Fibroadenomas with atypia: causes of under- and overdiagnosis by aspiration biopsy.

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern.     

Fine-needle aspiration cytology of ductal adenoma: Report of a case associated with a mucocele-like lesion

Ductal adenoma (DA) is an uncommon breast lesion that can histologically and clinically mimic carcinoma. We performed a fine-needle aspiration (FNA) of a DA. Cytologically, the lesion had features overlapping with those of mucinous carcinoma (MC), mucocele-like lesion, lactating adenoma (LA), and in retrospect with intraductal papilloma (IP). The smears were highly cellular and contained numerous monolayered sheets of ductal cells with prominent punched-out, small vacuoles distending the cytoplasm. The nuclei were mostly round to oval and had bland chromatin. Occasionally cells with enlarged nuclei and conspicuous nucleoli were present. The background showed large mucin pools, scattered single cells with mild nuclear atypia, some with apocrine metaplasia, rare stripped nuclei, and a fibrovascular stromal component. Calcifications were also present. We compare our cytologic findings with those of the lesions considered in the differential diagnosis. Due to its rare incidence and unusual features, DA may represent a diagnostic pitfall on FNA. Increased awareness of its cytologic appearance may help prevent a misdiagnosis. © 1995 Wiley-Liss, Inc.     

Histiocytic aggregates in benign nodular goiters mimicking cytologic features of papillary thyroid carcinoma (PTC)

Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB) specimens of thyroid nodules with varying degrees of cystic change. In some cases the histiocytic component of a cystic thyroid nodule can occur as large tissue fragments with marked nuclear atypia, including elongated nuclei with chromatin clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic cytologic features of papillary thyroid carcinoma (PTC), thus leading to diagnostic difficulty in interpretation of FNAB specimens of benign cystic thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273 cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty cases were selected due to the presence of large aggregates of histiocytic cells with the above-mentioned nuclear atypia. An immunostain for histiocytic cells using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic staining for CD68; thyroid follicular cells stained negative for CD68. We conclude that histiocytic cells in cystic goitrous nodules can show nuclear features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of value in differentiating between benign cystic thyroid nodules with histiocytic aggregates that mimic cytologic features of papillary carcinoma, and PTC with cystic change.     

乳腺粘液囊肿样病变组织病理学及针吸细胞学改变

目的 分析乳腺粘液囊肿样病变的组织病理学及细针吸取（针吸）细胞学特点,寻求在手术前根据针吸细胞学鉴别ＭＬＬ与乳腺粘液腺癌的依据。方法 重新评估７例ＭＬＬ（良性５例,恶性２例）的组织病理学及针吸细胞学材料,并以同期１４例粘液腺癌作对照,比较两种病变在组织学及针吸细胞学上的差异。     

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.     

Differentiating nonhigh-grade duct carcinoma in situ from benign breast lesions

This study was undertaken to determine the discriminating cytological features between nonhigh-grade duct carcinoma in situ (NHGDCIS) and benign breast lesions and to determine any histological characteristics which would influence the cytological categorization. Smears of 12 each of histologically confirmed NHGDCIS and benign breast lesions were reviewed with regard to cellularity, cell discohesion, nuclear atypia, crowding of cells, tubule formation, necrosis, and presence of bare atypical nuclei and regular bare bipolar nuclei, and statistically analyzed. Architectural pattern, presence of necrosis, and the size of the lesion assessed at histological examination were compared with the initial cytological categorization. NHGDCIS lesions showed more cell discohesion (P = 0.04), bare atypical nuclei (P = 0.05), necrosis (P = 0.03), and sparse bare bipolar nuclei (P = 0.02) than benign lesions. These differences were statistically significant. Cellularity (P = 0.8), nuclear atypia (P = 0.06), crowding of cells (P = 0.1), and tubule formation did not show a significant difference. Six (out of six lesions) with a solid architectural pattern and six (of seven) with necrosis could be cytologically categorized as suspicious or malignant. Size of the lesion did not influence this. We conclude that cell discohesion, bare atypical and bare bipolar nuclei, and necrosis are discriminating features between NHGDCIS and benign breast lesions and NHGDCIS lesions with a solid architectural pattern and necrosis are more likely to be satisfactorily categorized cytologically.     

Common epithelial tumors of the ovary: proliferating and of low malignant potential

Ovarian tumors of low malignant potential (LMP) must be distinguished from benign, "proliferating" ovarian tumors and from frank ovarian carcinoma. Serous and mucinous tumors of LMP demonstrate epithelial stratification, the formation of epithelial tufts, cytologic atypia, and mitotic activity, but they do not demonstrate stromal invasion by epithelial cells, which is a feature of frank carcinoma. Mucinous carcinoma may also be recognized by epithelial stratification exceeding three cell layers and the formation of true cribriform glandular patterns. Although controversial, we do not at present recognize a LMP tumor of endometrioid type but prefer to classify those endometrioid neoplasms with a prominent fibrous stroma and glandular complexity similar to adenomatous endometrial hyperplasia as proliferating endometrioid adenofibromatous and cystadenofibromatous tumors. There is only mild cytologic atypia in such tumors. Because of the moderate to marked cytologic atypia that occurs in some clear cell neoplasms with a prominent fibrous stroma, we believe those tumors do merit a designation of LMP tumors. In both the proliferating endometrioid and LMP clear cell adenofibromatous and cystadenofibromatous tumors, carcinoma must be excluded by an absence of stromal invasion, which is frequently recognized by a confluent glandular pattern. The histologic features of proliferating Brenner tumors are similar to those of low grade, papillary, noninvasive, urothelial carcinoma, whereas we propose that Brenner tumors of LMP show high grade cytologic atypia but remain noninvasive in the ovary.     

Cytologic features of metastatic sebaceous carcinoma: report of two cases with comparison to three cases of basal cell carcinoma.

The cytologic findings of two cases of metastatic sebaceous carcinoma are described and compared to three cases of locally recurrent basal cell carcinoma. Morphological findings for sebaceous carcinoma in fine-needle aspiration biopsy (FNAB) smears included cellular, loosely cohesive cell clusters with central necrosis, squamous pearl formation, and adjacent keratin debris. The tumor cells had moderate amounts of vacuolated cytoplasm, round to oval vesicular nuclei with clumped chromatin, nucleoli, some nuclear overlap, and numerous mitotic figures. An interesting finding was the presence of numerous multinucleated giant cells, probably responding to extravasated lipid or keratin material. In contrast, the FNAB smears of basal cell carcinoma typically were less cellular, with more tightly cohesive and smaller clusters of uniform hyperchromatic basaloid cells with high nuclear to cytoplasmic ratios, and a narrow rim of cytoplasm without vacuolization. The morphologic features of sebaceous carcinoma in FNAB smears appear to be distinct from those of basal cell carcinoma. FNAB can be a useful preoperative diagnostic technique to distinguish these two cutaneous malignancies.     

Mucinous endometrial epithelial proliferations: a morphologic spectrum of changes with diverse clinical significance.

BACKGROUND: Mucinous differentiation of the endometrium can occur in a spectrum of changes ranging from benign (metaplasia) to malignant (adenocarcinomas with mucinous differentiation). Mucinous proliferations with simple architecture are generally considered benign; however, more complex growth patterns have an uncertain biologic behavior, particularly when these changes are focal and/or are encountered in biopsy or curettage material. The disparity between the degree of cytologic atypia and the neoplastic potential makes their interpretation difficult in routine practice. We categorized and prospectively studied a series of these lesions based upon their degree of architectural complexity and correlated them with follow-up curettings and hysterectomies over a period of three years. METHODS: Mucinous proliferations of the endometrium were subdivided into three categories (A, B, or C) based upon increasing degrees of architectural complexity. Type A were mucin-containing epithelial cells, present singly or in small tufts, within architecturally benign glands or involving the endometrial surface. Type B proliferations were more complex, consisting of mucin-containing epithelial cells forming small pseudoglands with rigid, punched out spaces and no supporting stroma Conspicuous cytologic atypia or architectural features such as a filiform growth pattern characterized type C alterations. One hundred two curettings and 36 hysterectomies from 52 patients were reviewed. RESULTS: Patient's ages ranged from 39 to 71 years (median, 55 yr); 41 patients (80%) were over age 50. Twenty patients (40%) were receiving hormone replacement therapy. Nineteen type A, 17 type B, and 16 type C mucinous endometrial proliferations were analyzed. Excluding those cases in which a conventional coexisting precancerous lesion was also present in the initial endometrial sample, the percentages of endometrial carcinoma following a curettage diagnosis of types A to C, respectively, were 0, 64.7%, and 100%. Carcinomas following type B alterations were all well-differentiated and all were confined to the endometrium or inner third of the myometrium. CONCLUSION: Mucinous endometrial proliferations comprise a spectrum subdivisable into biologically meaningful subsets. A high percentage of type B alterations were found to have endometrial adenocarcinoma on follow-up; however, all were well-differentiated and showed either no or minimal invasion. This finding suggests that the absence of cytologic atypia in complex mucinous lesions identifies subsets of lesions at low concurrent risk for deeply invasive cancer. The presentation of type B lesions as predominantly microglandular surface lesions without co-existing atypical hyperplasias suggests that a subset of well-differentiated adenocarcinomas arise via neoplastic alterations in surface epithelium.     

Fine‐needle aspiration of metanephric adenoma of the kidney with clinical,radiographic and histopathologic correlation: A review

Metanephric adenoma of the kidney is an uncommon benign epithelial neoplasm with only a small number of reports that describe its cytologic features. We describe two additional cases of metanephric adenoma diagnosed on fine‐needle aspiration biopsy and review the available literature. Our cases showed similar cytology and were composed of cellular smears with numerous clusters of small, oval to round cells arranged in a microfollicular pattern and papillary configurations. The tumor cells had scant cytoplasm, fine chromatin and absent nucleoli. Psamomma bodies, nuclear atypia, cellular cpleomorphism, necrosis, and mitoses were absent. Because of the rarity of this tumor and the common cytologic features it shares with other lesions, including malignant tumors such as Wilms’ tumor and papillary renal cell carcinoma, awareness of the cytologic features of metanephric adenoma may aid in avoiding a diagnosis of malignancy, especially preoperatively, and in guiding the proper management for the patients. Diagn. Cytopathol. 2013;41:742–751. © 2013 Wiley Periodicals, Inc.     

Mucinous lesions of the breast: potpourri of old and new

Mucinous lesions of the breast encompass a range of benign and malignant entities characterized by extracellular mucin production. Increased sampling of mammary calcifications has identified a range of mucocele-like lesions, which are associated with benign proliferative and atypical intraductal epithelial proliferation ranging in architectural complexity from flat epithelial atypia to ductal carcinoma in situ. Mucinous carcinoma is a unique histologic subtype of breast cancer with a good prognosis. Mucinous carcinoma, especially in males and older females, can arise in association with solid papillary carcinoma. Recent molecular studies reveal distinct genomic changes in mucinous carcinoma. Micropapillary mucinous carcinoma is a recently described histologic variant of breast cancer with aggressive clinical features and poorer outcome. Not all mucinous lesions are of ductal epithelial phenotype; rarely, lobular carcinoma can present with extracellular mucin. This concise review discusses clinical features, histological findings, and differential diagnoses of mucinous lesions of the breast, including common and some rare lesions as well as recently described entities.     

Cytologic differentiation between proliferative and nonproliferative breast disease in mammographically guided fine-needle aspirates.

Fine-needle aspiration biopsy (FNAB) is considered a valid diagnostic procedure in management of patients with breast lesions. It is also important to differentiate benign nonproliferative change from proliferative breast changes, since the risk of development of breast carcinoma in patients with atypical hyperplasia is 4-5 times that of general population. Therefore, the recognition of proliferative breast disease with atypia significantly impacts on the patient's subsequent management. To assess the feasibility of a cytologic grading system to further characterize benign breast lesions, cytologic preparation of 87 mammographically guided FNABs were studied. Cellular aspirates were evaluated for the cellular arrangement, the degree of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. Values ranging from 1 to 4 were assigned to each cytologic criterion, and a score based on the sum of the individual values was calculated for each case. The minimum score attainable was thus 6. In our chosen criteria cytologic diagnosis of nonproliferative disease was entertained when the total score ranged from 6 to 10. Proliferative disease without atypia was diagnosed with a total score ranging from 11 to 14. Atypical hyperplasia was reported when the total score ranged from 15 to 18. A cytologic diagnosis of malignancy was entertained when the total score ranged from 19 to 24. The cytologic diagnosis was then compared to the reported histologic diagnosis from the excisional biopsies and the data were statistically analysed. A high degree of concordance was found between the cytologic findings and the histologic diagnosis. This study suggests that it is possible to apply a cytologic grading system to further subclassify benign breast disease and distinguish these forms from neoplastic lesions.     

PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma

Clear cell adenocarcinoma (CCA), a highly lethal histological subtype of ovarian carcinoma, is a type of human cancer with a high frequency of activating mutations in the PIK3CA gene. In this study, we aimed to determine how these mutations contribute to tumour development of CCAs. Exons 9 and 20 of the PIK3CA gene were analysed by direct genomic DNA sequencing of 23 CCAs with synchronous putative precursor lesions (ie endometriosis adjacent to carcinoma, with or without cytological atypia) and their mutational statuses were compared. Somatic mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all cases the type of mutation was H1047R in the kinase domain. The identical H1047R mutation was also detected in the coexisting endometriotic epithelium, adjacent to the CCAs, in nine of ten (90%) cases. Moreover, in six of the nine lesions, the H1047R mutation was identified even in the endometrioses lacking cytological atypia. These findings provide evidence that mutations of the PIK3CA gene occur in the putative precursor lesions of CCA, strongly suggesting that they are very early events in tumourigenesis, probably initiating the malignant transformation of endometriosis. A specific kinase inhibitor to mutated PIK3CA may potentially be an effective therapeutic reagent against these carcinomas.     

Sclerosing papillary lesion of the breast: a diagnostic pitfall for malignancy in fine needle aspiration biopsy

Papillary neoplasms of breast constitute a group of lesions that show broad spectrum of morphological changes, ranging from benign to malignant and posing challenges at all diagnostic levels. Some benign papillary lesions may form well-defined solid masses with a dominant sclerosed architecture, known as complex sclerosing papillary lesion or simply sclerosing papilloma. The purpose of this study is to apply the previously published criteria for papillary lesions and to identify the cytomorphologic findings that lead to false-positive diagnosis of these cases. We reviewed the fine needle aspiration biopsies (FNAB) of six histologically proven sclerosing papilloma that were called suspicious or malignant on FNAB. The patient age ranged from 40 to 69, with a mean of (43 +/- 6) yr. Three patients presented with a palpable lump and two patients had history of fibrocystic disease. All six patients had abnormal screening mammograms. FNAB was performed using a 23-gauge syringe attached to a commercial holder. FNA smears were markedly hypercellular with large number of epithelial fragments and papillary clusters, discohesive single cells that are hyperchromatic with mild to moderate nuclear pleomorphism. Bipolar cells were present in all cases, varying from low to abundant. Intraoperative consultation was requested on four cases. Touch preparations were made on two cases and were reported as suspicious based on the cellularity and nuclear atypia. All surgically excised specimens showed sclerosing complex papillary proliferative lesions with epithelial hyperplasia. In conclusion, FNA cytology of this proliferative lesions may be highly cellular and may display cellular atypia similar to breast carcinoma and thus leads to false-positive interpretation.     

Cytologic criteria to distinguish hepatocellular carcinoma from nonneoplastic liver.

The authors reviewed a series of fine-needle aspiration biopsy (FNAB) specimens of the liver to identify useful cytologic criteria to distinguish hepatocellular carcinoma (HCC) from nonneoplastic liver. Ten cytologic features were examined in this study: high cellularity, acinar pattern, trabecular pattern, hyperchromasia, pleomorphism, irregularly granular chromatin, uniformly prominent nucleoli, multiple nucleoli, increased nuclear/cytoplasmic ratio, and atypical naked hepatocytic nuclei. These features were examined in a series of 82 FNAB specimens from 52 patients with HCC and 30 patients with nonneoplastic lesions. With the use of a step-wise logistic regression analysis, three features were identified as predictive of HCC: increased nuclear/cytoplasmic ratio (P = 0.001), trabecular pattern (P = 0.002), and atypical naked hepatocytic nuclei (P = 0.03). When these three criteria were used, the sensitivity of diagnosing HCC by FNAB was 100%, and the specificity was 87%.     

Fine-needle aspiration of breast carcinomas with prominent lymphocytic infiltrate

Carcinomas of the breast with prominent lymphoplasmacytic background are commonly encountered in cytology. The aim of this study was to assess the prevalence of different types of carcinomas that share this common feature, identify possible distinguishing cytologic features, and evaluate the diagnostic pitfalls in this group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation was absent in the TMC but was common in IDC and AMC. No cytologic differences were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes and plasma cells may be seen in different types of breast carcinomas and should not be considered a diagnostic feature of TMC. Features potentially helpful in the cytologic differential diagnosis of a carcinoma with prominent lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2 microm in IDC and AMC, respectively) and the degree of nuclear atypia. Lymphocytosis may be part of the carcinoma or may originate from a lymph node involved by metastases. In rare cases, a prominent neutrophilic infiltrate may also be present.     

Can cytomorphology differentiate between benign nodules and tumors arising in Graves' disease?

Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves' disease (GD) can pose diagnostic difficulties because the cytomorphologic changes in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In addition, treatment of GD patients with radioactive iodine (RAI) may cause significant cytologic atypia, further increasing the diagnostic difficulty. From March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients with GD underwent FNA; 3 patients had received RAI treatment. Three cases were diagnosed as suspicious for PTC and 11 as benign. Three patients with the diagnosis of suspicious for PTC on FNA underwent surgery and were found to have papillary carcinoma. We assessed all cases to find key cytologic features that can differentiate between nodules with reactive/reparative nuclear atypia from PTC arising in GD. The cytologic features assessed included cellularity, amount of colloid, monotony of the cell population, oncocytic features, cell crowding, lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0 representing absence and 4 representing a predominance of the feature. The mean value of each feature was calculated and the benign and malignant lesions were compared using the unpaired t-test. Four features were found to be statistically significant in the diagnosis of PTC as compared to the benign nodules in GD. The nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli. All other features studied were not found to be statistically significant. There does exist an overlap between the cytologic features of benign nodules and PTC arising in GD. However, adherence to strict diagnostic criteria (nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the diagnosis of PTC arising in GD.     

Spectrum of carcinoembryonic antigen immunoreactivity from isolated ductal hyperplasias to atypical hyperplasias associated with infiltrating ductal breast cancer.

AIMS--To study the immunohistochemical expression of carcinoembryonic antigen (CEA) in ductal hyperplasia of the breast and to investigate its putative relation with atypia and co-existing infiltrating ductal carcinoma. METHODS--Paraffin wax embedded tissue from 37 cases of isolated ductal hyperplasia (five with atypia and 32 without atypia) and 25 cases of ductal hyperplasia associated infiltrating ductal carcinoma (IDC) (seven with atypia and 18 without atypia) was stained with a monoclonal anti-CEA antibody using a standard avidin biotin immunoperoxidase method. RESULTS--CEA immunoreactivity was observed in eight (12.8%) ductal hyperplasia cases. The percentage of CEA positivity in ductal hyperplasia cases with atypia (33.3%) was substantially higher than that observed in cases of ductal hyperplasia without atypia (8.0%). Six cases of ductal hyperplasia associated IDC reacted with CEA; in these six cases the neoplastic cells of the co-existing carcinoma were also CEA positive. The percentage of CEA immunoreactivity in ductal hyperplasia associated IDC was higher than that observed in isolated ductal hyperplasia (24.0 v 5.4%). The percentage of CEA immunoreactivity in atypical ductal hyperplasia associated IDC was similar to that observed in IDC alone (42.9 v 40.0%). CONCLUSIONS--The presence of CEA immunoreactivity has been confirmed in benign proliferative breast lesions. The prevalence of such immunoreactivity increases from 3.1% in isolated, nonatypical ductal hyperplasia to 42.9% in atypical ductal hyperplasia associated IDC. This finding and the similarity of the frequency of CEA positivity in atypical ductal hyperplasia associated IDC and in IDC alone suggests that there is a pathogenetic link between ductal hyperplasia and some types of breast cancer.     

Gynecomastia with marked cellular atypia associated with chemotherapy

Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy. The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized.     

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.