Cytologic characteristics and origin of naked nuclei in breast aspirate smears

To elucidate the origin of "naked nuclei" in breast aspiration smears, 17 cases of fibroadenoma were studied by light and electron microscopy. The ATPase reaction was also studied at both levels. The aspirates contained two types of naked nuclei: denuded degenerated nuclei and oval to spindle-shaped nuclei with very scanty cytoplasm. The cytoplasm of the latter was rich in free ribosomes and rough-surfaced endoplasmic reticulum but was devoid of cytoplasmic filaments and dense bodies. These cells were negative for ATPase activity. Stromal cells, not myoepithelial cells, characteristically demonstrated such cellular features in the aspirates and tissue sections studied. We conclude that most naked nuclei are derived from stromal 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.     

Aspiration cytology of tubular breast carcinoma

The cytologic features in smears of fine needle aspirates from 34 tubular breast carcinomas were studied. Uniform and bland epithelium in cohesive clusters dominated all specimens; two-thirds also showed some degree of cellular dissociation. Characteristic (but not quite pathognomonic) angular epithelial clusters with a tubular structure occurred in about 50% of the smears. Sparsely occurring atypical nuclei and/or cytoplasmic vacuoles, similar to those seen in lobular cancer, were found in half of the cases. Although a lack of myoepithelial cells was apparent in the majority of the smears, one-fourth of them showed a quite prominent myoepithelial component. Various combinations of atypical features resulted in a picture that was considered diagnostic of malignancy in 50% of the cases; the remaining specimens showed less pronounced atypia. Other pitfalls associated with the cytologic diagnosis of tubular carcinoma are discussed, and the importance of basing the management of small breast lesions on the mammographic as well as on the cytologic findings is emphasized.     

Salivary gland tumors with a prominent oncocytic component. Cytologic findings and differential diagnosis of oncocytomas and Warthin's tumor on fine needle aspirates

OBJECTIVE: To review aspirates from histologically documented oncocytomas and Warthin's tumor (WT) to highlight the cytomorphologic findings and determine the difficulties encountered in typing oncocytepredominant aspirates. STUDY DESIGN: Over a 19-year period (1982-2000) we reviewed aspirates from 45 cases with an oncocyte preponderance. In 24 of them tissue for histologic examination was available (5 oncocytomas and 19 WT). RESULTS: In 4 of the 5 histologically documented oncocytomas the aspirates were cellular, with oncocytic epithelial cells in sheets, papillary fragments and singly. Epithelial atypia was minimal and lymphoid component absent, though scant proteinaceous material with a sprinkling of lymphocytes was seen. In WT moderate (35%) to abundant (28%) oncocytic epithelial cells were seen predominantly in a sheetlike arrangement with occasional papillary fragments and single cells. A variable quantity of lymphoid component was seen in 90% of the aspirates, with 88% of them showing a proteinaceous background accompanied by necrotic debris in 43% of cases. Squamous metaplasia was identified in 30% of cases, with 3 showing atypical squamous cells. In four cases the lymphoid component was scant and oncocytes abundant, and both possibilities were entertained. CONCLUSION: Fine needle aspiration cytology is fairly accurate in the preoperative diagnosis of WT. When the lymphoid component, mucus and necrotic background are minimal or absent, the tumors can be confused with oncocytoma. In oncocytoma, the oncocytic epithelial cells are more often seen in papillary fragments, acini and singly in comparison to WT, where sheets of oncocytic cells are observed. Some degree of epithelial atypia can be seen in oncocyte-predominant benign lesions. Squamous metaplasia, especially if accompanied by atypia and necrosis, can prove challenging.     

Fine needle aspiration cytology of ductal breast carcinoma with neuroendocrine differentiation. Review of eight cases with histologic correlation

OBJECTIVE: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance. STUDY DESIGN: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation. RESULTS: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically. CONCLUSION: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.     

Immunocytochemical detection of estrogen receptors by staining with monoclonal antibodies on cytologic specimens of human breast cancer

A study was undertaken to test the possibility of determining the estrogen receptor (ER) content in human breast cancers by staining with commercial specific monoclonal antibodies (MAbs) on cytologic specimens (touch imprints and fine needle aspirates). The aspirates were suspended in a cell culture medium and cytocentrifuged onto slides to preserve their morphologic characteristics and to allow a proper immunocytochemical staining for ERs. MAb staining for ER was also performed on the respective surgical samples. The staining of cytologic samples for ER showed 100% specificity and 95% sensitivity in comparison to the staining of the histologic samples. Moreover, comparison of the percentage of stained cells in the cytologic specimens to the ER content in the respective surgical specimens, as assayed by the dextran-coated charcoal method, showed the MAb staining of cytologic samples to have 94% specificity and 100% sensitivity. These results support the reliability of MAb staining for ERs in cytologic samples and suggest that it could be the assay of choice in particular clinical settings in the evaluation of primary and recurrent breast cancers.     

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 (FNAC) of mammary granular cell tumour: a report of three cases

This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examipation consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S-100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.     

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.     

Cytodiagnosis of simple and proliferating trichilemmal cysts

OBJECTIVE: To elucidate the cytologic findings in simple trichilemmal (pilar) cysts and proliferating trichilemmal cysts (pilar tumors) and the clinical importance of these lesions. STUDY DESIGN: Aspirates from 12 simple pilar cysts and three pilar tumors, all histologically confirmed, were analyzed with a view to elaborating on specific cytologic features enabling a distinction from epidermal cysts and other adnexal tumors. RESULTS: Aspirates from pilar cysts showed two different pictures, depending on the age of the cyst. Young pilar cysts showed aspirates with an abundant background of blotchy keratin with or without calcification and inflammation. Older (degenerating) cysts showed oily fluid debris with cholesterol crystals and inflammatory cells. The epithelial component was sparse, and only an occasional syncitial cluster of small squamoid cells was seen. As opposed to this, epidermal cysts usually showed a cleaner background, with very cellular aspirates containing many nucleate and anucleate squames, keratin flakes, platelike crystals and no calcification. The pilar tumors showed a lesser amount of keratin as compared to pilar cysts and yielded large and small clusters of squamoid and basaloid cells, a few of which showed an abrupt association with anucleate, keratinized globules. CONCLUSION: The cytologic diagnosis of a pilar cyst should be made especially in scalp cysts, which yield either abundant, blotchy keratin or oily, cholesterol-rich debris with a sparse epithelial component and which lack a mixture of anucleate and nucleate squames. On aspiration, pilar tumors yield comparatively more cells and less keratin and show small, basaloid or squamoid cells abruptly associated with keratin globules. The cytologic diagnosis of pilar cysts is important because these cysts recur if incompletely excised and often undergo transformation to pilar tumors. Similarly, pilar tumors often clinically mimic squamous carcinomas, and hence there is a need to outline definitive cytologic features.     

Cytology of fine needle aspiration biopsy of primary breast rhabdomyosarcoma in an adolescent girl

A bilateral breast tumor in an 11-year-old girl was diagnosed as a malignant mesenchymal neoplasm by fine needle aspiration biopsy, and its muscular origin was suggested. An immunoperoxidase stain for the demonstration of intracellular myoglobin in destained cytologic aspirates exhibited a positive reaction of variable intensity in some of the undifferentiated round cells and in the more mature bipolar sarcomatous elements. These findings were confirmed in the histologic sections of the excised tissue. Needle aspiration is helpful in these rare cases of primary breast rhabdomyosarcoma, which often present with a solid, undifferentiated histologic pattern in this age group. In addition to the cytologic characteristics, the possibility of detecting muscle antigens as markers for these embryonal small cells, even in previously stained slides, provides a successful method for defining the specific type of sarcoma.     

Secretory carcinoma of the breast in an adult. Correlation of aspiration cytology and histology on the biopsy specimen

Needle aspiration was performed on the excisional biopsy specimen of a breast mass in a 63-year-old woman. The cytologic features in the aspirate included solid and papillary proliferations of tumor cells with abundant intracytoplasmic vacuolization and secretion. Histologic study of the lesion showed a secretory carcinoma. Although this is a rare breast neoplasm, especially in adults, the cellular features are characteristic and may permit a specific diagnosis on needle aspirates.     

Spindle cell malignant melanoma metastatic to the breast from a pigmented lesion on the back. A case report

BACKGROUND: Tumors metastatic to the breast are quite unusual (1.2% of all tumors). Malignant melanoma is an exception and is one of the principal metastasizing tumors, described mainly as a primary tumor. There are 5 different cytologic patterns; the spindled pattern is very uncommon, more difficult to diagnose and can be confused with a wide range of sarcomatous lesions. Nevertheless, there are some cytologic features that allow differentiation from similar tumors. CASE: A 30-year-old woman presented with a firm, deep, nontender mass in the upper outer quadrant of the right breast. Fine needle aspiration cytology was performed, and the aspiration smears showed spindle-shaped neoplastic cells arranged singly or in clusters with marked nuclear atypia. Melanin pigment was sometimes seen in the cytoplasm of some cells. Pathologic study of the breast tumor corroborated the diagnosis, and later study revealed lymph node metastases and relapse in the breast area and on a scar on the back. Two years earlier, biopsy of a pigmented lesion on the back was diagnosed as a cellular blue nevus. CONCLUSION: The cytologic features of spindle cell melanoma are distinctive. The presence of atypical fusiform cells with elongated cytoplasm; enlarged nuclei, some of them binucleated or multinucleated; prominent nucleoli; intranuclear cytoplasmic inclusions; and melanin pigment can help to diagnose these unusual metastases to the breast. This case was the first of malignant metastatic melanoma with the spindled pattern in which the diagnosis was made by fine needle aspiration cytology.     

Immunocytodiagnosis of carcinocythemia in disseminated breast cancer

A small number of large, malignant mononuclear cells were found in the blood of a patient with disseminated breast carcinoma. The detection of these scarce cells was facilitated by examining leukocyte concentrates. Cytochemical and immunochemical studies showed that these were epithelial cells, not hemopoietic cells. These findings, when correlated with the clinical features and the cytologic findings in blood and marrow, suggested that the malignant mononuclear cells in the blood were breast carcinoma cells. This study demonstrates the technical feasibility of accurately identifying cells in blood, which may stimulate interest in the study of cancer cells in the circulating blood. The method may also be applied to other cytologic specimens, such as fine needle aspirates, that contain only a few neoplastic cells.     

Diagnostic schemes for fine needle aspirates of breast masses

A comparison was made of four statistically based schemes for classifying epithelial cells from 243 fine needle aspirates of breast masses as benign or malignant. Two schemes were computer-generated decision trees and two were user generated. Eleven cytologic characteristics described in the literature as being useful in distinguishing benign from malignant breast aspirates were assessed on a scale of 1 to 10, with 1 being closest to that described as benign and 10 to that described as malignant. The original computer-generated dichotomous decision tree gave 6 false negatives and 12 false positives on the data set; another tree generated from the current data improved performance slightly, with 5 false negatives and 10 false positives. Maximum diagnostic overlap occurred at the cut-point of the original dichotomous tree. The insertion of a third node evaluating additional parameters resulted in one false negative and seven false positives. This performance was matched by summing the scores of the eight characteristics that individually were most effective in separating benign from malignant. We conclude that, while statistically designed, computer-generated dichotomous decision trees identify a starting sequence for applying cytologic characteristics to distinguish between benign and malignant breast aspirates, modifications based on human expert knowledge may result in schemes that improve diagnostic performance.     

Aspiration cytology of fibrosarcomatous variant of dermatofibrosarcoma protuberans with osteoclastlike giant cells in the chest wall: a case report

BACKGROUND: A case of fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) with osteoclastlike giant cells involved the dermis and subcutaneous tissue of the chest wall. This case was misdiagnosed as primary breast tumor clinically and had cytologic features similar to those of the metaplastic breast carcinoma (MRBC). CASE: A 53-year-old female presented with a nodular breast mass enlarging slowly over a long period of time and growing rapidly for about 3 months. The aspirates showed high cellularity with both individually scattered and fascicular arrays of spindle cells. A few multinucleated giant cells without nuclear atypia were intermixed with dissociated spindle cells. There was no epithelial component in the smear. Cytologic evaluation suggested the possibility of a low grade spindle cell sarcoma as well as MBC. Subsequently, the patient underwent modified radical mastectomy, and the diagnosis of FS-DFSP was made. CONCLUSION: Distinguishing FS-DFSP with osteoclastlike giant cells from other spindle cell tumors of the breast, especially MBC showing predominantly spindle cell components, may pose significant challenges to the pathologist. However, clinical and radiologic findings and a meticulous search for other components raised the possibility of FS-DFSP on aspiration cytology.     

Significance of squamous cells in fine needle aspiration cytology of the breast. A review of cases in a seven-year period

OBJECTIVE: To delineate the significance of detecting squamous cells in fine needle aspiration biopsy of breast lesions. STUDY DESIGN: The authors reviewed 15 cases of fine needle aspiration cytology of the breast with a discernible number of squamous cells from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a seven-year period from the start of 1994 to the end of 2001. The cytologic features were correlated with clinical, radiologic and histologic findings, if any. RESULTS: Among the 15 fine needle aspirates of the breast with a discernible number of squamous cells, 5 of them represented metaplastic carcinoma. The remaining consisted of 3 cases of fibroepithelial tumors, 1 case of duct ectasia, 3 cases of subareolar abscess, 2 cases of sclerosed intraduct papilloma and 1 case of benign breast cyst. In general, benign squamous cells were bland looking and often associated with anucleated squames. They were mitotically inactive and could show a good maturation pattern. Tumor cell cannibalism was rare. The presence of abundant, foamy macrophages in the background suggested a benign lesion. The primary diagnosis could be deduced by recognition of other features, such as the presence of myxoid stromal tissue and papillary structures. In contrast, malignant squamous cells in metaplastic carcinoma were more pleomorphic and mitotically active. Dyskeratosis and tumor cell cannibalism were obvious. Tumor diathesis and bizarre-shaped cells were sometimes found. CONCLUSION: Squamous cells occur in fine needle aspirates from a number of benign and malignant breast lesions. Benign conditions with abundant squamous cells may sometimes mimic malignant squamous lesions and vice versa. Careful assessment of the cytologic features of squamous cells and background appearance is crucial for achieving a correct diagnosis.