Granular cell tumors of the breast. Steroid receptor analysis and localization of carcinoembryonic antigen, myoglobin, and S100 protein.

Granular cell tumors occur in a variety of sites, including the breast (6%). Origins from histiocytic, myogenic, fibroblastic, and neurogenic elements have been proposed. Female predominance suggests that estrogenic hormones are involved. Four granular cell tumors of the breast and one in an axillary lymph node were studied for sex steroid receptor content, myoglobin, carcinoembryonic antigen, and S100 protein localization. Antimyoglobin antibody did not localize in these tumors. Carcinoembryonic antigen and S100 protein localized in the cytoplasm of these tumors. Neither estrogen nor progesterone receptor protein were present in these tumors in detectable amounts. Ultrastructural features of these granular cell tumors in the breast are similar to those described for extramammary granular cell tumors. These studies agree with previous data that suggest a neurogenic origin for granular cell tumors.

Correlation of mean nuclear area with estrogen receptor content in aspiration cytology of breast carcinoma.

Thin needle aspirates of 42 consecutive breast carcinomas were obtained at the time of excisional biopsy. Nuclear diameters of 100 cells from each case were measured, and the nuclear areas were calculated. The concomitantly acquired histologic sections were reviewed and assigned a histologic grade according to the National Surgical Adjuvant Breast Project protocol no. 4. Estrogen receptor (ER) content was analyzed by both the DCCA and SDGA techniques. The ER content of each case was then compared to both the mean nuclear area of the cells on the cytologic smears and the histologic grade. All 16 cases with mean nuclear areas of less than 60 sq micrometer contained significant levels of ER (greater than 10 fmol/mg protein), as did 6 of 11 cases with nuclei between 60 and 90 sq micrometer. Only 5 of 15 cases with nuclei larger than 90 sq micrometer contained significant ER levels. Comparison of the sensitivity, specificity and predictive values of both techniques suggests that a quantitative assessment of nuclear area in cytologic thin needle aspirates correlates more closely with ER content than does histologic grading.

The correlation of cytologic grade and steroid receptor content in effusions of metastatic breast carcinoma.

The synthesis of estrogen receptor (ER) and progesterone receptor (PR) proteins by mammary carcinoma cells is a manifestation of biochemical differentiation. This study was an attempt to determine whether this acquisition of functional differentiation correlates with cytologic differentiation. Malignant effusions from 30 patients with mammary carcinoma were studied. ER and PR were measured by sucrose density gradient analysis. Membrane filters of the effusions were prepared, and a cytologic grade was assigned based primarily on nuclear size and nucleolar prominence. Ten cases were classified as well differentiated, 15 as moderately differentiated and 5 as poorly differentiated. Four of the ten well-differentiated neoplasms contained greater than 7 fm/mg protein ER and PR. Six of the 15 moderately differentiated neoplasms contained significant levels of ER and PR. None of the five poorly differentiated neoplasms contained significant receptor. This study strongly suggests that there is a correlation between the cytologic grade and steroid receptor content in metastatic mammary carcinoma. In a prospective analysis of thin needle aspirations of breast cancers now underway, the nature of this relationship is being further defined.

Multicentric renal oncocytoma.

Renal cell oncocytomas are benign tumors of tubular epithelial origin. They usually occur as single nodules and may be confused clinically with renal cell carcinoma. We report an unusual case of multiple, discrete renal cell oncocytomas. The characteristic gross and light microscopic, and ultrastructural features are described. The potential of multicentricity is confirmed and its implications for therapy are discussed.

Adrenocorticotropin production by a mammary carcinoma.

A patient with clinical hypercortisolism and an infiltrating ductal carcinoma of the right mammary gland is presented. Provocative testing of adrenal function demonstrated the pattern of ectopic adrenocorticotropic hormone (ACTH) production. Ultrastructural analysis of the tumor revealed 150-200 nm electron-dense granules that when primarily fixed in OsO4 appeared as membrane-bound, centrally dense cored granules. ACTH was extracted from the tumor tissue and immunocytochemically localized in the tumor cell cytoplasm. A clinically significant level of estrogen receptor protein was present in the tumor tissue (120 fmol/mg protein). This case confirms the ability of mammary carcinoma to produce the ectopic ACTH syndrome.

Apocrine differentiation in human mammary carcinoma.

Six invasive carcinomas that contained apocrine differentiation as the primary morphologic pattern were selected from a series of 1500 prospectively examined breast carcinomas (0.4%). While apocrine features were seen in many breast tumors, these six cases were identified by uniformly fine granular, pale, eosinophilic cytoplasm with apical cytoplasmic projections similar to that seen in apocrine metaplasia. In each example, ultrastructural analysis revealed the presence of numerous 400-600 nm membrane bound vesicles with dense homogeneous osmophilic cores. These granules clustered toward the apex of the cytoplasm in the majority of the epithelial cells. All six tumors were deficient in high-affinity, low-capacity 8S estrogen and progesterone proteins, while a high-capacity, low-affinity, nonsaturable 4S progesterone-estrogen binding protein was observed. Cortisol did not bind to this protein. These observations characterize the ultrastructure of apocrine carcinoma as a variant of human mammary carcinoma.

Correlation of estrogen and progesterone receptors with histologic differentiation in mammary carcinoma.

Using a modification of the histologic grading system of the NSABP, we observed a trend towards higher levels of estrogen (E2R) and progesterone receptor (PR) content in well (grade I) and moderately (grade II) differentiated mammary carcinomas. This relationship between receptor content and histologic grade is enhanced by considering estrogen and progesterone receptor simultaneously. The rank correlation between the quantitative levels of E2R and PR was 0.74 among histologic grade I tumors and 0.64 among histologic grade II tumors. Among the grade III carcinomas, the majority of tumors displayed either a paucity of measurable receptor or a divergence between levels of estrogen versus progesterone receptor (r = 0.19). The use of ultrastructural evaluation of features of differentiation is discussed in the evaluation of grade III tumors and in the evaluation of specific histologic types of mammary carcinoma.

Comparison of sex steroid receptor analyses and carcinoembryonic antigen with clinical response to hormone therapy.

This study corroborates previous reports which suggested the efficacy of estrogen receptor (ER) analysis in predicting responses of patients with metastatic mammary carcinoma to hormonal therapeutic manipulation. The predictive value of multiconcentration titration and sucrose density gradient analyses of ERs and progesterone receptors (PRs) are compared. The predictive value of ER analyses can be improved by the discrimination of 8S versus 4S binding species or by the use of PR analysis in combination with ER analysis. The tumor-associated antigen, carcinoembryonic antigen (CEA), is evolving as an important quantitative aid in evaluating the clinical responses to patients receiving hormonal therapy.

Adenocarcinoma of Bartholin's gland.

Bartholin's gland carcinoma is an uncommon disease representing 0.1% of all female genital malignant neoplasms. Five Bartholin's gland adenocarcinomas were selected by the criteria of Chamlian and Taylor. Three patients died from metastatic disease within four years; two are free of apparent disease 14 months and 13 years, respectively, after initial diagnosis. Poor prognosis was associated with large tumor size, poor histopathologic differentiation, and lymph node involvement. Transmission electron microscopy verified the glandular nature of the poorly differentiated lesions. All five tumors demonstrated junctional complexes, abundant rough endoplasmic reticulum, secretory vacuoles, and glandular formation. Low levels of estrogen receptor and moderate levels of progesterone receptor were present in the one case measured. Endogenous peroxidase, and inducible enzyme in estrogen-sensitive tissues, was observed in two of the five tumors.

Energy dispersive x-ray detection of thorium dioxide.

Since the recognition of the development of certain malignant neoplasms in association with thorium dioxide (Thorotrast), its presence has been documented by light microscopic appearance and time-consuming autoradiography. Energy dispersive x-ray microanalysis can be used in the rapid documentation of thorium in paraffin-embedded tissues and it is confirmed that thorium is the principal component of the granular deposits described by light microscopy.

Cytologic detection of hepatic metastases.

Cytologic preparations and histologic specimens from 404 liver biopsies were reviewed. The cytologic specimens were prepared from the saline rinsings of the Klatskin biopsy needle. Malignant neoplasms were detected by both methods in 50 cases. In seven cases, neoplasms were diagnosed by cytologic techniques alone; in nine cases neoplasms were present in the biopsy only. No false-positive cytologic diagnoses of malignancy occurred. The results of this study show that cytologic examination of the rinsings of the biopsy needle is a sensitive and highly specific adjunct to biopsy in the detection of hepatic metastases.

Dirofilaria immitis: a zoonosis of clinical concern.

Dirofilaria immitis, the dog heartworm, is responsible for an endemic zoonosis in the Southeastern United States. The nematode is capable of infesting the lungs of man, causing pulmonary nodules. The epidemiologic, morphologic, and clinical features of D immitis infestation are discussed.