History of gynecological pathology. V. Dr. Walter Schiller.
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Austria↗
Biomedical subjects
L M Roth
Publications and source records attributed to L M Roth.
Unclassified sex cord-stromal tumors of the ovary: a report of eight cases.
OBJECTIVE: To evaluate the histologic features and biologic behavior of unclassified sex cord-stromal tumors. PATIENTS: The eight patients' ages at presentation ranged from 14 to 83 years. Presenting symptoms and physical findings included abdominal pain, abnormal uterine bleeding, ascites, and abdominal and pelvic masses. One patient also had bilateral sex cord tumors with annual tubules and probable Peutz-Jeghers syndrome. RESULTS: The tumors ranged from 4 to 27 cm in diameter and were described as partially encapsulated, solid, and cystic. Histologically, the tumors were composed of diffuse proliferations of sex cord cells, with cords, tubules, and follicle-like structures. The stromal cells were spindle-shaped, with scanty cytoplasm. The neoplasms were vimentin-positive and, sometimes, cytokeratin CAM 5.2- and AE1/3-positive and epithelial membrane antigen-negative. Six patients were disease-free from 2 months to 6 years after operation. One patient was lost to follow-up. The patient with probable Peutz-Jeghers syndrome had a tumor with unusual morphology and died of the neoplasm 4 years after the diagnosis. Three of 32 other cases with clinical follow-up mentioned in the pathology literature have been associated with a malignant behavior. CONCLUSION: The biologic behavior of unclassified sex cord-stromal tumors resembles that of Sertoli-Leydig cell tumors of intermediate differentiation rather than poorly differentiated tumors, which might have been expected in view of the lack of specific differentiation. This finding is important with regard to postoperative management.
Adolescent↗
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.
Aged↗
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.
Adult↗
Complete hydatidiform mole coexisting with a twin live fetus: clinical course.
A 33-year-old G4P0 white female presented for a pregnancy ultrasound at 9 weeks gestation and was found to have a complete hydatidiform mole coexisting with a live twin fetus (CHTF). The beta-hCG level was 600,000 mIU/ml and the chest X ray was negative. The pregnancy was uneventfully terminated by suction curettage and oral contraceptives were prescribed. The initial beta-hCG declined appropriately; however, it subsequently rose. The metastatic workup was negative and the patient was treated with weekly intramuscular methotrexate at 30 mg/m2. The hCG levels declined appropriately and then plateaued. Salvage chemotherapy with intravenous actinomycin D at 1.25 mg/m2 every 14 days was started. The hCG level normalized after 3 cycles and the patient was free of disease at 1 year follow-up.
Adult↗
Inhibin immunohistochemistry applied to ovarian neoplasms: a novel, effective, diagnostic tool.
Immunohistochemistry using monoclonal antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit follicle-stimulating hormone (FSH), has been recently applied to diagnostic anatomic pathology. This investigation hypothesizes that inhibin immunohistochemistry will aid in the crucial clinical distinction between sex cord-stromal and other primary ovarian neoplasms. Available H&E slides and clinical information from a retrospective surgical series of 186 primary ovarian tumors were reviewed to verify diagnoses, and representative paraffin sections were immunostained with anti-inhibin (R1 monoclonal, Serotec, Kidlington, Oxford, UK). Immunoreactivity was graded as weak/strong (W/S), and the proportion of strong staining cells was coded as follows: S1 = <10%, S2 = 10%-50%, S3 = >50%, respectively. Inhibin immunoreactivity for 137 sex cord-stromal lesions was as follows: 100% of 66 granulosa cell tumors: 80% S3, 20% S2; 100% of 17 Sertoli-stromal tumors: 90% S3, 10% S2; 100% of 13 hyperplastic follicular/stromal lesions: 90% S3, 10% S2; 100% of six steroid cell tumors: 100% S3; 90% of 18 thecomas: 40% S3, 10% S2, 10% S1, 30% W; 0% of 12 fibromas, three myxomas, and two sclerosing stromal tumors. None (0 of 49) of the other ovarian neoplasms exhibited inhibin: 22 carcinomas, 12 carcinosarcomas, seven small cell carcinomas, six germ cell tumors, and two lymphomas. In the typical case, the distinction between sex cord-stromal and other ovarian neoplasms requires nothing more than routine pathological examination. In diagnostically challenging cases, our data indicate that inhibin immunohistochemistry is a very useful adjunct because granulosa and sertoli-stromal tumors are positive whereas other potential mimickers have been negative thus far.
Adolescent↗
Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.
We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.
Adolescent↗
History of gynecological pathology. II. Dr. William H. Sternberg.
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Aged↗
Gynandroblastoma with elements resembling juvenile granulosa cell tumor.
Gynandroblastoma is an extremely rare sex cord-stromal tumor that exhibits significant ovarian and testicular differentiation. In most previously reported tumors, adult granulosa cell tumor has formed the ovarian-type component and Sertoli or Sertoli-Leydig cell tumor (SLCT) has formed the testicular-type component. In contrast, the ovarian-type element in the case reported here resembled juvenile granulosa cell tumor (JGCT). The testicular-type elements accounted for 20% of the tumor and resembled intermediate-grade SLCT. The Sertoli cells had strong cytoplasmic staining for cytokeratin CAM 5.2 and positive nuclear staining with estrogen and progesterone receptor, whereas the JGCT-like areas were negative for these antibodies. Ultrastructurally, the JGCT-like areas consisted of groups of cells that were invested by a basal lamina and had low nuclear-cytoplasmic ratios, cytoplasmic lipid droplets, and simple junctional complexes. The Sertoli cells in the SLCT-like areas had long, tight junctions and well-formed desmosomes. Gynandroblastoma usually presents clinically as an abdominal mass, often associated with either virilizing or feminizing manifestations. The prognosis is favorable and similar to that of the individual tumor components, but clinical follow-up in the small number of cases has been limited.
Adolescent↗
Transformation in recurrent ovarian granulosa cell tumors: Ki67 (MIB-1) and p53 immunohistochemistry demonstrates a possible molecular basis for the poor histopathologic prediction of clinical behavior.
Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers only a few clues. Grading, in particular, is largely ineffective. Ki67 (MIB-1) and p53 monoclonal antibodies (active on paraffin embedded tissues) provide insight into nuclear proliferation and control, respectively. In this study, the authors hypothesized that these molecular markers will help predict the clinical behavior of GCTs. Paraffin sections from 68 GCTs (arising in 56 patients: 53 primary and 15 recurrent) including 34 typical and 27 diffuse adult, and seven juvenile types were immunostained for Ki67 (MIB-1 clone; Immunotech, Westbrook, ME) and p53 (DO7 clone; Novacastra Laboratories, UK). The Ki67 proliferation index (Ki67PI = percentage immunoreactive on a count of at least 400 nuclei) ranges from 1 to 50% (mean, = 12.2%; median, 9.3%). Nineteen percent of GCTs exhibited focal p53 immunoreactivity; the number of GCTs and proportion of nuclei decorated were as follows: four, <1%; seven, 1% to 10%; and one, 20%. Ki67PI was higher in recurrent tumors (P<.001) and correlated with mitotic rate (r = .75; P<.0001). p53 staining was associated with juvenile type GCTs (P<.001) and higher Ki67PI (P<.005). Other histopathologic features exhibited no association with p53 staining or Ki67PI. Follow-up was available for 54 of 56 patients: 18 suffered recurrences after 16 to 229 months (mean, 72.1 months; median 59 months), and 36 were disease free 16 to 369 months (mean, 78.2 months; median, 70 months) after diagnosis. Curiously, high Ki67PI and mitotic rates of primary GCT correlated weakly with a disease-free course (P=.03 and .07 respectively). Disease recurrence was associated with stage >I (P<.0005), vessel invasion in the capsule (P<.001), ruptured tumors (P<.005), and older patients (P<.02). p53 staining and size or subtype of GCT exhibited no prognostic value. For 12 patients, paired primary and first recurrence of GCT showed a striking increase in Ki67PI (P<.00005) and mitotic activity (P<.02) in the recurrence. p53 expression also appeared (de novo) in two recurrent GCTs. The interpretation of focal p53 staining (>10% nuclei decorated in only one GCT) is controversial. Some investigators suggest that this represents overexpression of wild type p53 rather than p53 gene mutation. Primary GCTs exhibit a wide spectrum of proliferative activity, and the seven juvenile GCTs (the most proliferative type) demonstrated no recurrences in this study. Recurrent GCTs displayed a transformation of molecular markers to increased proliferative activity and overexpression of p53, fundamentally, by these markers, a different GCT than the primary one. These findings suggest a molecular basis for the lack of histopathologic predictors for recurrence. Factors other than proliferation of the primary GCT (which relates most closely to grading) either extrinsic to the neoplasm (host dependent) or as yet undetectable must determine malignant behavior.
Adolescent↗
DNA ploidy, cell cycle kinetics, and low versus high grade atypia in endometrial hyperplasia.
There have been few studies of DNA ploidy and cell cycle kinetics in endometrial hyperplasia. The authors studied archival cases of proliferative endometrium, simple, complex and atypical endometrial hyperplasia and well, moderately, and poorly differentiated endometrial adenocarcinoma by flow cytometry and also evaluated the significance of the degree of cytologic atypia (low versus high) in endometrial hyperplasia relative to the occurrence of carcinoma. All proliferative endometria, all types of hyperplasia and well and moderately differentiated carcinomas were diploid. Two-thirds of poorly differentiated adenocarcinomas were aneuploid. Neither S-phase fractions or proliferative fractions (S+G2M) could distinguish among the different types of hyperplasia or predict which hyperplasias were associated with carcinomas. The degree of cytologic atypia in atypical hyperplasia was not predictive of the occurrence of carcinoma. Poorly differentiated carcinomas showed significant differences in DNA ploidy, S-phase, and proliferative fractions from endometrial hyperplasia and lower grade carcinoma. These results support the concept that there are two fundamentally different types of endometrial carcinoma.
Adenocarcinoma↗
Cotyledonoid dissecting leiomyoma of the uterus. The Sternberg tumor.
We report four cases of an unusual uterine smooth muscle neoplasm. All patients were of reproductive age, ranging from 23 to 41 years old, and had a pelvic mass or an enlarged uterus. Two also had menstrual irregularities. At laparotomy, an exophytic congested bulky tumor resembling placental tissue extended from the uterine wall into the broad ligament and pelvic cavity. In one case the tumors were bilateral but unequal in size. On gross examination, these exophytic components were the most distinctive feature. On microscopic examination the basic lesion appeared to be a dissecting leiomyoma with growth at its periphery in sinuous dissecting patterns and extensive degenerative changes. Some microscopic features, including dissecting growth patterns, distinctive connective tissue alterations, and a rich component of vessels, overlap with those seen in several leiomyoma variants, including infiltrating leiomyoma, leiomyoma with perinodular hydropic degeneration, and intravenous leiomyomatosis. An intravascular component was not a feature. The distinctive gross appearance and microscopic features are embodied in the designation, "cotyledonoid dissecting leiomyoma." The follow-up information available for three cases supports the benign nature of the tumor.
Adnexa Uteri↗
Steroid cell tumor of the broad ligament arising in an accessory ovary.
OBJECTIVE: To determine the histogenesis of an unusual steroid cell tumor that occurred in the broad ligament. PATIENT AND METHODS: The tumor occurred in a 29-year-old woman who had evidence of virilization. The preoperative testosterone level was greater than 700 ng/dL, but it returned to normal after surgery. She was living and well without evidence of recurrent tumor 1 year after operation. The tumor was examined using light and electron microscopy and immunohistochemical stains. RESULTS: The tumor was composed of polygonal cells with prominent eosinophilic cytoplasm. No significant nuclear atypia or mitotic activity was identified; however, the tumor was large, and necrosis and hemorrhage were identified on gross and microscopic examination. A graafian follicle and a primordial follicle were present at the periphery of the tumor within the connective tissue stroma in one section, providing evidence for the presence of an accessory ovary. A separate normal ovary was present on the same side. The tumor mass was connected to the surface of the eutopic ovary by thin membranous tissue. CONCLUSION: To our knowledge, we report the first case in the modern literature of an extraovarian steroid cell tumor arising in the broad ligament, and we present evidence supporting its origin from an accessory ovary.
Adult↗
Adenoid cystic ovarian carcinoma compared with other adenoid cystic carcinomas of the female genital tract.
Adenoid cystic carcinoma (ACC) of the ovary is an extremely rare neoplasm referred to infrequently in the literature. A new case of a pure, primary, ovarian ACC is reported. The patient was a 45-year-old white woman who had a stage IA, well-circumscribed, unilateral, ovarian mass. Histologically, the tumor was composed of small, uniform, and basaloid cells exhibiting predominantly a tubular pattern, as well as demonstrating cribriform and focal solid areas. There was no necrosis and minimal nuclear pleomorphism; the mitotic rate was fewer than three cells per 10 high-power fields. Immunohistochemical examination showed that the tumor cells were strongly positive for cytokeratins CAM 5.2 and AE1/3 and carcinoembryonic antigen. The cells at the periphery of the epithelial aggregates in the cribriform and tubular areas were positive for muscle-specific actin and, occasionally, for S100 protein. Electron microscopic examination revealed that these cells had convoluted nuclei and filamentous structures associated with dense bodies. These findings support a myoepithelial component. A characteristic feature was the production of periodic acid-Schiff stain-positive basement membrane material, which appeared as reduplicated basal lamina by electron microscopic examination. The patient is currently alive, without evidence of recurrence or persistent tumor 7 years after surgical excision. The tumor demonstrated immunohistochemical and ultrastructural findings similar to those of ACCs of salivary gland origin and to other ACCs of the female genital tract. The histogenesis of most ovarian ACCs is through metaplasia of the celomic epithelium, but pure cases might also be of teratomatous origin.
Carcinoma, Adenoid Cystic↗
Medicolegal issues. An anatomic pathologist's perspective.
In the practice of anatomic pathology, the standard of care must be met in all instances if the possibility of an adverse legal action is to be avoided. Whether one practices surgical, cyto-, or necropsy pathology, one is at risk. Constant vigilance, following appropriate guidelines, and well-designed quality assurance programs are all important in reducing the possibility of litigation. During intraoperative consultations direct communication with the surgeon is often essential. If an adequate legal defense is to be had, documentation of the precautions taken in an individual case is necessary. Outside consultants should be chosen carefully based on their expertise in the area of concern, and preferably only one consultation should be requested on a particular case. House staff in training should be given graduated responsibility, but their work, in general, should be supervised by an attending pathologist who has hospital privileges. In giving testimony as a defendant, one should never admit a departure or deviation from the standard of care. As an expert witness, it is important that one's testimony be objective and impartial. One should not attempt to answer questions outside one's area of expertise.
Female↗
Transitional cell carcinoma and other transitional cell tumors of the ovary.
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Adult↗
Flow cytometric DNA analysis of extramammary Paget's disease of the vulva.
Vulvar extramammary Paget's disease (EMPD) is an uncommon disease entity that occurs predominantly in postmenopausal white women. The clinical behavior of this neoplasm is extremely variable, reflecting the various histological patterns that have been reported with this lesion. Flow cytometry has been used as a method of obtaining prognostic information about a number of gynecological neoplasms, yet to date there have been no flow cytometric studies performed on this unusual neoplasm. We performed flow cytometric analysis of 14 cases of paraffin-embedded vulvar EMPD in patients ranging from 45 to 86 years of age. We correlated histological features and clinical recurrence risk with DNA analysis. Although we were unable to show a statistically significant correlation between DNA ploidy or S-phase and time to recurrence, we did show a statistically significant correlation between DNA ploidy and histological features. Aneuploidy appears to be associated with in situ sweat gland adenocarcinoma, invasive carcinoma, and lymphatic invasion. These results suggest that Paget's cells with aneuploid DNA stem lines may be associated with the potential for aggressive biologic behavior.
Aged↗
Benign müllerian lymph node inclusions. An unusual case with implications for pathogenesis and review of the literature.
Endosalpingiosis with psammoma bodies within an intramammary lymph node presented as microcalcifications on mammography in the right breast of a 64-year-old woman. The radiographic differential diagnosis included primary breast carcinoma. The histologic differential diagnosis included metastatic papillary carcinoma, particularly of thyroid origin. To our knowledge, this is the first reported case of endosalpingiosis occurring above the diaphragm. The unusual location of these inclusions has relevant implications concerning their pathogenesis. Moreover, it is important for pathologists to be aware that endosalpingiosis may occur and mimic carcinoma at sites distant from the female pelvis.
Breast Diseases↗