Cytology of polychrome-stained equine synovial fluid smears. Comparison with clinical findings, histologic specimens, Wright-Giemsa-stained smears and outcome.

Polychrome-stained equine synovial fluid specimens from 34 normal joints and 129 joints with clinical abnormalities were examined cytologically. The smears from joints with abnormalities were categorized as within normal limits (4.7%), slight abnormality (27.9%), proliferative synovitis (21.7%), neutrophilic pattern (20.2%), elongated cell pattern (10.1%), other moderate to marked abnormality (11.6%) and unsatisfactory (3.9%). Cytologic abnormalities that were not restricted to a single category included spindle cells, crystals, stellate cells and cartilage fragments. Multinucleate cells and mononucleate cells with dense cytoplasm and a delicate periphery were seen in smears from cases with clinical diagnoses of osteochondrosis or fracture; interpretation of these cells as osteoclasts and their mononucleate precursors was supported by positive staining with tartrate-resistant acid phosphatase. Smears within the same cytologic category were not found to correspond with a single clinical diagnosis. The identification of several cytologic patterns in cases with the same clinical diagnosis suggests that multiple stages of disease were sampled. Except in cases with the cytologic neutrophilic pattern, there was not a consistent relationship between the histologic features in synovial biopsy specimens and the cytologic findings; the morphologic variation within synovial membrane sections and between sections from different locations was sometimes marked. When compared with air-dried, Wright-Giemsa-stained smears, the polychrome-stained smears were more sensitive in the detection of cytologic abnormalities and were less often falsely negative or unsatisfactory. Following surgery, cases with clinical diagnoses of osteochondrosis (29 cases) and fracture (25 cases) were analyzed according to clinical outcome and cytologic category. While 80% of the horses with proliferative synovitis in cytologic specimens were sound, only 67% of those with the elongated cell pattern, 50% of those with slight abnormality and 33% of those with other moderate to marked abnormality were sound. A statistically significant relationship (P less than .02) was found in cases with a diagnosis of osteochondrosis: animals with a proliferative synovitis pattern were almost three times as likely to be sound as compared to those with slight abnormality. These findings indicate that polychrome-stained equine synovial fluid smears (1) provide information that is different from that found in corresponding histologic sections and (2) are superior to air-dried, Wright-Giemsa-stained smears for cytologic examination. The polychrome-stained equine synovial fluid smears were found to provide information supportive of clinical, radiographic and prognostic data.     

Immunocytodiagnosis of carcinocythemia in disseminated breast cancer

A small number of large, malignant mononuclear cells were found in the blood of a patient with disseminated breast carcinoma. The detection of these scarce cells was facilitated by examining leukocyte concentrates. Cytochemical and immunochemical studies showed that these were epithelial cells, not hemopoietic cells. These findings, when correlated with the clinical features and the cytologic findings in blood and marrow, suggested that the malignant mononuclear cells in the blood were breast carcinoma cells. This study demonstrates the technical feasibility of accurately identifying cells in blood, which may stimulate interest in the study of cancer cells in the circulating blood. The method may also be applied to other cytologic specimens, such as fine needle aspirates, that contain only a few neoplastic cells.     

Cytologic diagnosis of the papillary variant of renal-cell carcinoma

The papillary variant of renal-cell carcinoma is characterized by distinctive histologic, clinical and angiographic features. A study was undertaken to delineate the cytologic features of this tumor as it is encountered in cellular samples. Cytologic specimens containing tumor cells from eight patients who underwent resection for papillary renal-cell carcinoma were examined and compared to corresponding cytologic samples obtained from ten other patients who had nonpapillary renal-cell carcinoma. The cytologic appearance of papillary renal-cell carcinoma, which is deceptively benign, is marked by distinctive papillary structures that often resemble branched chains. The cells are usually small and contain uniform nuclei; numerous macrophages with foamy cytoplasm are often found in the background. These cytologic features were not observed in the cellular specimens from the nonpapillary renal carcinomas. We conclude that papillary renal-cell carcinoma can be confidently recognized in cytologic specimens.     

Karyometry of breast epithelial cells acquired by random periareolar fine needle aspiration in women at high risk for breast cancer

OBJECTIVE: To establish whether karyometry was likely to detect change in the proportion of abnormal cells in random periareolar fine needle aspiration (RPFNA) specimens from high-risk women in a 6-month prevention trial with an aromatase inhibitor. STUDY DESIGN: Papanicolaou-stained ThinPrep slides of RPFNA samples from 11 of 42 women were digitally recorded at high resolution, with 200 cells measured per slide, at baseline (BL) and at the end of study (ES) after 6 months. The nuclear chromatin pattern characteristics were assessed by multivariate analytic techniques; determination of nuclear abnormalities was performed and cells that showed expression of abnormality were identified. RESULTS: The BL FNA samples contain approximately 90% cells with a chromatin pattern as expected in a normal cell population. A small subpopulation of cells had deviations from normal. At ES the proportion of these cells was reduced, to a statistically significant degree,from < 10% to 2-5%. CONCLUSION: Nuclear karyometry is a promising technique for characterizing the proportion of cells deviating from normal in cytologic specimens and should be explored further as an intermediate endpoint in prevention trials.     

Unusual cytologic findings in low grade papillary transitional cell carcinoma

OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells.     

The cytopathology of bone marrow transplantation

Bone marrow transplantation (BMT) is an increasingly effective treatment for patients with hematologic disorders and malignant neoplasms. From 1975 to 1986, 1,457 specimens were obtained for cytologic evaluation from 328 of the 635 patients who received BMTs at Memorial Sloan-Kettering Cancer Center. These specimens consisted of 1,049 cerebrospinal fluids (CSFs) from 265 patients, 292 bronchoscopy specimens from 92 symptomatic patients and 116 other specimens (including brushings from the liver and gastrointestinal tract, sputa, urines and cervico-vaginal smears). CSF specimens examined before and after BMT from 80 (30%) patients showed an increased number of benign, nonepithelial cells, which were mainly lymphocytic or histiocytic in origin. Malignant cells were detected in CSF specimens from 44 (17%) patients. Bronchoscopy specimens from 3 patients had suspicious cells present; those from 27 patients contained opportunistic organisms. Atypical epithelial or lymphoreticular cells were seen in bronchial specimens from 49 patients. All cytologic findings were correlated with the pertinent clinical information as well as biopsy and autopsy material, including histopathologic evidence of graft-versus-host disease. Cytologic evaluation, especially of bronchial and CSF specimens, was useful in diagnosing the presence of malignant neoplasms, infectious organisms, inflammatory responses, reactive lesions and cellular atypia due to treatment.     

Presentation of Sporothrix schenkii in pulmonary cytology specimens

Macrophages containing small ovoid intracytoplasmic yeast cells, surrounded by a slight "halo," were observed in Papanicolaou-stained smears of sputum submitted for cytologic examination from two patients with culture-confirmed pulmonary sporotrichosis. The cytologic findings are presented and discussed in relation to other pulmonary fungal infections and the appropriate stains to be used for their cytologic detection. The clinical symptoms of pulmonary sporotrichosis are nonspecific and may mimic those of tuberculosis or other diseases; the causative organism, Sporothrix schenkii, may remain undetected by routine microbiologic procedures unless there is cause to suspect the diagnosis. Sporotrichosis should be considered in the differential diagnosis when small ovoid intracellular yeast cells (2 microns to 4 microns in length) with an apparent "halo" are observed within macrophages in pulmonary cytology specimens; the recognition of these findings may aid in the diagnosis of this relatively rare disease.     

Intraocular tumors. A cytopathologic study

The cytologic characteristics and histopathologic correlates of common ocular tumors were examined using (1) cytologic and histologic specimens prepared from enucleated eyes with retinoblastoma and melanoma, (2) cytologic specimens prepared from clinically obtained intraocular fluids from eyes with lymphoma, metastatic adenocarcinoma and retinoblastoma and (3) cytologic specimens prepared from orbital aspirates and cerebrospinal fluids from a patient in whom retinoblastoma had spread to the orbit and central nervous system. Retinoblastoma cells occurred singly and in clusters and were associated with abundant necrotic debris and portions of capillaries with perivascular tumor infiltrates. Melanoma cells frequently had prominent nucleoli and variable amounts of fine cytoplasmic pigmentation and were found individually and in groups. Lymphoma cells were noncohesive, with scant cytoplasm. Metastatic intraocular adenocarcinoma cells had well-defined borders, multiple nucleoli and vacuolated cytoplasm. In general, the cellular morphology in the cytologic and tissue preparations of the intraocular tumors correlated well with each other. The findings suggest that common primary and metastatic intraocular tumors can be differentiated in cytologic preparations.     

Urinary cytology in renal transplant recipients with stable graft functions

The utility of routine urinary cytology in renal transplant recipients was investigated. Slides of 79 urine samples obtained from 59 renal transplant patients shortly after transplantation and of 275 urine sediments from 126 patients who had received a transplant before 1978 were screened for abnormal urothelial cells. None of the samples taken within one year of transplantation contained malignant cells. For five patients transplanted before 1978, repeated cytologic examinations showed malignant cells, but neither urologic examination nor clinical nor postmortem follow-up studies revealed a tumor. In all five cases, the abnormal cells disappeared from repeat samples within two to three months. None of the other 121 patients, with repeatedly normal urinary cytologies, exhibited a urinary tract carcinoma in the 24-month follow-up period. It would appear that the cytologic findings in the urine of renal transplant patients who have received long-term immunosuppressive medication may be transiently abnormal.     

Cytology of pleomorphic lobular carcinoma with apocrine cell differentiation of the breast. A case report

BACKGROUND: Pleomorphic lobular carcinoma (PLC) with apocrine differentiation is a rare breast carcinoma, and its cytologic findings have not been reported before. CASE: A 75-year-old woman had a mass in and skin rash on the left breast. Apocrine carcinoma was suggested on aspiration cytology of the mass. The cytologic smears showed a small number of rounded to oval, atypical cells that were poorly cohesive and individually scattered. The cytoplasm was relatively abundant and contained coarse granules and dropletlike, orange granules (Lendrum's granules). The cell border was distinct. Some atypical cells had intracytoplasmic lumina. The nucleoli were round and prominent, and nuclear chromatin was finely granular. The background was clean. Histologically, the tumor cells proliferated mainly in an Indian file pattern and showed a concentric, targetoid pattern around the non-neoplastic ducts. The cytoplasm was abundant, eosinophilic, granular, positive for the periodic acid-Schiff reaction and diastase resistant. Immunohistochemically the tumor cells were positive for gross cystic disease fluid protein-15 (GCDFP-15) and negative for E-cadherin. Lendrum's granules showed positive expression of GCDFP-15 and lysozyme. CONCLUSION: PLC with apocrine differentiation and apocrine carcinoma may be cytologically confused. Poor cellularity, less cohesiveness, finely granular chromatin, a nonpolyhedral cellular outline and clean background indicate the former rather than the latter. It is important to be aware that PLC presents a variety of cytologic configurations.     

Mycosis fungoides with pulmonary involvement. Cytopathologic findings

In order to define the cytologic features of pulmonary involvement by mycosis fungoides, 15 respiratory cytology specimens from four patients with biopsy-proven pulmonary mycosis fungoides were reviewed. The presence in sputum smears of occasional small or large cerebriform mononucleated cells against a background of numerous atypical lymphocytic cells permitted an antemortem cytologic diagnosis of probable or definite dissemination of mycosis fungoides with pulmonary involvement. Similar cells were seen in aspiration smears. The lymphocytic infiltrates were similar to those in corresponding skin biopsies in each case. The distinctive cytologic findings in these cases may therefore help to determine the underlying etiology of pulmonary lesions and may contribute to the antemortem diagnosis of visceral dissemination of mycosis fungoides.     

Fine needle aspiration cytology of sclerosing adenosis of the breast

OBJECTIVE: To analyze the cytologic findings of sclerosing adenosis of the breast. STUDY DESIGN: We reviewed the fine needle aspiration (FNA) cytologic slides of 7 cases of sclerosing adenosis of the breast and compared the cytologic findings with those of 10 cases of fibroadenoma and 7 cases of fibrocystic change. RESULTS: The smears of sclerosing adenosis were moderately to markedly cellular, consisting of small to large groups of benign epithelial cells arranged with variable architecture. Acinar sheets, scattered individual epithelial cells and small, dense, hyalinized stroma were found in all cases of sclerosing adenosis. Epithelial cells in sclerosing adenosis appeared more frequently as acinar sheets and discohesive individual cells than did those of fibroadenoma (P < .05). However, the branching pattern of epithelial sheets, large sheets and bipolar, naked nuclei were commonly found in fibroadenoma (P < .05). Fibroadenoma had large, hypocellular, fibromyxoid stroma, whereas sclerosing adenosis had small, dense, hyalinized stroma occasionally attached to the epithelial sheets. As compared with fibrocystic change, sclerosing adenosis had similar findings but showed more abundant cellularity, acinar sheets and individual epithelial cells, and the presence of stroma (P < .05). CONCLUSION: Findings of frequent acinar sheets and small, dense, hyalinized stroma attached to epithelial sheets can aid the FNA cytologic diagnosis of sclerosing adenosis. Awareness of the presence of scattered individual epithelial cells in cytologic smears of sclerosing adenosis can help prevent a misdiagnosis of malignancy.     

Cytologic findings in posttransplant lymphoproliferative disease

Transplant patients are at an increased risk of developing lymphoproliferative disorders (LPDs). To examine the role of cytology in diagnosing LPDs, the cytologic reports on all transplant patients seen at the University of Iowa from January 1983 to July 1988 were reviewed. Thirteen of 649 transplant patients developed LPD; 10 of those 13 patients had a total of 25 cytologic specimens obtained within two months of the diagnosis of LPD available for review. Ten specimens (four cerebrospinal fluids [CSFs], four effusions, one respiratory specimen and one liver aspirate) from six patients were positive for LPD. Immunophenotypic or immunogenotypic studies on cytologic specimens from four patients showed a clonal B-cell process. The cytologic features ranged from those of a plasmacytoid LPD to those of an immunoblastic or large-cell lymphoma. An additional seven specimens (five CSFs, one effusion and one liver aspirate) from four patients were suspicious for LPD, exhibiting rare atypical cells or cells with plasmacytoid features. Ten patients died with LPD within 12 months; three are alive. Cytologic specimens, especially body fluids, are frequently positive in LPD and may be useful diagnostically. Since the differential diagnosis includes reactive lymphocytosis, confirmatory immunophenotypic or immunogenotypic studies are recommended.     

Cribriform-morular variant of papillary thyroid carcinoma. Report of a case showing morules with peculiar nuclear clearing

BACKGROUND: There have been only 4 reported cases of cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) with cytologic findings from fine needle aspiration. In these reports, the cytologic findings do not fully reflect the histologic characteristics of this entity. We report a case of CMVPTC in which a cribriform pattern without colloid and epithelial morules with peculiar nuclear clearing (PNC) were present in smears, thus fulfilling the criteria for a cytologic diagnosis of CMVPTC. Protein truncation tests for APC molecule abnormality indicated the presence of germline mutation in the patient's APC gene. CASE: A 30-year-old woman had multiple thyroid tumors. Aspiration cytology revealed a large number of round to spindle-shaped atypical-cells showing sheet-like, cribriform, follicular, whorl-like and solid, 3-dimensional arrangements. The cribriform and follicular arrangements did not contain colloid in the lumen. The powdery chromatin pattern characteristic of papillary carcinoma was not observed, but there were scattered intranuclear cytoplasmic pseudoinclusions and grooved nuclei. The nuclei of the atypical cells presenting in the whorl formations showed enlargement, thickened nuclear membranes and entirely clear contents, consistent with PNC. Hyalinelike necrotic cells were also observed in the cell clusters or in the background. Histologic and immunohistochemical findings were typical of CMVPTC. CONCLUSION: The cribriform pattern without colloid, fascicular or whorl formation of spindle cells, and morules with PNC are identifiable on cytologic smears and are sufficiently distinctive to allow a cytologic diagnosis of CMVPTC.     

Colonic cytology. A retrospective study with histopathologic correlation

Three hundred sixty cytologic specimens obtained by colonoscopic brushing from 336 patients were compared with biopsy specimens simultaneously obtained for histologic examination. Of the cytologic specimens, 160 (44%) were positive for malignant cells, 37 (10%) contained suspicious cells, 54 (15%) had atypical glandular cells, 107 were cytologically negative, and 2 were considered unsatisfactory. Eight-four percent of the patients with cytologically positive smears and 54% of those with suspicious smears had malignant neoplasms in the simultaneously obtained tissue biopsies. Of the patients with follow-up, all with cytologically positive findings and nine with suspicious findings on the initial cytologic examination and simultaneous negative tissue biopsies, were subsequently found to have carcinoma of the colon. Cytology proved to have a sensitivity of 0.73 and a specificity of 1.00 while tissue biopsy showed a sensitivity of 0.81 and a specificity of 1.00. By combining the two methods, the sensitivity increased to 0.92. It is concluded that cytologic examination of colonic brushings is a highly accurate and reliable technique for the detection of malignant neoplasms of the colon and can preempt the use of biopsy forceps.     

Preoperative cytologic diagnosis of primary gastrointestinal malignant lymphoma

This report is based on the review and study of primary gastrointestinal malignant lymphomas as seen in cytologic brushing and washing specimens. During a period of 12 years (1970 to 1981), a total of 2,675 patients with malignant lymphoma involving the gastrointestinal tract were seen at Memorial Sloan-Kettering Cancer Center. Of these patients, 73 were diagnosed as having primary malignant lymphoma of the gastrointestinal tract. A total of 49 preoperative cytologic specimens obtained from 29 patients with histologically confirmed primary gastrointestinal malignant lymphoma were examined and are the basis for this study. Twenty-four patients had gastric primaries; three tumors were in the colon and two were small intestinal lymphomas. Thirty-three cytologic specimens taken from 25 patients were considered diagnostic for malignant lymphoma. A positive cytologic brushing was the only diagnostic preoperative specimen for 9 of the 29 patients. Combined cytologic and biopsy specimens provided a diagnosis of malignant lymphoma for 16 patients. Cytologic washings did not add to the diagnostic accuracy. The 29 cases of malignant lymphoma reviewed here were histologically subclassified as 23 large-cell, poorly differentiated and six small-cell, well-differentiated lesions. The cytomorphologic features of malignant lymphoma as observed in gastrointestinal specimens are outlined, and differential diagnoses are discussed. Clinicopathologic implications of the cytologic findings are considered.     

Aspiration cytology of tubular breast carcinoma

The cytologic features in smears of fine needle aspirates from 34 tubular breast carcinomas were studied. Uniform and bland epithelium in cohesive clusters dominated all specimens; two-thirds also showed some degree of cellular dissociation. Characteristic (but not quite pathognomonic) angular epithelial clusters with a tubular structure occurred in about 50% of the smears. Sparsely occurring atypical nuclei and/or cytoplasmic vacuoles, similar to those seen in lobular cancer, were found in half of the cases. Although a lack of myoepithelial cells was apparent in the majority of the smears, one-fourth of them showed a quite prominent myoepithelial component. Various combinations of atypical features resulted in a picture that was considered diagnostic of malignancy in 50% of the cases; the remaining specimens showed less pronounced atypia. Other pitfalls associated with the cytologic diagnosis of tubular carcinoma are discussed, and the importance of basing the management of small breast lesions on the mammographic as well as on the cytologic findings is emphasized.     

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.     

Cytologic study of tissue repair in human bronchial epithelium

The cytologic findings of atypical cells considered to be tissue repair cells after mechanical injury to the bronchial epithelium are reported. These cells were studied in sequential bronchial brushing smears from patients who underwent repeated bronchoscopies for the diagnosis of lung cancer. The cellular findings varied according to the length of time since the previous bronchial brushing. Many cell clusters of highly atypical cells in two-dimensional sheets with large nuclei and prominent nucleoli were observed in specimens taken two or three days after a previous brushing; mitotic figures were observed on day two. In specimens taken on days four and five, the number of atypical cells was decreased and the degree of atypia was slight.