Cytology of primary pulmonary mucoepidermoid and adenoid cystic carcinoma. A report of four cases

BACKGROUND: Mucoepidermoid and adenoid cystic carcinomas are very rare primary pulmonary neoplasms that can be classified under the broader heading of salivary gland-like neoplasms (SGN). Both entities need to be considered in the cytologic differential diagnosis of lung tumors. We reviewed cytologic findings in primary pulmonary neoplasms diagnosed at our institution during the time period 1981 to the present along with outside consultation cases. CASES: Three cases of primary mucoepidermoid carcinoma and one case of primary adenoid cystic carcinoma of the lung were diagnosed based on cytology during the period examined. Patient ages were 16, 25, 47 and 78 years, respectively. The mucoepidermoid cytology specimens were composed of three cell types, mucinous, squamous and intermediate cells, at times associated with extracellular mucin. The adenoid cystic carcinoma consisted of small, uniform cells with dark nuclei, scant cytoplasm and associated, acellular balls of basement membrane material. CONCLUSION: The differential diagnosis for primary pulmonary neoplasms needs to include the rare SGN. Cytologic features of adenoid cystic carcinoma are diagnostic; those of mucoepidermoid carcinoma are at least suggestive.     

Fine needle aspiration (FNA) cytology of adenoid cystic carcinoma and adenomyoepithelioma of breast: two lesions rich in myoepithelial cells

Adenoid cystic carcinoma and adenomyoepithelioma are relatively rare, but well described, breast lesions. The FNA cytology features in two cases of mammary adenoid cystic carcinoma and two cases of adenomyoepithelioma are described. In both cases of adenoid cystic carcinoma, aspirates consisted of tightly cohesive clusters of cells arranged around spheres and interconnecting cylinders of acellular material. The two aspirates of adenomyoepithelioma were composed of large tightly cohesive clusters of cells associated with small amounts of stromal material. In all four aspirates a dual population of epithelial and myoepithelial cells could be identified within cellular aggregates, and numerous bare nuclei were present. Histology revealed the characteristic features of adenoid cystic carcinoma and adenomyoepithelioma. Immunohistochemical staining of histological sections for S‐100 protein and alpha‐smooth muscle actin confirmed the presence of large numbers of myoepithelial cells within all four lesions, providing indirect evidence that bare nuclei in breast aspirates represent myoepithelial cells. The presence of a dual population of epithelial and myoepithelial cells and of numerous bare nuclei within a breast aspirate is generally indicative of a benign lesion. This is not always the case, as adenoid cystic carcinoma is a malignant tumour, and adenomyoepithelioma, while generally exhibiting benign behaviour, is capable of local recurrence and distant metastasis.     

Methodologic aspects of DNA assessment by means of image cytometry in tumors of the salivary glands. A comparison between the results obtained using sections and cytospin preparations from the same paraffin-embedded specimens

The image cytometric nuclear DNA assessments on paraffin-embedded tissue sections and on Cytospin preparations of disaggregated specimens from the same cases were compared in 98 salivary gland tumors, including 21 acinic cell carcinomas, 29 mucoepidermoid carcinomas, 21 adenocarcinomas and 27 adenoid cystic carcinomas. The histogram type (diploid, tetraploid or aneuploid) and the number of cells with DNA values greater than 2.5c (expressed in relative units) were considered as variables in the correlation. A high correlation between the results in different specimens was found in acinic cell carcinomas, mucoepidermoid carcinomas and adenocarcinomas; the histogram type and the number of cells with DNA values greater than 2.5c were essentially the same between specimen types in these three tumor entities. The cases of adenoid cystic carcinomas showed a considerably lower degree of correlation: in 8 of the 27 cases, the Cytospin preparations yielded diploid histograms, while the tissue sections yielded aneuploid histograms. The number of cells with DNA values greater than 2.5c was notably lower in the Cytospin preparations from adenoid cystic carcinoma; the reasons for this exceptional behavior of the cells of adenoid cystic carcinoma are discussed. These findings demonstrate that paraffin-embedded specimens of different tumor entities, even from the same organ, can be affected differently by disaggregation procedures. While retrospective studies on disaggregated paraffin-embedded specimens can yield reliable results, comparative assessments using both DNA analysis techniques, as in this study, should be performed before a large number of cases is evaluated.     

Mucinous cystadenocarcinoma of the parotid gland: report of a case with fine needle aspiration findings and histologic correlation

BACKGROUND: Mucinous cystadenocarcinoma of the salivary gland is a rare entity. Review of the literature from 1991 to 1999 revealed no previous reports on its cytologic features. CASE: A 25-year-old man had a slowly growing, painless mass in the left parotid gland. Fine needle aspiration biopsy, performed prior to surgical excision, showed clusters of minimally atypical epithelial cells in which occasional vacuolated cells containing mucin could be seen. Pathologic evaluation of the resected parotid mass showed it to be a mucinous cystadenocarcinoma. CONCLUSION: The cytologic differential diagnosis of mucinous cystadenocarcinoma is with low grade mucoepidermoid carcinoma and with mucinous adenocarcinoma. Mucinous cystadenocarcinoma must be cystic; cysts may be present in low grade mucoepidermoid carcinoma, but their size and prominence varies. Mucinous adenocarcinoma is not cystic but gelatinous. Nuclei are bland in both mucinous cystadenocarcinoma and low grade mucoepidermoid carcinoma but are atypical in mucinous adenocarcinoma. There is no squamous differentiation in either mucinous cystadenocarcinoma or mucinous adenocarcinoma, but it is subtle in low grade mucoepidermoid carcinomas. Mucinous cystadenocarcinoma should be considered a potential candidate in the differential diagnosis of mucinous lesions that can occur in the salivary gland.     

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.     

Glial fibrillary acidic protein and desmin in salivary neoplasms

The presence of intermediate filament proteins (IFP) in normal salivary gland tissue and in a number of salivary gland neoplasms has been investigated by immunohistochemical techniques on frozen sections. Cytokeratins (CKs) were seen in almost all normal epithelial cells. In the parotid gland and in palatal gland tissue, a co-expression of cytokeratin and glial fibrillary acidic protein (GFAP) was seen in some myoepithelial cells, but this was not apparent in the submandibular gland. In some pleomorphic adenomas, carcinomas in pleomorphic adenomas, one mucoepidermoid carcinoma, one mucus-producing adenopapillary carcinoma and one adenoid cystic carcinoma, cells expressing three different IFP classes were found (CKs, vimentin, GFAP). These cells were most often situated peripherally in the tumour cords or ducts. The cytokeratin pattern in these cells, as revealed by mAbs PKK1-3, was similar to that in normal myoepithelial cells. Furthermore, reactivity for a fourth class of IFP, desmin, could be seen in this cell type in two carcinomas in pleomorphic adenomas, and also in a few cells in a pleomorphic adenoma and an adenoid cystic carcinoma. Thus the pattern of IFP expression in salivary gland neoplasms, is very complex, and cannot always be related to the normal tissue.     

Basal-cell adenoma of parotid. Difficulty of differentiation from adenoid cystic carcinoma on aspiration biopsy

Two cases of basal-cell adenoma (basaloid monomorphic adenoma, dermal analogue tumor) seen in a one-year period were subjected to fine needle aspiration biopsy and subsequent histologic confirmation. Two cases of adenoid cystic carcinoma occurring in the parotid region were selected for comparison; a great similarity between the two types of tumors was noted. On aspiration smear both lesions consisted of clusters and sheets of uniform, small, regular cells with scant basophilic cytoplasm and regular round or oval bland nuclei. The smears contained varying amounts of homogeneous, pale, eosinophilic stromal substance within and around the cell clusters. Individual cell differences between the two lesions were minimal, with the adenoid cystic carcinomas tending to exhibit more nuclear hyperchromatism and irregularity; the architectural arrangements of the cell clusters and the stromal substance permitted differentiation between the two lesions.     

Cytomorphologic patterns in papillary cystic variant of acinic cell carcinoma of the salivary gland

OBJECTIVE: To study the cytomorphologic profile of the papillary and cystic variant of acinic cell carcinoma (ACC-PCV) of the salivary glands. STUDY DESIGN: We studied 6 aspirates from 5 cases of ACC-PCV. RESULTS: All the cases had varied cytomorphologic features depending upon the degree of vacuolation of cells. However, common to all was a papillary pattern and a cystic fluid background with or without mucin blobs; that led to misdiagnosing the tumor as mucoepidermoid carcinoma on 2 occasions. The smears showed papillary fragments, sheets or clusters of vacuolated/histiocyte like cells and granular cells. The histiocytelike cells resembled macrophages, with finely vacuolated cytoplasm and an eccentrically placed nucleus with frequent binucleation. Vascular cores were seen in a few aspirates. The granular cells were similar to those seen in the usual acinic cell carcinoma but were smaller. The tumor did not show any acinar pattern and lacked naked nuclei in the background. In 4 aspirates finely distributed, brown hemosiderin pigment was detected in the vacuolated cells. CONCLUSION: ACC-PCV is papillary and cystic and hence is often not recognized as acinic cell carcinoma. However, papillary fragments of vacuolated cells or histiocytelike cells and granular cells are clues to the diagnosis.     

Fine needle aspiration biopsy diagnosis of adenoid cystic carcinoma of the breast. A case report.

A case of adenoid cystic carcinoma arising in the breast is presented. The diagnosis was established on a fine needle aspiration (FNA) biopsy sample with histopathologic corroboration. The aspirate yielded a typical smear composed of round, multilayered clusters of uniform epithelial cells arranged around cores of homogeneous, acellular material. Both the conclusiveness of FNA biopsy in diagnosing this rare mammary neoplasm and its resulting in immediate treatment are stressed.     

Epithelial-myoepithelial carcinoma of the salivary gland. Fine needle aspiration cytologic findings

A case of epithelial-myoepithelial carcinoma of the salivary gland in a 78-year-old patient is presented. Fine needle aspiration cytologic smears showed a moderate number of tumor cells arranged in three-dimensional, well-outlined clusters reminiscent of the ball-like structures of adenoid cystic carcinoma. The nuclei were small and monotonous, with finely granular chromatin and small nucleoli. A large number of cells showed abundant clear cytoplasm; however, in some of the clusters the cytoplasms were very scant, again mimicking adenoid cystic carcinoma. Fragments of pale homogeneous acellular material, isolated or surrounding the cellular clusters, were another conspicuous finding.     

Exfoliative cytologic findings of primary pulmonary adenoid cystic carcinom: a report of 2 cases with a review of the cytologic features

BACKGROUND: Adenoid cystic carcinoma is a very rare primary pulmonary neoplasm. Cytologic findings of pulmonary washing and brushing in 2 cases of primary bronchial adenoid cystic carcinoma with special histologic features are described, with an emphasis on some points that have not been reported previously, together with the diagnostic pitfalls. CASES: Two cases of primary adenoid cystic carcinoma of the lung were diagnosed on exfoliative cytology. The patients' ages were 55 and 65 years old. Cytologic findings included large and small clusters of small cells in both 2 and 3 dimensions with occasional cystlike spaces containing mucoid material. The cells were arranged in spherical, cylindrical, basaloid and rosettelike arrangements. There were also abundant small and large mucoid globules, cylinders of homogeneous, acellular, mucous material and "cannon balls." Cytoplasmic and intranuclear round inclusions were noted in case 1. Rare findings of nuclear molding were noted. In case 2, chondromyxoid material and a bimorphic population of tumor cells caused diagnostic confusion with other salivary gland-type tumors of the lung. CONCLUSION: These cases showed characteristic cytologic findings of adenoid cystic carcinoma together with rare findings of intracellular and extracellular inclusionlike bodies, myxochondroid material, bimorphic populations and nuclear molding, which can cause diagnostic confusion with other lung tumors.     

Human kallikrein 6 expression in salivary gland tumors.

Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.     

Fine needle aspiration cytologic findings in metastatic basaloid squamous cell carcinoma of the head and neck.

Basaloid squamous cell carcinoma of the head and neck is a variant of squamous carcinoma the cytomorphology of which has not been examined previously. The cytologic features of metastatic basaloid squamous cell carcinoma in fine needle aspiration specimens from nine patients are described. The primary tumors, when known, were located in the base of the tongue, tonsil, epiglottis, nasopharynx, hypopharynx and false vocal cord. Each neoplasm had large fragments or clusters of crowded cells and scattered single cells in the cytologic smears. The cells had round or oval, hyperchromatic nuclei that often had single, small nucleoli. The nuclei usually were small or medium sized, but six tumors had a few cells the nuclei of which were large and pleomorphic. The cytoplasm was typically scant, and only three cases had occasional keratinized cells. Necrosis was present in six neoplasms. Three neoplasms, originally diagnosed as small cell undifferentiated carcinoma, contained numerous single cells and small clusters of cells with nuclear molding. On review, however, smears from these neoplasms also contained a few large fragments of tightly cohesive cells with larger, vesicular nuclei. Another basaloid squamous cell carcinoma had been interpreted elsewhere as an adenoid cystic carcinoma because of the presence of pseudoglandular structures with stromal cores. Although the cytologic features of basaloid squamous cell carcinoma may mimic those of other poorly differentiated carcinomas in fine needle aspiration specimens, they are sufficiently distinctive that a diagnosis of this variant of squamous cell carcinoma can be suggested for a patient whose primary neoplasm is located in the upper aerodigestive tract.     

Human kallikrein 13 expression in salivary gland tumors

The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.     

Fine needle aspiration of pancreatic cystic epithelial neoplasms.

Pancreatic cystic epithelial neoplasms present diagnostic challenges in cytology. An accurate diagnosis is important since the prognosis and treatment may vary. We report the cytologic features in fine needle aspirates of four cases of cystic neoplasms of the pancreas (two micro-cystic adenomas, one mucinous cystic neoplasm and one mucinous cystadenocarcinoma). Smears were evaluated as to their cellularity, content and predominant cell type. Aspirates from the microcystic adenomas yielded hypocellular material with rare strips of cuboidal cells having bland nuclei and pale cytoplasm. No mucinous material was identified in the background, but the cells stained positively with periodic acid-Schiff stain. Smears from the mucinous cystic neoplasm were moderately cellular and contained abundant mucinous material. The columnar epithelial cells were arranged in tight sheets, clusters and strips. Most cells had benign nuclear features with focal mild nuclear atypia. Key cytologic findings noted in the mucinous cystadenocarcinoma were moderate cellularity, loose clusters of cells, single cells, overt malignant nuclear features and occasional signet ring cells. Pancreatic pseudocysts can be distinguished from pancreatic cystic epithelial neoplasms by the predominance of histiocytes and inflammatory cells and absence or paucity of epithelial cells. To differentiate microcystic adenomas from mucinous cystic neoplasms, the above criteria coupled with periodic acid-Schiff and mucin staining should effectively differentiate these diagnostic entities.     

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.     

Cytodiagnosis of simple and proliferating trichilemmal cysts

OBJECTIVE: To elucidate the cytologic findings in simple trichilemmal (pilar) cysts and proliferating trichilemmal cysts (pilar tumors) and the clinical importance of these lesions. STUDY DESIGN: Aspirates from 12 simple pilar cysts and three pilar tumors, all histologically confirmed, were analyzed with a view to elaborating on specific cytologic features enabling a distinction from epidermal cysts and other adnexal tumors. RESULTS: Aspirates from pilar cysts showed two different pictures, depending on the age of the cyst. Young pilar cysts showed aspirates with an abundant background of blotchy keratin with or without calcification and inflammation. Older (degenerating) cysts showed oily fluid debris with cholesterol crystals and inflammatory cells. The epithelial component was sparse, and only an occasional syncitial cluster of small squamoid cells was seen. As opposed to this, epidermal cysts usually showed a cleaner background, with very cellular aspirates containing many nucleate and anucleate squames, keratin flakes, platelike crystals and no calcification. The pilar tumors showed a lesser amount of keratin as compared to pilar cysts and yielded large and small clusters of squamoid and basaloid cells, a few of which showed an abrupt association with anucleate, keratinized globules. CONCLUSION: The cytologic diagnosis of a pilar cyst should be made especially in scalp cysts, which yield either abundant, blotchy keratin or oily, cholesterol-rich debris with a sparse epithelial component and which lack a mixture of anucleate and nucleate squames. On aspiration, pilar tumors yield comparatively more cells and less keratin and show small, basaloid or squamoid cells abruptly associated with keratin globules. The cytologic diagnosis of pilar cysts is important because these cysts recur if incompletely excised and often undergo transformation to pilar tumors. Similarly, pilar tumors often clinically mimic squamous carcinomas, and hence there is a need to outline definitive cytologic features.