Fine needle aspiration biopsy of hepatocellular carcinoma. Some unusual features.

The cytologic features of fine needle aspiration smears from 28 hepatocellular carcinomas (HCC) were reviewed. All aspirations except one were guided. There were 14 well-, 11 moderately and 3 poorly differentiated HCC. The better-differentiated HCC were characterized by similarity of the tumor cells to hepatocytes (83%), cohesive cell clusters with a trabecular arrangement (72%) and presence of sinusoidal endothelial cells (66%). Other features included bile production (38%), atypical hepatocytic naked nuclei (52%), acinar formation (31%), intracytoplasmic vacuoles (14%) and abnormal vascular patterns (14%). Poorly differentiated HCC showed dyshesive pleomorphic cells. Unusual cytologic features from a well-differentiated HCC with fatty change and an HCC with a prominent acinar component are described. The identification of fatty change in dissociated well-differentiated hepatocytes or cytologic features suggestive of an adenocarcinoma do not preclude the diagnosis of HCC. The usefulness of cell blocks is emphasized.     

Cytologic, cytochemical, immunocytochemical and ultrastructural diagnosis of a sacrococcygeal chordoma in a fine needle aspiration biopsy specimen

The cytologic, cytochemical, immunocytochemical and ultrastructural findings on the aspirated material are presented for the case of a 57-year-old man with sacrococcygeal chordoma diagnosed by fine needle aspiration biopsy. Cytologically, two types of cellular elements were differentiated: medium-sized cells with few cytoplasmic vacuoles and classic physaliferous cells. Both types showed marked cytoplasmic positivity for keratin and S-100 protein; the absence of nuclear positivity in the physaliferous cells was notable. Ultrastructural study demonstrated the existence of true intracytoplasmic vacuoles and frequent rough endoplasmic reticulum-mitochondria complexes. The cytologic differential diagnosis with chondrosarcoma, myxoid liposarcoma, ependymoma and metastases of mucosecretory carcinomas is reviewed.     

Cytologic features of ovarian tumors of low malignant potential in peritoneal fluids

The distinction of ovarian tumors of low malignant potential (OTLMP) from invasive ovarian carcinomas has significant therapeutic and prognostic implications. This study was undertaken to define the cytologic features of OTLMP in peritoneal fluids and to compare them with the cytologic features of invasive carcinomas. Peritoneal fluids from 13 patients with OTLMP and 10 patients with invasive ovarian carcinoma contained neoplastic cells and were reviewed with attention to papillary fragment morphology, cellular pleomorphism and cytoplasmic and nuclear characteristics. Cytologic preparations from patients with OTLMP contained large, cohesive papillary fragments with smooth borders. The neoplastic cells were relatively small and uniform, with high nuclear-cytoplasmic (N/C) ratios (greater than 1:2), few intracytoplasmic vacuoles and inconspicuous nucleoli. Mitotic figures were rare. Peritoneal fluids from patients with invasive ovarian carcinoma contained smaller discohesive papillary fragments with irregular borders. The neoplastic cells were relatively large and pleomorphic, with low N/C ratios (less than or equal to 1:2), abundant intracytoplasmic vacuoles and prominent nucleoli; most preparations contained many single cells and mitotic figures.     

Cytologic findings of ascites from patients with ovarian dysgerminoma

The cytomorphologic observations of ascites from three patients with ovarian dysgerminomas are presented. As compared with those in adenocarcinoma, the cytologic findings in this rare malignant ovarian tumor showed more cells lying isolated or in sheetlike arrangements, fewer cells with discrete cytoplasmic vacuoles, less frequent thickening of the nuclear membrane and more frequent multinucleolation.     

Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy

OBJECTIVE: To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN: Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS: The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION: FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.     

Epithelioid hemangioendothelioma of the lung diagnosed by transesophageal endoscopic ultrasound-guided fine needle aspiration: a case report

BACKGROUND: Epithelioid hemangioendothelioma is a rare vascular tumor of the lung and is also known as intravascular sclerosing bronchoalveolar tumor. Although it has relatively low malignant potential, extensive pulmonary involvement and systemic metastasis have been described. The cytologic features of these tumors are not very well defined, with only few case reports describing the cytologic findings of epithelioid hemangioendothelioma of the lung on fine needle aspiration. CASE: Endoscopic ultrasound-guided fine needle aspiration of a hilar mass was performed on a 25-year-old female. The cytology showed loosely cohesive sheets and clusters of epithelioid cells. The cellular features included large, irregular nuclei with nucleoli and a moderate amount of vacuolated cytoplasm. Rare cells had a suggestion of cytoplasmic lumen formation. Histologic examination of tissue fragments on the cell block revealed a tumor composed of rounded to spindled epithelioid cells in a background of light blue stroma. The endothelial differentiation was evidenced by cytoplasmic vacuoles and lumens, some of which contained erythrocytes. The endothelial nature of these cells was confirmed by positive staining with factor VIII and CD34. CONCLUSION: The cytomorphologic features of epithelioid hemangioendothelioma described in the literature and observed in our case are distinctive and can help with the interpretation of cytologic smears and prevent misdiagnosis.     

Varicella-zoster viral glycoprotein envelopment: ultrastructural cytochemical localization

The periodate-thiocarbohydrazide silver proteinate (PA-TCH-SP) method was used to study the envelopment process in varicella-zoster virus-infected human melanoma cells. Viral envelopment could be seen at two sites, the nuclear membrane and at virus-induced intracytoplasmic vacuoles. Virus-associated glycoconjugates were detected by the PA-TCH-SP method at the plasmalemma and on the inner membrane of the intracytoplasmic vacuoles. Virion envelopes acquired at the nuclear membrane were PA-TCH-SP negative, whereas those acquired at intracytoplasmic vacuoles were PA-TCH-SP positive. All virions found inside these vacuoles contained periodate-reactive envelopes. Release of virions into the extracellular space, where virtually all virions were PA-TCH-SP positive, appeared to be via exocytosis. Thus, the PA-TCH-SP method identifies glycoprotein incorporation at specific cytoplasmic vacuoles distinct from nuclear envelope, endoplasmic reticulum, and Golgi lamellae. These results suggest that envelopment within the cytoplasm is a stage in the assembly of the varicella-zoster virion.     

Deviated formation of intestinal glycocalyx in human stomach cancer cells. Another type of signet ring cell.

The process of glycocalyx formation by the trilaminar membrane was investigated at the subcellular level by use of cultivated cancer cells derived from a human stomach adenocarcinoma. Glycocalyx was apparently synthesized on the characteristic trilaminar membrane of Golgi-derived vesicles which gave rise to cytoplasmic vacuoles which, in turn, fused to form an intracytoplasmic cyst. Characteristic microvilli similar to those of intestinal epithelium extended from the membrane lining the intracytoplasmic cyst. These ultrastructural features agree with earlier histochemical findings in suggesting intestinal metaplasia in the origin of the gastric tumor. The morphologic features of the cancer cells clearly indicated that glycoprotein is first synthesized in the Golgi complex and fully formed mucoprotein then emerges as membrane-bound glycocalyx in the vesicles budding from the Golgi stacks. The glycocalyx layer is an integral part of the external leaflet of the characteristic trilaminar membrane. Abundant deposits of glycocalyx in the intracytoplasmic cyst constituted the ultrastructural basis for a distinctive type of signet ring cell that differed from mucous signet ring cells derived from goblet cells.     

Cytoarchitectural findings in the diagnosis of primary soft tissue tumors

OBJECTIVE: To review the major cytologic and architectural criteria in the diagnosis of primary soft tissue tumors, highlighting the importance of clinical correlation and the value of ancillary methods. STUDY DESIGN: Given the variety and complexity of clinicopathologic entities, the initial approach is based on pattern analysis. Six basic categories are established as a function of cell shape, stromal characteristics and resemblance to normal tissue. RESULTS: First, in myxoid-rich matrix tumors, special attention should be paid to lipoblasts, ganglion type, stellate cells and metachromatic fibrillar matrix. Second, in round cell tumors the following cytoarchitectural findings are of special interest: atypical rhabdomyoblasts, atypical lipoblasts, neuroblast rosettes, cytoplasmic glycogen, melanin pigment, islets of mature cartilage, hyaline cytoplasmic inclusions and fragments of connective tissue closely associated with round cells. Third, in spindle tumors the most important cytoarchitectural findings are: biphasic cellularity; elongated, buckled or wavy, tapered nuclei; nuclear palisades; straight, elongated, blunt-ended nuclei; melanotic pigment; storiform pattern; tissue fragments with collagen fibers or degenerated elastin; intracytoplasmic hyaline globules; and scattered spindle cells in a background of red blood cells. Fourth, in pleomorphic tumors specific typing is often difficult, if not impossible, since cells display few or no differential features. Fifth, in epithelial like cell tumors the cytologic findings of major diagnostic interest are: melanin deposits, crystalline inclusions, intracytoplasmic lumina, anisonucleosis and nuclear cytoplasmic inclusions. Last, in maturelike cell tumors, the architectural pattern resembles that of mature tissues. CONCLUSION: Although cytologic analysis of primary soft tissue tumors is hampered by the paucity of diagnostic findings, the establishment of clinicocytologic correlations, taking into account architectural patterns, cytologic details and clinical characteristics of the lesion, allows precise diagnosis of a significant number of tumors. Application of new techniques (immunocytochemistry, electron microscopy and cytogenetics) to cytologic aspirates has prompted a substantial reduction in the number of doubtful clinicocytologic diagnoses and considerably broadened the diagnostic spectrum.     

Morphologic spectrum of hepatocellular carcinoma in fine needle aspiration biopsies

The light microscopic features of fine needle aspiration smears from 52 primary hepatocellular carcinomas were reviewed. Cytologic grading of these tumors, which indicated three grade I, 29 grade II and 20 grade III carcinomas, was compatible with grading done by histologic examination. In addition to the general cellular characteristics, other cytologic features observed in the smears included bile (48% of the cases), large cytoplasmic vacuoles (23%), small cytoplasmic vacuoles (46%), eosinophilic cytoplasmic inclusions (8%), basophilic cytoplasmic inclusions (48%) and intranuclear cytoplasmic inclusions (71%). The significance of these features is briefly discussed.     

Fine needle aspiration cytology of insular thyroid carcinoma. A report of four cases.

Four cases of poorly differentiated (insular) thyroid carcinoma (ITC) that underwent preoperative fine needle aspiration cytology were studied for the main cytologic features. Although ITC shows heterogeneity of histologic patterns, there are some cytologic characteristics suggesting the correct diagnosis, such as the presence of high cellularity, with large sheets of tumor cells showing a microfollicular pattern or smaller sheets showing a solid or trabecular pattern, intermingled with predominantly single cells on a hematic background with very scanty colloid. Nuclear overlapping is constant. The cytoplasm is poorly outlined, when present. Nuclear hyperchromasia is always present, with coarsely or finely granular chromatin. The variation in nuclear shape and size is moderate, with small nucleoli and occasional mitoses. A papillary arrangement, with the presence of intranuclear cytoplasmic inclusions (vacuoles) and nuclear grooves, is also visible.     

Logistic regression analysis of high grade spindle cell neoplasms. A fine needle aspiration cytologic study.

OBJECTIVE: To identify primary diagnostic cytologic criteria for various high grade spindle cell neoplasms. STUDY DESIGN: We reviewed 30 osteosarcomas, 29 malignant fibrous histiocytomas (MFH), 26 malignant melanomas, 13 chondrosarcomas, 12 leiomyosarcomas, 7 angiosarcomas and 5 liposarcomas. All specimens were coded as to the presence or absence of the following variables: high or low cellularity, tissuelike fragments, glandlike fragments, single cells, binucleated cells, multinucleated cells, lipoblastlike cells, histiocytelike cells, fibroblastlike cells, signet-ring cells, short spindle cells, long filamentous cells, stellate cells, osteoclastic giant cells, malignant giant cells, background cells, pointed nuclei, cigar-shaped nuclei, fishhook-shaped nuclei, round or ovoid nuclei, intranuclear vacuoles, macronucleoli, small nucleoli, mitotic figures, abnormal mitotic figures, pleomorphism, nuclear/cytoplasmic ratio (mild, moderate, marked increase), amount of cytoplasm (scant, moderate, abundant), fine or coarse granular cytoplasm, intracytoplasmic hemosiderin deposits, melanin, cytoplasmic vacuoles, fat, capillary vessel fragments, storiform pattern, necrosis, large or small amount of myxoid material, filamentous stroma, dense collagenous stroma, osteoid, chondroid and cells in lacunae. A logistic regression analysis was performed to identify the variables predictive of each diagnostic category. RESULTS: The statistical analysis selected positive expression of osteoid, osteoclastic giant cells and low cellularity as the primary criteria associated with osteosarcomas. Positive expression of fibroblastlike cells, large amount of myxoid material and multinucleated cells were identified to be the key criteria for MFH. The analysis selected the presence of melanin as the major criterion for malignant melanomas, cells lying in lacunae for chondrosarcomas, fishhook nuclei for leiomyosarcomas, intracytoplasmic iron deposits for angiosarcomas and lipoblastlike cells for liposarcomas. CONCLUSION: From the previously described cytologic criteria, statistical analysis helped identify several key features that are significant in the evaluation of pleomorphic spindle cell neoplasms.     

Medullary thyroid carcinoma. Rare cytologic findings

OBJECTIVE: To describe some rare cytologic findings in medullary thyroid carcinoma. STUDY DESIGN: Review of the fine needle aspiration smears from 15 cases of medullary thyroid carcinoma that were confirmed on histologic sections. The ages ranged between 31 and 67 years; 10 were female and 5 male. Thirteen were sporadic forms, and two were familial forms. RESULTS: Eight cases were classified as pleomorphic cell type and seven as monomorphic cell type. The smears revealed round, oval, triangular, polygonal and spindle-shaped cells, intracytoplasmic red granules, occasional intranuclear inclusions, amyloid, binucleated and multinucleated cells, and thick, granular chromatin. CONCLUSION: The rare cytologic findings in this study were grape cells, cytoplasmic nippling, elongated cytoplasmic processes, carrot-shaped nuclei, nuclear buddings, mast cell-like cells and a Burkitt's lymphoma-like appearance. These findings were rarely reported before.     

Signet-ring follicular adenoma of the thyroid diagnosed by fine needle aspiration. Report of a case with cytologic description

BACKGROUND: Follicular cells of the thyroid may undergo squamous, oncocytic or clear cell metaplastic changes. Of these, the clear cell change with signet-ring formation is the most unusual, and follicular adenoma of the thyroid with signet-ring formation is extremely rare. We describe for the first time the cytologic features of a clear cell adenoma of the thyroid obtained by fine needle aspiration (FNA). CASE: A 48-year-old woman in a euthyroid state presented with a 2-cm, right-sided thyroid nodule. Smears obtained by FNA of the nodule revealed clusters of large signet-ring cells in a bloody background. The signet-ring cells were round to oval, with large cytoplasmic vacuoles and hyperchromatic, eccentric nuclei. Colloid in the background was very scanty. Histologic examination of the right hemithyroidectomy specimen revealed a signet-ring follicular adenoma. CONCLUSION: Lack of familiarity with signet-ring cell adenoma of the thyroid could lead to an erroneous diagnosis of metastatic signet-ring cell carcinoma.     

Cytologic features of chordoid meningioma. A case report

BACKGROUND: Chordoid meningioma is a rare subtype of meningioma characterized by myxoid matrices deposited among epithelioid or vacuolated tumor cells and infiltrates of inflammatory cells, and its cytologic features have rarely been reported. CASE: A 57-year-old man with a history of headache and visual disturbance presented with a tumor in the suprasellar region. Intraoperative touch smear cytology of the tumor disclosed a cord-like arrangement of polygonal tumor cells occasionally containing intranuclear inclusions. Furthermore, periodic acid-Schiff-positive, mucinous matrices were deposited among the tumor cells. Also, infiltrates of lymphocytes and plasma cells were noted. Histologic, immunohistochemical and ultrastructural examination confirmed the diagnosis of chordoid meningioma. CONCLUSION: Intraoperative smear cytology in a case of chordoid meningioma showed distinctive cytologic features suggestive of the histologic patterns. The cytologic features, together with a histologic examination, are useful for its diagnosis.     

Paratesticular spindle cell rhabdomyosarcoma diagnosed by fine needle aspiration cytology: a case report

BACKGROUND: Spindle cell rhabdomyosarcoma is a rare, newly identified subtype ofembryonal rhabdomyosarcoma with improved behavior and a predilection for the paratesticular area. Fine needle aspiration (FNA) cytology findings of embryonal rhabdomyosarcoma have been described. However, there is no previous report on the cytologic findings of spindle cell rhabdomyosarcoma at testicular or extratesticular sites. CASE: A 13-year-old boy presented with a large, right sided scrotal mass. Fine needle aspiration (FNA) was performed for rapid diagnosis. The smears revealed numerous spindle cells and large fragments of cytoplasmic processes with cross-striations and were diagnosed as spindle cell rhabdomyosarcoma. The histologic sections were also diagnosed as spindle cell rhabdomyosarcoma. CONCLUSION: The cytologic findings of this rare tumor have not been reported before. The cross-striations were easily identified in FNA smears, so the diagnosis of spindle cell rhabdomyosarcoma was made confidently. The histologic sections showed only spindle cells with different patterns of arrangement, resembling leiomyosarcoma. The cross-striations were not identified in the histologic sections. In this case cytologic diagnosis aided the histologic diagnosis.     

Analysis of number, size and distribution patterns of lipid vacuoles in benign and malignant mesothelial cells

A quantitative analysis of the lipid vacuoles in benign hypertrophic and neoplastic mesothelial cells, using a size-independent distribution index, showed that computer-assisted image analysis for distribution patterns of cytoplasmic components can aid in distinguishing benign from malignant cells. Benign mesothelial cells had fewer lipid vacuoles, which were smaller and predominantly found around the nuclei. It is argued that, due to the high surface tension in the lipid vacuoles, the largest vacuoles are found in the center of the cells, which is the least flattened part of the air-dried mesothelial cells. It seems likely that the distribution pattern of rigid substructures, such as lipid vacuoles, varies between histologic and cytologic material as well as between cells processed by different cytologic methods with various cell-flattening artifacts. The study of the distribution of cytoplasmic components that differ in size was enhanced by using the defined size-independent distribution index, which incorporates the radius of the cell, the radius of the vacuoles and their respective centers of gravity.     

Accuracy of cytology vs. microbiopsy for the diagnosis of well-differentiated hepatocellular carcinoma and macroregenerative nodule. Definition of standardized criteria from a study of 100 cases

OBJECTIVE: To determine the accuracy of ultrasound (US)-guided fine needle aspiration (FNA) for the diagnosis of well-differentiated hepatocellular carcinoma (wd HCC) and macroregenerative nodule (MRN) and to identify the most useful cytologic and histologic criteria to distinguish between those two diagnoses. STUDY DESIGN: Cytologic and histologic specimens of 50 wd HCC and 50 MRN were reviewed blindly and the diagnosis compared to the final clinical diagnosis. Twenty-eight cytologic and 25 histologic criteria were examined and subjected to statistical analysis. RESULTS: Among 100 cases studied, the final diagnosis was available for 43. In those 43 cases, combining analysis of cytologic and histologic specimens, the sensitivity of US-guided FNA was of 75% and the specificity 100%. Cytologic analysis was better than isolated histologic analysis, with a sensitivity of 75% vs. 68%, respectively. Sensitivity of cytologic diagnosis was lower for smaller nodules and for those located in poorly accessible hepatic segments. With the use of stepwise logistic regression analysis, four cytologic features (increased nuclear/cytoplasmic ratio, cellular monomorphism, nuclear crowding, loss of bile duct cells) and four histologic features (increased nuclear/cytoplasmic ratio, decreased Kupffer cells, cellular monomorphism, increased trabeculae thickness) were identified as predictive of HCC.     

Cytologic presentation of alveolar soft-part sarcoma of the vagina. A case report

Alveolar soft-part sarcoma primary in the vagina is an exceptionally rare neoplasm. The cytologic features in a case of this rare sarcoma are described, with a discussion of the differential diagnosis. Structures suggestive of the characteristic PAS-positive, diastase-resistant cytoplasmic crystals were seen in the cytologic specimen; the crystals were well-demonstrated in the histologic material and at the electron microscopic level.     

Molluscum contagiosum. A case report with fine needle aspiration cytologic diagnosis and ultrastructural features

BACKGROUND: Cytomorphologic and ultrastructural features of molluscum contagiosum, a rare skin lesion of viral etiology, are presented. CASE: A 4-month-old female was referred for fine needle aspiration cytology of papules over the back and chest wall. A Giemsa-stained preparation of whitish material aspirated from the chest wall nodule showed numerous large, intracytoplasmic, basophilic bodies that pushed the host cell nucleus to the periphery, giving a signet-ring appearance to a few cells. A cytologic diagnosis of molluscum contagiosum was suggested. On electron microscopy numerous intracytoplasmic viral particles were demonstrated, thus confirming the cytologic diagnosis. CONCLUSION: In clinically unsuspected cases, the cytologic diagnosis of molluscum contagiosum can be suggested by demonstrating pathognomonic molluscum bodies in aspirated material.