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Biomedical subjects

L M Roth

Publications and source records attributed to L M Roth.

At least 55 records · Page 3Linked to original sources

Spermatocytic seminoma: an immunohistochemical study.

Spermatocytic seminoma (SS) is an unusual germ cell tumor that behaves in an indolent fashion. Because orchiectomy alone in adequate treatment, it is important to distinguish SS from classic seminoma and other germ cell tumors. Light microscopic distinction usually is possible; however, occasional cases of SS exhibit atypical features, including the presence of a lymphoid infiltrate or microcystic change, which simulate classic seminoma and yolk sac tumor, respectively. Immunohistochemistry might aid in this differential diagnosis, but the immunohistochemical profile of SS is not well reported in the literature. We examined seven SS cases (six men and one non-human primate) with a panel of 14 antibodies directed against placental-like alkaline phosphatase (PLAP), keratins (CAM 5.2, AE1/AE3), vimentin, human chorionic gonadotropin, alpha-fetoprotein, muscle-specific actin, carcinoembryonic antigen, S-100 protein, epithelial membrane antigen, desmin, leukocyte-common antigen, neuron-specific enolase, and human placental lactogen. A previously unreported finding was the presence of focal cytoplasmic staining for low molecular weight cytokeratin (CAM 5.2) in three cases. All other antibodies produced essentially negative results, including anti-PLAP. The PLAP and neuron-specific enolase negativity of SS are in contrast to the positivity of classic seminoma for these markers. A simplified panel of antibodies is recommended to assist in the differentiation of SS from other forms of germ cell neoplasia.

Adult↗

Immunohistochemical phenotype of ovarian granulosa cell tumors: absence of epithelial membrane antigen has diagnostic value.

Granulosa cell tumors (GCTs) represent 1.5% to 3% of primary and 6% to 10% of malignant ovarian neoplasms, and present little diagnostic difficulty in the typical case; however, other primary or metastatic tumors may mimic their various histologic patterns. For this reason, immunohistochemistry can be used to supplement routine histology to help determine a final tissue diagnosis. Previous reports on the utility of antibodies to intermediate filaments vary, as some investigators found keratin to be uniformly negative in GCTs while others reported immunoreactivity for keratin in 20% to 68% of cases. To determine the immunophenotype of granulosa cell tumors and to discover which antibodies are useful in differentiating GCTs from histologic look-alikes, we studied 52 GCTs, including 24 typical cases, 23 cases in which the diffuse pattern predominated, and five juvenile cases, with a panel of commercially available antibodies using an automated immunohistochemistry system. Immunoreactivity for granulosa cells in GCTs was as follows: 17 cases (32.7%) reacted with cytokeratin AE1/AE3, six cases (11.5%) reacted with cytokeratin MAK-6, three cases (5.8%) reacted with cytokeratin CAM 5.2, no case (0%) reacted with epithelial membrane antigen, 52 cases (100%) reacted with vimentin, no case (0%) reacted with desmin, 48 cases (92.3%) reacted with smooth muscle actin, and 26 cases (50%) reacted with S-100 protein. No attempt was made to quantify staining of background thecoma-like or fibroma-like elements in GCTs. Immunoreactivity was independent of the histologic subtype of GCT. Cytokeratin immunoreactivity showed a globoid pattern of staining and was consistent with the expression of 52.5-kD and 45-kD cytokeratins (8 and 18 of Moll's classification). For this reason, the presence of cytokeratin immunoreactivity by itself cannot be used to differentiate a primary or metastatic carcinoma from a GCT. The presence of smooth muscle actin and the absence of epithelial membrane antigen immunoreactivity are additional features that are characteristic of a GCT. S-100 protein immunoreactivity is a finding limited exclusively to GCTs among sex cord stromal tumors, and its presence may have some role in differentiating between Sertoli-stromal cell tumors and GCTs. Since epithelial membrane antigen immunoreactivity is present in many of the histologic look-alikes of GCTs, such as metastatic or primary carcinoma, the absence of staining in GCT has diagnostic value.

Adolescent↗

Proliferative activity and aneuploidy in pleomorphic adenomas of the salivary glands.

We used flow cytometry in a retrospective study of pleomorphic adenoma and carcinoma arising in pleomorphic adenoma, using paraffin-embedded tissue, to assess the relationship among proliferative activity, ploidy, and recurrence or malignant transformation. Twenty-four specimens obtained from 22 tumors were acceptable for analysis (co-efficient of variation, < or = 7.0), including multiple samples from two tumors. Fourteen tumors (13 benign and one malignant) were diploid. Six tumors were aneuploid: four benign pleomorphic adenomas and two carcinomas arising in pleomorphic adenoma. Two tetraploid tumors were malignant recurrences from the same patient. Of the recurrent tumors (nine benign and four malignant), 54% were aneuploid. The highest S-phase fractions were observed in recurrent and malignant pleomorphic adenomas. Immunostaining with p105, a nuclear proliferation antigen, revealed increased proliferative activity in a majority of pleomorphic adenomas. Increased proliferative activity and aneuploidy occurred in benign pleomorphic adenomas.

Adenoma, Pleomorphic↗

Vulvar melanoma reconsidered.

BACKGROUND: Melanoma of the vulva has traditionally been treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy. Cutaneous nonvulvar melanoma has been successfully treated with local excision with selective therapeutic regional node dissection. METHODS: A retrospective analysis of 16 patients with primary malignant melanoma of the vulva who underwent surgery from 1973 to 1988 at Indiana University Hospital was conducted. The purpose of this analysis was to determine if less radical surgery, such as that performed for cutaneous nonvulvar melanoma, might be adopted for patients with vulvar melanoma without compromising 5-year survival results. RESULTS: Surgical therapy included radical vulvectomy with bilateral inguinofemoral lymphadenectomy (n = 11), radical vulvectomy alone (n = 1), and wide local excision (n = 4). Treated International Federation of Gynecology and Obstetrics (1971) stages included I (n = 12), II (n = 3), and III (n = 1). The median age of the patients was 59 years (range, 29-79 years). The median depth of invasion according to the Breslow method was 3 mm (range, 0.1-8 mm). Patients were observed for a median of 24 months (range, 3-143 months). The Kaplan-Meier 5-year survival estimate was 30%. There were nine recurrences: five distant, one central, one nodal, and two mixed. A median depth of 0.9 mm (range, 0.1-1.75 mm) was noted in those who remained disease-free versus 4.6 mm (range, 3-8 mm) in those who experienced a recurrence (P < 0.01). None of the patients with lesion depths of 1.75 mm or smaller experienced a recurrence, whereas all of those with lesion depths larger than 1.75 mm suffered a recurrence (P = 0.0004). CONCLUSIONS: Patients with lesion depths of 1.75 mm or smaller may be treated with wide local excision. Patients with greater lesion depths are at high risk for the development of distant metastases. The patients with well-lateralized lesions may be equally well served with a less morbid procedure deferring therapeutic node dissection until there is a regional recurrence.

Adult↗

Ovarian metastases from cervical carcinomas other than pure adenocarcinomas. A report of 12 cases.

Twelve cases of ovarian metastases from cervical carcinomas, most with clinical manifestations of ovarian involvement, are reported. The patients were 23-73 years of age (average, 43 years). The ovarian and cervical tumors were synchronous in eight patients; in three, ovarian tumors were discovered 10 months, 2.5, and 3 years after the detection of a cervical neoplasm. In one patient, the cervical tumor was not discovered until autopsy 7 months after presentation. Four patients had abdominal swelling or distention, three had vaginal bleeding, three had an abnormal Papanicolaou smear, and two had masses discovered during pelvic examination. The ovarian tumors, six of which were bilateral, ranged from 5-17 cm (average, 9.5 cm) in maximal dimension in 11 patients; in the 12th patient, the involved ovary was not enlarged. The cervical tumors were grossly evident in 10 patients. They were usually deeply invasive, often with extracervical extension. Four were squamous cell carcinomas; two, small cell carcinomas; one, a mixed small cell carcinoma and adenocarcinoma; one, a mixed poorly differentiated carcinoid and adenocarcinoma; two, adenosquamous carcinomas; one, a transitional cell carcinoma; and one, an undifferentiated carcinoma. Various features, including bilaterality of the ovarian tumors, the finding that the histologic features of the ovarian tumors typically were unusual for a primary ovarian neoplasm, and the presence of extensive extracervical disease, led to the conclusion that the ovarian tumors were metastatic from the cervix. Although ovarian metastases of cervical carcinoma are uncommon, this series illustrates that, occasionally striking examples with clinical manifestations of ovarian involvement occur.

Adenocarcinoma↗

Vascular neoplasms of the parotid gland. Parotid vascular tumors.

Vascular neoplasms of the parotid gland are common in early childhood, particularly in females. We reviewed the clinical, histologic, and treatment details of 10 cases of hemangiomas and one case of lymphangioma that involved the parotid gland. Histologically, the cellularity and increased division figures in these lesions should not be interpreted as a sign of a malignant condition. A watchful expectancy for spontaneous regression and preservation of the facial nerve at surgery are advocated.

Adolescent↗

Ovarian Brenner tumors and transitional cell carcinoma: recent developments.

Brenner tumor variants--such as metaplastic, proliferating, and low-malignant-potential (three categories recently designated as intermediate Brenner tumors)--and malignant Brenner tumors are unusual tumors presenting problems in classification. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low-malignant-potential Brenner tumors. The category of "transitional cell carcinoma of the ovary" has been proposed for those primary ovarian carcinomas in which definite urothelial features are present, but no benign, metaplastic, and/or proliferating Brenner tumor is identified. Two subtypes have been described, the papillary and the malignant Brenner-like types. These tumors are more aggressive than malignant Brenner tumors, but they appear to respond better to chemotherapy than other types of ovarian epithelial cancer.

Brenner Tumor↗

Stage II carcinoma of the ovary: an analysis of survival after comprehensive surgical staging and adjuvant therapy.

Ninety-three women with FIGO stage II epithelial ovarian carcinoma underwent comprehensive surgical staging and were randomized prospectively to therapy consisting of either intraperitoneal radioactive phosphorus or oral melphalan. No patient had gross residual disease at the time of randomization. Ten of the forty-five women treated with melphalan experienced severe bone marrow depression at some time during therapy and two women expired from leukemia. Four of the forty-eight women treated with intraperitoneal phosphorus required surgical reexploration for intestinal obstruction or bowel injury. Twenty-one women died of their disease. Survival was not statistically different between the two treatment arms. The 5-year actuarial survival was 78%.

Adolescent↗

Flow cytometric analysis of DNA content and RAS P21 oncoprotein expression in ovarian neoplasms.

Flow cytometric analysis of DNA content and ras p21 expression were studied in paraffin-embedded normal ovary (NO, n = 10), serous cystadenoma (SA, n = 11), serous tumors of low malignant potential (LMP, n = 13), and papillary serous cystadenocarcinoma (SCa, n = 7). Tissue for DNA analysis was processed via a modified Hedley technique; a separate aliquot of the same sample was stained with a monoclonal antibody directed to oncoprotein ras p21 (clone Y13259). NO (10/10) and SA (11/11) demonstrated diploid DNA stemlines; 4/12 LMP and 5/7 SCa were aneuploid. S-phase fraction varied with significant differences (p less than 0.001) for SA (mean = 4.4%), LMP (mean = 9.0%), and SCa (mean = 12.7%). When all cases were evaluated, p21 expression was relatively lower in NO and SA (mean = 4.2%) in contrast to LMP and SCa (mean = 13.0% and 8.1%). Diploid cases were examined separately, and lesions with high p21 expression were associated with a diagnosis of LMP/SCa (p less than 0.001), whereas diploid tissues with low p21 expression were associated with a nonmalignant diagnosis (NO/SA). This study suggests that aneuploidy or diploidy with high p21 expression (greater than 10%) may be associated with LMP or frankly malignant ovarian tumors.

Aneuploidy↗

Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.

Adult↗

Flow cytometric DNA analysis of placental-site trophoblastic tumors.

The placental-site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia. Although originally considered benign, it is now apparent that this lesion can be associated with aggressive clinical behavior. Our study examined the DNA ploidy status and clinicopathologic features of four new cases of placental-site trophoblastic tumor. Three cases demonstrated diploid DNA stemlines with S-phase fractions ranging from 6% to 16%. These patients were alive and well at follow-up and had low-serum human chorionic gonadotrophin (hCG) levels. A fourth patient, who had a large tumor, demonstrated a tetraploid DNA peak with a prominent S-phase fraction. This patient exhibited an elevated serum hCG at limited follow-up. Flow cytometric DNA analysis may be a useful adjunct for the identification of placental-site trophoblastic tumors with malignant potential.

Adult↗

The mystique of the mistake. With proposed standards for validating proficiency tests in anatomic pathology.

Variability in classification in anatomic pathology does not necessarily indicate that a mistake has been made. It is usually an artifact, created when pathologists choose a single category from among two or more justifiable alternatives. This is most common when standard classifications with uniform terminology are not used. It also can occur when classification systems are not constructed so as to insure mutual exclusivity of categories. It is proposed that a proficiency test in anatomic pathology should not be considered scientifically valid until a professional organization primarily concerned with anatomic pathology has endorsed its proposed classification system as having categories that are close to 100% mutually exclusive in the hands of expert pathologists not involved in developing the system. All possible precautions should be taken to insure that the "right answers" for any proficiency test are generated in a way that excludes the possibility of multiple justifiable alternatives.

Clinical Competence↗

Spindle cell mural nodules in cystic ovarian mucinous tumors. A clinicopathologic and immunohistochemical study of five cases.

We studied five cystic ovarian mucinous tumors with spindle cell mural nodules to define their histologic and immunohistochemical properties. Three of these mural nodules consisted of carcinomatous nests surrounded by highly pleomorphic polygonal and spindle cells. There were transition zones between the pleomorphic cells and the cell nests. In all three cases, both cell populations coexpressed cytokeratin and vimentin, suggesting a diagnosis of anaplastic carcinoma. A fourth nodule consisted of moderately differentiated adenocarcinoma embedded in prominent, cytologically uniform spindle cells. These cells were histologically distinct from the carcinoma; there were no zones of transition. The carcinoma was strongly positive for cytokeratin but only weakly positive for vimentin; the spindle cells expressed vimentin but not cytokeratin. We diagnosed this lesion as carcinoma with a reactive spindle cell stroma. A fifth mural nodule was composed entirely of interlacing fascicles of uniform spindle cells that were negative for cytokeratin but positive for vimentin, muscle-specific actin, and desmin; these findings support a diagnosis of leiomyoma. Two of the four patients with malignant nodules died of disease; the rest are alive and disease-free after follow-up intervals ranging from 1 to 4 years. This study demonstrates the usefulness of immunohistochemistry in distinguishing variant forms of spindle cell mural nodules in cystic ovarian mucinous tumors. It further suggests that malignant nodules do not necessarily carry a poor prognosis.

Adenocarcinoma↗

Chemotherapy for advanced thymoma. Preliminary results of an intergroup study.

OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma. DESIGN: Nonrandomized, prospective phase I-II trial. SETTING: A Cooperative Oncology Group trial involving tertiary medical centers. PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response. INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle. MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity. CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.

Adult↗

Papillary serous carcinoma of the ovary with squamous differentiation.

Two cases of serous carcinoma of the ovary with squamous differentiation are described. These neoplasms occurred in two women who were 63 and 46 years old and who presented with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and III disease, respectively. The first tumor recurred following chemotherapy; radiotherapy was given, but the patient died of tumor at 4 years. The second neoplasm did not respond to chemotherapy and caused the patient's death at 2 years. In the first case, the squamous differentiation occurred as compact nests of ovoid to spindle cells intermixed with a papillary serous carcinoma component. The squamous component of the second case developed as single or small groups of enlarged, eosinophilic cells, often multinucleated, within nests of papillary serous carcinoma with typical psammoma bodies. In the latter case, intercellular bridges were identified by light microscopy. Both cases showed squamous features by immunohistochemistry, staining positively for 57-kd keratin, although in the first case but not the second there was also some weaker staining for 54-kd keratin, probably indicating incomplete squamous differentiation with retained glandular features. Electron microscopy in both cases revealed prominent cytoplasmic tonofilaments in the squamous component. These two cases reinforce the concept that squamous differentiation, although more frequent in some other types of common epithelial tumors, may occur in serous ovarian carcinomas as well.

Carcinoma, Papillary↗