Cytologic features of endometrial papillary serous carcinoma

Endometrial papillary serous carcinoma (EPSC) is an uncommon variant of endometrial carcinoma that histologically resembles ovarian serous carcinoma and has an aggressive clinical course. The cytomorphologic features of 17 patients with histologically confirmed EPSC of the endometrium were reviewed and compared with those of 20 patients with histologically typical endometrial adenocarcinoma (TEC). Preoperative cervicovaginal Papanicolaou smear results were available from 14 of the 17 patients with EPSC; 10 (71%) were positive, 1 (7%) was suspicious and 3 (21%) were negative for malignancy. Initial cervicovaginal smear results were available from all 20 patients with TEC; 7 (35%) were positive, 4 (20%) were atypical or suspicious and 9 (45%) were negative for malignancy. Twelve patients with EPSC had peritoneal washings or fluids examined; seven were positive and five negative. Twelve patients with TEC had peritoneal washings or fluids examined; two (17%) were positive and ten (83%) were negative. The cervicovaginal smears from patients with EPSC revealed numerous large tumor cells (with prominent nucleoli) frequently arranged in papillary clusters with background necrosis and, in two cases, amorphous material suggestive of psammoma bodies. In contrast, the smears of patients with TEC showed small to medium-sized cells with extensive phagocytosis and many background histiocytes. The diagnosis of EPSC should be considered when the cervicovaginal smear contains numerous papillary groups of large tumor cells with macronucleoli but without prominent phagocytosis, especially when structures suggestive of psammoma bodies are present. The peritoneal fluids in these patients are more often positive than in patients with TEC, a finding consistent with the propensity of EPSC to involve peritoneal surfaces.     

Cytologic diagnosis of vaginal papillary squamotransitional cell carcinoma. A case report

BACKGROUND: Papillary squamous and squamotransitional cell carcinomas of the cervix and vagina are infrequent morphologic variants of squamous cell carcinoma that may be underdiagnosed due to a bland histologic appearance. To our knowledge, this entity has not been previously detected by Pap smear evaluation. CASE: Vaginal wall pap smears were collected from a patient with a previous hysterectomy for microinvasive cervicovaginal squamous cell carcinoma and extensive carcinoma in situ. The smears were characterized by: (1) large, darkly staining, three-dimensional, branching, papillary epithelial fragments with prominent fibrovascular cores and lined with loosely cohesive epithelial cells; (2) a highly cellular background population of dissociated single epithelial cells with features of severe dysplasia, including hyperchromatic, coarse chromatin; scant, delicate, frayed cytoplasm and karyorrhectic debris; (3) syncytial aggregates of severely dysplastic epithelial cells morphologically similar to the single cells; and (4) lack of a recognizable, morphologically distinct "transitional cell" population. CONCLUSION: Papillary squamotransitional cell carcinoma of the vagina is a rare morphologic variant of squamous cell carcinoma that should be distinguished from benign vaginal squamous papillomas, condylomatous lesions and verrucous carcinoma. However, this lesion is also related to human papillomavirus infection, particularly the high-risk types. Papillary squamotransitional cell carcinoma can be suspected on Pap smear when high grade squamous intraepithelial lesion features are found in combination with three-dimensional papillary tissue fragments with prominent fibrovascular cores.     

Molecular basis of gestational trophoblastic diseases

Gestational trophoblastic disease (GTD) encompasses a diverse group of lesions with specific pathogenesis, morphological characteristics and clinical features. The modified World Health Organization-classification of GTD includes complete and partial hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, exaggerated placental site, and placental site nodule. The various forms of gestational trophoblastic disease can be defined and related to discrete pathologic aberrations occurring at different stages of trophoblastic differentiation. Some of these lesions are true neoplasms, whereas others represent abnormally formed placentas with a predisposition for neoplastic transformation of the trophoblast. Except hydatidiform moles in which the cytogenetic studies have been extensively reported, the pathogenesis of other trophoblastic lesions is poorly understood. Recent studies have shed light on the molecular mechanisms of trophoblastic function, especially as it relates to trophoblastic disease. This review will focus on these advances with special emphasis on the pathogenesis of each specific form of GTD. In addition, the morphology and clinical behavior of each of these entities will be briefly discussed.     

Measurement of subvisual changes in cervical squamous metaplastic cells for detecting abnormality.

Quantitative measures of visually normal squamous metaplastic cells exfoliated from the uterine cervix were obtained to test the hypothesis that these cells, like intermediate squamous and endocervical columnar cells, show subvisual evidence of atypia in cases of bonafide squamous intraepithelial neoplasia. The cells identified as squamous metaplastic were obtained from 14 abnormal (dysplastic) and 9 diagnostically negative cases. Although the cell populations so grouped showed no statistically significant differences in overall cell size, nuclear area or nuclear/cytoplasmic ratios, there were significant differences in nuclear and cytoplasmic densitometric features and in nuclear texture features. A combination of three features (nuclear density, texture and cytoplasmic density) permitted 76% of the cells to be categorized correctly as originating in normal versus abnormal slides. It is concluded that selected quantitative features of exfoliated metaplastic cell populations may contribute to improved diagnostic accuracy in automated screening for cervical abnormalities.     

Collection devices for cervicovaginal cytology: a comparison

OBJECTIVE: To compare cervicovaginal smears obtained by a cotton-tipped swab with those obtained by cervix brush and modified Ayre spatula. STUDY DESIGN: A combined cervicovaginal smear was collected from 100 women using 3 different collection devices: cotton-tipped swab, cervix brush, and modified Ayre spatula. In each patient a set of 3 smears was collected by the same cytotechnologist using all 3 devices in random order. Smears were evaluated using parameters mandatory for an optimal smear: evenly dispersed, well-preserved, adequate cells from the transformation zone. The cost and availability of the collection devices were also considered. RESULTS: The swab was the most effective device in obtaining thin, evenly spread, adequate, well-preserved smears as against the cervix brush and Ayre spatula. The pickup of abnormal cells was similar with the cotton-tipped swab and cervix brush, while the Ayre spatula failed to yield high grade squamous intraepithelial lesions, atypical glandular cells of undetermined significance and adenocarcinoma cells. The cotton-tipped swab proved to be the most cost effective. CONCLUSION: A properly prepared cotton-tipped swab is an inexpensive, readily available, nontraumatic collection device that yields smear of optimal quality.     

Cell cycle and apoptosis in normal and cloned bovine near-term placentae

The bovine maternal epithelium is composed of cuboidal cells interspersed with low columnar cells having centrally located nuclei. Bovine trophoblast is composed of two cell types: mononuclear trophoblastic and giant trophoblastic cells that can have two or more nuclei. Number of apoptotic cells and proliferative cells are variable in both cell populations. This study compared tissue growth and apoptosis by flow cytometry in the cell population found at distinct placental regions (central region of placentomes, ≤1-cm microplacentomes and the interplacentomal region) between normal and cloned near-term bovine pregnancies. After a morphological comparison between regions and groups (controls vs. clones), a lesser proportion of diploid to tetraploid cells was observed in the central region of placentomes and in microplacentomes from cloned-derived pregnancies. In addition, cloned animals had a fewer apoptotic cells in the central region of the placentome and in interplacentomal region and a greater proliferative capacity in all regions (cells in G₂/M) near term as opposed to control animals. These results may reveal the existence of a relationship between such changes in the proportions of uterine and trophoblastic epithelial cells at the end of pregnancy and normal placental function. This could be related to faulty placentation in early pregnancy, placental insufficiency during pregnancy or lack of placental and/or fetal maturation in late pregnancy, which may contribute to some of the abnormalities after in vitro embryo manipulations, such as poor preparation and initiation of parturition, prolonged gestation and lesser post-natal survival in some cloned animals.     

A Proteomic Analysis of Placental Trophoblastic Cells in Preeclampsia–Eclampsia

To explore the proteomic changes of placental trophoblastic cells in preeclampsia–eclampsia (PE), placental trophoblastic cells from normally pregnant women and women with hypertension during gestational period were prepared by laser capture microdissection (LCM), and proteins isolated from these cells were subjected to labeling and proteolysis with isotope-coded affinity tag reagent. A qualitative and quantitative analysis of the proteome expression of placental trophoblastic cells was made using two-dimensional liquid chromatography tandem mass spectrometry (2D LC–MS/MS). A total of 831 proteins in placental trophoblastic cells were identified by combined use of LCM technique and 2D LC–MS/MS. The result was superior to that of conventional two-dimensional electrophoresis method. There were marked differences in 169 proteins of placental trophoblastic cells between normally pregnant women and women with PE. Of 70 (41.4 %) proteins with more than twofold differences, 31 proteins were down-regulated, and 39 were up-regulated in placental trophoblastic cells of the woman with PE. Laminin expression in placenta trophoblastic cells of women with PE was significantly down-regulated as confirmed by Western blot analysis. These findings provide insights into the proteomic changes in placental trophoblastic cells in response to PE and may identify novel protein targets associated with the pathogenesis of PE.     

Involvement of gap junctions in placental functions and development

Connexin (Cx) expression and gap junctional intercellular communication (GJIC) are involved in development and differentiation processes. Mediating exchanges between mother and fetus, the placenta is formed when fetal membranes are apposed or even fusing or destroying the uterine mucosa. Therefore, an extraordinary variability of placental structures is observed throughout the mammalian species. This variability affect mainly, the maternofetal blood flow interrelationships, the kind and number of tissue layers separating maternal and fetal bloods, the trophoblast invasiveness and the formation of a syncytium (syncytiotrophoblast). Here, the expression, the localisation and the possible role of Cx and GJIC in placental functions and development are discussed. In rodents, gene knock out in mice have vastly improved our understanding of the role of Cx genes in mouse placental development: Cx26 in transplacental uptake of glucose, Cx31 in the proliferative process of trophoblastic cells and Cx45 in placental vascularisation. In human, it appears that Cx43 allows a GJIC required for the fusion process of cytotrophoblastic cells leading to the formation of the syncytiotrophoblast, the site of the numerous placental functions. On other hands, Cx40 plays a critical role in the switch from a proliferative to an invasive phenotype of the trophoblastic cells invading the endometrium. Owing to the striking diversity of Cx expression in placental structures, we must be careful when extrapolating findings from one species to another.     

Histiocytes and the detection of endometrial adenocarcinoma

Histiocytes have long been recognized as part of the milieu of endometrial carcinoma in gynecologic smears. In an effort to determine whether a quantitative assessment of histiocytes, especially in the absence of endometrial cells, could increase the effectiveness of the cervicovaginal smear for diagnosis of endometrial carcinoma, smears obtained prior to a tissue diagnosis of endometrial adenocarcinoma were evaluated from 44 postmenopausal women. Smears from 97 age-matched patients in the same clinic were also evaluated and used as a control group for the endometrial carcinoma patients. All smears were evaluated for the presence of histiocytes and for the presence of benign or malignant endometrial cells, with the histiocytes quantitated as minimal (less than 5 per high-power field [HPF]), moderate (5 to 10/HPF) or heavy (greater than 10/HPF). Sensitivity and specificity were calculated to assess the role of histiocytes in the presence and in the absence of endometrial cells using cytologic findings. Our data indicate that the presence of moderate or heavy numbers of histiocytes on cervicovaginal smears of postmenopausal women increased the cytologic sensitivity from 61% to 82% when considered a marker of disease along with endometrial cells. These results suggest that attention to the presence of histiocytes on cervicovaginal smears may increase the utility of cytology for the diagnosis of endometrial lesions and may be a useful guideline for the cancer-related gynecologic examination.     

Growth of mouse ectoplacental cone cells in subcutaneous tissues. Development of placental-like cells.

Ectoplacental cones of mouse embryos collected on day 8 of pregnancy were grafted into the dorsal subcutaneous tissue of host mice. The grafts were collected between days 3 and 8 after transfer and processed for light and electron microscope morphological analysis as well as for cytochemistry of nonspecific alkaline phosphatase. Fragments of normal mouse placentas collected between days 12 and 18 of pregnancy were processed similarly. About 37% of the grafts were nonhemorrhagic nodules formed by different kinds of trophoblastic cells. These cells had many morphological and cytochemical features of cells present in normal mouse placentas. Nonphagocytic giant cells, glycogen cells, as well as cells with a well-developed granular endoplasmic reticulum were similar to cells found in the placenta and were always present in the grafts. Cells showing features intermediate between the above-mentioned cells and those whose cytoplasm was poor in organelles also were found in the grafts. The latter resembled cells of layer 1 of the labyrinth of the placenta. These results suggest that trophoblastic cells of the ectoplacental cones had differentiated into placental cells following their transfer to the subcutaneous tissue.     

Atypical squamous cells of undetermined significance in women over 55. Comparison with the general population and implications for management.

OBJECTIVE: To determine the significance of atypical squamous cells of undetermined significance (ASCUS) in patients 55 years or older. STUDY DESIGN: From January 1994, to January 1997, 8,175 cervicovaginal smears were obtained from patients 55 years or older (mean age, 64.8; range, 56-84) at University Hospitals of Cleveland. Ninety-six of these patients were diagnosed with ASCUS only or ASCUS with a qualifying statement on the smear. Patient records, follow-up cervicovaginal smears and biopsies were reviewed for a period of one to four years following the diagnosis of ASCUS. RESULTS: The incidence of ASCUS only or ASCUS with a qualifying statement for patients 55 years or older was 1.8%. The ASCUS:SIL ratio was 2.6:1. An estrogen stimulation test was recommended in two cases. Women older than 55 with ASCUS were three times more likely to be receiving hormonal replacement therapy than similar-aged women with normal cervicovaginal smears. Follow-up cervicovaginal smears or biopsies were obtained on 93 (80 cervicovaginal smears, 13 biopsies). The results were the following: LSIL (13), squamous carcinoma in situ (1) and ASCUS (53); the remainder of the cases were normal. In the patients who received a second diagnosis of ASCUS, follow-up cervi covaginal smears or biopsies revealed low grade dysplasia in six. CONCLUSION: Although the incidence of ASCUS and the frequency of underlying dysplasia is lower in postmenopausal women than the general population, there is still a real risk that a postmenopausal woman with ASCUS has underlying intraepithelial neoplasia. Therefore, these patients should be managed as is the general population.     

Histopathologic correlation of atypical parakeratosis diagnosed on cervicovaginal cytology

OBJECTIVE: To retrospectively examine the histopathologic findings in women with the isolated finding of atypical parakeratosis (PK) on a Pap test. STUDY DESIGN: The cytology files (1999-2001) were searched for cervicovaginal Pap tests interpreted as atypical PK. Cases were included for study only if there was a subsequent cervicovaginal tissue sample within 1 year of the cytologic interpretation and there was no diagnosis of squamous intraepithelial lesion (SIL) within the previous five years. RESULTS: Of 355 patients with atypical PK, 109 (aged 14-69 years, mean 31.5) met the inclusion criteria of the study. The interval between the cytologic interpretation and cervicovaginal tissue examination ranged from 0.5 to 12 months (mean, 2.5). Sixty-one patients underwent both endocervical curettage (ECC) and cervical biopsy (CBx), 20 patients underwent ECC only, 19 patients underwent CBx only, and the remainder underwent other procedures. Histopathologic findings on the tissue samples included: no significant pathologic change but no squamous epithelium present for evaluation (n = 10, 9.2%), benign changes other than hyperkeratosis and/or PK (n = 50, 45.9%), hyperkeratosis and/or PK (n = 8, 7.3%), low grade SIL (n = 33, 30.3%), high grade SIL (n = 6, 5.5%) and invasive squamous cell carcinoma (n = 2, 1.8%). CONCLUSION: The isolated finding of atypical PK on a Pap test correlated with the presence of an underlying SIL or invasive carcinoma in approximately 40% of patients. Of these, 80% had low grade SIL. The cytologic finding of atypical PK warrants further investigation in order to exclude SILs and/or carcinoma. We suggest that atypical PK be routinely included in the category of atypical squamous cells of undetermined significance.     

Acantholytic cells exfoliated from pemphigus vulgaris of the uterine cervix. A case report

BACKGROUND: Pemphigus vulgaris of the uterine cervix is rare and almost always associated with cutaneous or mucosal lesions elsewhere on the body. Without a history of pemphigus, acantholytic cells in cervical smears may be misdiagnosed as malignant ones. CASE: A 52-year-old female presented with a vaginal discharge, and a routine cervical smear was collected for cytology. The smear displayed atypical cells lying singly and in loose clusters, having vesicular nuclei, a thin nuclear membrane, prominent nucleoli and well-defined cytoplasmic margins. These were labeled atypical glandular cells of undetermined significance, and colposcopic examination and biopsy were advised. On colposcopy vesicular lesions and erosions were noticed on the cervix. The biopsy revealed typical intact as well as denuded suprabasal bullae of pemphigus vulgaris. On reevaluation of the cytologic smear, the cytomorphologic features correlated well with the acantholytic cells of pemphigus. Thorough reexamination of the patient revealed 2 tiny vesicles on the oral mucosa that, on biopsy, confirmed the diagnosis of pemphigus vulgaris. CONCLUSION: Cytopathologists should be aware of the typical cytomorphologic features of pemphigus vulgaris and, in an appropriate clinical setting, should be able to diagnose or at least suspect this entity in even rare sites like the cervix. A false positive diagnosis of malignancy can be avoided if the cytologic findings are judiciously correlated with the history and with clinical and colposcopic examinations.     

Cytologic diagnosis of primary tubal cancer

A study was made of the 128 cases of primary tubal cancer reported to date in Japan, especially of the 61 cases with a preoperative cytologic examination, which was positive for malignancy in 28 cases (45.9%). A positive cytologic diagnosis was made on the cervicovaginal smear in 37.9% of the 58 cases so examined and on the endometrial smear in 80.0% of the 15 cases so examined. Of the 12 cases with positive endocervical smear cytologies, 11 were without endometrial invasion and 4 had no cancer cells in the cervicovaginal smear. Histologic examination of endometrial curettage specimens was positive for cancer in 8 (23.5%) of 34 cases so examined. Endometrial invasion by cancer cells was seen in 11.1% of the surgically extirpated endometrial specimens. The results of this study suggest that cytologic diagnosis is one of the most reliable methods for detecting primary tubal cancer before a surgical operation is undertaken. Its efficacy might be improved by more careful sampling and study in patients suspected of having primary tubal cancer.     

Signet ring cell lobular carcinoma of the breast presenting in a cervicovaginal smear. A case report

BACKGROUND: The presence of extragenital malignant cells in cervicovaginal smears is a rare and usually late event in a patient with a long history of cancer. This, to the best of our knowledge, is the first case of breast cancer initially diagnosed on a Pap smear. CASE: A 50-year-old woman presented with abdominal distension and weight gain. A Pap smear showed numerous signet ring cells and was diagnosed as signet ring cell adenocarcinoma, most likely metastatic from the breast or stomach. Subsequent evaluation revealed bilateral adnexal masses and inguinal lymphadenopathy, leading to hysterectomy and bilateral salpingo-oophorectomy. The ovaries, corpus and cervix were involved by signet ring cell carcinoma. The metastatic tumor proved to be positive for CK7, CEA, estrogen receptor and progesterone receptors and negative for CK20. Despite the absence of a discrete palpable breast mass, a mammogram was recommended based on these results, and an ensuing breast biopsy showed the presence of an infiltrating lobular carcinoma. CONCLUSION: Lobular carcinoma of the breast may present in a cervicovaginal smear. Correct interpretation of signet ring cells as metastatic, most likely from the breast or stomach, is helpful in guiding management.     

Immunohistochemical localization of laminin and fibronectin isoforms in human placental villi.

We studied the localization of laminin alpha1, alpha2, alpha3, alpha5, beta1, beta2, and gamma1 chains and extradomain A- (EDA), EDB-, and oncofetal fibronectin by immunohistochemistry in human placental villi during placental development. The laminin alpha2, alpha5, beta1, beta2, and gamma1 chains were detected in the trophoblastic basement membrane (BM) at all stages of gestation, suggesting the presence of laminin-2, -4, -10, and -11 trimers. The laminin alpha1 chain was selectively found at sites where the villous BM was in contact with proliferating cells in trophoblastic islands or columns. EDA-Fn, but not other Fn isoforms, was found in the trophoblastic BM during the first trimester. The laminin alpha2, beta1, beta2, and gamma1 chains were detected in the villous stroma and capillaries throughout placental development, while the laminin alpha5 chain emerged distinctly during development. Extensive EDA-Fn immunoreactivity was found in first-trimester villous stroma, but distinctly fewer Fn isoforms were seen in the villous stroma during the later stages of gestation. Our results also suggest that, during the formation of new villi, laminins are not found in trophoblastic sprouts before the ingrowth of the villous mesenchyme. Rather, laminins may be deposited at the villous epithelial-mesenchymal interface. Furthermore, the results show that distinct changes occur in the localization of various laminin and Fn isoforms during the maturation of villous trophoblastic and capillary BMs.     

Impact of liquid-based gynecologic cytology on an HIV-positive population

OBJECTIVE: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia. STUDY DESIGN: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population. RESULTS: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology. CONCLUSION: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.     

Microfilariae of Wuchereria bancrofti in cytologic smears

Microfilariae of Wuchereria bancrofti were observed in cytologic material in 35 cases. The material included cervicovaginal smears (17 cases), effusions (14), urine (2), bronchial washings (1) and ovarian cyst fluid (1). The initial diagnosis was made from the cytologic smear in all cases; none had clinical filariasis. Symptomatic vaginal bleeding in 9 of the 17 cases with microfilaria-positive cervicovaginal smears was reflected in the large numbers of red blood cells found in the smear. Blood eosinophilia was present in 11 of 19 cases investigated. Eosinophils were seen in the smears in 20 cases. In the majority of the cases of effusions with microfilariae the effusions were malignant. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 7 of the 35 cases. The significance of these findings is discussed.     

Exfoliative cytology of atypical polypoid adenomyoma. A case report.

BACKGROUND: An atypical polypoid adenomyoma (APA) is a well-defined entity. It occurs in the endometrium, lower uterine segment and endocervix. It is usually composed of atypical complex glands with squamous metaplasia admixed with myofibromatous stroma. CASE: A 35-year-old female presented with one-year history of irregular menstrual periods. A diagnosis of adenocarcinoma in situ was rendered on her cervicovaginal smear. Pelvic examination revealed an enlarged uterus due to a leiomyoma. Colposcopic examination revealed a 0.6-cm, sessile, polypoid mass at the junction of the endocervix and ectocervix. A cone biopsy of the lesion showed irregular, endometrial-type glands embedded in a prominent myofibromatous stroma. The atypical glandular component of the mass demonstrated varying degrees of architectural complexity, ranging from simple to complex hyperplasia. In tissue sections the lesion was diagnosed as APA of the cervix. The patient underwent a hysterectomy for the leiomyoma. The hysterectomy specimen showed an 8.5-cm leiomyoma. The cervix and uterine corpus revealed no residual APA. CONCLUSION: APA of the cervix should be considered among the differential diagnoses of atypical glandular cells of undetermined significance. The diagnosis of APA cannot be made on cytology; the final diagnosis requires histologic confirmation.     

Psammoma bodies in neuroendocrine carcinoma of the uterine cervix

A case of neuroendocrine carcinoma of the uterine cervix with focal papillary clusters and psammoma bodies, features not previously seen in this tumor, is documented. Papanicolaou-stained cervicovaginal smears and pelvic washings are correlated with tissue sections of endocervical curettage, hysterectomy and cul-de-sac biopsy specimens. Although there was some variation in the cytologic features, the tumor cells were generally distinguished by nuclear molding, indistinct nucleoli, finely granular chromatin and scant cytoplasm. Argyrophil-positive intracytoplasmic granules were identified in tissue sections of the tumor. These granules were positive for ACTH and neuron-specific enolase using the immunoperoxidase technique. Ultrastructural studies were consistent with these findings. Neuroendocrine carcinoma of the cervix is therefore a cytologically distinctive tumor in which psammoma bodies may occur.