Faculty Bibliography

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

Uterine polypoid adenomyomas, both typical and atypical variants, often arise in the lower uterine segment or endocervical canal as pedunculated polypoid masses that may be accessible for cytologic sampling. However, their cytologic findings have rarely been described in the literature. Two women in their reproductive age presented with abnormal vaginal bleeding. The cervicovaginal smear of the first patient contained sheets and strips of reactive endocervical cells in an inflammatory background. In addition, loose aggregates of spindle-shaped smooth muscle cells were also noted. The findings were consistent with those of a typical polypoid adenomyoma. The cervicovaginal smears of the second patient consisted of tightly packed, crowded clusters of glandular cells which were initially interpreted as atypical glandular cells, suspicious of adenocarcinoma. In retrospect, loose aggregates of smooth muscle stromal cells were noted. Subsequent curettage revealed an atypical polypoid adenomyoma. The cytologic findings of typical polypoid adenomyoma were nonspecific except for the presence of loose aggregates of smooth muscle cells. The cytologic features of an atypical polypoid adenomyoma may mimic that of a neoplastic glandular process. The findings of tightly packed clusters of glandular cells and loose aggregate of bland-appearing smooth muscle cells in premenopausal patients may suggest the diagnosis of atypical polypoid adenomyoma. Diagn. Cytopathol. 2000;22:176-180.

We report a case of desmoplastic malignant melanoma metastatic to the parotid gland initially evaluated by fine-needle aspiration. The cytologic findings consisted of scattered spindle cells in a background of heterogeneous lymphoid cells. The spindle cells were scant and displayed mild cytologic atypia. In addition, rare stromal fragments were also present. Cytoplasmic pigment and intranuclear cytoplasmic inclusions were not seen. The initial impression was that of a reactive lymph node with fibrosis. In retrospect, rare spindle cells displayed moderate atypia. In addition, the stromal fragments were cellular and contained spindle cells with mild atypia. These cytologic findings along with a known history of malignant melanoma should provide clues to the correct diagnosis of desmoplastic malignant melanoma. Diagn. Cytopathol. 2000;22:97-100.

Metastases or secondary deposits account for 16% of the malignant neoplasms involving the major salivary glands. A correct diagnosis of a secondary neoplasm is important to avoid unnecessary radical surgery and to guide further therapy. Fine-needle aspiration biopsy (FNAB) is an excellent noninvasive diagnostic tool for evaluating salivary gland lesions. We reviewed 36 secondary malignant salivary gland neoplasms evaluated by FNAB. Ancillary studies were performed in selected cases. Follow-up included clinical correlation and review of histologic material. For 4 adenocarcinomas, 4 squamous cell carcinomas, 1 undifferentiated carcinoma, 1 cutaneous basal cell carcinoma, 10 cutaneous melanomas including 1 desmoplastic variant, 3 osteosarcomas, 11 non-Hodgkin lymphomas, and 2 multiple myelomas, there was 1 false-negative FNAB result. The desmoplastic melanoma was interpreted as reactive lymphoid hyperplasia. A malignant diagnosis was given in all remaining cases except the secondary basal cell carcinoma, which was diagnosed as a neoplasm with basal cell features. FNAB is a reliable tool to differentiate hematologic malignant neoplasms and melanomas from other salivary gland neoplasms. A complete knowledge of the clinical history, review of previous pathologic materials, and, in some instances, the use of ancillary studies are crucial for recognizing solid malignant neoplasms secondarily involving the salivary glands

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.

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.

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: 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

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