Faculty Bibliography

BACKGROUND: The Bethesda System recommends qualifying atypical glandular cells with regard to their possible origin: endocervical versus endometrial. This study was undertaken to determine the clinical significance of atypical glandular cells of undetermined significance that favor an endometrial origin (AGUS-EM). METHODS: A computer search identified 62 cervicovaginal smears (5.25% of all smears classified as AGUS) with a diagnosis of AGUS-EM in the files of Shared Cytopathology Laboratory of New York University Medical Center/Bellevue Hospital Medical Center between January 1995 and December 1999. The patients ranged in age from 29 years to 88 years (mean age, 53 years). Thirty-four patients were postmenopausal (55%), and 5 patients were on hormonal replacement therapy. Follow-up was available for 56 patients (90%); 45 patients (73%) underwent biopsy, and 11 patients (17%) had repeat cervicovaginal smears. Six patients were lost to follow-up. RESULTS: Among patients who underwent biopsy, 14 patients (31%) had a clinically significant uterine lesions, including 6 (13%) endometrial adenocarcinomas, 5 (11%) endometrial hyperplasias, and 3 (7%) squamous lesions (2 high-grade squamous intraepithelial lesions and 1 squamous cell carcinoma). Ten of 11 patients with significant endometrial pathology findings were postmenopausal. The remaining 31 patients had benign pathology results, which included chronic cervicitis, endometritis, endometrial polyps, microglandular hyperplasia, and tubal metaplasia. Among the patients with repeat cervicovaginal smears, one patient had atypical squamous cells of undetermined significance; the remaining patients were within normal limits. CONCLUSIONS: Approximately one-third of women with a diagnosis of AGUS-EM had a significant uterine lesion on subsequent biopsy; the majority of these lesions were endometrial in origin. Patients with a diagnosis of AGUS-EM on cervicovaginal smears should be followed closely, and endometrial curettage or biopsy should be included in their initial work-up

Tubular adenocarcinoma is an invasive mammary adenocarcinoma associated with an excellent prognosis and a low incidence of axillary metastases. However, identification of tubular adenocarcinoma by fine-needle aspiration (FNA) biopsy has proven difficult. One hundred five patients with documented 'pure' tubular adenocarcinoma were diagnosed at Tisch Hospital from August of 1992 to December of 1998. Twenty-one of these patients had an FNA before excision. We reviewed the smears of these cases and compared them with cases of fibroadenoma and fibrocystic change to identify criteria for diagnosis. Moderately to highly cellular smears with angular cellular clusters with sharp borders and oval cells outlining these clusters, dispersed single cells with minimal atypia, and the absence or paucity of dispersed bare oval nuclei in the background were features that suggest a diagnosis of tubular adenocarcinoma in our study. Attention to these features in combination with appropriate mammographic findings should preclude a false-negative diagnosis in the majority of cases of tubular adenocarcinoma diagnosed by aspiration biopsy. We point to the presence of the peripheral perpendicular cells in the characteristic tubular arrays as an important clue to the diagnosis of tubular adenocarcinoma

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern

BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining

Endometrioma in an operative scar is rare. The majority of patients have no prior history of endometriosis, and symptoms may mimic postoperative hernias. Fine-needle aspiration biopsy (FNAB) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. We present the cytologic findings in three cases of abdominal wall endometriomas diagnosed by FNAB. The patients ranged from 31 to 51 years of age. None had a history of endometriosis, but all had prior abdominal operations (two abdominal hysterectomies for fibroids and one cesarean section). They presented 6 months to 7 years later with painful subcutaneous abdominal nodules in their scars ranging from 2 to 6 cm. FNAB was performed by a cytopathologist. The smears were cellular and comprised two distinct cell populations. An epithelial component consisted of flat sheets of polygonal cells with round to oval nuclei and scant cytoplasm. The second component consisted of clusters of fusiform stromal cells. Numerous hemosiderin-laden macrophages were noted in the background. Cytokeratin highlighted the epithelial clusters, and vimentin stained the stromal cells. Electron microscopy showed two epithelial cell types: one with cilia and abundant rough endoplasmic reticulum and the other with numerous microvilli and scattered mitochondria indicative of endometrial differentiation. FNAB provided a rapid and accurate preoperative diagnosis in each case

BACKGROUND: Spindle cell and mesenchymal lesions of the lung encompass a wide variety of benign and malignant conditions. However, to the authors' knowledge, because of their rarity, few reports concerning their cytologic findings are available in the literature. The current review emphasizes the cytomorphologic features, differential diagnosis, and potential pitfalls associated with these lesions. METHODS: Seven hundred seventy-nine percutaneous lung fine-needle aspiration (FNA) specimens were retrieved from the authors' cytopathology files over a period of 5 years. Sixty-one cases (7.8%) in which a spindle cell component was the dominant or key feature were identified. The authors reviewed the cytologic smears, immunocytochemical studies, and corresponding surgical material and clinical information. RESULTS: Of these 61 aspirates, 33 (54%) were reactive processes (31 granulomas, 1 organizing pneumonia, and 1 inflammatory pseudotumor). Five cases (0.8%) were benign neoplasms (2 hamartomas, 2 solitary fibrous tumors, and 1 schwannoma). Twenty-three cases (38%) were malignant neoplasms (8 cases were primary tumors [including 5 carcinomas with spindle cell or sarcomatoid features, 1 spindle cell carcinoid tumor, 1 leiomyosarcoma, and 1 synovial sarcoma] and 15 cases were secondary tumors [including 9 melanomas, 2 leiomyosarcomas, 1 malignant fibrous histiocytoma, 1 meningioma, 1 sarcomatoid renal cell carcinoma, and 1 uterine malignant mixed mullerian tumor]). A specific diagnosis was rendered in 52 cases (85%). No false-positive cases were encountered but there was one false-negative case. One patient who was diagnosed with granulomatous inflammation on FNA was found to have nonsmall cell lung carcinoma on subsequent transbronchial biopsy. No malignant cells were identified in the smears on review. The FNA from the organizing pneumonia was interpreted as a solitary fibrous tumor whereas the inflammatory pseudotumor was diagnosed as granulomatous inflammation. The FNA from one pulmonary hamartoma initially was considered to be nondiagnostic. One solitary fibrous tumor and the schwannoma were diagnosed as smooth muscle tumor and spindle cell tumor, not otherwise specified, respectively. Among the malignant tumors, the primary synovial sarcoma and one of the metastatic malignant melanomas initially were interpreted as primitive neuroectodermal tumor/Ewing sarcoma and poorly differentiated carcinoma, respectively. CONCLUSIONS: Spindle cell lesions of the lung rarely are encountered on transthoracic lung FNA and are comprised of a wide variety of benign and malignant entities. By correlating clinical and radiologic data, cytologic findings, and ancillary studies, a high diagnostic accuracy rate can be achieved with FNA. Cancer (Cancer Cytopathol)

Myofibroblastoma of the breast is a rare benign stromal neoplasm, which occurs primarily in men. Classical myofibroblastoma is a circumscribed, nonencapsulated tumor comprised of bipolar fusiform cells arranged randomly, or in fascicles alternating with broad collagenous bands. Additional histologic variants (the cellular, collagenized, infiltrative, and epitheloid types) have been described. Several case reports describe the cytopathologic features of the classical and cellular variants. We report on a 70-yr-old woman, who presented with a circumscribed mass in her left breast. Aspiration biopsy showed paucicellular smears with singly distributed atypical spindle-shaped cells and rare fragments of collagenized stroma, raising suspicion of a phyllodes tumor. Histologic examination revealed spindle-shaped cells distributed in a diffusely collagenized stroma. Some nuclear atypia was present. To the best of our knowledge, this is the first case reporting the cytologic features of the collagenized variant of myofibroblastoma. Although we believe a specific diagnosis of myofibroblastoma can be rendered in a male based on the typical cytologic and clinical findings in the classical type, the variant forms are difficult to classify accurately and require excision for a definitive diagnosis.

OBJECTIVE: To determine the frequency of atypical glandular cells of undetermined significance (AGUS) for three consecutive calendar years from three different referral sources. STUDY DESIGN: Cervicovaginal smears with a diagnosis of AGUS were identified from January 1995 through December 1997. The smears were submitted from three different sources: two were city government hospital clinics, one with predominantly African American and Hispanic patients and the other with predominantly Asian and Hispanic patients. The third referral source was private practitioners' offices with predominantly Caucasian patients. RESULTS: A diagnosis of AGUS was made in 707 cases, accounting for 0.56% of all smears examined. This was in contrast to 6,872 smears reported as atypical squamous cells of undetermined significance (ASCUS) (5.4%) and 3,347 reported as squamous intraepithelial lesions (SIL) or above (2.7%). The incidence of AGUS ranged from 0.16% to 1.00% among different patient populations. This difference was also noted in the rate of ASCUS and SIL in the same patient population. There was a steady increase in the rate of AGUS for each referral source during the study period. The overall rate of patients who underwent histologic evaluation and the incidence of biopsy-proven preinvasive and invasive lesions were 62.4% and 23%, respectively. There was no significant difference in the rate of significant lesions after a diagnosis of AGUS during the study period or between the three referral sources. CONCLUSION: The AGUS rate in our laboratory was low and within the range (0.17-1.83%) reported in the literature. The AGUS rate varies with different patient populations, particularly with the incidence of SIL and age distribution

OBJECTIVE: To study the clinical significance of atypical glandular cells of undertermined significance (AGUS) in pregnant and postpartum women. STUDY DESIGN: We evaluated 35 women who were pregnant (30) or within three months postpartum (5) and had a cytologic diagnosis of AGUS. Twenty-seven (77%) patients had follow-up: 17 (63%) patients underwent colposcopic examination and biopsy, and 10 (37%) had repeat Pap smears. Eight patients were lost to follow-up. RESULTS: Five (29.4%) patients had a squamous intraepithelial lesion (SIL), including three high grade and two low grade, on subsequent biopsy. The remaining (70.6%) patients had benign pathology, which included 5 chronic cervicitis, 4 endocervical and/or endometrial polyps, 2 Arias-Stella reaction and 1 microglandular hyperplasia. Among the patients with repeat Pap smears, two had persistent AGUS/atypical squamous cells of undetermined significance, the remaining cases were within normal limits. CONCLUSION: Pregnancy-related changes may present with glandular atypia. In addition, about one-third of pregnant and postpartum women with a diagnosis of AGUS had SIL on subsequent biopsy; that rate is similar to that in nonpregnant women. Therefore, pregnant women with a cytologic diagnosis of AGUS should be followed closely