Cervical primitive neuroectodermal tumor.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are rare and potentially aggressive malignancies. CASE: A 24-year-old woman in her eighth week of pregnancy presented with a cervical mass. Tissue biopsy demonstrated poorly differentiated carcinosarcoma with neuroendocrine features. Immunohistochemical studies confirmed the diagnosis of PNET. Treatment included alternating courses of cyclophosphamide, adriamycin, vincristine (CAV) and ifosfamide, etoposide (IE). A radical hysterectomy with bilateral ovarian transposition and periaortic lymphadenectomy was performed with postoperative chemotherapy and radiotherapy. The patient remains disease free 2 years from therapy. CONCLUSION: This is a rare case of cervical PNET occurring in a pregnant patient. A review of the literature indicates that cervical PNET is distinguishable from uterine PNET. This tumor affects younger women and may have a different histogenesis. Pregnancy should not delay diagnosis of this potentially aggressive tumor.

Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.

BACKGROUND: Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS: We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS: The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS: Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.

Brenner tumors but not transitional cell carcinomas of the ovary show urothelial differentiation: immunohistochemical staining of urothelial markers, including cytokeratins and uroplakins.

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.

Inverted follicular keratosis of the vulvar skin: a lesion that can be confused with squamous cell carcinoma.

Although seborrheic keratoses of the vulva are described in textbooks, to our knowledge, inverted follicular keratosis has not been reported. A 27-year-old woman underwent an excisional biopsy for a small lesion of the left labium majus. Squamous cell carcinoma was considered in the clinical differential diagnosis. The initial pathologic diagnosis suggested squamous cell carcinoma in situ, and the consultation diagnosis was superficially invasive squamous cell carcinoma. On pathologic examination, a symmetrical, endophytic, epithelial tumor was observed consisting of a proliferation of basaloid cells with many areas of reactive squamous cells showing numerous squamous eddies, focal reactive nuclear atypia, and occasional mitotic figures. After the pathologic diagnosis of inverted follicular keratosis was made, a history of close perineal shaving and total body tanning was obtained. Because inverted follicular keratosis is postulated to be related to follicular injury, it is likely that the trauma of close shaving is a significant etiologic factor. There is less evidence that ultraviolet ray exposure is of etiologic importance.

Cotyledonoid leiomyoma of the uterus: report of a case.

A 46-year-old woman presented with a pelvic mass. At the time of operation a large, exophytic, multinodular tumor extended into the peritoneal cavity and right broad ligament from a pedunculated attachment to the uterus in the region of the right cornu. On external examination the lesion had the appearance of cotyledonoid dissecting leiomyoma. On microscopic examination bulbous processes were composed of benign smooth muscle arranged in interlacing fascicles or swirls; there was focal hydropic degeneration. Significant nuclear atypia, mitotic activity, and coagulative tumor necrosis were not encountered. No intravascular involvement was present. There was no demonstrable parent leiomyoma or intramural dissecting component, and thus the case differed from previously reported cases of both cotyledonoid dissecting leiomyoma and intramural dissecting leiomyoma. This tumor represents another variation in the group of benign uterine smooth muscle tumors with unusual growth patterns.

Using faculty development to solve a problem of evaluation and management coding: a case study.

Compliance with billing and coding rules put forth by the Health Care Finance Administration (HCFA) is a challenge for practicing physicians, including those in academic settings. The authors, members of the academic practice at Wayne State University School of Medicine, Department of Family Medicine, designed and delivered a comprehensive curriculum as part of the practice's faculty development initiative surrounding the coding challenge. The authors defined outcomes expected on the way to achieving 100% compliance with HCFA's guidelines. Their curriculum covered topics of coding theory, chart auditing for coding, team building, effective meetings, and structured problem solving. The curriculum was delivered from January to May 1998. Chart audits of 251 charts (office notes) from before the intervention and 263 charts from after the intervention were performed to evaluate differences in coding accuracy. Errors were significantly reduced. The total error rate dropped from 50.2% to 31.1% (p < .05). Overcoding errors were reduced by one third (29.1% versus 19.7%), while undercoding errors were reduced by half (16.3% versus 8.4%). Other errors fell from 4.7% to 3%. The approach of defining and developing work teams and then using standard quality improvement tools may be an effective way to improve compliance with HCFA billing and coding rules. In addition, faculty development can be incorporated into the process of solving a problem that faces a faculty.

Sex cord-stromal tumors of the testis with entrapped germ cells: a lesion mimicking unclassified mixed germ cell sex cord-stromal tumors.

The authors describe 10 sex cord-stromal tumors of the testis that incorporated germ cells, thereby mimicking the unclassified type of mixed germ cell sex cord-stromal tumor (MGCSCST). These neoplasms occurred in patients from 3 to 48 years old (mean age, 26 years) who presented with testicular masses. On microscopic examination, nine tumors had a combination of tubular and cord-like arrangements of sex cord cells with transition to spindle-shaped tumor cells. They were diagnosed as either unclassified sex cord-stromal tumors (n = 5) or Sertoli-stromal cell tumors (n = 4). One tumor was a pure Sertoli cell tumor. The admixed germ cells were usually at the periphery and in clusters, but occasionally were in the center or more diffuse. In nine patients the germ cells resembled spermatogonia, having round nuclei with uniform, dusty chromatin and inconspicuous or small nucleoli. None of these cells stained with a variety of markers used for neoplastic germ cells, and in one case in which the non-neoplastic Sertoli cells were strongly reactive for inhibin but the neoplastic Sertoli cells were not, all the germ cells within the tumor occurred adjacent to inhibin-positive Sertoli cells. With static cytophotometry, a diploid deoxyribonucleic acid content was found in these germ cells in the two investigated cases. In one case the germ cells had the morphologic appearance of seminoma cells and they stained positively for the markers of neoplastic germ cells. This case was interpreted as a "collision" tumor between a Sertoli cell tumor and a seminoma. The authors conclude that sex cord-stromal tumors with entrapped germ cells of the testis are more common than unclassified MGCSCSTs--a bona fide testicular example of which has not been seen by any of the authors.

Trisomy 21 associated with ovarian dysgerminoma.

A 13-year-old G(0)P(0) white female with trisomy 21 presented with a complex pelvic mass. She underwent resection of the mass and complete staging for what was found to be a stage IIIC completely resected dysgerminoma. She was treated with three cycles of bleomycin, etoposide, and cisplatin chemotherapy and remains free of disease 1 year later. This association is presented as a rare case that may illustrate the relative increase in germ cell neoplasms in female patients with Down's syndrome. While the association of seminoma with Down's syndrome has been documented in a number of cases in males, the female counterpart of this tumor, dysgerminoma, in trisomy 21 has been reported quite infrequently. The potential for germ cell tumors in both male and female trisomy 21 is therefore illustrated.

Dissecting leiomyomas of the uterus other than cotyledonoid dissecting leiomyomas: a report of eight cases.

We report eight cases of benign uterine smooth muscle neoplasms with unusual growth patterns and intramural dissection. All the patients in our series were of reproductive age or perimenopausal (range, 36-51 years) and had an enlarged uterus or a pelvic mass, with the exception of one lesion that was found incidentally in a patient treated for uterine prolapse. Three also had abnormal uterine bleeding. On gross examination, the lesions had an unusual appearance and were often lobulated and irregular with indistinct margins. On microscopic examination of all the lesions in this study, a dominant benign smooth muscle tumor was associated with intramural dissection of the myometrium by fascicles of neoplastic smooth muscle. Of the eight cases showing intramural dissection, four were intramural dissecting leiomyomas; three were examples of intravenous leiomyomatosis; and one was a multinodular leiomyoma with hydropic degeneration. We excluded cotyledonoid dissecting leiomyomas from the study. In two of the three cases of intravenous leiomyomatosis, extrauterine extensions in continuity with the intramural components were noted at surgery and on gross examination. Intramural dissection of the myometrium by a benign smooth muscle tumor is one additional possibility to be considered in the differential diagnosis of leiomyosarcoma and low-grade stromal sarcoma.

Microcystic Leydig cell tumors mimicking yolk sac tumor: a report of four cases.

We report four cases of Leydig cell tumor of the testis with a microcystic pattern that mimicked yolk sac tumor. The patients ranged in age from 27 to 35 years and, except for one tumor that was discovered incidentally, presented with testicular masses. All tumors were intratesticular, and three were well circumscribed by a rim of fibrous tissue, whereas one showed minor, focal extension into the adjacent testis. The tumors typically had a vaguely lobular architecture subdivided by fibrous bands. Three of the cases had a complex microcystic appearance caused by individually vacuolated cells and coalescent cystic spaces; this pattern accounted for the majority of two tumors. Another case had focal collections of Leydig cells with prominent cytoplasmic vacuoles but lacked the coalescent spaces. The microcyst contents ranged from optically clear to eosinophilic or lightly basophilic, with the latter having the staining qualities of acid mucopolysaccharide. Three tumors had uniform, bland nuclei and low mitotic rates (<1 mitotic figure per 10 high power fields), but one had marked, random nuclear pleomorphism and an average mitotic rate of five mitotic figures per 10 high power fields. By immunohistochemistry, all were diffusely positive for vimentin; two of three were positive for inhibin, and one showed focal positivity for cytokeratin (CAM 5.2). All were negative for alpha-fetoprotein and placentalike alkaline phosphatase and, apart from having microcystic and solid areas, lacked other features typical of yolk sac tumor. Clinical follow-up ranged from 2 months to 2 years with no patient having recurrence or metastasis. The distinction of Leydig cell tumor from yolk sac tumor has important clinical implications because patients with the former usually receive only clinical follow-up, but the latter often requires chemotherapy.

Bleomycin, etoposide, and cisplatin combination therapy of ovarian granulosa cell tumors and other stromal malignancies: A Gynecologic Oncology Group study.

OBJECTIVES: The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies. METHODS: Patients with incompletely resected Stages II-IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2 x 9 weeks for a maximum dose of

Hormonal treatment of an endometrial stromal nodule followed by local excision.

BACKGROUND: Endometrial stromal nodule is a rare subtype of endometrial stromal tumor. Although such nodules are benign, hysterectomy has been considered the treatment of choice, because evaluation of the margin is required for diagnosis. The similarity between low-grade stromal sarcoma and stromal nodule suggests that stromal nodules might respond to hormonal management. CASE: Twenty-one-year-old nulligravida, diagnosed with endometrial stromal nodule, which decreased in size with leuprolide acetate treatment, underwent local excision of the tumor with preservation of reproductive function. CONCLUSION: Hormonal therapy was successful in decreasing the size of this stromal nodule which allowed for conservative management.

Interphase chromosome painting of paraffin-embedded tissue in the differential diagnosis of possible germ cell tumors.

Germ cell tumors (GCTs) are the most frequent cancer in men aged 15 to 34 years. These tumors are highly responsive to therapy with platinum-containing regimens, and 80% of cases so treated can be considered cured. Cytogenetically, 80% of GCTs have an i(12p) regardless of tumor site or histopathology, and those that are i(12p) negative have other manifestations of 12p amplification. GCTs occasionally arise extragonadally, and such cases can be especially difficult to distinguish from poorly differentiated somatic carcinomas, a situation that poses a diagnostic and treatment dilemma We developed a technique for two-color fluorescence in situ hybridization chromosome painting on nuclei released from paraffin-embedded sections. In four tumors for which GCT was a differential diagnosis, we examined the 12p and 12q chromosome arm distributions by this technique. By use of 12p and 12q painting probes developed by microdissection, 12p and 12q were distinguished and their relative distributions evaluated. In each of the four cases, 12p regions seemed to be rearranged and over-represented relative to 12q regions. In three of the cases, an apparent i(12p) could be identified. These results support a diagnosis of GCT or GCT origin in these four cases. In tumors for which specific cytogenetic abnormalities are known, chromosome painting by fluorescence in situ hybridization using paraffin-embedded tissue is a useful technique to aid in the diagnosis of tumors that are difficult to differentiate. The patients can then be placed on treatment regimens appropriate for their specific tumor type.

Pseudoinvasive, nodular extramammary Paget's disease of the vulva.

We report a case of recurrent extramammary Paget's disease of the vulva, which clinically, grossly, and microscopically mimicked an invasive lesion. A 76-year-old woman presented with recent onset of vaginal bleeding, a nodular vulvar lesion, and left inguinal lymphadenopathy. Following a vulvar biopsy and endometrial curettage, the patient underwent a total hysterectomy and bilateral salpingo-oophorectomy with lymph node dissection and a modified radical vulvectomy with left inguinal node dissection. Papillary serous adenocarcinoma was found involving the uterus and one right common iliac lymph node. Sections through the vulvar nodule revealed a marked intraepithelial proliferation, which resulted in a complex epidermal hyperplasia with deep invaginations. Tangential sections of rete pegs filled with Paget's cells and surrounded by papillary dermis displaced into the deep reticular dermis mimicked invasive nests of tumor cells. The loose fibrous tissue of the displaced papillary dermis resembled a desmoplastic reaction. No true stromal invasion was present, and none of the inguinal lymph nodes were involved by Paget's cells. The Paget's disease did not resemble the uterine carcinoma by histopathologic and immunohistochemical study. Recognition of the intraepithelial nature of Paget's disease has important clinical implications, inasmuch as stromal invasion can be associated with metastatic disease.