Salivary gland tumors with a prominent oncocytic component. Cytologic findings and differential diagnosis of oncocytomas and Warthin's tumor on fine needle aspirates

OBJECTIVE: To review aspirates from histologically documented oncocytomas and Warthin's tumor (WT) to highlight the cytomorphologic findings and determine the difficulties encountered in typing oncocytepredominant aspirates. STUDY DESIGN: Over a 19-year period (1982-2000) we reviewed aspirates from 45 cases with an oncocyte preponderance. In 24 of them tissue for histologic examination was available (5 oncocytomas and 19 WT). RESULTS: In 4 of the 5 histologically documented oncocytomas the aspirates were cellular, with oncocytic epithelial cells in sheets, papillary fragments and singly. Epithelial atypia was minimal and lymphoid component absent, though scant proteinaceous material with a sprinkling of lymphocytes was seen. In WT moderate (35%) to abundant (28%) oncocytic epithelial cells were seen predominantly in a sheetlike arrangement with occasional papillary fragments and single cells. A variable quantity of lymphoid component was seen in 90% of the aspirates, with 88% of them showing a proteinaceous background accompanied by necrotic debris in 43% of cases. Squamous metaplasia was identified in 30% of cases, with 3 showing atypical squamous cells. In four cases the lymphoid component was scant and oncocytes abundant, and both possibilities were entertained. CONCLUSION: Fine needle aspiration cytology is fairly accurate in the preoperative diagnosis of WT. When the lymphoid component, mucus and necrotic background are minimal or absent, the tumors can be confused with oncocytoma. In oncocytoma, the oncocytic epithelial cells are more often seen in papillary fragments, acini and singly in comparison to WT, where sheets of oncocytic cells are observed. Some degree of epithelial atypia can be seen in oncocyte-predominant benign lesions. Squamous metaplasia, especially if accompanied by atypia and necrosis, can prove challenging.     

Fine needle aspiration diagnosis of cysticercosis in soft tissue swellings

The cytomorphologic criteria for diagnosing cysticercosis in fine needle aspirates are described. A retrospective analysis of aspirates from 62 cases with subcutaneous swellings in various sites showed the presence of the parasite in 25 cases. In another 31 cases, the aspiration smears contained no larval parts, but did contain an inflammatory reaction (consisting of large numbers of eosinophils and palasading histiocytes) suggestive of a parasitic cyst. Corresponding histologic material from 19 of these cases were diagnostic of cysticercosis in 9 cases and suggestive of cysticercosis in 10. However, histology was diagnostic of cysticercosis in six cases that produced acellular aspirates. These results show that fine needle aspiration cytology can diagnose or suggest cysticercosis in many cases, but may be falsely negative in a few.     

Utility of fine needle aspiration cytology in mediastinal lesions: a clinicopathologic study of 1617 cases from a single institution

OBJECTIVE: To study the distribution, prevalence and cytomorphologic features of mediastinal lesions and assess the utility of fine needle aspiration cytology (FNAC) in such lesions by correlating with clinical, laboratory and imageologic parameters. STUDY DESIGN: A retrospective study was performed of mediastinal lesions that were referred for ultrasonographic/computed tomography-guided FNAC during the years 2001-2006. Correlation was done wherever possible using the following parameters: histology, bone marrow, imageology, tumor markers, cytology, immunohistochemistry, antecedent history and regression after therapy. RESULTS: A total of 161 patients underwent 182 aspirates. Diagnosis was possible in 130 (80.7%) patients, and, in 31 cases (19.3%), aspirates were unsatisfactory. In 71 (54.6%) correlation was done, and in 70 (98.5%) positive correlation was found. CONCLUSION: FNAC in correlation with clinical, imageologic and hematologic features proved to be an excellent diagnostic tool in diagnosing as well as classifying mediastinal lesions and can be used as a substitute to core biopsy.     

Cytopathology of thymoma

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.     

Wilms' tumor. Role of fine needle aspiration and DNA ploidy by image analysis in prognostication

OBJECTIVE: To evaluate the utility of cytomorphologic features and DNA ploidy estimation in fine needle aspirates (FNAs), from Wilms' tumors for prognostication. STUDY DESIGN: Twenty-three cases of Wilms' tumor having FNA and follow-up data were selected. Cytomorphology was analyzed by two observers. DNA ploidy was determined in 19 cases by image cytometry by destaining Papanicolaou-stained slides and restaining with Feulgen stain. Various parameters and patient outcomes were compared, and statistical evaluation was done. RESULTS: Poor outcome (12/23 cases) was associated with age < 2 years (P = .01), severe pleomorphism of blastemal cells (4/23 cases, P < .05), very large nucleoli (5/23 cases, P = .075), atypical mitosis (6/23 cases, P = .032) and aneuploidy/tetraploidy of tumor cells (6/29 cases, P = .005). Term unfavorable cytology is proposed when a combination of severe pleomorphism, very large nucleoli and atypical mitosis is seen in FNA smears. Four Wilms' tumor FNAs were characterized as showing unfavorable cytology, and all had a poor outcome (P = .0351). Three of the six cases with aneuploid/tetraploid features also showed unfavorable cytology. CONCLUSION: Unfavorable cytology and aneuploidy/tetraploidy in FNA smears of Wilms' tumor are associated with a poor prognosis.     

Warthin''s tumour: unusual vs. common morphological findings in fine needle aspiration biopsies

Fine needle aspiration biopsies (FNA) of 47 Warthin's tumours confirmed by histology were re-evaluated for cytomorphological findings. The majority of aspirates (37/47) contained a typical background with proteinaceous substance and cell debris, along with cellular elements represented by oncocytic, lymphoid, and mast cells with degranulated cytoplasm. Uncommon cellular findings were true squamous cells (1/47), atypical cells with vacuoles (1/47), osteoclastic giant cells (1/47), epithelioid cells (1/47), mast cells with preserved granules in cytoplasm (3/47), and siderophages (4/47). Uncommon findings in the background were corpora amylacea-like structures and homogeneous bright red droplets. Squamous cells and atypical cells with vacuoles caused diagnostic difficulties in distinguishing a Warthin's tumour from a squamous cell or mucoepidermoid carcinoma. However, other unusual cellular and background findings were not worrying; therefore, they are merely regarded as a curiosity in the cytomorphological appearance of the tumour.     

Critical role of fine needle aspiration cytology and immunocytochemistry in preoperative diagnosis of pediatric renal tumors

OBJECTIVE: To evaluate accuracy and role of immunocytochemistry (ICC) in cytologic diagnosis of pediatric renal tumors. STUDY DESIGN: Fine needle aspirates from 75 cases of pediatric renal tumors were studied. Radiologic-guided aspirations were performed, with 6-7 smears stained with Papanicolaou and Giemsa stains. Smears were screened without the knowledge of final histologic diagnosis. Subsequently, clinical details, final histology and diagnosis rendered by the original cytologist were noted to judge accuracy of diagnosis by a sensitized cytologist. Five neuroblastomas that entered close differentials for Wilms tumor were also evaluated. ICC studies were also performed after staining. RESULTS: Of 58 Wilms tumors, 5 were misdiagnosed; 3 renal rhabdoid tumors and 1 clear cell sarcoma were missed on cytology. Non-Hodgkin's lymphomas presenting as renal masses were accurately diagnosed on cytology, but primitive neuroectodermal tumors (n = 3) and renal cell carcinomas (n = 2) were not accurately diagnosed. Accuracy rate improved from 65% to 92% on review by a cytologist aware of cytologic features of pediatric renal tumors. CONCLUSION: A good accuracy rate of diagnosis of pediatric renal tumors can be achieved by priming pathologists to typical features of tumors. Immunocytochemistry plays a supportive role in cases with atypical morphology or unusual presentations.     

Fine needle aspiration cytology of leprous neuritis

OBJECTIVE: To document the cytomorphologic features of leprous neuritis and their correlation with bacterial density. STUDY DESIGN: A partly retrospective, partly prospective study of the fine needle aspiration cytology of enlarged nerves in leprosy. Cytomorphologic features of nerve aspirates from 28 patients were studied. May-Grünwald-Geimsa and Ziehl-Neelsen staining methods were employed. RESULTS: Five cytomorphologic patterns were observed in smears of nerve aspirates in 19 group I patients with concurrent skin and nerve lesions: (1) inflammation composed of epithelioid cell granulomas (5), bacillary index (BI) = 0; (2) epithelioid cell granulomas with necrosis (5), BI = 0-1+; (3) acellular necrosis (5), BI = 0-4+; (4) macrophage granuloma (3), BI = 5-6+; and (5) granulation tissue (1), BI = 1+. In 9 group II patients with pure neuritic leprosy, 3 patterns were seen: (1) epithelioid cell granulomas (5), BI 0-6+; (2) epithelioid granulomas with necrosis (1), BI = 0; and (3) acellular necrosis (3), BI = 0-6+. CONCLUSION: The entire spectrum of leprosy is seen in nerve aspirates. Necrosis is often a prominent feature. Recognition of the range of cytomorphologic patterns and their correlation with BI contribute to accurate calibration of the disease in nerves, resulting in appropriate choice of treatment.     

Fine needle aspiration cytology of hepatoblastoma. Recognition of subtypes on cytomorphology

OBJECTIVE: To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). STUDY DESIGN: Papanicolaou- and May-Grünwald-Giemsa-stained smears of aspirates from 26 cases of HBL were analyzed by 2 observers. Histologic material, available in 15 cases, was correlated. A cytology grouping system was proposed on the basis of which all cases were classified. RESULTS: The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was < or = 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of > or = 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respectively). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in 1 case. CONCLUSION: Epithelial HBL can be easily diagnosed in aspirates further classified into fetal and embryonal subtypes, which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.     

Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases

OBJECTIVE: To report atypical cytomorphologic features in fine needle aspiration biopsies (FNABs) from two cases of Merkel cell carcinoma (MCC), a primary neuroendocrine neoplasm of skin. STUDY DESIGN: Retrospective review of FNABs with histologic correlation from six patients with MCC and a report of findings from two whose smears showed atypical features. RESULTS: Typically the aspirates produce highly cellular smears of loosely clustered and individual, relatively monomorphic, small tumor cells with round to oval, regularly contoured nuclei. In two of our cases, the tumor cell nuclei exhibited a spectrum of pleomorphism ranging from moderately complex nuclear membranes with cleaves, indentations and protrusions in one case to large, markedly bizarre, convoluted nuclei and multinucleate tumor cells in the extreme case. Both cases were primary neoplasms, and the diagnosis was based on clinical, histologic and immunohistochemical data. Additionally, electron microscopy was performed on the tumor with bizarre nuclei and demonstrated rare, dense core neurosecretory granules and paranuclear bundles of intermediate filaments.     

Malignant mesothelioma. Cytopathology of 75 cases seen in a New Jersey community hospital

Seventy-five cases of diffuse pleural and/or peritoneal malignant mesothelioma (73 of body cavity fluids and 2 of fine needle aspirates) were studied by cytologic methods. Of the three major histologic varieties of mesothelioma (epithelioid, fibrous and mixed, or biphasic), the epithelioid and biphasic types were associated with four cytomorphologic features useful in the diagnostic evaluation: (1) the presence of abnormal cells, apparently mesothelial, (2) nuclei with subtle malignant features, (3) the presence of cells showing transitional forms from normal to abnormal in the same sample and (4) the presence of large tissue fragments. The fibrous mesotheliomas presented cytologically as sarcomatous neoplasms. Three histochemical reactions were found to be valuable adjuncts to diagnosis in the differentiation of the primary malignancies of the serous membranes from metastatic cancers. These stains were the periodic acid-Schiff, with and without diastase digestion, the Alcian blue, with and without hyaluronidase digestion, and the Van Gieson. The histochemistry was diagnostically useful in 42% of the cases in which the cytomorphologic impression was uncertain or equivocal; it served as an added confirmatory finding in 64% of the cytologically diagnosable mesotheliomas.     

In vitro control of blastema cell proliferation by extracts from epidermal cap and mesenchyme of regenerating limbs of axolotls

Summary The presence of a mitogenic activity in limb blastemas of axolotls was detected in crude extracts of blastemas at the mid-bud stage. The mitogenicity of the extracts was estimated from the mitotic index of blastema cells grown for 6 days in the presence of limb blastema extracts, with colchicine present for the last 2 days. All the extracts tested (whole blastema, blastemal mesenchyme, epidermal cap) significantly enhanced proliferation of blastema cells. The highest stimulation factors we observed were 7 × with 7 g protein/ml whole blastema extracts, 5.2 × with 14 g/ml blastemal mesenchyme extracts, and 11 x with 3.5 g/ml epidermal cap extracts. Hence the epidermal cap extracts appeared to be the most mitogenic. Extracts from the blastemal mesenchyme, although less mitogenic than the epidermal cap extracts, were more potent than nerve extracts [Albert P, Boilly B (1986) Biol Cell 58:251–262]. These results are discussed with regard to the production of growth factors during limb regeneration.     

Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions

OBJECTIVE: To differentiate hyperplastic nodules (HPN), follicular adenoma (FA) and follicular carcinoma (FCA) of the thyroid by cytomorphologic features combined with argyrophilic nucleolar organizer regions (AgNORs) and Ki-67 proliferative markers on fine needle aspiration cytology. STUDY DESIGN: Cytomorphologic patterns, along with two proliferation markers, Ki-67 and AgNORs, in fine needle aspirates of 123 histologically confirmed cases of thyroid follicular lesions, including 39 hyperplastic nodules, 70 follicular adenomas and 14 cases of follicular carcinomas, were recorded. RESULTS: Mean AgNOR (mAgNOR) counts and Ki-67 labelling index (LI) were consistently higher in FCA in comparison to FA and HPN irrespective of the cytologic patterns in fine needle aspiration smears. Between benign and malignant lesions, an overlap of 1.83% at the cutoff point of 4.0 was observed in cases of mAgNORs, whereas it was 11.09% at a cutoff of 5.0 in cases of Ki-67 LI. CONCLUSION: mAgNOR counting in fine needle aspiration smears is more sensitive, simple and cost effective as compared to Ki-67 LI for differentiating between benign and malignant thyroid follicular neoplasms.     

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.     

Cytologic diagnosis of reactive lymphadenopathy in fine needle aspiration biopsy specimens

Reactive or benign lymphadenopathies were cytologically diagnosed in the aspirates of 62 (23.5%) of 265 cases with enlarged lymph nodes of the head, neck or inguinal region subjected to fine needle aspiration (FNA) biopsy. The cytomorphologic features characteristic of reactive lymphadenopathy are described in detail; some of the cell patterns were suggestive of a specific disease process. The similarities of cells and cell patterns that may pose differential diagnostic problems with malignant lymphomas are pointed out. This study emphasizes the role of FNA cytology in the diagnosis of some benign conditions.