[A Case of Mucinous Cystoadenocarcinoma with Metastatic Liver Tumor in a Young Woman Lacking Specific Findings].

The patient was a 17-year-old woman. An abnormal urinalysis was observed, and abdominal echography showed a pancreatic cystic mass. At the first examination, computed tomography(CT)and endoscopic ultrasound(EUS)showed a unilocular cystic mass of 60mm in size in the pancreatic body and tail, and no malignant findings were observed. After 14 months, CT and positron emission tomography-computed tomography(PET-CT)showed that the cystic mass had a mural nodule with FDG accumulation, and presence of a tumor in hepatic S8 with FDG accumulation. Laparoscopic distal pancreatectomy and hepatic subsegmentectomy of S8 were performed for diagnostic and therapeutic purposes. The pathological diagnosis was mucinous cystadenocarcinoma(MCC)and metastatic liver cancer in the form of MCC. S-1 was administered after surgery. Nine months after resection, multiple metastatic liver tumors were found, and GEM plus nab-PTX was administered. After 2 courses of treatment, the patient is still alive without new lesions.

[Metastatic tumors in the ovary, difficulties of histologic diagnosis]. / A petefészek áttéti tumorai, a szövettani diagnosztika problémái.

The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections.

[Morphology of secondary ovarian tumors and metastases]. / Morphologie sekundärer Ovarialtumoren/Ovarmetastasen.

The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately 85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches.

Can CA-125 predict lymph node metastasis in epithelial ovarian cancers in Turkish population?

OBJECTIVE: The role of single preoperative serum CA-125 levels in predicting pelvic or paraaortic lymph node metastasis in patients operated for epithelial ovarian cancer has been investigated. METHODS: 176 patients diagnosed with epithelial ovarian carcinoma after staging laparotomy between January 2002 and May 2010 were evaluated retrospectively. RESULTS: The mean, geometric mean, and median of preoperative serum CA-125 levels were 632,6, 200,29, and 191,5 U/mL, respectively. The cut-off value predicting lymph node metastases in the ROC curve was 71,92 U/mL, which is significant in logistic regression analysis (P = 0.005). The preoperative log CA-125 levels were also statistically significant in predicting lymph node metastasis in logistic regression analysis (P = 0.008). CONCLUSIONS: The tumor marker CA-125, which increases with grade independent of the effect of stage in EOC, is predictive of lymph node metastasis with a high rate of false positivity in Turkish population. The high false positive rate may obscure the predictive value of CA-125.

Expression of urokinase plasminogen activator and plasminogen activator inhibitor type-1 in ovarian cancer and its clinical significance.

The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. In addition, the levels in patients with poorly differentiated and stage III-IV cancers, cancers with metastases as well as residual tumors >2 cm after surgery, were all obviously increased, consistent with their concentrations in serum. The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.

Metastatic mucinous ovarian cancer and treatment decisions based on histology and molecular markers rather than the primary location.

Approximately 22,000 cases of ovarian cancer occur each year in the United States, and likely fewer than 2000 cases of mucinous ovarian cancers. Although 90% of patients with mucinous ovarian cancer present with stage I disease and have curative surgeries, advanced-stage disease is known to have a poor response to standard platinum- and taxane-based chemotherapy. Despite limited enthusiasm, standard chemotherapy is still recommended for most patients with advanced-stage mucinous malignancies of the ovary. This report presents an unusual case of a woman with HER2-positive metastatic mucinous carcinoma of the ovary treated with chemotherapy regimens typically used for colorectal malignancies, followed by epidermal growth factor receptor-targeted therapies.

Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.

Ovarian metastases of pancreaticobiliary tract adenocarcinomas: analysis of 35 cases, with emphasis on the ability of metastases to simulate primary ovarian mucinous tumors.

Metastatic mucinous carcinomas in the ovary are readily recognized when they show characteristic features, including bilateral involvement, only moderate tumor size, surface and superficial cortical involvement, nodular growth, and an infiltrative pattern. However, it is well established that some metastatic mucinous carcinomas can simulate primary ovarian mucinous tumors grossly and microscopically. Metastatic pancreaticobiliary tract adenocarcinomas present a particular diagnostic challenge due to their ability to exhibit borderline-like and cystadenomatous growth patterns, which can be misinterpreted as underlying primary ovarian precursor tumors and can be erroneously used to support interpretation of the carcinomatous components as arising from these purported precursors within the ovary. Thirty-five cases of metastatic pancreaticobiliary tract adenocarcinomas were analyzed. The mean patient age was 58 years (median, 59 y; range, 33 to 78 y). In 15 cases (43%), the pancreaticobiliary tract and ovarian tumors presented synchronously and in 2 cases (6%) the ovarian tumors presented earlier as the first manifestation of the disease. Ovarian tumors were bilateral in 31 cases (89%). Mean and median tumor sizes were 10.6 and 9.5 cm, respectively (range, 2.5 to 21.0 cm). Nodularity was present in 22 cases (63%) and surface involvement was identified in 14 cases (40%). An infiltrative growth pattern was present at least focally in 28 cases (80%), accompanied by borderline-like and/or cystadenomatous areas in 17 (49%) cases and as the exclusive pattern in 11 cases (31%). Conversely, borderline-like and cystadenomatous patterns were identified in 24 cases (69%) and as the exclusive patterns (either pure or combined with one another) in 7 cases (20%). Dpc4 expression was lost in 20 of 33 tumors analyzed (61%). Of 25 patients with follow-up, 23 patients had died of disease (mean/median time, 9/6 mo; range, 1 to 39) and 2 patients were alive with disease (at 1 and 25 mo). Frequent bilateral ovarian involvement, moderate tumor size, nodularity, and infiltrative patterns are useful features for identifying these ovarian tumors as metastatic. However, many tumors exhibit borderline-like and cystadenomatous patterns that, when dominant and combined with synchronous presentation, make recognition as metastases an ongoing challenge. Loss of Dpc4 expression provides the most useful immunohistochemical evidence for establishing the pancreaticobiliary tract as the most likely source of these metastatic mucinous carcinomas in the ovary.

[Expression of EVEC in ovarian carcinoma and its biological significance].

OBJECTIVE: To investigate the expression of EVEC in ovarian carcinoma and explore its biological significance. METHODS: The expression of EVEC in 22 specimens of normal ovarian tissues and 63 specimens of ovarian cancers was detected by RT-PCR and Western blotting analysis, respectively. RESULTS: RT-PCR showed that the expression level of EVEC in stage I-II ovarian cancer (0.199 ± 0.014) was significantly higher than that in stage III-IV ovarian cancer (0.155 ± 0.015, P < 0.05), and significantly lower than that in normal ovarian tissues (0.415 ± 0.055, P < 0.05). There was no significant difference between the expression levels of EVEC in primary sites and that in corresponding metastatic sites of ovarian cancer (P > 0.05). Furthermore, the results of Western blot also showed that the protein expression level of EVEC in stage I-II ovarian cancer was also significantly lower than that in normal ovarian tissues (0.179 ± 0.026 vs. 0.543 ± 0.032, P < 0.05), and higher than that in stage III-IV ovarian cancer (0.179 ± 0.026 vs. 0.115 ± 0.023, P < 0.05). The EVEC expression level in the epiploic metastasis of stage I-II ovarian cancer was significantly higher than that of stage III-IV ovarian cancer (0.201 ± 0.028 vs. 0.101 ± 0.037, P < 0.05). The expression of EVEC in ovarian carcinoma had no correlation with age, pathologic classification and histological grade (P > 0.05). CONCLUSIONS: EVEC is closely related with carcinoma metastasis. The expression of EVEC in ovarian cancer and its metastatic sites was remarkably decreased. EVEC may play a negative role in the development and metastasis of ovarian cancer and may be a valuable marker in estimation of the prognosis for patients.

[Appendicular cystadenocarcinoma with cutaneous fistula]. / Cystadénocarcinome appendiculaire fistulisé à la peau.

BACKGROUND: Cutaneous metastasis of colorectal cancer is rare. We report a case of fistular lesions of the buttocks revealing a mixed tumour of the appendix involving mucinous cystadenocarcinoma and carcinoid tumour. CASE REPORT: A 67-year-old woman was admitted for four skin fistulae of the right buttock present for 6 years. Histological examination of skin biopsy specimens identified infiltration of the dermis by metastatic mucinous adenocarcinoma while colonoscopy showed a caecal tumour measuring 4 cm. Surgical excision was performed involving right hemicolectomy, evacuation of retroperitoneal mucin collection and excision of fistulae. Histopathological examination of surgical specimen confirmed mixed tumour consisting of perforated mucinous cystadenocarcinoma and carcinoid tumour of the appendix. Recurrence of the fistular lesions was seen. The patient was hospitalized several times for surgical drainage of mucin. She died one year later. DISCUSSION: Cutaneous metastasis of colorectal cancer is an uncommon event that usually occurs after identification of the primary tumour and generally indicates advanced-stage disease and an ominous prognosis. This case is particular and underlines the need to rule out a metastatic origin of cutaneous fistulae, even in patients otherwise apparently in good health.

Bladder metastases of appendiceal mucinous adenocarcinoma: a case presentation.

BACKGROUND: Appendiceal adenocarcinoma is rare with a frequency of 0.08% of all surgically removed appendices. Few cases of appendiceal carcinoma infiltrating the bladder wall for spatial contiguity have been documented. CASE PRESENTATION: A case is reported of a 45-years old woman with mucinous cystadenocarcinoma of the appendix with bladder metastasis. Although ultrasonography and voided urinary cytology were negative, abdomen computed tomography (CT) scan and cystoscopy and subsequent pathological examination revealed a mass exclusively located in the anterior wall of the bladder. Histopathology of the transurethral bladder resection revealed a bladder adenocarcinoma [6 cm (at the maximum diameter) x 2,5 cm; approximate weight: 10 gr] with focal mucinous aspects penetrating the muscle and perivisceral fat. Laparotomy evidenced the presence of a solid mass of the appendix (2,5 cm x 3 cm x 2 cm) extending to the loco-regional lymph nodes. Appendectomy and right hemicolectomy, linfoadenectomy and partial cystectomy were performed. The subsequent pathological examination revealed a mucinous cystadenocarcinoma of the appendix with metastatic cells colonising the anterior bladder wall and several colic lymph nodes. CONCLUSIONS: The rarity of the appendiceal carcinoma invading the urinary bladder and its usual involvement of nearest organs and the posterior bladder wall, led us to describe this case which demonstrates the ability of the appendiceal cancer to metastasize different regions of urinary bladder.

Factors in intraductal papillary mucinous neoplasms of the pancreas predictive of lymph node metastasis.

BACKGROUND: Little is known about the frequency of lymph node metastasis (LNM) in intraductal papillary mucinous neoplasms (IPMNs), and we have not been able to determine how much lymph node dissection is necessary in individual cases. The aim of this study was to investigate the predictive factors for the LNM in IPMNs. METHODS: Medical records of 120 patients pathologically diagnosed as having IPMN were reviewed, and 16 possible predictive factors regarding the LNM were analyzed. RESULTS: LNM was observed in 7 patients (6%), all of whom were diagnosed as having mural nodules preoperatively. Sensitivity, specificity, and accuracy of preoperative imaging for detecting mural nodules of IPMNs in this study were 84, 97, and 90%, respectively. Univariate analysis using 61 patients having mural nodules preoperatively revealed that the size of mural nodules ≥10 mm and positive imaging findings for invasive tumor and possible LNM were significant predictive factors for the LNM. Multivariate analysis demonstrated that only an imaging finding for invasive tumor was an independent significant predictive factor. Positive and negative predictive values of the imaging finding of invasive IPMNs for LNM were 50 and 98%, respectively. CONCLUSIONS: Standard lymph node dissection would be recommended in patients with IPMNs with mural nodules demonstrating preoperative imaging findings for invasive carcinomas. and IAP.

Notch1 expression correlates with tumor differentiation status in ovarian carcinoma.

Notch signaling and its receptor Notch1 are expressed in ovarian epithelial tumors, but the relationship between Notch signaling and ovarian cancer remains to be elucidated. In this study, we detected the expression of Notch1 in ovarian tissues and human ovarian cancer cell lines. We also analyzed the expression of Notch1 and its relationship with differentiation status and FIGO (Federation International of Gynecology and Obstetrics) stage in ovarian cancer tissues. Immunohistochemistry, real-time polymerase chain reaction and Western blot were used to detect the expression of Notch1 in 109 ovarian cancer tissues, 65 patient-matched opposite side normal ovarian tissues and 48 normal ovarian tissues, together with A2780, HO-8910 and IOSE 144 cell lines. Our results showed that the expression of Notch1 in ovarian cancer tissues was higher than that in matched normal tissues and normal tissues, Notch1 is highly expressed in ovarian cancer cells A2780 and HO-8910. Moreover, expression of Notch1 increased gradually with the poor differentiating of cancer tissues and the increasing of FIGO stage in ovarian cancer tissues. It was concluded that Notch1 might be involved and play an oncogenic role in the development of ovarian cancer.

Gingival metastasis of ovarian carcinoma: report of a case and review of the literature.

Diagnosing gingival metastases is difficult because clinically they can mimic benign oral lesions. The authors report an unusual case of metastatic ovarian carcinoma in the gingiva of a 46-year-old woman 5 years after ovariectomy. The tumor presented as an exophytic growth at the molar region of the mandible. Histological examination showed invasive proliferation of atypical glandular structures composed of mucin-producing cells laying in a fibrous stroma. Tumor cells were immunopositive for carcinoembryonic antigen, MUC1 mucin, and lysozyme, while stromal fibroblasts were immunopositive for vimentin and estrogen receptor. The diagnosis of metastatic ovarian mucinous cystadenocarcinoma was made. A review of the English literature revealed this to be the first report of gingival metastasis of an ovarian carcinoma.

Primary retroperitoneal mucinous tumors: a clinicopathologic study of 18 cases.

Primary retroperitoneal mucinous tumors (PRMTs) are uncommon neoplasms occurring almost exclusively in women. PRMTs are divided into mucinous cystadenoma (MC), mucinous borderline tumors or tumors of low malignant potential (MLMP), and mucinous carcinomas (MCas). In this retrospective study, we present the clinicopathologic features of 18 such cases, the largest series to date. All patients were women, ranging in age from 20 to 63 years (mean 38.6 y). All except 2 patients presented with an enlarged mass during a routine examination or by self-palpation. All tumors were located exclusively in the retroperitoneum, with histologic or clinical confirmation of the lack of ovarian involvement. The tumors ranged from 7 to 26 cm (mean 13.2 cm). The gross appearance was variable: unilocular cyst with a thin wall (4 cases), predominantly cystic with papillary areas or nodule(s) (8 cases), multiloculated cyst with or without nodules (1 case each), and predominantly solid with cystic areas (4 cases). Histologically, there were 2 cases of MC, 7 of MLMP (7 cases; 3 of them with intraepithelial carcinoma and 1 with microinvasion), and 9 of MCas (9 cases, 5 of them associated with MLMP and 1 associated with MC). Three of the MCas had areas of anaplastic or sarcomatoid carcinoma whereas 1 had an associated sarcoma. Immunohistochemical studies were performed in 6 cases. Cytokeratin 7 was diffusely positive in all cases studied, whereas cytokeratin 20 and cytokeratin 17 were focally positive in 4 and 2 cases, respectively. All patients underwent surgical resection of the entire tumor. Two patients with MCa and sarcoma or sarcomatoid carcinoma received chemotherapy. Follow-up was available in 16 cases, ranging from 1 to 148 months (mean 40 mo, median 22 mo). Two patients died of disease at 5 and 9 months; both had MCa with anaplastic carcinoma or sarcoma. Three patients with MCa were alive with disease at 14, 26, and 58 months. The remaining patients were alive with no evidence of disease. In this study, MLMP and MCa were more common than MC. PRMTs seem to be nonaggressive neoplasms, except in cases containing anaplastic carcinoma or sarcoma.

WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Bone metastasis from ovarian cancer.

We report a case of epithelial ovarian cancer, which presented with lumbar vertebral metastasis soon after treatment, as a part of distant spread. This patient was then treated by palliative radiotherapy and put on second line chemotherapy i.e, Topotecan. She responded to treatment well.