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.     

Cytologic features of pilocytic astrocytoma in cerebrospinal fluid specimens

OBJECTIVE: To illustrate the cytomorphologic features of pilocytic astrocytoma (PA) in cerebrospinal fluid (CSF) samples. STUDY DESIGN: A search of records from 1965 to 2001 was performed to identify all patients with a diagnosis of PA in whom CSF samples were examined. Slides from CSF samples originally reported as atypical, suspicious or positive were reviewed and the cytomorphologic features assessed. RESULTS: Two hundred ninety-three patients with a diagnosis of PA were identified. Of these, 44 had a total of 65 cytologic preparations of CSF. In 34 patients (77.2%) the CSF cytology was negative, in 5 (11.4%) either atypical or suspicious, and in 5 (11.4%) positive for neoplastic cells. The tumors in the 5 positive cases arose in the cerebellar hemispheres (2), cerebellar vermis (1), thalamus (1) and tectum with extension into the fourth ventricle (1). All positive samples were hypercellular, with an average of 5 cell clusters per case (range, 3-11). The clusters were composed of cohesive epithelioid cells with a mean of 8 cells per cluster. In addition, some cases had scattered, isolated, single cells. These single neoplastic cells had prominent, hairlike cytoplasmic processes. The cells in clusters appeared epithelioid, with oval nuclei, mild nuclear pleomorphism, finely or slightly coarsely granular chromatin and cobweblike cytoplasm. CONCLUSION: The cytomorphologic features of PAs recapitulate their histologic characteristics. The tumor cells are recognizable in CSF samples and readily distinguishable from histiocytes and ependymal cells.     

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.     

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.     

Histiocytoid change in breast carcinoma: a report of 3 cases with an unusual cytomorphologic pattern of apocrine change

BACKGROUND: Breast carcinomas composed predominantly or exclusively of cells with foamy and/or granular cytoplasm have been termed histiocytoid breast carcinoma. CASES: Three cases of HBC had fine needle aspirates that were moderately cellular and composed of cells with abundant foamy and/or granular cytoplasm, arranged in loosely cohesive groups and dispersed singly. The cells showed subtle cytologic atypia, including nuclear hyperchromasia and slightly irregular nuclear outlines. Definitive cytologic diagnosis was not possible in the 3 cases, and they were reported as "suspicious for malignancy." Core biopsies of 2 cases showed a typical Indian file pattern of invasive lobular carcinoma, while the third case was composed of sheets of discohesive histiocytoid cells admixed with a prominent lymphoid infiltrate. All 3 cases were E-cadherin negative, confirming their lobular nature. CONCLUSION: HBC represents an unusual morphologic pattern of apocrine change that may be seen in lobular and ductal breast carcinomas. Recognition of these lesions is vital in that they may be mistaken for a variety of other entities composed of foamy/granular cells; some of those entities have vastly different implications for treatment and prognosis.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.     

Intracytoplasmic lumina in medullary carcinoma of the thyroid gland. Report of a case with cytologic and immunocytochemical features

BACKGROUND: Intracytoplasmic lumina (ICL) have been observed frequently in breast carcinoma cells. However, they are extremely rare in thyroid gland tumors. We encountered a medullary carcinoma of the thyroid (MCT) with ICL and present a case with cytologic, immunocytochemical and ultrastructural features. CASE: A 15-year-old female was admitted with a left thyroid mass. Ultrasound examination revealed a well-defined tumor in the left lobe of the thyroid. Fine needle aspiration cytology showed mainly dispersed spindle cells with oval nuclei and some polymorphic or triangular tumor cells. The tumor cells containing ICL were noted at high magnification. The ICL contained sparse microvilli and abundant granular material with dense, round bodies on ultrastructural sections. Immunocytochemically, these tumor cells were positive for calcitonin and carcinoembryonic antigen (CEA). Moreover, CEA was recognized in the ICL with immunocytochemical staining. All tumor cells were negative for thyroglobulin. Pathologic examination confirmed the diagnosis of medullary carcinoma of the thyroid gland. CONCLUSION: MCT can include ICL with granular material containing CEA.     

Features of benign granular cell tumor on fine needle aspiration.

OBJECTIVE: To describe the cytomorphologic features of benign granular cell tumor (GCT) on fine needle aspiration (FNA) biopsy and discuss the differential diagnosis. STUDY DESIGN: We reviewed three fine needle aspirates of surgically confirmed benign GCT. Immunocytochemical staining for S-100 was performed on the aspirate smear in one case. RESULTS: Two GCT were thigh lesions, where lipoma and fibromatosis were the leading clinical diagnosis, and the third was a breast mass clinically suspected to be a fibroadenoma. All FNA specimens were highly cellular and composed of fairly uniform cells with eccentric, round-to-slightly oval nuclei and abundant, finely granular cytoplasm. The cells were fragile, with stripped nuclei in a background of finely granular material. Occasional cells with nuclear pleomorphism and small-but-conspicuous nucleoli were identified. There was no evidence of necrosis or mitotic activity. Rare intranuclear cytoplasmic inclusions were identified in two cases. The granular cells were immunoreactive for S-100 in the case studied. CONCLUSION: Benign GCT has a distinctive cytomorphologic appearance that permits its diagnosis on FNA. High cellularity, occasional cells with nuclear pleomorphism and prominent nucleoli are features that can be present in benign GCT. Mitotic figures and necrosis should be identified before a diagnosis of malignancy is rendered.     

Nodular fasciitis of the breast: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Nodular fasciitis is a rare benign pseudosarcomatous proliferation of fibroblasts in the breast, in which the clinical examination and mammographic findings may closely mimic mammary carcinoma. CASE: A case of nodular fasciitis was diagnosed by fine needle aspiration. A 15-year-old girl was admitted to our hospital with a recently noticed, rapidly growing mass in the right breast. The aspirate contained cohesive groups of fusiform cells with elongated and oval nuclei, regular nuclear membranes and inconspicuous nucleoli, intermingled with scattered lymphocytes, red blood cells and characteristic granular background substance. A cytologic diagnosis of nodular fasciitis was made and confirmed histologically. CONCLUSION: Mammary nodular fasciitis is often clinically suspicious for carcinoma and rarely diagnosed by fine needle aspiration cytology. A literature search yielded only five reported cases. The cytologic diagnosis of this entity helps to choose the correct surgical procedure, preventing psychological trauma to the patient.     

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.     

Cytologic findings of atypical adenosis of the breast. A case report

BACKGROUND: Atypical apocrine adenosis, a well-described histopathologic entity, can sometimes be misdiagnosed as carcinoma. Apocrine cells can also appear atypical in cytopathology and be mistaken for carcinoma. Occasional case reports describe false positive cases due to the presence of apocrine cells in a few cases of radial scars and atypical apocrine metaplasia and in a degenerated cyst. CASE: A 37-year-old female underwent ultrasound-guided fine needle aspiration of an ill-defined breast nodule. The aspirate showed clusters and single cells containing abundant granular to focally vacuolated cytoplasm; enlarged, pleomorphic nuclei with irregular nuclear membranes; granular chromatin; and prominent nucleoli. These cells were distinct from and larger than the surrounding ductal and myoepithelial cells. Excision showed a nodular area of atypical apocrine adenosis adjacent to previous biopsy changes, correlating with the cytologic findings. CONCLUSION: Atypical apocrine adenosis can mimic carcinoma in histopathology and cytopathology. One should be cautious when reviewing apocrine cells in cytology, given their atypical features, especially their single, dispersed nature. However, the presence of accompanying benign cellular elements supports a benign diagnosis. Surgical biopsy should be recommended based on the cytologic findings.     

Medullary thyroid carcinoma. Rare cytologic findings

OBJECTIVE: To describe some rare cytologic findings in medullary thyroid carcinoma. STUDY DESIGN: Review of the fine needle aspiration smears from 15 cases of medullary thyroid carcinoma that were confirmed on histologic sections. The ages ranged between 31 and 67 years; 10 were female and 5 male. Thirteen were sporadic forms, and two were familial forms. RESULTS: Eight cases were classified as pleomorphic cell type and seven as monomorphic cell type. The smears revealed round, oval, triangular, polygonal and spindle-shaped cells, intracytoplasmic red granules, occasional intranuclear inclusions, amyloid, binucleated and multinucleated cells, and thick, granular chromatin. CONCLUSION: The rare cytologic findings in this study were grape cells, cytoplasmic nippling, elongated cytoplasmic processes, carrot-shaped nuclei, nuclear buddings, mast cell-like cells and a Burkitt's lymphoma-like appearance. These findings were rarely reported before.     

Cytologic appearances in invasive lobular carcinoma of the breast. A study of 21 cases

OBJECTIVE: To examine the fine needle aspiration cytologic features of invasive lobular carcinoma of breast and to discuss problems that may occur in cytodiagnosis. STUDY DESIGN: Fine needle aspiration cytologic smears from 21 cases of invasive lobular carcinoma (ILC) of breast were subjected to detailed cytomorphologic analysis. Features studied included pattern of cells, size of cells, nuclear placement, pleomorphism, presence of intracytoplasmic lumina (ICL) and signet ring cells. RESULTS: Cellularity was generally moderate or high, and the pattern was predominantly or partly dissociated in 86% of cases. Rosettelike pattern was discerned in alveolar-type ILC. Cell size was usually small or intermediate, with nuclei placed eccentrically in most cases. ICLs with or without signet ring cells were present in 12 cases (57%). CONCLUSION: A cytologic picture consisting of predominantly dissociated small or intermediate-sized tumor cells with eccentric nuclei, with some of the cells showing ICLs, is highly suggestive of ILC. Indian file pattern, another characteristic feature of ILC, is, however, focal and inconsistent. Variant patterns of ILC may show other cytologic features, such as rosettelike pattern (alveolar variant of ILC) or large cell pattern (pleomorphic variant of ILC) and may consequently be difficult to categorize on cytologic smears.     

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast 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.     

Low-grade cribriform ductal carcinoma in situ of the breast. Fine needle aspiration cytology in three cases.

This paper presents the cytologic features of fine needle aspiration biopsy specimens from three cases of ductal carcinoma in situ characterized by small and uniform tumor cells growing in a predominantly cribriform pattern without comedo necrosis (low-grade cribriform ductal carcinoma in situ). On cytology, most of the tumor cells were clustered in three-dimensional ductal structures. Occasionally in the clusters the tumor cells were seen bordering central lumina, quite similar to the architecture in histology. A few single tumor cells and no myoepithelium were seen. The background was clear or slightly hemorrhagic, without necrosis. The tumor cells were uniform and had a cylindroid shape, with round or oval nuclei. Morphometrically the mean largest nuclear diameter was 1.5-1.6 times that of a red blood cell. The chromatin was finely granular, with a minute nucleolus and slight condensation along the nuclear membrane. In cut sections all three tumors showed strong immunoreactivity for neuron-specific enolase. Unless the cribriform growth pattern is recognized in the smear, the cytologic diagnosis of this entity is difficult.     

Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the breast: review of 37 cases with histologic correlation

OBJECTIVE: To analyze fine-needle aspiration cytology (FNAC) material from 37 cases of breast glycogen-rich clear cell cancer (GRCC) and correlate cytomorphologic features with histologic appearance to determine characteristics of GRCC on FNAC. STUDY DESIGN: We reviewed cytologic features of 37 cases of breast GRCC from the archives of Ege University Hospital diagnosed between 1994 and 2006. RESULTS: Thirty-seven patients with available aspirate and confirmed GRCC were identified. The female patients ranged from 32 to 81 years (mean 52 years). The initial cytologic diagnoses were adenocarcinoma for 27 and atypical or suspicious for cancer for 10. The cytologic picture was characterized by hypercellular tumor cells in loosely cohesive syncytial groups and some single cells. Most tumor cells had abundant, finely granular eosinophilic cytoplasm or foamy to clear cytoplasm with well-defined cytoplasmic membranes and moderate to marked nuclear pleomorphism with prominent nucleoli. Histologic examination confirmed all cases to be pure GRCC. ConCLUSION: Breast GRCC is a rare, distinct category with cytologic features that overlap considerably with those of other carcinomas. Awareness of variability in cytomorphologic appearance of GRCC and routine assessment for glycogen facilitate accurate diagnosis of these lesions by FNAC and enable prompt treatment of these poor-prognosis breast cancers.     

Exfoliative cytology of multiple endobronchial granular cell tumor

A multicentric endobronchial granular cell tumor (GCT) in a 50-year-old man was diagnosed by the cytologic study of bronchial lavage specimens. The paraffin-embedded sections contained small clusters of medium-sized round tumor cells that had eccentric nuclei without nucleoli and eosinophilic finely granulated cytoplasm, which was positive with the periodic acid-Schiff stain. These cells were distinguishable from the macrophages and bronchial and squamous cells also found in the specimens. The excised tumors histologically mimicked a squamous cell carcinoma. Since 10% of all GCTs occur in the lung, where a multiple presentation can especially mimic a metastatic malignant process, it is important that the possibility of a granular cell tumor be considered in the screening of exfoliative cytologic specimens from the lung.