Correlation of tumor size with other prognostic factors in uterine serous carcinoma: a large multi-institutional study.

OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p<0.0001), angiolymphatic invasion (p<0.0001), peritoneal washings (p=0.03), stage (p=0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. CONCLUSIONS: Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.

Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis.

AIMS: Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH. METHODS AND RESULTS: Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P

A candidate precursor to serous carcinoma that originates in the distal fallopian tube.

The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial BRCA1 or 2 mutations (BRCA+). Somatic p53 tumour suppressor gene mutations in these tumours suggest a pathogenesis involving DNA damage, p53 mutation, and progressive loss of cell cycle control. We recently identified foci of strong p53 immunostaining-termed 'p53 signatures'-in benign tubal mucosa from BRCA+ women. To examine the relationship between p53 signatures and TIC, we compared location (fimbria vs ampulla), cell type (ciliated vs secretory), evidence of DNA damage, and p53 mutation status between the two entities. p53 signatures were equally common in non-neoplastic tubes from BRCA+ women and controls, but more frequently present (53%) and multifocal (67%) in fallopian tubes also containing TIC. Like prior studies of TIC, p53 signatures predominated in the fimbriae (80-100%) and targeted secretory cells (HMFG2 + /p73-), with evidence of DNA damage by co-localization of gamma-H2AX. Laser-capture microdissected and polymerase chain reaction-amplified DNA revealed reproducible p53 mutations in eight of 14 fully-analysed p53 signatures and all of the 12 TICs; TICs and their associated ovarian carcinomas shared identical mutations. In one case, a contiguous p53 signature and TIC shared the same mutation. Morphological intermediates between the two, with p53 mutations and moderate proliferative activity, were also seen. This is the first report of an early and distinct alteration in non-neoplastic upper genital tract mucosa that fulfils many requirements for a precursor to pelvic serous cancer. The p53 signature and its malignant counterpart (TIC) underline the significance of the fimbria, both as a candidate site for serous carcinogenesis and as a target for future research on the early detection and prevention of this disease.

Pathologic findings in eight cases of ovarian serous borderline tumors, three with foci of serous carcinoma, that preceded death or morbidity from invasive carcinoma.

We sought to assess the frequency of previously reported adverse histopathologic findings in ovarian serous borderline tumors (SBTs) in cases that preceded a patient's death or caused serious morbidity due to invasive carcinoma. SBTs with foci of invasive carcinoma that occupied a minority of the tumor and were associated with similar outcomes were also studied for potential additional insights. Eight cases were found over a 22-year period. Ten tumors in 5 patients were purely SBT; at initial staging, 1 patient had invasive peritoneal implants; 3 had noninvasive peritoneal implants; 1 was stage I. At last follow-up 3 of the 5 patients had died of carcinoma, 1 was alive with carcinoma, and 1 had no clinical evidence of disease 4 years after a sigmoid colectomy for invasive serous carcinoma of the bowel wall. Four tumors in 3 patients had foci of invasion that were more than microinvasive; at initial staging, all 3 patients had invasive peritoneal implants, and all died of carcinoma. All 14 of the ovarian tumors in the 8 cases had surface involvement by tumor cells, and in 8 tumors in 5 cases they were confined primarily to the ovarian surface. Foci of "micropapillary serous carcinoma" accompanied more obvious areas of infiltrative carcinoma in 2 of the 4 ovarian tumors, the peritoneal implants in 1 of the cases with purely SBTs, and a recurrence in this case and 1 other case. No morphologic finding in the 10 purely SBTs was predictive of subsequent malignant behavior. We conclude that extraovarian invasive serous carcinomas, either following or concurrent with an ovarian SBT, develop from borderline foci that may originate in the ovary, but frequently are likely to have arisen independently in the peritoneum. The carcinomas may be preceded or accompanied by noninvasive-appearing micropapillary foci in the peritoneum in some cases, but micropapillary foci in the ovarian tumors are infrequent and not a necessary antecedent.

Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva.

Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas. Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear. Tissue from a recurrent aggressive angiomyxoma was investigated by cytogenetic and expression analysis for HMGIC and HMGIY. The trypsin-Giemsa-banded karyotype showed a clonal translocation between chromosomes 8 and 12 [46,XX,t(8;12)(p12;q15)]. Fluorescence in situ hybridization (FISH) analysis with whole chromosome paint probes for chromosomes 8 and 12 excluded cryptic involvement of other chromosomes. The chromosome 12 breakpoint was mapped with two-color FISH analysis using cosmid probes at the 5' and 3' termini of HMGIC. Both cosmid probes showed hybridization to the normal chromosome 12 and the der(12) chromosome, indicating that the breakpoint was 3' (telomeric) to the gene. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed HMGIC expression in the tumor, and immunohistochemistry localized HMGIC expression to the tumor's spindle cells. Like numerous benign mesenchymal tumors, this locally aggressive tumor is associated with rearrangements near or within HMGIC, but chimeric gene formation was not required for tumorigenesis. Inappropriate expression of this DNA binding protein, however, may be important in the pathobiology of this tumor. Understanding the pathogenetic mechanism may also be helpful in developing new diagnostic tools for identifying residual disease.

h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors.

Distinction of endometrial stromal neoplasms from cellular smooth muscle tumors of the uterus is sometimes difficult. Immunohistochemistry is often not helpful because muscle actins and desmin are expressed in both neoplasms. This study's goal was to determine whether h-caldesmon, a smooth muscle-specific isoform of a calcium, calmodulin, and actin binding protein, could effectively distinguish endometrial stromal tumors from uterine smooth muscle tumors. The authors analyzed immunohistochemical expression in 24 endometrial stromal neoplasms (21 sarcomas and three nodules), 29 leiomyosarcomas, 32 leiomyomas (10 "usual," 14 cellular leiomyoma, and eight "highly cellular" types), 40 myometria, and 25 endometria. h-Caldesmon was diffusely positive in all myometria, leiomyomata, and leiomyosarcomas. Of note, 16 leiomyosarcomas (55%) were positive for h-caldesmon in more than 50% of tumor cells. In five "highly cellular" leiomyomas, h-caldesmon expression was markedly decreased or absent in areas morphologically resembling endometrial stromal tumors, raising the possibility that these tumors may be mixed smooth muscle-endometrial stromal neoplasms. In contrast, h-caldesmon expression was absent in all endometria and endometrial stromal neoplasms apart from accompanying small vessels. Desmin was diffusely positive in all myometria and leiomyomata. The fraction of cells expressing desmin was greater than that of h-caldesmon in only 10% of leiomyosarcomas. Focal desmin expression was also present in eight of 25 (32%) endometria and 12 of 24 (50%) endometrial stromal neoplasms. h-Caldesmon appears to be a more sensitive and specific marker of smooth muscle differentiation in the uterus than desmin and may be a useful tool for distinguishing and classifying uterine mesenchymal tumors.

Ectopic prostatic tissue in the uterine cervix: a report of four cases and review of ectopic prostatic tissue.

We report four examples of prostatic tissue occurring in the uterine cervix of patients aged 22, 25, 31, and 77 years. Three were incidental findings in loop excisions (two patients) and cone biopsy (one patient) of the cervix for high-grade squamous dysplasia. One presented as a cervical mass, clinically suspected to represent a fibroid. The prostatic tissue consisted of ducts and acini, some of which had papillary or cribriform patterns. Squamous metaplasia was prominent in all cases. No Wolffian duct tissue was present. The glandular epithelium in all cases was positive for prostatic acid phosphatase and prostate-specific antigen. High molecular weight keratin, performed in two cases, highlighted basal cells in a manner similar to the normal prostate. These unusual cases, only one of which is documented previously, further complicate the often-challenging area of interpretation of benign glandular lesions of the cervix. The unusual phenomenon of ectopic prostate tissue in general is reviewed.

Vulvovaginal soft tissue tumours: update and review.

Differences in biological behaviour make familiarity with (and accurate diagnosis of) vulvovaginal soft tissue tumours essential. Since ancillary studies such as immunoperoxidase staining and electron microscopy may not always be helpful in their distinction, one must often rely on morphological features to distinguish between different tumour types. This is particularly pertinent with regard to the relatively site-specific stromal tumours of this region. The purpose of this review article is to reacquaint the reader with these specific types of vulvovaginal soft tissue tumour, particularly focusing upon the salient morphological features that help in their distinction, as well as to review their clinical aspects and pathogenesis. The following soft tissue lesions are described: fibroepithelial stromal polyp, cellular angiofibroma, angiomyofibroblastoma, superficial angiomyxoma and aggressive angiomyxoma. Because of continued difficulty in predicting their behaviour, a discussion of vulvar smooth muscle tumours is also included, with a particular focus upon a practical approach to their diagnosis.

Cellular pseudosarcomatous fibroepithelial stromal polyps of the lower female genital tract: an underrecognized lesion often misdiagnosed as sarcoma.

Fibroepithelial stromal polyps of the vulvovaginal region are benign lesions that, when bland or hypocellular, are readily recognized. However those that exhibit bizarre cytomorphology, atypical mitoses, or hypercellularity, raising the possibility of malignancy, continue to be underrecognized. The authors reviewed a series of fibroepithelial stromal polyps to characterize further the morphologic features that can lead to a misdiagnosis of sarcoma. A total of 33 of 65 consecutive cases of fibroepithelial stromal polyps retrieved from the authors' consultation files were remarkable for marked hypercellularity (33 of 33), marked cytologic pleomorphism (21 of 33), mitotic counts of more than 10 mitoses per 10 high-power fields (12 of 33), and the presence of atypical mitoses (14 of 33). A total of 16 of 33 lesions had three or more of these features. Important morphologic clues to the diagnosis (shared with usual polyps at this site) were lack of an identifiable lesional margin, extension of abnormal stromal tissue up to the mucosal-submucosal interface, and the frequent presence of individually scattered multinucleate stromal cells, most often located close to the surface epithelium. Immunohistochemically, seven of 12 cases were desmin positive and one of 11 cases were smooth muscle actin positive. The age range of patients was 16 to 75 years (median, 32 years), and 21 patients (64%) were premenopausal. Sites included the vagina (18 of 33), cervix (seven of 33), and vulva (eight of 33). A total of 14 of 33 patients were pregnant, three patients were taking Tamoxifen, and one patient was on oral progesterone. Eight of 33 patients had multiple lesions at the time of presentation, of whom five were pregnant. Clinical follow-up was available in 21 of 33 patients. Three of 21 patients with follow-up had local, nondestructive recurrence. Two of these patients had multiple recurrences. None of the patients followed developed metastases. Cytologic atypia has been a previously recognized feature in these lesions; however, the occurrence of marked stromal cellularity and a mitotic rate of more than 10 mitoses per 10 high-power fields have not been emphasized previously. Moreover, the combination of these features has only rarely been documented. Awareness of the spectrum of histologic features that these lesions can exhibit is crucial in their accurate recognition, thus avoiding potential overtreatment.

Lobular endocervical glandular hyperplasia, not otherwise specified: a clinicopathologic analysis of thirteen cases of a distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum.

We report 13 cases of a previously undescribed pseudoneoplastic lesion of the uterine cervix, which we have designated "lobular endocervical glandular hyperplasia, not otherwise specified." The patients' ages ranged from 37 to 71 years (mean, 45 years; median, 49 years). Three (27%) patients had a history of hormone use. Seven lesions were incidental findings in hysterectomy specimens. In the six other cases, the patient came to clinical attention because of a mucoid cervical discharge (two cases), increased vaginal discharge (two cases), abdominal discomfort (one case), or a 3.5-cm cervical mass found when being examined because of ovarian carcinoma (one case); hysterectomy was performed in each of these six cases. Microscopic examination showed a distinctly lobular proliferation of small to moderately sized rounded glands often centered around a larger central gland. The lobular proliferation was well to poorly demarcated and usually confined to the inner half of the cervical wall. Glands within the lobules were usually separated from each other by unaltered or hypercellular cervical stroma and were lined by columnar mucinous cells similar to the normal endocervix. Occasional reactive atypia of the endocervical cells and mitoses were seen, but no significant cytologic atypia was identified. Neither of the two cases stained showed cytoplasmic immunoreactivity for carcinoembryonic antigen. Follow-up of seven patients showed no evidence of recurrence of the cervical lesion, with an average length of follow-up of 3.4 years; three patients were lost to follow-up and three cases are recent. The principal consideration in the differential diagnosis was adenoma malignum (minimal deviation adenocarcinoma). The features most helpful in this distinction, in addition to the orderly lobular arrangement of the glands, were a lack of the following: irregular stromal infiltration, a desmoplastic stromal response, and focal malignant cytologic features. Lobular endocervical gland hyperplasia should be added to the list of previously described pseudoneoplastic glandular lesions of the cervix and, like them, not misinterpreted as neoplastic.

Perineural invasion in prostate needle biopsy specimens. Correlation with extraprostatic extension at resection.

The significance of perineural invasion in prostate needle biopsy specimens for predicting extraprostatic extension is controversial. We correlated the presence of perineural invasion in needle biopsy specimens from 340 men with the presence of extraprostatic extension in corresponding radical prostatectomy specimens. Perineural invasion was present in 57 biopsy specimens. The sensitivity of perineural invasion for predicting extraprostatic extension was 32%, the specificity 88%, and the positive predictive value 42%. Biopsy specimens with perineural invasion had significantly more core specimens involved with tumor and higher biopsy-determined Gleason scores than those without invasion. Biopsy specimens with perineural invasion were significantly more likely to show extraprostatic extension and Gleason scores were higher in the resection specimens than those without perineural invasion. Multivariate logistic regression analysis showed that perineural invasion remained an independent predictor of extraprostatic extension. However, in multivariate analysis, including preoperative serum prostate-specific antigen (PSA) for 173 of the patients, the only independent predictor of extraprostatic extension was PSA. While perineural invasion in biopsy specimens is a predictor of extraprostatic extension at resection that is independent of other histologic features, the positive predictive value is low and it is not an independent predictor when serum PSA is included.

Mucinous endometrial epithelial proliferations: a morphologic spectrum of changes with diverse clinical significance.

BACKGROUND: Mucinous differentiation of the endometrium can occur in a spectrum of changes ranging from benign (metaplasia) to malignant (adenocarcinomas with mucinous differentiation). Mucinous proliferations with simple architecture are generally considered benign; however, more complex growth patterns have an uncertain biologic behavior, particularly when these changes are focal and/or are encountered in biopsy or curettage material. The disparity between the degree of cytologic atypia and the neoplastic potential makes their interpretation difficult in routine practice. We categorized and prospectively studied a series of these lesions based upon their degree of architectural complexity and correlated them with follow-up curettings and hysterectomies over a period of three years. METHODS: Mucinous proliferations of the endometrium were subdivided into three categories (A, B, or C) based upon increasing degrees of architectural complexity. Type A were mucin-containing epithelial cells, present singly or in small tufts, within architecturally benign glands or involving the endometrial surface. Type B proliferations were more complex, consisting of mucin-containing epithelial cells forming small pseudoglands with rigid, punched out spaces and no supporting stroma Conspicuous cytologic atypia or architectural features such as a filiform growth pattern characterized type C alterations. One hundred two curettings and 36 hysterectomies from 52 patients were reviewed. RESULTS: Patient's ages ranged from 39 to 71 years (median, 55 yr); 41 patients (80%) were over age 50. Twenty patients (40%) were receiving hormone replacement therapy. Nineteen type A, 17 type B, and 16 type C mucinous endometrial proliferations were analyzed. Excluding those cases in which a conventional coexisting precancerous lesion was also present in the initial endometrial sample, the percentages of endometrial carcinoma following a curettage diagnosis of types A to C, respectively, were 0, 64.7%, and 100%. Carcinomas following type B alterations were all well-differentiated and all were confined to the endometrium or inner third of the myometrium. CONCLUSION: Mucinous endometrial proliferations comprise a spectrum subdivisable into biologically meaningful subsets. A high percentage of type B alterations were found to have endometrial adenocarcinoma on follow-up; however, all were well-differentiated and showed either no or minimal invasion. This finding suggests that the absence of cytologic atypia in complex mucinous lesions identifies subsets of lesions at low concurrent risk for deeply invasive cancer. The presentation of type B lesions as predominantly microglandular surface lesions without co-existing atypical hyperplasias suggests that a subset of well-differentiated adenocarcinomas arise via neoplastic alterations in surface epithelium.

Angiosarcoma of the ovary: clinicopathologic and immunohistochemical analysis of four cases with a broad morphologic spectrum.

Angiosarcoma most frequently occurs in the skin of the head and neck region of elderly persons, lymphedematous limbs, or in deep soft tissue but only rarely has been described to occur in the female genital tract. Four cases of angiosarcoma of the ovary are described herein. They occurred in patients 25 to 42 years old (median, 31 years). The most common clinical presentation was abdominal pain. All of the tumors were unilateral, hemorrhagic, and ranged from 3.5 cm to 14 cm (median, 13 cm). The histologic appearance of the tumors was varied, and often the vascular nature of the tumor was not apparent immediately. Some of the tumors had a fascicular growth pattern composed of spindle-shaped cells with ovoid nuclei and ample eosinophilic cytoplasm closely mimicking leiomyosarcoma. Other tumors resembled ovarian yolk sac tumor with a reticular growth pattern, whereas, in other areas, cystic structures lined by hobnailed hyperchromatic enlarged nuclei simulated clear cell carcinoma of the ovary. Despite these misleading morphologic findings, all cases were characterized, at least focally, by vasoformative channels or discrete cytoplasmic vacuoles, and all were immunoreactive for vascular markers. Two patients with spread of tumor outside of the ovary died 1 month and 2 years after initial diagnosis, respectively. Two patients with tumor confined to the ovary are alive without evidence of disease 3 and 14 months after diagnosis, respectively. The differential diagnosis of this unusual neoplasm is discussed, and the literature is reviewed.

Liposarcoma (atypical lipomatous tumors) of the vulva: a clinicopathologic study of six cases.

Liposarcoma, the most common soft tissue sarcoma, usually arises in the limbs, trunk, or abdomen, but very rarely in the vulva. Six cases of liposarcoma of the vulva are described here. They were characterized by their occurrence in predominantly middle-aged women (median age 52), variable size, and focally infiltrative margin. The preoperative clinical diagnosis for all patients was of a benign lesion, with a diagnosis of lipoma in two. Four of six cases had the usual histologic appearance of a well-differentiated liposarcoma/atypical lipomatous tumor with variation in adipocyte size, adipocytic nuclear atypia, and occasional lipoblasts. Two of the six cases had a very unusual histologic appearance, not previously described, with an admixture of neoplastic bland spindle and round cells along with adipocytes showing variation in size as well as numerous mainly bivacuolated lipoblasts. Liposarcomas of other types were not identified. Follow-up data were available for five of the six patients and all were treated by excision with no additional treatment. Four showed no sign of recurrence at 12, 14, 18, and 84 months. One tumor was incompletely excised, regrew over a 10-year period, was re-excised, and showed no further recurrence 31 months thereafter. Liposarcoma can occur in the vulva, is predominantly of the well-differentiated subtype, can show an unusual histologic appearance with an admixture of spindle cells and numerous lipoblasts, and seems to have a behavior similar to these tumors in other anatomic locations.

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases.

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.

Cellular angiofibroma: a benign neoplasm distinct from angiomyofibroblastoma and spindle cell lipoma.

Four cases of a distinctive soft-tissue tumor of the vulva are described. They were characterized by occurrence in middle-aged women (39-50 years), small size (< 3 cm), and a usually well-circumscribed margin. The preoperative clinical diagnosis was that of a labial or Bartholin gland cyst in three of the four cases. The microscopic appearance was remarkably consistent and was characterized by a cellular neoplasm composed of uniform, bland, spindled stromal cells, numerous thick-walled and often hyalinized vessels, and a scarce component of mature adipocytes. Mitotic activity was brisk in three cases (up to 11 mitoses per 10 high power fields). The stromal cells were positive for vimentin and negative for CD34, S-100 protein, actin, desmin, and epithelial membrane antigen, suggesting fibroblastic differentiation. Two patients with follow-up showed no evidence of recurrence. The differential diagnosis of this distinctive tumor includes aggressive angiomyxoma, angiomyofibroblastoma, spindle cell lipoma, solitary fibrous tumor, perineurioma, and leiomyoma. The designation of "cellular angiofibroma" is chosen to emphasize the two principal components of this tumor: the cellular spindle cell component and the prominent blood vessels.

Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma in a series of 16 cases.

Aggressive angiomyxoma is a distinctive soft tissue tumor associated with a high risk of local recurrence but lacks metastatic potential. This tumour occurs nearly exclusively in the soft tissues of the pelvis and perineum of adult women. The line of differentiation is not firmly established, but a fibroblastic/myofibroblastic origin has been proposed. We report 16 new cases of aggressive angiomyxoma of the pelvic soft tissue in women. In all cases bundles of cells, most often adjacent to vessels, with histological features of smooth muscle cells were identified. In 11 of 14 cases the myoid bundles were immunoreactive for desmin; they were also positive for smooth muscle actin in 10 of 11 cases. In 13 of 14 cases lesional stromal cells showed immunoreactivity for desmin. Three cases showed areas with histological features similar to those of angiomyofibroblastoma of the vulva, thus representing previously undescribed morphological overlap between these two entities. We conclude that aggressive angiomyxoma and angiomyofibroblastoma are related neoplasms in a spectrum of tumours showing myofibroblastic origin. Furthermore, the demonstration of immunoreactivity for desmin in aggressive angiomyxomas implies that this antibody is not helpful in discriminating between these two tumours, and the principal means of distinction remains histomorphological analysis.

Phenotypic and genotypic characteristics of aberrant crypt foci in human colorectal mucosa.

Aberrant crypt foci (ACF) in colorectal mucosa are proposed to be the earliest morphological lesion in the development of neoplasia, but their characteristics remain controversial. We therefore studied the epithelial phenotype and genotype of ACF from patients with familial adenomatous polyposis (FAP) and of sporadic ACF by evaluating glycoprotein markers associated with neoplasia (lectins Dolichus biflorus agglutinin and peanut agglutinin; monoclonal antibody CA 19-9 against sialyl Lewis-a blood group substance), expression of proliferating cell nuclear antigen, and ras proto-oncogene mutations. The utility of the markers was established by comparing adenomas and hyperplastic polyps. Most FAP ACF resembled adenomas and were found to differ from sporadic ACF in their high frequency of dysplasia, staining with Dolichus biflorus agglutinin, expression of sialyl Lewis-a, proliferation in the epithelium of upper crypts, and low frequency of ras gene mutations (P = .04 to < .0000001). By contrast, sporadic ACF and a subset of FAP ACF had phenotypic characteristics resembling hyperplastic polyps but usually had ras mutations, which were inversely related to dysplasia (P = .00009). Our findings suggest that "aberrant crypt focus" is a generic term analogous to "polyp" and requires further histopathologic, phenotypic, or genotypic classification into dysplastic and heteroplastic (hetero = other, plasia = form) types. Dysplastic ACF represent potential precursors to colorectal adenomas and adenocarcinomas, but heteroplastic ACF appear to be associated, rather than precursor, lesions.

Pseudobowenoid change of the vulva: a histologic variant of untreated condylata acuminatum.

Vulvar condylomata are distinguished from vulvar intraepithelial neoplasia by orderly maturation, a low mitotic index, and the absence of nuclear atypia in the lower epithelial layers. Podophyllin therapy might produce changes in condylomata mimicking vulvar intraepithelial neoplasia but can be distinguished, particularly with a recent history of podophyllin use. This report describes five patients with vulvar condylomata that morphologically resemble both podophyllin effect and vulvar intraepithelial neoplasia. The mean age was 30.5 years. All lesions exhibited superficial keratinocytes in various stages of apoptosis, with a spectrum of nuclear degenerative changes characterized by absence of the nuclear membrane and dispersed nuclear chromatin. The characteristic finding was a perichromatin halo delineated by a rim of dense cytoplasm, beyond which a second zone of uniform clearing was observed, similar to changes noted in vulvar intraepithelial neoplasia. There was an absence, however, of either nuclear atypia in the lower cell layers or apoptosis and mitotic arrest observed in vulvar intraepithelial neoplasia and podophyllin therapy. Two (50%) of four lesions tested positive for human papillomavirus nuclei acids, one by polymerase chain reaction and the other by DNA-DNA in situ hybridization. No common human papillomavirus types were found. Pseudobowenoid change might represents a distinct type of vulvar condyloma, perhaps related to an unusual human papillomavirus.