Distinguishing adenoid cystic carcinoma from cylindromatous adenomas in salivary fine-needle aspirates: the cytologic clues and their ultrastructural basis.

The utilization of fine-needle aspiration (FNA) biopsy in salivary tumors is hindered by the reluctance of many cytopathologists to report adenoid cystic carcinoma (ACC) because its cylindromatous stroma is observed occasionally in pleomorphic adenoma (PA) and basal cell adenoma (BA), and a diagnosis of ACC results in radical surgery. The aim of this study is to identify dependable features to distinguish the look-alike entities and illustrate their ultrastructural base. We compared 20 cases of ACC to 15 cases of cylindromatous PA and 9 cases of BA. All were direct smears stained with Diff-Quik, hematoxylin and eosin, Papanicolaou, or Ultrafast Papanicolaou (UFP) stain. In addition to the presence of cylindromatous pattern, the amount of cytoplasm in the neoplastic cells and nuclear features were compared. Tissue was dissected from paraffin blocks and processed for electron microscopy in selected cases. The difference in nuclear features can be distinguished in UFP-stained smears and electron microscopy. The nuclei of ACCs were heterochromatic with coarse chromatin and irregular nucleoli, whereas the nuclei of PAs were euchromatic with fine chromatin and small compact nucleoli. The nuclei of BAs were hyperchromatic but finely textured. The cytoplasm of PAs was detectable with every stain at 40x objective, but the cytoplasm of BAs required UFP stain and 100x objective to be detected. The cytoplasm of majority of neoplastic cells of ACCs are invisible, because the thin rim of cytoplasm measured <1 microm ultrastructurally, well beyond the resolution of a light microscope. Rare cohesive fragment of epithelial cells in ACC have scanty blue cytoplasm in UFP stain and can be recognized as ductal cells. In conclusion, in our analysis of salivary tumors with a cylindromatous pattern, the seemingly naked nuclei of neoplastic cells with their coarse nuclear chromatin and irregular nucleoli, as revealed by the UFP stain, reliably distinguished ACC from cylindromatous adenomas.

Fascin-1 expression in papillary and invasive urothelial carcinomas of the urinary bladder.

Fascin-1 is an actin-bundling protein that plays an important role in cell motility and adhesion. The level of fascin-1 is low or undetectable in normal epithelial cells. However, overexpression is reported in transformed epithelial cells and in several common types of carcinomas [Bioessays. 2002;24:359-361]. Up-regulation of fascin-1 is associated with higher grades and with aggressive tumors with poorer prognoses. We found no report on the role or the protein expression of fascin-1 in urothelial carcinomas (UCs) of the urinary bladder. In this study, we examined by immunohistochemistry the expression of fascin-1 in the normal human transitional epithelium, benign vesical lesions, and different types of UCs. We found no detectable fascin-1 in the normal transitional epithelium. There was no increase of fascin-1 expression in cystitis cystica, cystitis glandularis, nephrogenic adenoma (n = 10), inverted papilloma (n = 5), and classic exophytic papilloma (n = 4) or in adjacent transitional epithelia associated with these conditions. Patchy or diffusely weak fascin-1 expression was observed in 42% (5/12) of superficial papillary UCs (Ta), and 95% (19/20) of invasive UCs (T2 or higher) demonstrated diffuse strong staining for fascin-1. The microinvasive foci in the lamina propria of UC (T1, n = 8) were also positive for fascin-1, although they were not as strongly stained as in the deeply invasive tumors. Interestingly, the neoplastic cells in the tips of microinvasive carcinomas were distinctly positive for fascin-1. There were significant numbers of fascin-1-positive cells (>50% of the neoplastic cells) in UCs in situ (n = 10). These findings suggest an association between increased fascin-1 expression and increased invasiveness of carcinomas in the urinary bladder.

Utility of CD10 and RCCma in the diagnosis of metastatic conventional renal-cell adenocarcinoma by fine-needle aspiration biopsy.

The cytologic diagnosis of primary conventional renal-cell adenocarcinoma (cRCC) is usually straightforward; however, metastatic cRCC must be distinguished from a variety of neoplasms with clear-cell features. CD10, a cell membrane-associated neutral endopeptidase, and renal-cell carcinoma marker (RCCma), an antibody against human proximal tubular brush border antigen, have recently been shown to be useful in the diagnosis of cRCC. We compared CD10 and RCCma in cell block material from fine-needle aspiration biopsies (FNABs) to assess their utility in the diagnosis of metastatic cRCC, in cytologic specimens. Seven primary and sixteen metastatic cRCCs were immunostained with CD10 and RCCma. The immunoreactivity results were compared with those of a variety of neoplasms originating from other sites such as the liver, lungs, breast, and the gastrointestinal tract. The sensitivity and specificity of CD10 for cRCC were 100% and 59%, respectively. The sensitivity and specificity of RCCma for cRCC were 35% and 100%, respectively. We conclude that CD10 has limited value in confirming the diagnosis of cRCC because of its low specificity. RCCma, when positive, is highly specific for cRCC, but its low sensitivity hinders its diagnostic usefulness.

Aspiration biopsy of mammary lesions with abundant extracellular mucinous material. Review of 43 cases with surgical follow-up.

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and "suspicious" for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia.

The Use of Stereotaxic Core Biopsy and Stereotaxic Aspiration Biopsy as Diagnostic Tools in the Evaluation of Mammary Calcification.

We compared stereotaxic fine needle aspiration biopsy (SFNA) with stereotaxic core needle biopsy (SCB) in the evaluation of radiographically clustered mammary microcalcification, a common finding at screening mammography. Over a 4-year period, 181 specimens were obtained from 175 patients who underwent both SFNA and SCB of clustered microcalcification. Aspiration and core biopsies were performed by radiologists at a community-based diagnostic radiology facility. All aspiration smears were air dried, stained on site, and assessed for adequacy by the radiologists, then sent to the cytopathologists at New York University for interpretation. Core biopsy specimens were formalin fixed, paraffin embedded, hematoxylin and eosin stained, and interpreted by surgical pathologists at a community hospital. Of 181 SFNA specimens, 133 (74%) were benign, 18 (10%) were atypical, 13 (7%) were suspicious, and 16 (9%) were malignant. One (0.5%) aspiration biopsy was nondiagnostic. Excisional biopsies were performed after 12 benign SFNAs and in 46 of the 47 cases with an atypical, suspicious, or malignant diagnosis on SFNA. Mammographic follow-up in 111 of the 133 cases (92%) diagnosed as benign showed no radiologic change (mean 29.2 months, range 6-60 months). The false-negative rate for cancer was 4% (6 cases) for SFNA alone. There were no false-positive diagnoses for SFNA. There was one false-positive diagnosis on core biopsy [focal cribriform ductal carcinoma in situ (DCIS)], which at excisional biopsy and correlation with the core biopsy was diagnosed as ductal hyperplasia; the false-negative rate for cancer was 8% (13 cases) for SCB alone. Aspiration biopsy identified calcification in 180 procedures, core needle biopsy revealed calcification in 170. SFNA was superior to SCB for the confirmation of clustered mammary microcalcification (99% versus 94%) and in the identification of cancer associated with microcalcification (false negative rate of 4% versus 8%). Patients with benign findings on stereotaxic aspiration and core biopsy can reasonably be followed mammographically.

Improvements in breast cancer pathology practices among medicare patients undergoing unilateral extended simple mastectomy.

The information contained in pathology reports of breast cancer specimens is of critical importance to treating physicians for selection of local regional treatment, adjuvant therapy, evaluation of therapy, estimation of prognosis, and analysis of outcomes. This information is also of great importance to patients and their families. In 2000, a Breast Cancer Pathology Advisory Group was formed to advise on the design of a project to assess the quality of pathology reports on unilateral extended simple mastectomy (ICD-9-CM procedure code 85.43) specimens from Medicare patients in New York State. This group comprised clinical pathologists, breast surgeons, medical oncologists, clinical breast cancer specialists, and a radiation oncologist. The group suggested that the reports be examined for several elements (quality indicators) that are relevant to patient care and prognosis. Baseline random sample data assessing these elements were established from a random sample of all cases for the calendar year 1999. A random sample of 748 cases (43.5%) of unilateral extended simple mastectomy was chosen from among 1718 cases for the calendar year 1999. Of these, 555 (74.2%) were suitable for review. The remaining 193 (25.8%) cases did not satisfy the inclusion criteria. Aggregate performance on 7 quality indicators (presence of carcinoma, laterality of specimen, number of lymph nodes present, number of positive nodes, documentation of lymph nodes, histologic type, and largest dimension of the tumor) was 83.7% or better, whereas performance was 69.4% or less on 10 others (resection margin status, verification of tumor size, gross observation of the lesion, histologic grade, angiolymphatic invasion, nuclear grade, location of the tumor, mitotic rate, extent of tubule formation, and perineural invasion). The last, perineural invasion, was used as a control element and was not considered an evaluative quality indicator. Performance levels for New York State were significantly lower for histologic grade, resection margin status, and angiolymphatic invasion than in similar studies elsewhere. In addition, there were significant interhospital disparities in the performance levels for these quality indicators. Whereas some hospitals always recorded certain indicators, others never did. This in part reflects differing degrees of adoption of recommended specialty society protocols. The second phase of the project consisted of an educational feedback program involving the directors of pathology laboratories in New York State. The aggregate findings of the baseline study were shared with all the pathologists. In addition, each hospital that performed unilateral extended simple mastectomies during the study period received its own specific data so that it could compare its performance with the aggregate performance. The results of the baseline study also were shared with the New York Pathological Society and the New York State Society of Pathologists. The latter described the results in its newsletter. A postintervention review of the medical charts of a sample of 297 Medicare patients discharged from New York State acute care hospitals with an ICD-9-CM procedure code of 85.43 (unilateral extended simple mastectomy) was conducted for the 6-month period from December 1, 2001, through May 31, 2002. The 8 quality indicators, performance for which was below 84% in the baseline, were chosen for this remeasurement. Statistically significant improvements (P < .0001) occurred in all the 8 quality indicators, ranging from 12.6% to 19.9%. The results of this study indicate that the issues identified by breast cancer pathology reports are amenable to improvement. Such improvement can serve both the patients and the treating physicians better in making adjuvant treatment decisions, estimating prognosis, and evaluating outcomes. It also will be of help to patients and their families in making other life decisions.

Significance of the cytologic diagnosis of endocervical glandular involvement in high-grade squamous intraepithelial lesions.

The cytologic criteria for the diagnosis of endocervical gland involvement (EGI) by high-grade squamous intraepithelial lesions (HGSILs) have been described, and this diagnosis occasionally is made. This study evaluates the accuracy of a cytologic diagnosis compared with that of follow-up cone biopsies. Twenty-eight patients with Papanicolaou (Pap) smear diagnoses of HGSILs with EGI, with follow-up cone biopsies, were identified from New York University computerized files. Results were compared with those of a control group of 28 patients showing cervical intra-epithelial neoplasia grades II/III (CIN-II/III), irrespective of previous Pap smear findings. On subsequent cone biopsy samples, 26 of the 28 study cases showed signs of HGSIL. Of these 26 patients, 17 (65%) showed evidence of HGSIL with EGI. Among the 28 control cases, 20 (71.4%) had EGI on the cone biopsies (P = NS). We also examined previous Pap smear findings in a control group of 42 cone biopsies with CIN-II or CIN-III, with or without EGI. EGI was diagnosed in previous Pap smears in 3 of the 31(10%) cases that showed signs of EGI on cone biopsies and in 2 of the 11 cases (18%) that did not evidence EGI on subsequent cone biopsies (P = NS). In our experience, the cytologic diagnosis of EGI on Pap smears did not identify a group of patients with increased frequency of EGI on subsequent cone biopsies.

Aspiration cytology of cystic carcinoma of the breast.

Cystic carcinomas of the breast are rarely encountered in fine-needle aspiration (FNA) biopsies. The most common entities comprise intracystic papillary adenocarcinoma, ductal adenocarcinoma with cystic degeneration including comedo forms of ductal adenocarcinoma in situ, medullary carcinoma, squamous carcinoma, and cystic hypersecretory ductal adenocarcinoma. The cytologic diagnosis is often hampered by sparse cellularity, abundant obscuring blood, necrotic debris, and degenerative changes in diagnostic cells. We report on the cytologic features of 10 cases of cystic carcinoma, including 12 FNA biopsies with radiologic and surgical correlation. The original cytologic diagnoses for these cases were: benign (2 cases), atypical (2 cases), suspicious (3 cases), and positive for malignant cells (3 cases). On repeat FNA, one benign case and one atypical case were reclassified, respectively, as atypical and suspicious for carcinoma. The follow-up diagnoses were 5 intracystic papillary adenocarcinomas and 5 cystic ductal adenocarcinomas. Despite 2 false-negative cases, all cases were adequately managed. Correlation with clinical and radiologic findings and direct sampling of any solid component of these cystic neoplasms are crucial in diagnosis and management.

Metaplastic carcinoma of the breast with rhabdomyosarcomatous element: aspiration cytology with histological, immunohistochemical, and ultrastructural correlations.

We studied a metaplastic breast carcinoma with a rhabdomyosarcomatous element from a 62-yr-old woman. In the fine-needle aspirates processed by Ultrafast Papanicolaou stain, there were small undifferentiated cells with scanty cytoplasm and differentiated cells with red macronucleoli and abundant cytoplasm. Some differentiated cells contained a brown inclusion with a blue rim. Ultrastructurally, the brown inclusion correlated to a central aggregate of sarcomeres and the blue rim correlated to actin filaments surrounding the sarcomeres. The differentiated cells without cytoplasmic inclusions expressed cytokeratin and contained tonofilaments. A transitional cell type containing both sacromeres and tonofilaments was absent. Immunohistochemically, the small undifferentiated cells expressed vimentin diffusely and showed >90% MIB-1 proliferating index, whereas the differentiated cells expressed cytokeratin, actin, or myoglobin and had virtually absent MIB-1 nuclear labeling. Histologically, the small cells were more concentrated along the capsule and the large cells were more concentrated in the center of the tumor. These findings suggest the bidirectional differentiation of the small undifferentiated cells into carcinoma cells and rhabdomyosarcoma cells in this tumor.

Parachordoma or chordoma periphericum? Case report of a tumor of the thoracic wall.

We report the findings from an aspiration biopsy and resection of a chordoma-like tumorous mass in the wall of the thorax of a 36-yr-old man with immunohistochemical, ultrastructural, and cytogenetic studies. The 4-cm oval tumor was an incidental finding on physical examination, and no other lesions were identified after comprehensive radiologic studies. The aspirate was composed of sheets and nests of cells with distinct borders in a myxoid and fibrillary extracellular matrix. The neoplastic cells were uniform and round or polygonal with abundant pale blue vacuolated cytoplasm and small round, central or eccentric nuclei. On electron microscopy, mitochondrial rough endoplasmic reticulum complexes were seen in neoplastic cells. These features were similar to those of a conventional chordoma. However, the cytogenetic pattern, 43, XY ,-1, -2, der (5)t(1p;5q), -6, add(8p) ,add(10q), was not typical. In addition, the neoplastic cells were positive for vimentin, S-100, AE1/AE3, CAM 5.2, and CK 19; were focally positive for EMA and smooth muscle actin; and were negative for cytokeratin 1 and 10 (34 beta E12), CK 7, CK 8 (35H 11B), CK 17, and CK 20. The cytogenetic and immunohistochemical patterns were different from conventional chordoma and its peripheral counterpart, chordoma periphericum, suggesting the diagnosis of parachordoma. To the best of our knowledge, this is the first report of fine-needle aspiration of this newly defined and rare entity.

Cytologic diagnosis of invasive lobular carcinoma: factors associated with negative and equivocal diagnoses.

Fine-needle aspiration biopsy (FNAB) of invasive lobular carcinoma (ILC) is associated with notoriously high rates of false negative and equivocal diagnoses. To identify causative factors, we reviewed the cytologic features of presurgical FNAB smears of ILC and correlated the cytologic findings with the number of passes, tumor size, mammographic findings, and the histologic characteristics of the tumor. Smear cellularity, presence of single intact epithelial cells, nuclear size, nuclear atypia, palpability of the tumor, and histologic type of ILC (classic versus nonclassic) were statistically significant in establishing an unequivocally positive diagnosis. We also found that the cytologic cellularity of the lesion does not reflect the actual cellularity of the tumor but instead is an indicator of the architectural arrangement of the neoplastic cells; tumors that form epithelial cell groups, such as in nonclassic ILC, tend to yield more cellular aspirates that are diagnostic for carcinoma. In contrast, classic ILC, in which single neoplastic cells are embedded in fibrous stroma, is more likely to yield a paucicellular smear with subtle atypia and rare single intact epithelial cells. As such, an inconclusive diagnosis in a certain percentage of classic ILC cases may be unavoidable.

Aspiration biopsy in a case of apocrine adenocarcinoma with foam cells (myoblastomatoid or histiocytoid adenocarcinoma).

We found only one report of a case of apocrine adenocarcinoma with foamy cells diagnosed by aspiration biopsy. Herein, we describe a second case with cytologic, histologic, and immunohistochemical findings and discuss the differential diagnosis of foamy cells on aspiration smears obtained from mammary nodules.

Cytologic findings with histologic correlation in 43 cases of mammary intraductal adenocarcinoma diagnosed by aspiration biopsy.

OBJECTIVE: To review the cytologic and subsequent histologic findings in intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to evaluate the role of aspiration biopsy (AB) in identifying and grading the disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS who underwent preoperative AB were reviewed. Smears were assessed for cellularity, cellular arrangement (including dissociation, nuclear size and pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases, 22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases were low grade (LG). Cytologic findings of HG DCIS was as follows: high cellularity (22/22), clusters of pleomorphic cells with large nuclei and increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had moderately to highly cellular smears with cohesive, 3-dimensional sheets of uniform, small cells with inconspicuous nucleoli arranged around a central lumen, forming "punched-out" spaces. Single cells were prominent in 2 of 14 cases. IG DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets with punched-out spaces, abundant single cells, moderate pleomorphism and focal necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however, distinction from invasive carcinoma may not be possible. The cytologic diagnosis of LG DCIS is difficult, and 50% of our cases were called atypical on AB. Recognition of cohesive cellular arrangements with crowding and punched-out spaces is crucial as single cells and prominent atypia are often lacking.

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland.

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.

Training, credentialing and re-credentialing for the performance of a thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.

The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding training for the performance of thyroid FNA via palpation; training for the performance of thyroid FNA via ultrasound imaging, and credentialing/re-credentialing for the performance of a thyroid FNA. (http://thyroidfna.cancer.gov/pages/info/agenda/)

PAX2: a reliable marker for nephrogenic adenoma.

Nephrogenic adenoma is a rare lesion of the urinary tract. The diagnosis usually is straightforward when characteristic microscopic and clinical findings are present, and the entity is familiar. However, misdiagnosis, in particular of adenocarcinoma of the prostate gland, may occur. Immunohistochemical stains often are needed to make such a distinction, but currently available markers offered only partial help. It recently was demonstrated that nephrogenic adenoma in renal transplant patients originated from the renal tubular epithelium. This newly proved, but long sought information may be helpful in the differential diagnosis of nephrogenic adenoma. In this study, we investigated the expression of a renal transcription factor, PAX2, in 39 nonrenal transplant-related nephrogenic adenomas, 100 adenocarcinomas of the prostate gland, and 47 urothelial carcinomas of the urinary tract. A strong and distinct nuclear staining of PAX2 was found in all 39 cases of nephrogenic adenoma (100%), but not in normal prostate tissue, normal urothelium, adenocarcinomas of the prostate gland, and invasive urothelial carcinomas. Focal CD10 was detected in six of 13 nephrogenic adenomas in the superficial papillary component and in normal prostate epithelium, normal urothelium, lymphocytes, adenocarcinoma of the prostate gland, and urothelial carcinoma. There was no uroplakins detected in nephrogenic adenoma. Therefore, these findings are suggesting that nephrogenic adenoma in nonrenal transplant patients may also arise from the renal epithelium, as did the comparable lesions after transplantation. PAX2 is a specific and sensitive immunohistochemical marker in identification and differential diagnosis of nephrogenic adenoma.