Editorial: Pseudomyxoma Peritonei: More Questions Than Answers (appendix/ovarian

JCO: Pseudomyxoma Peritonei: More QuestionsThan Answers

"Chances are, if you ask most physicians and surgeons about
pseudomyxoma peritonei (PMP), they will respond with more questions
than answers. The confusion that surrounds PMPis not surprising
because the origin, pathology, treatment, prognosis, and very
definition of PMP are still under debate. PMP is a clinical syndrome
that is characterized by mucinous ascites that result from rupture of a
mucin-producing neoplasm, typically of appendiceal origin....."

"...The appendix is the primary cause of PMP; the ovaries are typically
only secondarily involved...."

A benign multicystic peritoneal mesothelioma mimicking recurrence of ovarian borderline tumor: a case report

A benign multicystic peritoneal mesothelioma mimicking recurrence of ovarian borderline tumor: a case report:

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 Introduction
Benign multicystic peritoneal mesothelioma (BMPM) is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain.

Case presentation
The case was 23 years-old Japanese woman and had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been histologically diagnosed as mucinous borderline tumor. Two years and 9 months after the initial operation, multiple cysts were found in the patient. Laparotomy was performed, and the uterus, left ovary, omentum, and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. Histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather BMPM. There were no residual lesions, and the patient was followed up with ultrasonography. She remains free from recurrence 9 months after treatment.

Conclusion:
We report a case of BMPM mimicking recurrence of ovarian borderline tumor. BMPM should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

abstract: Hormone Therapy and Different Ovarian Cancers: A National Cohort Study (postmenopausal women/does not include reference to clear cell ovarian)

 Blogger's Note: the abstract makes no reference to clear cell ovarian, given the number of women followed this omission (in the abstract) is curious


Hormone Therapy and Different Ovarian Cancers: A National Cohort Study

Abstract

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. 

Using Danish national registers, the authors identified 909,946 women who were followed from 1995–2005. The women were 50–79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. 

Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology......... In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. 

Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors and endometrioid tumors but decreased risk of mucinous tumors. Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. 

Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

abstract: Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type.

Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type [Am J Surg Pathol. 2012]

Abstract

The role of endometriosis in ovarian cancer, disease progression, and survival is a subject of active investigation. A series of 144 ovarian cancers with clear cell or endometrioid histology or associated endometriosis, all classified on the basis of strict histologic criteria, was evaluated to further explore the relationship between endometriosis-associated ovarian cancer and age at presentation, FIGO stage, histology, presence of synchronous primary disease elsewhere in the mullerian tract, and survival.

Patients with endometrioid carcinomas were significantly younger (mean, 52 y) in comparison with patients with either clear cell carcinoma (mean, 55 y) or mixed tumors (mean, 59 y; P=0.002).

Clear cell carcinoma presented as low-stage disease (FIGO I) in 33% of cases compared with endometrioid carcinomas in 97% of cases and mixed carcinomas in 27% of cases. Endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas, and 45% of mixed tumors (P<0.001). Synchronous primary tumors, observed in 31% of endometrioid tumors, 5% of mixed tumors, and in 2% of clear cell tumors (P<0.001), were unlikely to be associated with endometriosis (P=0.04). Univariate analysis of the aggregate cohort demonstrated that the single best overall predictor of disease-free survival was FIGO stage at presentation (P<0.001), followed by histologic subtype (P=0.003).

Endometriosis did not have a significant relationship with disease-free survival (P=0.7). We conclude that the link between endometriosis and ovarian cancer is much stronger for clear cell carcinoma than for other histologic subtypes (P<0.001). Furthermore, when uniform histologic criteria are applied, true mixed endometrioid and clear cell carcinomas are uncommon; most endometriosis-associated mixed tumors are heterogenous mixtures of endometrioid, mucinous, and serous histology with areas of clear cell cytoplasm. Endometriosis per se does not appear to predict prognosis in clear cell and endometrioid tumors, with the possible exception of tumors with mixed histology. Until more data are collected, pathologists should classify ovarian tumors with mixed histology as a separate and potentially unique biological and prognostic group.

Pathol. 2012 - abstract (Japan) "Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms (mucinous/mixed/clear cell/borderline/ER....)

Hum Pathol. 2012 Mar 19. [Epub ahead of print]

"Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms.

Abstract

The nature of "piling up" proliferation of clear cells in müllerian mucinous/mixed borderline tumor has not been well characterized. The purpose of this study was to clarify whether or not such clear cells represent concomitant clear cell neoplasms.

First, we carefully reviewed hematoxylin and eosin slides taken from 139 ovarian tumors diagnosed as clear cell carcinoma (112 cases) and müllerian mucinous/mixed borderline tumor (27 cases) to clarify (1) the frequency of piling-up clear cells in müllerian mucinous/mixed borderline tumor and (2) the frequency of the coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor.

Second, we investigated the immunohistochemical expression of estrogen receptor, hepatocyte nuclear factor-1β, and glypican-3 in proliferating clear cells in both tumors.

We identified piling-up clear cells in 56% of müllerian mucinous/mixed borderline tumors. Such clear cells lacked the severe nuclear atypia, complex branching, and dense hyalinized cores of typical clear cell carcinoma. We did not find coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor in any tumors.

Piling-up clear cells and endocervical-like mucinous cells were positive for estrogen receptor but negative for hepatocyte nuclear factor-1β and glypican-3. Most clear cell carcinomas showed a hepatocyte nuclear factor-1β-positive/estrogen receptor-negative immunophenotype, and about half of them were glypican-3 positive.

In conclusion, piling-up clear cells in müllerian mucinous/mixed borderline tumor do not represent concomitant clear cell neoplasms because clear cell carcinoma and müllerian mucinous/mixed borderline tumor hardly ever coexist and because such clear cells in both tumors are immunophenotypically distinct.

Dr Maurie Markman: Clinical Oncology News - A Provocative Intersection: Rare cancers, “approved” anti-neoplastics and preclinical models

Clinical Oncology News - A Provocative Intersection: Rare cancers, “approved” anti-neoplastics and preclinical models

"Preclinical results describing a novel approach to the treatment of an uncommon malignant condition raise a provocative question: How, in the current increasingly rigid “guideline-based” era of cancer management, can such observations ever leave the realm of the laboratory to be examined in the clinic? And can a rational approach to this highly relevant dilemma be devised?
Primary mucinous tumors comprise a very small proportion (<5%) of morphologic subtypes found in patients with advanced epithelial ovarian cancer......."

"....One might even argue that the outcome of such individual non-investigative experiences be posted in an easily identified, well-organized, condition-specific online database (with absolutely no accompanying patient-specific identifiers), so the oncology community would be aware of any clinically beneficial effects observed if colleagues had previously attempted to employ this novel approach in an individual patient with a metastatic mucinous ovarian cancer.....

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC... - Abstract - UK PubMed Central

"The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype."

abstract: A rare case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary (Taiwan)

Abstract

Clear cell carcinomas and endometrioid carcinomas are associated with endometriosis. The association of clear cell carcinomas with mucinous lesions has only been reported infrequently, and with mucinous cystadenoma has been rarely reported.

This is the second reported case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary.

A 57-year-old woman presented with lower abdominal pain for three weeks. Ultrasonography revealed a 16 x 14 x 10 cm mass in the left ovary with solid and cystic components. Hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathological examination of the left ovary revealed the presence of clear cell carcinoma, mucinous cystadenoma, and endometriosis. Continuity between the areas of mucinous epithelium and clear cell carcinoma were noted; this may suggest that clear cell carcinoma may arise from endometriosis or mucinous cystic tumors.

abstract: A Systematic Review of Papers Examining the Use of Intraoperative Frozen Section in Predicting the Final Diagnosis of Ovarian Lesions Intl Jnl Gyn Pathology (clear cell, mucinous, borderline, invasive...)

Abstract

"This systematic review assesses the accuracy of the frozen section classification of benign and borderline lesions or invasive carcinoma when compared with the final diagnosis on paraffin section. A Pubmed database search identified 18 retrospective cohort studies, published since 2005 that satisfied the criteria, on the critical appraisal sheet of the center for evidence-based medicine, The University of Oxford.

The sensitivity, specificity, and negative and positive predictive values suggest that frozen section is more accurate at discriminating between benign lesions and invasive carcinoma than between benign and borderline or borderline lesions and invasive carcinoma and indicate a tendency to overcall benign tumors as borderline and borderline tumors as invasive malignancies.
A narrative review of individual papers and abstracts suggests that this particular difficulty is encountered when dealing with clear cell carcinoma and mucinous lesions of all sorts.
This may have greater importance in the future with the introduction of targeted chemotherapy requiring accurate typing to guide the use of genetic analysis. It would be beneficial if future researchers comparing the results of frozen section and paraffin sections presented their results in the context of preoperative assessment of the clinical and radiological findings or the intraoperative appearances of the tumor and abdominal cavity, which would allow the identification of those cases in which the frozen section allowed a refinement of the diagnoses made using these modalities."

abstract: Importance of Histologic Subtype in the Staging of Appendiceal Tumors.

Blogger's Note: common feature is mucinous cell type; understudied is familial appendiceal carcinoid

BACKGROUND:

Malignant neoplasms of the appendix have different behavior based on their histologic subtypes in anecdotal series. Current staging systems do not capture the diversity of histologic subtypes in predicting outcomes.

METHODS:

We queried all patients with appendiceal malignancies captured in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2007. Tumors were classified as colonic type adenocarcinoma, mucinous adenocarcinoma, signet ring cell type, goblet cell carcinoid, and malignant carcinoid. We compared incidence, overall survival, and disease-specific survival for these tumors on the basis of patient, tumor, and therapy characteristics. Estimates from Cox proportional hazard modeling were used to predict hazard ratios for differing histologic subtypes with similar tumor, node, metastasis system (TNM) stages.

RESULTS:

Of the 5672 patients identified, we included 5655 (99%) in our analysis. The 5-year disease-specific survival rates were 93% for malignant carcinoid, 81% for goblet cell carcinoid, 55% for colonic type adenocarcinoma, 58% for mucinous adenocarcinoma, and 27% for signet ring cell type. Predicted estimates of adjusted hazard ratios revealed an 8-fold difference between histologic subtypes for similar TNM stages.

CONCLUSIONS:

Histologic subtype is an important predictor of disease-specific survival and overall survival in patients with appendiceal neoplasms. Addition of the histologic subtype to the TNM staging is simple and may improve prognostication.

Correspondence: Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas' (includes stats on serous/endometrioid/clear cell/mucinous)

Blogger's Note: without a subscription ($$$), the following is available for viewing:

Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas':
In a study involving a large series of epithelial ovarian carcinomas (EOCs), McCaughan et al1 reported human epidermal growth factor receptor 2 (HER2) protein overexpression and amplification in all major histological subtypes, an observation consistent with the literature.2 3 Specifically, they document HER2 gene amplification in 3.0% (7/259) of serous papillary carcinomas, 2.1% (2/92) of endometrioid carcinomas, 25.0% (3/12) of mucinous carcinomas, 4.0% (1/25) of clear cell carcinomas and 11.9% (7/60) of mixed type carcinomas. Although their number of mucinous carcinomas was low (n=12), the higher prevalence of HER2 gene amplification relative to the other histological subtypes is also consistent with the literature.4 5
We had previously reported similar findings of primary ovarian mucinous carcinomas having the highest prevalence of HER2 genomic amplification and protein overexpression among the various EOC histological subtypes and had proposed that ovarian mucinous carcinomas represent a...

Emergence of CA125 Immunoreactivity in Recurrent or Metastatic Primary Ovarian Mucinous Neoplasms of the Intestinal Type : eClips Consult

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. 

Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. 

There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). 

Mucinous Tumors of the Ovary: Diagnostic Challenges at Frozen Section and Clinical Implications

Conclusions

Our study showed a 34% rate of discordance between FS and final diagnosis. Given that 5 cases (7%) were of GI origin, intraoperative assessment of the appendix should be performed in all mucinous ovarian tumors.

Highlights

► We examined 73 consecutive cases of mucinous ovarian tumors that had frozen section (FS) at the time of surgery.
► The rate of discordance between FS and final diagnosis was 34%.
► Consideration of appendiceal tumors is important as 7% of all cancers were found to be gastrointestinal in origin.

abstract: Circulating free DNA and p53 antibodies in plasma of patients with ovarian epithelial cancers (serous/mucinous)

Blogger's Note: the connection between KRAS mutations/mucinous may be due to GI (particularly colorectal cancer eg. common denominator = KRAS mutation/mucinous cell type), see also mucinous article - to be posted subsequent to this item

BACKGROUND:
This study was conducted in order to evaluate the significance of circulating free DNA (CFDNA), blood plasma p53 antibodies (p53-Ab) and mutations of KRAS gene in the prognosis of ovarian epithelial cancers.

PATIENTS AND METHODS:

A total of 126 patients were included in this study. KRAS mutations and CFDNA were detected by means of the PCR-restriction fragment length polymorphism (PCR-RFLP) and enriched by the PCR-RFLP method. Enzyme-linked immunosorbent assay was used to analyze plasma p53-Ab.

RESULTS:

KRAS mutations were detected in 27 (21.4%) of examined tumors. The frequency of KRAS mutations was especially high in mucinous cancers (P < 0.001). CFDNA and p53-Ab were frequently detected in patients with serous cancers in high grade (P < 0.001). The overall survival rate was significantly lower for patients with serous tumors and CFDNA and p53-Ab-positive than negative tumors (P = 0.022 and P < 0.001, respectively). In mucinous ovarian cancer, a worse overall survival was correlated with the KRAS mutations (P = 0.03).

CONCLUSIONS:

The results of the present study suggested that a presence of KRAS mutations in mucinous ovarian cancer and CFDNA and p53-Ab in serous tumors was correlated with the highest risk of cancer progression.

abstract: Mucinous tumor of low malignant potential ("borderline" or "atypical proliferative" tumor) of the ovary: a study of 171 cases with the asses

Abstract

Mucinous tumors of the ovary are a continuing source of controversy in the field of gynecologic pathology. We examined a series of 171 intestinal-type mucinous tumors of low malignant potential ("borderline" or "atypical proliferative" tumors) to clarify the clinical significance of intraepithelial carcinoma (IECA) and microinvasion (area ≤ 10 mm²). The diagnosis of IECA was based on the presence of marked nuclear atypia (grade 3). Stromal microinvasion was classified as low grade and high grade (with nuclear grade 3). IECA was observed in 67 of 171 cases (39.2%). Microinvasion was identified in 31 (18.1%) cases, low grade in 22 (12.9%) cases, and high grade in 9 (5.3%) cases. Follow-up status was known in 144 cases and tumor recurrence was observed in 6 patients (4.2%). The risk factors for recurrence included International Federation of Gynecology and Obstetrics stage ≥ IC (P=0.002), microinvasion (P=0.013), age less than 45 years (P=0.032), and IECA (P=0.042). The amount of IECA ≥ 10% was also associated with the risk of recurrence (P=0.007). Among tumors with microinvasion, there was no significant association between the clinicopathologic variables and recurrence. When considering tumors with stage ≥ IC, tumor recurrence was significantly associated with IECA ≥ 10% (P=0.031) and age less than 45 years (P=0.047). It is important that mucinous tumors of low malignant potential should be staged and be optimally sampled for pathologic examination to document the status of the external surface or peritoneal involvement and to identify the worst degree of epithelial proliferation. Tumor stage ≥ IC, IECA ≥ 10%, microinvasion, and age less than 45 years were the features that were associated with tumor recurrence.
The study results also support the use of nuclear grade 3 as the sole criterion of IECA.

Targeting Src in Mucinous Ovarian Carcinoma (dasatinib/oxaliplatin)

"Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach in this disease."

Search Results: 'mucinous' 'ovarian' |2011 ASCO Abstracts

Find ALL words: mucinous ovarian

Found 8 documents

abstract: Mucinous carcinomas of the ovary and colorectum: different organ, same dilemma : The Lancet Oncology

Mucinous carcinomas of the ovary and colorectum: different organ, same dilemma

Dr Linda E Kelemen ScD a d , Martin Köbel MD b c

Summary

Mucinous carcinomas are uncommon histological types that affect several organ sites. 

 

Primary mucinous carcinomas of the ovary are distinct from other ovarian carcinoma types, but they can pose a particular challenge for correct diagnosis from metastases, which most usually originate from the colorectum. 

 

Correct diagnosis is the mainstay of treatment, because standard practice states that protocols are tailored to the primary organ site. Little is known of mutational alterations in primary and metastatic mucinous carcinomas of the ovary, and few markers exist that can discriminate between them. 

 

We reviewed commonalities between ovarian and colorectal mucinous carcinomas with respect to aetiology, molecular alterations, differential diagnosis, and implications for treatment. 

 

Although primary mucinous carcinomas of the ovary and colorectum share similar mutational patterns and unfavourable outcomes at advanced stage, compared with their non-mucinous counterparts, important differences exist with respect to mucin localisation and specific molecular alterations.  

 

Technologies—eg, next-generation sequencing—could aid identification of additional driver molecular changes that will help clarify the relation between mucinous carcinomas from different organ sites. Perhaps, then, we can consider moving towards testing and adoption of therapeutic approaches tailored to molecular characteristics of mucinous carcinomas, irrespective of organ site, so patients' survival can be optimised.

abstract: Fertility-sparing surgery in young women with mucinous adenocarcinoma of the ovary.