Pleural effusions in non-Hodgkin's lymphoma. A cytomorphologic, cytochemical and immunologic study

Review of the records of 243 cases of cytologically diagnosed non-Hodgkin's lymphomas (NHL) revealed pleural effusions in 21 (8.6%). Cytologic examination of pleural fluid was done in 17 cases, of which 16 were reported as positive. Cytologic examination was supplemented with cytochemical staining (acid phosphatase, alpha naphthyl acetate esterase and periodic-acid-Schiff reactions) and E-rosetting studies in 12 cases. Of the 16 positive cases, 11 were malignant lymphomas consisting of convoluted lymphocytes. Acute lymphatic leukemia of the prothymocytic type (T-ALL) and chronic lymphocytic leukemia of the T-cell type (T-CLL) comprised one case each, and there were three cases of follicular center cell lymphomas, two of the cleaved-cell type and one of the Burkitt-type. Comparison of the cytomorphology of the tumor cells in the pleural effusion with those in fine needle aspiration smears from the solid tumors in 14 cases showed an identical appearance in 13 cases; in one, the Burkitt-type lymphoma, the cells were larger and more pleomorphic in the pleural effusion. This study indicates that the cytologic diagnosis and categorization of NHL of the convoluted-cell type is greatly enhanced by the study of neoplastic lymphocytes in a pleural effusion.     

Diagnosis of intestinal malakoplakia by fine needle aspiration cytology

Two cases of intestinal malakoplakia were diagnosed by fine needle aspiration (FNA) cytology. Clinically, these cases were mistaken for a lymphoma and a tuberculosis. Percutaneous abdominal FNA material showed numerous macrophages with the characteristic Michaelis-Gutmann bodies. These bodies were easily identified both inside and outside the macrophages in the smears.     

Fine needle aspiration cytology of eyelid tumors

Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears.     

Cytomorphologic differentiation of Hodgkin's lymphoma and Ki-1+ anaplastic large cell lymphoma in fine needle aspirates

OBJECTIVE: To cytomorphologically differentiate Hodgkin's lymphoma (HL) from Ki-1+ anaplastic large cell lymphoma (ALCL) in fine needle aspirates. STUDY DESIGN: We blindly reviewed 63 fine needle aspiration (FNA) smears from histologically and immunophenotypically proven cases of ALCL (n = 15) and HL (n = 48). The smears were reviewed for the following criteria: (1) estimated percentages of abnormal cells, (2) pattern of the smears (polymorphous vs. dimorphous), and (3) presence or absence of multilobated cells. RESULTS: All cases were phenotyped by immunohistochemistry for CD3, CD15, CD20, CD30 and CD45, with flow cytometric immunophenotpyping in 41 cases. Flow cytometric phenotyping was not successful in any of the cases. The smears were polymorphous in all 15 cases of ALCL and in 1 case of HL (2%). The percentage of abnormal cells ranged from 10% to 90% in cases of ALCL (median, 30%) whereas it ranged from 1% to 25% in HL (median 3%; P = .0003). Three cases of HL showed abnormal cells constituting > or = 20% of the smears. They were all grade 2 disease. Multilobated cells were identified in 14 of the 15 cases of ALCL (93%) and in 3 of the 48 cases of HL (6.25%; P = .0008). CONCLUSION: Our findings indicate that the differentiation of ALCL from HL can be achieved in FNA smears through identification of abnormal cells representing > 30% of the population, a spectrum of abnormal cells and the presence of multilobated nuclei. Rare cases of grade 2 HL may be difficult to differentiate from ALCL.     

Cytology of leukemic lymphadenopathy

OBJECTIVE: To describe the cytomorphologic features of leukemic cells in lymph node aspiration material. STUDY DESIGN: We studied lymph node fine needle aspiration (FNA) smears of 36 leukemic patients. In 23 cases the lymphadenopathy was noticed simultaneously with marrow leukemia, and in the other 13 cases the lymphadenopathy was noticed during a relapse. Special stains, such as periodic acid Schiff, Sudan Black-B, Oil Red-O and nonspecific esterase, were used in special cases. RESULTS: Thirty-three cases were diagnosed as lymphoma, 1 as extramedullary hematopoiesis and 2 as leukemic involvement. CONCLUSION: Leukemic lymphadenopathy can be misdiagnosed as lymphoma on FNA smears. The clinical findings, previous history, hematologic studies and immunocytochemical studies are essential to the differentiation of leukemic smears from lymphoma. However, in some cases the leukemic infiltration can be diagnosed with certainty, provided that the smears show the characteristic findings, such as Auer rods and neoplastic promyelocytes with azurophilic granules.     

Breast myeloma: a report of 3 cases with fine needle aspiration cytologic findings

BACKGROUND: Multiple myeloma of the breast is very rare, and the fine needle aspiration (FNA) findings have not been reported before. CASES: Two cases of multiple myeloma presented with bilateral breast nodules during treatment with chemotherapy. One case of multiple myeloma presented initially with a left breast mass. FNA smears of all 3 cases revealed numerous plasma cells, plasmablasts and multinucleated giant plasma cells. The smears were diagnosed as plasma cell tumors. Serum immunoelectrophoresis revealed IgG myeloma in 2 cases and IgA myeloma in 1. Marrow aspirates revealed > 30% plasma cells. Two patients died, and 1 was alive at this writing. CONCLUSION: The aspiration cytology findings of myeloma can be confuse, with primary and secondary tumors of the breast. The previous clinical history and ancillary studies, such as bone marrow study and serum immunoelectrophoresis, are essential to the correct diagnosis.     

Grading follicular lymphoma on fine needle aspiration specimens. Comparison with proliferative index by DNA image analysis and Ki-67 labeling index

OBJECTIVE: To determine whether follicular lymphoma (FL) can be graded on fine needle aspiration (FNA) biopsies by determining the percentage of centroblasts in the neoplastic follicles on the smears. STUDY DESIGN: Eighty-nine cases of histologically confirmed cases of FL, including 31 grade 1, 46 grade 2 and 12 grade 3, were evaluated. Proliferative index (PI) by DNA image analysis (DIA) and Ki-67 labeling index (LI) were obtained on all cases. A minimum of 200 cells were counted per case (range, 200-800 cells) at 40x magnification, and the number of large cells (centroblasts) was expressed as a percentage of the total number of cells counted within the follicles. RESULTS: The percentage of centroblasts in the follicular aggregates was 9.7 +/- 2.9% in grade 1 FLs, 24.7 +/- 5.6% in grade 2 and 48.4 +/- 7.5% in grade 3. These differences were significant (P < .05). DNA image analysis of PI and Ki-67 LI differed significantly between grade 1 FLs and grade 2 and 3 FLs (P < .05), but there were no significant differences between grade 2 and 3 FLs. CONCLUSION: Determining the percentage of centroblasts in the follicular aggregates on FNA specimens is a good method of grading FLs. Using the percentage of centroblasts per follicular structure, FL grades 1, 2 and 3 were adequately distinguished. PI by DIA and Ki-67 LI clearly distinguished FL grade 1 from FL grades 2 and 3; however, it did not clearly distinguish between grades 2 and 3.     

Fine needle aspiration cytology of "minimal" breast cancer

The value of fine needle aspiration (FNA) cytology in the diagnosis of "minimal" breast cancer was studied. Sixteen (76.2%) of 21 cases of invasive breast cancer less than 1.0 cm in diameter and 14 (73.3%) of 19 cases of noninvasive breast carcinoma were given a positive diagnosis by FNA cytology. One "suspicious" and the five false-negative diagnoses occurred in cases of invasive carcinoma; the reasons were considered to be either a faulty technique of needling the tumor or the presence of prominent fibrosis in the tumor. In noninvasive carcinoma, atypical cells were misdiagnosed in two of the five smears that had been originally reported as negative. The results of the retrospective analysis showed that FNA cytology had a higher accuracy in the diagnosis of small lesions than did radiologic and echographic criteria, and FNA cytology was thus used as the main criterion for deciding on the necessity for preoperative surgical biopsies.     

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.     

Cytologic features of clear cell carcinoma of the female genital tract. Diagnostic value of the "raspberry body" in nonexfoliative cytologic specimens

OBJECTIVE: To evaluate the presence of basement membrane stromal material in fine needle aspiration (FNA) and scrape cytologic specimens from patients with clear cell carcinoma (CCC) of the female genital tract. STUDY DESIGN: The study group consisted of 6 patients with CCC (5 ovarian and 1 cervical). Four samples corresponded to FNA specimens and 3 to scrape material obtained during intraoperative consultation for ovarian tumors. FNA was performed on a pelvic recurrence and on liver, pulmonary and lymph node metastases. The 6 cases had a complete histopathologic study. RESULTS: In addition to large, clear cells, all cases showed basement membrane stromal material that assumed several forms. The most common was globular, hyaline structures, either naked or surrounded by neoplastic epithelial cells ("raspberry bodies"). Other fragments were larger, with several spherules and elongated prolongations. Scrape material showed stromal material resembling reduplicated basement membrane material. In Diff-Quik-stained smears (QCA, Tarragana, Spain) it showed metachromatic staining with a pink to purple color. Its recognition on Papanicolaou-stained smears was more difficult since it did not stain or was gray. CONCLUSION: Basement membrane stromal material and, more precisely, "raspberry bodies," are a characteristic cytologic feature of CCC of the female genital tract. The combination of clear, atypical cells and basement membrane stroma is highly specific to this neoplasm and can be observed not only in exfoliative specimens but also in FNA and scrape samples.     

Detection of Epstein-Barr virus-associated antigen in fine needle aspiration smears from cervical lymph nodes in the diagnosis of nasopharyngeal carcinoma

Epstein-Barr virus (EBV) has consistently been shown to be associated with undifferentiated nasopharyngeal carcinoma, and an EBV-associated nuclear antigen (EBNA) has been detected in the cells of nasopharyngeal carcinoma. A study on the applicability of EBNA detection in fine needle aspiration (FNA) smears from cervical lymph nodes in the diagnosis of metastatic nasopharyngeal carcinoma was performed. All 11 cases (100%) with metastatic nasopharyngeal carcinoma showed EBNA-positive tumor cells, characterized by bright, granulated nuclear fluorescence. Three (50%) of six cases with other metastatic head and neck carcinomas also showed EBNA-positive tumor cells. These findings suggest that the presence of EBNA-positive tumor cells in FNA smears from cervical lymph nodes is not specific for metastatic nasopharyngeal carcinoma. On the other hand, a negative result in the presence of tumor cells may help to exclude it. A larger study is required to verify these preliminary findings.     

Assessment of fine needle aspiration as a screening test for occult prostatic carcinoma

As part of an ongoing study of objective parameters of prognostic value in prostatic carcinoma, a routine procedure was developed to aspirate all prostates prior to surgery. These targets were different from those of other workers in the field of prostatic fine needle aspiration (FNA), who generally advocate that FNA be confined to suspicious nodules. The aspirations were performed by a large group of practicing urologists who had no special training in prostatic FNA except for guidelines provided by their peers and information available in the literature. This approach permitted an assessment of the performance of FNA as a screening test rather than as a diagnostic procedure. During the period from January 1983 to February 1987, 1,683 patients had prostatic FNAs performed (plus subsequent histologic study). The following diagnoses were rendered: "inadequate/scanty specimen" in 625 cases (37%), "negative/atypical" in 844 cases (50%) and "suspicious/positive" in 214 cases (13%). Histologic examination showed stage A1 prostatic adenocarcinoma in 18 patients. The cytologic diagnoses on these 18 patients were inadequate/scanty in 3 (17%), negative/atypical in 13 (72%) and suspicious/positive in 2 (11%). Of the 214 patients with a positive/suspicious diagnosis by FNA, the diagnosis of prostatic carcinoma was confirmed by tissue evidence in 200; the other 14 patients had either no evidence of prostatic carcinoma on surgical biopsy (needle biopsy/transurethral resection/suprapubic prostatectomy) or had no surgical biopsy. Eight of the 14 patients developed clinical evidence of carcinoma, 1 died of urinary bladder carcinoma and 1 was lost to follow-up. In the remaining four patients, there is still no evidence of prostatic carcinoma after about one-and-one-half years of follow-up. These results indicate that (1) specialized training is required in order to obtain adequate smears by prostatic FNA; (2) prostatic FNA is not a good screening technique for detecting stage A1 prostatic carcinoma; and (3) a positive diagnosis by prostatic FNA, even when not confirmed by tissue biopsy, is still an indication of disease.     

Fine needle aspiration cytology of pulmonary carcinoid tumors

Twenty-four cases coded as pulmonary carcinoid tumors initially sampled by fine needle aspiration (FNA) biopsy were reviewed in order to determine the cytologic features most useful in making the FNA diagnosis. The diagnosis of carcinoid tumor had been confirmed in 23 cases; the remaining case, though closely resembling a carcinoid tumor on the FNA specimen, proved to be a sclerosing hemangioma of the lung. Comparison of the original and review interpretations of the FNA specimens revealed that all typical spindle cell carcinoids and all atypical carcinoids were correctly diagnosed and classified. Of the 15 typical round cell carcinoids, the original cytologic diagnosis was lymphoma in 2 cases and benign bronchial lining cells in 2 cases. Thus, it appears that diagnostic errors are most likely in "typical" carcinoids. Review of the FNA findings suggests that the frequently stripped cytoplasm (with resulting non-cohesive bare nuclei), coupled with the almost universal plexiform vascularity (seen in 21 of 23 cases), should allow an accurate cytologic diagnosis in virtually all cases.     

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.     

Nucleic acid amplification of Mycobacterium tuberculosis complex DNA from archival fine needle aspiration smear scrapings vs. fresh fine needle aspirates of tuberculous lymphadenitis

OBJECTIVE: To assess the efficacy of the nucleic acid amplification (NAA) technique for Mycobacterium tuberculosis (MTB) complex from archival fine needle aspirate (FNA) smear scrapings of confirmed cases of extrapulmonary tuberculosis (EPTB) for a retrospective diagnosis of EPTB as compared to NAA from fresh FNA material from the same cases. STUDY DESIGN: Smear scrapings from 51 cases; 33 cases of tuberculous lymphadenitis (from patients who had undergone NAA 1 year before for MTB from fresh FNA material); 13 negative controls from nontuberculous, archival FNA smears; and 5 known acid-fast bacilli (AFB)-positive sputum smears, were subjected to NAA using the IS6110 primer sequence of M tuberculosis. Ziehl-Neelsen staining was done in all the smears. RESULTS: Of the 33 cases of tuberculous lymphadenitis, 15 (45.4%) were AFB positive and 18 (64.5%) AFB negative. MTB NAA was positive in 73.3% (11 of 15 AFB-positive cases) in the freshly aspirated material and was observed in 60% (9 of 15 AFB-positive cases) when done on DNA extracted from the archival smear scrapings of the same cases. Similarly, in the 18 AFB-negative cases, MTB NAA positivity was 72.2% (13 of 18) on fresh material and 44.4% (8 of 18) on archival smear scrapings from the same AFB-negative cases. Overall NAA positivity was 51.5% for archival smear scrapings as compared to 71% for fresh FNA of the same cases. CONCLUSION: Low NAA sensitivity of MTB DNA in archival material of known tuberculous cases limits the routine use of NAA based retrospective molecular diagnosis of MTB complex.     

FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation

OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation. METHODS: Retrospective analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical pathology follow-up was available in 33. Two pathologists were asked to categorize smears from 67 cases of breast lesions while blinded to the clinical finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The same set of slides was re-circulated to one of the pathologists, and his first and second round results were compared. RESULTS: Pre-review cytohistological correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall agreement between the two observers was 87% [Kappa = 0.74, 95% confidence interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33 (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93) with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic errors included marked dissociation, pleomorphism, poorly cellular smears from hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic changes. Multinucleated giant cells were frequently encountered in FNA smears from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a highly sensitive method for the diagnosis of fibroadenoma. Current cytological criteria were reliable and gave high inter- and intra-observer reproducibility.     

Cytodiagnosis of bone tumors by fine needle aspiration

A retrospective study was undertaken of bone lesions examined by preoperative fine needle aspiration (FNA) cytology in our hospital during the ten-year period from 1970 to 1979. The 430 cytologically examined lesions were classified into three groups: inflammatory lesions, tumorlike lesions and tumors. A total of 54 patients had undergone surgery, with most of the lesions in those cases proven to be tumors or tumorlike by histologic study. Correlation between the histologic and FNA cytologic findings showed complete compatibility in 76% of the cases, partial compatibility in 13% and incompatibility in 11%. It is concluded that FNA biopsy is appropriate for identifying bone tumors and tumorlike lesions if sufficient numbers of tumor cells are obtained for morphologic examination. Although aspiration cytodiagnosis can be of considerable value in the recognition of certain bone lesions, it cannot replace formal tissue biopsy in the diagnosis of primary bone neoplasms. The morphology of several common bone tumors is described in detail and their differential diagnosis is discussed.     

Fine needle aspiration cytologic findings in four cases of pilomatrixoma (calcifying epithelioma of Malherbe).

Four cases of pilomatrixoma studied by fine needle aspiration (FNA) biopsy prior to resection and histologic diagnosis were reviewed to identify the cytologic features useful in making the FNA cytodiagnosis. Cytopathology had initially correctly diagnosed two cases while misdiagnosing one as a carcinoma and one as a suspected carcinoma. The aspirates from all cases contained either clustered or isolated basaloid cells, with variably sized nuclei and prominent nucleoli. "Ghost cells" were also present in most smears stained with the Giemsa stain and could thus be very helpful for making the FNA diagnosis of pilomatrixoma. The occurrence of either foreign-body giant cells or calcium deposits in the aspirates could also contribute to suggesting the correct diagnosis of pilomatrixoma in some cases.     

Fine needle aspiration of lymphadenopathy in visceral leishmaniasis

OBJECTIVE: To illustrate the cytomorphologic features of Leishmania lymphadenitis associated with visceral leishmaniasis (V/L) and post-kala-azar dermal leishmaniasis (PKDL) and to highlight the fact that Leishmania lymphadenitis must he included in the differential diagnosis of patients presenting with lymphadenopathy, particularly in areas endemic for the disease. STUDY DESIGN: Fine needle aspiration (FNA) was routinely done in 21 cases of lymphadenopathy in VL (18 cases) and PKDL (3 cases), and the detailed cytomorphologic features were correlated with the respective histopathologic findings. RESULTS: Amastigote forms of Leishman-Donovan (LD) bodies were seen in 19 cases both intracellularly, in histiocytes and multinucleate giant cells, and extracellularly. The FNA smears revealed a polymorphous population of cells composed of lymphocytes, histiocytes, plasma cells, giant cells and tingible body macrophages. In a few cases, epithelioid cell granulomas were also seen. The cytomorphologic features were confirmed and correlated on histopathology. CONCLUSION: Not all lymphadenopathy in VL and PKDL is due to Leishmania lymphadenitis. Demonstration of LD bodies on FNA smears helps with the early diagnosis of VL and PKDL with lymphadenopathy where the diseases are endemic.     

Grave's disease. Appearance in cytologic smears from fine needle aspirates of the thyroid gland

The cytomorphologic features were analyzed in thyroid samples obtained by fine needle aspiration (FNA) from 54 cases proven to be Grave's disease (toxic goiter) by a multiparameter study. A fire-flare appearance of the follicular cells and a good cellularity of the smears were the features most frequently observed in these cases. Hürthle cell changes were present in 47% of the cases, and small numbers of lymphocytes were seen in smears from 41% of the cases. Epithelioid cell granulomata and multinucleated giant cells were observed in less than one-fourth of the cases. About half of the cases showed some degree of pleomorphism of the follicular cells. Twenty cases of toxic multinodular goiter were similarly analyzed; the features that distinguished this entity from Grave's disease were the absence of epithelioid cells and multinucleated giant cells in the FNA smears.