Immunodiagnosis of melanoma using chimpanzee antihuman melanoma antiserum.

Three cases of metastatic malignant lesions are presented. By conventional pathologic examination these lesions were diagnosed as undifferentiated carcinomas. They were studied using a chimpanzee antiserum specific for human melanoma-associated antigens. In each case, cells from the tumor were reactive with the anti-melanoma antiserum. The tumors were also studied using the DOPA test. All three tumors were positive in the DOPA test, suggesting the presence of tyrosinase within the tumor cells. The results suggest that serologic identification of melanoma may provide a rapid, inexpensive means for tumor diagnosis.

Biochemical correlates of morphologic differentiation in human breast cancer.

In 115 breast carcinoma tissues, histologica grade and cell cytosol concentrations of estrogen receptor (ER) and progesterone receptor (PR) and two breast cyst fluid proteins (gross cystic disease fluid protein [GCDFP-15] and nonreceptor progesterone-binding protein [PBP]) were deterMined. Higher levels (expressed as femtomoles per milligram of protein) of ER (128 +/- 28 versus 11 +/- 1, P less than 0.001) and PR (82 +/- 16 versus 3 +/- 1, P less than 0.001) were found in grade 1 (well-differentiated) carcinomas as compared with grade 3 (poorly differentiated) carcinomas. Similarly, higher concentrations (expressed as nanograms per milligram of cytosol protein) of GCDFP-15 (2110 +/- 840 versus 210 +/- 40, p less than 0.001) and PBP (4920 +/- 1200 versus 370 +/- 60, P less than 0.001) were found in grade 1 as compared with grade 3 carcinomas. Tumor cytosols that contained low levels of both cyst proteins (less than 225 ng/mg GCDFP-15 and less than 750 ng/mg PBP) had a high incidence of grade 3 (35 of 46, 78%) or grade 2 (15 of 46, 33%) histologic findings and had a high incidence of receptor-negative specimens (27 of 52, 52%). Based on these cutoff levels, grade 2 lesions were subdivided into a "high" cyst protein group, which had ER and PR levels similar to grade 1 tumors (93.1 +/- 26.7 for ER and 84.7 +/- 32.4 for PR, P greater than 0.3), and a "low" group, which had receptor values similar to grade 3 carcinomas (14.1 +/- 5.3 for ER and 9.1 +/- 5.2 for PR, P less than 0.3). Although the mean cytosol content of carcinoembryonic antigen (CEA) was significantly higher in malignant tissues (125 +/- 27 ng/mg cytosol protein) than in benign tissues (4.8 +/- 1 ng/mg cytosol protein), the CEA content was not significantly different between grades 1 and 3 tumors.

Germ cell malignancies of the ovary.

Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of "pure" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators.

Fatal pulmonary bile embolism following acute acalculous cholecystitis.

A 52-year-old man died during reoperation for bleeding after the development of acute postoperative acalculous cholecystitis. While the liver was being manipulated during surgery, the pulmonary artery diastolic pressure increased suddenly, cardiac output and blood pressure decreased, and soon afterward the patient had a cardiac arrest from which he could not be resuscitated. During resuscitative efforts, the maximum partial arterial oxygen pressure achieved was only 55 mm Hg despite 100% inspired oxygen. At autopsy, bile aggregates were found within necrotic liver parenchyma, portal and central vein branches, and numerous pulmonary arterioles and capillaries. The pulmonary arterial bile most likely resulted from embolization of inspissated hepatic bile aggregates during surgical manipulation.

Surgical management of pancreatic lymphoma.

The clinical and pathologic records of 12 patients with pancreatic lymphoma were reviewed retrospectively to determine distinguishing clinical features. Radiologically, all patients had large abdominal masses in the region of the pancreas. Preoperative percutaneous cytologic biopsy specimens failed to make the diagnosis, and two specimens were interpreted incorrectly as poorly differentiated adenocarcinoma. The diagnosis was difficult to make in two cases, even at laparotomy. Four patients underwent a biliary bypass, and two underwent a concomitant gastric or duodenal bypass. Two patients died postoperatively. Four patients responded well to chemotherapy and/or radiation therapy, and two did not have any recurrences at 3 and 7 years postoperatively. Although rare, lymphoma should be considered in patients with undiagnosed pancreatic masses. The diagnosis may only be made with appropriate preoperative or intraoperative suspicion, and treatment may be rewarding, particularly in comparison with pancreatic adenocarcinoma.

Cutaneous pigmentation secondary to amiodarone therapy.

Amiodarone (Cordarone) is an iodinated cardiac antiarrhythmic drug that causes a slate-gray discoloration of the sun-exposed skin and a yellow-brown stippling of the cornea. Histopathologically, biopsy specimens of aminodarone pigmentation sites disclose yellow-brown refractile granules in the reticular dermis. These granules were characterized by transmission electron microscopy as being concentrically arranged intralysosomal inclusions ("myelinlike" bodies) in dermal endothelial cells and perivascular smooth-muscle cells. Electron probe x-ray analysis of these same inclusions disclosed definite peaks for iodine, evidence for the presence of amiodarone or a metabolite of the drug at these sites. Amiodarone, then, concentrates in lysosomes and causes an accumulation of lipids similar to what has been seen with other cationic amphiphilic compounds, such as the glycosphingolipid stored in Fabry's disease. Amiodarone must be recognized as a cause of a drug-induced lipid storage disease with cutaneous and corneal manifestations.

Thymolipoma in association with myasthenia gravis.

A patient with a 100-g thymolipoma and myasthenia gravis experienced marked improvement in neuromuscular symptoms following removal of the tumor. Although 60 examples of thymolipoma have been reported, we believe that this is the first example of this tumor associated with myasthenia gravis. The clinical, radiologic, and histopathologic manifestations of previously reported cases of thymolipoma are discussed in relation to our patient's case.

Lymphocytic lymphoma and systemic lupus erythematosus: their coexistence with antibody to the Sm antigen.

The serologic and clinical features of a 32-year-old women with coexistent systemic lupus erythematosus and lymphoma were studied. A cervical node biopsy specimen demonstrated nodular, poorly differentiated lymphocytic lymphoma; subsequent development of polyarthralgias prompted evaluation for connective-tissue disease, and a high titer of antinuclear antibody was found. Immunochemical studies proved that this antibody was directed to the Sm antigen, a serologic finding highly specific for systemic lupus erythematosus. This antibody has been maintained throughout the course of the patient's disease, characterized by persistent lymphadenopathy, pleuropericarditis, arthritis, hypocomplementemia, hyperglobulinemia, and a slight elevation of titers of anti-DNA antibody. The course of the lymphoproliferative disorder has been consistent with that of an indolent non-Hodgkin's lymphoma. In sera from other patients with lymphoproliferative disorders, anti-Sm antibody was not found. These findings emphasize the importance of establishing the antigenic specificity of antinuclear antibodies detected in the sera of patients with neoplasia.

Paraovarian cysts associated with prenatal diethylstilbestrol exposure. Comparison of the human with a mouse model.

The association of prenatal exposure to diethylstilbestrol (DES) and abnormalities in structures of müllerian (paramesonephric) origin has been well documented. In a murine model, exposure to DES in utero results in persistent mesonephric remnants in adult female mice. Six women exposed prenatally to DES had paraovarian cysts excised during routine gynecologic surgery; and in 4, histologic abnormalities were observed, including thickened fibromuscular walls with tall columnar epithelium in a papillary or pseudoglandular configuration. Four of 25 nonexposed and 8 of 9 DES-exposed infertile women undergoing surgery for infertility had paraovarian cysts, and the difference was statistically significant (P less than 0.02). These findings raise the possibility that structures derived from the mesonephric ducts or tubules may also be affected in women exposed in utero to DES.

Multiple hairy pacinian neurofibromas (nerve-sheath myxomas).

Pacinian neurofibromas are unusual tumors with components that resemble Vater-Pacini corpuscles and are probably a variant of nerve-sheath myxoma. Lesions composed predominantly of these structures have occurred on or near the buttocks in three previously reported cases; however, all were solitary and congenital. Two of these patients, with lesions that closely resembled mature Vater-Pacini corpuscles, had underlying skeletal anomalies. Our patient had multiple hairy pacinian neurofibromas (nerve-sheath myxomas) on the buttocks that were not associated with radiographic evidence of and underlying skeletal anomaly. Skeletal anomalies may be associated with "sacrococcygeal paciniomas" but probably not with true pacinian neurofibromas.

Correlation of estrogen and progesterone receptors with histologic differentiation in endometrial adenocarcinoma.

Endometrial carcinomas from 58 patients were graded histologically, and the histologic grade was compared with the estrogen and progesterone receptor content of the tumor tissues. Receptor content was determined by multiple concentration saturation analysis and sucrose density gradient analysis. A positive correlation was found between the presence of estrogen and progesterone receptors and the degree of tumor differentiation. The majority (85%) of well-differentiated lesions contained significant amounts of both steroid receptor proteins. In contrast, only 13% of the poorly differentiated lesions were characterized by the presence of detectable levels of both estrogen and progesterone receptor proteins. The relationship of receptor content and degree of differentiation to prognosis and potential for response to hormonal therapy is discussed.

PIP: The histologic grade of endometrial carcinoma is compared with the quantitation of both estrogen and progesterone receptor proteins. 58 patients of 100 consecutive cases of endometrial neoplasia seen at Duke University Medical Center had adequate tissue for complete evaluation. The study covered a 22-month period from September 1, 1976 to July 1, 1978. The patient population ranged in age from 28-92 years and had both locally invasive and metastatic endometrial neoplasia. Receptor content was determined by multiple concentration saturation analysis and sucrose density gradient analysis. A positive correlation was found between the presence of estrogen and progesterone receptors and the degree of tumor differentiation. 85% of well-differentiated lesions contained significant amounts of both steroid receptor proteins while only 13% of poorly differentiated lesions were characterized by the presence of detectable levels of both estrogen and progesterone receptor proteins. Attention is directed to the relationship of receptor content and degree of differentiation to prognosis and potential for response to hormonal therapy.

Management of stage IA carcinoma of the cervix.

One hundred fourteen patients with Stage IA carcinoma of the cervix were retrospectively reviewed in regard to depth of invasion, capillary-like space involvement, stromal reaction, status of conization margins, and the incidence of lymph node metastasis. Type of treatment, recurrences, and deaths were also evaluated. Patients with less than 3 mm invasion can be treated conservatively, including conization, if fertility is desired. No lymph node metastasis or recurrence appeared in this group of patients irrespective of type of treatment. Patients with 3 to 5 mm invasion do appear to be at higher risk for recurrence, but conservative therapy may be used in individualized situations. Size of conization and status of surgical margins appear to be important determining factors in regard to conservative therapy. Data in the literature, as well as our experience, although limited, suggest that the status of capillary-like space involvement does not influence lymph node metastasis or recurrence. Invasion of 5 mm or more in depth should be treated as a Stage IB occult lesion.

The correlation of histologic changes in the human breast with the menstrual cycle.

Histologic changes in the normal human mammary gland associated with the menstrual cycle were sought in tissues derived from a defined population of patients undergoing subcutaneous mastectomy or reduction mammoplasty for reasons other than neoplasia. Ninety patients were selected for their regular menstrual cycling, abstinence from hormone use, and absence of disease which might influence pituitary-ovarian cycling. Morphologic changes in the mammary stromal and epithelial components were identified as they related to specific pituitary-ovarian events, and histologic criteria were identified that allowed reproducible morphologic categorization of the mammary gland into five specific phases: proliferative (Days 3-7); follicular phase of differentiation (Days 8-14); luteal phase of differentiation (Days 15-20); secretory (Days 21-27); and menstrual (Days 28-2). Double-blind reviews of tissues confirmed the validity and the reproducibility of these histologic criteria in identifying the menstrual phase. The findings further characterize the morphologic correlates of hormone responsiveness of the normal human mammary gland. The recognition of menstrual-cycle-dependent histologic changes may be expected to provide a basis for extending the interpretation of the morphologic characteristics of the breast in surgically acquired specimens that may be associated with hormonal aberrations.

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.