Faculty Bibliography

BACKGROUND: The presence of malignant cells in peritoneal washings is an independent prognostic factor in the evaluation of gynecologic malignancies. The differentiation between reactive mesothelial cells and carcinoma cells can be a diagnostic challenge based on morphology alone. The expression of some cell adhesion molecules may be helpful in the differential diagnosis. METHODS: To evaluate the specificity of 2 transmembrane cell adhesion proteins (E-cadherin and CD44) in the differentiation of mesothelial cells from carcinoma cells in pelvic washings, formalin fixed, paraffin embedded cell blocks of pelvic washings from 19 cases of metastatic ovarian adenocarcinoma and 16 cases of benign peritoneal washings were immunostained with monoclonal antibodies to E-cadherin and CD44. The staining patterns were evaluated blindly by three observers. Positive staining was defined as uniform membranous staining for each marker. RESULTS: Fourteen benign peritoneal washings (87.5%) demonstrated immunoreactivity with anti-CD44. On the contrary, only four adenocarcinomas (21.1%) demonstrated anti-CD44 immunoreactivity. E-cadherin expression was identified in only 2 benign peritoneal washings (12.5%) whereas 16 adenocarcinomas (84.2%) strongly expressed E-cadherin. The differences in immunostaining for both CD44 and E-cadherin between benign and malignant peritoneal washings were statistically significant. The combination of positive staining for E-cadherin and negative staining for CD44 was 100% specific for metastatic adenocarcinoma, whereas a combination of negative staining for E-cadherin and positive staining for CD44 was 100% specific for reactive mesothelial cells. CONCLUSIONS: Both E-cadherin and CD44 reliably distinguish reactive mesothelial cells from adenocarcinoma. The combination of E-cadherin/CD44 is highly specific and is a useful diagnostic adjunct with which to distinguish benign reactive mesothelial cells from adenocarcinoma in pelvic washings

Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings

A substantial percentage of women with a diagnosis of atypical glandular cells of undetermined significance (AGUS) on cervical smears harbor a significant squamous or glandular, preneoplastic or neoplastic lesion on subsequent follow-up. Attempts to subclassify AGUS smears by conventional methods have had mixed results. To determine whether subclassification of AGUS cervical smears using computer-assisted rescreening based on the neural network would improve correlation with subsequent histologic follow-up, 91 cervical smears, conventionally diagnosed as AGUS without concomitant squamous lesions, were subjected to analysis by a computer-assisted automated screening system. Computer-generated images were evaluated by a cytotechnologist without the knowledge of the histologic outcomes. Prior to manual review, each case was classified as either within normal limits, no review required; or abnormal, review required. Based on the degree of abnormality, the latter category was further subclassified into either low probability or high probability of abnormality. The results of the computer-assisted reclassification were then compared with the histologic follow-up of all patients. Thirty-three cases (38.8%) had a significant lesion on histologic follow-up. The lesions included 4 CIN I, 7 CIN II/III, 12 endocervical adenocarcinomas (ACA), and 10 endometrial ACA. Based on computer-generated images, 65% of the smears that were triaged as high probability of abnormality, 11.5% that were triaged as low probability of abnormality, and 10.5% that were triaged as within normal limits had a significant lesion on subsequent follow-up. We conclude that computer-assisted rescreening aids in the triage of AGUS smears and that computer-assisted rescreening based on the neural network or other algorithms may be a useful ancillary tool for subclassifying AGUS cervical smears.

BACKGROUND AND OBJECTIVES: The ability to achieve clean margins with breast conserving therapy varies greatly even when the diagnosis of carcinoma is known beforehand. Although several reports reveal that the incidence of positive margins decreases after stereotaxic core biopsy of nonpalpable lesions and fine-needle aspiration biopsy of palpable lesions, the data on the results following mammotome biopsy (mmbx) is scanty. METHODS: Two hundred and ninety-eight biopsy specimens for mammographically indeterminate microcalcification from 1/97 through 3/30/98 were reviewed. Biopsies were performed using the biopsys method utilizing an 11-gauge multidirectional, vacuum-directed device. RESULTS: Ten percent (n = 31) of the mammotome biopsies were atypical and 9% (n = 27) were malignant. These 58 cases (19%) were recommended for surgical excision. The incidence of positive margins in this subset was determined. Of patients who underwent lumpectomy as their initial surgical procedure 69% had negative surgical margins. Seventy-seven percent of patients with carcinoma diagnosed by mammotome biopsy had definitive initial surgery with a single surgical procedure. CONCLUSIONS: Mmbx facilitates fewer surgical procedures to achieve negative margins, and thus provides a better cosmetic result.

BACKGROUND: The differentiation between malignant mesothelioma and adenocarcinoma based on morphology alone can be a diagnostic challenge. The majority of the available antibodies recognize molecules expressed by adenocarcinoma whereas to the authors' knowledge specific markers for mesothelial cells are lacking. Calretinin, a calcium-binding protein, has been reported to be a selective marker for mesothelioma and largely is absent from adenocarcinoma on histologic material. The results with cytologic preparations have been inconsistent. METHODS: To evaluate the specificity of calretinin in differentiating mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma and 16 cell blocks from 9 patients with malignant mesothelioma were stained with a monoclonal antibody against calretinin. The immunoreactivity was evaluated blindly by two observers. Positive staining was defined as nuclear and cytoplasmic staining with or without intense membranous decoration. The former resulted in a characteristic 'fried egg' appearance. RESULTS: Calretinin staining was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The latter contained predominantly spindle-shaped neoplastic mesothelial cells in the cell block preparations. All adenocarcinoma specimens were classified as negative for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%) showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or membranous staining. Benign reactive mesothelial cells, when observed in association with adenocarcinoma, also showed the characteristic 'fried egg' appearance. The difference in the staining pattern of calretinin between cells of mesothelial origin and adenocarcinoma cells was statistically significant. CONCLUSIONS: Calretinin is a useful marker in differentiating mesothelioma of the epithelial type from adenocarcinoma in serous effusions. The 'fried-egg' appearance or cytoplasmic and nuclear staining pattern is characteristic of cells of mesothelial origin

BACKGROUND: The presence of lymph node metastases in patients with malignant melanoma implies a significant decrease in survival. The authors investigated the efficacy of fine-needle aspiration biopsy (FNAB) in the diagnosis of metastatic malignant melanoma in 115 patients with melanoma and clinically suspicious regional lymph nodes. METHODS: One hundred thirty-three FNABs were performed by cytopathologists after referral from surgeons or oncologists using a 25-gauge or 27-gauge needle. RESULTS: The cytologic diagnosis was negative in 35, atypical in 1, suspicious in 2, and positive for malignant melanoma in 95. Regional lymph node dissections were performed in 78 patients. Of these, 70 positive FNABs were confirmed with no false-positive results. The atypical FNAB was proven positive for malignant melanoma at surgery. Of the two suspicious FNABs, one was confirmed as positive and one showed dermatopathic lymphadenopathy. Of the 35 negative FNAB specimens, 5 patients underwent surgery; 3 FNABs were found to be negative and 2 FNABS were falsely negative. Twenty patients with negative aspirates were followed clinically for 22-45 months (mean, 32 months); 19 patients had no evidence of disease and 1 patient died of disseminated melanoma. CONCLUSIONS: FNAB of palpable lymphadenopathy in patients with malignant melanoma can provide a rapid and accurate assessment of lymph node status and expedite the therapeutic management of these patients

OBJECTIVE: To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions. STUDY DESIGN: A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996. RESULTS: In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy. CONCLUSION: Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears

BACKGROUND: Fine-needle aspiration (FNA) biopsy of palpable breast masses along with clinical and radiologic findings can provide rapid distinction between benign and malignant lesions. A preoperative determination of invasive or in situ carcinoma assists in the planning of definitive treatment. Previous studies have concentrated on whether cytologic features adequately distinguish invasion, but to the authors' knowledge the predictive value of clinicopathologic correlation has not been investigated. The authors attempted to determine whether a malignant cytologic diagnosis for a palpable breast mass is sufficient for its definitive surgical management as an invasive neoplasm. METHODS: The authors reviewed 351 FNAs from palpable breast lesions with a cytologic diagnosis of 'adenocarcinoma.' The presence of invasive disease was determined by histologic demonstration of invasive carcinoma in the corresponding surgical specimen or by identifying metastatic carcinoma in the absence of another primary source. RESULTS: Three hundred forty-three (97.7%) palpable tumors diagnosed as adenocarcinoma by FNA proved to be invasive adenocarcinoma. The remaining eight tumors contained high grade ductal carcinoma in situ, and two of these contained foci suggestive of microinvasion. CONCLUSIONS: A palpable breast mass with an FNA diagnosis of adenocarcinoma usually represents invasive carcinoma. A definitive treatment plan therefore can be planned based on these clinical and FNA findings

Metastases of tumors of extramammary origin to the breast are extremely uncommon. We report the case of an 81-year-old man with a history of prostatic adenocarcinoma treated with adjuvant estrogen therapy, who presented with bilateral palpable mammary masses. Mammographic study showed irregular solid nodules. Fine needle aspiration (FNA) biopsy was performed. The aspiration smears showed single cells with high nuclear/cytoplasmic ratios, prominent nucleoli, and rare acinar formations. Immunocytochemical studies using antibodies against prostate-specific antigen and prostate-specific acid phosphatase confirmed the diagnosis of metastatic prostatic adenocarcinoma, allowing appropriate treatment

Fine-needle aspiration biopsy (FNA) is an accurate and cost-effective procedure for evaluating salivary gland lesions. Lymphoproliferative lesions may manifest as salivary gland enlargement. We report our experience with 43 cases of reactive and neoplastic lymphoproliferative lesions of the salivary glands evaluated by FNA, including 23 cases of reactive lymphoid hyperplasia and 20 neoplastic lymphoproliferative processes. The latter included 2 multiple myelomas and 18 non-Hodgkin lymphomas (small lymphocytic lymphoma/chronic lymphocytic leukemia, 1; small cleaved cell lymphoma, 1; lympho-plasmacytoid lymphoma, 1; mucosa-associated lymphoid tissue lymphoma, 2; mixed cell lymphoma, 4; lymphoblastic lymphoma, 1; and large cell lymphoma, 8). There were no false-negative diagnoses. Aspiration smears from 3 patients with reactive lymphoid hyperplasia and 4 patients with malignant lymphoma initially were interpreted as atypical lymphoid proliferations or as suggestive of malignant lymphoma. Thus, FNA had a sensitivity of 100% and a specificity of 87%. The majority of patients were treated medically without surgical intervention. Among the patients who underwent surgical resection of the salivary gland, 7 had an equivocal cytologic diagnosis and 2 had a benign cytologic diagnosis, but their parotid swelling failed to regress despite medical treatment. In most instances, FNA provides useful information for subsequent disease management and obviates surgical intervention