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 cytology of epithelial-myoepithelial carcinoma of salivary glands. A report of three cases.

BACKGROUND: Epithelial-myoepithelial carcinoma is a rare, low grade malignant tumor of the salivary glands. Histologically, it has a biphasic cellular composition and exhibits a high degree of differentiation. The fine needle aspiration cytology of this rare tumor is rarely described in the literature. CASES: We report the fine needle aspiration cytology of three epithelial-myoepithelial carcinomas, arising in the right parotid, left parotid and minor salivary gland of the hard palate. Cytology showed a biphasic population consisting of cells of ductal epithelial and myoepithelial origin arranged in small clusters and sheets. The myoepithelial cells had small, uniform nuclei; ample, clear cytoplasm and distinct cell borders, while the ductal epithelial cells had larger, mildly pleomorphic nuclei and scanty cytoplasm. These ductal cells tended to form tubules among background sheets of clear myoepithelial cells. This feature, if present, was an important diagnostic clue. Hyaline material surrounding cell clusters and focal adenoid cystic carcinoma-like areas with orangeophilic globules were also not uncommon. CONCLUSION: While the cytologic appearance of epithelial-myoepithelial carcinoma may closely mimic that of other salivary gland tumors, such as adenoid cystic carcinoma, pleomorphic adenoma and basal cell adenoma, certain peculiar cytologic features may allow a distinction to be made on fine needle aspiration biopsy.     

Seminal vesicle epithelium as a potential pitfall in the cytodiagnosis of presacral masses. A report of two cases

BACKGROUND: Whenever abdominoperineal resection is performed because of a rectal adenocarcinoma, the prostate and seminal vesicles may be displaced backward to the presacral space, giving rise to a false radiologic image of a presacral tumor. Due to cytologic atypia associated with the epithelium of seminal vesicles, there is a real possibility, in fine needle aspiration biopsy (FNAB), of erroneously giving a malignant diagnosis. CASES: Two men, aged 53 and 57 years, presented with presacral masses three months and six years, respectively, after abdominoperineal resection for rectal adenocarcinoma. In both cases, FNAB smears showed some groups and single cells with large and irregular nuclei. These cells suggested a recurrence of carcinoma. The presence of cytoplasmic coarse pigment and a background with spermatozoa and blobs of inspissated secretory product were sufficient to determine that these presacral masses represented the seminal vesicles. CONCLUSION: Awareness that seminal vesicles may give rise to a radiologic impression of presacral tumor after abdominoperineal resection of the rectum will avoid unnecessary FNAB and a cytologic false positive diagnosis of colorectal adenocarcinoma.     

Fine needle aspiration cytopathology of phyllodes tumor. Differential diagnosis with fibroadenoma

The differential diagnosis of benign or borderline phyllodes tumors of the breast in fine needle aspiration biopsy smears was studied. Smears from five histologically proven cases and 20 proven cases of fibroadenoma were evaluated with regard to their cytologic features. The findings indicate that the presence of a high cellularity of stromal fragments (including bipolar naked nuclei), clusters of hyperplastic ductal cells and giant cells and the absence of apocrine metaplasia may suggest a diagnosis of phyllodes tumor, as opposed to fibroadenoma. The borderline phyllodes tumor showed a sarcomatous atypia and/or small intranuclear cytoplasmic invaginations in some cells. The differential diagnosis of this tumor with malignant phyllodes tumor and plasma-cell mastitis is also discussed.     

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.     

Prostate basal cell lesions can be negative for basal cell keratins: a diagnostic pitfall

BACKGROUND: Prostate basal cell lesions can have architectural and cytologic atypia that mimic prostate adenocarcinoma. Immunohistochemical stains for basal cell markers are most helpful in the differential diagnosis. All of the published studies show basal cell lesions are positive for basal cell keratins, whereas adenocarcinoma is negative for both. We reported two cases of prostate basal cell lesions with negative basal cell keratin expression by immunohistochemistry. STUDY DESIGN: We reported the histologic and immunohistochemical profiles of two cases of basal cell lesions of the prostate. RESULTS: Histologically, both cases were highly suspicious for prostate adenocarcinoma with infiltrative growth pattern and significant nuclear atypia. The atypical glands in both cases were negative for basal cell keratins. However, both lesions were positive for another basal cell marker, p63, confirming that they were basal cells in origin, rather than prostate adenocarcinoma. CONCLUSION: Prostate basal cell lesions can occasionally be negative for basal cell keratins by immunohistochemistry and therefore may be misdiagnosed as prostate adenocarcinoma. We recommend using both p63 and basal cell keratins simultaneously in the workup of atypical prostate lesions to avoid such a misdiagnosis.     

Papillary carcinoma of the breast. Cytologic study of nine cases.

OBJECTIVE: To study the cytologic findings of papillary breast carcinoma by fine needle aspiration. STUDY DESIGN: The study group consisted of fine needle aspiration (FNA) specimens of breast tumors from nine patients performed during the period 1988-1997. Eight were female, and one was male. The FNA results were compared with the final histologic diagnosis. RESULTS: The tumor sizes were 4-6.5 cm. The aspirations yielded a good amount of bloody material. The smears revealed high cellularity, papillary clusters, isolated low-to-tall columnar cells, mild to moderate atypia, hemorrhagic background, foam and hemosiderin-laden macrophages, calcification, rare mitoses, palisading row of cells and bipolar cytoplasmic eosinophilic granules. The smears were diagnosed as either suspicious or suggestive of papillary carcinoma. The histologic examination revealed invasive papillary carcinoma. CONCLUSION: Papillary carcinoma of the breast can be diagnosed by using a panel of cytologic findings that includes hypercellularity, papillary clusters, hemorrhagic background, palisading rows of tall columnar cells, cellular atypia and calcification. The interesting finding in this study was the presence of eosinophilic bipolar cytoplasmic granules, which has not been reported before.     

Fine needle aspiration cytology of primary thyroid paraganglioma. Report of a case with cytologic,histologic and immunohistochemical features and differential diagnostic considerations

BACKGROUND: Thyroid paraganglioma is a rare tumor and can cause diagnostic difficulties when using fine needle aspiration cytology (FNAC), especially when associated with some cytologic atypia. This case report appears to be the first on FNAC of primary thyroid paraganglioma. CASE: FNAC of a thyroid nodule situated in the right lobe was performed on a 46-year-old female. FNAC showed single cells and loose clusters of large, oval cells with round to oval nuclei, evenly dispersed chromatin, focally discrete nucleoli, moderate anisocytosis and anisonucleosis. A few larger cells showing irregular nuclei and coarser chromatin. The tumorous appearance of the lesion and some cytologic atypia led to a right lobe thyroidectomy, revealing a primary thyroid paraganglioma associated with capsular invasion; slight, focal cytologic atypia; and no vascular invasion. CONCLUSION: The atypia probably originated in the area of capsular invasion. To avoid misdiagnosing these tumors as malignancies, paraganglioma should be added to the differential diagnosis list when dealing with thyroid FNAC showing some atypia.     

Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters

Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178+/-12 for fibroadenoma; 275+/-11 for DCIS; 299+/-10 for grade I IDC; 251+/-10 for grade II IDC; and 314+/-11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors.     

Morphologic scales and relative distances between lesions identified on Papanicolaou smears.

We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily given scales (pseudoscalar transform) of a two-way discrete classification table by maximizing the likelihood (entropy) and computing morphologic scales of clusters of objects identified by visual judgments. The scales give the relative distance between pairs of categories or states. Morphologic scales of histologic lesions (states) identified on Papanicolaou smears were computed from a confusion matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears and colposcopically directed biopsies available from the Gynecologic Cytology Laboratory, University of Minnesota, between 1985 and 1987. The original (uncollapsed) confusion matrix consisted of eight cytologic categories and histologic states: normal plus atypical benign, reactive atypia (including condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma in situ; invasive squamous cell carcinoma; and other malignancies. The morphologic scales are expressed numerically, which reflects a degree of confusion between two diagnostic categories or states. Except for malignancies other than squamous cell carcinoma, morphologic scales of histologic states seen from cytology retained the order of clinical severity. We detected a high degree of confusion between severe dysplasia and carcinoma in situ. Malignancies other than squamous cell carcinoma fell between moderate and severe dysplasia. Such a transposition of the scales in this group containing adenocarcinoma was likely due to frequent association of adenocarcinoma with cervical intraepithelial neoplasia. Morphologic scales of cytologic categories seen from histology showed high degrees of confusion and transpositions between mild and moderate dysplasia and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast: review of cases in a three-year period.

OBJECTIVE: To describe the fine needle aspiration cytology findings of invasive micropapillary carcinoma and correlate them with the histologic appearance. STUDY DESIGN: We reviewed the cytologic features of three cases of pure invasive micropapillary carcinoma in the files of Pamela Youde Nethersole Eastern Hospital from 1998 through 2000. Immunohistochemical study for epithelial membrane antigen was performed retrospectively on the cell block sections. Ultrastructural examination was also carried out on one of the cases. RESULTS: Two of the tumors were at pathologic stage II, and the remaining case was at stage III. Ipsilateral axillary lymph node metastases with similar morphology were seen in two of them. Cytologically, the smears were of moderate cellularity and composed of three-dimensional tumor cell balls, abortive and sometimes branching papillae, angulated tumor cell clusters, morules and occasional acini. Some of the tumor cell balls possessed scalloped borders. Focally, the tumor morules clustered together and were separated from each other by small, slitlike spaces. A small number of isolated malignant cells was also present in the background. The cell block sections showed mainly dispersed acini of tumor cells. The "reverse polarity" highlighted in histologic sections by immunohistochemical study for epithelial membrane antigen was not consistently demonstrated in the cell block material. Ultrastructural examination confirmed the focal presence of surface microvilli on the periphery of the tumor cell morules. CONCLUSION: Invasive micropapillary carcinoma of the breast possesses some subtle but distinctive cytologic features. With the help of cell block morphology and ancillary techniques, the preoperative suspicion of this rare subtype of ductal carcinoma, which carries a high propensity for lymphatic permeation, is possible.     

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.     

Pulmonary metastasis of a postradiation breast epithelioid angiosarcoma mimicking adenocarcinoma. A case report

BACKGROUND: Epithelioid angiosarcoma (EAS) is a mesenchymal neoplasm that may appear indistinguishable from carcinoma, melanoma and other tumors with epithelioid/epithelial differentiation. We report a case of metastatic postradiation EAS to the lungs that was mistaken for adenocarcinoma. CASE: A 45-year-old woman who received radiotherapy for ductal carcinoma in situ (DCIS) 5 years previously had a local recurrence a year earlier and recent development of bilateral small pulmonary nodules. Fine needle aspiration biopsy of the lung lesions showed round to oval tumor cells with amphophilic cytoplasm. An interpretation of adenocarcinoma was rendered during assessment for specimen adequacy. The original breast tumor was typical of cribriform DCIS. Review of the recurrent breast tumor (initially reported as DCIS) and a prior wedge resection of the lung nodules (reported as EAS) showed an epithelial-appearing tumor exhibiting an endothelial immunophenotype CONCLUSION: The cytologic features of EAS may resemble those of other neoplasms. In evaluating tumors with epithelioid morphology, mesenchymal tumors should also be considered so that appropriate antibodies can be included in the panel for immunohistochemistry. The importance of reviewing the patient's previous biopsy materials cannot be overemphasized.     

Cytologic study of noninvasive intraductal papillary-mucinous carcinoma of the pancreas

OBJECTIVE: To examine the cytologic features of noninvasive intraductal papillary-mucinous carcinoma (IPMC) in an attempt to differentiate it cytologically from hyperplasia, invasive IPMC and invasive ductal adenocarcinoma (IDA). STUDY DESIGN: Tumor samples from 23 patients clinically diagnosed with a mucin-producing tumor of the pancreas, including 10 cases of hyperplasia, 10 noninvasive IPMCs and 3 invasive IPMCs, and tumor samples from 21 patients with IDA, were examined cytologically. Cytologic specimens were obtained in various ways, such as by fine needle aspiration, imprint, brushing, vinyl tube aspiration and aspiration from a cannula at endoscopic retrograde cholangiopancreatography. RESULTS: Cytologically, all 10 noninvasive IPMCs exhibited clearly defined cytoplasmic boundaries (+1, ++4, ++ and mainly small nuclei (++7, +++3), with nuclear size and cytoplasm similar to those of hyperplastic cells, and irregular chromatin distribution (+2, ++8) and prominent nucleoli (-2, +4, ++3, +++1), all atypical nuclear features similar to those of invasive IPMC or IDA. There also were small papillary cohesive clusters (-1, +2, ++4, +++3) and euchromatin (+1, ++1, +++8), which were found only in IPMCs. CONCLUSION: The cytologic features of small, malignant nuclei and small papillary cohesive clusters are suggestive of noninvasive IPMC. Furthermore, the addition of clearly defined cell borders and euchromatin and the presence of some goblet cells are more strongly suggestive of noninvasive IPMC.     

Fine needle aspiration cytology of lactating adenoma of the breast. A comparative light microscopic and morphometric study

Six cases of lactating adenoma of the female breast diagnosed by fine needle aspiration (FNA) were reviewed. The FNA cytologic diagnostic features included a usually moderately cellular aspirate with an abundant foamy background material, intact epithelial lobules or acini and small groups and solitary epithelial cells that contained uniform nuclei, fine chromatin and prominent nucleoli. When present, the cytoplasm was finely vacuolated or wispy; many nuclei appeared stripped of their cytoplasm. These features were compared light microscopically with the cytopathologic features of six cases of invasive well-differentiated ductal adenocarcinoma, seven cases of invasive lobular carcinoma, one case of granulocytic sarcoma and one case of primary histiocytic lymphoma of the breast. In addition, cytomorphometric analysis demonstrated no statistically significant differences in the nuclear areas of lactating adenoma as compared with those of well-differentiated ductal carcinoma and lobular carcinoma.     

Two cytologic patterns in invasive ductal adenocarcinoma of the pancreas

OBJECTIVE: To clarify 2 cytologic patterns: severe ductal dysplasia (SD)/carcinoma in situ (CIS) and invasive components of invasive ductal adenocarcinoma of the pancreas (IDAP). STUDY DESIGN: Tumor samples from 12 patients with IDAP were examined cytologically and histologically. Cytologic specimens were obtained by fine needle aspiration (ENA) and imprint smears from resected pancreases. RESULTS: In the 12 IDAP cases, roughly 2 cell populations, SD/CIS-type cells and invasive component-type cells, were detected cytologically. The former composed a small portion of the tumor cells, exhibited a small nuclei without anisonucleosis and had a decreased total quantity of chromatin as compared with invasive component-type cells. SD/CIS-type cells were found in small papillary-cohesive and compactly packed clusters and had clearly defined cytoplasmic borders, a nucleus individually enveloped in well-preserved cytoplasm and small amount of cytoplasm (< 15 microm in short diameter) without prominent anisocytosis. The latter comprised mostly of the tumor cells, were present characteristically as a loose and discohesive population and contained a combination of hyperchromatin, large nuclei (> 15 microm) and abundant cytoplasm (>21 microm). Histologically, these 12 cases exhibited IDAP with SD/CIS. Hence, the invasive component-type cells appeared to originate with ordinary invasive spread of IDAP, and the SD/CIS type cells appeared to originate with noninvasive intraductal spread. CONCLUSION: Two cytologic patterns originating with SD/CIS and invasive components of IDAP could be differentiated.     

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

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

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A case report

BACKGROUND: Invasive micropapillary carcinoma of the breast is uncommon and was characterized only recently. Awareness of this entity and its cytologic appearance is important to allow early diagnosis by fine needle aspiration cytology (FNAC). To our knowledge, only two cases of FNAC of this lesion have been reported in the English-language literature. CASE: An 80-year-old female presented with a firm, nontender mass in the upper outer quadrant of the left breast. FNAC showed ductal carcinoma, and mastectomy showed invasive micropapillary carcinoma. The patient had axillary metastases and received tamoxifen. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive, with clusters of cells showing hyperchromatic, irregular and crowded nuclei and peripherally located cytoplasm with a rare central lumen. Fibrovascular cores are absent. Although FNAC experience with this lesion is limited, the characteristic cytologic features, including "inside-out" cell clusters, should raise the suspicion of this variant of ductal carcinoma. Differentiation from other papillary lesions and malignancies may be possible, but more experience is needed as the number of reported cases remains limited.     

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.