Mucinous Cystadenoma of the Urachus and Review of Current Classification of Urachal Mucinous Cystic Neoplasms.

Urachal neoplasms are uncommon and represent a minor portion of bladder tumors. According to the recently updated World Health Organization classification (2016), these tumors are classified as adenomas, adenocarcinomas, nonglandular neoplasms, and mixed carcinomas. The mucinous cystic neoplasms represent a small percentage of urachal tumors with morphologic spectrum ranging from benign mucinous cystadenoma to borderline mucinous cystic tumor of low malignant potential and to malignant mucinous cystadenocarcinoma. Benign urachal mucinous cystic adenomas are exceedingly rare, and only a few cases have been reported in the literature to date. The goal of this review is to summarize the clinical features, histopathologic characteristics, treatment, and prognosis of urachal mucinous cystadenoma in light of differentiating them from mucinous cystic tumor of low malignant potential and mucinous cystadenocarcinoma.

Tumores papilares mucinosos intraductales y cistoadenomas mucinosos: postura actual y recomendaciones / Intraductal papillary mucinous neoplasms and mucinous cystadenomas: current status and recommendations

La prevalencia real de las lesiones quísticas de páncreas sigue siendo una incógnita. El potencial de malignidad de algunas de estas lesiones supone una causa de preocupación significativa en la práctica clínica diaria. Por lo tanto, es necesario determinar una estrategia para poder discriminar claramente los quistes potencialmente malignos de aquellos que no suponen ningún tipo de riesgo. Los tumores papilares mucinosos intraductales y los cistoadenomas mucinosos son neoplasias quísticas mucinosas potencialmente malignas que han ido ganando mayor importancia y reconocimiento en los últimos años. Sin embargo, pese a los múltiples estudios que se han realizado hasta la fecha, su diagnóstico diferencial respecto a otros subtipos de quistes, así como su manejo terapéutico, continúan suponiendo un reto. Este manuscrito contiene una revisión crítica de las recomendaciones actuales y de las estrategias en el manejo de los tumores papilares mucinosos intraductales y los cistoadenomas mucinosos, así como hace hincapié en las limitaciones de las guías actuales (AU)

The real prevalence of pancreatic cystic lesions remains unknown. The malignant potential of some of these lesions remains a cause for significant concern. Thus, it is mandatory to develop a strategy to clearly discriminate those cysts with a potential for malignant transformation from those that do not carry any significant risk. Intraductal papillary mucinous neoplasms and mucinous cystadenomas are mucinous cystic neoplasms with a known malignant potential that have gained greater recognition in recent years. However, despite the numerous studies that have been carried out, their differential diagnosis among other cysts subtypes and their therapeutic approach continue to be a challenge for clinicians. This review contains a critical approach of the current recommendations and management strategies regarding intraductal papillary mucinous neoplasms and mucinous cystadenomas, as well as highlighting the limitations exposed in current guidelines (AU)

Sarcoma-Like Mural Nodule in a Borderline Mucinous Tumour of Ovary.

A 37-year female presented with complaint of lower abdominal pain and amenorrhoea to the Military Hospital, Rawalpindi. Ultrasound of pelvis showed a right adnexal cystic lesion. On investigation, CA-125 was raised. Her MRI scan of pelvis revealed a right adnexal mass of fluid intensity measuring 15.2 x 12.9 x 9.2 cm. Right ovarian cystectomy was performed and the specimen was sent for histopathological examination. Grossly, the mass was cystic in appearance and measured 13.5 x 10 x 10 cm. On sectioning, it was unilocular and filled with turbid material. The cyst wall showed multiple papillary structures along with a nodule measuring 1.1 x 1 cm. Microscopically, the sections revealed borderline mucinous tumour with a sarcoma-like mural nodule composed of spindle shaped cells and epulis-like giant cells. Sarcoma-like mural nodules are rare nodules which are associated with mucinous tumours of the ovary. However, they have excellent prognosis and should not be interpreted as malignant.

Glandular neoplasms of the urachus: a report of 55 cases emphasizing mucinous cystic tumors with proposed classification.

Published experience remains limited for glandular neoplasms of the urachus, especially mucinous cystic tumors. We reviewed 55 glandular urachal neoplasms to evaluate their clinical features and histopathologic spectrum and to devise a classification system for the mucinous cystic forms. Within the 55 cases studied, we observed 2 groups with differing clinical, gross, and histopathologic features. The first group, invasive, noncystic adenocarcinomas (n=24), had clinicopathologic features in accord with the known spectrum of urachal adenocarcinoma (mean age 50 y, female:male ratio 1.7, with recurrence or death from disease in 9/16 cases over a 45 mo mean follow-up). The second group, mucinous cystic tumors (n=31), morphologically resembled mucinous cystic tumors of the ovary and appeared classifiable by the same approach (mean age 47 y, female:male ratio 1.4) and included mucinous cystadenoma (n=4), mucinous cystic tumor of low malignant potential (n=22, including 2 cases with intraepithelial carcinoma), and mucinous cystadenocarcinoma with microscopic (n=4) or frank invasion (n=1). Follow-up information was available for 13 patients with mucinous cystic tumors (mean 41 mo); we observed no local recurrence or distant metastasis. This experience suggests that there is a distinct group of glandular, cystic tumors of the urachus that is classifiable in a manner similar to ovarian neoplasms and that has a favorable prognosis after complete excision. As with cystic neoplasms of other organs, rigorous sampling is recommended to identify potentially small foci of carcinoma that could be missed by inadequate sampling. Accordingly, classification based on methods other than complete surgical excision may be hazardous.

Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary.

AIMS: Mucinous borderline tumours of the ovary are subclassified as intestinal-type (IMBT) and endocervical-like (EMBT), which differ in their clinicopathological features. In this study, we attempted to elucidate characteristics of the mucinous epithelium in each subtype. METHODS AND RESULTS: The expression of claudin-18, a marker of gastric differentiation, MUCs, CDX2, CK7, CK20, oestrogen receptor (ER), progesterone receptor (PgR), CA-125 and vimentin in IMBTs (n = 54), EMBTs (n = 25) and serous borderline tumours (SBTs) (n = 22) were compared by immunohistochemistry. Claudin-18 positivity was identified in 98% of the IMBTs, whereas only 4% of the EMBTs were claudin-18-positive. Expression of intestinal markers such as CDX2 and MUC2 was relatively infrequent in IMBTs (48% and 33%, respectively). Müllerian-lineage markers such as ER, PgR and vimentin were expressed rarely in IMBTs, while most EMBTs and SBTs were positive for these markers. Hierarchial clustering revealed a close association between EMBTs and SBTs, while IMBTs were clearly separate. CONCLUSIONS: Claudin-18 positivity is a specific phenotype that is characteristic of IMBTs. Frequent and diffuse expression of gastric markers, along with less frequent and usually focal expression of intestinal markers, suggests that IMBTs are essentially composed of gastrointestinal-type mucinous epithelium (gastric-type epithelium with a variable degree of intestinal differentiation).

Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors.

Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (P<0.05), including beta-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-kappaB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (P<0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (P<0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (P<0.05, both). NF-kappaB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also beta-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-kappaB positivity, and beta-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.

[Carcinoma of the pancreas at the site of an intraductal papillary mucinous neoplasia]. / Pankreaskarzinom auf dem Boden eines intraduktal papillär-muzinösen Tumors.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are intraductally located, mucin-producing cystic neoplasms of the pancreas with a malignant potential. We report about a 54-year-old female who underwent segmental resection of the pancreas for non-invasive IPMN. The surgical margins were tumour-negative. Three years later a highly suspicious tumour of the pancreatic tail was detected during routine follow-up. Resection of the pancreatic tail was performed. The histological analysis revealed an adenocarcinoma. This case suggests the development of a pancreatic carcinoma from a non-invasive IPMN and raises the question about the extent of surgery of non-invasive IPMNs of the pancreas.

Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors.

Hepatocyte nuclear factor 4 alpha (HNF4 alpha) is a member of the nuclear receptor superfamily and is expressed in several endodermal tissues. The aim of the present study was to examine the expression of HNF4 alpha on ovarian epithelial tumors with immunocytochemistry and immunohistochemistry using mAbs recognizing P1 and P2 promoter-driven HNF4 alpha. Ovarian mucinous adenoma, mucinous tumors of borderline malignancy, and mucinous adenocarcinoma had positive nuclear staining for HNF4 alpha (41/45, 91%). One-third (34%) of mucinous tumors had P1-positive staining and most had P1/P2-positive staining (93%). MUC2- and MUC5AC-positive staining was observed in 34% and 95% of mucinous tumors, respectively. The histological subtype of these mucinous tumors was not correlated with HNF4 alpha expression. On cytology it was found that cancer cells in the ascites from ovarian mucinous adenocarcinomas were HNF4 alpha positive, but tumor cells in ascites from other types of ovarian carcinomas were negative for HNF4 alpha. Thus, HNF4 alpha is demonstrated to be a useful marker for histological and cytological diagnosis of ovarian mucinous tumors.

Nuclear morphometry and AgNOR quantification: computerized image analysis on ovarian mucinous tumor imprints.

OBJECTIVE: To determine the morphometric characteristics of nuclei and silver-stained nucleolar organizer regions (AgNORs) on cytologic imprints and their value in differential cytodiagnosis of benign, atypical proliferative (borderline) and malignant ovarian mucinous tumors. STUDY DESIGN: Forty-six mucinous ovarian tumor imprints (16 benign, 15 borderline, 15 malignant), were analyzed. Nuclear area, outline, "shape factor" and "form factor" were measured on Papanicolaou-stained smears. AgNOR quantification included 7 variables related to the number and area of single, cluster, total and relative AgNOR content per nucleus and the size distribution of AgNORs. RESULTS: Nuclear area and shape factor allowed distinguishing borderline and malignant tumors. The nuclear area in benign tumors was larger than that in borderline tumors; malignant tumors had the highest values. Single and cluster AgNORs were statistically significantly different in borderline tumors compared with malignant tumors, except for the cluster AgNOR area. The total AgNOR area, number and relative area increased from benign through malignant tumors, with statistically significant differences among all groups. By AgNOR size distribution, small AgNORs discriminate malignant from borderline and benign tumors. CONCLUSION: Combining nuclear morphometry and AgNOR analysis on cytologic imprints could be a diagnostically useful method in the assessment of mucinous ovarian tumors.

[Management of ovarian cysts]. / Prise en charge des kystes ovariens.

Ovarian cysts occur frequently in women of reproductive age. These are usually functional cysts which resolve spontaneously and whose evolution can be followed with ultrasound. Non-functional cysts have diverse histologic origins. The most common are serous and mucinous cystadenomas which arise from the epithelial wall of the ovary, endometriomas which arise in the setting of pelvic endometriosis, and dermoid cysts which arise from the germinal cells of the ovary. Endovaginal ultrasound with Doppler enhancement is the best imaging technique to establish the nature of cysts and to distinguish cysts suspicious for malignancy which require more invasive investigation. Pelvic laparoscopy is the surgical approach of choice for the treatment of non-functional benign ovarian cysts. Conservative treatment to shell out the cyst and preserve functional ovarian tissue should be reserved for women desirous of future pregnancies. The risk of ovarian cancer remains a major preoccupation of the surgeon. Where malignancy is suspected, laparoscopy is contraindicated and a median laparotomy is appropriate for radical extirpative surgery. This article describes the diagnostic techniques which allow a laparoscopic approach to presumably benign cysts and discusses surgical techniques specifically adapted to their different histologic nature of ovarian cysts.

Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group.

PURPOSE: To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. PATIENTS AND METHODS: Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. RESULTS: Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. CONCLUSION: Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.

Mucinous borderline ovarian tumors: points of general agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior.

This report focuses on the borderline category of ovarian mucinous tumors and summarizes the points of general agreement and persistent controversies identified by experts in the field who participated in the Borderline Ovarian Tumor Workshop held in Bethesda, MD, in August 2003. Points of agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior are addressed for the following ovarian mucinous tumor categories: mucinous borderline ovarian tumor (M-BOT; synonymously referred to as atypical proliferative mucinous tumor of ovary or mucinous ovarian tumor of low malignant potential), M-BOT with intraepithelial carcinoma, and M-BOT with microinvasion. The morphologic spectrum of M-BOTs with regard to distinction from mucinous cystadenoma and the confluent glandular/expansile type of invasive mucinous carcinoma is also addressed. Non-ovarian mucinous tumors, including the secondary ovarian mucinous tumors associated with pseudomyxoma peritonei and metastatic mucinous carcinomas with a deceptive pattern of invasion, are recognized as tumors that can simulate primary M-BOTs. Improved classification of these mucinous tumors has clarifed the behavior of true M-BOTs by excluding these simulators from the M-BOT category.

Mucinous cystadenoma with mesenchymal over-growth: a new variant among pancreatic mucinous cystadenomas?

We report an unusual type of mucinous cystadenoma of the pancreas, characterised by a predominantly solid gross appearance due to the presence of an abundant ovarian-type stroma. The tumour, located in the body of the pancreas, was discovered after episodes of acute pancreatitis. It was composed of several mucus-secreting benign cysts placed within a highly cellular ovarian-type stroma, composed of undifferentiated spindle cells with mild atypia but without any increase of mitotic activity and with a low proliferative index. These cells expressed oestrogen and progesterone receptors, but they did not express CD34, CD117, p53 protein or bcl-2. Recognition of this peculiar mainly solid mucinous cystadenoma containing an abundant ovarian-type stroma is difficult. It is conceivable that the mesenchymal component described in our case could represent an early stage in the development of sarcoma in mucinous cystadenoma of the pancreas.

Histology of cystic tumors of the pancreas.

The cystic tumors of the pancreas constitute a considerable diagnostic challenge because of their overlapping clinical, radiologic, and pathologic features. They may be difficult to differentiate from one another and from benign lesions such as pseudocysts. Because many of the tumors in this group are potentially curable, correct diagnosis is essential for proper patient management. Even when correctly diagnosed, thorough microscopic evaluation is required for the mucin-producing tumors to correctly determine their degree of malignant progression in any given case. Most recently, molecular analysis of these tumors has demonstrated definitively that the serous and mucinous types of cystic neoplasms of the pancreas are unrelated pathogenetically. Conversely, molecular data indicate similarities between the mucinous types of cystic tumors and ductal adenocarcinoma of the pancreas, but the essential molecular differences that underlie the differences in biological behavior are as yet undetermined.

Problems in histological diagnosis of intraductal papillary-mucinous tumor (IPMT).

IPMTs (intraductal papillary-mucinous tumors) of the pancreas have been recognized as a distinct clinical entity. WHO used this term in most recent classification (1996). The present report reviews the WHO classification and recent descriptions of IPMT. Problems regarding the histological diagnosis and differential diagnosis are also discussed. In the WHO classification, IPMTs are classified into three categories: intraductal papillary-mucinous adenoma, intraductal papillary-mucinous tumor with moderate dysplasia and intraductal papillary-mucinous carcinoma. The classification is based on the tissue morphology, such as degree of dysplasia and pattern of proliferation. Some immunohistochemical and molecular markers have been reported for differential diagnosis and estimating the prognosis of IPMT. MUC1, Dpc-4, p53 and Ki-67. In making a differential diagnosis, mucinous cystic tumors are the most problematic. Communication with the pancreatic ducts, the presence of ovarian type stroma and capsular formation are key histological factors for a differential diagnosis between IPMTs and mucinous cystic tumors. The prognosis of IPMTs is favorable in general. However, once massive invasion has occurred, the prognosis is very poor, as in cases of ductal carcinoma. For further studies of IPMT, pathologists and clinicians involved in the diagnosis and treatment of IPMTs need to understand the concept of IPMTs and use the WHO classification.

Intraductal papillary-mucinous tumor of the pancreas: a historical review of the nomenclature and recent controversy.

A number of studies on mucin-producing cystic neoplasm of the pancreas have been reported since the first report of the tumor in 1982. There has been some controversy about nomenclatures and clinicopathologic entities of mucin-producing cystic tumor, mucinous cystic tumor, and intraductal papillary tumor of the pancreas. In 1996 and 1997, new classifications of pancreatic neoplasms were published by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP). According to the new WHO and AFIP classifications, mucin-producing cystic neoplasm of the pancreas corresponds mainly to intraductal papillary-mucinous tumor and mucinous cystic tumor of the pancreas. and these two diseases are independent conditions. Intraductal papillary-mucinous tumor is regarded as a unique clinical entity, but controversy remains about the term and clinicopathologic entity. Some confusion and problems remain betweeen the two lesions. In this review, we review their historical background, terminology, WHO and AFIP classification, and problems with classification.

Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management.

HYPOTHESIS: Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT). DESIGN: Retrospective study. SETTING: University hospital from January 1988 through December 1994. PATIENTS AND INTERVENTION: We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT. RESULTS: The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease. CONCLUSIONS: Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.

Two-dimensional gel analysis of protein expression in ovarian tumors shows a low degree of intratumoral heterogeneity.

The process of tumor progression leads to the emergence of multiple clones, and to the development of tumor heterogeneity. One approach to the study of the extent of such heterogeneity is to examine the expression of marker proteins in different tumor areas. Two-dimensional gel electrophoresis (2-DE) is a powerful tool for such studies, since the expression of a large number of polypeptide markers can be evaluated. In the present study, tumor cells were prepared from human ovarian tumors and analyzed by 2-DE and PDQUEST. As judged from the analysis of two different areas in each of nine ovarian tumors, the intratumoral variation in protein expression was low. In contrast, large differences were observed when the protein profiles of different tumors were compared. The differences in gene expression between pairs of malignant carcinomas were slightly larger than the differences observed between pairs of benign tumors. We conclude that 2-DE analysis of intratumoral heterogeneity in ovarian cancer tissue indicates a low degree of heterogeneity.

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases.

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.