Cytologic differential diagnosis of papillary pattern in breast aspirates: correlation with histology

Papillary neoplasms, fibroadenoma, fibrocystic change, low-grade ductal carcinoma, and apocrine carcinoma are among "gray zone" lesions in breast cytology. They often have cellular smears with a papillary or pseudopapillary pattern. To better define cytologic criteria useful in distinguishing these entities, we correlated them with histology. Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei. Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background. The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern. Ann Diagn Pathol 5:34-42, 2001.     

Spectrum of male breast lesions diagnosed by fine needle aspiration cytology: a 5-year experience at a tertiary care rural hospital in central India

This study examines the spectrum of lesions in the male breast at a tertiary care rural hospital in central India and explores the role of Fine Needle Aspiration Cytology (FNAC) in the diagnosis of these lesions. Male breast lesions formed 5.89% (119 cases) of the 2017 breast lesions which were sent for FNA in the cytology section over a period of 5 years (January 2005-December 2009). Of these, biopsy had been performed only on 37 (31.1%) patients. Benign lesions comprised 102 (85.7%) cases, malignant lesions comprised 14 (11.8%) cases and inflammation/abscess was found in 3 (2.5%) cases. Gynecomastia was the commonest benign lesion in 86 (84.3%) cases. The cytologic features of gynecomastia included mild to moderate cellularity, cohesive sheets of bland cells, bipolar bare nuclei. Mild nuclear atypia was found in 19 cases. The cytologic features of malignancy comprised of dyshesive groups of ductular cells with moderate to severe degree of nuclear atypia and absence of bare nuclei. Histology was done in 37 cases and diagnostic accuracy of FNAC for gynecomastia was 100% and for malignancy 85.7%. This study showed that FNAC is a reliable tool for diagnosing male breast lesions. We conclude that FNAC should be performed as a standard procedure in the clinical evaluation of male breast masses. Many unnecessary surgical biopsies for histopathologic diagnosis can thus be avoided.     

Cytologic diagnosis of invasive lobular carcinoma: factors associated with negative and equivocal diagnoses

Fine-needle aspiration biopsy (FNAB) of invasive lobular carcinoma (ILC) is associated with notoriously high rates of false negative and equivocal diagnoses. To identify causative factors, we reviewed the cytologic features of presurgical FNAB smears of ILC and correlated the cytologic findings with the number of passes, tumor size, mammographic findings, and the histologic characteristics of the tumor. Smear cellularity, presence of single intact epithelial cells, nuclear size, nuclear atypia, palpability of the tumor, and histologic type of ILC (classic versus nonclassic) were statistically significant in establishing an unequivocally positive diagnosis. We also found that the cytologic cellularity of the lesion does not reflect the actual cellularity of the tumor but instead is an indicator of the architectural arrangement of the neoplastic cells; tumors that form epithelial cell groups, such as in nonclassic ILC, tend to yield more cellular aspirates that are diagnostic for carcinoma. In contrast, classic ILC, in which single neoplastic cells are embedded in fibrous stroma, is more likely to yield a paucicellular smear with subtle atypia and rare single intact epithelial cells. As such, an inconclusive diagnosis in a certain percentage of classic ILC cases may be unavoidable.     

Fine needle aspiration cytology of breast cancer in women aged 70 years and older

Aims: Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. Methods: The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. Results: We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Conclusions: Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.     

Cytologic diagnosis of papillary carcinoma of the breast in needle aspirates

Eleven cases of rare papillary carcinoma of the breast diagnosed by fine-needle aspiration cytology (FNAC) are reported. Five of these were pure papillary carcinomas and six were mixed papillary and ductal, lobular, or mucinous carcinomas. In each case, cytological material was collected by washing the needle and syringe contents into 30% alcohol in saline, and the Gelman cytosieve method was used for the cytological preparations. In this article, the cytological features of these tumors are described, including the presence of single papillae and papillary clusters, tall columnar cells, diathesis of blood with hemosiderin-laden macrophages, naked nuclei, and high cell recovery.     

Cytologic criteria for fibroadenoma. A step-wise logistic regression analysis

The authors reviewed the fine-needle aspiration biopsy smears from 62 subjects with proven fibroadenoma, 60 subjects with proven ductal carcinoma, and 42 subjects with proven fibrocystic disease. All smears were coded as to the presence or absence of the following variables: epithelial cells, stroma, honeycomb sheets, antler horn clusters, naked nuclei, nucleoli, marked cellularity, foam cells, apocrine cells, anisokaryosis, atypical nuclear hyperchromasia, single cells with cytoplasm, mitotic figures, and nuclei greater than two red blood cell diameters. Step-wise logistic regression analyses were performed to determine the variables predictive of fibroadenoma. The statistical analyses selected stroma, antler horn clusters, and marked cellularity as the key cytologic criteria to differentiate fibroadenomas from fibrocystic disease. The statistical analyses selected stroma, antler horn clusters, and honeycomb sheets as the key cytologic criteria to differentiate fibroadenoma from ductal carcinoma.     

Fine-needle aspiration cytology of the male breast in a cancer center

All fine-needle aspirates (FNA) performed on the male breast at The University of Texas M. D. Anderson Cancer Center from 1985 to 1992 were reviewed, totaling 64. The patients' ages ranged from 19 to 86 years, with a mean of 56 years. Thirty-three patients had a history of an extramammary malignancy. The diagnoses established by FNA were gynecomastia (45), mammary carcinomas (6), neoplasms metastatic to the breast (5), suspicious for carcinoma (1), intra-mammary lymph node (1), and lipoma (1). In five cases the aspirates were nondiagnostic. Two of these proved to be gynecomastia on subsequent histologic examination. Of the six FNA cases initially thought to represent primary breast carcinomas, two were found to be secondary because of involvement of the underlying chest wall by mesothelioma (1), and mucinous adenocarcinoma, unknown primary (1). No false-positive diagnosis was rendered. We conclude that fine-needle aspiration of the male breast is a reliable means of assessment; however, unique problems may be encountered compared with aspiration of the female breast. These include the epithelial hyperplasia frequently associated with gynecomastia, the relatively equal frequency of primary and metastatic breast lesions when a malignant process is discovered, and chest wall lesions masquerading as breast lesions.     

Breast masses in males: multi-institutional experience on fine-needle aspiration

Male breast masses are uncommon pathologic findings. They are rarely aspirated, resulting in limited cytopathologic experience. The following study describes the cytopathology of male breast lesions from data collected for a period of 10 yr from three large institutions. A total of 14,026 breast aspirations were performed of which 614 were from male patients. All cases were reviewed and correlated with the appropriate clinicopathologic follow-up. The FNA diagnoses were as follows: benign, 427 cases (gynecomastia 353, fat necrosis 21, miscellaneous 53); malignant, 32 cases (ductal carcinoma nos 15, metastatic tumors 17); and atypical/suspicious, 61 cases. Ninety-four cases were nondiagnostic due to scant cellularity. Male breast aspirates accounted for 4.3% of the total breast FNAs performed. The clinicopathologic follow-up in both the benign and malignant categories showed 100% correlation. The overall sensitivity was 95.3%, specificity was 100%, and diagnostic accuracy was 98%. A relatively high specimen unsatisfactory rate was seen (>15%). The commonest cytopathologic diagnosis was gynecomastia, followed by ductal carcinoma. Florid duct atypia in gynecomastia may mimic adenocarcinoma, necessitating a higher threshold for cytopathologic interpretation for malignancy in males.     

Fine‐needle aspiration cytology of triple‐negative basal‐like breast cancer

Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal‐like (BL) and normal‐like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine‐needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC. Diagn. Cytopathol. 2013;41:283–287. © 2011 Wiley Periodicals, Inc.     

Fine‐needle aspiration cytology for the diagnosis of solid basaloid adenoid cystic carcinoma of the breast: Its role,limitation, and perspective

Solid basaloid adenoid cystic carcinoma (SB‐AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine‐needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB‐AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB‐AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB‐AdCC between 2012 and 2019 identified four patients with SB‐AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon‐like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB‐AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB‐AdCC of the breast.     

Cytodiagnosis of secretory carcinoma of the breast: a report on two cases

Secretory carcinoma of the breast is a rare (<1%) low grade breast carcinoma which shows distinct features at histology. Diagnosis of this carcinoma at fine needle aspiration cytology (FNAC) is difficult. Two cases of secretory carcinoma of the breast presenting as a breast mass, one in a 24-year-old female and the other in a 40-year-old female are reported, highlighting their appearance at FNAC. In both the cases the aspirates were cellular and consisted of clusters and single cells with uniform round nuclei showing minimal nuclear atypia. Most of the cells had moderate to abundant cytoplasm with prominent intracytoplasmic vacuoles. Many cells showed a plasmacytoid appearance and others were binucleate. A typical amphophilic bubbly cytoplasm of the tumor cells was observed. Both cases were confirmed as secretory carcinoma on histology. The differences in cell morphology at FNAC of secretory carcinoma of the breast from other breast carcinomas, and its utility of making a preoperative diagnosis are discussed.     

Cytological study of 20 cases of solid-papillary carcinoma of the breast

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade intraductal carcinoma but there are few cytological studies. We examined 20 cases of SPC of the breast, aged 31-80 (mean age 66.0 yr), to define the cytological features. In each of the cytological specimens, we could find both malignant and benign cytological features; the former were characterized by hypercellularity, highly discohesive clusters, numerous isolated cells, and severe overcrowding cells, while the latter were marked by small and bland nuclei, a low nuclear-cytoplasmic ratio, and inconspicuous nucleoli. Neither abnormal naked nuclei of tumor cell origin nor oval naked nuclei of myoepithelial cell origin were seen.We also reviewed the cytological findings of SPC as well as neuroendocrine carcinomas with intraductal components that had been reported and we concluded that the coexistence of malignant and benign features was the most characteristic cytological feature of SPC.     

Fine-needle aspiration biopsy of breast adenomyoepithelioma: A potential false positive pitfall and presence of intranuclear cytoplasmic inclusions

Cytologic diagnosis of adenomyoepithelioma can be very challenging. We report fine needle aspiration cytology (FNAC) findings of a benign adenomyoepithelioma. The cytologic features are characterized by hypercellularity and the presence of numerous atypical dispersed cells with epithelioid morphology and intact cytoplasm. The nuclei showed stippled chromatin, irregular nuclear membrane, and prominent eosinophilic nucleoli. No necrosis or mitoses were seen. The presence of naked nuclei, and extensive intranuclear cytoplasmic inclusions were identified and raised the possibility of adenomyoepithelioma. Immunohistochemically, the atypical cells showed strong positivity for myosin heavy chain, p63, and CK5/6, while the epithelial cells reacted with estrogen receptors. This immunophenotypic pattern supports the myoepithelial origin of the atypical cell proliferation and favors the diagnosis of benign adenomyoepithelioma. However, biopsy was recommended to exclude malignancy. Histologically, the tumor showed prominent myoepithelial cells with significant atypia, intranuclear cytoplasmic inclusions, and dense cytoplasm. No evidence of malignancy was identified. In conclusion, we report a case of adenomyoepithelioma with a significant cytological atypia that may result in confusion with malignant breast tumors. The presence of intranuclear cytoplasmic inclusions, naked nuclei, and expression of myoepithelial markers should provide clues to the right diagnosis and benign nature of this lesion. Cytopathologists should be familiarized with this entity to avoid a misdiagnosis of carcinoma. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.     

Cytopathological grading, as a predictor of histopathological grade, in ductal carcinoma (NOS) of breast, on air-dried Diff-Quik smears

Fine-needle aspiration cytology (FNAC) is a widely practiced technique in the diagnosis of breast carcinoma, and it is the only diagnostic procedure performed before definitive treatment, at most institutions. While the histological grading of breast carcinoma has become routine in many centers worldwide, the cytopathological grading of breast carcinoma is not commonly used. Grading of breast carcinoma, while the tumor is still in vivo, would be the most ideal and desirable situation, as it would be helpful in the selection of patients for appropriate therapy. The objective of this study, therefore, was to devise a simple system for grading breast carcinoma, based on the cytological features alone. We reviewed 125 cases of breast carcinoma retrospectively, which were initially diagnosed by FNAC, with subsequent histopathological confirmation. These included 105 ductal, 6 lobular, 2 tubular, 1 papillary, and 1 medullary carcinoma. There was 1 ductal carcinoma in situ. Nine cases were rendered insufficient for grading. Thus 105 cases of ductal carcinoma (NOS) were evaluated for final cytological grading. Air-dried Diff-Quik-stained smears were reviewed at least twice independently by four histopathologists and were then compared with the original histological grades. Six cytological features used for grading were found to be statistically significant: cellular pleomorphism, nuclear size, nuclear margin, nucleoli, naked tumor nuclei, and mitoses. A scoring system based on these six essential parameters was used, to classify ductal carcinoma into three cytological grades, which showed close correlation with the established histological grades. In addition, two less consistent, but still important, features were the presence or absence of necrosis and stromal invasion. Another six parameters, including smear cellularity, degree of cell dispersion or clustering, lymphoplasmacytic infiltrate, presence of tubular structures, cytoplasmic appearance of the tumor cells, and smear background, were not statistically significant. However, these additional parameters were found helpful in assigning the correct grade, in cases with borderline scores. The concordance rate with histology was 100% for grade 1, 98% for grade 2, and 93% for grade 3.     

Cytopathology of the breast--benign and malignant neoplastic conditions]

Breast cancer is one of the most common malignancies in women and the incidence has been increasing. Cytology plays a very important role not only in the diagnosis of breast lesions, but also in keeping the benign-to-malignant biopsy ratio low, so that unnecessary surgery is not performed. A fundamental feature of a benign aspirate is the presence of a dual population of ductal epithelial cells (variable within limits, but cohesive and orderly) and myoepithelial cells (naked, bipolar nuclei). Several cytologic features must be assessed to make the diagnosis of malignancy, including high cellularity, cell dissociation, large nuclear and cell size, cell pleomorphism, intracytoplasmic lumens (containing mucin), irregular nuclear margin, coarse chromatinic pattern, prominent nucleoli, and the presence of abnormal mitoses. Other criteria of lesser importance include necrosis, absence of myoepithelial cells and intranuclear inclusions. However, breast carcinomas do not always show every feature of malignancy. The well-differentiated or low-grade carcinomas are often difficult to differentiate from benign cells. It may be helpful to consider the clinical and radiological findings. We reported here, typical neoplastic lesions of the breast by correlating cytological with histopathological features.     

Fine-needle aspiration cytology of medullary breast carcinoma: report of two cases and review of the literature with emphasis on differential diagnosis

Medullary carcinoma is a rare variant of breast carcinoma with a relatively good clinical prognosis as strictly defined. Characteristic features on fine-needle aspiration cytology (FNAC) allow medullary carcinoma to be considered in the cytologic differential diagnosis. We present two FNAC cases with such features, including high cellularity with clusters and single intact malignant cells, bizarre stripped nuclei with prominent nucleoli in a lymphoplasmacytic background, and illustrate one case in liquid-based preparation. Surgical excision revealed that one patient had medullary carcinoma, while the second patient had high-grade infiltrating ductal carcinoma. Breast FNAC samples with syncytial fragments, bizarre nuclei with prominent nucleoli, and a chronic inflammatory infiltrate should raise the possibility of medullary carcinoma. However, the differential diagnosis also includes high-grade ductal carcinoma, lymphoma, or metastasis to breast or intramammary lymph nodes; thus, histopathologic analysis is required for definitive diagnosis.     

Leiomyosarcoma of the breast: a difficult diagnosis on fine-needle aspiration biopsy

Leiomyosarcoma of the breast is rarely encountered in fine-needle aspiration (FNA) cytologic material. We report a case of primary leiomyosarcoma of the breast in a 52-yr-old female. Aspiration cytology showed large, dissociated round to spindle cells with abundant vacuolated cytoplasm, pleomorphic nuclei, prominent nucleoli, and occasional intranuclear cytoplasmic invaginations. Mitotic figures, osteoclast-like giant cells, and stromal fragments were identified. A diagnosis of malignant neoplasm representing either a sarcoma, a poorly differentiated carcinoma, or a metaplastic carcinoma was made. The patient underwent a wide excision of the lesion after negative work-up. Histologic examination and immunohistochemical studies established the diagnosis of leiomyosarcoma. This case is presented here because we feel that, although FNA cytology with eventual ancillary studies is a valuable diagnostic tool to evaluate any breast mass, malignant spindle cell neoplasms of the breast still represent a diagnostic challenge for the cytopathologist. Recognition of all cytologic features of leiomyosarcoma may help to formulate a correct diagnosis.     

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report

The breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.     

Mucinous breast carcinoma with myoepithelial‐like spindle cells

Appearance of spindle cells has been believed as a benign index of breast cytology. But, we have frequently observed the spindle cells in smears from mucinous carcinoma of the breast. Here, we characterized the biochemical nature of the spindle cells, so as to clarify their identity in cytology. Nineteen cases of breast mucinous carcinoma were used for cytological examination. The spindle cells were located at edges of tumor cell nests and in the backgrounds of cytological specimens. Immunohistological examination revealed that the spindle cells exhibited both immunoreactivity against carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Immunoreactivity against vimentin, cytokeratin, or alpha‐smooth muscle actin was, however, not observed. The mode of distribution of biochemical markers suggests that the positive cells for anti‐CEA antibody and anti‐EMA antibody are tumor cells compressed by mucin, while the vimentin‐positive cells are fibroblasts. We assert that the presence of spindle cells can be a characteristic feature of mucinous carcinoma of the breast. Discrimination of the spindle cells in mucinous carcinoma from myoepithelial cells and naked bipolar nuclei in benign lesions was established here. It should facilitate precise diagnosis of breast cancer. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.