Coexpression of glial fibrillary acid protein, keratin and vimentin. A unique feature useful in the diagnosis of pleomorphic adenoma of the salivary gland in fine needle aspiration biopsy smears

Positive staining for glial fibrillary acidic protein (GFAP) of tumor cells in fine needle aspirates of 11 of 12 pleomorphic adenomas of the parotid gland is reported. Tumor cells in these neoplasms also coexpressed keratin and vimentin to varying extents. Coexpression of GFAP, keratin and vimentin in tumor cells in aspirates is an unusual feature, so far demonstrated only in pleomorphic adenomas. Thus, intermediate filament typing may help to distinguish: (1) pleomorphic adenomas of the salivary glands from head and neck tumors of nonsalivary gland origin; (2) intracranial metastases of malignant mixed tumors of the salivary gland from gliomas; and (3) pleomorphic adenomas from extracranial gliomas.     

Fine needle aspiration cytology of primary soft tissue tumors. Morphologic analysis of the most frequent types.

We reviewed 98 cases of fine needle aspiration of soft tissue tumors with histologic confirmation performed during an eight-year period and propose a working morphologic classification based on the most prominent cytologic features. Six main tumor groups are recognized: myxoid, round cells, spindle cells, pleomorphic cells, polygonal cells and well differentiated. We believe that this classification allows recognition of the most common soft tissue tumors while helping with the differential diagnosis of other neoplasia, primary or secondary, with similar morphology and a similar presentation.     

Fine needle aspiration biopsy cytology of paragangliomas. Cytologic, light microscopic and ultrastructural studies of three cases

Paragangliomas are uncommon tumors arising in paraganglion tissue, which is especially well represented in the head and neck. In our hospital three head and neck masses recently proved to be paragangliomas on aspiratory biopsy cytology, with subsequent histologic confirmation. One was an apparently benign carotid body tumor, while the others were metastatic nasopharyngeal paragangliomas. The latter two tumors were clearly malignant, with roentgenographically proven pulmonary metastases in one and widespread lymph node involvement in the other. Histologically all were vascular tumors composed of large cells with abundant cytoplasm and pleomorphic, sometimes bizarre nuclei. These characteristic chief cells were clearly evident on cytology, with pleomorphic nuclei, prominent nucleoli, clumped chromatin and generally eosinophilic, finely granular or reticular cytoplasm. However, the distinction between benign and malignant tumors depended on the presence of mitoses or a tumor diathesis. Cytology seems to be able to provide a diagnosis of paraganglioma and, in these cases at least, an estimation of the biologic behavior.     

MET Gene Copy Number Alterations and Expression of MET and Hepatocyte Growth Factor Are Potential Biomarkers in Angiosarcomas and Undifferentiated Pleomorphic Sarcomas

Soft tissue sarcomas are a heterogeneous group of tumors with many different subtypes. In 2014 an estimated 12,020 newly diagnosed cases and 4,740 soft tissue sarcoma related deaths can be expected in the United States. Many soft tissue sarcomas are associated with poor prognosis and therapeutic options are often limited. The evolution of precision medicine has not yet fully reached the clinical treatment of sarcomas since therapeutically tractable genetic changes have not been comprehensively studied so far. We analyzed a total of 484 adult-type malignant mesenchymal tumors by MET fluorescence in situ hybridization and MET and hepatocyte growth factor immunohistochemistry. Eleven different entities were included, among them the most common and clinically relevant subtypes and tumors with specific translocations or complex genetic changes. MET protein expression was observed in 2.6% of the cases, all of which were either undifferentiated pleomorphic sarcomas or angiosarcomas, showing positivity rates of 14% and 17%, respectively. 6% of the tumors showed hepatocyte growth factor overexpression, mainly seen in undifferentiated pleomorphic sarcomas and angiosarcomas, but also in clear cell sarcomas, malignant peripheral nerve sheath tumors, leiomyosarcomas and gastrointestinal stromal tumors. MET and hepatocyte growth factor overexpression were significantly correlated and may suggest an autocrine activation in these tumors. MET FISH amplification and copy number gain were present in 4% of the tumors (15/413). Two samples, both undifferentiated pleomorphic sarcomas, fulfilled the criteria for high level amplification of MET, one undifferentiated pleomorphic sarcoma reached an intermediate level copy number gain, and 12 samples of different subtypes were categorized as low level copy number gains for MET. Our findings indicate that angiosarcomas and undifferentiated pleomorphic sarcomas rather than other frequent adult-type sarcomas should be enrolled in screening programs for clinical trials with MET inhibitors. The screening methods should include both in situ hybridization and immunohistochemistry.     

Spontaneous infarction of a parotid gland pleomorphic adenoma. Report of a case with cytologic and radiographic overlap with a primary salivary gland malignancy.

Pleomorphic adenoma is the most common neoplasm of the parotid gland, generally presenting as a slowly enlarging, firm, well-circumscribed, painless nodule. Occasional cases have presented after a short period of rapid growth or have been associated with pain. The vast majority of these tumors are solid, but rare examples have been associated with cystic degeneration or hemorrhage. Spontaneous and tumor-associated infarction of the parotid has been reported, but these examples have been limited to infarctions of Warthin's tumors and postoperative infarctions of salivary glands. We present the case of a 48-year-old male with a one-year history of a painful, enlarging, left parotid mass associated with paresthesia of the tongue. Computed tomographic examination of the parotid demonstrated a left superficial lobe mass with a rim of enhancement and low attenuation center. Fine needle aspiration yielded necrotic debris and atypical squamous elements that were thought to be compatible with carcinoma. A superficial parotidectomy with intraoperative frozen section revealed a pleomorphic adenoma with extensive central necrosis. To our knowledge, this represents the first reported case of an infarcted pleomorphic adenoma and illustrates the potential for misinterpretation of these cytologic and radiologic findings as indicative of malignancy.     

Myoepithelioma of the salivary glands. Fine needle aspiration biopsy findings

OBJECTIVE: To evaluate the cytologic findings and pitfalls in the diagnosis of myoepithelioma of the salivary glands. STUDY DESIGN: Smears from 7 cases of myoepithelioma of the salivary glands, 3 plasmacytoid, 2 spindle and 2 mixed types, all histologically confirmed, were evaluated with special attention to cytologic features that may be helpful for the diagnosis. RESULTS: A correct cytologic diagnosis was not made in any of the cases. Three were diagnosed as plasmacytomas or cellular pleomorphic adenomas, 2 as benign spindle cell tumors and 2 as cellular pleomorphic adenomas. Mitoses and marked pleomorphism were absent. Nuclear striations were noted frequently. CONCLUSION: Diagnosis of myoepithelioma was difficult on fine needle aspiration smears. Nuclear striations (zebra lines) were noted in 5 cases. This finding is not reported in previously published papers.     

Leiomyoblastoma of the lesser omentum sac. A case report

Localization of primary solid tumors on the omentum is rare and of leiomyoblastoma exceptional. A 57-year-old patient presented on the omentum an encapsulated, lumpy tumoral formation, 9 x 4.5 x 2.5 cm, with whitish-grey and hemorrhagic cystic zones. Predominant histopathologically were images of leiomyoblastoma infiltrated with fascicular and pleomorphic zones, recent thrombosis and hemorrhage. The postoperative evolution was satisfactory after three years.     

Fine needle aspiration and touch imprint cytology of a malignant fibrous histiocytoma of the spermatic cord. Case report

BACKGROUND: No cytologic reports on spermatic cord sarcomas have been published. CASE: A 64-year-old man presented with a slowly growing, painless, left spermatic cord enlargement. Fine needle aspiration (FNA) obtained < 1 mL of bloody fluid consisting of solitary, mark-edly anaplastic and pleomorphic tumor giant cells occasionally arranged in small fragments. Rare atypical spindle cells could be observed. Some reactive lymphocytes were observed intermingled with tumor cells. Immunohistochemistry displayed vimentin reactivity and negativity for keratins and leukocytic common antigen. The specimen removed showed a well-circumscribed, 30-mm, yellowish solid tumor. Touch imprints displayed pleomorphic tumor cells showing intense anisonucleosis; a moderate amount of clear, sometimes microvacuolated cytoplasm; and tissue fragments with a storiform pattern. Histologic examination revealed microscopic and immunohistochemical features of malignant fibrous histiocytoma (MFH) arising in soft tissues of the spermatic cord. CONCLUSION: FNA of a spermatic cord lesion may reveal a pleomorphic sarcoma. A pleomorphic appearance together with some spindle elements and compatible immunocytochemistry could help diagnose spermatic cord MFH. This is one of the few reports dealing with FNA cytology of paratesticular tumors and the first report, to the best of our knowledge, showing the cytologic characteristics of a case of spermatic cord MFH.     

A cell line from pleomorphic adenoma of the rat salivary gland

Pleomorphic adenoma of rat salivary gland is extremely rare, and culture of cells obtained from rat salivary gland tumors has not been reported. We have established a long-term cell line from a pleomorphic adenoma of a Sprague-Dawley rat submaxillary gland. The pleomorphic adenoma was composed of oval or spindle-shaped cells occasionally forming a small duct. Alcian blue-positive intercellular matrices, consisting mainly of glycosaminoglycans, were abundant. The cultured cells showed characteristics similar to those of the original tumor. This cell line should be useful for biological and biochemical studies of glycosaminoglycan-synthesis of pleomorphic adenoma cells.     

Metastatic carcinoma with myxoid stroma in the salivary gland: a case report

BACKGROUND: Most epithelial salivary gland tumors with a myxoid stroma are pleomorphic adenomas. Rare metastatic carcinomas have prominent myxoid stroma and therefore can mimic pleomorphic adenomas cytologically. CASE: A 62-year-old man presented with a left canthal tumor. A biopsy and computed tomography revealed an adenocarcinoma of the left ethmoid sinus with medial canthal extension. The patient was treated with tumor resection and chemoradiation. An enlarging, left parotid mass developed that was reported as a pleomorphic adenoma on a fine needle aspirate. However, a parotidectomy showed metastatic adenocarcinoma with a myxoid and fibroblastic stroma in an intraparotid lymph node. CONCLUSION: Before concluding cytologically that a biphasic epithelial/myxoid stromal salivary gland lesion is a pleomorphic adenoma, the patient's previous malignancies should be reviewed, and the smears should be scrutinizedfor the absence of diffuse epithelial atypia and presence of spindle cells transitional between the 2 tissue phases.     

Fine needle aspiration cytology of epithelial-myoepithelial carcinoma of salivary glands. A report of three cases.

BACKGROUND: Epithelial-myoepithelial carcinoma is a rare, low grade malignant tumor of the salivary glands. Histologically, it has a biphasic cellular composition and exhibits a high degree of differentiation. The fine needle aspiration cytology of this rare tumor is rarely described in the literature. CASES: We report the fine needle aspiration cytology of three epithelial-myoepithelial carcinomas, arising in the right parotid, left parotid and minor salivary gland of the hard palate. Cytology showed a biphasic population consisting of cells of ductal epithelial and myoepithelial origin arranged in small clusters and sheets. The myoepithelial cells had small, uniform nuclei; ample, clear cytoplasm and distinct cell borders, while the ductal epithelial cells had larger, mildly pleomorphic nuclei and scanty cytoplasm. These ductal cells tended to form tubules among background sheets of clear myoepithelial cells. This feature, if present, was an important diagnostic clue. Hyaline material surrounding cell clusters and focal adenoid cystic carcinoma-like areas with orangeophilic globules were also not uncommon. CONCLUSION: While the cytologic appearance of epithelial-myoepithelial carcinoma may closely mimic that of other salivary gland tumors, such as adenoid cystic carcinoma, pleomorphic adenoma and basal cell adenoma, certain peculiar cytologic features may allow a distinction to be made on fine needle aspiration biopsy.     

Accuracy of the analysis of multiple small fragments of glial tumors obtained by stereotactic biopsy.

To examine the reliability of the diagnoses reached on multiple small fragments of cerebral glial tumors obtained via stereotactic biopsy, samples obtained from 100 consecutive glial tumors (during real or simulated biopsy) were studied by cytology and histology. In comparison to the definitive diagnosis made on the whole tumor, a correct positive diagnosis on the biopsy sample was made by histology in 96% of cases and by cytology in 93% of the cases (with 96% correct results when combining both methods). A correct identification of the tumor type and grade was achieved by histology in 82% of cases and by cytology in 80% of the cases (with 85% correct results when combining both methods). The limits of stereotactic biopsy are related to the difficulty of identifying all of the typical tumor features on tiny tissue fragments of a pleomorphic neoplasm, such as a glioma. This study demonstrates that better results may be obtained by using both cytology and histology to study multiple stereotactic biopsy samples from glial tumors.     

Pleomorphism and acetylene-reducing activity of free-living rhizobia.

Cowpea-type Rhizobium sp. strain 32H1 and Rhizobium japonicum USDA 26 and 110 grown on a glutamate-mannitol-gluconate agar medium showed increases in the number of pleomorphic cells coincident with their acetylene-reducing activity. Pleomorphs appeared to be inhibited in growth nonuniformly, because acetylene-reducing cultures were mixtures of rod, branched (V, Y, and T), and other irregularly shaped cells. In contrast, strain USDA 10 consistently failed to reduce acetylene, even though it also could grow and yield pleomorphic cells under various conditions. With minimal inhibitory supplements (5 micrograms per ml of medium) of nalidixic acid and novobiocin as cell division inhibitors, an increase in pleomorphic cells was observed, but the inhibited cultures displayed lower acetylene-reducing activity. A study of pleomorphic cells derived in different ways indicated that not all pleomorphs reduce acetylene.     

Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous features: a report of 2 cases

BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs) include both benign and malignant entities, such as benign soft tissue giant cell tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of breast cancer. CASES: We report the cytologic features, pathologic findings and immunohistochemical profile in 2 cases of this unusual variant of breast carcinoma. Two women aged 53 and 50 years women presented with a history of left and right breast lump but no local lymphadenopathy, respectively. Fine needle aspiration cytology (FNAC) of both cases revealed abundant MGC with highly pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous differentiation with multinucleated syncytiotrophoblast-like giant cells is extremely rare in breast tumors. Although rare, FNAC of breast cancer with pleomorphic MGC requires careful search for differential diagnosis; breast carcinoma with giant cell features (choriocarcinomatous features, OGC features) must be differentiated from metastatic tumors and other breast lesions containing giant cells.     

Eosinophilic globule cells in mouse MFH-like sarcomas. Light and electron microscopic studies

Light and electron microscopic observations were made on eosinophilic globule (EG) cells found in 27 subcutaneous malignant fibrous histiocytoma (MFH)-like sarcomas in aged ICR mice. These tumors, which were composed of fibroblast-like cells as the major component, with small numbers of histiocyte-like cells and undifferentiated cells, showed one or more of five growth patterns: storiform, pleomorphic, fascicular, myxoid, and hemangiopericytoma-like. EG cells were interspersed among the tumor cells and were also present in metastatic lesions. They were pleomorphic in shape and contained various numbers of cytoplasmic globules, which were positive with the periodic acid-Schiff reaction and resistant to diastase digestion. Electron microscopic observation revealed that these cells had small finger-like and pseudopodia-like projections, and contained varied numbers of characteristic osmiophilic globules and glycogen particles in the cytoplasm which seemed to become more abundant as the cells differentiated. The osmiophilic globules consisted of a dense homogeneous core and a marginal area rich in small vesicular membranous structures. A small population of EG cells exhibited features suggesting differentiation to fibroblasts; these were characterized by an increased amount of rough endoplasmic reticulum. It is suggested that the EG cell is a neoplastic cell, perhaps derived from a primitive mesenchymal cell, although an inflammatory cell origin is also possible.     

Pleomorphic lobular carcinoma of the breast. A case report

BACKGROUND: Pleomorphic lobular carcinoma of the breast is associated with aggressive behavior. CASE: Fine needle aspiration cytology was performed on a breast lump in a 55-year-old woman. The aspirates showed highly pleomorphic, large cells in a dyscohesive pattern, with a tendency of few cells to aggregate in small groups. A diagnosis of ductal carcinoma was made on cytology. On histology, the paraffin sections showed features of pleomorphic lobular carcinoma of the breast. CONCLUSION: The cytologic features of pleomorphic lobular carcinoma overlap with those of infiltrating ductal carcinoma. It is very difficult to make a diagnosis of pleomorphic lobular carcinoma prospectively on cytology. However, if Indian file arrangement and cytoplasmic vacuolation are present, pleomorphic lobular carcinoma must at least be suggested for the differential diagnosis as it has different clinical implications.     

P63 is expressed in basal and myoepithelial cells of human normal and tumor salivary gland tissues.

p63 is essential for epithelial cell survival and may function as an oncogene. We examined by immunohistochemistry p63 expression in human normal and tumor salivary gland tissues. In normal salivary glands, p63 was expressed in the nuclei of myoepithelial and basal duct cells. Among 68 representative salivary gland tumors, 63 displayed p63 reactivity. In all tumor types differentiated towards luminal and myoepithelial lineages (pleomorphic adenomas, basal cell adenomas, adenoid cystic carcinomas, and epithelial-myoepithelial carcinomas), p63 was expressed in myoepithelial cells, whereas luminal cells were always negative. Similarly, in mucoepidermoid carcinomas, basal, intermediate, and squamous cells expressed p63, in contrast to luminal mucous cells. p63 reactivity was also restricted to basal cells in Warthin tumors and oncocytomas. Myoepitheliomas and myoepithelial carcinomas all expressed p63. The only five negative tumors were three of four acinar cell carcinomas and two of three adenocarcinomas. In conclusion, p63 is expressed in the nuclei of normal human salivary gland myoepithelial and basal duct cells. p63 expression is retained in the modified myoepithelial and basal cells of human salivary gland tumors, which suggests a role for p63 in oncogenesis of these complex tumors.     

Cytomorphology of lipomatous tumors of soft tissue

OBJECTIVE: To evaluate the cytomorphologic features of benign and malignant lipomatous tumors of soft tissue on fine needle aspirates (FNA) and determine if the variants of liposarcoma could be identified. STUDY DESIGN: FNA of histologically documented benign (51 cases) and malignant (39 cases) lipomatous tumors were reviewed. Twenty-six of the 51 FNA from lipomas and 34 of the 39 FNA from malignant lipomatous tumors were satisfactory for evaluation. RESULTS: FNA from 26 cases of lipomas were cellular, with lobulated, fibroadipose tissue. Thin and thick capillaries were seen in 92% and 65% of cases, though a chicken wire vascular pattern was seen in only 4 cases (15%). A cytodiagnosis of liposarcoma could be made in 23 cases (88%), and these could be further subtyped into well-differentiated (4 cases), myxoid (8), pleomorphic (4), round cell (3) and liposarcoma, ?type (4). Only 50% of the well-differentiated liposarcomas, 3 of the 10 pleomorphic liposarcomas and 8 of the 17 myxoid liposarcomas were diagnosed as such on FNA. Cytologic diagnosis of the remaining 9 cases of myxoid liposarcoma were pleomorphic liposarcoma (1); liposarcoma, ?type (3); malignant mesenchymal tumor (1); suspicious for malignancy (2); and benign (2). There were no false positives, but there were 3 false negative cases (1 well-differentiated and 2 myxoid liposarcoma). CONCLUSION: Lipomas can be diagnosed readily. Arborizing vessels can be seen in lipomas and should be interpreted with caution. Subclassification of liposarcomas on FNA is possible but not very reliable. Myxoid liposarcomas pose a problem, and aspirates from them can mimic a wide range of morphologic subtypes. The role of FNA in identification of variants of liposarcoma is limited.     

Malignant phyllodes tumor metastatic to the lung with osteogenic differentiation diagnosed on fine needle aspiration biopsy. A case report

BACKGROUND: Osteosarcomatous differentiation in malignant phyllodes tumors is rare. No cases of either primary or metastatic lesions were identified in the literature that were initially diagnosed on fine needle aspiration biopsy. CASE: Cytologic and histologic findings of a metastatic malignant phyllodes tumor with osteosarcomatous differentiation in a 63-year-old woman are presented. This case was diagnosed initially on fine needle aspiration biopsy and confirmed with histologic examination of the pulmonary lesion. CONCLUSION: Although rare, the differential diagnosis of metastatic phyllodes tumor should be considered in the appropriate clinical setting when examining a pleomorphic spindle cell tumor with heterologous elements on fine needle aspiration biopsy.     

Epithelial myoepithelial carcinoma of the parotid gland with malignant ductal and myoepithelial components arising in a pleomorphic adenoma: a case report with cytologic, histologic and immunohistochemical correlation

BACKGROUND: To describe the cytologic, histologic and immunohistochemical findings of a case of epithelial myoepithelial carcinoma (EMC) arising from a pleomorphic adenoma (PA) of the parotid with both malignant epithelial and myoepithelial components. CASE: A 29-year-old female presented with a 1.5 x 1.5-cm, palpable mass of the left parotid of 7-8 months' duration with recent enlargement and pain. Fine needle aspiration biopsy (FNAB) revealed biphasic epithelial (small cell) and myoepithelial (large/clear cell) clusters arranged in a pseudopapillary and trabecular pattern with abundant hyaline material with many naked nuclei, together with areas typical of pleomorphic adenoma (PA) was noted. The cytology was reported as salivary gland neoplasm, "suggestive of adenoid cystic carcinoma, less likely pleomorphic adenoma." The mass was excised and histologically reported as "pleomorphic adenoma, with focal invasion of one resected margin." Four months later the tumor recurred, and FNAB showed almost the same cytologic features as did the previous aspirate. Due to early recurrence, previous histologic sections were reviewed, and typical areas of a biphasic pattern of EMC with atypicality and mitosis of both components was found. The final diagnosis was EMC ex PA. CONCLUSION: Although previous reports mention the difficulties in diagnosing EMC and differentiation from the more common salivary gland neoplasms such as PA, we like to emphasize the cytologic confusion that results when the tumors coexist.