Qualification of atypical squamous cells of undetermined significance in an independent laboratory: is it useful or significant?

OBJECTIVES: Correlation of cervical smears and biopsy samples emphasizes the significance of atypical squamous cells of undetermined significance as a diagnostic category. STUDY DESIGN: A retrospective study (October 1, 1995-March 21, 1997) was performed on all Papanicolaou smears diagnosed at DIANON Systems, Inc (Stratford, Conn). RESULTS: During this period 1551 patients with Papanicolaou smears had subsequent cervical biopsies performed within 90 days of cytologic sampling. There were 560 diagnoses of atypical squamous cells of undetermined significance. Tissue specimen results were positive in 203 cases (36.2%) and negative in 357 cases (63.8%). Of the positive biopsy results after a smear with atypical squamous cells of undetermined significance, 109 showed low-grade squamous intraepithelial lesions and 94 showed high-grade squamous intraepithelial lesions. CONCLUSIONS: This study, the largest cytologic and histologic correlation of atypical squamous cells of undetermined significance, demonstrates that a significant percentage of smears with atypical squamous cells of undetermined significance represent squamous intraepithelial lesions and that qualification of atypical squamous cells of undetermined significance as reactive or dysplastic is useful and should serve as a guide for patient management.

A triple stain for the detection of Helicobacter pylori in gastric brushing cytology.

OBJECTIVE: Helicobacter pylori is a surface bacterium associated with gastritis. The triple stain (TS), combining silver, hematoxylin and eosin, and alcian blue at pH 2.5, is valuable in the detection of H pylori in tissue. We evaluated the usefulness of TS as compared with Papanicolaou stain in detecting H pylori in gastric brushings and biopsy specimens. STUDY DESIGN: Gastric brushings and biopsy specimens were obtained from 21 patients. The Papanicolaou-stained slides were restained with TS, and the brushings and biopsy specimens were independently evaluated by the authors. RESULTS: H pylori was found in 9 of 21 randomly selected cases using TS. Of these, two cases were positive on brushings alone and three on biopsy alone. Only three of the nine cases were positive by Papanicolaou stain. None of the 21 samples were positive with Papanicolaou stain yet negative with TS. Detection of H pylori was restricted to patients with gastric ulcerations but was not limited by paucity of glands. CONCLUSION: TS is useful for detecting H pylori in gastric brushings and provides excellent cytologic detail. Furthermore, TS is superior to Papanicolaou stain for H pylori detection and is a valuable adjunct to biopsy.

Angiotropic large cell lymphoma presenting as primary adrenal insufficiency.

Angiotropic large cell lymphoma is reported in two patients who developed severe metabolic acidosis and unexplained hypotension before death. In addition to the usual multiorgan involvement of the disease, the adrenal glands of both patients were symmetrically enlarged. Histologically, the cortical vessels were engorged and filled with neoplastic lymphoid cells of B-cell lineage, whereas the parenchymal cells were compressed and atrophic. Angiotrophic large cell lymphoma seems to be a distinct and unrecognized cause of primary adrenal insufficiency, and should be included in the differential diagnosis of adrenal hormone deficiency.

On-site adequacy assessments for image-directed fine needle aspirations: a study of 341 cases.

On-site adequacy assessments (OSAA) are reported to decrease the unsatisfactory and nondiagnostic rates of fine needle aspirations (FNAs). These have been routine in many institutions but were only recently introduced to our large teaching hospital. The results of FNAs performed in diagnostic radiology between January to December 1992 were compared to aspirations done by the same clinical staff during the first year (1993) after the addition of an on-site adequacy assessment service. In the year prior to OSAA, 154 FNAs were performed in diagnostic radiology and the material obtained was processed by a cytotechnologist. Of these, 89 (58%) cases were positive for malignant cells. Approximately half of these cases had confirmatory tissue biopsies processed in the surgical pathology department of our institution. The remaining 65 (42%) of cytology specimens were determined to be negative or nondiagnostic for malignancy. These canes either had no tissue follow-up or the tissue obtained was nondiagnostic. Before beginning OSAA, nine cases (6%) were interpreted as negative for malignancy, but subsequent tissue biopsies were malignant. There were no false positives during this time. Diagnostic sensitivity was 86% before OSAA. One hundred seventy-seven image directed FNAs were performed in the first year following the establishment of OSAA. Of these, 102 (58%) cases were interpreted as positive for malignant cells. About half of these patients went on to have confirmative tissue biopsies. Fifty-six (32%) cases were interpreted as negative for malignancy or nondiagnostic on FNA and follow-up tissue biopsies were also either negative or nondiagnostic. The false negative rate was 1% after OSAA and there were no false positives during this period. Diagnostic sensitivity was 98% after OSAA. In addition, the average overall number of passes per patient have decreased from 2.4 before OSAA to 1.6 after OSAA.

Bronchoscopic diagnosis of malignancy in the lower airway. A cytologic review.

OBJECTIVES: To determine the significance of a "suspicious" cytology report, to evaluate diagnostic accuracy for these specimens in the laboratory and to review the correlation of tumor subclassification in cytology versus histology. STUDY DESIGN: Retrospective review and comparison of 269 bronchoscopic cytology and histology specimens from a six-year period, 1984-1990. The relative and combined sensitivities of the sampling methods were studied. RESULTS: There were 17 suspicious cytologic diagnoses during this period. One of 17 was a false suspicious diagnosis, representing 0.03% of all reports on submitted samples. There were no false positive cytologic diagnoses. The majority (94%) of patients with a suspicious cytologic report had a final diagnosis of malignancy. Carcinoma was diagnosed in 244 of the 269 patients. CONCLUSION: Combined bronchoscopic cytology and biopsy was more sensitive (92%) than biopsy alone (82%) in making the initial diagnosis.

DNA ploidy in testicular germ cell tumors: can an atypical seminoma be identified?

Recent immunohistochemical and DNA ploidy analyses indicate that seminoma serves as a precursor to nonseminomatous germ cell tumors. It is believed that tumor progression from classical seminoma to nonseminoma is accompanied by inactivation and deletion of genetic material, and that these deletions are reflected in DNA ploidy. Twenty-three primary testicular germ cell tumors were studied by DNA flow cytometry to investigate whether a proposed histologic intermediate "atypical seminoma" (AS) could be separated from classical seminoma by ploidy analysis. The mean DNA indices (DI) for classical seminoma (N = 16), atypical seminoma (N = 5), and nonseminoma (N = 2; both embryonal carcinoma) were 1.53, 1.34, and 1.35, respectively. When a single "outlier" case of atypical seminoma was removed from consideration the mean DI for the AS rose to 1.45. This data is consistent with the interpretation of atypical seminoma as an intermediate between classical seminoma (CS) and embryonal carcinoma (ES). It suggests that genetic deletions characterizing progression from CS to nonseminoma may, in part, already be extant in atypical seminoma.

Cytologic appearance of Rhodococcus equi in bronchoalveolar lavage specimens. A case report.

Immunocompromised patients are at risk of developing infections caused by Rhodococcus equi, a gram-positive bacillus that can cause pneumonia in patients with acquired immunodeficiency syndrome. To the author's knowledge this is the first report describing the cytologic features of the infection in a patient who had a confirmatory tissue biopsy and positive culture. Infection with R equi may go unrecognized by pathologists unaware of its presentation and appearance in cytologic material.

Morphometric comparison of a metastatic transitional cell carcinoma simulating squamous metaplasia in sputum cytology. A case report.

Sputum cytology was performed to rule out primary lung carcinoma in a patient with a cough of recent onset, an infiltrate on chest roentgenography and a history of bladder and prostate carcinoma. The cytology was interpreted correctly as metastatic transitional cell carcinoma. Review of the cytology by other pathologists without the benefit of the previous history or histologic material resulted in interpretations of reactive/metaplastic tissue. A morphometric comparison of nuclear parameters between the cells in the sputum and the squamous metaplastic cells seen in the sputum of a patient with viral pneumonia from our archives was performed. Evaluation of the current sputum cytology without the benefit of clinical information or additional studies may have led to a false-negative diagnosis.

Atypical seminoma--histologic features, immunohistochemical characterization, and correlation with survival.

Classical seminoma and embryonal carcinoma are two points in the spectrum of histologic differentiation in testicular germ cell tumors. The validity of an intermediate category, ie, atypical seminoma (AS) is questionable. Histopathologic and clinical data on 42 patients treated for primary testicular germ cell tumor from 1975 to 1985 were reviewed. Twenty-seven cases were identified as classical seminoma and nine were embryonal carcinoma. The remaining six cases were somewhat problematic to classify, combining the growth pattern of seminoma with cytologic features of embryonal carcinoma. Immunocytochemically, four of these tumors suggested some progression towards the embryonal carcinoma phenotype on the basis of cytokeratin expression. Survival for classical seminoma, AS, and embryonal carcinoma were 90%, 80%, and 63% respectively (mean follow-up, 8.6 years). Although the survival differences were not statistically significant, when considered with morphologic and selected immunocytochemical data, they tend to support the concept of an AS as an intermediate lesion between classical seminoma and embryonal carcinoma.

Detection of occult metastatic lobular carcinoma in axillary lymph nodes using anticytokeratin monoclonal antibodies.

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

The ectopic ovary. A case report and review of the literature.

We describe an ectopic ovary in a stillborn female. To our knowledge, this is the first report of an extra ovary in an infant. This case prompted a review of ectopic ovarian tissue, which is known by a variety of terms, the most common being accessory ovary and supernumerary ovary. We suggest that (1) many of the past cases should be classified as ovarian implants rather than true embryologically derived ectopic tissue; and (2) the terms accessory ovary and supernumerary ovary are imprecise and should be modified.

Brief clinical report: a 46,XY phenotypic female with Smith-Lemli-Opitz syndrome.

A phenotypic female infant with Smith-Lemli-Opitz (SLO) syndrome was found to have a 46,XY karyotype. Autopsy showed normal tests for age and normal Wolffian duct structures. The serum testosterone level was unusually high, suggesting that the failure of virilization of the external genitalia in the child might be due to a defect in testosterone conversion to dihydrotestosterone or a lack of end-organ receptors for the same. An additional feature not previously described in association with SLO syndrome was present, which was clinical hypoglycemia with nesidioblastosis.

Emetine identified in urine by HPLC, with fluorescence and ultraviolet/diode array detection, in a patient with cardiomyopathy.

A 15-year-old girl with a four-month history of cardiac failure from undetermined cause was admitted to the hospital with weakness, fatigue, and weight loss. During her hospitalization she was found to have abused diet aids, laxatives, and cathartics. Although an electrocardiogram revealed nonspecific T-wave abnormalities and laboratory studies showed supranormal enzyme test results for creatine kinase and lactate dehydrogenase, no definite explanation of the cardiomyopathy was forthcoming. Ipecac abuse leading to cardiomyopathy was suspected early in the hospitalization. HPLC analysis of a urine sample showed emetine, a principle component of ipecac, the presence of which was later confirmed by more-specific HPLC analysis with photodiode array detection.

Familial hemophagocytic lymphohistiocytosis.

The cytologic features of familial hemophagocytic lymphohistiocytosis in two infant siblings were reviewed and compared to the histopathologic features in the same cases. The cytologic features of familial hemophagocytic lymphohistiocytosis in imprint smears from the spleen, lymph nodes, and liver were distinct, with proliferation of benign histiocytes engulfing erythrocytes and platelets. Hemophagocytic activity was more readily identifiable in imprint smears than in paraffin-embedded histologic sections. The differential diagnosis of histiocytic proliferative syndromes is also discussed.

Mediastinal teratoma associated with Klinefelter's syndrome.

The clinical and autopsy findings in a case of histologically benign teratoma of the mediastinum in a 19-year-old man with Klinefelter's syndrome are presented. A rough statistical analysis based on a review of the literature revealed that the incidence rate of Klinefelter's syndrome among the patients with mediastinal germ cell tumor is 30 to 40 times that of Klinefelter's syndrome among the general control population. The pathogenesis of this neoplasm appears to be related to the genetic abnormality in Klinefelter's syndrome, and this seems to predispose to the development of extragonadal mediastinal germ cell neoplasms.

Comparison of polyethylene glycols as fusogens for producing lymphocyte-myeloma hybrids.

In order to improve the yield of hybridomas for monoclonal antibody production, 8 different sources and molecular weights of polyethylene glycol (PEG) were compared as fusing agents. Sp2/0 myeloma cells were fused with murine splenic lymphocytes immunized with sheep red blood cells. The Kodak 1450 PEG produced the maximum number of hybridomas. The optimal technique consisted of slowly adding 1 ml of freshly prepared fusogen (5 g Kodak 1450 PEG, 0.5 ml dimethylsulfoxide, and 5 ml of phosphate-buffered saline, pH 7.0) to the cells over a 1 min period, incubating the mixture at 37 degrees C for 90 s, then gradually diluting the mixture in 50 ml of Hanks' buffered salt solution. After 10 min, the cells are centrifuged, resuspended in selective medium with feeder macrophages and cultured. This procedure routinely produces between 600-3,000 hybridomas per fusion.