Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882).

To investigate the effect of adding tamoxifen to megestrol in the hormonal therapy for advanced endometrial cancer, 66 patients were entered in this study. Initially, 41 patients were randomized to either the standard progestin therapy of megestrol or to the combination of megestrol and tamoxifen between October 1982 and October 1984. The megestrol arm was terminated because of poor accrual and 25 patients were directly assigned to the combination arm. Among the 20 eligible cases on the megestrol arm, the response rate of 20% consisted of I complete response and 3 partial responses. The response rate on the megestrol plus tamoxifen arm was 19% with 1 (2%) complete response and 7 (17%) partial responses among 42 eligible cases. The median survival times were 12.0 months and 8.6 months, respectively. Only mild and moderate toxicities were observed on megestrol compared with more toxic complications observed on the combination of megestrol and tamoxifen, including a life-threatening case of pulmonary embolism. Although we could not carry out a comparative evaluation as intended, we conclude that the combination of megestrol and tamoxifen offers no clinical advantage over megestrol alone in the treatment of advanced endometrial carcinoma.

A retrospective analysis of breast cancer based on outcome differences.

We reviewed tumors from two groups of patients with breast cancer, distinguished by differences in outcome. One group (85 cases) survived more than 8.5 years without tumor recurrence; the other 85 cases had recurrent disease within 2 years. Histologic and immunocytochemical studies on all cases were performed without patient identifiers and prior to review of clinical prognostic factors. As expected, lymph node and estrogen receptor status differed substantially between the groups, but menopausal status and family history for breast cancer did not. We noted that 27% of node-negative patients died within 5 years, and nine patients with four or more tumor-containing nodes were symptom-free for over 8.5 years. Histologic grade (degree of tubule formation) and nuclear grade (including mitotic rate) differed significantly between the groups, as did vascular invasion, including both lymphatics and blood vessels. Prognostic value attached to tumor border only when fat was invaded without fibroblastic or inflammatory response (P = .012). Subgrouping cases of infiltrating ductal carcinoma (not otherwise specified) was prognostically informative in the B subgroup, 69% of whom were in the rapidly recurrent tumor group. Immunocytochemical staining for c-erbB-2 was positive in 19.3% of cases, but was equally distributed between the two outcome groups. We conclude that traditional histologic parameters are highly informative, and that c-erbB-2 studies do not increase the value of histologic diagnosis.

Pulmonary calcification caused by Pneumocystis carinii pneumonia. A clinicopathological study of 13 cases in acquired immune deficiency syndrome patients.

Pulmonary microcalcifications were identified in 13 patients with Pneumocystis carinii pneumonia (PCP) and acquired immune deficiency syndrome (AIDS). Several patterns of calcification were noted including bubbly, plate-like, elongate, and conchoidal forms. All calcifications contained P. carinii cysts within them as demonstrated by Grocott's methenamine silver stain. In eight of the 13 cases, the typical intra-alveolar exudate of P. carinii was absent. Therefore, the calcifications were the only histopathologic indication of prior P. carinii infection. The above-mentioned calcifications are important because in five cases they occurred without a prior diagnosis of PCP, subsequent therapy, or prophylaxis. This indicates that in some patients there is destruction of P. carinii organisms with subsequent calcification, and this can occur without therapy.

Fine needle aspiration biopsy of cystic benign lymphoepithelial lesion of the parotid gland in patients at risk for the acquired immune deficiency syndrome.

Cystic benign lymphoepithelial lesion (BLL), a previously rare lesion of the parotid gland consisting of marked lymphoid hyperplasia with accompanying squamous-lined cysts, has recently been described in patients with the acquired immune deficiency syndrome (AIDS) or AIDS risk factors. Thirteen fine needle aspiration (FNA) samples of parotid gland masses from patients with AIDS (one case), AIDS risk factors (five cases) or denial of AIDS risk factors (two cases) and a histopathologic diagnosis of BLL were examined. The FNA features that correlated best with the histopathologic findings were (1) a heterogeneous lymphoid population, (2) scattered single and/or clustered foamy macrophages and (3) superficial and/or anucleated squamous cells. Most aspirates showed some combination of these three components. The differential diagnostic considerations, the clinical and radiologic correlations and the relationship of this lesion to HIV infection are discussed. Patients with parotid masses whose aspirates consist of some combination of squamous cells, lymphocytes and foamy macrophages should be questioned for possible AIDS risk factors.

Bacillary angiomatosis presenting as a soft-tissue tumor without skin involvement.

A patient with human immunodeficiency virus infection presented with a soft-tissue mass which histologically and clinically mimicked an angiosarcoma. Ultrastructural study, however, revealed bacteria identical to those seen in cutaneous bacillary angiomatosis, but the patient had no skin lesions. To our knowledge, this represents the first report of soft tissue involvement by bacillary angiomatosis without the presence of skin lesions.

Limitations in the CT diagnosis of acute diverticulitis: comparison of CT, contrast enema, and pathologic findings in 16 patients.

Pitfalls in CT diagnosis of acute diverticulitis were investigated in 16 patients with the disease who had misleading or equivocal CT features. The CT appearance was correlated with contrast enemas (13 cases) and with surgical assessment and pathologic evaluation of resected specimens (12 cases). Limitations in the CT diagnosis were related to (1) marked thickening of the colonic wall, between 1 and 3 cm in cross section simulating colonic neoplasm (all patients); (2) inability to visualize small amounts of fibropurulent exudate in the absence of pericolic inflammatory changes (eight patients); (3) failure to detect discrete intramural abscess (five patients). Resected surgical specimens available in 12 cases proved that colonic wall thickening was caused by muscular hypertrophy and various degrees of submucosal inflammation, edema, fibrosis, or focal organized inflammatory tissue. Contrast enema was useful in 10 out of 13 patients by excluding carcinoma of the colon and confirming the diagnosis of acute diverticulitis.

Phase II trial of continuous drug infusions in advanced ovarian carcinoma: acivicin versus vinblastine.

Sixty-six women with advanced ovarian carcinoma of coelomic epithelial origin were randomly assigned to one of two intravenous single-agent infusion treatment regimens, either acivicin (60 mg/m2/course, administered as a 72-hr infusion) or vinblastine (7.5 mg/m2/course, administered as a 120-hr infusion) every three weeks. All had progressive disease after one to three prior chemotherapeutic regimens. Of 62 patients who were evaluable for response, survival and toxicity, there was one partial response (2%) produced by vinblastine. Median survival was 13 weeks on either treatment arm. Three patients (10%) on the acivicin arm experienced life-threatening myelosuppression. Severe toxicities resulting from this treatment included myelosuppression (26%), neurotoxicity (16%), mucositis (3%) and vomiting (6%). Vinblastine was associated with one lethal pneumonia and five cases of life-threatening myelosuppression (16%); severe toxicities included myelosuppression (58%), genitourinary toxicity (6%), infection (3%), and edema (3%). Neither regimen produces useful clinical results in patients who have relapsed after prior chemotherapy for ovarian carcinoma.

Perirectal abscess in the Hermansky-Pudlak syndrome.

The Hermansky-Pudlak syndrome (HPS) is a triad of tyrosine-positive albinism, platelet dysfunction, and the deposition of an abnormal ceroid-like pigment in the tissues. Complications of the syndrome, such as pulmonary fibrosis, renal failure, and cardiomyopathy, have been described. Granulomatous colitis has been documented in several families with the HPS. The bowel disease of the HPS is a unique type of inflammatory bowel disease with clinical features suggestive of idiopathic ulcerative colitis and pathologic features suggestive of Crohn's disease. Analogous to the presentation of Crohn's disease with perianal and perirectal involvement, we describe the occurrence of perianal disease and a perirectal abscess in a 29-yr-old woman with HPS and mild granulomatous colitis.

Cystic parotid lesions in patients at risk for the acquired immunodeficiency syndrome.

Twenty-three patients at risk for the acquired immunodeficiency syndrome presented with cystic lesions of the parotid gland. Fourteen patients had unilateral parotid cysts and nine had bilateral enlargement. Ten patients were positive for antibodies to the human immunodeficiency virus (HIV), three were negative for antibodies to the human immunodeficiency virus, and ten refused testing. Fine-needle aspiration cytology and computed tomography were helpful in making the diagnosis of benign lymphoepithelial cyst. Superficial parotidectomy confirmed the diagnosis. Concurrent malignancy (Kaposi's sarcoma) was diagnosed in one patient from a parotid specimen. Follow-up has ranged from four months to five years.

Benign lymphoepithelial parotid cysts and hyperplastic cervical adenopathy in AIDS-risk patients: a new CT appearance.

The contrast material-enhanced computed tomographic (CT) scans of 18 patients at risk for acquired immunodeficiency syndrome (AIDS) who had painless facial swelling were reviewed. All scans demonstrated parotid cysts and diffuse homogeneous cervical adenopathy. The cysts were bilateral in all but three cases. Eleven of 13 patients tested had antibodies to the human immunodeficiency virus (HIV), and two of the five untested patients later developed AIDS. The authors believe that the CT findings of multiple parotid cysts and cervical adenopathy suggest that the patient may be infected with the HIV virus, and the radiologist should alert the referring physician so that appropriate precautions and treatment may be initiated.

Eosinophilic pustular folliculitis in patients with acquired immunodeficiency syndrome. Report of three cases.

Eosinophilic pustular folliculitis is a rare disease. Highly unusual is its occurrence in three patients with acquired immunodeficiency syndrome (AIDS), described herein. This association may be the result of immunologic aberrations that are described in AIDS and may represent an abnormal reaction to skin saprophytes and dermatophytes.

Seborrheic-like dermatitis of acquired immunodeficiency syndrome. A clinicopathologic study.

We studied twenty-five skin biopsies from twenty-one patients with acquired immunodeficiency syndrome or its prodrome who presented with the "seborrheic dermatitis" associated with acquired immunodeficiency syndrome and compared them with an equal number of biopsies from patients with seborrheic dermatitis who had neither acquired immunodeficiency syndrome nor its risk factors. We found that although the eruption in acquired immunodeficiency syndrome closely resembles seborrheic dermatitis, histologically it is distinctive because it shows spotty keratinocytic necrosis, leukoexocytosis, and a superficial perivascular infiltrate of plasma cells and, frequently, neutrophils that show occasional leukocytoclasis. In long-standing lesions, hyperkeratosis is often present. None of these histologic features are commonly encountered in seborrheic dermatitis, psoriasis, or other eruptions known to us.

Acquired immunodeficiency syndrome. Clinicopathologic study of 56 autopsies.

We studied 56 patients with acquired immunodeficiency syndrome who underwent autopsy at the New York University Medical Center. We uncovered several entities that were not previously described or emphasized in prior series. These were as follows: (1) three cases of necrotizing arteritis with cytomegalovirus inclusions; (2) dissemination in 95% of cases of Kaposi's sarcoma; (3) unusual clinical and histologic presentations of Kaposi's sarcoma presenting diagnostic difficulties for both clinicians and pathologists; and (4) a very high incidence of serious nonmycobacterial infections. In addition, previous autopsy studies have disagreed over such matters as the incidence of disseminated candidiasis, hemophagocytosis, and severe adrenal necrosis in acquired immunodeficiency syndrome. All of these studies, except one, involved ten to 12 cases each. Our study of 56 cases helps to resolve these disagreements.

Immunostaining for carcinoembryonic antigen does not discriminate for early recurrence in breast cancer. The ECOG experience.

Carcinoembryonic antigen (CEA) immunohistochemistry was evaluated by 11 surgical pathologists with sections from 147 postmenopausal women with node-positive breast cancer. Carcinoembryonic antigen staining in breast cancer tissues has been correlated with a worse prognosis. This association was studied with a clinically characterized population of Eastern Cooperative Oncology Group (ECOG) patients using precisely the peroxidase-antiperoxidase methodology which had been employed in another published study. In 50% of the cases, the study pathologists were uncertain whether CEA was or was not present in the cancers. Various groupings of the pathologists' interpretation were compared with the observed disease-free intervals in the patients. These analyses suggested no association of perceived CEA staining with the biological course of the cancers. Two reference pathologists who examined the sections in a similar way also gave non-prognostic interpretations. There is no convincing evidence that pathologists can reliably interpret the CEA content in the same breast cancer tissue sections. There is no observed correlation between immunohistochemical evidence of CEA in a breast cancer tissue section and the biological behavior of that cancer.

Hermansky-Pudlak syndrome: a clinicopathologic study.

The Hermansky-Pudlak syndrome is a rare disease characterized by multisystemic involvement. Seven families with the disorder were identified in the Puerto Rican population of one municipal hospital, suggesting that the incidence in the Puerto Rican community is sufficient to warrant both dissemination of information about the disease and further investigation. The present study was an attempt to achieve both of these goals.

Epidemiology of minimal breast cancer among women screened in New York City.

A case-control study based on a screened population in New York City examined epidemiologic risk factor differences between minimal breast cancer (in situ and small invasive carcinomas) and all other breast carcinomas, referred to as clinical breast cancer. Histopathologic re-review of the original slides identified 113 minimal and 792 clinical breast cancers among 1,290 eligible cases; 2,173 randomly selected screenees served as controls. Among those who developed cancer, black women were twice as likely to develop minimal, as compared to clinical, breast cancer. Women who were less than 20 years of age at first live birth had more than double the probability of being diagnosed with minimal breast cancer, whereas women with first live birth at age 30 years or greater and nulliparous women were at 1.5 times the risk of clinical breast cancer. The relative proportion of minimal breast cancer increased with increasing number of children breast fed, being twofold among women who nursed 2 children or more. Unlike clinical breast cancer, minimal breast cancer was not associated with either family history of breast cancer or obesity. Meaningful histologic differences were not apparent between the case subgroups. Except possibly for obesity, these results could not be explained by any plausible diagnostic bias.

Fibrous hamartoma of infancy: an ultrastructural study.

The fine structures of three fibrous hamartomas of infancy were studied. All three components of these lesions were examined. The principal cells in the fibrous and myxoid areas were fibroblasts. Cells with stellate cytoplasmic projections were more prominent in myxoid areas. Myofibroblasts were abundant in two cases and not in the other. The adipose tissue component was formed by lipocytes and occasional preadipose fibroblasts. Blood vessels were more numerous in myxoid areas. Larger vessels were accompanied by smaller vessels and by clusters of cells with primitive junctions, suggesting early blood vessel formation. Some small vessels were surrounded by concentric layers of mesenchymal cells, as if attempting to form media. Electron microscopy seems to confirm the hamartomatous nature of fibrous hamartomas of infancy. The lesion appears to recapitulate the formation of blood vessels and fat, as seen in fetal tissues. Cellular myxoid areas showed prominent vasoformative proliferation, which decreased in the adipose tissue and was least prominent in the dense fibrous component. The latter may represent the end stage of the fibrous proliferation.