Diagnostic pitfalls in fine needle aspiration cytology of atypical apocrine metaplasia in a breast lesion. A case report

BACKGROUND: Apocrine metaplastic cells are frequently encountered in fine needle aspirates of breast lesions. Atypical apocrine metaplastic cells with signet ring features can also occur, and their presence may present a diagnostic dilemma in the differentiation of benign versus malignant lesions. CASE: A fine needle aspirate of a 2.5 x 1.0-cm, subareolar mass in a 47-year-old female showed atypical cells with signet ring morphology. Also present were clusters of cells that were enlarged and showed nuclear atypia, prominent nucleoli and cytoplasmic granules. Papillary cohesive clusters of ductal cells were also identified. The fine needle aspiration diagnosis was mucinous carcinoma. The nodule was excised, and the histologic diagnosis was sclerosing ductal papilloma with atypical apocrine metaplasia. CONCLUSION: Atypical apocrine cells can be misinterpreted as mucinous carcinoma or usual duct adenocarcinoma on fine needle aspiration cytology. We present clues that may help in rendering the correct interpretation.     

Fine needle aspiration cytology of invasive cribriform carcinoma of the breast with osteoclastlike giant cells: a case report

BACKGROUND: Nonneoplastic osteoclastlike giant cells are occasionally associated with carcinoma of the breast, pancreatobiliary and gastrointestinal systems. In the breast, this uncommon stromal response is seen mainly in invasive carcinoma with low grade cytology, among which invasive cribriform carcinoma is the classic example. Details of the fine needle aspiration cytology of this phenomenon, especially in thin-layer preparations, have been described rarely. CASE: The fine needle aspiration cytology of an invasive cribriform carcinoma of the breast occurred in a 66-year-old woman. Cytology showed cohesive sheets and three-dimensional cribriform clusters of bland-looking and mitotically inactive ductal cells in a blood-stained background. Scattered multinucleated, osteoclastlike giant cells, some containing hemosiderin granules, were also seen. Myoepithelial cells and naked nuclei were not obvious. The cellular composition was more discernible in liquid-based cytologic preparations. Histologic examination of the excisional biopsy showed an invasive cribriform carcinoma associated with many osteoclastlike giant cells in a hypervascular stroma. CONCLUSION: In view of the extremely low grade cytology of the malignant ductal cells, invasive cribriform carcinoma may closely mimic benign proliferative breast diseases on fine needle aspiration biopsy. Recognition of this special relationship with osteoclastlike giant cells, which are rarely present in certain subtypes of breast cancer but not benign lesions, can help to arrive at a correct cytologic diagnosis.     

Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features

BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle aspiration cytologic features suggested sarcoma. CASE: A 55-year-old female presented with a rapidly growing breast lump of 1 month's duration. On examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial and lateral quadrants of the right breast. Fine needle aspiration cytology showed variably sized, dissociated and loosely clustered polygonal, plump and spindle cells with pale blue cytoplasm and vesicular nuclei that were round, oval or irregular. Occasional giant forms and nucleolated and mitotic cells were present. A single cluster of benign ductal cells was seen. The tumor cells did not express immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of sarcoma was given with differential diagnoses of metaplastic carcinoma and malignant phyllodes tumor. Histologic study established the diagnosis of leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration cytologic features of sarcoma, but specific tumor typing may not be possible, especially when the cytologic material is inadequate for ancillary staining required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant phyllodes tumor.     

The gray zone in breast fine needle aspiration cytology. How to report on it?

OBJECTIVE: To study the "gray zone" in breast fine needle aspiration cytology in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. STUDY DESIGN: This study compared cytology and histopathology of 72 breast lesions in which an initial cytologic diagnosis of atypia was given. RESULTS: There were 36 benign (50%) and 36 malignant (50%) histologic biopsy cases in the cytologic atypia group. Anisonucleosis, chromatin and nuclear membrane irregularity, and presence of myoepithelial cells were significantly different in benign and malignant cases. CONCLUSION: The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle aspiration cytology causes no delay in treatment as excisional biopsy is recommended for all equivocal cases.     

Fine needle aspiration cytology of apocrine carcinoma of the breast. Review of cases in a three-year period

OBJECTIVE: To describe the fine needle aspiration cytology findings of apocrine carcinoma of breast and correlate them with the histologic appearance. STUDY DESIGN: The author reviewed the fine needle aspiration cytology findings of two cases of pure apocrine carcinoma of the breast in the files of Pamela Youde Nethersole Eastern Hospital during a three-year period, 1998-2000. RESULTS: The cytologic findings in both cases were similar. The smears were of moderate to high cellularity, consisting of predominantly dispersed or loosely cohesive tumor cells in a focally granular background. The carcinoma cells contained abundant, dense to granular cytoplasm; round or oval and sometimes eccentrically located nuclei; a smooth nuclear outline; evenly dispersed chromatin; and solitary macronucleoli. The cell borders were mostly discrete. In contrast to benign apocrine cells, the malignant cells showed nuclear overlapping, more frequent nuclear pleomorphism, increased nuclear/cytoplasmic ratios and occasional mitotic figures. Histologic examination of the excised specimens showed extensive, solid apocrine carcinoma in situ with focal stromal invasion. CONCLUSION: Apocrine carcinoma, a subtype of breast carcinoma characterized mainly by its cytologic features, needs to be distinguished from benign apocrine lesions or other eosinophilic and granular cell tumors of the breast. Recognition of the subtle cytologic differences renders a definitive preoperative diagnosis possible.     

Silver-binding nucleoli and nucleolar organizer regions in fine needle aspiration cytology of the breast

Silver staining was used to demonstrate nucleoli and nucleolar organizer regions (NORs) in cytopreparations from breast fine needle aspiration (FNA) biopsies, with the resulting black dots being a combination of silver-binding nucleoli and dispersed NORs. Discrete black dots in 200 nuclei were manually counted in 25 silver-stained biopsies; the cytologic diagnoses were made on routine Papanicolaou-stained cytopreparations from the same aspirates. Although malignant breast lesions showed higher counts than did benign breast disease, an overlap of one malignant and three benign lesions occurred. Therefore, the method cannot be recommended for reliably discriminating between malignant and benign routine breast specimens obtained by FNA; it may have some value in assessing tumor behavior.     

Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions

OBJECTIVE: To differentiate hyperplastic nodules (HPN), follicular adenoma (FA) and follicular carcinoma (FCA) of the thyroid by cytomorphologic features combined with argyrophilic nucleolar organizer regions (AgNORs) and Ki-67 proliferative markers on fine needle aspiration cytology. STUDY DESIGN: Cytomorphologic patterns, along with two proliferation markers, Ki-67 and AgNORs, in fine needle aspirates of 123 histologically confirmed cases of thyroid follicular lesions, including 39 hyperplastic nodules, 70 follicular adenomas and 14 cases of follicular carcinomas, were recorded. RESULTS: Mean AgNOR (mAgNOR) counts and Ki-67 labelling index (LI) were consistently higher in FCA in comparison to FA and HPN irrespective of the cytologic patterns in fine needle aspiration smears. Between benign and malignant lesions, an overlap of 1.83% at the cutoff point of 4.0 was observed in cases of mAgNORs, whereas it was 11.09% at a cutoff of 5.0 in cases of Ki-67 LI. CONCLUSION: mAgNOR counting in fine needle aspiration smears is more sensitive, simple and cost effective as compared to Ki-67 LI for differentiating between benign and malignant thyroid follicular neoplasms.     

Hemangioendothelioma. Cytologic appearances in two cases presenting with multiple soft tissue and bone lesions

Two cases of hemangioendothelioma were detected by fine needle aspiration cytology in two women presenting with multiple soft tissue and bone lesions. The aspirates were hemorrhagic, and the smears showed mostly dissociated and predominantly monomorphic tumor cells. Focal rosettelike clustering of tumor cells was also present. A prominent cytologic feature of these two cases of hemangioendothelioma was the close association of tumor cells with endothelium-lined vascular structures, a pattern that can be seen in other sarcomas and sometimes in malignant epithelial tumors.     

Phyllodes tumor of the breast. A cytohistologic study of 80 cases

OBJECTIVE: To study the cytologic features of phyllodes tumor (PT) of the breast and determine the accuracy of their subclassification in fine needle aspirates. STUDY DESIGN: Eighty cases of histologically diagnosed PT between 1982 and 1997 with a previous fine needle aspiration (FNA) were evaluated. The FNA smears of each case were reviewed without knowledge of the initial cytologic diagnosis and subclassified into benign, borderline or malignant PT. RESULTS: Benign PTs were characterized by a dimorphic mixture of stromal and epithelial cells. The stromal fragments showed mild to moderate cellularity with absent to minimal pleomorphism and no mitosis. There were occasional, if any, single stromal cells. Borderline PTs had stromal fragments with moderately cellular stroma exhibiting moderate pleomorphism. Two additional features were the presence of single stromal cells and an occasional mitosis in the stromal fragments/single cells. Aspirates from malignant PT were very cellular, with a high stromal/epithelial ratio and marked stromal cellularity. The stromal cells were highly pleomorphic, with frequent mitosis and atypical single stromal cells in the background. Fifty-seven of the 80 histologically documented cases (71.3%) were diagnosed as PT on FNA (40 benign, 10 borderline and 7 malignant). In 81% (46 of 57 PTs), good cytohistologic correlation (32 benign, 8 borderline and 6 malignant) was observed. In another eight cases, one grade differentiation between cytologic and histologic grade was observed. Six of the nine malignant PTs on histology were correctly subclassified on cytology. There were one false positive and two false negative cases. CONCLUSION: Cytologic diagnosis and grading of PT on FNA is possible. Special care should be undertaken in interpreting phyllodes fragments, cellularity of stroma, pleomorphism and mitosis. Single stromal cells are also important morphologic criteria for subclassification. Multiple-site aspiration is advisable to avoid diagnostic errors.     

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.     

Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous features: a report of 2 cases

BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs) include both benign and malignant entities, such as benign soft tissue giant cell tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of breast cancer. CASES: We report the cytologic features, pathologic findings and immunohistochemical profile in 2 cases of this unusual variant of breast carcinoma. Two women aged 53 and 50 years women presented with a history of left and right breast lump but no local lymphadenopathy, respectively. Fine needle aspiration cytology (FNAC) of both cases revealed abundant MGC with highly pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous differentiation with multinucleated syncytiotrophoblast-like giant cells is extremely rare in breast tumors. Although rare, FNAC of breast cancer with pleomorphic MGC requires careful search for differential diagnosis; breast carcinoma with giant cell features (choriocarcinomatous features, OGC features) must be differentiated from metastatic tumors and other breast lesions containing giant cells.     

Metaplastic breast carcinoma. A diagnostic problem in fine needle aspiration biopsy.

Fine needle aspiration (FNA) was used to evaluate a breast lump and enlarged lymph nodes in a woman with a prior history of lumpectomy on the contralateral breast and a recent negative mammogram. The FNA cytologic findings included markedly atypical fibroblast-like cells lying singly and in groups in a myxoid background, highly atypical multinucleated cells and numerous mitoses, features that were interpreted as a high-grade malignant mesenchymal tumor. The carcinomatous cells in the aspirates were only fully appreciated after histologic examination of the mastectomy specimen and the axillary lymph node metastases showed a dual differentiation consisting of both epithelial and mesenchymal components, leading to a final diagnosis of metaplastic carcinoma. Electron microscopic study of histologic samples confirmed the dual differentiation, and both keratin and vimentin intermediate filaments were recognized by immunohistochemical staining. The regional lymph node metastases were predominantly sarcomatous, which apparently is a rare event. The entity of metaplastic carcinoma is discussed in relation to other mixed epithelial-mesenchymal lesions of the breast, and the previous literature on this entity is briefly reviewed.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

Polyclonal carcinoembryonic antigen staining in the cytologic differential diagnosis of primary and metastatic hepatic malignancies.

In order to assess the utility of immunocytochemical staining of bile canaliculi with a polyclonal antiserum to carcinoembryonic antigen (pCEA) in the differentiation of primary hepatocellular carcinomas from metastatic malignancies, pCEA staining was performed on fine needle aspiration specimens from hepatic lesions in 60 patients. The original cytologic diagnoses were hepatocellular carcinoma in 22 patients, metastatic neoplasm or cholangiocarcinoma in 27 patients and benign hepatocytes in 11 cases. The cytologic diagnoses of malignancy were confirmed by surgical excision, autopsy or clinical investigations in 82% of the patients. Follow-up data, supported by pCEA staining, reversed the original cytologic diagnosis in three cases. Bile canalicular pCEA staining was identified in 18 of 22 cases of hepatocellular carcinoma and in all 11 benign hepatocellular aspirates. All 27 cases of metastatic malignancy or cholangiocarcinoma were negative for canalicular pCEA staining, although 11 cases exhibited cytoplasmic staining. Interpretation of pCEA staining was not affected by the intermingling of malignant cells and benign hepatocytes. Predictive values were 100% for a positive test and 87% for a negative test. These findings indicate that staining with pCEA antiserum is a useful adjunct in the differential cytologic diagnosis of malignant hepatic lesions.     

Fine needle aspiration cytology of a thyroid metastasis of metaplastic breast carcinoma: a case report

BACKGROUND: Metaplastic breast carcinoma is defined as mesenchymal and/or squamous cell components associated with ductal carcinoma. Because of the heterogeneous nature of this tumor, cytologic interpretation on fine needle aspirates can be quite challenging. This is especially true of metastatic lesions of this rare tumor type. Metastasis to the thyroid has not been previously reported. CASE: A 57-year-old woman with a history of metaplastic breast carcinoma for which she underwent mastectomy, chemotherapy and radiation therapy 2 years earlier presented with a fast-growing left thyroid mass with progressive hoarseness and dysphasia. Clinical presentation and findings from a neck computed tomographic scan were strongly suggestive of a primary thyroid malignancy. The aspirate specimen was composed of scant, highly atypical epithelial cells in a background of an abundant chondromyxoid matrix and scattered, benign follicular cells. A literature review confirmed the novelty of this case. CONCLUSION: This case emphasizes the value of clinical information and the importance of generous sampling in achieving a correct diagnosis of metastatic metaplastic carcinoma.     

Giant cystic metaplastic carcinoma of the breast: a case report with diagnosis by fine needle aspiration

BACKGROUND: Breast cysts are mainly benign and are reported in association with fibrocystic disease and phyllodes tumor. Rarely have cystic changes been reported to occur in malignant tumors. They are usually small but large in rare cases. Giant breast cysts are very rare, and only a few cases have been reported. CASE: A 37-year-old woman presented with a rapidly growing breast mass. Mammography showed a huge, well-circumscribed cystic mass (17 x 16 x 16 cm) suggestive of a benign lesion. Cytologic examination revealed a highly cellular tumor composed of malignant cells of various sizes and shapes in a necrotic background. The smears were diagnosed as positive for malignancy and suggested metaplastic carcinoma. Mastectomy was performed, and histologic study confirmed the cytologic diagnosis. CONCLUSION: This is the first reported case of a breast cyst of this size. Clinically the cyst was confused with a benign lesion. The fine needle aspiration aided the diagnosis and planning of treatment.     

Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.     

Fine needle aspiration diagnosis of malignant lymphoma with confirmation by immunoperoxidase staining

Cytospin preparations of fine needle aspirates in 14 cases of suspected lymphoma were studied by immunoperoxidase techniques. The combination of cytologic smears and immunoperoxidase studies resulted in a working diagnosis in 13 of the 14 cases. The immunologic markers in conjunction with the cytologic appearance of the aspirates were reliable and consistent in differentiating between malignant and benign lymphoproliferative lesions and in determining the B-cell or T-cell nature of the process.     

Aspiration cytology of breast cysts

A cytologic evaluation was made of 57 samples of fluid aspirated from cystic breast masses during the past 12 years in our hospital. The cytologic diagnosis of the cyst aspirates from 17 cancer cases was positive in 10 cases, suspicious in 2 and negative in 5. No false-positive cytologic diagnosis was made in 40 cases of benign cystic disease. Blood-tinged aspirates were observed in 14 of the 17 cases of malignant cystic disease but in only 2 of 40 benign cases. Ductal cell clusters were detected in aspiration smears from 16 of the cases of malignant cystic disease and 15 of the cases of benign cystic disease. Apocrine cells were seen in the aspiration smears from 12 of the cases of benign cystic disease but in none of the aspirates from the 17 cancer cases.