Faculty Bibliography

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

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.

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)

INTRODUCTION: Peripheral T-cell lymphoma (PTCL) accounts for 10-20% of all non-Hodgkin lymphomas in the United States. In this study, the authors reviewed the cytologic and immunophenotypic findings of 33 fine-needle aspirations (FNAs) of PTCL. METHODS: Thirty-three FNAs from 26 patients (12 females and 14 males) with PTCL were identified during 1991-1999. The patients' age ranged from 19 to 96 years. Immunophenotyping was performed in 24 cases by using either flow cytometry (FC; 21 cases) or immunocytochemistry (IC; 3 cases). Follow-up included review of prior or current histology and clinical records. RESULTS: Nine cases were associated with mycosis fungoides, three cases were classified as T-cell chronic lymphocytic leukemia, and two were angioimmunoblastic adenopathy (AILD)-like T-cell lymphoma. The remaining 19 were classified as PTCL, not otherwise specified. The latter consisted of eight mixed cell variant, eight large cell variant, and three anaplastic variant. One of the mixed cell variant and one of the large cell variants contained numerous epithelioid histiocytes (Lennert lymphoma). Thirty (91%) cases had a definitive diagnosis of malignant lymphoma. Twenty-two cases (2 IC and 20 FC) showed a predominant population of T lymphocytes without a monoclonal B-cell population. In addition, FC revealed an aberrant expression of T-cell markers in 13 cases. Two cases were interpreted as 'atypical lymphoid population'; one case was an AILD-like T-cell lymphoma, and the other case was PTCL, large cell type. One case initially was interpreted as granulomatous lymphadenitis; subsequent biopsy revealed PTCL, Lennert type. CONCLUSIONS: Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of diagnosing peripheral T-cell lymphoma

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

The popularity of screening mammography has led to increased detection of mammographic lesions that require pathologic diagnosis. Stereotaxic needle biopsy techniques to sample such lesions can be used to either identify those lesions that require excision from those that can be followed, or to confirm a mammographic impression of malignancy prior to excision. Stereotaxic core biopsy (SCBX) and stereotaxic fine needle aspiration (SFNA) have rarely been directly compared. For this review we undertook a uniform re-analysis of the data that was presented in the published studies of SFNA and/or SCBX. The main endpoint was the negative predictive value (NPV) that measures the frequency that a benign diagnosis is truly benign. There was variability in NPV (likely due to sampling methods) and specific aspects of sampling techniques are discussed. The NPV was compared to indicators of selection of lesions to biopsy (frequency of invasive cancer in the study population), mammographic characteristics (masses or microcalcifications), and the reported nondiagnostic rates. The general conclusion is that SFNA and SCBX are equivalent in accuracy, with considerable variability that reflects the types of lesions that are selected for biopsy and the thoroughness of sampling. For SFNA studies, nondiagnostic rates were inversely related to NPV, and therefore have clinical implications. This was not shown for SCBX studies, and probably reflects an inability to correctly identify non-representative tissue biopsies. The main advantage for including cytologic methods with stereotaxic breast biopsy is immediate sample assessment, and this advantage can also be applied to core needle procedures.

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: Although stereotaxic fine-needle aspiration biopsy or core biopsy (14-gauge) have proven to be accurate techniques for the evaluation of mammographically detected microcalcification, the development of the Mammotome Biopsy System (Biopsys Medical, Inc., Irvine, CA) has led many medical centers to use this vacuum-assisted device for the sampling of microcalcification. METHODS: One hundred forty-two women underwent 160 stereotaxic Mammotome core biopsies of mammographic calcification over a 1-year period. The stereotaxic procedure was performed by radiologists using the Mammotome Biopsy System. Microcalcification was evident on specimen radiographs and microscopic slides in 99% of the cases. Excisional biopsy was recommended for diagnoses of atypia or carcinoma. Patients with benign diagnoses underwent mammographic followup. RESULTS: One hundred thirty-two benign, 12 atypical, and 15 adenocarcinoma diagnoses (comprising 1 lobular adenocarcinoma in situ [LCIS], 1 invasive ductal adenocarcinoma [IDC], and 13 intraductal adenocarcinomas [DCIS]: 10 comedo, 1 cribriform, 2 mixed cribriform and micropapillary) were rendered. Surgical excision in eight patients with atypia on Mammotome biopsy (two refused surgery, two were lost to followup) showed ductal hyperplasia in three, atypical ductal hyperplasia (ADH) in three and DCIS (low grade, solid) in two patients. Surgical excisions in 14 patients diagnosed with carcinoma (1 patient lost to followup) showed ADH in 3, ADH and LCIS in 1, residual DCIS in 8, IDC in 1, and microinvasive carcinoma in 1 patient. CONCLUSIONS: A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was low for microcalcification diagnosed as DCIS on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling and diagnosis of mammary microcalcification

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