [6] or “low-grade mucinous neoplasm” by Misdraji et al. [5], typically shows a predominant Colloid pattern and has a much better prognosis than those with less of a Colloid pattern. There is yet N. V. Adsay (*) Department of Pathology, The Karmanos Cancer Institute and Harper University Hospital, Wayne State University, Detroit, MI, USA e-mail: adsayv@med.wayne.edu Tel.: +1-313-9932965 Fax: +1-313-7459299

  • Colloid Carcinoma of the pancreas
    Current Diagnostic Pathology, 2004
    Co-Authors: Aleodor A. Andea, David S. Klimstra, Jeanette D. Cheng, N. Volkan Adsay
    Abstract:

    Abstract Pancreatic Colloid Carcinoma, also known as mucinous non-cystic Carcinoma or gelatinous Carcinoma, is a Carcinoma of ductal origin, characterized morphologically by well-circumscribed pools of mucin that contain detached floating epithelial elements. Its distinction from conventional ductal adenoCarcinoma is important because beyond the morphological dissimilarities, there are molecular and biologic differences between Colloid and ordinary ductal Carcinoma of the pancreas. Clinically, patients with Colloid Carcinoma often present with abdominal/epigastric pain and diarrhoea. They usually have larger tumours than ordinary ductal adenoCarcinoma at presentation. Often, an associated intraductal papillary mucinous neoplasm is found. Macroscopically, Colloid Carcinoma is frequently well demarcated and characterized by gelatinous appearance. Microscopic examination reveals well-delineated mucin pools that contain detached and scanty malignant epithelial cells. In contrast with the mixed Carcinomas, which may focally exhibit a similar pattern, pure mucinous Carcinomas (those in which most of the tumour is composed of Colloid pattern) seem to have a more indolent course with longer survival rates than conventional adenoCarcinoma. Even in the presence of lymph node metastases, the patients can sometimes attain prolonged survival. There are certain characteristics of Colloid Carcinoma that are being recognized increasingly as the potential reasons for its distinctive clinicopathologic attributes. One distinctive feature of Colloid Carcinoma cells is that they exhibit altered cell polarity in which the secretory activity of the cell is manifested at its stroma-facing surfaces. In addition, it seems that production of MUC2 type mucin, which is specific for Colloid Carcinoma or its precursors, might act as a barrier limiting the growth and spread of the tumor and partially explaining the indolent nature of these cancers. The frequent association of Colloid Carcinoma with intraductal papillary mucinous neoplasms and also the observation that they share a similar profile of MUC1 and MUC2 expression have suggested that these neoplasms may be characterized by a different carcinogenetic pathway than ordinary ductal adenoCarcinoma, which is believed to originate from pancreatic intraepithelial neoplasia.

  • Pathogenesis of Colloid (pure mucinous) Carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of
    The American Journal of Surgical Pathology, 2003
    Co-Authors: N. Volkan Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p

  • Colloid mucinous noncystic Carcinoma of the pancreas
    The American Journal of Surgical Pathology, 2001
    Co-Authors: N. Volkan Adsay, Fazlul H. Sarkar, Christopher R. Pierson, Murray F. Brennan, Judith Abrams, Donald W Weaver, Kevin C Conlon, David S. Klimstra
    Abstract:

    In the past, Colloid (mucinous noncystic) Carcinoma (CC) of the pancreas had been included under the category of ordinary ductal adenoCarcinoma, a tumor with a dismal prognosis, or was frequently misdiagnosed as mucinous cystadenoCarcinoma. The clinicopathologic features of CC have not yet been well characterized, because most cases on record have been parts of studies on either mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasms (IPMN), with which Colloid Carcinomas are frequently associated. To determine the clinicopathologic characteristics of CC, 17 pancreatic tumors composed predominantly (>80%) of CC (defined as nodular extracellular mucin lakes with scanty malignant epithelial cells) and in which the invasive Carcinoma measured larger than 1 cm were studied. Ten of these were originally classified as mucinous ductal adenoCarcinoma and four as mucinous cystadenoCarcinoma. The mean age of the patients was 61 years; 9 were men and 8 were women. The mean size of the CC was 5.3 cm (range, 1.2-16 cm). In more than half of the patients, CC represented the invasive component of an IPMN (in nine cases) or MCN (in one case). The tumors were composed of well-defined pools of mucin with sparse malignant cells in various patterns of distribution. Signet-ring cells floating in the mucin (but not as individual cells infiltrating stroma, a characteristic finding of signet-ring cell adenoCarcinomas) were commonly identified and were prominent in five cases. Perineurial invasion was noted in six cases and regional lymph node metastases in eight. Mutation in codon 12 of the k-ras gene was detected in only 4 of 12 cases studied and p53 mutation in 2 of 9. Immunohistochemical and histochemical mucin stains suggested luminalization of the basal aspects of the cells. Five-year survival was 57%. At an overall mean follow up of 57 months, 10 patients were alive with no evidence of disease (median, 79 mos), including four with lymph node metastasis, three others with perineurial invasion, and another with vascular invasion. Four patients died of disease (18, 18, 25, and 26 mos), and three died of thromboembolism (with persistent disease) at 2, 5, 10 months. All seven patients who died with or of tumor had undergone incisional biopsy of the tumor either before the operation or intraoperatively, whereas none of the patients who were alive had incisional biopsy. When compared with 82 cases of resectable ordinary ductal adenoCarcinoma on whom follow-up and staging information was complete, it was found that the patients with CC present with larger tumors (p = 0.03) but lower stage (p = 0.01). The prognosis of CC is significantly better: 2-year and 5-year survival are 70% versus 28% and 57% versus 12%, respectively (p = 0.001). In conclusion, pancreatic CC may occur with or without an identifiable IPMN and MCN component, and should be distinguished from mucinous cystadenoCarcinoma, ordinary ductal adenoCarcinoma, and signet-ring cell adenoCarcinoma. CC of the pancreas is associated with a significantly better prognosis than ordinary ductal adenoCarcinoma. In addition to its distinctive morphologic and clinical characteristics, CC of the pancreas also appears to have a low incidence of mutation in codon 12 of the k-ras gene. In cases with a clinical suspicion of Colloid Carcinoma, the possibility that an incisional biopsy may contribute to thromboembolic complications or even dissemination of the tumor may need to be considered. The luminalization of the basal aspects of the tumor cells may be the cause of stromal mucin accumulation that characterizes Colloid Carcinoma and may act as a containing factor.

Ralph H. Hruban - One of the best experts on this subject based on the ideXlab platform.

  • Invasive Intraductal Papillary Mucinous Neoplasms: CT Features of Colloid Carcinoma Versus Tubular AdenoCarcinoma of the Pancreas
    AJR. American journal of roentgenology, 2020
    Co-Authors: Daniel Fadaei Fouladi, Ralph H. Hruban, Siva P. Raman, Elliot K. Fishman, Satomi Kawamoto
    Abstract:

    OBJECTIVE. The purpose of this study is to compare the CT features of Colloid Carcinoma and tubular adenoCarcinoma of the pancreas arising in association with intraductal papillary mucinous neoplas...

  • Pathogenesis of Colloid (pure mucinous) Carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of
    The American Journal of Surgical Pathology, 2003
    Co-Authors: N. Volkan Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p

  • pathogenesis of Colloid pure mucinous Carcinoma of exocrine organs coupling of gel forming mucin muc2 production with altered cell polarity and abnormal cell stroma interaction may be the key factor in the morphogenesis and indolent behavior of collo
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Volkan N Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p <0.0001 in both organs). No labeling was detected in normal ducts. In conclusion, it appears that coupling of two factors is important for the distinctive morphologic characteristics and slow growth of CCs: The first one is the alteration in cell orientation as evidenced by the direction of surface glycoproteins and secretory organelles to the stroma-facing surface of the cells and the disruption of cell-stroma interaction as manifested by lack of basal lamina formation. Apparently, this altered polarity allows the CC cells to secrete the mucin toward the stroma. The mucin produced, MUC2 (also called gel-forming mucin), is highly specific for CC and is known to form strong bonds with the stroma, and also was found recently to have tumor suppressor activity. This distinctive mucin, accumulated in the stroma surrounding the CC cells, may act as a containing factor, slackening the spread of the cells.

Tauseef Ahmed - One of the best experts on this subject based on the ideXlab platform.

  • Mucinous (Colloid) Carcinoma of urinary bladder following long-term cyclophosphamide therapy for Waldenstrom's macroglobulinemia.
    The American journal of surgical pathology, 1996
    Co-Authors: Anjum Siddiqui, Myron R. Melamed, Rakesh K. Abbi, Tauseef Ahmed
    Abstract:

    Carcinoma of the urinary bladder is a known complication of cyclophosphamide therapy. Almost all such cases have been transitional cell Carcinomas. We report here the second example of an adenoCarcinoma of bladder and the first purely mucinous (Colloid) Carcinoma of urinary bladder developing after long-term cyclophosphamide therapy. The patient, a 77-year-old woman, had been treated for Waldenstrom's macroglobulinemia for at least 24 years, during which time treatment for this disease varied from 50 to 100 mg per day. The disease terminated in acute myelogenous leukemia, and she died of severe disseminated intravascular coagulopathy associated with hypermacroglobulinemia. The mucinous (Colloid) Carcinoma of the urinary bladder was an incidental finding at autopsy.

Jeanette D. Cheng - One of the best experts on this subject based on the ideXlab platform.

  • Colloid Carcinoma of the pancreas
    Current Diagnostic Pathology, 2004
    Co-Authors: Aleodor A. Andea, David S. Klimstra, Jeanette D. Cheng, N. Volkan Adsay
    Abstract:

    Abstract Pancreatic Colloid Carcinoma, also known as mucinous non-cystic Carcinoma or gelatinous Carcinoma, is a Carcinoma of ductal origin, characterized morphologically by well-circumscribed pools of mucin that contain detached floating epithelial elements. Its distinction from conventional ductal adenoCarcinoma is important because beyond the morphological dissimilarities, there are molecular and biologic differences between Colloid and ordinary ductal Carcinoma of the pancreas. Clinically, patients with Colloid Carcinoma often present with abdominal/epigastric pain and diarrhoea. They usually have larger tumours than ordinary ductal adenoCarcinoma at presentation. Often, an associated intraductal papillary mucinous neoplasm is found. Macroscopically, Colloid Carcinoma is frequently well demarcated and characterized by gelatinous appearance. Microscopic examination reveals well-delineated mucin pools that contain detached and scanty malignant epithelial cells. In contrast with the mixed Carcinomas, which may focally exhibit a similar pattern, pure mucinous Carcinomas (those in which most of the tumour is composed of Colloid pattern) seem to have a more indolent course with longer survival rates than conventional adenoCarcinoma. Even in the presence of lymph node metastases, the patients can sometimes attain prolonged survival. There are certain characteristics of Colloid Carcinoma that are being recognized increasingly as the potential reasons for its distinctive clinicopathologic attributes. One distinctive feature of Colloid Carcinoma cells is that they exhibit altered cell polarity in which the secretory activity of the cell is manifested at its stroma-facing surfaces. In addition, it seems that production of MUC2 type mucin, which is specific for Colloid Carcinoma or its precursors, might act as a barrier limiting the growth and spread of the tumor and partially explaining the indolent nature of these cancers. The frequent association of Colloid Carcinoma with intraductal papillary mucinous neoplasms and also the observation that they share a similar profile of MUC1 and MUC2 expression have suggested that these neoplasms may be characterized by a different carcinogenetic pathway than ordinary ductal adenoCarcinoma, which is believed to originate from pancreatic intraepithelial neoplasia.

  • Pathogenesis of Colloid (pure mucinous) Carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of
    The American Journal of Surgical Pathology, 2003
    Co-Authors: N. Volkan Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p

  • pathogenesis of Colloid pure mucinous Carcinoma of exocrine organs coupling of gel forming mucin muc2 production with altered cell polarity and abnormal cell stroma interaction may be the key factor in the morphogenesis and indolent behavior of collo
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Volkan N Adsay, Kambiz Merati, Hind Nassar, Fazlul H. Sarkar, Christopher R. Pierson, Jeanette D. Cheng, Daniel W. Visscher, Ralph H. Hruban, Jinru Shia, David S. Klimstra
    Abstract:

    : In the exocrine organs, breast and pancreas, Colloid Carcinoma (CC, pure mucinous Carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal Carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional Carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p <0.0001 in both organs). No labeling was detected in normal ducts. In conclusion, it appears that coupling of two factors is important for the distinctive morphologic characteristics and slow growth of CCs: The first one is the alteration in cell orientation as evidenced by the direction of surface glycoproteins and secretory organelles to the stroma-facing surface of the cells and the disruption of cell-stroma interaction as manifested by lack of basal lamina formation. Apparently, this altered polarity allows the CC cells to secrete the mucin toward the stroma. The mucin produced, MUC2 (also called gel-forming mucin), is highly specific for CC and is known to form strong bonds with the stroma, and also was found recently to have tumor suppressor activity. This distinctive mucin, accumulated in the stroma surrounding the CC cells, may act as a containing factor, slackening the spread of the cells.