Faculty Bibliography

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

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

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.

INTRODUCTION. Although the cytologic features of Hodgkin disease (HD) has been well described, HD accounts for most of the false-negative fine-needle aspiration (FNA) biopsies of malignant lymphomas. In this study, the authors examined the factors contributing to a false-negative diagnosis of HD. METHODS: Eighty-nine cases from 72 patients (23 females and 49 males) with HD evaluated by FNA were identified between 1990 and 1999. The patients' ages ranged from 5 to 90 years (median, 38 years). Eighty-five FNAs were from lymph nodes, and 4 were from extranodal sites. Histologic correlation was available for all patients. RESULTS: Based on the original cytologic diagnosis, 43 (48.3%) cases had a positive diagnosis of HD, 20 (22.5%) suspicious or atypical diagnosis, 13 (14.6%) a benign diagnosis (false-negative cases), and 10 (11.2%) were nondiagnostic. Three (3.4%) additional cases had a malignant diagnosis other than HD. After review, three false-negative cases were reclassified as HD and seven as atypical lymphoid proliferation. Three of these 10 cases also showed conspicuous collections of histiocytes mimicking poorly formed granulomas. In those 'atypical' cases, only rare Reed-Sternberg (R-S) cells variants were identified. No R-S cells or its variants were identified in the remaining three false-negative cases; subsequent excisional biopsy showed partial involvement of the lymph node by HD in two cases. Among the nondiagnostic cases, nine cases showed considerable fibrosis in the resected lymph node. In addition, six cases were performed without on-site assessment. CONCLUSIONS: The cytologic diagnosis of HD can be challenging when classic R-S cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node by HD, sampling error, and misinterpretation. On-site assessment significantly minimizes the false-negative diagnostic rate. Furthermore, additional material can be obtained for ancillary studies. Cancer (Cancer Cytopathol)

BACKGROUND: Glandular atypia in Papanicolaou (Pap) smears from postmenopausal women is encountered frequently. This finding can be the result of artifactual alterations such as drying artifacts and inflammatory changes or may represent a squamous or glandular, preneoplastic or neoplastic process. Therefore, it is important to determine the clinical implication of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in postmenopausal patients. METHODS: A total of 30,036 Pap smears were obtained from postmenopausal women between 1995 and 1997. Among these smears, 154 (0.51%) had a diagnosis of AGUS. Follow-up was available for 133 patients (86.4%); 110 patients (82.7%) had histologic follow-up (including cervical biopsy, endocervical [EC] curettage, and/or endometrial [EM] biopsy) and 23 patients (17.3%) had repeat smears. RESULTS: Thirty-six of 110 patients (32.7%) were found to have a clinically significant lesion (defined as a preneoplastic or neoplastic, glandular or squamous lesion) on subsequent histologic follow-up. Nineteen patients (53%) had glandular lesions (15 EM adenocarcinoma [ACA] cases, 2 EC ACA cases, 1 EC adenocarcinoma is situ case, and 1 EM hyperplasia case). Seventeen patients (47%) had a squamous intraepithelial lesion (SIL) (6 cases of low-grade SIL, 9 cases of high-grade [HGIL], and 2 cases of squamous cell carcinoma). Among those patients with repeat Pap smears, five patients had persistent AGUS/atypical squamous cells of undetermined significance and one patient had an SIL. CONCLUSIONS: The incidence of AGUS among postmenopausal patients was similar to that of the general population (0.51% vs. 0.56%; P > 0.05). A significant percentage of these patients were found to have a clinically significant lesion on subsequent follow-up. Furthermore, a majority of these lesions were ACA (53%) or HGSIL (26%). The findings of the current study strongly suggest the need for the close follow-up of postmenopausal patients with a diagnosis of AGUS. Cancer (Cancer Cytopathol)