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Ovarian clear cell adenofibromatous tumors. Benign, of low malignant potential, and associated with invasive clear cell carcinoma.

The authors have studied 17 cases of ovarian clear cell tumors having an adenofibromatous pattern and classified them on a histologic basis into three categories: benign, of low malignant potential, and associated with invasive clear cell carcinoma. Clear cell adenofibroma is characterized by orderly tubules and glands lined by uniform epithelium with little or no nuclear atypia set in an abundant stroma with an interlacing pattern resembling ovarian stroma. Clear cell adenofibromatous tumors of low malignant potential had a similar stroma, but exhibited moderate to marked degrees of epithelial proliferation and atypia. In the third category there were cases of invasive clear cell carcinoma in which a distinct portion of the tumor met the criteria for clear cell adenofibroma, or clear cell adenofibromatous tumor of low malignant potential. Cases of invasive clear cell carcinoma exhibiting a desmoplastic reaction or a diffuse fibrous stroma, but lacking typical adenofibromatous areas, were not included in this study. The benign and low malignant potential tumors showed no clinical evidence of aggressive behavior, whereas those associated with invasive clear cell carcinoma often did. Although there have been no recurrences in our small group of patients with tumors of low malignant potential, the histologic similarity of the epithelium in these tumors to that seen in invasive carcinomas justifies such a categorization. Further studies of larger series using the proposed classification should yield more information concerning the biologic behavior of these types of clear cell adenofibromatous tumors.

Adenocarcinoma↗

Tumors of the fimbriated end of the fallopian tube: a clinicopathologic analysis of 20 cases, including nine carcinomas.

Twenty tumors that were primary in the tubal fimbriae are reported. They were found in patients aged 17 to 83 (average 57) years. All were of mullerian type. Nine tumors were benign (eight adenofibromas, one cystadenoma), of which seven were serous and two, endometrioid. Two tumors were borderline, a serous papillary cystic tumor of borderline malignancy and an endometrioid adenofibroma of borderline malignancy. Nine tumors were carcinomas, of which four were serous, three endometrioid, and two undifferentiated. Follow-up information was available for six patients with carcinoma. One with serous carcinoma was well at 1 year; a second had ascites with malignant cytologic features nine years postoperatively and is currently on chemotherapy. One patient with endometrioid carcinoma was alive without disease after 8 years, and the other died of tumor at 6.5 years. One patient with undifferentiated carcinoma was alive without disease at 5 years and the other died of disease at eight months. The occurrence of fallopian tube tumors that arise in the fimbriae has received scanty attention in the literature. A fimbrial origin for the tumors is often overlooked initially. Carcinomas confined to the fimbriae cannot be adequately staged according to the current staging system of the International Federation of Gynecology and Obstetrics. It is proposed that they be placed in a new category, Stage I(F), because the tumor cells are exposed directly to the peritoneal cavity even though they do not invade the tubal wall. Although experience is limited it appears that they may have a worse prognosis than Stage I tubal tumors that are nonfimbrial.

Adenofibroma↗

Benign adenomatous kidney neoplasms in children with polycythemia: imaging findings.

PURPOSE: To correlate pathologic, computed tomographic (CT), and ultrasound (US) characteristics of nephrogenic adenofibromas and embryonal adenomas (uncommon pediatric renal tumors) in children. MATERIALS AND METHODS: Medical records and imaging and pathologic findings were reviewed in three children (aged 6 1/2, 7, and 11 years) with adenomatous renal tumors and polycythemia. Specimens were reviewed at the National Wilms Tumor Study Pathology Center (Loma Linda, Calif). RESULTS: All tumors were smaller than 3 cm in greatest dimension. They were hyperechoic on US scans and had high attenuation on unenhanced CT scans. Two patients underwent nephrectomy for initial diagnosis of Wilms tumor. The third underwent local excision. At pathologic examination, embryonal-appearing adenomatous epithelial cells were found to form tubules and papillae with abundant psammomatous calcifications. Two masses were classified as embryonal adenomas and one as nephrogenic adenofibroma. CONCLUSION: Increased attenuation on CT scans and increased echogenicity on US scans of renal adenomatous tumors are distinctive findings that may reflect the presence of tubulopapillary structures and psammomatous calcifications.

Adenofibroma↗

Spontaneous uterine neoplasms in the fat sand rat (Psammomys obesus).

Sacrifice of 69 fat sand rats (Psammomys obesus) bred at the Hebrew University--Hadassah Medical School, yielded 19 cases with spontaneous uterine tumours. These consisted of 5 leiomyomas, 3 endometrial polyps, 10 adenofibromas and one possibly malignant mixed mesodermal tumour. The relatively high incidence of adenofibromas histologically resembling the human neoplasm, could make this animal a useful model for further study of Müllerian mixed tumours.

Adenofibroma↗

[The expression of proliferating cell nuclear antigen in breast phylloides cystosarcoma and its significance].

OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in breast phylloides cystosarcoma and its clinicopathological signification. METHODS: Immunohistochemistry (SP method) with monoclonal antibodies PC10 against PCNA was performed in 100 cases of phylloides cystosarcoma and 39 cases of adenofibroma. RESULTS: The positive rate of PCNA in phylloides cystosarcoma was 86%. The average PCNA index (PI) of phylloides cystosarcoma was significantly different among every histologic grading (F = 85.33, P < 0.01). The degree of differentiation was lower, the PI was higher. The PI was closely correlated with histologic grading (r's = 0.77). The PI in grade I phylloides cystosarcoma was higher than that in the group of adenofibroma with abundant mesenchymal cells (t = 3.42, P < 0.01). There was only a low correlation between PI and mitotic figures in phylloides cystosarcoma (r = 0.39). CONCLUSIONS: These findings suggest that the detection of PCNA has considerable practical value in reflecting the proliferation of activity of phylloides cystosarcoma, assisting the pathologists to make histologic grading; distinguishing the malignancy from benign ones (differential diagnosis) and evaluating the prognosis.

Adenofibroma↗

Proliferative endometrioid tumors and endometrioid tumors of low malignant potential of the ovary.

Endometrioid epithelial tumors occur as adenofibromas, proliferative endometrioid tumors, endometrioid tumors of low malignant potential, and endometrioid carcinoma. Criteria for each category are given. Proliferative endometrioid tumors are benign, and the low-malignant-potential ones seldom, if ever, metastasize; they should not be designated carcinomas or regarded as malignant. However, invasive carcinoma may arise in both, and both may be associated with a similar tumor outside ovary, the latter a result of either a second primary neoplasm or rupture of the primary ovarian tumor. Endometrioid tumors of low malignant potential do not need a staging procedure. Their behavior is more akin to that of Brenner and mucinous tumors of low malignant potential than to that of serous tumors of low malignant potential. Vague terms such as "malignant adenofibroma" and "borderline endometrioid tumor" have been attached to a variety of intermediate endometrioid neoplasms and should be dropped in favor of more specific designations defined by semiquantitative criteria.

Adenocarcinoma↗

Papillary and metanephric adenomas of the kidney.

Papillary renal adenomas are the commonest neoplasms of the renal tubular epithelium, occurring in up to 40% of adults. If these criteria are met, the diagnosis of adenoma can be made with confidence: (1) papillary, tubular, or tubulopapillary architecture; (2) diameter less than or equal to 5 mm; and (3) does not histologically resemble clear cell, chromophobe, or collecting duct renal cell carcinomas. They are composed of epithelial cells with variable amounts of cytoplasm with variable tinctorial qualities including clear. Metanephric adenoma and metanephric adenofibroma are closely related neoplasms that appear to be benign. Although they have a morphological resemblance to Wilms' tumor, there is some genetic evidence relating them to papillary adenoma and papillary renal cell carcinoma. Metanephric adenoma and metanephric adenofibroma occur at all ages, have a 2:1 predominance of female patients, and are associated with polycythemia. No instance of malignant behavior has been reported. The adenomatous component is composed of uniform small cells arranged in tubular or papillary architectural patterns. The fibromatous component is moderately cellular and composed of bland spindle cells.

Adenofibroma↗

Uterine adenosarcoma: a clinicopathologic study of 11 cases with a reevaluation of histologic criteria.

Eleven biphasic uterine tumors with epithelial components and homologous stroma were reevaluated. Originally these were diagnosed as adenofibroma, adenosarcoma, carcinosarcoma, or mixtures thereof, but were now reclassified as adenosarcomas of which seven were "pure" and four mixed with foci of carcinosarcoma. Nine of the tumors arose in the endometrium and two in the endocervix. The mean patient's age was 55 years. The most common complaint was vaginal bleeding. Macroscopically these tumors presented as polypoid masses. The epithelial component consisted mainly of endometrial, endocervical, ciliated, and clear cells. Squamous metaplasia and focal hyperplasia were occasionally observed. Malignant epithelial change was only present in foci of carcinosarcoma. The stroma showed prominent cellular periglandular cuffs, occasionally round solid or perivascular nodules, and areas of focal or diffuse stromal hypercellularity. In all these areas stromal cells were atypical and/or pleomorphic. Stromal foam cells were seen in three cases. Mitotic activity was low ranging from one to three mitoses per 10 high power fields (HPF). Follow-up was negative exept in two cases with recurrence and abdominal metastases. It was concluded that stromal hypercellularity with atypism and pleomorphism in periglandular, perivascular location as well as of focal or diffuse nature, is characteristic of uterine adenosarcoma. Adenofibromas present a fibro-collagenous stroma lacking the crowded cellular areas. Mitotic activity is too variable to serve as a reliable diagnostic criterion. Uterine adenosarcomas are usually tumors of low grade malignancy but the lack of correlation between histologic appearance and biologic behaviour precludes prognostication in the individual patient.

Adult↗

Metanephric stromal tumor: report of 31 cases of a distinctive pediatric renal neoplasm.

We report 31 cases of a novel pediatric renal neoplasm, metanephric stromal tumor (MST). Mean patient age was 2 years, and the most common presentation was that of an abdominal mass. Gross examination typically revealed a fibrous lesion centered in the renal medulla containing smooth-walled cysts (mean tumor size, 5.5 cm). MST is histologically identical to the stromal component of metanephric adenofibroma (MAF, previously termed nephrogenic adenofibroma) and is an unencapsulated spindle cell lesion that entraps native kidney. Characteristic histologic features of MST include alternating cellularity that imparts a nodular low-power appearance, onion-skin cuffing around entrapped renal tubules, heterologous differentiation (glia or cartilage), and vascular alterations (angiodysplasia of entrapped arterioles, juxtaglomerular cell hyperplasia in entrapped glomeruli). Three tumors in which the vascular alterations were particularly florid were associated with extrarenal vasculopathy and attendant morbidity. A majority of cases stained for CD34, although the degree of staining was variable. Most patients were treated with surgical excision alone, and none experienced recurrence or metastasis. Recognition of this entity can spare a child potentially toxic adjuvant chemotherapy that might be used for lesions in its differential diagnosis, specifically clear cell sarcoma of the kidney.

Biomarkers, Tumor↗

Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases.

Although inhibin has been shown to be a sensitive marker for ovarian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. Calretinin, a mesothelial marker, has shown promise as a marker for sex cord-stromal neoplasms. The aim of this study was to evaluate and compare calretinin and inhibin as immunohistochemical markers for sex cord-stromal and fibrous neoplasms. A total of 215 ovarian neoplasms were immunostained with commercially available antibodies to calretinin and inhibin. These tumors included 87 sex cord-stromal (39 granulosa cell, 13 Sertoli-Leydig, 4 Sertoli, 9 thecomas, 14 fibrothecomas, and 8 other stromal tumors), 37 fibrous (20 fibromas, 9 adenofibromas, and 8 fibrosarcomas), 65 epithelial, 22 germ cell, and 4 miscellaneous neoplasms. The staining was evaluated on a 0-4 scale based on percentage of neoplastic cells labeling: 0 = none; 1+ = 1-25%; 2+ = 26-50%; 3+ = 51-75%; 4+ = 76-100%. Calretinin reactivity was detected in 100% of sex cord-stromal and 90% of fibrous neoplasms, including 32 that were inhibin negative (2 granulosa cell tumors, 1 Sertoli-Leydig cell tumor, 1 thecoma, 3 fibrothecomas, 16 fibromas, 6 adenofibromas, and 3 fibrosarcomas). All four calretinin-negative fibrous neoplasms were inhibin negative. Calretinin staining was also detected in 22% of epithelial neoplasms but none of the germ cell and miscellaneous neoplasms tested. Inhibin staining was detected in 92% of sex cord-stromal neoplasms, 22% of fibrous neoplasms, 2% of epithelial neoplasms, and none of the germ cell and miscellaneous neoplasms tested. Calretinin has a 97% sensitivity and 85% specificity for sex cord-stromal and fibrous neoplasms, whereas inhibin has a 71% sensitivity and 99% specificity. This study shows that both calretinin and inhibin are useful in the diagnosis of ovarian sex cord-stromal and fibrous neoplasms. Calretinin is a more sensitive but less specific immunohistochemical marker than inhibin. Calretinin is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative. The high frequency of calretinin in fibrous neoplasms suggests that a subgroup of these neoplasms may be derived from specialized gonadal stromal cells, perhaps thecal cells.

Biomarkers, Tumor↗

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases.

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.

Adolescent↗

The stromal component of large endometrial polyps.

Benign endometrial polyps belong in the differential diagnosis of adenofibroma and adenosarcoma. There is, however, little information about the range of stromal mitotic activity, stromal cellularity, and stromal atypia in benign endometrial polyps, rendering the differential diagnosis with the aforementioned tumors problematic. In this study, the stroma of 66 polyps 1 cm or more in greatest dimension from 56 patients was analyzed for stromal mitotic activity, cellularity, and atypia. Sixteen (24%) had an almost completely fibrotic stroma that had rare mitoses, little cellularity, and no atypia. However, 50 polyps (76%) had stroma that was predominantly endometrial or was a mixture of endometrial-type stroma and fibrous stroma. In these polyps stromal mitoses were relatively common, averaging 1.2/10 MFs/HPFs (range, 0-5.8 MFs/10 HPFs). Stromal cellularity was frequently equal to or mildly increased over adjacent nonpolypoid endometrial stroma and mild nuclear atypia (enlarged stromal nuclei) was also common. Twelve polyps (24%) from the group of 50 had two or more MFs/10 HPFs, a mitotic rate present in some adenosarcomas. None of these polyps had other features necessary for the diagnosis of adenofibroma or adenosarcoma and follow-up in all patients was uneventful (average follow-up, 96 months). It is concluded that benign polyps that retain areas of endometrial-type stroma often have mitotic activity and that significant stromal mitotic activity (> or = 2 MFs/HPFs) is relatively common. These polyps do not have significant stromal atypia nor do they have a marked increase in stromal cellularity. Thus, in the absence of other supportive features, stromal mitotic activity alone should not be regarded as a worrisome finding.

Adult↗

Breast cancer--the diagnostic and therapeutic problem.

The progress made in recent years in the diagnostics of breast cancer, the universal character of mammographic and ultrasonographic screening examinations and the growth of social awareness with respect to this disease have caused a great deal of diagnostic problems. Cases of big, ulcerating cancer tumours, which infiltrate skin have now become history, and are reported sporadically. However, physicians are now facing the problem, which is the diagnosis of 1-5 mm changes detected in examinations. The necessity to diagnose small tumours in combination with 80-90% mammographic sensitivity reported compelled clinical physicists to verify these changes with histopathological examination. In the cases when the clinical examination, the result of a mammographic examination and that of fine needle aspiration biopsy do not provide a coherent picture, a surgeon has to qualify a patient for tumorectomy with an intra-operative study. In the years 1997-2000, 173 breast tumorectomies were made. Patients with benign neoplasm (e.g. adenofibroma, papilloma mammae) or patients with arousing suspicion of oncological anxiety breast tumour were qualified for surgical procedures. Operations were performed in one-day surgery conditions and intra-operative examination was performed in every case. In cases of non-palpable tumours, which were visible in ultrasonography or mammography the changes were marked by an "anchor" in order to be removed and examined histopathologically. The operated patients were 17-89 years old. In the obtained 173 tissue fragments dysplasia benign was recognized in 47.98% of cases, in 42.2% adenofibroma, in 2.31% papilloma mammae, in 1.73% mastitis chronica, in 4.62% ca ductale invasivum and in 1.16% ca ductale in situ has been observed.

Adolescent↗

Endometrial adenosarcoma with pelvic involvement following uterine perforation.

An 85-year-old woman had a 7-year history of recurrent uterine adenosarcoma. One year after curettage-related uterine perforation, she developed a pelvic mass that was attached to the uterine serosa and was histologically identical to her endometrial lesions. The pelvic neoplasm probably resulted from implantation of tumor through the myometrial tear and is the first reported example of serosal adenosarcoma following myometrial perforation. The definition of sarcomatous stroma in Müllerian adenosarcoma, and thus its separation from adenofibroma, has not been delineated. A review of the literature indicates, however, that lesions recurring after hysterectomy have greater than three mitotic figures per 10 high-power fields. Incompletely excised neoplasms, treated by dilation and curettage only, often regrow, regardless of mitotic rate. Adenosarcoma may have a deceptively bland low-power pattern and must be differentiated from adenofibroma and benign polyps.

Aged↗

[Tumoral vascular density in breast tumors and their effect on recurrence-free survival].

Angiogenesis quantitation of 106 patients with primary breast cancer and 35 patients with adenofibroma of the breast was compared and examined to its prognostic relevance for five-years disease-free survival in breast cancer patients. Immunocytochemical staining for Factor VIII-related antigen was performed to outline vascular endothelium. We found a significant higher vessel density in breast cancer patients who experienced recurrence (17.4) than in those with no recurrence (9.4) or with adenofibroma (8.7) [p < 0.0001]. The probability of five-years recurrence-free survival for patients with a primary tumor of high vessel density was at 52.3% and 86.4% for tumors of low microvessel density (p < 0.0011). Microvessel density proved to be an independent prognostic factor for breast cancer recurrence in the Cox-Model (relative risk 2.047, p = 0.0002).

Biomarkers, Tumor↗

Benign and low grade variants of mixed mesodermal tumor (adenosarcoma) of the ovary and adnexal region.

Eleven examples of a rare group of neoplasms composed of both epithelial and mesenchymal components are reported. Ten arose from the ovary and one arose separately in the para-ovarian region. The neoplasms are distinctive in that the stoma is more cellular than that of adenofibromas, but epithelial component is not malignant, as in carcinosarcoma and mixed mesodermal tumors, and the stoma is not sarcomatous in the low grade varieties. The 11 cases were highly variable in the cellularity and atypism of the stromal cells. The term, adenosarcoma, for these tumors is not acceptable because some were too low a grade to be regarded as sarcomas, and reports of the uterine counterpart disclose that some contain heterologous elements. For that reason, a term that will embrace the full spectrum of changes in the stroma--benign through sarcomatous--is needed. We propose that they be regarded as variants of mixed mesodermal tumor so that both the benign neoplasms and low grade sarcomas can be accommodated under one designation. Of the 11 cases, five lowest grade examples were all confined to the ovary and did not recur after surgical excision, but some of these were borderline in malignancy and probably would have progressed if untreated. Two of the 3 intermediate grade neoplasms extended beyond the ovary but were arrested by surgical excision. The 3 highest grade neoplasms were overly sarcomatous. One of these extended beyond the ovary but was arrested by combination chemotherapy. The para-ovarian adenosarcoma (also high grade) metastasized and proved fatal.

Adenofibroma↗

Modification of radiation carcinogenesis by marihuana.

Male, female, and ovariectomized female Sprague-Dawley rats were irradiated with 400 rads, 150 rads, or 300 rads, respectively, of 60Co gamma rays when they were between 40 and 50 days of age. The animals were injected three times weekly with either marihuana extract or with alcohol-emulphor carrier. Comparable unirradiated groups were similarly injected. Mean survival time in males was significantly shorter in the 400 rad + marihuana group compared with the three other groups whose mean survival times did not differ. Through the 546 days that the males were observed, the total number of tumors other than fibrosarcomas was significantly greater following radiation and marihuana (22) than radiation alone (6). Fifteen of the tumors were of breast or endocrine tissues. No differences were seen in the unirradiated groups. In the females, which were observed for 635 days, the total number of breast tumors was greater with the combined treatment (38) compared with radiation alone (22). This was entirely due to a marked difference in the adenocarcinoma incidence, which was 21 (radiation + marihuana) compared with four (radiation alone). The number of adenofibromas was similar in the two groups. In the unirradiated female groups the breast adenocarcinoma incidence was eight in the marihuana group and two in the control group. Ovariectomy resulted in a lower breast tumor incidence in all groups. Nonbreast tumors were more frequent in the ovariectomized-irradiated groups. Radiation plus marihuana produced more nonbreast tumors (25) than radiation alone (17) in the ovariectomized females.

Adenocarcinoma↗

Trisomy 12 is a consistent chromosomal aberration in benign ovarian tumors.

Clonal karyotypic abnormalities were detected in 7 of 42 cytogenetically analyzed benign ovarian tumors. An adenofibroma had -X and a mucinous cystadenoma had t(1;11)(q25;q23) as the sole abnormality. Trisomy 12 was found in the remaining five tumors. It was the only change in two fibromas and a serous cystadenoma; the fourth tumor, a mucinous cystadenoma, had one clone with +12 and one with +12 and +10, and the fifth tumor, a fibrothecoma, had +4,+9,+12. The finding of trisomy 12 in five of seven karyotypically aberrant tumors suggests that this aberration characterizes a hitherto unrecognized cytogenetic subgroup of benign ovarian neoplasms.

Adenofibroma↗