abstract: Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma.

Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma

Abstract

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The κ value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting.

Biology-driven medicine: tissue matters : The Lancet Oncology

Biology-driven medicine: tissue matters : The Lancet Oncology

The Lancet Oncology, Volume 13, Issue 4, Page 319, April 2012

Next Article>

doi:10.1016/S1470-2045(12)70142-0

 "Deciding who to test, how, and when, will help realise the vast potential of personalised medicine for cancer. However, integration of biology-driven therapy into the clinic is becoming increasingly complex and intratumoral heterogeneity could prove to be the Achilles' heel of targeted therapy in an era in which tissue has become an extremely precious resource that must be used sparingly, pragmatically, and within a multidisciplinary decision-making team."

 The Lancet Oncology

 

"Cancer therapy has been revolutionised by the advent of targeted agents. As a result, patient selection through genetic testing is a rapidly growing industry, but this has posed extra challenges for the patient and oncological team including cost, legal obstacles, test accuracy, and management of tissue. In this context, a recent report in the New England Journal of Medicine suggests intra-tumoral heterogeneity might be an even more complex issue than previously thought. The report showed that up to two-thirds of genetic results in renal-cell carcinoma will vary throughout the tumour specimen when tissue is assessed in a multiregional sequencing analysis. So what are the consequences of this finding for the use of single biopsies to guide treatments in the clinic?............

" Furthermore, according to speakers at the 13th European Congress on Perspectives in Lung Cancer held in Amsterdam, Netherlands, on March 9—10, 2012, the role of the pathologist is paramount in ensuring not only that enough tissue is left after histological diagnosis to do essential tests—such as those to predict benefit from the EGFR inhibitors—but also that testing is not done until the evidence linking the target to the efficacy of the drug, and any potential future treatments, are considered. A multidisciplinary environment is therefore essential to ensure an appropriate discussion of the timing of any pathological testing, and, where possible, to enable tissue to be saved to help guide future decision-making. This point was affirmed in a recent comment in the Journal of Clinical Oncology in which the authors suggested that excluding patients without the proposed target for treatment of breast and gynaecological cancer with PI3K/mTOR inhibitors should not be done until “a stronger predictive relationship emerges”. The comment also acknowledged the challenge of testing for rare mutations. Resistance to therapy can also develop, necessitating further testing to select potential responders to subsequent therapy. Use of blood might help overcome some of the difficulties associated with tissue resources, and several studies have been done using serum samples to define predictors of response to treatment, but these investigations are fraught with difficulties, including linking any serum changes to the tumour itself...........

abstract: Primary gynaecological tumours mistaken for metastases: report of two cases with review of literature

Primary gynaecological tumours mistaken... [Eur J Gynaecol Oncol. 2012] - PubMed - NCBI

 Abstract

We describe two neoplasms of rare occurrence, one of ovarian and the other of uterine origin that were sent for consultation. Both lesions were diagnosed as metastatic carcinomas by pathologists with special interest in gynaecological pathology. The cases were referred for a second opinion because of subsequent failure to identify the primary source. We discuss the differential diagnoses, the need for generous sampling particularly in ovarian mucinous neoplasms and the value of including particular antibodies in the panel to aid the diagnostic process. Metastatic tumours mimicking primary tumours are always challenging. These two cases illustrate the need to be vigilant against the reverse scenario as well.

(open access journal) Journal of Ovarian Research - Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report (Iran)

Journal of Ovarian Research -  Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report

Case report

Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report

Journal of Ovarian Research 2012, 5:10 doi:10.1186/1757-2215-5-10
Published: 21 March 2012

Abstract (provisional)

Struma ovarii is a rare form of ovarian neoplasm in a form of mature teratoma and is composed predominantly of thyroid tissue. In the literature review, there has only been 10 cases of this tumor, associated with ascites and pleural effusion (Meig's Syndrome) and increased CA125 so far. In such cases, the tumor mimics malignant ovarian tumor. In this article, the case of a 72-year-old symptomatic woman with a pelvic mass, pleural and peritoneal effusion and high level of serum CA125  (607.4)  is presented. Cytological evaluation for the pleural fluid was performed. She underwent hysterectomy and bilateral salpingo-oophorectomy. The result of pathologic diagnosis is presented in this paper. The patient was well in postoperative period and paraclinical tests including CA 125 were normal as well.

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

open access: Ten problematical issues identified by pathology review for multidisciplinary gynaecological oncology meetings -- McCluggage 65 (4): 293 -- Journal of Clinical Pathology

Ten problematical issues identified by pathology review for multidisciplinary gynaecological oncology meetings

• Accepted 16 August 2011
• Published Online First 19 October 2011   
• J Clin Pathol 2012;65:293-301 doi:10.1136/jclinpath-2011-200352

Take-home message

Pathology review of gynaecological cancer specimens is often carried out as part of the working of gynaecological oncology multidisciplinary team meetings. Some errors are interpretational errors while others are non-interpretational but may result in the incorrect information being relayed to the clinician. Studies have identified more numerous and clinically significant diagnostic discrepancies in the field of gynaecological oncology than in other areas of pathology.

abstract: Does smoking kill? A study of death certification and smoking -- Proctor et al. 65 (2): 129 -- Journal of Clinical Pathology

Conclusion
This study demonstrates that smoking is rarely cited on death certificates, even in cases where the causal link with smoking is very strong. There are many reasons why smoking is not cited on death certificates. One frequently cited reason is the reluctance of doctors to stigmatise the deceased. Interestingly, such reluctance did not extend to citing alcohol as a COD. By not recording smoking on death certificates doctors are failing to gather important epidemiological and pathological data.

open access: Jan 2012 Archives of Pathology & Laboratory Medicine Online - The Practice of Pathology in Canada: Decreasing Pathologist Supply and Uncertain Outcomes

Abstract (and full text):  

Context.—

Pathology organizations in the United States are preparing for a new era of health care reform. Trends in the supply of pathologists in Canada's managed care system may provide some useful insights in any analysis and projection of future pathologist needs in the United States.

Objective.—In this study, population-based Canadian databases were used to devise a parameter for physician supply, cancer cases per physician. The trend in this supply parameter for pathologists was compared to that for radiation oncologists.


Results.—
The annual number of new cancer cases increased from 129 300 to 171 000 from 1999 to 2009. The absolute numbers of both pathologists and oncologists also increased in this time period. However, while the increase in the number of radiation oncologists led to an 8.2% decrease in cancer cases per radiation oncologist, the modest increase in the number of pathologists led to an increase of 17.1% in cancer cases per pathologist.

Conclusions.—

There is a trend toward a decreasing supply of Canadian pathologists relative to that of cancer demands. This finding confirms an earlier population-based study showing a decreased supply relative to population and number of clinical physicians. It is uncertain whether this decreased supply is a result of appropriate application of new, efficient methods or whether health care has been rationed or adversely impacted. Outcome measures to monitor Canadian pathology practice quality are clearly needed.

open access: Ovarian Steroid Cell Tumour: Correlation of Histopathology with Clinicopathologic Features - Jnl Pathology Research International

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%). 

Quality of pathology reports for advanced ovarian cancer: Are we missing essential information? : : An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

Conclusion

This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy.

abstract: Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-Shifting the paradigm.

Adequacy of risk-reducing gynaecologic surgery in BRCA1 or BRCA2 mutation carriers and other women at high risk of pelvic serous cancer

"...Four serous ovarian cancers and one endometrioid endometrial cancer were detected during surgery or pathological examination.
In conclusion Australasian women attending a specialist gynaecologic oncologist for RRGS (risk reducing gynaecologic surgery) are most likely to have adequate surgery and pathological examination.
Additional education of clinicians and consumers is needed to ensure optimal surgery and pathology in these women."

abstract: Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma

Abstract:

ARID1A is a recently identified tumor suppressor gene that is mutated in approximately 50% of ovarian clear cell and 30% of ovarian endometrioid carcinomas. The mutation is associated with loss of protein expression as assessed by immunohistochemistry.

In this study, we evaluated ARID1A immunoreactivity in a wide variety of carcinomas to determine the prevalence of ARID1A inactivation in carcinomas. Mutational analysis of ARID1A was carried out in selected cases. Immunoreactivity was not detected (corresponding to inactivation or mutation of ARID1A) in 36 (3.6%) of 995 tumors.

Uterine low-grade endometrioid carcinomas showed a relatively high-frequency loss of ARID1A expression, as 15 (26%) of 58 cases were negative. The other tumor that had a relatively high-frequency loss of ARID1A expression was gastric carcinoma (11%). Mutational analysis showed 10 (40%) of 25 uterine endometrioid carcinomas; none of 12 uterine serous carcinomas and none of 56 ovarian serous and mucinous carcinomas harbored somatic ARID1A mutations. All mutations in endometrioid carcinomas were nonsense or insertion/deletion mutations, and tumors with ARID1A mutations showed complete loss or clonal loss of ARID1A expression.

In conclusion, this study is the first large-scale analysis of a wide variety of carcinomas showing that uterine low-grade endometrioid carcinoma is the predominant tumor type harboring ARID1A mutations and frequent loss of ARID1A expression. These findings suggest that the molecular pathogenesis of low-grade uterine endometrioid carcinoma is similar to that of ovarian low-grade endometrioid and clear cell carcinoma, tumors that have previously been shown to have a high-frequency loss of expression and mutation of ARID1A.

full free access: PLoS ONE: Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis (Mar 15/2011)

Note: research/technical/primary focus on serous cell type

N.L. may send more cancer tests to Ontario - Nfld. & Labrador - CBC News (pathology)

"The departure of a pathologist from Newfoundland and Labrador's largest health authority last month may force the province to send breast cancer laboratory samples out of the province for assessment.

Breast cancer pathologist Dr. Nikita Makretsov resigned from the health authority, effective February 14, 2011......"cont'd

Correlation of macroscopic and microscopic pathology in risk reducing salpingo-oophorectomy: Implications for intraoperative specimen evaluation

Abstract Objective

A minority of risk-reducing salpingo-oophorectomy (RRSO) specimens from BRCA mutation carriers will contain clinically occult carcinoma that is detectable only using a specialized pathologic evaluation protocol. Although intraoperative detection of cancer may alter immediate surgical management, technical complications impairing pathologic diagnosis may result if fresh tissue dissection and frozen sections are performed on unselected RRSO specimens. We hypothesize that macroscopic specimen findings may predict which RRSO specimens contain cancer and therefore may guide selection of specimens for intraoperative pathologic evaluation. The aim of this study was to correlate the macroscopic and microscopic pathologic findings in RRSO.

 Research highlights

► Most occult carcinomas detected in RRSO specimens were not grossly visible.
► A minority of visible nodules >5 mm in the ovary or tube harbored occult carcinoma.
► No cancer was identified in any of the grossly visible cysts of the ovary or tube.

abstract: Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases (metastatic breast, GI neoplasms....)

OBJECTIVE: To present the clinicopathological features of metastatic ovarian neoplasms with emphasis in the diagnostic challenge.
METHODS: This is a retrospective study including 97 patients with pathological diagnosis of metastatic ovarian neoplasms, examined during the decade 2000-2009. The gross, microscopical and immunohistochemical characteristics as well as the clinical data (age of the patients, origin of the neoplasm, symptoms, treatment options) and 5-year survival rates were examined.
RESULTS: The mean age of the patients is 55 years (range 26-78 years). 62.89% of the tumors were metastatic from extragenital organs (from stomach 21.65%, breast 15.46%, colon 15.46%, appendix 3.09%, pancreas 2.06%, lung 1.03% and kidney 1.03%, sarcoma 1.03% melanoma 1.03%) and 37.11% tumors originated from the genital tract. The 3-year survival rates ranged from 25.39% for metastatic ovarian neoplasms originating outside the genital tract up to 29.41% for those originating from the genital tract. Tumor immunohistochemistry is a helpful aid in the differential diagnosis mainly between primary mucinous ovarian tumors and metastatic colon cancers and in the recognition of metastatic breast cancers and other neoplasms of the GI tract.
CONCLUSION: The management of metastatic ovarian neoplasms should include specific immunohistochemical methods in order to identify the primary neoplasm site. The differential diagnosis of a pelvic mass should always include metastatic neoplasms of the ovaries.

Ovarian adenosarcoma arising from benign cystadenoma and associated intraoperative consultation pitfalls

Pathologic findings following false-positive screening tests for ovarian cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening

Abstract

OBJECTIVE: In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 produced a large number of false-positive tests. We examined relationships between histopathologic diagnoses, false-positive test group, and participant and screening test characteristics.

CONCLUSIONS: False-positive ovarian cancer screening tests were associated with a range of histopathologic diagnoses, some of which may be related to patient and screening test characteristics. Further research into the predictors of false-positive ovarian cancer screening tests may aid efforts to reduce false-positive results.

Quality of pathology reports for advanced ovarian cancer: Are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial