Intestinal differentiation in ovarian mucinous tumours

Summary Fifty-five ovarian mucinous tumours, 22 benign, 16 borderline and 17 malignant, were examined for intestinal differentiation (ID). This was defined by the presence of one or more of endocrine, absorptive, goblet or Paneth cells, and identified by routine haematoxylin and eosin as well as histochemical and immunoperoxidase techniques. Twenty benign (91%), 14 borderline (88%) and all malignant tumours contained foci of ID. The frequency of ID was not significantly different between the mucinous tumour types (chi-squared test for independence). Follow-up was available on all patients with borderline tumours: 14 were stage Ia, including both cases without ID, and 2 were stage Ic at presentation. All are alive and free of disease at 9–39 months (median 15.5 months). We conclude that the presence of ID in borderline mucinous tumours is unlikely to be of prognostic significance, and that a subdivision of these tumours into müllerian and intestinal types is unnecessary.Preliminary results were presented at the second meeting of the International Gynaecologic Cancer Society, October 1989     

O-acylated sialic acid variants in mucinous tumours of the ovary

Summary O-acylated sialic acid variants (site 8) can be demonstrated histochemically by the PB/KOH/PAS method. They are secreted by goblet cells of the lower gastrointestinal tract, by colorectal adenocarcinomas, and by their metastases. Since the metastases are positive only when the primary tumour is positive, O-acylated sialomucins can be considered to be specific markers of colorectal adenocarcinomas if identified in metastases of a tumour of unknown origin. In our histochemical study we evaluated 29 mucinous cystomas of the ovary (23 benign and 6 malignant). We found that six cases were positive to PB/KOH/PAS. The positivity was observed in a limited number of cells and only in areas which presented an intestinal type epithelium. It was also more evident in malignant cystomas than in benign ones. We therefore think that the PB/KOH/PAS positivity can not only be considered a marker of colorectal adenocarcinomas, but also of all neoplasms which originate from an intestinal epithelium or appear to an intestinal type epithelium.This work is partially supported by the M.P.I. (40%)     

Quantitation of borderline and malignant mucinous ovarian tumours

Discrimination between borderline and malignant mucinous ovarian tumours is a well-known diagnostic problem. In order to obtain objective reproducible and consistent features for differential diagnosis, 32 quantitative microscopical features were assessed in 10 benign, 10 borderline and 22 malignant mucinous ovarian tumours. There were many significant differences between the three groups, but using multivariate analysis there was 93% agreement between the histopathological assessment of these sections and the qualitative analyses. The following features were useful in the quantitative classification: the mean area, the mean perimeter and the mean of the short axis of the nucleus; the volume percentage of the epithelium; the mitotic activity. In three cases, there was a difference between the original histopathological and computer classification. It was debatable whether the original diagnosis was correct, and therefore, all the cases were independently reassessed blind by three pathologists. Their diagnoses lend strong support to the computer classification in two of the three cases. The computer classification seems therefore to be even better than 93%. The present quantitative techniques are inexpensive, relatively easy to use, and, we believe, have a useful place in diagnostic histopathology.     

Histological discrimination of malignancy in mucinous ovarian tumours

Eight histological features were measured quantitatively in a group of 77 ovarian mucinous carcinomas and a group of 28 benign mucinous cystomas. These were compared with the duration of survival of the patients and the clinical staging of the tumours. Using the method of discriminant function analysis it was possible to identify a group of tumours of 'borderline malignancy'. Although single histological features were inadequate indicators of prognosis a combination of three features proved fairly accurate.     

同源异型盒基因CDX1和CDX2使食管腺癌细胞恶性降低

目的探讨同源异型盒基因CDX1和CDX2对食管腺癌细胞表型的影响。方法用携带人CDX1或CDX2的表达载体转染食管腺癌细胞系SEG-1,观察形态、生长率变化、分裂指数、致瘤性等。结果CDX1或CDX2单独作用都使SEG-1出现类腺样生长排列、生长率下降、分裂指数降低、致瘤性减弱,CDX2的作用大于CDX1。结论CDX1和CDX2均能促进食管腺癌细胞SEG-1分化,减低其恶性。     

CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.     

Invasive mucinous cystic neoplasms of the pancreas

Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma. It is now recognized that colloid carcinomas characteristically arise from IPMN. We set out to see if we could find MCN that invaded as colloid carcinomas and found no examples in MCN collected in two academic medical centers. We then sought to expand the number of MCN by evaluating series from additional centers. This yielded no examples of colloid carcinomas associated with 291 MCN, however one MCN exhibited a minor component with colloid (non-cystic mucinous) growth pattern within the fibrous wall of the neoplasm. The expression of CDX2, a marker of intestinal differentiation that is found in colloid carcinomas was examined by immunostaining in the original MCN series and in the MCN with the intratumoral colloid growth pattern. Focal expression of CDX2 was found in 22 of 43 MCN including the MCN that exhibited the intratumoral colloid growth pattern. Overall, the data suggest that MCN rarely, if ever, invade as colloid carcinoma but the expression of CDX2 by some MCN and the observation of intratumoral colloid growth pattern in one MCN seems to leave open the possibility that MCN might rarely invade as colloid carcinoma.     

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: A tissue microarray study

ObjectivesThe aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis.Materials and methodsAn immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score.ResultsBoth of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression.ConclusionsIn ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors.     

SATB2 is a supplementary immunohistochemical marker to CDX2 in the diagnosis of colorectal carcinoma metastasis in an unknown primary

CDX2 is routinely used for identifying gastrointestinal origin of metastatic adenocarcinomas; but a high percentage of other carcinomas also show positivity with this antibody. SATB2 is a new immunohistochemical marker with a few studies showing that it is specifically expressed in a large majority of colorectal adenocarcinomas. We assessed SATB2 along with CDX2 in patient material with metastasis in order to determine whether the primary site could be identified as ‘colon‐rectum’. Metastasis in 67 liver biopsies, 108 lymph nodes from resection specimens and 36 serous effusions was analyzed retrospectively. Blinded slides stained for CDX2 and SATB2 were assessed individually by two pathologists and sensitivity, specificity and kappa statistics were calculated. Sensitivity for CDX2 in metastasis from colorectal adenocarcinomas was 93%; while in SATB2 it was 79%. The combination of CDX2 and SATB2 yielded a sensitivity of 79% and a high specificity of 93%. There was an acceptable level of agreement (κ = 0.64) between the pathologists for both the markers in case of colorectal adenocarcinoma metastasis. CDX2 is a sensitive marker compared to SATB2; while the specificity of combination of CDX2 and SATB2 is high for metastasis from colorectal adenocarcinoma. SATB2 can be used as a supplementary marker along with CDX2 to identify colorectal origin for material received from patients clinically presenting with metastasis.     

Pathology of primary and metastatic mucinous ovarian neoplasms

Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian 'borderline' mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra-abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a 'maturation' pattern in metastases can result in the same appearance.     

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

OBJECTIVE:

Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors.

METHODS:

A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody.

RESULTS:

Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis.

CONCLUSIONS:

The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.     

Mixed ovarian large cell neuroendocrine carcinoma, mucinous adenocarcinoma, and teratoma: A report of two cases and review of the literature

Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma.     

Parathyroid hormone-related peptide expression in primary and metastatic liver tumours

Parathyroid hormone-related peptide (PTHrP) is a major factor in the pathophysiology of hypercalcaemia of malignancy. Recent evidence suggests that PTHrP may play an important role in the growth and differentiation of neoplastic as well as non-neoplastic cells. PTHrP was originally detected in normal fetal, but not adult, liver. We have used immunocytochemistry to show that reactive human bile ductules expressing a neuroendocrine phenotype contain immunoreactive PTHrP. These observations raised the possibility that PTHrP immunoreactivity may be useful in the differential diagnosis of primary liver tumours and metastases of adenocarcinoma. A total of 24 primary liver tumours and 22 metastases of adenocarcinoma were studied. All cholangiocarcinomas showed immunopositivity for PTHrP and chromogranin A, while all hepatocellular carcinomas were negative for PTHrP and showed only focal and weak positivity for chromogranin A. Mixed types of primary liver tumour contained PTHrP immunoreactivity only in the areas of cholangiocellular differentiation. Moreover, all metastatic adenocarcinomas were negative for PTHrP and chromogranin A except for two out of five metastatic breast adenocarcinomas. These two patients had bone metastases and hypercalcaemia and thus did not yield differential diagnostic problems with cholangiocarcinoma. None of the patients with cholangiocarcinoma and hepatocellular carcinoma had hypercalcaemia. We conclude that PTHrP is a useful marker for primary cholangiocarcinoma. especially in the differential diagnosis of hepatocellular carcinoma and metastatic adenocarcinoma.