Role of fine needle aspiration cytology in nodular sclerosis variant of Hodgkin's lymphoma

OBJECTIVE: To assess the efficacy of fine needle aspiration cytology (FNAC) in the diagnosis of nodular sclerosis variant of Hodgkin's lymphoma (NSHL) and to analyze cytologic features that could help in subtyping a case of Hodgkin's lymphoma into this variant. STUDY DESIGN: FNAC smears of 18 histopathologically proven cases of NSHL were analyzed for a variety of features. RESULTS: On initial cytologic assessment, 14 of 18 cases were diagnosed as Hodgkin's lymphoma. No further subtyping was performed. In this retrospective analysis it was possible to revise the diagnosis in the remaining 4 cases. Of the various cytologic features analyzed, presence of numerous lacunar-type cells along with fibroblasts and collagenous material were useful pointers toward a diagnosis of nodular sclerosis variant. Fibroblasts were seen in 83.33%, collagenous material in 27.77% and numerous lacunar cells in 77.77%. CONCLUSION: Subtyping of NSHL based on cytologic features alone has been a matter of debate for a long time. Of the various subtypes, nodular sclerosis poses the greatest diagnostic difficulty. Though certain cytologic features may help in suggesting a diagnosis of nodular sclerosis variant, the primary role of fine needle aspiration is to diagnose a case of Hodgkin's lymphoma as such and advise histopathologic examination for further categorization.     

Olfactory neuroblastoma. Cytodiagnostic features in a case with ultrastructural and immunohistochemical correlation

In a case of olfactory neuroblastoma, originally misdiagnosed as an undifferentiated carcinoma, cytologic examination of material scraped from the superior nasal vault revealed tumor cells suggestive of neuroblastoma. The most significant cytodiagnostic feature was the presence of a fibrillary cytoplasm with ill-defined borders. Also noteworthy were the smudged hyperchromatic nuclei and structures resembling rosettes or pseudorosettes. The diagnosis was confirmed by electron microscopy, which revealed the presence of dense-core neurosecretory granules, clear vesicles, neurotubules and neurofilaments, and by immunohistochemistry, which showed positive staining for neuron-specific enolase but negative staining for keratin and glial fibrillary acidic protein. Since olfactory neuroblastoma has a relatively good prognosis and aggressive surgical resection may be curative, it is important that this tumor be distinguished from other small cell malignancies arising in the nasal cavity. The present case shows that the diagnosis can be made by the cytologic examination of scrapings from the tumor.     

Positive effusion cytology as the initial presentation of malignancy

During a period of four years (1981 to 1984), 641 ascitic, 860 pleural and 47 pericardial fluid specimens were examined cytologically. Of these, 154 ascitic samples, 174 pleural specimens and 10 pericardial effusions, obtained, respectively, from 108, 133 and 7 patients, were found to contain malignant cells. In 7 patients, ascites, and in 18 cases, pleural effusions were the first indication of cancer. None of the positive pericardial fluids was the initial presentation of malignancy. The cytologic findings and follow-up data on these 25 patients are the subject of this study. The most common type of neoplasm in these effusions was adenocarcinoma (86% of the ascitic and 78% of the pleural fluids). Most of the malignant neoplasms in ascitic fluids were derived from ovarian tumors (5 of 7) while those in pleural effusions came mainly from lung tumors (12 of 18). Mammary carcinoma, which was the most common malignant tumor found in cases of pleural effusions, did not present initially with an effusion in any of our cases. The cytologic diagnosis was confirmed in all cases by either biopsy or strong clinical evidence. The prognosis in patients who initially presented with an effusion was poor. All of the patients with an adequate follow-up died within 29 months in cases of ascites and within 19 months in cases of pleural effusions.     

Exfoliative sputum cytology in pulmonary embolism

In a prospective, double-blind, randomized study of cytologic changes found in pulmonary infarction, nine roentgenologically proven cases of pulmonary embolism were studied with sputum samples from the 1st to 26th postinfarction days. Maximum atypical cytologic changes were seen during the second and third postinfarction weeks. Specific cytologic features included three-dimensional clusters of glandular cells with enlarged nuclei and macronucleoli: they were malignant-appearing cells except for their inconsistent morphology, fewer numbers, transient appearance and lack of solitary atypical cells. A similar study in a canine model is discussed, and a case of pulmonary embolism with abnormal cytology and corresponding histology is presented.     

Giant-cell carcinoma of the lung. A cytologic study

A case of giant-cell carcinoma of the lung, confirmed at autopsy, is presented. The cytologic features seen in sputum samples, bronchial washings and brushings and fine needle aspiration biopsy material as well as the histologic findings are described. The possible relationship to bronchioloalveolar carcinoma is discussed. The cytologic features of giant-cell carcinoma of the lung, when seen in the context of the clinical and radiologic setting, should allow the cytologic identification of the tumor prior to surgical intervention.     

Fine needle aspiration cytology of the thyroid: a cytohistologic study with evaluation of discordant cases

OBJECTIVE: To analyze the diagnostic efficacy of fine needle aspiration cytology (FNAC) in the initial evaluation of thyroid nodules, with special emphasis on discrepant cytologic diagnoses. STUDY DESIGN: A total of 192 thyroid fine needle aspirates with subsequent histopathologic follow-up were analyzed. The cytologic diagnoses were divided into 4 categories: positive for malignancy, negative for malignancy, indeterminate for diagnosis and nondiagnostic. The detailed cytologic features were studied along with histopathology sections in all these cases by 2 observers (S.J. and P.D) independently. RESULTS: Cytohistologic correlation was seen in 78.1% of cases and discordance in 21.9%. Indeterminate diagnoses accounted for 15.1% of cases. The majority of these were "follicular neoplasms." The overall sensitivity was 84.44% and specificity 99.11 %. A false positive diagnosis was made in 1 case (0.5%), proven a follicular adenoma on histopathologic examination. A false negative diagnosis was seen in 3.6% of cases. These were cases of papillary microcarcinoma. CONCLUSION: FNAC is a safe, sensitive and specific technique in the initial evaluation of thyroid nodules. A correct cytologic diagnosis can be achieved in a majority of cases, thus obviating the need for a second surgical intervention. A careful and diligent search for various cytologic features and accurate sampling can help in reducing the number of indeterminate, false positive and false negative diagnoses.     

Occurrence of Poecilochirus austroasiaticus (Acari: Parasitidae) in forensic autopsies and its application on postmortem interval estimation

Despite the fact that mites were used at the dawn of forensic entomology to elucidate the postmortem interval, their use in current cases remains quite low for procedural reasons such as inadequate taxonomic knowledge. A special interest is focused on the phoretic stages of some mite species, because the phoront-host specificity allows us to deduce in many occasions the presence of the carrier (usually Diptera or Coleoptera) although it has not been seen in the sampling performed in situ or in the autopsy room. In this article, we describe two cases where Poecilochirus austroasiaticus Vitzthum (Acari: Parasitidae) was sampled in the autopsy room. In the first case, we could sample the host, Thanatophilus ruficornis (Küster) (Coleoptera: Silphidae), which was still carrying phoretic stages of the mite on the body. That attachment allowed, by observing starvation/feeding periods as a function of the digestive tract filling, the establishment of chronological cycles of phoretic behavior, showing maximum peaks of phoronts during arrival and departure from the corpse and the lowest values in the phase of host feeding. From the sarcosaprophagous fauna, we were able to determine in this case a minimum postmortem interval of 10 days. In the second case, we found no Silphidae at the place where the corpse was found or at the autopsy, but a postmortem interval of 13 days could be established by the high specificity of this interspecific relationship and the departure from the corpse of this family of Coleoptera.     

Mycosis fungoides with pulmonary involvement. Cytopathologic findings

In order to define the cytologic features of pulmonary involvement by mycosis fungoides, 15 respiratory cytology specimens from four patients with biopsy-proven pulmonary mycosis fungoides were reviewed. The presence in sputum smears of occasional small or large cerebriform mononucleated cells against a background of numerous atypical lymphocytic cells permitted an antemortem cytologic diagnosis of probable or definite dissemination of mycosis fungoides with pulmonary involvement. Similar cells were seen in aspiration smears. The lymphocytic infiltrates were similar to those in corresponding skin biopsies in each case. The distinctive cytologic findings in these cases may therefore help to determine the underlying etiology of pulmonary lesions and may contribute to the antemortem diagnosis of visceral dissemination of mycosis fungoides.     

Overexpression of HER2/neu oncoprotein in cytologic specimens

OBJECTIVE: To assess the rate of HER2/neu overexpression in cytologic specimens by immunocytochemistry (ICC) and compare these results in matched surgical specimens by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), when available. STUDY DESIGN: All cytologic specimens processed for HER2/neu evaluation by ICC (72 cases) and available corresponding histologic specimens (16 cases) were retrieved from our files. ICC was applied to previously Papanicolaou stained, routine fine needle aspirations specimens (64 cases) and cytocentrifuged, alcohol-fixed, fluid specimens (8 cases). FISH was performed on 6 histologic specimens. RESULTS: Overexpression of HER2/neu was seen in 7/22 breast cancers (31.8%), 3/18 pulmonary adenocarcinomas (16.6%), 2/5 colorectal adenocarcinomas (40%), 1/2 adenocarcinomas of the biliary system (50%), 1/3 thyroid papillary carcinomas (33.3%) and 1/3 prostate adenocarcinomas (33.3%). Sixteen cases had IHC in matched histologic specimens: 14 (87.5%) cases were concordant (11 negative and 3 positive in both specimens), 1 case was negative in the cytologic specimen and positive in the histologic specimen (with no amplification by FISH), and 1 case was positive in the cytologic specimen and negative in the histologic specimen (not informative by FISH). CONCLUSION: Our data suggest that overexpression of HER2/neu oncoprotein can be successfully detected in routine cytologic specimens, providing a simple, fast and cost-effective method of selecting patients for specific treatment.     

Cytology of angiosarcoma in effusions

The cytologic and immunocytochemical findings in pleural effusions from three cases of angiosarcoma are presented. In two of the cases, the primary lesion was on the scalp; in the third case, an angiosarcoma of the small intestine developed after radiotherapy for Hodgkin's disease. Single malignant cells and small clusters of cells were seen in cytologic preparations from two cases while only single cells were seen in preparations from one case. The malignant cells had delicate, finely vacuolated cytoplasm with distinct borders. No specific morphologic features were noted. Immunoperoxidase studies revealed binding of Ulex europaeus and reactivity for vimentin in all three cases and expression of Factor VIII-related protein in two of the cases but no expression of epithelial markers. The clinical history and immunoperoxidase studies are necessary to distinguish angiosarcoma from metastatic adenocarcinoma and other malignancies in effusions.     

The cytopathologic diagnosis of esophageal adenocarcinoma

The diagnostic cytologic features were analyzed in 18 cases of histopathologically proven esophageal adenocarcinoma accessioned at the Johns Hopkins Hospital between 1975 and 1988 for which cytologic material was available. Primary esophageal adenocarcinoma was diagnosed in 15 of 18 cytologic specimens (83%); in 3 cases (17%), carcinoma was suspected, but the changes were nondiagnostic. The most consistent cytologic changes included both architectural features (loss of orientation and nuclear crowding) and criteria of malignancy (high nuclear/cytoplasmic ratios and prominent nucleoli). In the 15 diagnostic cases, the nucleoli were small in 8 and round in 11; in the majority of these cases, the nuclei contained one to three nucleoli. In addition, nuclear and cytoplasmic molding was seen in 9 of these 15 cases, hyperchromasia was present in 8, coarse chromatin clumps were seen in 5, and tissue fragments tended to be multilayered. Review of the three nondiagnostic cases showed that scant material was present in two; the third case had abundant material, but only nondiagnostic changes, suggesting a sampling error. Barrett mucosa was seen in 7 of the 18 cases. These cases show that esophageal adenocarcinoma can be reliably diagnosed on cytologic preparations, based on the consistent architectural features and the usual cellular criteria of malignancy.     

Esophageal tuberculosis. Endoscopic cytology as a diagnostic tool

OBJECTIVE: To study the utility of endoscopic cytology in the diagnosis of esophageal tuberculosis in clinically unsuspected cases. STUDY DESIGN: During a period of four years, endoscopic cytology of esophageal lesions was performed on 228 patients. In eight (3.5%) the cytologic diagnosis of esophageal tuberculosis was suggested on smears. Upon endoscopic examination, the sites of involvement were mid esophagus (five cases), upper esophagus (two cases) and lower esophagus (one case). Linear ulcer was seen in six cases; growth and narrowing of the lumen were seen in one case each. Endoscopic brush smears in seven cases and fine needle aspiration cytology smear in one case were collected. Air-dried smears stained by Giemsa stain were reviewed for detailed cytologic assessment. RESULTS: Smears showed well-defined granulomas with necrosis in five cases and granulomas without necrosis in three. Cytologic evidence of concurrent poorly differentiated squamous cell carcinoma was observed in one case. Tubercle bacilli were demonstrated in five cases. Endoscopic biopsy showed granulomas in three cases and tubercle bacilli in one case. In six cases there was no clinical or radiologic evidence of tuberculosis at other sites, thereby suggesting the possibility of primary esophageal tuberculosis. The remaining two cases had a past history of tuberculosis; one presented with cervical lymphadenopathy and one mediastinal lymphadenopathy. All patients received antitubercular treatment, and the patient with concurrent malignancy also received radiotherapy. All but one of the patients who succumbed to aspiration pneumonia responded to treatment. CONCLUSION: Endoscopic cytology is a useful modality in the diagnosis of esophageal tuberculosis in clinically unsuspected cases.     

Primary cardiac lymphoma initially diagnosed by routine cytology. Case report and literature review

A case of primary cardiac lymphoma initially diagnosed by routine cytologic examination of pericardial fluid is presented. In a 64-year-old woman woman who originally presented with chest pain and heart block, the initial clinical impression was ischemic heart disease. However, coronary angiography failed to reveal significant disease. An echocardiogram demonstrated pericardial fluid, which was drained. A small amount was sent for cytologic examination, and the diagnosis of malignant lymphoma, large cell type, was made. Subsequent radiologic examinations revealed an intracardiac mass involving the atrioventricular canal; surgical biopsy confirmed the diagnosis of a large cell lymphoma. While primary malignant lymphoma of the heart is rare, this case highlights the efficacy of routine cytologic examination of an effusion fluid (often drained therapeutically) in establishing the correct diagnosis.     

Diagnostic accuracy of toluidine blue-stained wet films in effusion cytology

OBJECTIVE: To evaluate the usefulness of toluidine blue-stained wet films in the preliminary cytologic evaluation of serous effusions by means of specificity, sensitivity, and positive and negative predictive value. STUDY DESIGN: One hundred seventy-six samples consisting of 122 pleural and pericardial effusions and 54 peritoneal effusions from 160 patients were included in the study. A toluidine blue-stained wet film of each sample was evaluated, and diagnoses were compared with the diagnoses by conventional smears and cell blocks on the same sample. RESULTS: The sensitivity of wet films was 69%, 68% in pleural and pericardial effusions and peritoneal effusions, respectively, and the specificity of wet films was 93%, 92% in pleural and pericardial effusions and peritoneal effusions, respectively. Positive predictive values of smears alone were 78% and 75%; negative predictive values of smears alone were 96% and 95% in pleural and pericardial effusions and peritoneal effusions, respectively. CONCLUSION: Preliminary cytologic evaluation of serous effusions with toluidine blue-stained wet films is simple and economical. It provides the opportunity to plan additional procedures for the samples.     

Significance of squamous cells in fine needle aspiration cytology of the breast. A review of cases in a seven-year period

OBJECTIVE: To delineate the significance of detecting squamous cells in fine needle aspiration biopsy of breast lesions. STUDY DESIGN: The authors reviewed 15 cases of fine needle aspiration cytology of the breast with a discernible number of squamous cells from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a seven-year period from the start of 1994 to the end of 2001. The cytologic features were correlated with clinical, radiologic and histologic findings, if any. RESULTS: Among the 15 fine needle aspirates of the breast with a discernible number of squamous cells, 5 of them represented metaplastic carcinoma. The remaining consisted of 3 cases of fibroepithelial tumors, 1 case of duct ectasia, 3 cases of subareolar abscess, 2 cases of sclerosed intraduct papilloma and 1 case of benign breast cyst. In general, benign squamous cells were bland looking and often associated with anucleated squames. They were mitotically inactive and could show a good maturation pattern. Tumor cell cannibalism was rare. The presence of abundant, foamy macrophages in the background suggested a benign lesion. The primary diagnosis could be deduced by recognition of other features, such as the presence of myxoid stromal tissue and papillary structures. In contrast, malignant squamous cells in metaplastic carcinoma were more pleomorphic and mitotically active. Dyskeratosis and tumor cell cannibalism were obvious. Tumor diathesis and bizarre-shaped cells were sometimes found. CONCLUSION: Squamous cells occur in fine needle aspirates from a number of benign and malignant breast lesions. Benign conditions with abundant squamous cells may sometimes mimic malignant squamous lesions and vice versa. Careful assessment of the cytologic features of squamous cells and background appearance is crucial for achieving a correct diagnosis.     

Importance of guided fine needle aspiration cytology (FNAC) for the diagnostics of thyroid nodules - own experience

The aim of our study was to assess the accuracy and limitations of ultrasound guided fine-needle aspiration cytology (FNAC) of thyroid nodules. METHODS: The usg-FNAC results of 245 patients with thyroid nodules, who afterwards underwent thyroid surgery or who died, and autopsies were carried out, and compared retrospectively with cytologic results. Patients with malignant cytologic conclusion without histological confirmation after surgery or autopsy were excluded from the study (9 persons). The usg-FNAC results were divided as follows: group 1: diagnosis of malignancy (n = 30), group 2: suspicion of malignancy (n = 28), group 3: benign (n = 126), group 4: inconclusive (n = 29). RESULTS: Assuming the cytologic results of group 1 and group 2 were interpreted as being malignant and those of group 3 as being benign, the sensitivity, specificity and accuracy of usg-FNAC were 90 %, 85 % and 86 % respectively. Comparing the cytologic conclusions between a group of patients with follicular lesions and a subgroup of other lesions a statistically significant difference (p < 0,01) between both subgroups using Fisher's test was found. Sensitivity, specificity and diagnostic accuracy in subgroup of follicular lesions were low (71 %, 63 %, 67 %), while in the subgroup of other lesions were high (94 %, 86 %, 88 %). FNAC can specify the nature of focal lesion with high sensitivity, specificity and diagnostic accuracy in the cases of non-follicular lesions. Histological evaluation is required to specification of the nature in cases in which cytology is indicative of follicular proliferation.     

Cytology of polychrome-stained equine synovial fluid smears. Comparison with clinical findings, histologic specimens, Wright-Giemsa-stained smears and outcome.

Polychrome-stained equine synovial fluid specimens from 34 normal joints and 129 joints with clinical abnormalities were examined cytologically. The smears from joints with abnormalities were categorized as within normal limits (4.7%), slight abnormality (27.9%), proliferative synovitis (21.7%), neutrophilic pattern (20.2%), elongated cell pattern (10.1%), other moderate to marked abnormality (11.6%) and unsatisfactory (3.9%). Cytologic abnormalities that were not restricted to a single category included spindle cells, crystals, stellate cells and cartilage fragments. Multinucleate cells and mononucleate cells with dense cytoplasm and a delicate periphery were seen in smears from cases with clinical diagnoses of osteochondrosis or fracture; interpretation of these cells as osteoclasts and their mononucleate precursors was supported by positive staining with tartrate-resistant acid phosphatase. Smears within the same cytologic category were not found to correspond with a single clinical diagnosis. The identification of several cytologic patterns in cases with the same clinical diagnosis suggests that multiple stages of disease were sampled. Except in cases with the cytologic neutrophilic pattern, there was not a consistent relationship between the histologic features in synovial biopsy specimens and the cytologic findings; the morphologic variation within synovial membrane sections and between sections from different locations was sometimes marked. When compared with air-dried, Wright-Giemsa-stained smears, the polychrome-stained smears were more sensitive in the detection of cytologic abnormalities and were less often falsely negative or unsatisfactory. Following surgery, cases with clinical diagnoses of osteochondrosis (29 cases) and fracture (25 cases) were analyzed according to clinical outcome and cytologic category. While 80% of the horses with proliferative synovitis in cytologic specimens were sound, only 67% of those with the elongated cell pattern, 50% of those with slight abnormality and 33% of those with other moderate to marked abnormality were sound. A statistically significant relationship (P less than .02) was found in cases with a diagnosis of osteochondrosis: animals with a proliferative synovitis pattern were almost three times as likely to be sound as compared to those with slight abnormality. These findings indicate that polychrome-stained equine synovial fluid smears (1) provide information that is different from that found in corresponding histologic sections and (2) are superior to air-dried, Wright-Giemsa-stained smears for cytologic examination. The polychrome-stained equine synovial fluid smears were found to provide information supportive of clinical, radiographic and prognostic data.     

Langerhans cell histiocytosis in lymph nodes. Cytomorphologic diagnosis and pitfalls

OBJECTIVE: To delineate the cytomorphology of Langerhans cell histiocytosis (LCH) in lymph nodes. STUDY DESIGN: Nine histologically documented LCH cases with a prior lymph node aspirate and five more cases in which a cytologic diagnosis of LCH was rendered in a background of corroborative clinical and radiologic findings were included in a retrospective study over a 12-year period (January 1988-January 2000). Papanicolaou- and May-Grünwald-Geimsa-stained smears were reviewed by two independent observers. Staining for S-100 protein was available in four cases. RESULTS: Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. The ages ranged from 5 months to 27 years, with 11 males and 3 females. An initial cytologic diagnosis of LCH had been rendered in six, suspected in four and missed in four. On review, all were reclassified as LCH except two cases, which were still thought to be reactive and necrotizing lymphadenitis. The pathognomic feature of LCH, the "LCH cell," was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in six cases, and plasma cells were rarely seen. CONCLUSION: Lymph node involvement by LCH can be identified by fine needle aspiration in 85% of cases. The presence of the LCH cell is a must. The differentials to be considered are dermatopathic lymphadenitis, sinus histiocytosis with massive lymph-adenopathy, Hodgkin's lymphoma and malignant histiocytosis.