The value of tumor markers in a mixed tumor, mucinous and neuroendocrine carcinoma of the ovary

Serum CA125 is frequently used to monitor the treatment response and to detect early recurrence during the follow-up of patients who have epithelial ovarian tumors. In this report, the level of serum CA125 and urinary 5-hydroxyindole acetic acid of a patient with a carcinoid tumor which occurred in association with a mucinous adenocarcinoma of the ovary is described. The level of serum CA125 decreased despite the presence of a clinically progressive tumor. There was a rise of the 5-hydroxyindole acetic acid level 16 weeks before pelvic recurrence was detected clinically. This indicates that it was the neuroendocrine component, and not the mucinous component of the tumor, that was not responsive to the chemotherapy. The problem of using tumor markers to monitor patients with mixed tumors is discussed.     

Primary ovarian carcinoid tumor with luteinized stromal cells

Background  Primary ovarian carcinoid tumors are rare. Distinct histologic patterns have been described in the literature as insular, trabecular, mucinous and mixed types. Case report  We describe a case of 71-year-old woman diagnosed with a left ovarian tumor. Frozen section examination identified the mass as a sex-cord stromal tumor. The surgically resected tumor was diagnosed as an insular carcinoid tumor with unusual luteinized stromal cells. Histologic diagnosis complied with results acquired by immunohistochemical with positivity of tumor cells for neuroendocrine markers and positivity of luteinized stromal cells for alpha-inhibin, calretinin and Melan A. Conclusion  Ovarian carcinoid tumor can be extremely heterogeneous. The purpose of our report was to show that the ovarian carcinoid tumor can be associated with stromal luteinization, mimicking a sex-cord stromal tumor.     

An immunohistochemical study of neuroendocrine cells in gynecologic tumors

Various gynecologic tumors with argyrophilia were studied immunohistochemically for chromogranin using two antibodies, antichromogranin and antineuroendocrine. Of seven small cell carcinomas of the cervix, four were immunoreactive with antichromogranin and seven with antineuroendocrine. Argyrophil cells of six cervical adenocarcinomas were all immunoractive with both antibodies. Type I argyrophil cells of 20 endometrial carcinomas were likewise stained positively. However, of the 30 endometrial carcinomas with type II argyrophil cells, 19 showed positive immunoreactivity for chromogranin and 22 for neuroendocrine. Of the ovarian tumors tested, argyrophil cells of 11 mucinous tumors, three carcinoid tumors, and the pancreatic tissue of a malignant mixed germ cell tumor were all chromogranin- and neuroendocrine-immunoreactive. Type I argyrophil cells of five endometrioid carcinomas of the ovary were also immunoreactive with both antibodies. Of the 13 endometrioid carcinomas with type II argyrophil cells, only four showed positive immunoreactivity for chromogranin and only five for neuroendocrine. In conclusion, both antichromogranin and antineuroendocrine detect the specific neuroendocrine markers in close association with argyrophilia in gynecologic tumors, the latter being more sensitive for small cell carcinoma of the cervix, and for type II argyrophil cells in adenocarcinoma of the endometrium and endometrioid carcinoma of the ovary.     

A clinicopathologic study of ovarian tumors (author's transl)

A clinicopathologic study was undertaken on 504 ovarian tumors which were treated in Osaka University Hospital during the past 18 years period. Also, marker substances were examined with some tumors. Most of the ovarian tumors were benign and cystic; 191 dermoid cysts, 106 serous cystadenomas, and 68 mucinous cystadenomas. Among the intermediate and malignant tumor groups, common epithelial tumors were the commonest and seen in older ages. Androblastomas, a granulosa cell tumor arising in dermoid cyst, and a possible juvenile granulosa cell tumor were rarely seen. Dysgerminomas and embryonal carcinomas were fairly popular in young ages. Malignant changes of dermoid cyst were rare and in older ages; the include an insular carcinoid, a strumal carcinoid, squamous cell carcinomas, an adenocarcinoma, and a malignant fibrous histiocytoma. Ovarian tumors in pregnancy were mostly dermoid cyst and fibroma. Bilaterality was more frequent in malignant tumors (20%) than others. The serum levels of marker substances have recently been utilized for the diagnosis, treatment and follow-up studies. Immunohistology was useful for the classification of some tumors. Radical operation and chemotherapy were chosen for the treatment of malignant ovarian tumors except some low grade malignancies, but the prognoses were generally poor.     

Immunohistochemical demonstration of HNK-1-defined antigen in gynecologic tumors with argyrophilia

Gynecologic tumors with argyrophilia were tested immunohistochemically for reactivity with monoclonal antibody HNK-1, which detects normal and neoplastic cells derived from the neuroectodermal and the amine-precursor-uptake and decarboxylation (APUD) systems. The tumors included six small cell carcinomas and four adenocarcinomas of the cervix; 23 adenocarcinomas of the endometrium (13 with type I and 10 with type II argyrophil cells); and 11 mucinous tumors (three benign, three borderline, and five malignant), eight endometrioid carcinomas (four with type I and four with type II argyrophil cells), and two carcinoid tumors (one insular and one strumal) of the ovary. HNK-1 reactive cells were found in almost every category of tumor: in four small cell carcinomas and two adenocarcinomas of the cervix; 11 adenocarcinomas of the endometrium (eight with type I and three with type II argyrophil cells); and four mucinous (two benign and two borderline), two endometrioid (one with type I and one with type II argyrophil cells), and two carcinoid tumors of the ovary. These cells corresponded to at least some of the type I argyrophil cells in endometrial and ovarian endometrioid carcinomas and to similar cells in mucinous and carcinoid tumors of the ovary and small cell carcinoma and adenocarcinoma of the cervix. However, the remaining type I and similar argyrophil cells and almost all type II argyrophil cells were HNK-1 negative, and some of the nonargyrophil tumor cells were HNK-1 positive. Although the significance of such discrepancies in reactivity with HNK-1 antibody remains unknown, the present results suggest that some of the gynecologic tumors with argyrophilia are related to APUDomas.     

Primary mucinous carcinoid tumor of the ovary. A case report

A case of primary ovarian mucinous carcinoid tumor in a 36-year-old woman is described. The tumor was present in the wall of a mature teratoma and microscopically showed tubules and glands containing goblet cells interspersed among columnar to cuboidal cells with uniform round nuclei and granular cytoplasm. The cytoplasm of the tumor cells contained argyrophil granules on Grimelius stains. Immunohistochemical stains utilizing antibodies against carcinoembryonic antigen, chromogranin, and pancreatic polypeptide were positive. Although primary mucinous carcinoid tumors are generally believed to exhibit more aggressive behavior than other categories of carcinoid tumors, the patient was treated conservatively with a right salpingo-oophorectomy and remains well 3 years later, suggesting that unilateral salpingo-oophorectomy and careful follow-up are adequate therapy in a young woman when the tumor is confined to the ovary.     

A rare case of primary ovarian carcinoid

We present a rare case in an elderly Caucasian lady of primary ovarian carcinoid tumor, causing symptoms of the carcinoid syndrome and severe carcinoid heart disease. Carcinoid tumors are the commonest neuroendocrine tumors, the majority of which are found in the gastrointestinal tract and lungs. Ovarian carcinoids represent only 0.1% of all ovarian neoplasms and 1% of all carcinoid tumors. Carcinoid syndrome can present with flushing, diffuse watery diarrhea, wheezing and breathlessness and in advanced cases lead to carcinoid heart disease. This involves damage to the right heart structures and pulmonary hypertension, which can cause significant breathlessness and peripheral edema, and is associated with a worse prognosis. Diagnosis involves multi-modality radiological imaging and biochemical analysis of neuroendocrine tumor markers, and the first line treatment should always be resection of the tumor where possible. Prognosis is generally favorable, except in some cases with metastasis.     

Ovarian strumal carcinoid: immunohistochemical, ultrastructural, and clinicopathologic observations

A review of 13 ovarian strumal carcinoids in the files of the Armed Forces Institute of Pathology has established further evidence that these tumors have both endocrine and neuroendocrine differentiation. The two functional routes of differentiation occur even within individual tumor cells. Immunohistochemical reaction for thyroglobulin was positive in the strumal regions of all 12 cases tested. This positivity was also present in transitional zones where the thyroid follicles merged with nests of carcinoid cells. Electron microscopy performed in six cases showed cells with neuroendocrine granules in the thyroid follicles; these cells resemble the C-cells of the normal thyroid gland. An immunoperoxidase reaction for calcitonin, however, revealed no positivity in any of the cells corresponding to the neuroendocrine cells within the follicles or those in the carcinoid component. Variable positivity for serotonin was observed, however. It is proposed that cells within the struma that have morphologic similarities to the C-cells of the thyroid give rise to the carcinoid component. These cells appear capable of producing thyroglobulin as well as neuroendocrine granules.     

Primary ovarian mucinous carcinoid tumor: A case report and review of literature

ObjectiveOnly a few cases of primary ovarian mucinous carcinoid tumor have been documented in the literature till date. We present a case of primary ovarian mucinous carcinoid tumor, atypical type, and review the reported cases.Case reportA 33-year-old woman with a left ovarian tumor was diagnosed with primary ovarian mucinous carcinoid tumor, atypical type. She underwent left salpingo-oophorectomy and ipsilateral lymph node dissection. After 5 years, the tumor recurred on the right side, with large para-aortic lymphadenopathy that caused hydronephrosis. Complete surgical staging was performed, followed by nine cycles of weekly paclitaxel and gemcitabine. The tumor progressed after discontinuing the chemotherapy, and the patient died of disease 26 months after recurrence.ConclusionOur patient demonstrated a more aggressive clinical course compared to that reported in previous literature. Based on this experience, complete surgical staging is highly recommended after the patient accomplished her fertility plan. Ovarian carcinoid tumors are relatively chemoresistant compared with epithelial ovarian cancers. The regimen of weekly paclitaxel and gemcitabine stabilized the disease but did not reach remission of the tumor. Further studies are required to determine the appropriate chemotherapy regimen.     

Ovarian borderline mucinous tumor in a premenarchal girl: review on ovarian epithelial cancer in young girls.

Ovarian tumors constitute the most common gynecological neoplasms during childhood. Unlike in adult women, ovarian epithelial tumors are uncommon in young girls and extremely rare prior to menarche. To our knowledge this is the first report of a borderline malignant mucinous tumor of the ovary in a premenarchal girl. It was successfully treated by conservative surgery. In our review of ovarian neoplasms in girls under 20 years of age, epithelial tumors were found in 19.3%, with a malignancy rate of 15.9%. Of these malignant tumors, 39.4% were of the mucinous type and 30.3% were borderline malignant. The occurrence of such a tumor at this age underscores the possibility of malignant transformation of the ovarian epithelium even prior to menarche. Its mucinous nature confirms the predominance of the mucinous subgroup in young girls. Hypotheses on the origin of mucinous tumors are discussed.     

CD56 expression in ovarian granulosa cell tumors, and its diagnostic utility and pitfalls

OBJECTIVE: The purpose of this study is to investigate CD56 staining in ovarian granulosa cell tumor and its morphological mimics in order to determine the value of CD56 staining in a diagnostic setting. MATERIALS AND METHODS: Tissue samples taken from 82 ovarian tumors, 26 extra-ovarian tumors and 11 normal ovaries were immunohistochemically stained using monoclonal anti-CD56 antibody. Ovarian tumors comprised 32 granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 6 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 17 endometrioid adenocarcinomas and 9 poorly differentiated serous adenocarcinomas. Extra-ovarian tumors comprised 22 uterine endometrial stromal sarcomas and 4 pulmonary small cell carcinomas. Normal ovaries contained 47 ovarian follicles. RESULTS: All of the 32 granulosa cell tumors, all of the 3 Sertoli-stromal cell tumors, all of the 4 small cell carcinomas, 1 of 1 large cell neuroendocrine carcinoma, 11 of 14 fibrothecomas, 5 of 6 carcinoid tumors, 17 of 22 endometrial stromal sarcomas and 7 of 9 poorly differentiated serous adenocarcinomas were positive for CD56. No immunoreactive cells were observed in 17 endometrioid adenocarcinomas or 47 ovarian follicles. All the immunoreactive cells showed membranous staining except for fibrothecomas where vague cytoplasmic staining was seen. CONCLUSION: CD56, known as a neuroendocrine marker, is a sensitive marker of granulosa cell tumors, but since granulosa cell tumors and neuroendocrine tumors may be morphologically similar, CD56 positivity represents a significant diagnostic pitfall. CD56 is useful in distinguishing between granulosa cell tumor and normal ovarian follicles or endometrioid adenocarcinoma. Lack of membranous CD56 expression in fibrothecoma may help differentiate it from granulosa cell tumor. However, CD56 is of limited use for distinguishing between granulosa cell tumor and poorly differentiated carcinoma or endometrial stromal sarcoma. Appropriate and cautious interpretation of CD56 expression should lead to a more accurate diagnosis of granulosa cell tumor.     

Ovarian neoplasm composed of an insular carcinoid tumor and a borderline mucinous cystadenoma arising in a mature cystic teratoma: a case report

We report the case of a 57-year-old female patient with an ovarian neoplasm of insular carcinoid and mucinous cystadenoma of low malignant potential, arising in a cystic teratoma of the right ovary. Additionally, a mature teratoma of the left ovary was present. This is an extremely rare combination of primary tumors in the ovary. The possible common histogenesis of the afore-mentioned tumors is discussed.     

原发性卵巢成熟性囊性畸胎瘤合并甲状腺肿类癌一例报告

卵巢成熟性囊性畸胎瘤合并甲状腺肿类癌是一种罕见的卵巢恶性肿瘤,甲状腺肿类癌来源于生殖细胞肿瘤中的内胚窦瘤,发病率极低,仅占卵巢恶性肿瘤的0.1%。甲状腺肿类癌属于低级别神经内分泌肿瘤,恶性度低,预后良好。诊断中应先排除转移性癌,再与卵巢颗粒细胞瘤、支持细胞瘤、卵巢恶性甲状腺肿等相鉴别。治疗上主要以手术为主,但因该病罕见,尚未建立一套标准的治疗方案。近年来,对于原发性卵巢成熟性囊性畸胎瘤合并甲状腺肿类癌在临床特征、病理及免疫组织化学、治疗等方面均有新的进展,报道1例并就该病的研究进展进行探讨,为后续治疗提供参考。     

Protein studies in cystic and peritoneal fluids of ovarian tumors with special reference to CEA

The levels of total protein, Ig, AFP, beta-HCG, CEA, SC, SP1 and alpha 2-PAG were measured in cystic and peritoneal effusions obtained from 70 females with benign and malignant ovarian tumors. This study was carried out to test out parameters those are useful for tumor monitoring of ovarian cancer. Our results indicate that determining CEA in peritoneal effusions could be one of useful methods in tumor monitoring of mucinous cystadenocarcinomas in cases of known histology and praetherapeutic estimated CEA levels in cystic or peritoneal effusions. Our results demonstrate that CEA-levels greater than 100 micrograms/l are mostly found in mucinous cystadenocarcinomas and in mucinous cystadenomas, too. High cystic CEA levels support the histology aiming for demonstration of mucinous component.     

Primary carcinoid tumor of the ovary: a case report

Introduction Carcinoid tumors commonly occur in the gastrointestinal tract and lungs. However, carcinoid tumors of the ovary are rare, primary carcinoid tumors being even rarer, forming 0.3% of all carcinoid tumors. Case report We present a case of a 55-year-old woman presented with symptoms of abdominal discomfort, weakness and fatigue. Pelvic ultrasound revealed a left-sided lobulated ovarian mass, which was solid with occasional internal scattered fluid areas. No other abnormality was detected on pelvic and abdominal ultrasonography. The findings of biochemical investigations were within normal limits. The patient underwent total abdominal hysterectomy and bilateral salphingo-oophorectomy for a clinical suspicion of ovarian tumor. Gross examination revealed a large tumor completely replacing the ovary, which was predominantly solid with few cystic areas and yellowish in color. Microscopically, the tumor was composed of uniform population of polygonal cells with abundant granular cytoplasm, arranged in small acini, solid sheets, ribbons and trabecular pattern. No teratomatous component was seen either grossly or microscopically. The tumor cells showed the strong expression of Chromogranin A and synaptophysin on immunohistochemistry. On the basis of this, a diagnosis of primary ovarian carcinoid was made. Conclusion We conclude that it is important to be aware of this entity in the pathological diagnosis of ovarian tumors, even in the absence of any clinical indicator of carcinoid tumor/syndrome, as it carries a markedly better prognosis and clinical outcome in comparison with most other malignant ovarian tumors.     

Mucinous tumors of the ovary: analysis of 38 cases.

Ovarian mucinous tumors stem from ovarian surface epithelium and are divided into benign, borderline and malignant. It is difficult to differentiate borderline and malignant mucinous tumors. Thirty-eight cases of ovarian mucinous tumors which were diagnosed at the Pathology Department of Dicle University Medical Faculty were reviewed. Of these, 18 (47.3%), six (15.7%) and 14 (36.8%) were benign, borderline and malignant, respectively. The patients' ages ranged from 18 to 67 (average 44.5) years. Bilaterality was detected in 1/18 (5.5%), 0/6 and 4/14 (28.5%) of benign, borderline and malignant mucinous tumors, respectively. Mean tumor size was 26.4 cm. Microscopically, there was no stratification in the benign tumors. The borderline tumors had papillary infoldings and 2-3 layers of atypical epithelial cells but no invasion of the stroma. Malignant tumors had four or more layers of atypical epithelial cells and stromal invasion.     

Clinical characteristics and prognosis of mucinous tumors of the ovary

OBJECTIVE: Ovarian mucinous tumors consist of benign, borderline, and carcinomatous tumor, but the clinical characteristics of these 3 types have not been investigated in detail. In this study, we compared the clinical characteristics and prognosis among these 3 types of mucinous tumors. METHODS: One hundred sixty-one patients with mucinous cystadenocarcinoma and 143 patients with mucinous borderline tumor were registered between 1986 and 2003. All patients were reviewed by two pathologists, then the mixed type and cases showing other organized malignant tumors were excluded from this study. Patients with mucinous carcinoma staged Ib or more were treated postoperatively with 6 cycles of platinum-based chemotherapy. Survival probability was analyzed by the Kaplan-Meier method and differences in survival rates were calculated using log-rank test. RESULTS: Mean patient ages were 43.9, 44.7, and 49.7 years in patients with benign, borderline, carcinomatous tumor, respectively. The ratio of early stage (I, II) to advanced stage (III, IV) was significantly lower in carcinoma than in borderline tumor. The levels of tumor markers tended to increase with the level of malignancy. CA72-4 is the most useful discriminating marker according to ROC analysis. In borderline tumor, 5 patients died of disease, and all of these patients had stage III disease with residual tumor after the initial surgery. Patients with borderline tumor showed significantly better prognosis than those with carcinoma; however, there were no significant differences in prognosis between borderline tumor and carcinoma in patients with stage III tumor or residual tumor. CONCLUSIONS: In mucinous tumors, measurement of CA72-4 is recommended to distinguish malignant from benign tumors. Even in borderline tumor, patients with residual tumor showed a poorer prognosis than carcinoma, suggesting that complete resection is necessary for a good prognosis.     

Low malignant potential tumors of the ovary: a study of 76 cases

This study analyzes the clinical and pathological features of 76 patients who were diagnosed as having ovarian low malignant potential tumor over a 20-year period: 39 (51.3%) of the tumors were mucinous, 29 (38.2%) serous, three (3.9%) endometrioid, and five (6.6%) mixed. Patients with serous tumors were significantly younger (mean age 40 years) than those with mucinous tumors (mean age 50.5 years). Serous tumors were more frequently bilateral (48.3%) than mucinous tumors (12.8%). The extent of tumor (FIGO stage) at the primary laparotomy was related to the prognosis: the survival of 14 patients with stage III and six patients with stage II tumor was significantly inferior to that of the 56 patients with stage I tumors (P less than .01). Patients with stage III mucinous low malignant potential tumors and pseudomyxoma peritoneii fared badly. Four patients with stage II and 13 patients with stage III tumors had residual tumor after primary surgery. Five of these patients received no subsequent treatment of whom four are alive and well from 5.5 to 19 years after diagnosis. Three patients received pelvic radiotherapy. Eleven patients were treated with chemotherapy for residual or recurrent tumor but only one (9.1%) had an unequivocal response.     

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.