Cytodiagnosis of endometrial malignant mixed mesodermal tumor

The accuracy of endometrial aspiration smears obtained with the Isaacs cell sampler in the diagnosis of malignant mixed mesodermal tumors (MMMT) was compared to the results obtained with routine cervical and vaginal smears in five cases of MMMT found in a series of 220 endometrial aspirations. Cervical and vaginal smears previously taken on these patients were positive for adenocarcinoma or MMMT in two cases and suspicious for adenocarcinoma in the remaining three cases. Endometrial aspirates were positive for MMMT in three cases and positive for adenocarcinoma or MMMT in two cases. The endometrial aspiration smears contained a variety of cells: malignant glandular, squamous, spindly stromal, undifferentiated, osteoid and tumor giant cells; chondrocytes and free psammoma bodies were also observed. These cases indicated that endometrial aspiration can accurately detect the heterologous cellular elements found in MMMT and is an effective technique in its diagnosis.     

Preparation of monolayer smears from paraffin-embedded tissue for image cytometry

A method is described for the preparation of monolayer smears from paraffin-embedded tissue suitable for automated image analysis and DNA measurements. The proposed technique uses enzyme treatment and syringing for cell dispersal. Slide preparation is performed by centrifugal cytology. After Feulgen staining the quality of the monolayer smears is sufficiently high to enable visual morphologic evaluation. Automated DNA measurements using the Leyden television analysis system (LEYTAS) show coefficients of variation (CV) of 4.5% for the diploid cell population of the suspended tissue. This is approximately the same as the CV in fresh material from the same tumor. Formalin fixed trout red blood cells are used as reference cells. By applying image cytometry to paraffin-embedded tissue this method allows retrospective studies of, for instance, the significance of DNA content with regard to the behavior of a tumor.     

Tumor marker studies of cervical smears. Potential for automation

The distribution of three tumor markers, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and prekeratin (PK) was studied in exfoliated epithelial cells in cervical smears using an immunoalkaline phosphatase staining technique to demonstrate the antigens. EMA was expressed by abnormal cells in a consistent and reproducible fashion whereas the other two markers were variably expressed by both normal and abnormal cells. Our results suggest that immunocytochemical staining for EMA could be of value not only for the diagnosis of cervical intraepithelial neoplasia but also for the automated screening of cervical smears.     

Neutrophilic phagocytosis by tumor cells. A feature to consider in the differential diagnosis in fine needle aspiration smears

OBJECTIVE: To analyze neutrophilic phagocytosis by tumor cells in fine needle aspirate (FNA) smears from different types of tumor. STUDY DESIGN: A retrospective review of a total of 7 cases showing prominent neutrophilic phagocytosis by tumor cells in FNA smears during the period July 2003-December 2004. RESULTS: This feature was seen in malignant fibrous histiocytoma and poorly differentiated renal cell carcinoma in addition to giant cell carcinoma of the lung. CONCLUSION: Neutrophilic phagocytosis by tumor cells is seen in FNA smears and on cytomorphology. The differential diagnoses should include both pleomorphic sarcomas and carcinomas.     

Carcinoid tumor metastatic to breast diagnosed by fine needle aspiration. Case report and literature review

Fine needle aspiration (FNA) biopsy was used to study a mass in the left breast in a patient with a previous history of an ileal carcinoid tumor and later lymph node metastases who presented with bilateral palpable breast masses. The FNA specimens showed the lesion to be a carcinoid tumor. The metastatic nature of the lesion was proven by positive restaining of FNA smears by both the Sevier-Munger technique (demonstrating abundant argyrophilic cytoplasmic granules) and the Fontana-Masson method (showing argentaffin cytoplasmic granules). The distinction between primary and metastatic carcinoid tumors of the breast is discussed, as is their origin and their differentiation from other malignancies of the breast.     

Evaluation of an antibody to human milk fat globule antigen in the detection of metastatic carcinoma in pleural, pericardial and peritoneal fluids

An antibody to human milk fat globule-2 (HMFG-2) antigen was investigated to assess its value in detecting tumors in pleural, pericardial and peritoneal fluids. One hundred forty consecutive fluids were evaluated using the avidin-biotin complex (ABC) technique. Conventional cytology and HMFG-2-stained smears were compared using the former as the standard for tumor detection. Discrepant results were found in 15 specimens (8 false negatives and 7 false positives). Causes for discrepancy between the methods included lack of HMFG-2 antigen on tumor cells, random sampling error and endometrial cells ectopically located in the pelvic cavity or introduced during uterine instrumentation. We conclude staining for HMFG-2 may be a useful adjuvant technique for the detection of rare tumor cells in body fluids provided there is a high index of suspicion of metastasis from an HMFG-2-positive primary neoplasm.     

Ag-NOR technique in fine needle aspiration cytology of salivary gland masses.

Because of their complexity, salivary gland lesions are often difficult to identify correctly with fine needle aspiration cytology. To see whether the Ag-NOR staining technique for nucleolar organizer regions would be useful in this respect, we studied a series of smears from benign and malignant salivary gland lesions. The smears, previously treated with Papanicolaou and May-Grünwald-Giemsa stain, were destained and restained with Ag-NOR silver. The correlation between the cytologic-histologic diagnosis and the number of Ag-NORs in benign (sialadenitis, pleomorphic adenoma, oncocytoma and Warthin's tumor) and malignant lesions (adenoid cystic carcinoma, adenocarcinoma, carcinoma ex pleomorphic adenoma and squamous carcinoma) was statistically significant (P = less than .05). The Ag-NOR technique appears useful in the diagnosis of salivary gland lesions. One great advantage is that previously stained slides can be reused for silver staining, thus providing an excellent guide to the diagnosis, especially in doubtful cases and when corresponding histologic specimens or extra unstained slides are unavailable.     

Confirmation of genital herpes simplex viral infection by an immunoperoxidase technique

Over the 12-month period from April 1984 to April 1985, 512,000 gynecologic (Papanicolaou) smears were examined in the Provincial Screening Program in British Columbia. During this time, 307 patients were found to have smears that contained cells consistent with, or suggestive of, a herpes simplex viral (HSV) infection. The Papanicolaou-stained smears from these 307 cases were subsequently restained, without prior destaining, using an immunoperoxidase technique specific for type 2 HSV (HSV-2) and cross reactive with HSV-1. Of the 205 smears containing cells considered to be consistent with a herpes infection, 187 were positive using the immunoperoxidase technique. Of the 102 smears showing reactive cell changes though unlikely to be causes by an HSV infection, only 5 were positive using the immunoperoxidase technique. The results show that the immunoperoxidase technique is a rapid and reliable method of confirming a suspected diagnosis of herpetic infection and that it is particularly useful in those patients in whom the Papanicolaou smear findings are equivocal.     

Cytology of desmoplastic medulloblastoma in imprint smears: a report of 2 cases

BACKGROUND: Desmoplastic medulloblastoma is a rare subtype of medulloblastoma with astroglial differentiation. The cytomorphologic features in intraoperative imprint smears from 2 cases of desmoplastic medulloblastoma are described. CASE REPORTS: A 22-year-old man and 27-year-old woman with a cerebellar tumor underwent craniotomy and tumor resection. The imprint cytologic smears contained cellular zones and nodular hypocellular areas containing astroglial and oligodendrogliallike elements. The cytology was misinterpreted as glial tumors, while the final histologic diagnosis in both cases were desmoplastic medulloblastoma. CONCLUSION: Desmoplastic medulloblastoma shows distinctive cytology in intraoperative smears. However, the occurrence of this rare type in adults and the presence of astroglial elements in imprint smears may cause a cytologic misinterpretation as gliomas.     

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.     

Prognostic value of histochemical evaluation of steroid binding sites in breast tumors

Frozen tumor sections and/or cytological smears and aspirates from 614 patients were studied utilizing the fluorescent estrogen binding technique of Lee. Survival analyses of the results indicated that women less than 55 years of age and with positive tumors had a statistically better disease-free interval and survived significantly longer than older patients. The method is thus an independent predictor of survival and disease-free interval in this subgroup of breast cancer patients.     

Cytology of bronchial benign granular-cell tumor

The cytologic features of a case with multiple bronchial benign granular-cell tumors are reported and compared with those of previously reported cases. Characteristic tumor cells were found in the bronchoscopic brushing smears and in cell block sections (but not smears) prepared from the washing fluid. These findings were confirmed by the bronchial biopsy and histologic study of the resected tumors. A cytologic diagnosis of bronchial granular-cell tumor should not be difficult because the cytologic appearance of the tumor cells is characteristic; however, the possibility of a concomitant tumor, such as adenocarcinoma or small-cell carcinoma, should be considered and excluded.     

Basement membrane material and tigroid background in a fine needle aspirate of clear cell adenocarcinoma of the cervix. A case report

BACKGROUND: Although cytologic findings of clear cell adenocarcinoma of the female genital tract have been reported sporadically, the background on the smear has received little attention. CASE: A 16-year-old female had a large, necrotic mass in the cervix. As cervical brushing cytology and a punch biopsy of the mass could not make a definitive diagnosis, fine needle aspiration cytology was performed from the mass. The smears revealed loose, three-dimensional clusters and sheet arrangements of atypical cells. Dispersed atypical cells were also seen. The atypical cells were large and had abundant, weakly stained cytoplasm and round or oval nuclei with large nucleoli. There were a few tumor cells with clear cytoplasm and distinct cell borders in Papanicolaou-stained smears. The background in Diff-Quik-stained smears revealed a tigroid background and basement membrane material. CONCLUSION: The malignant tumor, revealing both a tigroid background and basement membrane material, seems to have been clear cell adenocarcinoma. Both features are diagnostic clues to clear cell adenocarcinoma in the female genital tract. Our case indicates that aspiration cytology is also an effective method of diagnosing a cervical tumor when the tumor is polypoid and the surface is extensively necrotic.     

Adult-type rhabdomyoma of the palate. Cytologic presentation of two cases with histologic and immunologic study

The cytologic presentations of two adult-type rhabdomyomas of the soft palate are reported. Fine needle aspiration smears of the lesions contained globular tumor cells that had striations and intracytoplasmic rod-shaped inclusions. These inclusions, corresponding to hypertrophied Z bands, were pathognomonic of rhabdomyoma tissue. The cytologic diagnosis was confirmed by histologic and immunologic studies in both cases. The cytologic preparations fixed in alcohol or air dried did not show the "spiderweb cells" observed in the histologic sections of tissue fragments fixed in formaldehyde; this clearly illustrates that the morphology of the cells of this tumor depends primarily on the specimen preparation technique used. These cases suggest that aspiration cytology can establish the diagnosis of this benign tumor of striated muscle, for which total surgical removal is usually sufficient to effect a cure. The differential diagnosis is discussed in detail.     

Problem of size dependence in fluorescence DNA cytometry

The relationship among fluorescence intensity, area, thickness, and DNA concentration of DNA-bearing polyacrylamide film, stained with 50 ng/ml DAPI, was studied using an epi-illumination cytofluorometer. Measurements and theoretical analysis suggest the inevitability of the size-dependent effect on human cell nuclei in which the order of the DNA concentration is approximately 10 mg/ml, and that this effect can be virtually negated if the nuclei are stretched and flattened to less than 0.33 microns in thickness on the smears. Alternative practical ways to minimize this effect are to decrease the dye concentration of a staining solution and to make smears as thin and uniform as possible by some means such as hypotonic treatment and/or using an automatic centrifuge smearing apparatus. The size-dependent effect, nevertheless, should be taken into account particularly when determining the DNA content of different cell types and the DNA aneuploidy of tumor cells, regardless of the technique used for measurement.     

Efficacy of cotton-tipped applicators for obtaining cells from the uterine cervix for Papanicolaou smears

A study was made of the efficacy of two techniques for the preparation of Papanicolaou smears. In one technique ("swab-spatula technique"), a scraping of the endocervix with a saline-moistened cotton-tipped applicator was combined with a scraping of the ectocervix with a plastic spatula. In the second technique ("swab technique"), the endocervix and ectocervix were scraped with only a saline-moistened cotton-tipped applicator. The swab technique produced more inadequate smears with a scanty cellular yield (24/408 = 6%) than did the swab-spatula technique (9/361 = 3%). The swab technique also produced higher false-negative rates (60% for CIN I, 42% for CIN II, 16% for CIN III, 20% for invasive cancer, and 32% overall) as compared with those of the swab-spatula technique (27% for CIN I, 29% for CIN II, 14% for CIN III, 0% for invasive cancer and 18% overall). Because of the higher rates of inadequate samples and false negativity in smears prepared by cotton-tipped applicators alone, it is recommended that the spatula not be omitted in taking cervical samples for the preparation of Papanicolaou smears for the detection of dysplasia or cancer. This study also reflects a poor performance of a cervical cancer detection system in the setting of a major medical school and suggests the need for instruction and periodic evaluation of the performance of the staff taking the smears. This study also substantiates doubt on the value of a second recent smear as a follow-up procedure for cervical dysplasia.     

Assessment of histogenesis and proliferative potential in cytologic specimens of human brain tumors. Value of immunocytochemistry and nucleolar organizer regions.

The value of immunocytochemistry and nucleolar organizer regions (NORs) for the histogenetic identification and the estimation of the proliferative potential of brain tumors was assessed by the investigation of imprint smears of 51 neurosurgical tumor specimens. A panel of five monoclonal antibodies was used to cover a broad range of immunohistochemical markers. For the assessment of NORs, a silver staining technique (AgNOR) was used. NORs were enumerated and measured by means of an interactive image analysis system. The immunocytochemical results were similar for the smears and paraffin-embedded sections for 95.6% of the investigations performed and for 76.2% of the cases. Glial fibrillary acidic protein (GFAP) was positive in 9 of 17 tumors of glial origin, but was negative in 9 metastatic tumors. Vimentin was positive in 10 of 10 and fibronectin in 9 of 10 meningiomas investigated. The number of NORs increased steadily with the increasing grade of malignancy. Especially in glioblastomas, the number of NORs per cell exhibited a wide range, which might reflect the heterogeneity of these neoplasms. Metastases revealed a higher number of NORs per cell than did glioblastomas. In the cytologic differential diagnosis of these tumors, an absence of GFAP expression combined with a high NOR count is suggestive of a metastatic tumor.     

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.     

Detection of Epstein-Barr virus-associated antigen in fine needle aspiration smears from cervical lymph nodes in the diagnosis of nasopharyngeal carcinoma

Epstein-Barr virus (EBV) has consistently been shown to be associated with undifferentiated nasopharyngeal carcinoma, and an EBV-associated nuclear antigen (EBNA) has been detected in the cells of nasopharyngeal carcinoma. A study on the applicability of EBNA detection in fine needle aspiration (FNA) smears from cervical lymph nodes in the diagnosis of metastatic nasopharyngeal carcinoma was performed. All 11 cases (100%) with metastatic nasopharyngeal carcinoma showed EBNA-positive tumor cells, characterized by bright, granulated nuclear fluorescence. Three (50%) of six cases with other metastatic head and neck carcinomas also showed EBNA-positive tumor cells. These findings suggest that the presence of EBNA-positive tumor cells in FNA smears from cervical lymph nodes is not specific for metastatic nasopharyngeal carcinoma. On the other hand, a negative result in the presence of tumor cells may help to exclude it. A larger study is required to verify these preliminary findings.