Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy. STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied. RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified. CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.     

Fine needle aspiration cytology of mammary duct ectasia: report of a case with novel cytologic and immunocytochemical findings.

BACKGROUND: Mammary duct ectasia (MDE), or periductal mastitis, is a well-defined clinical entity with a characteristic histopathologic appearance on breast biopsy specimens. However, the cytologic features of MDE have been described only recently in the cytopathology literature, and fine needle aspiration (FNA) cytologic findings are based mainly on a small number of case reports in the English-language literature. Therefore, awareness of this entity and recognition of its cytomorphologic features could aid in a more accurate diagnosis. We report the novel cytologic and immunocytochemical findings on a case of MDE that was confirmed by histologic examination on a subsequent biopsy. CASE: We report the findings of breast FNA cytology in a 50-year-old female with a mammographically and clinically suspicious lesion. Cytology displayed a paucicellular aspirate, typified by a few scattered, cohesive clusters of ductal epithelial cells with mild nuclear atypia and distinct, peripherally located myoepithelial cells. Intermingled within the ductal elements were numerous polygonal cells with abundant, finely vacuolated cytoplasm that were immunoreactive for macrophage-specific antibody, CD68. The background consisted of a variable number of foam cells and negligible amount of blood. CONCLUSION: The current case of MDE demonstrates cytomorphologic features that may pose diagnostic problems, particularly as a consequence of variable cytologic atypia this entity may present on FNA cytology. This diagnostic difficulty is compounded because of the abnormal mammographic and suspicious clinical findings that may be associated with MDE. CD68 immunoreactivity is a useful ancillary tool to verify the histiocytic, rather than epithelial and potentially neoplastic, nature of multivacuolated cells. To the best of our knowledge, there has been no prior reported case of MDE in the English-language literature studied utilizing CD68 antibody. This case report emphasizes that MDE is a heterogeneous entity with diverse cytomorphologic features. FNA cytology in conjunction with immunocytochemistry might permit accurate classification in the proper clinical setting.     

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 primary epithelioid sarcoma. A report of 2 cases

BACKGROUND: Epithelioid sarcoma is a rare soft part tumor, the cytologic features of which have not been fully elucidated to date. We describe the cytologic features in 2 cases of primary epithelioid sarcoma with samples obtained by fine needle aspiration (FNA). CASES: Case 1 was a 50-year-old male who complained of a small mass in his left palm. Case 2 was a 56-year-old female who presented with a mass on the medial aspect of her right forearm. Preoperative FNA smears in both cases showed loose, aggregated and isolated tumor cells that were round to polygonal, with eccentrically located nuclei, against a background of inflammation and necrosis. The tumor cells showed moderate atypia, irregularity in size and many mitoses. In case 1 a presumptive diagnosis of epithelioid sarcoma was made by FNA cytology, while in case 2, FNA cytology revealed a high grade sarcoma with abundant matrix mimicking osteoids, difficult to differentiate from an extraskeletal osteosarcoma. CONCLUSION: Epithelioid sarcoma may be difficult to differentiate from an extraskeletal osteosarcoma in cases with abundant hyalinized collagen on FNA cytology.     

Fine needle aspiration of the liver. Significance of hepatocytic naked nuclei in the diagnosis of hepatocellular carcinoma

Fine needle aspiration (FNA) smears from 60 cases of histologically (34) or clinically (26) confirmed hepatocellular carcinomas were reviewed. In about 90% of the cases, the cytologic preparations contained clusters of malignant cells with variable degrees of hepatocytic features and a distinctive type of naked nuclei. These naked nuclei had features similar to those of the malignant hepatocytes, but with more evident atypia. They were numerous in about 75% of the cases and less frequent in 15%; in three cases, they were practically absent. All three cases of well-differentiated hepatocellular carcinomas presented with numerous naked nuclei with slight atypia. Flowerlike-configured naked nuclei were especially found in poorly differentiated hepatocellular tumors. Hepatocytic naked nuclei were rarely found in FNA smears from normal liver, metastases, cysts or degenerative, regenerative and inflammatory liver processes; when seen in these cases, they showed no atypia. The presence of atypical hepatocytic naked nuclei appears to be a very useful criterion for the diagnosis of hepatocellular carcinoma.     

Cytologic findings in calcifying epithelial odontogenic tumor: a case report

BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT), or Pindborg's tumor, is a rare, benign, odontogenic neoplasm first described by Pindborg in 1955. It is most commonly seen in the fourth and fifth decades of life, usually arises in the mandibular premolar-molar areas and accounts for approximately 1% of all intraosseous odontogenic tumors. This report describes the cytologic findings in a case of CEOT. CASE: A 62-year-old woman was referred to the ear, nose and throat clinic with a right maxillary mass. The fine needle aspiration (FNA) smears showed numerous calcifications; amorphous, eosinophilic material; and clusters of round epithelial cells embedded in a bloody background. The smears were diagnosed as suspicious for malignancy. Maxillectomy was done. The histologic sections were diagnosed as CEOT. CONCLUSION: FNA findings of calcifying epithelial odontogenic tumor have been described rarely. The clusters of epithelial cells with prominent nucleoli are mistaken for features of a malignant tumor.     

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 radiation-induced changes in nonneoplastic breast lesions. Possible pitfalls in cytodiagnosis

The range of radiation-induced changes in fine needle aspiration (FNA) smears of the breast is described. In 41 of more than 800 patients who underwent breast-conserving treatment, a palpable breast lesion developed, and FNA was performed. In six cases, a recurrent carcinoma was present. In the remaining cases, three patterns of nonneoplastic lesions could be discerned: epithelial atypia (14 cases), fat necrosis (10 cases) and poorly cellular smears without epithelial atypia or fat necrosis (13 cases). It is important to be familiar with the patterns of radiation-induced epithelial atypia, since such atypia may lead to a misdiagnosis of recurrent carcinoma. These atypical cells may show impressive anisocytosis and anisonucleosis; however, the nuclear/cytoplasmic ratio remains normal and an admixture of bipolar cells is present. Cell dissociation and necrotic cell debris, as often seen in breast cancer smears, were never encountered in FNA smears from radiated nonneoplastic breasts.     

Cytology of recurrent ameloblastoma with malignant change. A case report

BACKGROUND: Ameloblastoma is a rare tumor of the jaw that arises from the odontogenic epithelium. Ameloblastomas have a propensity for local recurrence and, rarely, for metastasis. The term malignant ameloblastoma is reserved for those metastasizing tumors that retain the typical morphology of ameloblastoma. Fine needle aspiration (FNA) reports on ameloblastomas are scant, and those on malignant ameloblastomas are still more so. CASE: In a case of malignant ameloblastoma diagnosed by FNA cytology, the clinical presentation was that of a malignant neoplasm. FNA smears were highly cellular and showed isolated, scattered cells and small groups of basaloid cells and polygonal squamous epithelial cells. Stellate and spindle-shaped cells were also seen in the background. The cytologic diagnosis was subsequently confirmed on histopathology. CONCLUSION: The characteristic combination of cells in FNA smears facilitated the diagnosis of ameloblastoma. Since the biologic behavior of the tumor was that of a malignant neoplasm, the slides were reviewed. The cytologic smears did not exhibit sufficient features of malignancy to label the lesion malignant.     

Aspiration cytology of tubular breast carcinoma

The cytologic features in smears of fine needle aspirates from 34 tubular breast carcinomas were studied. Uniform and bland epithelium in cohesive clusters dominated all specimens; two-thirds also showed some degree of cellular dissociation. Characteristic (but not quite pathognomonic) angular epithelial clusters with a tubular structure occurred in about 50% of the smears. Sparsely occurring atypical nuclei and/or cytoplasmic vacuoles, similar to those seen in lobular cancer, were found in half of the cases. Although a lack of myoepithelial cells was apparent in the majority of the smears, one-fourth of them showed a quite prominent myoepithelial component. Various combinations of atypical features resulted in a picture that was considered diagnostic of malignancy in 50% of the cases; the remaining specimens showed less pronounced atypia. Other pitfalls associated with the cytologic diagnosis of tubular carcinoma are discussed, and the importance of basing the management of small breast lesions on the mammographic as well as on the cytologic findings is emphasized.     

Primary osteogenic sarcoma of the breast: cytomorphologic study of 3 cases with histologic correlation

BACKGROUND: Primary osteogenic sarcomas of the breast are extremely rare neoplasms. The histologic and cytologic features are comparable to those of their soft tissue and skeletal counterparts. To assess the utility of fine needle aspiration (FNA) in preoperative identification of osteogenic sarcomas, we retrospectively reviewed the FNA findings of 3 cases diagnosed in our hospital over 2 1/2 years. CASES: Three women, aged 48, 55 and 76 years, presented with a palpable lump of a few months' duration in their breasts. FNA was indicative of malignancy, and mastectomy with ipsilateral axillary lymph node dissection was performed. The cytologic features were of hypocellular or hypercellular smears with pleomorphic cells; scarce or abundant metachromatic amorphous material, suggestive of osteoid; osteoclast-like giant cells; and stromal fragments. CONCLUSION: Although cytologic features can be suggestive of osteosarcoma in the appropriate clinical setting, prompt preoperative diagnosis of malignancy in FNA samples of these tumors can avoid undertreatment, because mammographic and clinical findings are in many cases confused with the features of a benign lesion, more specifically calcified fibroadenoma.     

Cytologic findings of breast ductal lavage and concurrent fine needle aspiration in pleomorphic lobular carcinoma in situ: a case report

BACKGROUND: Breast ductal lavage (DL) is a noninvasive procedure for sampling ductal epithelial cells. Patients at risk for breast cancer or with prior history can be monitored by DL. This report compares cytomorphology in concurrent DL, fine needle aspiration (FNA) and histology in a case of pleomorphic lobular carcinoma in situ (PLCIS) with signet ring features. CASE: A 57-year-old woman had DL and FNA performed after quadrantectomy for lobular carcinoma in situ with signet ring cell features. DL and FNA were diagnosed as suspicious and positive for malignancy, respectively. Subsequent biopsy showed PLCIS. Cytomorphologic features of DL, FNA and histology were compared. DL showed epithelial cells in small clusters or single-file arrangement and single-lying; in FNA, single cells predominated. DL and FNA showed nuclear atypia and cytoplasmic vacuoles, the latter more prevalent in FNA. Both samples showed cells with signet ring features. The atypical epithelial cells present in DL and FNA were identical to those seen in the histologic material. CONCLUSION: Cytomorphologic findings in DL, although less striking, are comparable to those seen in FNA. Architecture, nuclear atypia and intracytoplasmic vacuoles are helpful features in DL for establishing a diagnosis of suspicious if not positive for malignancy in LCIS.     

Cytodiagnosis of extraosseous mesenchymal chondrosarcoma of meninges: a case report

BACKGROUND: Extraosseous mesenchymal chondrosarcoma (MC) is a rare neoplasm. Most reports in the literature are based on histologic diagnosis. Cases diagnosed on the basis of cytologic features are few. CASE: A 30-year-old woman presented with complaints of headache, vomiting and swelling in the right temporal region for the previous 2 months. Fine needle aspiration (FNA) smears showed scant material consisting mainly of monomorphic small round cells with granular cytoplasm and central round nuclei lying in a background of myxoid matrix. Occasional giant cells were also seen. Cells were periodic acid-Schiff negative. One of the smears showed a tiny fragment of cartilaginous component. A provisional diagnosis of extraosseous MC was made. Peroperatively the mass was arising from meninges and the diagnosis was confirmed by histology. CONCLUSION: Extraosseous MC should be considered in FNA smears showing small round cells in a myxoid background. Demonstration of cartilage and a correlation of clinical presentation and imaging studies with cytologic findings are important.     

Diffuse alveolar damage. Morphologic features in bronchoalveolar lavage fluid

OBJECTIVE: To evaluate the overall cytologic characteristics of diffuse alveolar damage (DAD) in bronchoalveolar lavage (BAL) specimens in search of features that could be useful in cytologic diagnosis. STUDY DESIGN: We evaluated BAL samples from patients with DAD obtained simultaneously with transbronchial biopsies (n = 8) or open lung biopsies (n = 2) or within 24 hours of autopsy (n = 2). The material was processed routinely for cytologic and histologic evaluation. RESULTS: The smears were moderately to highly cellular. All cases had large numbers of alveolar macrophages and/or desquamated alveolar cells. The epithelial component displayed various degrees of nuclear atypia. Some epithelial clusters were three-dimensional, with peripheral cells showing clear cytoplasm, protruding outwards and resembling hobnails. Other aggregates appeared two-dimensional, as sheets of cells with flattened and dense cytoplasm (squamotized). Both types of cell clusters were often associated with dense, basophilic or amphophilic, amorphous extracellular material. Counterparts of all the cytologic features were observed in the histologic material, including atypia of the alveolar lining with hobnailing, squamotization, amorphous extracellular material and hyaline membranes. CONCLUSION: The cytologic features of BAL represent a constellation of alveolar cell injury. Based on these features, DAD can be correctly diagnosed or suggested in BAL samples in the appropriate clinical setting.     

Fine needle aspiration cytology of inflammatory pseudotumor of the lung (plasma cell granuloma). Report of four cases

The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of the lung are described. Histologic material was available for comparison in three of the four cases. FNA of these lesions usually yielded moderately to poorly cellular smears. The smears showed a mixture of chronic inflammatory cells and tissue fragments, without a predominance of plasma cells. Characteristic cytologic findings were not observed. The cytologic findings can be distinguished from those of other circumscribed benign and malignant lesions, however. The diagnosis of an inflammatory pseudotumor of the lung may be suggested by a combination of roentgenographic (a localized density) and FNA findings, which may justify a more conservative surgical approach.     

Fine needle aspiration cytology in a case of diffuse sclerosing carcinoma of the thyroid

The fine needle aspiration (FNA) cytologic findings in a rare case of bilateral diffuse sclerosing carcinoma of the thyroid are described. Along with a generally papillary architecture, the FNA biopsy smears showed a number of features not usually seen in thyroid carcinomas: psammoma bodies, an abundance of squamous metaplasia and a dense inflammatory component. The FNA diagnosis was multifocal papillary carcinoma with squamous metaplasia; histopathologic examination made the final diagnosis.     

Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive diagnosis.     

Fine needle aspiration biopsy and immunostaining findings in an aggressive inflammatory myofibroblastic tumor of the lung: a case report

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) can vary from benign pseudosarcomatous tumors to low grade sarcomas. To date, fine needle aspiration (FNA) findings of lung IMTs, especially in the aggressive form, have not been fully described. Here we present FNA biopsy findings in conjunction with immunohistochemical studies in a case of primary and recurrent pulmonary IMT. CASE: A 22-year-old man first presented with a left lung mass and 4.5 years later with a recurrent mass. Preoperative computed tomography-guided FNA was performed on both tumors. FNA cytologic smears of both specimens consisted of scant, distorted spindle cells suggestive of a spindle cell lesion but were insufficient for further classification. Needle core biopsies as well as touch imprints were performed during the FNA procedures. The imprints revealed abundant, well-preserved spindle cells with mild to moderate atypia and intermixed lymphocytes and plasma cells. The spindle cells in both specimens were immunoreactive for vimentin and smooth muscle actin and were negative for pancytokeratin, desmin, CD34 and c-kit. Thirty percent of the tumor cells were positive for p53. The findings were compatible with those of IMT. Histologic examination of the surgically resected initial and recurrent masses confirmed the diagnosis of lMT. CONCLUSION: The cytologic findings of pulmonary IMT in FNA specimens are suggestive of, although not specific for, IMT. Immunohistochemical studies can assist in the diagnosis by excluding other spindle cell lesions. Cytologic atypia and p53 immunoreactivity may be indicators of aggressive IMTs.     

Cytopathologic findings in breast masses in men with HIV infection

OBJECTIVE: To report the cytologic findings on 15 men with HIV infection who presented with breast masses and underwent fine needle aspiration (FNA). STUDY DESIGN: The cytopathology files of The Johns Hopkins Hospital (JHH) and the University of Texas Southwestern Medical Center (UTSW) were searched for cases of men with breast masses evaluated by FNA. The HIV status of these men was then ascertained. A total of 15 cases (9 at JHH, 6 at UTSW) of 259 (5.79%) were identified in which the patient was HIV seropositive. The pathologic diagnoses were reviewed, and the clinical history, along with the medication list at the time of FNA, was determined. RESULTS: The men ranged in age from 12 to 51 years (mean, 38). Breast masses were present on either the right (n = 6) or left (n = 7) side or were bilateral (n = 2). In all 15 cases, the masses were retroareolar, firm and tender. FNA showed a ductal and stromal proliferative process, often with focal cytologic atypia and numerous background naked myoepithelial nuclei, features consistent with a diagnosis of gynecomastia. Thirteen of these men were on drug regimens, which included indinivir, stavudine and saquinivir. Two of the men were on azidothymidine only. CONCLUSION: Gynecomastia, although rare in young men, was the sole cause of breast masses in HIV-seropositive men in this study. It has been described as an extremely rare side effect of certain antiretroviral medications, including indinivir, stavudine and saquinivir. FNA is an important tool in determining the benign nature of these lesions and excluding other causes of breast masses in this patient population, such as infections, malignant lymphoma and breast carcinoma.     

Fine needle aspiration cytology of spermatocytic seminoma. Report of a case

The clinical, radiologic, cytopathologic and histologic features of a case of spermatocytic seminoma in a 56-year-old man are reported and discussed. The cytologic findings in fine needle aspiration (FNA) smears suggested a diagnosis of spermatocytic seminoma, which was confirmed by subsequent histopathologic studies. The case suggests that spermatocytic seminoma can be suspected and distinguished from other types of seminoma and germ cell neoplasms by FNA cytology. The following criteria appear to be the most useful in making the cytodiagnosis: the presence of three different types of cells (large, medium and small), a clean background, an absence of a lymphoid component and "tigroid" substances and the relative paucity and clumping tendency of the neoplastic cells in the smears.