Eosinophilic Cells, Autoimplants, Degree of Cellular Proliferation, and Adenofibroma Pattern are Important Histologic Findings in Ovarian Borderline Tumors.

Ovarian borderline tumors can show histologic features, such as different degrees of cellular proliferation, eosinophilic cells, autoimplants, and adenofibromatous architecture, the importance of which is not known. The aim of the study was to describe these features and correlate them with clinical characteristics. Eighty-three ovarian borderline tumors were studied for the aforementioned features. These were correlated with clinicopathologic features. Epithelial proliferation was associated with the T stage in serous tumors (P=0.0009), but not in mucinous tumors (P=0.97). It was positively associated with bilateral tumors (P=0.01) and the presence of autoimplants (P<0.0001). It was associated with the presence of eosinophilic cells, as tumors with extensive eosinophilic cells had a mean proliferation of 80.7%, for those with no such cells it was 23.8% (P<0.0001), and for those with a limited presence of eosinophilic cells it was 48.7% (P=0.03). Cellular proliferation was not associated with the size of the tumor. An adenofibromatous architecture was associated with unilateral tumors (P=0.02) and showed a trend (P=0.08) with regard to T stage in serous tumors. It was not associated with the size of the tumor. The presence of autoimplants was marginally associated (P=0.07) with bilateral tumors and it was not associated with the size of the tumor or the T stage. The presence of eosinophilic cells was not associated with the T stage, the size of the tumor, or bilateral tumors. The degree of epithelial proliferation, autoimplants, adenofibromatous architecture, and the presence of eosinophilic cells are important features in ovarian borderline tumors.

A case of unclassified multicystic biliary tumor with biliary adenofibroma features.

A 40-year-old Japanese man was admitted to our hospital for evaluation of upper abdominal pain. Abdominal computed tomography (CT) revealed a well-circumscribed multicystic mass measuring approximately 7 × 6 cm. The mass contained a solid lesion measuring 3 × 2 cm. Biopsy of a swollen cervical lymph node led to a diagnosis of diffuse large B-cell lymphoma. After initial chemotherapy for lymphoma, the multicystic mass was surgically resected. The tumor was composed of a multicystic lesion and a solid lesion. Histopathologic examination of the multicystic lesion revealed that the locules were lined by biliary epithelium, demonstrating various degrees of cytological atypia. The stroma was fibrous, and the tumor showed marked apocrine snouts. Part of the tumor showed papillary growth with strong cytological atypia. The solid lesion showed tubulocystic proliferation of tumor cells, with prominent apocrine snouts, embedded in dense and partially hyalinized fibrous stroma. The morphology of the solid part was quite similar to that of reported biliary adenofibroma. Despite lengthy discussion, an appropriate pathological diagnosis could not be found among the current classifications of biliary tumor. The tumor was finally diagnosed as unclassified multicystic biliary tumor with adenofibroma features.

A composite renal tumor: metanephric adenofibroma, Wilms tumor, and renal cell carcinoma: a missing link?

A coexistence of different renal tumors has rarely been reported. The most commonly described association is of Wilms tumor and renal cell carcinoma. Metanephric adenofibroma has also been associated with Wilms tumor or papillary renal cell carcinoma. Another reported association is metanephric adenoma and papillary renal cell carcinoma with sarcomatoid dedifferentiation. Herein we describe a complex renal tumor containing areas of metanephric adenofibroma, Wilms tumor, and undifferentiated renal cell carcinoma in a previously healthy 18-year-old boy. The tumor showed histologic and immunohistochemical features of these 3 different tumors, offering additional support to the view that these 3 tumors are related.

Treatment with mANT2 shRNA enhances antitumor therapeutic effects induced by MUC1 DNA vaccination.

In this study, we developed a combination therapy (pcDNA3/hMUC1+mANT2 shRNA) to enhance the efficiency of MUC1 DNA vaccination by combining it with mANT2 short hairpin RNA (shRNA) treatment in immunocompetent mice. mANT2 shRNA treatment alone increased the apoptosis of BMF cells (B16F1 murine melanoma cell line coexpressing an MUC1 and Fluc gene) and rendered BMF tumor cells more susceptible to lysis by MUC1-associated CD8(+) T cells. Furthermore, combined therapy enhanced MUC1 associated T-cell immune response and antitumor effects, and resulted in a higher cure rate than either treatment alone (pcDNA3/hMUC1 or mANT2 shRNA therapy alone). Human MUC1 (hMUC1)-loaded CD11c(+) cells in the draining lymph nodes of BMF-bearing mice treated with the combined treatment were found to be most effective at generating hMUC1-associated CD8(+)IFNγ(+) T cells. Furthermore, the in vitro killing activities of hMUC1-associated cytotoxic T cells (CTLs) in the combined therapy were greater than in the respective monotherapies. Cured animals treated with the combined treatment rejected a rechallenge by BMF cells, but not a rechallenge by B16F1-Fluc cells at 14 days after treatment, and showed MUC1 antigen-associated immune responses. These results suggest that combined therapy enhances antitumor activity, and that it offers an effective antitumor strategy for treating melanoma.

Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma.

Mullerian adenosarcomas are rare mixed tumors of low malignant potential that occur mainly in the uterus and also in extrauterine locations. Microscopically, they may be difficult to distinguish from adenofibromas. In this clinicopathologic study of 55 adenosarcomas, the mean patient age was 50 years (range: 13 to 83 y). Thirty-seven tumors were of the uterine corpus, 11 of the cervix, 4 of the ovary, and 1 each of the fallopian tube, vagina, and Douglas peritoneum. Abdominal pain and vaginal bleeding were the usual complaints. Treatment was known in 50 patients: 10 had polypectomy, 1 cone biopsy, and 39 hysterectomy, which was accompanied by bilateral salpingo-oophorectomy in 24 and lymphadenectomy in 4. Five patients had radiotherapy and 2 of them had chemotherapy. Stage was known in 41 cases. Of 30 tumors of the uterine corpus, 17 were stage IA, 11 stage IB, 1 stage IC, and 1 stage IIIC. Four cervical tumors were stage IB. Three of the 4 ovarian tumors were stage IA and the other was stage IIIC. The tumor of the fallopian tube was stage IC, and the tumors of the vagina and recto-uterine pouch were confined to their site of origin. Most uterine tumors were polypoid masses ranging from 1 to 20 cm (mean: 6.5 cm). Microscopically, sarcomatous overgrowth was found in 18 cases (33%), heterologous elements in 13 (24%), and sex cordlike differentiation in 7 (13%). Fourteen of 30 uterine tumors (47%) had myometrial invasion that was minimal in 5, involved one-third of the myometrial thickness in 7, and more than 50% in 2. Of 4 cervical tumors, 2 were endocervical polyps, 1 invaded one-third of the cervical wall, and the other invaded its full thickness. Follow-up information (2 mo to 18 y; average: 7.5 y) was available in 29 patients. Six developed metastases and 5 of them died of tumor. Four had adenosarcomas with sarcomatous overgrowth; however, the other 2 patients had typical low-grade adenosarcomas of the uterine corpus and cervix, respectively, exhibiting only mild nuclear atypia of the stromal component and

Clear cell adenocarcinoma associated with clear cell adenofibromatous components: a subgroup of ovarian clear cell adenocarcinoma with distinct clinicopathologic characteristics.

We occasionally encountered clear cell adenofibromatous (CCAF) components coexisting in the ovarian clear cell adenocarcinoma (CCA). To reveal the clinicopathologic significance of CCAF components in CCA, we classified 67 cases of surgically resected CCA into CCA with and without CCAF components [CCAF(+) and (-) groups], and compared clinicopathologic parameters, that is, patient age, clinical stage, the degree of optimal cytoreduction, patient outcome, histologic grade and Ki-67 labeling index of the CCA, and the presence of endometriosis, between these 2 groups. Fourteen cases (21%) and 53 cases were classified as CCAF(+) and CCAF(-) groups, respectively. Of these 14 CCAF(+) cases, the CCAF components with atypia were observed adjacent to the CCAF components without atypia in 10, and adjacent to the obvious CCAs in 13 cases. In comparison with the CCAF(-) group, the CCAF(+) group showed a higher frequency of histologically low-grade tumors [93% (13 of 14) vs. 43% (23 of 53), P=0.0027], a lower Ki-67 labeling index (mean 35.9% vs. 44.0%, P=0.0492), and better patient prognosis (5-year survival 78.8% vs. 49.3%, P=0.0277). Endometriosis was much less frequent in the CCAF(+) group than in the CCAF(-) group [14.7% (2 of 14) vs. 67.9% (36 of 53), P=0.00096]. Multivariate analysis identified only optimal cytoreduction as independent favorable prognostic factor. These results suggest that CCAF besides endometriosis is associated with the development of CCA, and that the CCAF(+) group may be a distinct subgroup of CCA with less aggressive biologic behavior.

Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction.

BACKGROUND: Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX-CTXRT). However, the influence of CTX-CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX-CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma. METHODS: A prospectively collected database on 71 consecutive patients who underwent CTX-CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis. RESULTS: Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50-50.6)] and body mass index (BMI) of 26 kg/m(2) or above [relative risk 4.08 (95% confidence interval 1.08 to 15.4)] were significant risk factors for overall complications. CONCLUSIONS: CTX-CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.

Positive emission tomography for evaluating a complete clinical response in patients with ovarian or peritoneal carcinoma: correlation with second-look laparotomy.

OBJECTIVE: Positive emission tomography (PET) provides a novel means of imaging malignancies. The following study was undertaken to evaluate the predictive value of PET in determining a pathologic complete response in patients with advanced ovarian or peritoneal carcinoma who had a complete clinical response following primary chemotherapy. METHODS: Twenty-two patients with advanced-stage ovarian (N = 17) or peritoneal (N = 5) carcinoma who had achieved complete clinical and radiologic remission and normal CA-125 level after six cycles of chemotherapy and who had consented to a second look laparotomy procedure were studied. All patients received platinum based therapy and all but one patient, treated elsewhere, received paclitaxel in combination with platinum. Following IV administration of 20 mCi [(18)F]fluorodeoxyglucose (FDG), the entire abdomen and pelvis were scanned. Various technical modifications including bladder activity dilution, intravenous hydration with diuretic therapy, and mechanical bowel preparations, were used to reduce background activity. Second-look laparotomy findings were classified as negative, macroscopically positive if a biopsy of a suspicious area was histologically positive, or microscopically positive if only a nonsuspicious area was histologically positive. The effect of patient preparation prior to PET imaging was evaluated. RESULTS: Persistent disease was found in 13 of the 22 patients (59%). Only one of nine sites with macroscopic and none of four with microscopic disease were accurately predicted. The sensitivity was only 10% and the specificity 42%. Intravenous hydration, diuretic therapy, and bowel preparation did not improve the results. CONCLUSIONS: These results suggest that despite technical modifications the sensitivity of PET before second-look laparotomy for small-volume persistent disease is low.

[Value of fine needle aspiration cytology in the diagnosis and management of fibroadenoma of the breast].

Cytological and histopathological biopsies were obtained from 121 breast lumps clinically diagnosed as fibroadenomas. Of these 98.3 percent of the lesions were benign. The cytological diagnosis was benign in 95.1 percent of 101 (83.4% of total) cases confirmed as fibroadenomas, histopathologically, but inadequate for diagnosis in 4.9 percent. The remaining 20 lesions included one breast cancer and one primary malignant lymphoma. In this group aspiration cytology was inadequate for diagnosis in 20 percent of the cases (P < 0.05). The cytological reports cast suspicion in the two malignant cases. No lesion with benign cytology was subsequently shown to be malignant. Ninety-five (78.5%) cases of the lesions, representing 72 women under 35 years of age, which has been clinically diagnosed as fibroadenomas, showed fibroadenoma, histopathologically, in 89.5% of these cases. The other 26 (21.5%) lesions in 21 patients, who were over 35 years in age, had 61.5 percent fibroadenomas, cytological results cast suspicion of fibroadenoma in 87.1 percent of these cases. The other 16 histopathologically diagnosed fibroadenomas in patients over 35 years of age showed 62.5% were cytologically suspected of being fibroadenomas (P < 0.025). As a result of this study it is reasonable to suggest that a typical clinical fibroadenoma can be treated conservatively in women under 35 years, but only if an adequate cytological smear obtained by fine needle aspiration does not show malignant of suspicious cells.

Conservative management of breast fibroadenomas.

Is it conservative or radical management to excise all fibroadenomas of the breast, especially in women less than 30 years old? Once a definite diagnosis is established by physical examination, fine-needle aspiration cytologic testing, and mammography, is it prudent to monitor women with small fibroadenomas (less than 4 cm in diameter)? We reviewed 498 cases of biopsy-proved fibroadenomas and 17 cases of phyllodes tumors (by biopsy) seen at Los Angeles County/University of Southern California Medical Center from 1986 to 1989. Analysis of patient age and measured tumor size in 203 fibroadenomas and 10 phyllodes tumor specimens revealed similar ranges for both tumors. The mean values were 28.5 years and 2.3 cm for fibroadenomas and 44 years and 3.8 cm for phyllodes tumors. No cases of coincident carcinoma within a fibroadenoma or of metastatic malignant phyllodes tumors were present in this review. As an alternative to excising all breast tumors, cytologically diagnosed fibroadenomas can be monitored, because they have no intrinsic premalignant potential and tend to regress with time. All breast tumors that rapidly increase in size should probably be excised at any age.

Benign breast tumours in an African population.

A detailed prospective clinical study of 238 women presenting with benign breast swellings in the South Eastern equatorial rainforest of Nigeria clearly shows that 94% of lesions were due to two disorders, fibroadenomas and bacterial infections, and that they affected mostly young women in the peak of their reproductive life. Fibroadenoma which accounted for disease in no less than 69% of the women was multiple in 8%, bilateral in 11%, and was considered giant in size in 5% of the cases; by contrast, fibroadenosis was rare, accounting for swellings in only eight patients. Bacterial infections, chronic pyogenic mastitis and tuberculosis together caused breast swellings in 25% of the women studied. In tropical Africa, multiple chronic discharging sinuses suggest tuberculosis of the breast.

Fibroadenoma of the breast: a follow-up of conservative management.

This report details the outcome after clinical diagnosis of mammary fibroadenoma in 110 women aged under 35 years. After fine needle aspiration cytology, and subsequent exclusions and failures of follow-up, 92 lesions were observed for a mean of 47 weeks (range 13-90 weeks), with regular measurements until removal of persisting lesions at 12 months. Fifteen lesions disappeared and 56 had the classical histology of fibroadenoma, mean size 2.5 cm; 30 of the latter continued to grow throughout the study. Cytology is essential to exclude malignancy if conservative treatment is considered, and is helpful in identifying a benign lesion. A period longer than 12 months may be required for resolution of a fibroadenoma and removal under local anaesthesia as a day case offers a simple alternative.

Endometrioid proliferative and low malignant potential tumors of the ovary. A clinicopathologic study of 46 cases.

We evaluated 41 endometroid neoplasms with features intermediate between a benign endometrioid tumor and endometrioid carcinoma. Although these tumors showed various degrees of epithelial proliferation, they lacked the destructive stromal invasion of carcinoma. Intermediate endometrioid tumors were subdivided into proliferative endometrioid tumors (PET), endometrioid tumors of low malignant potential (ETLMP), and ETLMP with microscopic areas of invasion. PET were adenofibromas with solid aggregates of epithelial proliferation not exceeding 5 mm in any dimension, whereas ETLMP either had noninvasive cytologically malignant epithelium or aggregates of atypical epithelium measuring at least 5 mm in any dimension uninterrupted by fibromatous stroma. Of the seven PET, five were purely adenofibromatous, while two were mixtures of adenofibromatous and papillary components. Of the 31 ETLMP, 12 were adenofibromatous and 19 were either purely papillary or had mixtures of papillary and adenofibromatous components. An additional three ETLMP had one or more areas of microscopic invasion of the stroma in the form of an irregular or cribriform infiltration by atypical glands, often with squamous differentiation. These three neoplasms were designated "ETLMP with microinvasive carcinoma." The only neoplasm with extraovarian implantation at presentation, however, was an ETLMP with mixed adenofibromatous and papillary features, without microinvasion. None of the other patients with ETLMP had a metastasis or developed one within a follow-up period of between 0.8 and 11.2 years. Because they are very low-grade neoplasms, ETLMP should be separated from endometrioid carcinoma and not confused with PET, because PET have no malignant potential.

Case for conservative management of selected fibro-adenomas of the breast.

To assess the safety of a conservative approach to fibro-adenoma of the breast we prospectively studied 321 women with this clinical diagnosis, and performed aspiration cytology and excision biopsy. There was histological confirmation of fibro-adenoma in 217 (68 per cent), the remainder having various benign conditions and 4 (1.3 per cent) had carcinoma. Aspiration cytology had a sensitivity of 87 per cent and a specificity of 76 per cent for fibro-adenoma. Three cases of carcinoma were identified cytologically and the fourth was regarded as suspicious. To estimate the risk of missing carcinoma we compared the annual frequency of carcinoma with fibro-adenoma in young women and found a ratio of 1:470 between 15 and 19 years, 1:133 between 20 and 24 years and 1:9 in the 25-29 age group. To assess patients' views on non-operative treatment of benign breast masses we asked 124 women, 10 days postoperatively, whether they preferred a conservative approach for a cytologically benign lump: 26 (21 per cent) opted for conservative management in the future and 8 (7 per cent) would have preferred conservatism rather than their recent excision. A conservative approach is safe for clinically and cytologically benign breast lumps in women under 25 years, but very few will accept it.