Cytology and immunocytochemistry of bilateral breast metastases from prostatic cancer. Report of a case

The cytologic findings in fine needle aspirates of a previously treated prostatic cancer metastatic to both breasts in a 65-year-old man are described. The prostatic origin of the poorly differentiated adenocarcinoma cells was demonstrated by identification of cytoplasmic prostate-specific antigen. The clinical importance of a conclusive diagnosis differentiating a primary from a metastatic lesion is discussed; this case illustrates the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis in making such determinations.     

Stereologic estimates of volume-weighted mean nuclear volume in aspiration smears of ductal breast carcinoma. Correlation with cytologic grade, tumor size and lymph node status

OBJECTIVE: To estimate cytologic volume-weighted mean nuclear volume and correlate it with other prognostic factors, such as tumor diameter and cytologic grading in relation to nodal infiltration. STUDY DESIGN: The relationships between nodal status and nuclear VV, tumor diameter and cytologic grading, according to the modified Black nuclear grading system, were analyzed on fine needle aspirates of 49 cases of breast cancer by univariate and multivariate logistic regression. RESULTS: Volume-weighted mean nuclear volume (nuclear VV) estimated on fine needle aspiration smears showed a significant correlation with grade of tumor differentiation. CONCLUSION: Stereologic evaluation of nuclear size by nuclear VV is an objective method for the cytologic grading of ductal carcinoma of the breast and has independent prognostic value in relation to nodal status higher than those of tumor diameter and cytologic grade.     

Immunocytochemical Detection of the Androgen Receptor In Fine Needle Aspirates From Benign and Malignant Human Prostate

A monoclonal antibody to the androgen receptor was applied to fine needle aspirates from patients with benign and malignant prostatic disease. The series includes six patients with benign hyperplasia and 24 patients with prostatic carcinomas. The androgen receptor was detected in most nuclei of both benign and malignant epithelial cells. The intensity of immunostaining varied. No obvious relation was observed between the intensity of the staining in benign versus malignant cells. In addition no clear differences were found in the proportion of androgen receptor positive cells in benign aspirates as compared with aspirates from well differentiated or moderately well differentiated prostatic carcinomas. The relative number of androgen receptor positive cells was highest in smears from poorly differentiated prostatic carcinomas.     

Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy?

OBJECTIVE: To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB). STUDY DESIGN: Ninety-five FNABs from 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M- and P-HCC) and benign aspirates and histologically verified. RESULTS: There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. CONCLUSION: Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases.     

Cytologic grading of invasive breast carcinoma. Correlation with clinicopathologic variables and predictive value of nodal metastasis

OBJECTIVE: To estimate cytologic grade and correlate it with the other known prognostic factors, such as tumor differentiation, growth fraction, estrogen receptor status and nodal status. STUDY DESIGN: Fine needle aspirates from 104 invasive ductal carcinomas were stained by the Papanicolaou method and examined for necrosis, cellular size, nuclear/cytoplasmic ratio, nuclear pleomorphism, nucleoli, chromatin granularity and density of chromatin. We established a semiquantitative scoring system based on the above features and correlated cytologic findings with clinicopathologic variables. RESULTS: Histologic grade correlated positively with cytologic grade and negatively with estrogen receptor positivity. Moreover, high cytologic grade was associated with nodal metastasis and proliferative index labeling by MIB-1. CONCLUSION: This study showed that our grading system for breast cancer on fine needle aspiration cytology is feasible on a routine diagnostic basis. Cytologic grading can provide more information than usual on tumor biologic behavior.     

Specific tumor markers in diagnostic cytology. Immunoperoxidase studies of carcinoembryonic antigen, lysozyme and other tissue antigens in effusions, washes and aspirates

The immunoperoxidase technique was used to identify specific tumor markers in exfoliated cells in fine needle aspirates and body fluids. Carcinoembryonic antigen (CEA) and lysozyme staining was evaluated in cytocentrifuge preparations from 42 malignant effusions and aspirates and 16 benign effusions. Reactive mesothelial cells were negative for CEA and lysozyme or showed faint peripheral cytoplasmic staining. Malignant cells from 50% of the adenocarcinomas studied were positive for CEA. All tumors studied were negative for lysozyme. These staining patterns are helpful in the differential diagnosis of reactive mesothelial and adenocarcinoma cells, a frequent diagnostic dilemma. Moreover, demonstration of specific tumor antigens (e.g., prostatic acid phosphatase, calcitonin and immunoglobulin) helped define the origin of metastatic malignancy in selected cases. Estrogen receptor activity was also identified in tumor cells using this technique. Immunoperoxidase was helpful in the evaluation of malignant cytologic specimens from patients with more than one tumor. Interpretation of staining patterns is discussed, with reference to the limitations of the technique. Immunoperoxidase methods maintain cytologic detail, are readily adaptable to diagnostic cytology and increase the specificity of cytologic diagnosis.     

Fine needle aspiration cytology of atypical carcinoid of the lung

The cytologic features of eight atypical carcinoid tumors of the lung, as observed in fine needle aspiration (FNA) specimens, are described in detail. They were compared with 21 pulmonary squamous-cell carcinomas, 16 adenocarcinomas, 5 small-cell undifferentiated carcinomas, 3 large-cell undifferentiated carcinomas and 1 typical carcinoid tumor. Atypical carcinoid tumor was easily distinguished from the other pulmonary neoplasms in most instances. Only two poorly differentiated squamous-cell carcinomas (one of which had atypical carcinoid as a component) and one small-cell undifferentiated carcinoma had similar cytologic features. One atypical carcinoid also had cytologic features similar to small-cell undifferentiated carcinoma. Because atypical carcinoid and small-cell undifferentiated carcinoma, at times, may be difficult to separate in FNA specimens, surgical resection of all stage I neoplasms with cytologic features evocative of either neoplasm is recommended.     

BCA-225 immunostain: is it of value in liver fine needle aspiration?

OBJECTIVE: To determine the utility of BCA-225 immunostain in differentiating hepatocellular carcinoma (HCC) from other malignant tumors in liverfine needle aspiration specimens. STUDY DESIGN: Cell block materialfrom 87fine needle aspirates of liver lesions, including 25 HCCs, 9 neuroendocrine carcinomas, 12 adenocarcinomas metastatic from the colon, 19 other metastatic adenocarcinomas, 13 other metastatic tumors and 2 cholangiocarcinomas, were immunostained with BCA-225 antibody using both the EnVision avidin-biotin method (Dako U.S.A., Carpinteria, California, U.S.A.), and the traditional avidin-biotin method, without antigen retrieval. Three independent observers evaluated the cases, and a consensus was reached. RESULTS: Strong immunostaining for BCA-225 in at least 10% of malignant cells was considered positive. Two of 25 HCCs, 9 of 19 adenocarcinoma metastases, 1 of 9 neuroendocrine carcinomas, 4 of 13 other metastases and 1 of 2 cholangiocarcinomas were positive. No colon metastases were considered positive. CONCLUSION: BCA-225 may help exclude the diagnoses of metastatic colon adenocarcinoma, neuroendocrine carcinoma and well- to moderately differentiated HCC in this cytologic setting.     

Fine needle aspiration of primary pleomorphic liposarcoma of the breast. A case report

BACKGROUND: Primary liposarcoma of the breast is an extremely rare lesion. Only two cases describing the aspiration biopsy findings have been reported in the literature. We report the cytologic findings in an additional case, stressing the cytologic clues necessary to distinguish this neoplasm from a primary adenocarcinoma. CASE: A 53-year-old female presented to the emergency room with bleeding from a 20-cm, ulcerating mass in the right breast. Four months earlier she had been seen at another institution, where a diagnosis of poorly differentiated carcinoma was made by aspiration biopsy. Computed tomography had been negative for metastatic disease, and the patient refused further evaluation. Aspiration biopsy of the breast mass was repeated at our institution and interpreted as consistent with a poorly differentiated carcinoma. Histologic, immunophenotypic and ultrastructural evaluation of the mastectomy specimen revealed a pleomorphic liposarcoma. CONCLUSION: With increasing utilization of fine needle aspiration to evaluate breast lesions, it can be anticipated that unusual entities, including liposarcomas, will be encountered increasingly in breast aspirates. Therefore, it is important to consider liposarcoma in the differential diagnosis of aspirates showing isolated spindle and polygonal cells with vacuolated cytoplasm, nuclear scalloping and pleomorphism to avoid a misdiagnosis of carcinoma.     

Fine needle aspiration cytology of a metastatic duct carcinoma of the prostate: a case report

BACKGROUND: Prostatic ductal carcinoma (PDC) is a rare variant of prostatic adenocarcinoma. Without proper clinical information, a fine needle aspiration (FNA) diagnosis of metastatic PDC can be challenging as this tumor can morphologically mimic adenocarcinomas from other sites. To our knowledge, FNA findings of metastatic PDC have not been previously reported. CASE: An 85-year-old man presented with a large, destructive pelvic bone lesion with soft tissue extension. He had undergone a prostatectomy 30 years earlier for "benign prostatic hypertrophy" but had no known history of malignancy. The aspirates were hypercellular and composed of numerous monolayered or folded cohesive sheets of tumor cells with minimal cytologic atypia. The tumor cells had abundant, clear cytoplasm, evenly spaced nuclei, finely granular chromatin, inconspicuous nucleoli and occasional mitotic figures. The background was clean and contained a few wisps of thin mucin. Cell block sections revealed tumor cells forming tubulopapillary architecture lined with tall columnar cells with focal nuclear pseudostratification, reminiscent of uterine endometrial carcinoma. Positive immunoreactivity for prostate-specific antigen and prostatic acid phosphatase confirmed the tumor's prostatic origin. CONCLUSION: Because of the rarity and nonspecific cytomorphologic characteristics of this tumor, clinical history, radiologic findings and a high index of suspicion in conjunction with ancillary studies are important in achieving a correct FNA diagnosis of metastatic PDC.     

Fine needle aspiration biopsy of hepatocellular carcinoma. Some unusual features.

The cytologic features of fine needle aspiration smears from 28 hepatocellular carcinomas (HCC) were reviewed. All aspirations except one were guided. There were 14 well-, 11 moderately and 3 poorly differentiated HCC. The better-differentiated HCC were characterized by similarity of the tumor cells to hepatocytes (83%), cohesive cell clusters with a trabecular arrangement (72%) and presence of sinusoidal endothelial cells (66%). Other features included bile production (38%), atypical hepatocytic naked nuclei (52%), acinar formation (31%), intracytoplasmic vacuoles (14%) and abnormal vascular patterns (14%). Poorly differentiated HCC showed dyshesive pleomorphic cells. Unusual cytologic features from a well-differentiated HCC with fatty change and an HCC with a prominent acinar component are described. The identification of fatty change in dissociated well-differentiated hepatocytes or cytologic features suggestive of an adenocarcinoma do not preclude the diagnosis of HCC. The usefulness of cell blocks is emphasized.     

Diagnosis of pancreatic carcinoma by fine needle aspiration cytology and computerized cytomorphometry

Eighty-one fine needle aspirations (FNAs) of pancreatic masses were performed between 1980 and 1988. Histologic or clinical follow-up was available for correlation with 78 aspirates. The FNA cytologic diagnosis of pancreatic carcinoma had a sensitivity of 79% and a specificity of 91%. Fifteen of the FNA specimens were examined with the Zeiss IBAS image analysis system to determine nuclear area, form (shape), diameter, density and integrated optical density (IOD). Nuclear area and IOD correlated most highly with the final diagnoses. Negative aspirates from benign cases and "false negatives" from malignant cases had similar morphometric values. Cells from adenocarcinoma had greater nuclear area and IOD values in cases cytologically labeled positive than in cytologically suspicious cases. Diagnoses based upon IOD values had a sensitivity and a specificity of 100% and 86%, respectively, while the use of nuclear area measurements produced values of 100% and 100%, respectively. These data indicate that nuclear area and IOD measurements can be valuable adjuncts to qualitative cytology for the diagnosis of pancreatic fine needle aspirates.     

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.     

Fine needle aspiration cytology of granulomatous prostatitis

The fine needle aspiration (FNA) cytologic findings are presented for 18 cases of granulomatous prostatitis (12 nonspecific, 5 tuberculous and 1 eosinophilic cases). These cases represented 19% of all prostatitis cases and 2% of all prostatic aspirates examined from January 1986 to December 1987. The cytomorphologic differences between the three types of granulomatous prostatitis are described, with emphasis on the differentiation between the nonspecific and specific varieties. The differential diagnostic features between reactive changes and well-differentiated adenocarcinomas of the prostate are also presented. The findings in these cases indicate that FNA cytology is a reliable procedure for the morphologic diagnosis of granulomatous prostatitis, which can clinically mimic prostatic carcinoma when it presents as a diffuse or nodular enlargement with increased consistency.     

Fine needle aspiration of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma: a case report

BACKGROUND: Poorly differentiated oxyphilic (Hürthle cell) carcinomas are a more recently described variant of poorly differentiated thyroid carcinoma and are characterized by a prominent Hürthle cell component in a solid or trabecular arrangement. Clinically, poorly differentiated oxyphilic carcinomas behave more aggressively as compared to classic Hürthle cell carcinomas, which have a predominantly follicular pattern. Although the histology of these rare thyroid tumors has been reported in the literature, the cytologic features on fine needle aspiration biopsy have not been described before. CASE: A 73-year-old man with a long history of radioactive iodine and levothyroxine therapy for multinodular goiter presented with a painful, rapidly expanding, 6-cm, left thyroid mass with aggressive radiologic features. Fine needle aspiration biopsy of the mass yielded extremely cellular smears with a dual population of medium-sized follicular cells and numerous Hürthle cells. Subsequent thyroidectomy confirmed the malignant nature of this Hürthle cell-rich tumor, warranting a diagnosis of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma. CONCULSION: Poorly differentiated oxyphilic thyroid carcinoma is an aggressive variant of Hürthle cell carcinomas and must enter the differential diagnosis when fine needle aspiration biopsy of a radiologically aggressive thyroid mass yields extremely hypercellular smears with a prominent Hürthle cell component.     

Apocrine adenocarcinoma of the vulva with associated Paget's disease. Diagnosis of lymph node metastases by fine needle aspiration biopsy

The cytologic features of a fine needle aspiration biopsy of lymph node metastases from a vulvar adenocarcinoma with apocrine differentiation are documented. Cytologic findings that suggested apocrine differentiation included extreme nuclear eccentricity, punctate eosinophilic cytoplasmic granules and moundlike protrusion of apical cytoplasm. The cytologic findings correlated well with the histologic and histochemical features of the primary vulvar adenocarcinoma and its lymph node metastases.     

Fine needle aspiration diagnosis of transitional cell carcinoma metastatic to the brain. A case report

BACKGROUND: Transitional cell carcinoma (TCC) rarely metastasizes to the brain. In this case, aspiration of a cystic brain lesion was performed and a cytologic diagnosis made. To the best of our knowledge, this is the first reported case of TCC metastatic to the brain diagnosed by fine needle aspiration. CASE: A 72-year-old male with a past medical history of invasive TCC, colonic adenocarcinoma and prostatic adenocarcinoma presented with a large, right, temporal, cystic mass. Fine needle aspiration was performed intraoperatively, and a cytologic diagnosis of metastatic TCC was rendered and confirmed by subsequent tissue examination. CONCLUSION: Intraoperative fine needle aspiration of cystic tumors can be useful in identifying the primary site. The cytologic features of intracerebral metastatic TCC can differ significantly from those observed in urinary tract specimens of high grade TCC. A predominance of large fragments of malignant cells with numerous mitotic figures and apoptotic bodies was seen in the former. The background showed high grade, single transitional cells similar to those observed in urinary tract samples of TCC.     

Comparison of fine needle aspirates of breast cancers to imprint smears by means of digital cell image analysis

Morphonuclear assessments were performed using the SAMBA 2005 cell image processor on cell nuclei in fine needle aspirates and corresponding imprint smears from 17 not-otherwise-specified (NOS) breast carcinomas to study the influence of cell sampling on the morphonuclear measurements. Fourteen parameters related to densitometric (nuclear DNA content), morphometric (nuclear area) and textural (chromatin organization and distribution) characteristics were computed for each nucleus. The results demonstrated that such morphonuclear features evolved significantly and positively with respect to conventional histopathologic grading. The method of cell sampling significantly influenced the results, but without altering the general conclusions regarding evolution of the morphonuclear features.     

Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture

The monoclonal antibody (MAb) B72.3, reactive with a high-molecular-weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been previously shown to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct for the diagnosis of carcinoma in cell blocks and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 41 patients. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. MAb B72.3 has recently been used with fine needle aspiration (FNA) biopsy specimens and the corresponding surgically excised tumors to determine cellular reactivity. Using the ABC immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumors were analyzed for TAG-72 expression. Positive staining with MAb B72.3 was observed in needle aspirates of 27 of 27 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, 6 of 6 adenocarcinomas of the colon and in carcinomas from other body sites. In contrast, 21 small-cell carcinomas of the lung, 13 malignant melanomas, 2 lymphomas and 2 sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B72.3. In more than 90% of these patients, the staining patterns of the tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies, it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, that is most selectively expressed in carcinomas and that may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in fine needle aspiration biopsies.