Deborah J. Gersell

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.

Histologic types of benign breast disease and the risk for breast cancer

Specific histologic types of benign breast disease (BBD) may increase breast cancer risk. The authors analyzed data from a population‐based, case‐control study of women aged 20 to 54 with newly diagnosed breast cancer and control subjects randomly selected from the general population. A panel of pathologists classified the histologic findings of biopsy slides for 433 women with breast cancer and 261 control subjects, all of whom had a history of biopsy for BBD, as to the presence of epithelial hyperplasia, atypia, and other histologic features. When compared with women who had never had a breast biopsy, women with BBD without hyperplasia had an odds ratio of 1.5 (95% confidence limits [CL] 1.3 to 1.9), women with hyperplasia without atypia had an odds ratio of 1.8 (CL = 1.3, 2.4), and women with hyperplasia and atypia had an odds ratio of 2.6 (CL = 1.6, 4.1). Fibroadenoma was an independent risk factor for breast cancer (odds ratio = 1.7; CL = 1.1, 2.5). These findings suggest that women with BBD with epithelial hyperplasia either with or without atypia and women with fibroadenoma should be monitored carefully because of their elevated risk for breast cancer. Cancer 1992; 69:1408‐1414.

Small-cell neuroendocrine carcinoma of the cervix : a human papillomavirus type 18-associated cancer

Small-cell undifferentiated carcinomas comprise a rare but aggressive subset of uterine cervical neoplasms. Analogous to small-cell anaplastic carcinoma of the lung, these tumors frequently exhibit neuroendocrine differentiation. Although human papillomaviruses (HPV) types 16 and 18 are strongly associated with the development of cervical squamous carcinoma, there is as yet little information describing the relationship of these viruses to small-cell carcinomas. To address this question, we analyzed 20 cases of small-cell carcinoma of the cervix using in situ hybridization to detect HPV gene expression. In addition, immunohistochemistry was used to evaluate three markers of neuroendocrine differentiation. Eighteen of 20 tumors (90%) demonstrated some evidence of neuroendocrine differentiation; 17 of 20 (85%) expressed HPV type 16 or 18 messenger RNA. Of the neuroendocrine-positive cases, 14 of 18 expressed HPV 18 messenger RNA. In contrast, both of the cases with squamous differentiation were HPV 16 positive. These findings broaden the spectrum of HPV-associated cervical neoplasia and strongly suggest that HPV 18 is a viral type specifically associated with cervical small-cell neuroendocrine carcinomas.

Small-cell undifferentiated carcinoma of the cervix. A clinicopathologic, ultrastructural, and immunocytochemical study of 15 cases.

The clinicopathologic, immunocytochemical, and ultrastructural features of 15 small-cell undifferentiated carcinomas (SCUC) of the uterine cervix are reported. Patients ranged in age from 25 to 87 (median, 42 years) and presented as stages IB (nine patients), IIA (one patient), IIB (two patients), IIIB (two patients), and IV (one patient). A variety of treatment regimens were employed. Ten patients died of disease (3–71 months; median, 11 months), one patient has a suspicious lung nodule 10 months after diagnosis, one patient is comatose with brain metastases 4 months after diagnosis, and three patients are alive and well 5, 11, and 78 months after diagnosis. Histologically and cytologically, the tumors were identical to pulmonary small-cell undifferentiated carcinoma. Six tumors were associated with other forms of carcinoma, in situ or invasive or both, including epidermoid carcinoma in situ (two cases), adenocarcinoma in situ and epidermoid carcinoma in situ (one case), adenocarcinoma (three cases), and epidermoid carcinoma (three cases). All 13 tumors expressed one or more epithelial markers and at least one neuroendocrine marker. Electron microscopy demonstrated dense-core granules in six of seven tumors, dendrite-like processes in seven tumors, filament bundles in four tumors, and intracytoplasmic lumina in one tumor. Small-cell undifferentiated carcinoma of the cervix is an aggressive tumor with a propensity for rapid metastasis and high mortality. These tumors may demonstrate multidirectional differentiation, including the frequent expression of neuroendocrine features.

Tubular carcinoma of the breast. Clinical and pathological observations concerning 135 cases.

Clinical and pathological features of 135 tubular carcinomas are discussed. Tumor silc varied from 0.2 to 2.5 cm with a mean diameter of 0.9 cm. In situ carcinoma was found associated with tubular cancer in 86 cases (63.6%). In 82 of 86 (95.3%) it was of micropapillary/cribriform intraductal type. Twelve of 109 patients in whom axillary; diseais was performed were found to have axillary metastases. Six patients (4) developed recurrent or disseminated metastatic carcinoma during a mean follow-up period of 7.2 years. Two of these patients are dead of disease. Tubular carcinoma shneld be distinguished from microglandular adenosis, an uncommon form of selerosing adenosis.

Regional distribution and concentration of pancreatic polypeptide in the human and canine pancreas.

The regional concentrations of pancreatic polypeptide (PP), insulin, and glucagon and the cellular distribution of PP were studied in 13 human and nine canine pancreases by radioimmunoassay, immunoperoxidase localization, and cell quantitation. PP concentration was highest in both the uncinate process and the head of the human pancreas and in the right lobe of the canine pancreas. In contrast, glucagon and insulin levels were higher in the body and tail of both the human and canine pancreases. Human F-cells, which contain PP, were located primarily at the periphery of the islets, although a few F-cells were scattered throughout the ducts and acini. Canine F-cells were located in ducts, acini, and islets; the relative proportion of canine F-cells in the endocrine and exocrine tissues differed according to location. Cellular quantitation of F-cells in both species correlated significantly with the tissue concentration of PP in all regions studied, validating the use of morphometric techniques to quantitate the regional distribution of PP.

Neoplastic angioendotheliomatosis. Histologic, immunohistochemical, and ultrastructural findings in two cases

Two cases of neoplastic angioendotheliomatosis are described. Both patients presented with subacute development of dementia punctuated by focal neurologic signs. Postmortem examination in both cases disclosed a vasculocentric distribution of neoplastic cells in many organs. Two characteristic histologic patterns were seen: (1) distension of vascular spaces by free‐floating, intraluminal cells and (2) asymmetric, subendothelial tumor growth. Intravascular tumor and secondary vascular changes were associated with microinfarcts in involved organs. Immunohistochemical localization of factor VIII‐related antigen in the neoplastic cells of one case provides evidence for their endothelial origin. The neoplastic cells in both cases exhibited similar but nonspecific ultrastructural features. In addition, dramatic fine structural changes including the acquisition of numerous pinocytotic vesicles and bundles of fine filaments with periodic densities were found in the non‐neoplastic endothelial cells.

Ovarian metastases from cervical carcinomas other than pure adenocarcinomas. A report of 12 cases.

Twelve cases of ovarian metastases from cervical carcinomas, most with clinical manifestations of ovarian involvement, are reported. The patients were 23–73 years of age (average, 43 years). The ovarian and cervical tumors were synchronous in eight patients; in three, ovarian tumors were discovered 10 months, 2.5, and 3 years after the detection of a cervical neoplasm. In one patient, the cervical tumor was not discovered until autopsy 7 months after presentation. Four patients had abdominal swelling or distention, three had vaginal bleeding, three had an abnormal Papanicolaou smear, and two had masses discovered during pelvic examination. The ovarian tumors, six of which were bilateral, ranged from 5–17 cm (average, 9.5 cm) in maximal dimension in 11 patients; in the 12th patient, the involved ovary was not enlarged. The cervical tumors were grossly evident in 10 patients. They were usually deeply invasive, often with extracervical extension. Four were squamous cell carcinomas; two, small cell carcinomas; one, a mixed small cell carcinoma and adenocarcinoma; one, a mixed poorly differentiated carcinoid and adenocarcinoma; two, adenosquamous carcinomas; one, a transitional cell carcinoma; and one, an undifferentiated carcinoma. Various features, including bilaterality of the ovarian tumors, the finding that the histologic features of the ovarian tumors typically were unusual for a primary ovarian neoplasm, and the presence of extensive extracervical disease, led to the conclusion that the ovarian tumors were metastatic from the cervix. Although ovarian metastases of cervical carcinoma are uncommon, this series illustrates that, occasionally striking examples with clinical manifestations of ovarian involvement occur.

Chronic Chorioamnionitis: A Clinicopathologic Study of 17 Cases

Summary:The clinicopathologic features of 17 cases of an unusual variant of Chorioamnionitis distinguished by a pure or predominantly chronic inflammatory infiltrate in the fetal membranes rather than the usual acute inflammatory reaction are reported. In six cases, there was an equal (one case) or minor (five cases) component of acute inflammation in the fetal membranes as well. Concomitant villitis, found in 11 cases, was almost uniformly lymphohistiocytic and destructive, but it varied greatly in severity. Immunoperoxidase stains for cytomegalovirus, herpes simplex I and II, and Toxoplasma gondii; Warthin-Starry, Gomori methenamine silver, Dieterle, Gram and acid fast stains; placental or amniotic fluid culture; and limited maternal serologic studies failed to identify a specific infectious etiology in any case. Seven women had experienced at least one previous spontaneous abortion, fetal death in utero, or preterm birth. No patient reported a history of fever, rash, or flu-like syndrome during pregnancy. Serious antenatal complications were numerous. Preterm birth occurred in 13 cases. Gestational age ranged from 25 to 42 weeks (mean 32 weeks) and birth weight ranged from 740 to 3,230 g (mean 2,100 g). When expressed as a percentile for gestational age, 47% of infants had a birth weight at or below the 25th percentile, and 76% were at or below the 50th percentile. Two infants were born with gross anomalies, and one infant died in the neonatal period.

Placental site nodule: a clinicopathologic study of 38 cases.

This report describes the clinical, histological, and immunohistochemical features of 38 cases of placental site nodule (PSN), a recently described lesion of intermediate trophoblast (IT). The patients ranged in age from 20 to 47 years (mean, 31.1 years). PSNs were diagnosed in endometrial (30 cases), endocervical (seven cases), and both endometrial and endocervical specimens (one case). The majority of biopsies were prompted by an abnormal Pap smear (13 cases) or complaints of menorrhagia (21 cases). All PSNs were microscopically detected, lobulated nodules composed of acellular, hyalinized material admixed with IT. Mitotic activity was noted in seven cases. Immunohistochemically, the IT expressed human placental lactogen (hPL) in 78% of cases and human chorionic gonadotropin (hCG) in 42% of cases, but their expression was weak and focal in contrast to uniform, strong staining for placental alkaline phosphatase (PLAP) (100%), cytokeratins (96%), and epithelial membrane antigen (EMA) (84%). Type IV collagen outlined the IT and stained the extracellular material in the cellular areas. Vimentin-positive cells within the lesions were fewer in number and in a different distribution than those expressing PLAP, CK, and EMA. Two consecutive PSNs occurred in one patient, but no patient developed gestational trophoblastic disease or a significant gynecologic neoplasm.