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Biomedical subjects

E S Wargotz

Publications and source records attributed to E S Wargotz.

At least 19 recordsLinked to original sources

Intraductal (intracystic) papillary carcinoma of the breast and its variants: a clinicopathological study of 77 cases.

The clinical and pathological features of 77 cases of intraductal (intracystic) papillary carcinoma (IPC) of the breast are reported. It should be recognized as an intraductal carcinoma variant and distinguished from invasive papillary carcinoma. Intraductal papillary carcinoma remains a difficult diagnosis as there are four different epithelial growth patterns any of which may predominate. Low grade nuclear features occur in one third of cases, a so-called "stratified spindled cell" epithelial proliferation with bland morphology occurs in one quarter of cases, and a dimorphic population of malignant cells, which may in part be confused with myoepithelial cells, occurs in one quarter of cases. The 77 cases studied were from the 10-year interval 1970 to 1979. The effect on prognosis of cytoarchitectural features, duct wall and stromal invasion, and associated intraductal carcinoma were evaluated. The contribution of immunohistochemistry to the diagnosis using antibodies to smooth muscle actin, S-100 protein, and CAM 5.2 was examined. The 10-year survival rate was 100%, and the 10-year disease-free survival rate was 91%. Mastectomy had been performed in 72% of patients. Three of the patients developed metastases; two were alive with tumor and one died of other causes. Six patients had local recurrence in the chest wall; one was alive without disease, two were alive with tumor, and three died of other causes. An associated intraductal carcinoma of usual nonnecrotic or comedo type was present in 40% of all cases. When IPC recurred or metastasized, it did so as invasive papillary carcinoma in six of seven cases. Stromal invasion was found in 13 patients. Local recurrence developed in two of these. Invasion was not seen in any of the three patients who developed metastases. However, this may be a function of sampling as there was an average of 5.2 tumor sections per case. Patients with low grade tumors had no recurrence or metastasis, and in the absence of invasion may be treated by local excision. Patients with higher grade tumors have an increased risk of recurrence and metastasis.

Adult↗

Oropharyngeal teratomas: a clinicopathologic study of four cases.

Oropharyngeal teratomas (OPT) represent an uncommon congenital tumor with significant morbidity and mortality. Optimal management requires prenatal diagnosis. The clinicopathologic features of four OPT (one stillbirth, two livebirths, and one therapeutic abortion) are reviewed and compared with cases previously reported in the literature. Diagnosis, management, clinical outcome, and the natural history of the entity are discussed.

Adult↗

Fibrosarcoma-malignant fibrous histiocytoma of the breast. A clinicopathological study of 32 cases.

We report the clinical and pathologic features of 32 sarcomas of the breast with features spanning the spectrum of fibrosarcomas-malignant fibrous histiocytomas. Neoplasms were categorized as high- or low-grade lesions depending on a combination of the degrees of atypia and mitotic activity. The majority of high-grade lesions had marked (3+) nuclear atypia and at least five mitotic figures per 10 hpf. High-grade lesions with moderate (2+) nuclear atypia had a mitotic activity of six or more mitotic figures per 10 hpf. All low-grade lesions had five or fewer mitotic figures per 10 hpf, and none had a score of the nuclear grade times mitotic figures of more than 10. The average mitotic activity in low-grade lesions was two mitotic figures per 10 hpf; the high-grade lesions had 12 mitotic figures per 10 hpf. Sixty-nine percent of the low-grade fibrosarcomas-malignant fibrous histiocytomas showed mild (1+) cytologic atypia, and 69% of the high-grade lesions showed severe (3+) cytologic atypia. The herringbone pattern was associated with a more favorable prognosis than the malignant fibrous histiocytoma pattern. Compared to the high-grade lesions, low-grade fibrosarcomas-malignant fibrous histiocytomas were slow-growing, produced fewer recurrences, and did not metastasize. Of the 16 women with low-grade lesions, all were free of tumor at last contact, despite recurrence in more than half of the patients. In contrast, 31% of the patients with high-grade lesions died of tumor, and 13% were alive with disease. Twenty-five percent of women with high-grade lesions developed distant metastases.

Adult↗

Low nm23 protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival.

Protein levels corresponding to nm23 were determined in normal and neoplastic breast tissues by immunoperoxidase staining. Nm23 protein levels were highest in normal breast epithelium, and lower in intraductal carcinomas. Based on nm23 staining, 39 infiltrating ductal carcinomas were separated into two groups: tumors with homogeneously high nm23 protein content, and tumors with low staining in either a homogeneous or heterogeneous pattern. Patients with low nm23 staining tumors, determined by three pathologists independently, had reduced survival times (alpha = 0.034, alpha = 0.012, alpha = 0.052 by the log rank test). Nm23 expression approached significance as an independent predictor of survival in Cox's proportional hazards model. The data provide the first correlation of low nm23 protein expression and reduced breast carcinoma patient survival.

Breast Neoplasms↗

Hamartomas of the breast.

The clinical and pathologic findings of 17 hamartomas of the breast were studied. All neoplasms were evident as clinically and mammographically discrete masses. The pathologic findings were varied and included circumscribed fibrocystic disease, adenolipoma, fibroadenoma with fat and fibroadenoma with lobules. The heterologous elements identified were cartilage and smooth muscle. All lesions were treated by simple excision. In this study, four different microscopic patterns of hamartoma are described and the necessity for a close clinicopathologic correlation is pointed out in the diagnosis of this lesion.

Adenofibroma↗

Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin.

The clinical and pathologic features of 22 examples of pure ductal squamous cell carcinoma (SqCC) of the breast are reported. All patients were women with a mean age of 53 years. Only two of the 19 women with axillary dissection had metastases, but one woman had a positive supraclavicular lymph node in the presence of negative axillary nodes. All metastases were squamous carcinoma. All patients were eligible for a minimum of 5 years' follow-up; the cumulative 5-year disease-specific survival rate was 63%. Eight women developed metastases and one also developed local recurrence, all within 2 years, and all eight died from tumor within 4 years of initial therapy (mean, 2 years). Prophylactic postoperative radiation therapy and radiation for lymph node metastases at initial surgery did not prolong survival as four of the five recipients died from tumor. Although there were no statistically significant gross or histologic differences between recurrent and nonrecurrent neoplasms, larger neoplasms tended to metastasize. Immunohistochemical study for S-100 protein identified an immunoreactive cell component in five of seven neoplasms tested. This and light microscopic findings suggest myoepithelial proliferation, differentiation, or origin.

Adult↗

Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells.

The clinical and pathologic features of 29 examples of mammary metaplastic carcinoma with osteoclastic giant cells (OGC) in the stroma are reported. A bland spindle cell or sarcomatous component dominated these neoplasms, although infiltrating duct carcinoma was present in 23 cases, and intraductal carcinoma was present in six cases. In all 29 neoplasms, the carcinoma was admixed or contiguous with the stroma. Osteoclastic giant cells were admixed within the cellular stroma, and were intimately associated with prominent thin-walled vessels. Hemorrhage and hemosiderin deposition were common. Osteoclastic giant cells were immunoreactive for vimentin and, to a lesser extent, actin, and uniformly not immunoreactive for keratins, confirming their mesenchymal nature. The stromal component of 63% of neoplasms tested was immunoreactive for keratin, 33% was immunoreactive for epithelial membrane antigen, 54% reacted for S-100 protein, 84% reacted for actin, and 100% was immunoreactive for vimentin. Nineteen neoplasms had osteoid, bone, or cartilage, but these were a prominent component in only five neoplasms and OGC were not limited to these areas. The disease-specific cumulative 5-year survival rate for patients with metaplastic carcinoma with OGC was 68%, similar to rates for patients with matrix-producing carcinoma (68%), spindle cell carcinoma (64%), and squamous carcinoma of ductal origin (63%), but notably different from that of patients with carcinosarcoma (49%). Of 17 women with axillary node dissection, only two had metastases. Eleven women developed distant metastases, most commonly to the lungs. Metastasis present at or following initial surgery was an ominous sign, as all 11 women with metastases died from tumor. Size and microscopic circumscription were significant factors in predicting disease progression.

Adult↗

Flow cytometric analysis of granulosa tumors.

Paraffin blocks from 17 granulosa tumors, nonmetastatic (n = 10) and metastatic (n = 7), were analyzed by flow cytometry. Three neoplasms, one with and two without metastases, were found to have cells with an abnormal DNA (DNA aneuploid) content. The occurrence or absence of DNA aneuploid cells did not predict behavior. In addition, there was no correlation of tumor DNA content with tumor size or patient age at the time of surgery. There was no significant difference in cell proliferation (%S + %G2/M) between metastatic and nonmetastatic DNA diploid tumors, however, there was an increase in cell proliferation in tumors with a DNA aneuploid stemline. Granulosa tumors are low-grade neoplasms. At least 90% are seen in Stage I, and metastasis occurs subsequently in 5% to 15% of these cases. Features of Stage I neoplasms associated with subsequent metastasis in some reports, but not all, are involvement of the capsule (Stage IC), large size, and high mitotic rate, 1-5 Providing definitive statements about the behavior of granulosa tumors is hampered by their rarity, the subjectivity of the diagnosis, and their sluggish behavior. We attempted to determine if flow cytometric analysis of DNA could identify granulosa tumors with metastatic potential. We compared DNA histograms from ten Stage IA granulosa tumors that did not metastasize during 22 to 47 years of follow-up with seven granulosa tumors that showed malignant behavior.

Adult↗

Metaplastic carcinomas of the breast. III. Carcinosarcoma.

The clinical and pathologic features of 70 examples of carcinosarcoma (CS) of the breast are reported. Thirty-three neoplasms had infiltrating carcinoma, seven had in situ carcinoma, and 28 had both admixed or contiguous with the sarcomatous component. Squamous carcinoma, present in 15 neoplasms, was the exclusive epithelial component of two. The admixed carcinoma often appeared distinct from the sarcoma component; however, at high magnification transitional differentiation zones and more subtle merging of infiltrating carcinoma with sarcoma were present in most neoplasms. A total of 40 neoplasms were studied by immunohistochemistry for keratins, EMA, vimentin, S-100 protein, and actin. The sarcomatous component in 55% of CS was immunoreactive for keratin, and 98% were immunoreactive for vimentin. A majority were also immunoreactive for actin (77%), and S-100 protein (55%). Ultrastructural examination of the sarcoma in eight neoplasms yielded variable nonspecific findings compatible with sarcoma. These findings indicate biphasic differentiation by cells possessing epithelial and mesenchymal characteristics and suggest myoepithelial origin or differentiation. The cumulative 5-year survival rate for CS was 49%, worse than for other forms of metaplastic carcinoma. The respective 5-year survivals for TNM clinical Stages I, II, and III were 100%, 63%, and 35%. Of patients with axillary dissection, 26% had metastases to axillary lymph nodes with carcinoma as the most frequent component to metastasize. Metastasis was an ominous sign as 33 of 34 patients who developed metastases died from tumor. Local recurrence was not as ominous as 40% who had only local recurrence subsequently died from tumor. Size and microscopic circumscription were also significant prognostic factors.

Adult↗

Metaplastic carcinomas of the breast. II. Spindle cell carcinoma.

The clinical and pathologic features of 100 examples of spindle cell carcinoma (SpCC) of the breast are reported. Eighty-three neoplasms contained overt carcinoma; 72 had infiltrating ductal or intraductal carcinoma and in 11 the carcinomatous component was purely squamous. Seventeen neoplasms lacked overt carcinoma, but were identified as SpCC by immunoreactivity for keratin and the typical bland spindle cell proliferation forming a variable complex of fibrocollagenous stroma with feathered, myxoid, angioid, and storiform patterns. Areas of epithelium merging imperceptibly with the spindle cell component were commonly observed. Sixty neoplasms were studied by immunohistochemistry for the presence of keratin, epithelial membrane antigen (EMA), vimentin, S-100, and actin. The spindle cell component in 98% of SpCC was immunoreactive for keratin. Most were also immunoreactive for vimentin and actin, and in approximately one half, S-100 immunoreactivity was noted. These findings, in conjunction with histopathologic features, and ultrastructural observations from three cases, support myoepithelium as an integral component of SpCC. The cumulative 5-year survival rate for SpCC was 64%, better than survival rates usually reported for metaplastic carcinomas. Of 47 patients with axillary dissection, only 6% had metastases to axillary lymph nodes. Development of metastasis was an ominous sign as 29 of the 30 patients who developed metastases died from tumor. Local recurrence was not as ominous as only 29% who had only local recurrence subsequently died from tumor. The difference in size between tumors that recurred (mean, 5.0 cm) and those that did not (mean 3.7 cm), and the presence or absence of complete microscopic circumscription, were both significant prognostic factors.

Adult↗

Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.

The clinical and pathologic features of 26 examples of a histopathologically distinct form of metaplastic carcinoma of the breast are reported. All neoplasms had overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic giant cells. Therefore, we designate this distinctive form of metaplastic carcinoma as "matrix-producing carcinoma" (MPC). All patients were women, the average age was 58 years, and all patients were eligible for a minimum of 5 years follow-up (mean follow-up period, 8.6 years). Twenty-three patients were treated by a form of mastectomy and three were treated by local excision. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate for MPC was 68%. All of the nine lesions that recurred did so within 2.5 years of initial therapy. Eight of these patients (89%) died from tumor within 4 years of initial therapy. The ninth was alive at last contract. Radiation and chemotherapy were of limited effectiveness. Significant features of the neoplasm associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia. Ultrastructural examination of one case and immunohistochemical evaluation of 12 cases revealed MPC to have myoepithelial characteristics.

Age Factors↗

Granulomatous angiopanniculitis of the breast.

The clinical and pathologic features of six examples of nonnecrotizing granulomatous angiopanniculitis (GAP) of the breast are reported. The patients presented with a solitary ill-defined breast mass causing clinical suspicion of carcinoma. Histopathologically, all lesions consisted of multiple nonnecrotic, noncaseous granulomas with a giant cell component predominantly involving the subcutaneous adipose tissue, extending into the underlying mammary tissue without affecting lobules or ducts. A nonleukocytoclastic lymphocytic angiitis involved small vessels and capillaries. None of the patients had a history of an autoimmune disorder or had previous diagnoses of erythema nodosum or multiforme, leukocytoclastic or nonleukocytoclastic vasculitis, or Weber-Christian disease. Treatment was limited to biopsy in all six patients. Studies for infectious agents on specimens were negative. Five of the six patients developed one or more recurrences in the breast or elsewhere on the body. Four patients experienced spontaneous regression of their recurrent lesions. GAP appears to be a self-limited disorder of uncertain etiology which involves the breast and other sites. It may represent a variant of Weber-Christian disease, as the two diseases share similar clinical and histologic features. GAP must be distinguished from causes of granulomatous inflammation of the breast for which specific medical therapy is available.

Adipose Tissue↗

Brenner tumor of the ovary: immunoanalysis of steroidogenic enzymes in 23 cases.

Immunohistochemical analysis of cytochromes P-450 aromatase and P-450 17 alpha-hydroxylase, which catalyze the production of estrogens and androgens, respectively, was performed for 23 cases of ovarian Brenner tumor. Immunoreactivity for P-450 aromatase was observed in the epithelial cells of the tumor distinctly in two cases and faintly in four cases, while immunoreactivity for P-450 17 alpha-hydroxylase was seen in two cases. No immunoreactivity was observed in the stromal cells of the tumors, nor were luteinized cells observed in the cases examined. No correlation was observed between the immunoreactivity of cytochromes P-450 in the epithelial cells of the tumor and endometrial abnormalities. These findings, together with a review of the literature, suggest that the usual Brenner tumor is not associated with specific steroidogenesis. Rare massive Brenner tumors may, however, be capable of androgenic or estrogenic activity.

Aromatase↗

Thorotrast-associated gliosarcoma. Including comments on thorotrast use and review of sequelae with particular reference to lesions of the central nervous system.

The occurrence of a glioblastoma with sarcoma, a gliosarcoma, in the left frontal-temporal area of a 49-year-old woman with a history of Thorotrast exposure, is described. Thorotrast-laden histiocytes and free Thorotrast material were found in both components of the tumor. An overlying, adherent dural cranial lesion was found to contain massive deposits of Thorotrast embedded in a dense fibrotic and sclerotic stroma with focal calcification. These features are typical of "Thorotrastoma." Thorotrast stains greenish-brown with hematoxylin and eosin and appears as refractile granular particles of relatively uniform size either within histiocytes or as free material. The radioactivity of the deposits was confirmed through the use of a scintillation counter, and 232 thorium was definitively identified though the use of scanning electron microscopy with energy-dispersive X-ray analysis. Immunohistochemical studies of the tumor demonstrated glial fibrillary acid protein (GFAP) immunoreactivity in areas of glioma and focal vimentin and actin immunoreactivity in areas of sarcoma. Thorotrast-associated lesions of the central nervous system (CNS) are infrequently reported, and a Thorotrast-associated gliosarcoma has not yet been reported. The use of Thorotrast, its radiobiology, and sequelae are reviewed with particular emphasis on lesions occurring in the CNS.

Brain Neoplasms↗

Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria.

Fifty-three cases of mammary carcinoma originally diagnosed as medullary carcinoma (MC) or infiltrating duct carcinoma (IDC) with medullary features were reviewed and reclassified using the strictly defined histologic criteria applied a decade ago by Ridolfi et al. Our study interval (1961 to 1982) allowed for a minimum follow-up of 5 years for each patient, with a mean follow-up period of 7.2 years. When reclassified, 24 tumors fulfilled the criteria for MC, 16 tumors were determined to be atypical MC, and ten tumors were found to be IDC; the observed 5-year survival rates were 95%, 80%, and 70%, respectively. These findings confirmed those of other investigators, that when specific criteria are applied, MC proves to be a form of mammary carcinoma with a favorable prognosis. However, we also found that when tumors were excluded from the MC category solely on the basis of in situ carcinoma, focal marginal infiltration, or a sparse mononuclear infiltrate, the survival rate of these patients was similar to that of patients in the medullary category. Thus, we propose that one of these criteria alone should not suffice to exclude the diagnosis of MC. On the other hand, tumors with two or more of these atypical features, or with extensive marginal infiltration, no mononuclear cellular infiltrate, and/or less than 75% syncytial growth, should be classified as IDC with medullary features. Typical MC with bland nuclei or a focal microglandular growth pattern only were not observed in this series; however, these findings should probably also cause a tumor to be classified in the IDC category. By dividing our cases into two rather than three groups, we found a statistically significant difference between the survival rates of 94% and 64% for MC (34 tumors) and IDC (14 tumors), respectively. Although the latter figure probably exceeds the survival rate for IDC without medullary features, the difference does not appear great enough to warrant a separate diagnostic category.

Adult↗

Asymptomatic blood methanol in emergency room patients.

Over a four-month period, methanol was found in the blood of 18 patients among 687 sequential emergency room admissions screened for alcohols by gas chromatography. In the patients with positive results, blood ethanol ranged from 6 to 570 mg/dL (1.3-123.7 mmol/L), blood methanol from 2.3 to 4.0 mg/dL (0.72-1.25 mmol/L). Methanol exposure during preparation of the sampling site or in the course of specimen handling, ingestion of denatured alcohol, as well as methanol production from the metabolism of aspartame are ruled out as causes for these findings. The authors conclude that endogenous methanol production is the probable major cause, while methanol as a fermentation congener may be a contributory minor cause.

Alcoholism↗