Sarcomatoid carcinoma of the larynx with neck and distant subcutaneous metastases. A case report with fine needle aspiration cytology.

BACKGROUND: Sarcomatoid carcinoma of the upper aerodigestive tract is an unusual neoplasm with divergent cellular differentiation. Typically this carcinoma is a squamous cell carcinoma with spindle and giant cell components and may be misinterpreted as a sarcoma. CASE: A 56-year-old, diabetic male presented with a 2.5-cm, left-sided neck mass. Fine needle aspiration showed a mixture of malignant squamous and spindle cells. A third population of osteoclastlike giant cells was also present. Similar cells were aspirated from a subcutaneous left leg lesion months later. CONCLUSION: The diagnosis of a sarcomatoid carcinoma of the larynx should be considered when malignant epithelial, spindle and giant cells are present in aspirated smear material from the neck.

Cervicovaginal cytology in uterine adenocarcinoma and adenosquamous carcinoma. Comparison of cytologic and histologic findings.

To investigate the diagnostic accuracy and to characterize the findings in false-negative cases, the results of cervicovaginal cytology in 56 adenocarcinomas and 25 adenosquamous carcinomas (42 cervical, 36 endometrial, 2 metastatic and 1 arising synchronously from both cervix and endometrium) were reviewed, including review of the actual slides in 56 cases. Overall, 80% of the initial cytologic diagnoses resulted in diagnostic curettage (i.e., cytology was effectively positive); 84% of the postreview diagnosis were effectively positive. Nine cytology slides showed no malignant cells; eight of these negative smears showed repair, five were atrophic, two showed a high estrogen effect and one had enlarged atypical bare nuclei. These false-negative diagnoses were associated with an endometrial primary site (P less than .01), endometrioid histology (P less than .005), low-grade or intermediate-grade histology (P less than .005), small size of tumor (P less than .05) and absence of cervical involvement (P less than .005) in those cases in which a hysterectomy was performed. False-negative diagnoses were not associated with an absence of endocervical cells or with scanty cellularity. Of 39 cervical and 28 endometrial carcinomas with a positive cytologic diagnosis (initially or after review of the available slides), cytology correctly identified the primary site in 18% and 54% of the cases, respectively. Cytology incorrectly classified the anatomic site of four cervical and three endometrial carcinomas and considered one case arising in both the endometrium and cervix to be endometrial. Routine cervicovaginal cytology does have a role in screening for uterine glandular carcinoma; to maximize its diagnostic sensitivity, we suggest using a recommendation for curettage in the report of positive cases so that all of the varied cytologic diagnoses associated with glandular carcinomas will receive a uniform clinical response. In those cases with preserved cancer cells, a correlation can be made with the histologic type of the carcinoma, rather than with the anatomic site.

Cervicovaginal cytology in an indigent population. Comparison of results for 1964, 1981 and 1989.

To evaluate the usefulness of cervicovaginal cytology in decreasing the incidence of cervical carcinoma in an indigent population, the cytologic findings from 10,000 consecutive smears in 1964 (when cytology screening started) were compared to the results of 10,000 consecutive smears in 1981 and 1989. There was a marked (statistically significant) decrease in invasive cervical squamous carcinoma at all ages between the first and later periods. Squamous carcinoma in situ showed a significant decrease beginning in patients under 40 in 1981. The number of atypias and mild dysplasias showed a proportional increase, from 2% in 1964 to 13.4% in 1981 to 21.8% in 1989, predominantly in young patients. These results reaffirm that cervicovaginal cytology remains the most inexpensive and effective diagnostic tool for the elimination of cervical cancer.

Cytology of primary versus secondary genital herpesvirus infection.

Certain authors state that primary genital herpes infections mainly produce cells with ground-glass nuclei, whereas secondary infections produce a higher percentage of multinucleated or single cells with prominent intranuclear inclusions. The cervicovaginal smears of 11 patients with primary genital herpes infection and 16 patients with secondary infection were studied to determine the validity of this differentiation. The percentage per patient of virally infected cells containing distinct inclusions ranged from 0% to 35% in the primary herpes group and 0% to 100% in the secondary herpes group. In eight additional patients, the initial herpes simplex virus (HSV)-positive smear was compared with recurrent positive smears taken from 2 to 120 mo later. No statistical difference in the incidence of distinct inclusions in the infected cells was detected. Finally, primary rabbit kidney and the heteroploid A549 cell cultures were inoculated with herpes viruses and followed by fixation with several agents at various time intervals. Alcohol and Bouin's fixative favored the recognition of distinct inclusions, as did the duration of the infection.

Retrospective evaluation of gynecologic cytodiagnosis. II. Interlaboratory reproducibility as shown in rescreening large consecutive samples of reported cases.

Two laboratories exchanged and rescreened a large sample of cases with cervicovaginal smears they had consecutively accessioned to examine the reproducibility of gynecologic cytodiagnosis under optimum conditions. At least a "working agreement" (diagnoses within +/- 1 category on a ten-category scale) was achieved in diagnoses of normal, benign reaction and squamous abnormality (from minimal dysplasia though invasive cancer) in 18,859 cases (96.8%), of endometrial abnormality in 21 cases (42%) and of "unsatisfactory" in 99 cases (20.7%). Larger differences occurred in greater than or equal to 30% of cases except in the categories of "normal" and "benign reaction," reaching a maximum of 82% for moderate dysplasia. Reexamining 382 cases decreased disagreement by category to the 20% to 65% range only in the five categories of dysplasia plus carcinoma in situ. Agreement was not predicated on the presence of endocervical cells or squamous metaplasia; the basis for "unsatisfactory" calls was not uniform. Comparison of the laboratories' diagnoses with referee diagnoses or, on 178 cases, with tissue diagnoses also demonstrated differences in diagnostic criteria.

Fine needle aspiration cytology of myositis ossificans.

Fine needle aspiration was performed on a large soft tissue mass of the left thigh and hip region in a 27-year-old paraplegic man. Cytologic examination revealed sheets of immature fibroblasts and scattered skeletal muscle cells in various stages of degeneration compatible with myositis ossificans. This case is probably the first needle aspiration cytology of this lesion. The danger of confusing the cytology with that of a sarcoma is emphasized.

Retrospective evaluation of gynecologic cytodiagnosis. I. Reproducibility using an experimental diagnostic scale.

A system for the exchange of specimens between two independent laboratories ("A" and "B") was designed to enable them to review a consecutive series of one another's gynecologic smears. Another cytopathologist "refereed" diagnoses differing beyond agreed limits and examined all smears called carcinoma in situ or a more severe lesion by either laboratory. A ten-numeral gradient nomenclature scale was developed to code all cytodiagnoses for data processing. This analysis of the reproducibility of the experimental diagnostic system is based on all participants' examination of 100 selected specimens, half contributed by reviewing laboratory A and half by reviewing laboratory B, with the target value of each specimen established by the contributor. Intralaboratory reproducibility, expressed by a correlation coefficient (r), ranged from 0.78 to 0.93. After adjusting for straightforward squamous-cell lesions, r ranged from 0.88 to 0.91. Intralaboratory agreement +/- 1 scalar category, defined as a "working consensus," ranged from 77% to 84%. Interlaboratory correlation ranged from r = 0.74 to 0.94. Adjustment for squamous-cell lesions exerted less effect than it had on intralaboratory reproducibility. Interlaboratory agreement within one category ranged from 58% (laboratory B reviewing specimens contributed by laboratory A) to 92% (referee examining specimens contributed by laboratory B). Initially, laboratory A tended to classify a given specimen higher on the scale than did laboratory B and the referee, but as the study progressed, both laboratories tended to converge toward a more congruent diagnostic position, with referee greater than A greater than B. The level of discrimination attained by all participants validates use of this system to compare a larger series of diagnoses.

Comparison of written-visual and microslide-screening test measures in cytotechnology.

A study was conducted to ascertain the relationships among different competence assessment methods for cytotechnologists. Of primary concern was the extent to which examinations using multiple choice questions, color plate photomicrographs and filmstrip formats measure abilities in common with or predict performance levels on a practical, job-sample-microslide examination format in gynecologic cytopathology. The majority of cytotechnologists who volunteered for these tests were trained in schools of cytotechnology approved by the Committee on Allied Health Education and Accreditation (CAHEA) of the American Medical Association (AMA). School training, certification by the International Academy of Cytology (IAC) and by the American Society of Clinical Pathologists (ASCP) and participation in current continuing education activities were all associated with relatively higher test scores. The filmstrips format was least consistent in reflecting these distinctions. Overall, participants' scores in each test correlated to varying degrees with their scores on all other tests. Combinations of certain formats appear to have limited potential as performance evaluation methods; some of their drawbacks are presented.

Pelvic colonization with Actinomyces in women using intrauterine contraceptive devices.

Recent reports suggest a relationship between intrauterine contraceptive device (IUD) use and colonization or infection of the genital tract with Actinomyces species. This prospective, case-controlled study was designed to determine the incidence of colonization or infection with Actinomyces in IUD users. None of 50 control patients and four of 50 study patients (8%) had Actinomyces identified. None of the patients with positive results had symptomatic pelvic infection. Cervical cytology was effective in detecting each of the four study patients with positive results. It appears that the presence of any type of IUD is a major predisposing factor to colonization with Actinomyces.

PIP: Recent reports indicate that colonization or infection of the genital tract with Actinomyces israelli (an anaerobic, gram-positive, non-acid fast, obligate parasite classified between the true bacteria and complete fungi) may be related to IUD use. To determine the incidence of Actinomyces infection in IUD users and a comparable samples of nonusers, a prospective controlled study was undertaken using 50 study and 50 control patients from the Grady Memorial Hospital's gynecology and family planning clinics. The age and parity of the 2 groups ranged from 17 to 52 years, and 1.9 to 2.8, respectively. Selected risk factors predisposing to colonization or infection with Actinomyces were considered and included frequency of intercourse per week; contraceptives used; and histories of appendicitis and pelvic inflammatory disease (PID). Both groups were divided into women less than 35 years of age and those more than 35 years of age. There were 29 control and 9 study patients in the older group. Of the 9 study patients, 4 (44.4%) had Actinomyces compared to none of the 29 control patients (p .01). The Lippes loop, which was used by 50% of the IUD users, was the most commonly removed IUD. The characteristics of the 4 patients were described in Table 5. Cervical cytology was used in detecting the Actinomyces infection or colonization of the 4 study patients, who were managed by IUD removal and follow-up biopsies or Pap smears. Symptomatic patients should have their IUDs removed and should be treated with antibiotics to provide both aerobic and anaerobic coverage.

Preoperative diagnosis of pancreatic carcinoma by percutaneous aspiration biopsy.

Carcinoma of the pancreas and chronic pancreatitis may be extremely difficult to differentiate by standard diagnostic methods preoperatively as well as at the operating table. Operative pancreatic biopsy may have a high morbidity, rare mortality, and can be misleading. Percutaneous aspiration biopsy may be of great potential benefit. It provides additional histological material not usually available, and an accurate diagnosis of malignancy can be made. In select patients a needless laparotomy may be avoided. It appears to be a safe procedure that should be considered in the evaluation of the patient with suspected pancreatic malignancy in which a mass lesion is demonstrated by ultrasonography, computerized tomography, angiography, or retrograde pancreatography.

Viruses and cancer of the lower genital tract.

The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV-2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV-2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer.

A preliminary report on investigation of oncogenic potential of herpes simplex virus type 2 in Cebus monkeys.

A total of 301 female and 133 male Cebus monkeys have been placed under study during a 3-year period. Females are inoculated intradermally into the cervix every 6 months; 225 receive virus and 76 receive control material. More than 50% of the animals were infected on primary inoculation, and a similar percentage was foundon the 1st reinoculation. Males are housed with females at 1:1 to 1:3 ratios. Eighteen % of the males exposed to virus-inoculated females have become infected. To date, a total of 55 pregnancies have produced 14 live births and 8 abortions. The remaining 33 animals are still pregnant. No neonatal herpes simplex virus type 2 infections have been identified. Cytological changes of mild (atypia) to moderate (dysplasia) anaplasia have persisted for 12 to 32 months in 13 herpes simplex virus type 2-infected females. These animals received their 1st inoculation 14 to 50 months ago. Persistent anaplasia has not been found in control animals.

[The present status of the theory of induction of carcinoma of the cervix in man by herpes virus (author's transl)]. / Der augenblickliche Stand der Herpesvirus-Zervixkarzinom-Theorie

A large body of evidence has accumulated during the past decade suggesting that HSV-2 infection of the cervix may be a major precursor of cervical carcinoma. A brief review of the more significant findings to date is presented.

Epidemiological studies relating genital herpetic infection to cervical carcinoma.

PIP: Epidemiological studies relating genital herpetic infection to cervical carcinoma are reviewed. The high frequency of herpes simplex virus type 2 (HSV-2) antibodies in young women (21 years or younger) with cervical carcinoma in situ and in women with dysplasia or carcinoma in situ, matched for various sexual attributes to control women, provide support for a causal relation. However, various laboratory, histopathological, and statistical problems associated with all epidemiological studies do not yet permit a firm conclusion as to the etiological role to the genital virus in cervical carcinogenesis. With the use of herpes-related cancer antigens or purified HSV-2 type-specific antigens, and with the possible development of protective HSV-2 vaccines, the application of epidemiological approaches may be necessary to provide the most finite evidence of causality.^ieng

Relation of cytohistopathology of genital herpesvirus infection to cervical anaplasia.

PIP: Cytological changes resulting from herpes simplex virus (HSV) were detected in 673 (.26%) of 279,589 cervicovaginal smears from an indigent hospital population. Histopathological features of HSV infection were observed in 45 of 126 biopsies taken from the group of 673. Most of the lesions were multifocal and were located on the squamocolumnar junction; diagnostic cells were found at the base of normal squamous epithelium or at the surface of anaplastic epithelium. The cytological and histological changes and diagnostic procedures for HSV infection are given in detail; cytological detection is 2/3 as sensitive as viral isolation. The presence of anaplasia in about 2/3 of the 673 HSV cases either before or at the same time as the detection of HSV suggests that anaplastic tissue is more susceptible to HSV infection. However, serological evidence showing HSV antibodies before the onset of cervical anaplasia, the recurring nature of HSV, and epidemiological evidence showing the age of acquisition of HSV to be 5-30 years before diagnosis of cervical cancer are all compatible with the view that HSV causes cervical cancer.^ieng