Basaloid carcinomas of salivary glands

Three cases of carcinoma of major salivary glands with basaloid morphology are presented. One case was a clear example of a basal cell adenocarcinoma, an uncommon and infrequently recognized, low-grade tumour of major salivary glands. The remaining two cases showed a higher cytological grade of malignancy but shared some features of basal cell adenocarcinoma. Common features included the architectural pattern and myoepithelial cell differentiation, as demonstrated by smooth muscle-specific actin positivity, in cells associated with the deposition of extracellular basal lamina-like material. The relationship between these cases and adenoid cystic carcinoma is discussed.     

Selected topics in salivary gland tumour pathology

The complexity of salivary tumours is largely due to the participation of neoplastic myoepithelial cells which exhibit remarkable phenotypic and secretory abilities. The proportions and morphologic appearances of ductal and myoepithelial cells, type of tumour matrix and relation of tumour cells with extracellular matrix is what defines entities such as mixed tumours, myoepitheliomas, adenoid cystic carcinomas, epithelial/myoepithelial carcinoma, and basal cell adenocarcinoma. Other lesions such as polymorphous low-grade adenocarcinoma, acinic cell carcinoma, and hyalinizing clear cell carcinoma show little or no myoepithelial differentiation. Understanding this so-called morphogenetic concept is quite important in the diagnosis of these tumours. Pathologic grading of salivary gland tumours is generally implied in the diagnosis; however, tumour grade provides significant prognostic information in mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma, and adenoid cystic carcinoma.     

Salivary gland-type neoplasm of the lung

Salivary gland-type tumours of the lung, which include adenoid cystic carcinoma and mucoepidermoid carcinoma, are rare entities. Histologically, they show morphologies that are similar to those of salivary gland origin. For classification purposes, the terminology applied to tumours of salivary gland origin is also applied to their pulmonary counterparts. Of these types of tumours, adenoid cystic carcinoma is the most common followed by mucoepidermoid carcinoma. Epithelial-myoepithelial carcinoma and pleomorphic adenoma are uncommon. The possibility of metastasis from the salivary glands is important to exclude through careful examination of patients' medical history because low-grade salivary cancers can metastasize after long latencies. A gene rearrangement analysis is helpful in making a definitive diagnosis, particularly in cases with an unusual morphology. Molecular-based classification may be useful to understand the nature of morphologically varied tumours. The immunohistochemical profile of the tumours is also a valuable tool for an accurate diagnosis in difficult cases.     

Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.

Distinguishing adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma of the salivary glands is important for their management. We studied the expression of several myoepithelial and basal/stem cell markers (smooth muscle actin, calponin, smooth muscle myosin heavy chain, metallothionein, maspin, and p63) by immunohistochemistry in 23 adenoid cystic carcinoma and 24 polymorphous low-grade adenocarcinoma, to identify the most useful marker or combination of markers that may help their diagnoses. The results were analyzed using hierarchical cluster analysis and chi(2) test for trend. We noted diffuse expression of smooth muscle actin in 20 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), calponin in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), smooth muscle myosin heavy chain in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P=0.001), metallothionein in 22 adenoid cystic carcinoma vs eight polymorphous low-grade adenocarcinoma (P<0.001), maspin in 22 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma, and p63 in 21 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma. Hierarchical clustering of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was virtually identical (kappa< or =0.0035), suggesting no significant advantage to their use in combination than individually. Diffuse smooth muscle actin expression showed the highest accuracy (91.5%) and positive predictive value (95.2%) for adenoid cystic carcinoma. Thus, diffuse expression of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was highly predictive of adenoid cystic carcinoma, whereas maspin and p63 were frequently expressed in both tumors. In differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, smooth muscle actin as a single ancillary test in support of the histological findings, appears to be as efficient as multiple immunohistochemical tests.     

Diagnostic difficulties in lesions of the minor salivary glands

A wide range of lesions arise from the intra-oral salivary glands, which present a diagnostic challenge to specialists and generalists alike. Of the salivary neoplasms, pleomorphic adenoma is the commonest, but its morphological diversity may bring several other entities to mind, notably polymorphous low-grade adenocarcinoma, particularly in a small incisional biopsy. Polymorphous low grade adenocarcinoma in turn shares features with adenoid cystic carcinoma. When the differential diagnosis includes these three tumours, immunohistochemistry can assist in the face of overlapping morphology. The other salivary neoplasms most likely to be encountered in the oral cavity are canalicular adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. Of the non-neoplastic conditions, necrotizing sialometaplasia is most likely to be misdiagnosed as neoplastic on both clinical and histological grounds. However, careful consideration of the clinicopathological features of an adequate tissue specimen will enable correct diagnosis.     

The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: Cytokeratin and integrin expression

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.     

WHO International Histological Classification of Tumours. Tentative Histological Classification of Salivary Gland Tumours

The principles of the proposed modified WHO Histological Typing of Salivary Gland Tumours are based on the following: 1) The classification of tumours is oriented to the routine work of the practicing surgical pathologists, those who do not see tumours of the salivary glands very often. The inclusion of rare, but clearly defined tumour entities should be helpful to surgical pathologists consulting with clinical specialists. 2) The different types of carcinomas must be distinguished not only by precise histopathological definitions, but also considering differences in prognosis and treatment. For example, the polymorphous low-grade adenocarcinoma and the epithelial-myoepithelial carcinoma are characterized by a relatively good prognosis in contrast to the salivary duct carcinoma. 3) Special points of discussion are: subclassification and grading of carcinomas (e.g. acinic cell carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma), the classification of basal cell tumours (basal cell adenoma, basal cell carcinoma, solid type of adenoid cystic carcinoma), malignant tumours in pleomorphic adenomas and the differential diagnosis between primary tumours and metastases.     

Cell proliferation in salivary gland adenocarcinomas with myoepithelial participation

We used three markers of cell proliferation — mitotic counts, mitotic index and expression of proliferating cell nuclear antigen - to assess the proliferative activity of a series of 78 low-grade salivary adenocarcinomas with myoepithelial participation classified according to: their histological type, the predominant architectural type, and the predominant cytological type. The series included adenoid cystic carcinomas (40), epithelial-myoepithelial carcinomas (19), polymorphous low-grade adenocarcinomas (12) and basal cell adenocarcinomas (7). The proliferation indicators were found to be similar in the first three groups, being significantly lower than in the last. Tumours formed by basal cells had statistically significant higher mitotic indexes than those predominantly composed of clear cells of myoepithelial type and ductal cells. Tubular tumours, irrespective of the histological classification of the neoplasm, had proliferation indexes similar to those found in cribriform neoplasms. Solid tumours, whether formed by ductal or clear myoepithelial-type cells, had higher indexes than the neoplasms with differentiated (cribriform and tubular) patterns. The highest mean values for every proliferation indicator used were found in tumours with solid organization that were predominantly formed by basal cells. These results agree with the hypothesis that cell proliferation is inversely related to neoplastic differentiation. The identification of the prevalent cell phenotype and architecture may extend our knowledge from adenoid cystic carcinoma, whose solid variant carries a worse prognosis, and supports that the usual classification of this group of salivary adenocarcinomas would benefit to be complemented with information on tumour architecture and cellular composition.     

Stromal differences in salivary gland tumors of a common histopathogenesis but with different biological behavior: a study with picrosirius red and polarizing microscopy

Salivary gland neoplasms - pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma - share a common histogenetic trait, but differ markedly in their biological properties. The objective of the study was to assess the polarization colors of picrosirius red-stained stromal collagen fibers in these salivary gland neoplasms to evaluate their possible role in the histopathogenesis of the tumors and to evaluate the potential usefulness of this approach as a diagnostic tool. Ten cases of each tumor type and 10 cases of mucous extravasation phenomenon (control) were examined using picrosirius red staining and polarizing microscopy. In each case, at least 50 thin ( approximately 0.8 microm) and 50 thick (1.6-2.4 microm) collagen fibers were counted and classified as green-yellow or yellow-orange, the mean percentage was calculated and statistical differences analyzed by one-way ANOVA. Results showed a similar thin fiber distribution in all tumor types and controls (82-88% green-yellow, 12-18% yellow-orange, p>0.05). Thick fibers showed a different distribution in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (approximately 50% green-yellow) compared to pleomorphic adenoma and mucous extravasation phenomenon (approximately 13% green-yellow) (p=0.001). Thick fiber distribution was similar in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (p>0.05). We conclude that with picrosirius red staining and polarizing microscopy, stromal collagen fibers differ significantly in pleomorphic adenoma from those in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma, but not from mucous extravasation phenomenon. Similarity between polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma may indicate that these tumor types represent a single entity with a broad spectrum of biological behavior.     

涎腺基底细胞腺瘤和腺癌与腺样囊性癌的比较观察

目的 研究涎腺基底细胞腺瘤和基底细胞腺癌与腺样囊性癌的形态学特征、免疫表型和鉴别诊断。方法 对5例基底细胞腺瘤，5例基底细胞腺癌和7例腺样囊性癌进行了免疫组化和双重免疫电镜(2例)的观察。结果 基底细胞腺瘤和基底细胞腺癌在免疫表型方面非常相似；基底细胞腺瘤(癌)与腺样囊性癌之间在免疫表型和超微结构方面有一定的差别。结论 基底细胞腺瘤和基底细胞腺癌的鉴别诊断基于两者的生长方式和组织学特征。免疫组化和免疫电镜观察有助于基底细胞腺瘤(癌)与腺样囊性癌的鉴别诊断。     

Fine-needle aspiration cytological findings in five cases of epithelial-myoepithelial carcinoma of salivary glands

The cytologic features of five cases of epithelial-myoepithelial carcinoma arising in major salivary glands (four parotid and one submandibular gland) are presented. All cases were initially diagnosed as low-grade malignancies. The smears were generally cellular, with no specific architectural pattern. Single cells and naked nuclei were prominent in all cases. A biphasic epithelial (small-cell) and myoepithelial (large/clear-cell) pattern was identified readily in two cases and with difficulty in one case. The biphasic pattern may be subtle or absent since the clear cells have a fragile cytoplasm and often appear as naked nuclei. The differential diagnosis includes adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and cellular pleomorphic adenoma.     

Salivary gland tumours studied by means of the AgNOR technique

Difficulty is sometimes encountered in distinguishing between pleomorphic adenoma, adenoid cystic carcinoma and adenocarcinoma, especially in small biopsies from salivary glands. The argyrophil (AgNOR) staining technique for nucleolar organizer regions (NORs) has been applied to a series of benign and malignant salivary gland tumours. We studied 35 salivary gland tumours, 13 benign and 22 malignant. In all specimens clearly defined silver-stained intranuclear AgNOR dots were visible. The differences between the numbers of AgNORs in the benign and malignant groups, notably pleomorphic adenomas, adenoid cystic carcinoma and adenocarcinoma, were highly significant. In view of this difference we propose that the AgNOR staining technique is of diagnostic help in distinguishing between these salivary gland tumours.     

Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma

AIMS: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. METHODS AND RESULTS: Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. CONCLUSIONS: Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.     

Hybrid carcinoma of the salivary gland: salivary duct adenocarcinoma adenoid cystic carcinoma

AIMS: Hybrid tumours of the salivary gland are rare neoplasms that have been described only in the parotid and palate. Their recognition is important particularly when the component tumours have different biological behaviours. The occurrence of a submandibular hybrid tumour has not been reported. METHODS AND RESULTS: We describe a case of a 36-year-old woman with a hybrid carcinoma composed of salivary duct adenocarcinoma and adenoid cystic carcinoma of the right submandibular gland. There was no evidence of a pre-existing or concurrent pleomorphic adenoma. The presence of the two components was verified by differential immunohistochemical staining using a panel of cytokeratin, vimentin, smooth muscle actin and S100. The patient subsequently developed metastases to the pelvis, lumbar, vertebra and wrist. The clinical course in this patient was consistent with the behaviour of the salivary duct adenocarcinoma component. CONCLUSIONS: The histogenesis of hybrid tumours is largely unknown, but in this case it may represent diverging differentiation of luminal tumour cells. Because some histological features of different salivary gland tumours overlap, immunohistochemistry is a valuable tool especially when used to delineate the components of a hybrid tumour.     

Intraduct papilloma of parotid gland.

Intraduct papillomas of the salivary glands are rare solitary tumours. Most of the reported cases have occurred in minor salivary glands. A case which occurred in the parotid gland is reported. Fine needle aspiration was performed on this tumour, and the cytological appearances of the aspirate were suggestive of an adenoid cystic carcinoma. This is an important potential diagnostic pitfall which should be borne in mind when interpreting aspirates from salivary gland tumours.     

Immunoexpression of c-erbB-2 and p53 in benign and malignant salivary neoplasms with myoepithelial differentiation.

AIM: To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and progression of salivary tumours with myoepithelial differentiation. METHODS: 233 tumours from 211 patients were studied. These included 76 primary and 24 recurrent adenocarcinomas (polymorphous low grade adenocarcinoma, 13; epithelial-myoepithelial carcinoma, 19; adenoid cystic carcinoma, 56; and basal cell adenocarcinoma, 12) and 133 pleomorphic adenomas and myoepitheliomas, 96 being primary and the remaining recurrent tumours. All cases were formalin fixed and paraffin wax embedded. A StrepABC peroxidase method and polyclonal c-erbB-2 and p53 specific antisera were used. RESULTS: Cell membrane staining of c-erbB-2 was not found in any benign or malignant tumour. There was p53 protein accumulation in one primary and one recurrent pleomorphic adenoma and in 10 adenocarcinomas (polymorphous low grade adenocarcinoma, one; epithelial-myoepithelial carcinoma, one; adenoid cystic carcinoma, five; and basal cell adenocarcinoma, three), three of them being recurrences. CONCLUSIONS: The c-erbB-2 and p53 proteins are not involved in the pathogenesis of pleomorphic adenoma and myoepithelioma and do not constitute biomarkers in assessing the risk of recurrence. c-erbB-2 is not involved in the genesis of low grade salivary neoplasia with myoepithelial differentiation. The percentage of this type of neoplasia with p53 accumulation is low (10%) and does not appear to be related to tumour recurrence.     

Terminal duct carcinoma of minor salivary glands. A nonpapillary subtype of polymorphous low-grade adenocarcinoma

The clinicopathologic features of five terminal duct carcinomas arising in minor salivary glands are presented. These nonpapillary, low-grade adenocarcinomas are part of the spectrum of polymorphous low-grade adenocarcinoma. The patients ranged in age from 47 to 77 years. Symptoms were nonspecific and related to a mass that usually was present for several years. Histologically, the tumors had a ductal pattern with areas of solid and cribriform architecture. Cytologically, they were composed of uniform, cuboid cells with round to oval nuclei and fine chromatin. One patient developed a recurrence after 13 years, but none of the tumors has metastasized. One lesion in this series was studied ultrastructurally and demonstrated both glandular and pseudoglandular structures analogous to those of adenoid cystic carcinoma. Nonetheless, terminal duct carcinoma is cytologically distinctive from adenoid cystic carcinoma and appears to have a more favorable prognosis.     

Vaginal adenoid cystic carcinoma: a case report

Adenoid cystic carcinoma generally arises from the salivary glands and is rarely found in the female genital tract. Infection with HPV is implicated in this cervical lesion. Differential diagnosis includes adenoid basal carcinoma, polymorphous low-grade adenocarcinoma and basaloid squamous cell carcinoma. Only one case of vaginal localisation was previously described. We report a case of adenoid cystic carcinoma in a 48-year-old woman with previous cervical HPV infection. Histological examination revealed nests of cells with peripheral palisading organisation and glandular lumina containing material produced by the tumor cells.     

Basaloid-squamous carcinoma of the upper aerodigestive tract and so-called adenoid cystic carcinoma of the oesophagus: the same tumour type?

Basaloid-squamous carcinoma of the larynx, pharynx and base of tongue and the so-called adenoid cystic carcinoma of the oesophagus are rare but distinctive tumours associated with a grave prognosis. They occur most commonly in elderly males and present at an advanced stage. Our study of four such laryngeal tumours and five such oesophageal tumours shows that they are histologically and immunohistochemically identical, providing support for the idea that they are the same tumour type. They show a biphasic pattern in which basaloid tumour is intimately associated with a neoplastic squamous component which can be invasive or in situ. The basaloid component is in the form of invasive lobules with frequent comedo-necrosis and hyalinization. The constituent cells possess pale pleomorphic nuclei with frequent mitoses. Immunoreactivity for cytokeratin in the basaloid component is remarkable for its absence or weak and focal nature. Review of the literature shows that only a few cases of 'adenoid cystic carcinoma' of the oesophagus are bona fide examples of adenoid cystic carcinoma as it occurs in the salivary glands, while the others are identical to basaloid-squamous carcinoma of the upper aerodigestive tract. Their distinction is important because genuine adenoid cystic carcinoma is much less aggressive than basaloid-squamous carcinoma.     

Sinonasal tubulopapillary low-grade adenocarcinoma: a specific diagnosis or just another seromucous adenocarcinoma?

Histopathologically, sinonasal adenocarcinomas fall into four categories: the intestinal type, the conventional salivary gland type (eg, adenoid cystic carcinoma, acinic cell carcinoma), the seromucous type, and the low-grade not otherwise specified type. Recently, a new type of sinonasal adenocarcinoma has been described, called tubulopapillary low-grade adenocarcinoma. In this commentary, the histologic features of this type of tumor are compared with those of the other types of sinonasal adenocarcinoma. The clinicopathologic characteristics and probable origin of this type of adenocarcinoma are also discussed.