Cytology of nipple discharge in florid gynecomastia

OBJECTIVE: To determine the cytomorphologic spectrum of nipple discharge in florid gynecomastia. STUDY DESIGN: During a 22-year period (July 1979-June 2001), nipple discharge from nine males with breast lesions were examined. Smears from four of these cases with histologically documented gynecomastia were reviewed along with the tissue sections. RESULTS: In the three patients with florid gynecomastia the smears were cellular, with numerous benign ductal cells and papillary fragments along with foam cells and inflammatory cells. Epithelial atypia was mild in two cases and moderate in one. One of the three cases had an associated breast lump that showed features of florid gynecomastia on fine needle aspiration cytology. The biopsy from this case showed cystic hyperplasia of the breast similar to that in women with an intraductal papilloma. One case of simple gynecomastia on histology showed two fragments of benign ductal cells with occasional apocrine and foam cells. CONCLUSION: Nipple discharge in florid gynecomastia may pose problems in identification as the cellularity and atypia may lead to a misdiagnosis of carcinoma.     

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.     

Infiltrating micropapillary carcinoma of the breast. Cytologic findings

OBJECTIVE: To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior.     

The role of nipple discharge cytology in the diagnosis of breast disease: a study of 1948 nipple discharge smears from 1530 patients

In this study a review of 1948 nipple discharge (ND) samples from 1530 patients in the age range of 18-83 years was undertaken to determine whether cytological findings from ND smears could provide useful diagnostic information regarding various breast lesions. The study included 1494 females and 36 males and was carried out during a period of 20 years 8 months. The clinical information in all patients was obtained from clinicians (coauthors), medical records and a review of biopsies in 205 patients who had undergone surgery following the cytodiagnosis. Of the ND samples examined, 1480 were unilateral while 468 were from 234 bilateral ND. The cytodiagnoses were: benign 624, inadequate (despite two to three repeat samples) 492, inflammatory 96, papillary lesion not otherwise specified (NOS) 229, suspicious 22 (21 females, one male) and malignant 67 (63 females, four males). A breast biopsy in the 22 suspicious cases revealed breast carcinoma in 18 cases (females n = 17, male n = 1), atypical ductal hyperplasia (female n = 1), fibroadenoma (female n = 1) and a papilloma in two females. In the 67 cases with a diagnosis of malignancy 65 revealed a breast carcinoma in the biopsy (female n = 62, male n = 3) while one female was diagnosed as fibroadenoma and one male as florid gynaecomastia. In 63 cases (females n = 61; males n = 2) with clinical lumpy areas consistent with the diagnosis of fibrocystic condition in ND, the biopsy confirmed a fibrocystic process. In 53 of 229 cases with ND findings suggestive of a papillary lesion (NOS) the biopsy revealed a papilloma in 41 cases while in 12 cases no lesion was found. In the remaining cases of all the groups only a clinical follow-up and appropriate investigations were performed with no untoward outcome. Based on our study it is felt that cytological examination of ND smears seems to be a reasonably specific method in the diagnosis of malignant and suspicious cases but may be somewhat less specific for other diagnoses.     

Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases

S. Mandal, and S. Jain
Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases Objective: An adenoid cystic pattern in thyroid tumours is a rare finding that may be seen in papillary carcinoma of thyroid (PCT), the follicular variant of PCT (FV‐PCT), a rare cribriform‐morular variant of papillary carcinoma of thyroid (CMV‐PCT) and follicular carcinoma. There is little published cytological literature describing these patterns. We report four cases of PCT with this unusual pattern. Methods: Fine needle aspiration (FNA) cytology was performed on four patients with a neck lump using a 22‐G needle; smears were stained with Giemsa and Papanicolaou stains. Immunocytochemical staining for thyroglobulin was done in all cases. Results: The patients were female and ranged in age from 18 to 46 years. They presented with a gradually increasing mass in the neck. FNA smears in all cases showed nuclear features of PCT. There were also prominent follicular areas with hyaline globules in some of the cell clusters reminiscent of adenoid cystic carcinoma and, in places, morula‐like groups of neoplastic cells were also seen. Immunocytochemistry for thyroglobulin was positive in all cases but negative in the hyaline globules. Conclusions: Adenoid cystic areas with morula‐like groups in PCT are a rare finding. Cytopathologists and clinicians should be aware of these distinct features in thyroid tumours to avoid diagnosing metastatic adenoid cystic carcinoma. It is also important to rule out CMV‐PCT since that variant is mostly associated with familial adenomatous polyposis, although sporadic occurrence is known.     

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.     

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.     

Fine needle aspiration cytology of neoplasms metastatic to the breast

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.     

Papillary adenoma of the kidney with mucinous secretion

Although infrequently, mucin secretion has previously been reported in papillary renal cell carcinoma. We here investigate the presence of mucin in a series of 93 renal papillary adenomas in 58 patients. Acid mucin was present in four cases (4.3% of the tumors; 6.9% of the patients), in which basophilic mucin secretion was evident with hematoxylin-eosin. To the best of our knowledge mucin secretion has not been reported in renal papillary adenoma. We describe two different types of mucin secretion: intracytoplasmic and luminal. The secretion was intracellular in numerous scattered tumor cells in two cases, focal luminal in one case, and mixed intracellular and luminal in another case. Mucin production, despite its low frequency, can be considered as an additional feature of renal papillary adenoma. Mucin production suggests that renal papillary adenoma and papillary renal cell carcinoma are actually not two independent biological processes, but a continuum of one biological process.     

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.     

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.     

Thyroid papillary microcarcinoma. Is it really a pitfall of fine needle aspiration cytology?

OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the diagnosis of papillary microcarcinoma. STUDY DESIGN: Eight cases of papillary microcarcinoma were diagnosed by fine needle aspiration. On histologic examination they were found to be adjacent to larger nodules of interest. The microcarcinomas were inadvertently sampled when sampling the larger, dominant nodules. RESULTS: None of the eight dominant nodules were papillary carcinoma; seven were benign lesions, and one was an angioinvasive Hürthle cell carcinoma. In three cases the microcarcinomas were situated within the capsule of a hyperplastic nodule. On histologic examination, five cases had multifocal microcarcinomas, with one case having multiple lymph node metastases. Based on the clinical findings and morphologic features, there were no definitive cytologic findings that could distinguish between "incidental" microcarcinoma and clinically significant papillary carcinoma. CONCLUSION: The detection of microcarcinoma by FNA should not be considered a false positive finding since the exact nature of the lesion cannot be determined until complete histologic evaluation reveals it to be truly incidental and clinically insignificant.     

Diagnostic dilemmas of hyalinizing trabecular tumours on fine needle aspiration cytology: a study of seven cases with BRAF mutation analysis

T. Kim, Y. L. Oh, K. M. Kim and J. H. Shin Diagnostic dilemmas of hyalinizing trabecular tumours on fine needle aspiration cytology: a study of seven cases with BRAF mutation analysis Objective: Hyalinizing trabecular tumours (HTTs) are rare follicular‐derived neoplasms that behave in an almost benign manner. HTT is frequently misdiagnosed as papillary carcinoma by fine needle aspiration (FNA) cytology or as papillary or medullary carcinoma on surgical resection. Methods: The authors examined FNA material from seven cases of histologically verified HTT. Cytological findings were reviewed and correlated with ultrasonographic and histological features. In addition, MIB‐1 and calcitonin immunostaining was performed on surgical specimens, and BRAF mutation analysis on three pre‐operative FNA specimens and seven histology specimens. Results: The original cytological diagnosis was either suspicious or positive for papillary carcinoma in all patients. The FNA‐based differential diagnoses included HTT, papillary carcinoma or, less likely, medullary carcinoma in two patients. Aspirates showed oval to spindle‐shaped cells with frequent intranuclear inclusions, isolated in loosely cohesive groups with a trabecular or syncytial pattern in a bloody background. Radiating arrangements of tumour cells surrounding hyaline stroma with serrated calcifications and a lack of papillary or sheet‐like fragments may suggest HTT on FNA. Spherical calcified bodies and possible psammoma bodies were frequently found in three cases. Retrospectively, six of the seven cases showed membranous immunoreactivity for MIB‐1, but none of the seven possessed the BRAF (V600E) mutation or showed calcitonin reactivity. Conclusions: Although the recognition of HTT on FNA cytology is difficult, because of its morphological similarities to papillary and medullary carcinoma, its characteristic cytological features along with ultrasonographic findings may suggest the diagnosis preoperatively and avoid surgical over‐treatment.     

Solid papillary carcinoma of the breast with neuroendocrine features in a pregnant woman: a case report

Solid papillary carcinoma, a special form of breast carcinoma with neuroendocrine differentiation, usually presents in women aged 60 years or more. (Koern 2010). According to our best knowledge, we present the second case of such a tumor in pregnant women.     

Prevalence of psammoma bodies in Papanicolaou-stained cervicovaginal smears

Reports from sequential series of 234,318 cervicovaginal smears from a period of three years were reviewed to ascertain the prevalence and significance of psammoma bodies. Seven smears contained psammoma bodies. Three of the seven were associated with benign conditions and four were associated with a cancer (two serous papillary endometrial adenocarcinomas, one ovarian serous cystadenocarcinoma and one serous papillary carcinoma of the peritoneum). The prevalence of psammoma bodies in benign cases was much higher than reported in previous studies, in which most findings of psammoma bodies were associated with malignancy, particularly ovarian carcinoma. A consistent and useful feature in distinguishing psammoma bodies associated with benign or malignant disease was the presence of a few adherent small bland-appearing glandular cells in benign disorders and adherent malignant glandular cells in cases of carcinoma. A more conservative work-up may be merited in young women with clearly benign cells associated with psamoma bodies in a cervicovaginal smear and an otherwise negative physical examination and noncontributory endometrial sampling.     

Cytology of collagenous spherulosis of the breast: a diagnostic dilemma – report of three cases

Collagenous spherulosis is a rare incidental finding seen in association with benign breast lesions. Cytological findings in three cases of collagenous spherulosis diagnosed on fine needle aspiration are presented. The presence of hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears was a diagnostic feature. Associated lesions were atypical papillary hyperplasia (2) and fibroadenoma (1). Adenoid cystic carcinoma was the close differential diagnosis on cytology. Awareness of this entity is important to avoid a false positive diagnosis of malignancy.     

Searching for RET/PTC rearrangements and BRAF V599E mutation in thyroid aspirates might contribute to establish a preoperative diagnosis of papillary thyroid carcinoma

OBJECTIVE: Searching for multiple molecular markers in thyroid aspirates appears to be a promising approach for establishing a preoperative diagnosis of papillary thyroid carcinoma (PTC). METHODS: Based on this hypothesis, a total of 63 samples from 55 patients, were collected at random. RNA was extracted from the residue cells inside the needle used for fine needle aspiration cytology (FNAC) and thereafter molecular analysis was carried out both for RETrearrangements (type 1, 2, 3) and BRAF codon 599 mutation molecule. Results were compared with the cytological and histopathological diagnoses in 24 patients submitted to surgery. RESULTS: 58% PTCs presented a genetic alteration either RET/PTC rearrangement, BRAF V599E mutation or both: three cases of PTCs (25%) presented a RET/PTC rearrangement; three cases of PTCs (25%) presented a BRAF V599E mutation and in one case (8%) both alterations were identified. CONCLUSIONS: The present results suggest that searching for multiple molecular markers in thyroid aspirates may enhance the accuracy of FNAC and refine preoperative diagnosis of PTC.     

Cytologic findings in the follicular variant of papillary carcinoma of the thyroid.

Fine needle aspirates from 8 thyroid papillary carcinomas, follicular variant, were studied. Histologically the tumors were composed exclusively of follicles (four cases) or an admixture of follicular and trabecular structures (four cases). Follicles were identified in smears from seven cases (87.5%) and sheets reminiscent of a trabecular pattern in one (12.5%). Colloid material presented as intraluminal (one case) or extraluminal, dense, round masses (six cases). Nuclear cytoplasmic inclusions occurred in seven (87.5%) of the cases. All these features have been described for follicular lesions or neoplasia together with occasional nuclear grooves, as occurred in two (25%) of the studied cases. In the other six (75%) cases, a moderate to high proportion of neoplastic cells with nuclear grooves facilitated the diagnosis of papillary carcinoma. Our findings suggest that a careful microscopic search for nuclear grooves should be attempted in aspirates yielding a diagnosis of follicular neoplasia that could otherwise be indistinguishable from the follicular variant of papillary carcinoma of the thyroid.     

The value of dynamic contrast enhanced breast MRI in mammographically detected BI-RADS 5 microcalcifications

Aims: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in the diagnosis of BI-RADS-5 type of microcalcifications of the breast, to compare the size of the microcalcification lesions using mammography (MG) and MRI, and to determine the value of MRI in surgery for microcalcifications. The study also determines the morphology of microcalcification lesions, assesses kinetic curves and compare MRI features of ductal carcinoma in situ (DCIS) for different histopathological grades. Methods: Our group consisted of 32 patients with mammographically detected BI-RADS 5 microcalcifications. The MRI was done in this group of women which was later followed by stereotactic vaccum-assisted biopsy (SVAB). Surgery was performed on all patients with a biopsy that resulted in a diagnosis of breast cancer or atypical ductal hyperplasia (ADH). Results: Of our group of 32 patients, there were 35 mammograhically detected microcalcification lesions, 32 DCIS, one ADH and two benign findings according to the final histology. The microcalcification lesions were larger using MRI than in MG in 10 women. We diagnosed DCIS multifocality in 6 women and bilateral carcinoma in one woman. As with kinetic curve assessment, we found in 67 % of DCIS a rapid rise, 27 % a moderate and in 6 % a slow initial rise. With the pattern of enhancement in the delayed phase, we found in 30 % of DCIS a washout pattern, 67 % a plateau and in 3 % a persistent pattern. Noted difference between high and low grade DCIS was confirmed. Conclusions: MRI sensitivity in the detection of DCIS was 94 % in our group of patients and was the sole evidence for detection of multifocality and bilateral incidence of carcinoma. In 26 % of women the outcome of MRI was the most important for converting breast conserving surgery to mastectomy.