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Mucinous noncystic (colloid) adenocarcinoma of the pancreas.Zhonghua
Bing Li Xue Za Zhi. 2005 Jul;34(7):389-92.
OBJECTIVE: To
determine the clinicopathologic characteristics and the relationship
between related gene expression and pathobiologic behavior of
pancreatic mucinous noncystic adenocarcinoma. METHODS: Among the 249
pancreatic carcinoma cases from the department files, 6 tumors were
identified to meet the pathologic criteria of colloid carcinoma.
Envision immunohistochemical staining technique was used to detect
expression of p21(ras), p21(WAF1), p16, p33(ING1), p53, ATM, MDM2,
PCNA, Cyclins (D1, D3, A, B and E). Intra- and extra- cellular mucin
production were determined by AB-PAS staining. Clinically, all of 6
cases were followed to June, 2003. RESULTS: In all 6 cases, the tumors
were located in the head of the pancreas and all displayed similar
microscopic findings. Duodenal invasion was seen in 4 cases and
perineural invasion was seen in 1 case. Tumor metastasis in the liver
was seen in 2 cases and in the regional lymph nodes in 2 cases.
Positive immunostaining was seen in 5 cases with p21(ras), 3 cases
with p21(WAF1), 1 case with p16, 4 cases with p33(ING1), 2 cases with
p53, 3 cases with ATM, 3 cases with MDM2, 6 cases with PCNA, 3 cases
with cyclinA, 3 cases with cyclinD1, 4 cases with cyclinD3, 4 cases
with cyclinB and 6 cases with cyclinE. Both extracellular and
intracellular mucin was strongly positive for AB-PAS staining.
Clinical follow-up found that 2 patients died of their tumors at 14
and 20 months. Three patients were alive after 28, 49 and 87 months of
follow-up. One case were lost contact. CONCLUSIONS: Pancreatic
mucinous noncystic adenocarcinoma has distinct morphologic features
and biologic behavior. Multiple gene products including many cyclins
may be involved in the pathogenesis of pancreatic colloid carcinoma.
The tumor has an aggressive behavior with a high frequency of invasion
and metastases, though the prognosis could be better than that of
ordinary ductal adenocarcinoma of pancreas.
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 colloid carcinoma in the
breast and pancreas.Am
J Surg Pathol. 2003 May;27(5):571-8.
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.
Colloid (mucinous
noncystic) carcinoma of the pancreas.
Am J Surg
Pathol. 2001 Jan;25(1):26-42.
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.
Rare primary signet ring carcinoma of the pancreas.Mo
Med. 1995 Jun;92(6):298-302.
Signet ring
carcinoma of the pancreas is a rare mucin-producing variant occurring
in less than 1% of pancreatic carcinoma. The fourth leading cause of
cancer deaths in the U.S., pancreatic carcinoma is increasing in
incidence and mortality. It is difficult to detect during the early
stages of the disease and usually become apparent when extrahepatic
biliary obstruction occurs. Early radiologic findings may be negative
and there is no well defined tumor marker for this neoplasm.
Signet-ring mucinous adenocarcinoma of the pancreas.Chin
Med Sci J. 1994 Sep;9(3):176-8.
An 88-year-old
man presented symptoms and signs of ascending cholangitis and died 20
days after the onset of illness. Postmortem examination revealed a
mucinous tumor arising from the head of the pancreas, encasing the
common bile duct and invading the liver with multiple hepatic
metastasis. The tumor showed a unique and uniform histological
appearance, consisting of signet-ring neoplastic cells floating in
mucin pools. The rapid clinical course and widespread hepatic
metastasis of this patient suggest that this pure, signet-ring variant
of mucinous adenocarcinoma of the pancreas might have a poorer
prognosis.
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