Prophylactic oophorectomy: clinical considerations

Ovarian cancer usually remains clinically silent until it is far advanced, and is associated with significant morbidity and mortality. In view of the modest impact of adjuvant treatments on survival, much effort is devoted to early detection programs and prevention strategies. However, the usefulness of early detection programs remains to be established, with only one randomized study indicating improved median survival in screened individuals. At present, oral contraceptives and prophylactic oophorectomy are the only options for prevention of ovarian cancer. Indications for prophylactic oophorectomy either as a primary procedure, or secondary to abdominal surgery, will vary according to the estimated risk, and to the individual's perception of that risk. Genetic screening allows better identification of pre-symptomatic individuals who would benefit the most from prophylactic oophorectomy. Data concerning the benefit of prophylactic surgery, and the safety of established or innovative hormone replacement therapies in individuals at risk, are encouraging.     

Prophylactic oophorectomy in Ontario

Objective: To determine the indications, patterns of practice, and complication rates for prophylactic oophorectomy in Ontario.Methods: From hospital discharge abstracts, 82 hospitals were identified where at least one patient had a prophylactic oophorectomy since 1992. Ethics approval for the chart review was obtained from 41 hospitals (50%), was denied at 10 (12%) and is pending at 31 facilities. Using the International Classification of Disease diagnostic code for family history of ovarian cancer (V16.4) and prophylactic oophorectomy (V50.42), the medical records departments were asked to retrieve the charts. One abstractor reviewed the charts using a standard form to collect demographic information, indications for surgery, details of surgery and complications. Results: From 1992–1998, 263 women underwent PO in 41 hospitals. A BRCA1 or BRCA2 mutation was recorded in 16 cases. Thirty-six patients had a past history of breast cancer. In 127 women, a family history was the sole reason for surgery; the remaining 136 women had a coexisting gynecologic complaint. Laparotomy was used exclusively in 155 cases, laparoscopy in 79 and vaginal access in 12 cases. Seventeen women required conversion to laparotomy during the operation. The mean length of hospital stay was 3.7 days (0–14 days). Thirty-six women (14percnt) had complications.Conclusion: We have described the indications for surgery, trends in surgical practice and surgical complications for women receiving prophylactic oophorectomy in Ontario. Prior to prophylactic oophorectomy, the indications and benefits should be clear to both patient and physician. Optimally, all women should receive genetic counseling to help define risk for ovarian and breast cancer, medical and surgical options, impact of oophorectomy on cancer risk, risk of surgical complications, and the consequences and management of surgical menopause.     

Primary gastrointestinal malignant lymphomas. A morphologic and immunohistochemical study

Thirty-nine primary gastric and 22 intestinal malignant lymphomas collected from 1969 to 1980 have been studied morphologically and immunohistochemically. Eighteen of the 61 gastrointestinal lymphomas were of low-grade malignancy (9 lymphoplasmacytoid/cytic, 3 centrocytic, 6 centroblastic/centrocytic) and 43 were of high-grade malignancy (14 centroblastic, 7 lymphoblastic, 22 immunoblastic malignant lymphomas) according to the Kiel classification. The peroxidase-antiperoxidase (PAP) method was used in 53 of the 61 cases. Twenty-seven of them revealed a monoclonal positivity for intracytoplasmic IgS: kappa light chains in 18 and lambda light chains in 7 cases. Two cases represented alpha chain disease, revealing only a heavy chain positivity. The most frequent staining pattern of the lymphoma cells was that of kappa/mu. Cells with a mixed centrocytic and plasma cell configuration (centrocytoid plasma cells) proved to be positive for intracytoplasmic IgS. Lymphoma cells of all tested cases proved to be negative for all histiocytic markers. Histologically and immunohistochemically, the Greek cases of primary gastrointestinal malignant lymphomas seem to resemble "western" type lymphomas.     

Prophylactic oophorectomy in premenopausal women with stage II breast carcinoma

Prophylactic oophorectomy, as an additional treatment for stage II breast cancer, is controversial. In a retrospective study, a group of 37 premenopausal women with stage II infiltrating duct carcinoma and one to three positive axillary lymph node involvement after modified radical mastectomy and bilateral oophorectomy were compared to a matched group of 34 women treated by modified radical mastectomy only. Prophylactic oophorectomy prolonged the disease free interval significantly as compared to the control group. However, it did not prolong survival. This raises the question whether the prolongation of survival achieved by late oophorectomy in women with advanced breast cancer is preferable to an improvement in quality of life resulting from longer disease free intervals.     

Prominent plasmacytic differentiation in the recurrence of a parotid immunocytoma. A morphologic and immunohistochemical study

We report and discuss a case consisting of 2 lesions that developed at different times in the same parotid gland. Although the first lesion showed morphologic features similar to those of the benign lymphoepithelial lesion, a monotypic IgM/K pattern was also revealed by the immunoperoxidase method in its lymphoid infiltrates. Thus, on cytologic grounds, the first lesion was classified as lymphoplasmacytic immunocytoma (according to Kiel criteria). In the second lesion, which recurred 3 years later, the prominent feature was a marked predominance of plasma cells with the same monoclonal IgM/K as the preceding lymphoma. These findings suggests that a B-lymphomatous cell monoclone may undergo morphologic maturation along the lineage of its competence. Secondly, they indicate that every case of benign lymphoepithelial lesion of the salivary glands should undergo thorough immunologic evaluation to exclude the possibility of signs of precocious lymphomatous transformation.     

Relationship of ectopic ACTH production to tumor differentiation: a morphologic and immunohistochemical study of prostatic carcinoma with Cushing's syndrome

A case of Cushing's syndrome in a patient with an ACTH-producing prostatic carcinoma is presented. Initial transurethral biopsy showed a moderately well-differentiated adenocarcinoma. The development of Cushing's syndrome was associated with a change in the morphology of the tumor; repeat transurethral prostatic biopsy and autopsy showed an admixture of moderately well-differentiated adenocarcinoma and anaplastic carcinoma. Immunoperoxidase studies revealed ACTH only within the anaplastic component of the tumor, which also showed strong argyrophilia. Electron microscopic studies revealed abundant dense-core granules within the anaplastic portion of the tumor with only very scanty granules in the differentiated portion. This case strongly supports the contention that cells with APUD characteristics can differentiate within epithelial tissues of multiple embryologic origins, and that the possession of APUD features does not necessarily imply origin from any specific neuroendocrine progenitor cell.     

Prophylactic oophorectomy versus screening: psychosocial outcomes in women at increased risk of ovarian cancer

This study investigated the psychosocial outcome of prophylactic oophorectomy versus regular screening in women at increased risk of ovarian cancer. Women who had undergone prophylactic oophorectomy (n=29) were compared with women who remained on the ovarian screening programme (n=28). Assessments were made retrospectively by postal questionnaire. The surgical group showed significantly poorer functioning on two sub-scales of the Short Form (SF)-36 Health Status Questionnaire (role-emotional (p=0.04) and social functioning (p=0.01)), and there was a trend (p=0.06) for them to report more menopausal symptoms. General Health Questionnaire (GHQ) scores were significantly higher (p=0.03) in the surgical group. There were no significant differences between the groups for cancer worry or sexual functioning. Experience of the operation was better (p=0.01) and incidence of self-reported post-operative problems was lower (p=0.02) for women who had undergone the 'keyhole' rather than an 'open' procedure. Being pre-menopausal at the time of surgery predicted higher GHQ (p=0.04) and longer subjective recovery time (p=0.04). Women who have undergone prophylactic oophorectomy may have more physical and emotional symptoms than women who remain on an ovarian cancer screening programme, and may report equivalent levels of cancer worry. Those who are pre-menopausal at the time of the operation may be particularly vulnerable to psychological distress and take longer to recover post-operatively. A larger prospective study is needed to evaluate the casual versus causal role of oophorectomy in these findings, and the extent to which it allays patients' fear of cancer.     

Survival patterns after oophorectomy in premenopausal women: a population-based cohort study

BACKGROUND: A statistical model of death due to ovarian cancer, breast cancer, coronary heart disease, hip fracture, and stroke has suggested that women who undergo prophylactic bilateral oophorectomy are at increased risk of death for all causes. We aimed to investigate survival patterns in a population-based sample of women who had received an oophorectomy and compare these with women who had not received an oophorectomy. METHODS: From an existing cohort of all women who underwent unilateral or bilateral oophorectomy while residing in Olmsted County, MN, USA, in 1950-87, we analysed those who had received an oophorectomy for a non-cancer indication before the onset of menopause. Every member of the cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. 1293 women with unilateral oophorectomy, 1097 with bilateral oophorectomy, and 2390 referent women were eligible for the study. Women were followed up until death or the end of the study (staggered over 2001-06) by use of direct or proxy interviews, medical records in a records-linkage system, and death certificates. FINDINGS: Overall, mortality was not increased in women who underwent bilateral oophorectomy compared with referent women. However, mortality was significantly higher in women who had received prophylactic bilateral oophorectomy before the age of 45 years than in referent women (hazard ratio 1.67 [95% CI 1.16-2.40], p=0.006). This increased mortality was seen mainly in women who had not received oestrogen up to the age of 45 years. No increased mortality was recorded in women who underwent unilateral oophorectomy in either overall or stratified analyses. INTERPRETATION: Although prophylactic bilateral oophorectomy undertaken before age 45 years is associated with increased mortality, whether it is causal or merely a marker of underlying risk is uncertain.     

Solitary fibrous tumor: a clinico-morphological and immunohistochemical study

Solitary fibrous tumor is a rare neoplasm which may occur at any site although it is more frequent in the pleura, mediastinum and lung. The study used 4 cases of tumor localization in the pleura and orbit. Three cases presented as a "hemangiopericytic" variety of spindle cells; there were numerous giant cells in orbit tumor. Solitary fibrous tumor revealed enhanced expression of vimentin, CD34, bel-2 and CD99. Expression of S-100, desmine and non-striated muscle actin was found in few cells in some cases. Such features as large size (over 10 cm), necrosis, high cellularity, nuclear polymorphism and high mitotic index (more than 4 mitoses within 4 visual fields, at high magnification) were used as malignancy criteria:. Tumor histological pattern of "hemangiopericytic" variety could be reliably identified thanks to immunohistochemical procedure.     

Imaging, morphologic, and immunohistochemical correlation in gastrointestinal stromal tumors

BACKGROUND: Gastrointestinal stromal tumors (GISTs) recently have been distinguished morphologically, immunohistochemically, and genetically from other gastrointestinal-tract spindle cell neoplasms. The objective of this study was to correlate clinical and imaging findings with morphology and immunohistochemistry to diagnose GISTs and to differentiate them from other spindle cell lesions in the gastrointestinal tract. METHODS: The authors reviewed 9 patients who had tumors that were diagnosed as GIST by image-guided and endosonographic-guided fine-needle aspiration (FNA) with or without core biopsy (7 stomach tumors and 2 intraabdominal tumors). The male:female ratio was 3:6, and the patients ranged in age from 38 years to 80 years. Onsite evaluation, preliminary cytologic evaluation, and immunohistochemistry were provided for 6 patients. Immunostains were performed, depending on sample size, on aspirates and/or core biopsies. RESULTS: On imaging studies, most tumors were smooth and homogenous, consistent with GIST. Tumors ranged in size from 1.8 cm to 22 cm. The largest neoplasm showed solid/cystic and necrotic components. Aspirates consisted of spindle cell, neoplastic proliferation arranged in fascicles that exhibited focal, nuclear palisading; indistinct, cytoplasmic borders; and no significant atypia or mitosis. Focal epithelioid changes or cytologic atypia and mitoses were observed in 2 tumors. Immunostains revealed tumor expression of CD117 and/or CD34 in 5 of 6 tumors, expression of actin in 3 of 6 tumors, and expression of desmin in 1 of 6 tumors. All tumors were diagnosed as GIST (or consistent with GIST for tumors that lacked immunochemical analysis). Five patients underwent surgical excision, and the GIST diagnosis was confirmed in 3 patients, whereas 1 tumor proved to be neurofibroma, and another tumor was leiomyoma. No surgical follow-up was available for the remaining 4 patients, who had imaging and morphologic findings consistent with GIST. CONCLUSIONS: In the setting of consistent clinical and radiologic findings, the combined use of cytomorphology and immunohistochemistry on FNA and/or core biopsy in most instances provides a reliable pathologic diagnosis of GIST. The need of sufficient material for performing ancillary studies and the usual impossibility of excluding malignancy are limitations of FNA cytology of GIST.     

Dural invasion of meningioma: a histological and immunohistochemical study

Meningioma usually grows and expands into the brain, but invasion into the brain parenchyma is relatively rare. Meningioma arises from arachnoid cap cells, and infiltration into dura mater is the main growth pattern of meningiomas. However, little is known about the mechanism of meningioma invasion into the dura mater. In this study, seven specimens, including dural attachments, from seven cases of meningioma were used for immunohistochemical analysis. Matrix metalloproteinase (MMP)-1, -2, -9, urokinase-type plasminogen activator (uPA), vascular endothelial growth factors (VEGF), flt-1, E-cadherin, estrogen receptor (EgR), progesterone receptor (PgR), and aquaporin (AQP)-1, -4 were used as primary antibodies. There were several patterns of meningioma invasion into the dura mater: papillary-shaped invasion with destruction of dural structure, infiltration along the fibers of the dura mater, and invasion of several tumor cell units with fibroblast infiltration. Strong immunostaining was obtained with MMP-1, followed by AQP-1 and uPA, within the invading tumor cells. Neovasculature and extravasated erythrocytes, which stained with AQP-1, were also occasionally observed around the invading tumor cells. Simpson grade II removal of meningiomas results in high recurrence rates, and the inhibition of meningioma growth via dural invasion will facilitate improved remission in many cases with meningioma. In this study, MMP-1, AQP-1, and uPA are considered to have some role in the dural infiltration of meningioma cells. The fact that AQP-1 was highly expressed at the dural attachment and invading front of meningioma may indicate that dural invasion of the meningioma may be facilitated by AQP-1-induced water flow and neovascularization.     

Virus-induced pancreatic cancer in guinea fowl: a morphologic study

The morphologic lesions in the pancreas of 350 guinea fowls infected with avian osteopetrosis virus strain Pts-56 were studied. Focal unspecific changes in the acinar tissue, including reduction of zymogen content, diminution of cytoplasm, and dilatation of acinar lumens accompanied with substitution of the affected acini by tubular structures lined with centroacinar-like cells, developed 2 months from post infection (p.i.) in about 30% of the birds. Adenomatous growths of ductules with mucin-producing or mucin-nonproducing epithelium were observed independently or parallelly to these changes after 3 months p.i. Pancreatic carcinomas arose as early as 4 months p.i. The number and size of the neoplastic foci increased with time, and after the 6th month neoplastic foci were established in almost all infected guinea fowls. Neoplastic proliferations of type A and D endocrine cells were identified in the carcinoma foci of separate cases. Other associated neoplasms were bone tumors and papillomatous growths of the duodenal mucosa.     

Malignant epithelioid schwannoma: a light microscopic and immunohistochemical study

Malignant epithelioid schwannoma is a rare variant of malignant nerve sheath tumor that can be confused with both other neuroectodermal neoplasms and carcinomas. The light microscopic and immunohistochemical findings of a malignant epithelioid schwannoma arising in the mandibular region of a 27-year-old female are described. The differential diagnosis of this unusual neoplasm from malignant melanoma and poorly differentiated carcinoma is discussed.     

Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study

Worldwide, colorectal cancer is the second most common cancer and third cause of cancer death in women. Estrogen exposure has been inversely associated with colorectal cancer. Oophorectomy reduces circulating estrogen, but the effect on colorectal cancer remains uncertain. The aim of this study was to examine the association between unilateral and bilateral oophorectomy and subsequent risk of colorectal cancer, and whether this association varied by menopausal status at time of oophorectomy, use of hormone replacement therapy (HRT) at baseline, hysterectomy and baseline body mass index (BMI). The study included 25 698 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from baseline until date of colorectal cancer, death, emigration or end of follow-up at December 31, 2018, whichever came first. We examined the association between oophorectomy and colorectal cancer (all ages and stratified by menopausal status). The potential modifying effects of hysterectomy, HRT use at baseline and BMI were investigated. During 542 140 person-years of follow-up, 863 (3.4%) nurses were diagnosed with colorectal cancer. Bilateral oophorectomy was associated with a 79% increased colorectal cancer rate, adjusted rate ratio (aRR) (95% confidence interval [CI]): 1.79 (1.33-2.42). Effect estimates following unilateral oophorectomy also showed higher rate of colorectal cancer, although less pronounced and nonstatistically significant (aRR) (95% CI): 1.25 (0.86-1.82). Similar results were seen when stratifying by menopausal status. The association was not modified by baseline HRT use, hysterectomy or BMI. Oophorectomy was associated with increased rate of colorectal cancer, with highest rates among women with bilateral oophorectomy.     

Ovarian Brenner tumour: A morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium

BackgroundBrenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium.Aim and MethodsWe hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal junction which, when embedded in the ovary as Walthard cell nests, may progress to BTs. The aim of this study was to validate this hypothesis by a morphologic and immunohistochemical (IHC) analysis.ResultsThe IHC analysis revealed that fallopian tube secretory cells, transitional metaplasia, Walthard cell nests and the epithelial component of BTs shared a similar IHC profile, consistently expressing AKR1C3 (an enzyme involved in androgen biosynthesis) and androgen receptor, but not calretinin. The tumour stromal cells that immediately surrounded the epithelial nests showed strong expression of calretinin, inhibin and steroidogenic factor 1 (markers of steroidogenic cells) in the majority of BTs. Using a highly sensitive immunofluorescent staining method, we detected small groups of cilia in transitional metaplasia and Walthard cell nests, multifocal stretches of cilia and/or ciliated vacuoles in benign BTs and well-developed cilia in atypical proliferative BTs.ConclusionsOur findings suggest a tubal origin of BTs through transitional metaplasia and Walthard cell nests, based on their anatomic proximity, similar IHC profile and the presence of cilia. In addition, we hypothesise a role of androgenic stimulation in the pathogenesis of BT, based on the IHC staining pattern of calretinin, inhibin and steroidogenic factor 1 expressed in the luteinised stromal cells surrounding the epithelial nests of the tumours, and AKR1C3 and androgen receptor expressed in both the epithelial and stromal components.