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Biomedical subjects

M T Mazur

Publications and source records attributed to M T Mazur.

At least 37 records · Page 2Linked to original sources

Metastatic gestational choriocarcinoma. Unusual pathologic variant following therapy.

Two cases of metastatic gestational choriocarcinoma to the lungs have been encountered that presented unusual histologic patterns. Both lesions were solitary metastases that followed multiple courses of chemotherapy, and the patients had low serum beta-human chorionic gonadotropin (hCG) levels. Surgical excision appeared to be curative in both cases. Both neoplasms were characterized by a predominance of uniform but highly atypical mononucleate trophoblastic cells. These cells infiltrated pulmonary parenchyma, forming nests of tumor with central dense necrotic debris. Syncytiotrophoblastic cells (STB) were present but showed scant cytoplasm and little vacuolization. Hemorrhage was only focal. Immunohistochemistry revealed that some of the multinucleate STB and occasional mononucleate cells produced hCG, while human placental lactogen was focally produced in the tumors. By electron microscopy the STB were identified but lacked open lacunae lined by microvilli. Most mononucleate cells showed greater maturation evidenced by a more complex cytoplasm than is seen in typical cytotrophoblastic cells (CTB). The results suggest that these tumors are a distinctive subtype of choriocarcinoma composed largely of a form of trophoblastic cell with features intermediate between CTB and STB, yet different from the intermediate trophoblast of the placental site tumor. Identification of this morphologic variant of choriocarcinoma may have clinical utility as additional cases are studied.

Adult↗

Trophoblastic tumors: ultrastructural comparison of choriocarcinoma and placental-site trophoblastic tumor.

Ten trophoblastic tumors, including seven classical choriocarcinomas, two choriocarcinomas with atypical histology, and one placental-site trophoblastic tumor (PSTT), were studied to compare their fine structural features. Ultrastructurally, the classical choriocarcinomas showed well-defined cytotrophoblasts and syncytiotrophoblasts. The cytotrophoblasts were primitive epithelial cells, while the syncytiotrophoblasts were complex cells with multiple nuclei and dense cytoplasm containing dilated endoplasmic reticulum, lysosomes, vesicles, and tonofilaments. The syncytiotrophoblast cell membranes often contained numerous microvilli. In the choriocarcinomas, scattered intermediate trophoblasts showed features transitional between the cytotrophoblasts and the syncytiotrophoblasts, with moderately complex cytoplasm containing some of the organelles found in the syncytiotrophoblasts. Histologically, the atypical choriocarcinomas showed a predominance of mononucleate and binucleate cells and indistinct syncytiotrophoblasts. Ultrastructurally, these atypical tumors were composed largely of intermediate trophoblasts, yet contained scattered syncytiotrophoblasts with microvilli in compressed aggregates. The PSTT was composed primarily of intermediate trophoblasts that contained prominent paranuclear filaments not seen in the intermediate trophoblasts of the choriocarcinomas. Rare cells resembling syncytiotrophoblasts were found in the PSTT, but no cytotrophoblasts were observed. Immunoreactivity for human chorionic gonadotropin and human placental lactogen was found in the intermediate trophoblasts and syncytiotrophoblasts of both the choriocarcinomas and the PSTT, demonstrating functional homology between these tumors despite some ultrastructural differences. These results demonstrate ultrastructural features of trophoblastic cells that correlate with the morphologic diversity seen in these tumors by light microscopy. Furthermore, the comparisons suggest that the PSTT is composed of a distinct form of intermediate trophoblast that appears to reflect its origin from the extravillous trophoblast.

Choriocarcinoma↗

Uterine herpes virus infection with multifocal necrotizing endometritis.

A case of herpes simplex virus (HSV) infection was diagnosed by biopsy of the cervix and endometrium in a 28-year-old woman with abnormal uterine bleeding. The cervical biopsy demonstrated surface ulceration and underlying patchy necrosis of endocervical clefts and stroma. The endometrium was late secretory, with striking patchy necrosis of gland epithelium and stromal cells. Both sites contained occasional epithelial and stromal cells with nuclear inclusions consistent with HSV infection. Viral culture further confirmed the presence of HSV. Immunohistochemistry demonstrated the presence of HSV antigens in the tissue, and ultrastructural study of the endometrium revealed viral particles within epithelial and stromal cells. The results suggest endometrial involvement via an ascending infection from the cervix. Recognition of this unusual pattern of endometrial inflammation may facilitate diagnosis of additional cases.

Adult↗

Endometrial biopsy in the cycle of conception: histologic and lectin histochemical evaluation.

The histologic features and lectin binding patterns of endometrial tissue obtained in 16 cases of inadvertent biopsy during the cycle of conception were studied. Six biotinylated lectins that bind to specific glycoconjugates of secretory or gestational endometrium in paraffin-embedded tissue were used. These lectins were wheat germ agglutinin (WGA), Ricinus communis agglutinin-I (RCA-I), Concanavalin A agglutinin (Con-A), peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), and soybean agglutinin (SBA). On review, the histologic sections showed day 20 to 26 patterns. In retrospective analysis, 15 of the 16 cases had increased stromal edema and vascular congestion compared with endometria of equivalent postovulatory dates not associated with conception. In 2 cases, spiral arterioles showed increased thickness. There was no evidence of renewal or prominence of glandular secretions. Most lectin binding was similar to that of the secretory phase of the menstrual cycle (WGA, RCA-I, gland lumenal secretions and stromal granulocytes; Con-A, gland cell cytoplasm and predecidua). There was focal, irregular staining of gland secretions with PNA, DBA, and SBA, lectins that generally react only with gland secretions in later gestation. These results indicate that vascular changes including edema and congestion appear to be the earliest persistent morphologic manifestations of the pregnant endometrium. Secretory gland changes, however, are subtle and are not identifiable by routine histology.

Adult↗

Endodermal sinus tumor and mucinous cystadenofibroma of the ovary. Occurrence in an 82-year-old woman.

We encountered an unusual ovarian tumor consisting of a mixture of typical endodermal sinus tumor (EST) and mucinous cystadenofibroma that occurred in the ovary of an 82-year-old female patient. The EST component showed the classic histologic features of this tumor. Serum alpha-fetoprotein (AFP) level was not determined. Tumor stains were negative for AFP but positive for alpha-1-antitrypsin. The malignant germ cell component was intimately associated with the benign mucinous component. Focal production of epithelial mucin and carcinoembryonic antigen (CEA) in the EST component suggested a probable association between the two tumor types. The tumor was confined to one ovary, and the patient is disease-free 2 years after surgical therapy. This neoplasm is unique not only for the malignant germ cell component occurring in an 82-year-old woman, but for the unusual combination of tumor types. The pathogenesis is unknown.

Adenofibroma↗

Glycoconjugate distribution in normal human endometrium. A lectin histochemical study.

A battery of nine lectins was applied to routinely processed endometrial biopsies to evaluate changes in glycoconjugate expression during the menstrual cycle and early gestation. Specific staining patterns emerged for glands, surface epithelium, predecidual and decidual cells, stromal granulocytes, and endothelium. Three lectins--wheat germ agglutinin (WGA), Ricinus communis-I (RCA-I), and Concanavalin ensiformis (Con-A)--showed consistent binding to epithelial and stromal cells in the menstrual cycle. WGA and RCA were bound to gland secretions whereas Con-A labeled epithelial cytoplasm. These three lectins stained occasional stromal cells early in the cycle, but WGA and RCA marked granulocytes whereas Con-A labeled predecidua in the late secretory phase. Succinylated WGA had a distribution similar to WGA but lacked its consistency and intensity. In the menstrual cycle peanut agglutinin reacted with ciliated cells. In addition, this lectin along with soybean agglutinin and Dolichos biflorus labeled gland secretions in pregnancy. The remaining lectins, Phaseolus vulgaris leucoagglutin and Ulex europaeus, marked some components, especially endothelium, but generally had less reactivity than the other lectins did. The results indicate that glycoconjugate production is correlated with the functional status of the endometrium. Presumably these glycoconjugates play a role in endometrial development necessary for nidation, and alterations in lectin distribution may reflect functional abnormalities not apparent by light microscopic study.

Adult↗

Cystic epithelial-stromal tumor of the seminal vesicle.

A cystic tumor composed of atypical glands in a cellular stroma arose in the pelvis of a 49-year-old man. Two years later an identical tumor was again excised from the pelvis. Morphologic, immunohistochemical and ultrastructural studies indicate that this neoplasm arose in the seminal vesicle, possibly from a seminal vesicle cyst. The tumor did not involve the prostate gland, and immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase were negative. Ultrastructural study showed that both the glandular and mesenchymal components of the tumor recapitulated features of normal seminal vesicle, further establishing origin from this site. This tumor resembles the rare cystadenoma of the seminal vesicle, yet the cytologic atypia suggests low grade malignant potential. Following the second excision, the patient has had a disease-free interval of 18 months. Long term follow-up and recognition of additional cases is necessary to define the biologic potential of this unusual tumor.

Cystadenoma↗

Evaluation of the reproducibility of the World Health Organization classification of common ovarian cancers. With emphasis on methodology.

Seven pathologists independently classified 50 slides of ovarian tumors using category I of the World Health Organization classification (WHO I), each case being seen twice under different random code numbers. Intraobserver reproducibility and interobserver reproducibility, based on consistent interpretations, were both suboptimal. However, scrutiny suggested that no pathologist was a source of excessive variability, nor was suboptimal interobserver reproducibility simply due to intraobserver variability. Neither could excessive variability be attributed to skewing of results by a subgroup of unclassifiable cases. However, clearcut sources of variability were identified among the categories of WHO I, namely, mixed epithelial, unclassified epithelial, and undifferentiated carcinoma. There was also considerable variability in distinguishing serous and endometrioid neoplasms, and in identifying tumors of low malignant potential. These findings should not be misconstrued as implying that pathologists in routine practice cannot diagnose common ovarian cancers reproducibly for patient care purposes. Availability of clinical and macroscopic data, extensive sampling, histochemistry, and consultation combine, in an uncontrolled and highly individualistic fashion, to render routine service work very different from this highly controlled formal exercise. Furthermore, at the current state of the therapeutic art, many of the taxonomic problems identified in this study may have little clinical significance. Nonetheless, this study has strengthened the evidence that there may be important problems in classifying common ovarian cancers reproducibly using WHO I, and that WHO I may require greater clarity to enhance reproducibility. Current emphasis on quality assurance dictates reconsideration of the literature on reproducibility of histopathologic taxonomy, which has tended to inculpate pathologists as sources of variability. Virtually all of this literature is subject to some degree of skepticism due to deficiencies in methodology. Consideration of the question of how to measure reproducibility in anatomic pathology leads us to suggest that the community of pathologists should address the need to decrease ambiguity in classification systems as an important step toward optimizing reproducibility.

Female↗

Clear cell leiomyoma (leiomyoblastoma) of the uterus: ultrastructural observations.

The ultrastructure of a benign uterine epithelioid leiomyoma with prominent clear cells ("leiomyoblastoma") was studied to define the subcellular changes that yield the distinctive light microscopic pattern of this rare lesion. The main constituent of the cytoplasm was multiple cytolysosomes composed of vesicular, membranous material. Aggregates of glycogen also contributed to the clear appearance of the cytoplasm seen by light microscopy. In addition, the cells contained scattered aggregates of typical smooth muscle myofilaments with densities that certified that the lesion was a variant of a leiomyoma. The fine structural features of this lesion are distinctly different than those described in gastrointestinal leiomyoblastomas and indicate that the uterine clear cell leiomyoma is a unique lesion that should be separated from nonuterine leiomyoblastomas. Furthermore, the ultrastructural features of the uterine clear cell tumor suggest the lesion represents a leiomyoma that has undergone sublethal cell injury. The term "leiomyoblastoma" implies a primitive tumor and is inappropriate; "epithelioid leiomyoma, clear-cell type" is preferred.

Actin Cytoskeleton↗

Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study.

Eight cases of acute interstitial pneumonia were studied to define the clinical and pathologic features and to determine the relationship to chronic interstitial pneumonia. Clinically, this disease differs from the chronic interstitial pneumonias by a sudden onset and a rapid course. Five patients died of respiratory failure after 23 days to 2 months, and two died of other complications after 3 1/2-6 months. An etiologic agent could not be identified in any case. The histologic hallmark was interstitial fibrosis and edema associated with type II pneumocyte hyperplasia. The fibrosis differed from that seen in the chronic interstitial pneumonias by extensive fibroblast proliferation and relatively little collagen deposition. Autoradiographic studies of tritiated thymidine (3H-TdR) uptake showed high labeling indices in interstitial cells and type II pneumocytes. Evidence of acute lung injury, including both endothelial and epithelial cell damage, was a prominent ultrastructural feature. These findings emphasize that acute interstitial pneumonia is a clinically and pathologically distinct form of interstitial pneumonia that should be separated from the group of chronic interstitial pneumonias.

Acute Disease↗

Pelvic fibromatosis: an unusual gynecologic tumor.

Pelvic fibromatoses are only unusually encountered in gynecologic practice, but then consistently create a diagnostic and therapeutic challenge. The reported patient typifies the difficulties encountered in surgical excision. A discussion of theories of etiology and management options follows.

Adult↗

The koilocyte and cervical intraepithelial neoplasia: time-trend analysis of a recent decade.

To determine whether the role of the human papillomavirus in the development of cervical intraepithelial neoplasia has changed recently, cervical biopsy specimens from the years 1972 and 1982 were reviewed to compare the frequency of diagnosis of human papillomavirus-associated koilocytosis in patients with suspected cervical intraepithelial neoplasia. No significant difference was found in the frequency of koilocytosis in biopsy specimens with cervical intraepithelial neoplasia between the years, koilocytosis being present in about half of the cases of cervical intraepithelial neoplasia during both years. In each year koilocytosis was more common in grades 1 and 2 lesions. Koilocytotic atypia without cervical intraepithelial neoplasia also was present in a relatively constant proportion of cases over the decade (8.0% and 6.5%). The average patient age was younger in 1982 than in 1972 (27.6 versus 32.6 years), but analysis of patients by age groups again showed no significant difference in the occurrence of koilocytosis. This study suggests that the relative importance of human papillomavirus in the evolution of cervical intraepithelial neoplasia has remained unchanged in the recent past.

Adult↗

Metastases to the female genital tract. Analysis of 325 cases.

In order to better define the frequency and patterns of metastasis to the female genital tract, all cases of nonhematopoietic metastases to the adnexa, uterus, vagina, and vulva encountered in patients treated at Barnes Hospital between 1950 and 1981 were reviewed. Three hundred twenty-five metastatic cancers from 269 patients were recovered. One hundred forty-nine cases were from extragenital primaries; the remaining tumors were intragenital metastases. Ovary and vagina were the most frequent metastatic sites for both extragenital and genital primaries. The majority of the extragenital metastases were adenocarcinomas from the gastrointestinal tract, but a variety of other primaries did spread, on occasion, to the genital tract. Twenty-seven percent of the metastases presented as possible primary gynecologic lesions, and 75% of these tumors had an extragenital origin. It is shown that despite certain trends in the distribution of metastases, all sites in the female genital tract are at risk for the occurrence of metastases.

Adenocarcinoma↗

Optically clear endometrial nuclei.

The ultrastructure of optically clear endometrial nuclei is presented. These nuclear alterations have been found in spontaneous abortion, term pregnancy, endometriosis, and uterine choriocarcinoma.

Adult↗

Gastric stromal tumors. Reappraisal of histogenesis.

Twenty-eight gastric wall tumors classified by light microscopy as leiomyomas or leiomyosarcomas were reevaluated for histogenesis. Each case was analyzed for the presence of S-100 protein, a marker for cells derived from neuroectoderm, by the immunoperoxidase technique. Eight tumors contained cells with positive immunostaining for S-100 protein. Usually this staining was focal, but in one case staining was diffuse. In three additional cases the immunostaining outlined a nerve within the tumor. In contrast, two esophageal and 10 uterine leiomyomas, as well as normal gastric smooth muscle, gave negative reactions for S-100 protein. Twelve cases had tissue processed for electron microscopy. Only two of the tumors, one leiomyoma and one leiomyosarcoma, contained cytoplasmic myofilaments with densities expected in cells derived from smooth muscle; neither of these tumors stained for S-100 protein. In one case, the tumor with diffuse staining for S-100 protein, the cells resembled Schwann cells ultrastructurally. The remaining nine cases had neither smooth muscle nor Schwann cell features. They did contain interposed cell processes, primitive junctions, and large cytoplasmic vacuoles. The results of this study indicate that many gastric wall tumors are not derived from smooth muscle. The presence of S-100 protein suggests a nerve sheath origin in some cases. While the ultrastructure of many gastric tumors does not resemble nerve sheath cells in most peripheral nerves, the myenteric nervous system is a possible source for perineurial or mesenchymal nerve sheath cells with distinctive fine structure. Further study is needed to refine our knowledge of the histogenesis of gastric stromal tumors.

Esophageal Neoplasms↗

Optically clear nuclei. An alteration of endometrial epithelium in the presence of trophoblast.

Examples of focal clearing of endometrial epithelial nuclei associated with the presence of trophoblastic tissue have been observed recently in our surgical pathology laboratories. These nuclear alterations were initially observed in endometria from first- and second-trimester spontaneous abortions, term pregnancies, and a uterus harboring choriocarcinoma. Subsequently, an identical change was seen in small foci of endometriosis removed during postpartum tubal ligation. The prominent vacuolated appearance to the nuclei resembled, in some cases, the inclusions seen in herpesvirus infection, but electron-microscopic study showed that the nuclear clearing was due to replacement of normal chromatin by a network of fine filamentous material rather than herpesvirus DNA. A subsequent review of 200 consecutive first-trimester abortions found less-striking degrees of this change in 7% of cases. The endometrial nuclear clearing was focal; often the endometrium also contained cells which demonstrated the Arias-Stella reaction. The etiology of this type of nuclear clearing is not known, but the fibrils may represent a thread-like substructure of normal chromatin which forms as a result of hormonal stimulation of endometrial epithelial cells.

Abortion, Spontaneous↗