Polymorphous low-grade adenocarcinoma of the salivary glands

Six cases of polymorphous low-grade adenocarcinoma (terminal duct adenocarcinoma) of the minor salivary glands are presented. In all but one there was a history of a painless intra-oral mass of fairly long duration. The histopathological appearances were characterized by cytological uniformity in a variety of morphological patterns, including tubular, solid, fascicular and cribriform areas. At a cellular level, the tumours possessed regular, often vesicular nuclei and generally eosinophilic cytoplasm. Five of the patients are still alive, although one had recurrent disease 16 years after her original operation; none died of their tumour. These findings are compared with those of six salivary adenoid cystic carcinomas, a neoplasm with many similar histological features, but with a much worse prognosis. The microscopic differences were mainly cytological and, to a lesser extent, morphological. The immunohistochemical reactions of the two tumours were not sufficiently dissimilar to be of practical value. Polymorphous low-grade adenocarcinoma has only rarely been reported in Britain, but we believe it deserves wider recognition as a distinct clinicopathological entity and, in particular, separation from adenoid cystic carcinoma.     

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.     

Lobular carcinoma of the breast metastatic to the oral cavity mimicking polymorphous low-grade adenocarcinoma of the minor salivary glands

The oral cavity is a rare site of metastatic lesions; however, metastatic breast carcinoma must be included in the differential diagnosis of tumors of that site in women. We describe a 54-year-old woman who presented with a lesion of the floor of the mouth that histologically resembled polymorphous low-grade adenocarcinoma of the minor salivary glands, which was eventually established to represent metastatic lobular breast carcinoma. The final diagnosis was based on comparison with a primary tumor resected 13 years earlier and immunohistochemical reactivity with antibodies to steroid receptors. Relevant aspects of lobular breast carcinoma, polymorphous low-grade adenocarcinoma, and metastatic oral cavity lesions are discussed.     

Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands. METHODS AND RESULTS: Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20-30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an 'Indian-file' array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for alpha-smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour. CONCLUSIONS: PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.     

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.     

Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate,report of a case and review of literature

Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good.     

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.     

Polymorphous low-grade adenocarcinoma of the nasopharynx: a case report and brief review

Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumour that mostly affects oral minor salivary glands. Our review of the literature found that there are only two reported cases of PLGA originating in the nasopharynx. Another nasopharyngeal PLGA in a 14-year-old boy is reported, focusing on the histopathological features and ultrastructural findings.     

Diagnostic difficulties in lesions of the minor salivary glands

A wide range of lesions arise from the intra-oral salivary glands, and often present a diagnostic challenge to specialists and generalists alike. Of the salivary neoplasms, pleomorphic adenoma is the most common, but its morphological diversity may bring several other entities to mind, notably polymorphous adenocarcinoma, particularly in a small incisional biopsy. Polymorphous adenocarcinoma in turn shares features with adenoid cystic carcinoma. Immunohistochemistry and molecular cytogenetic studies can assist diagnosis in the face of overlapping morphology. The other salivary neoplasms most likely to be encountered in the oral cavity are canalicular adenoma, mucoepidermoid carcinoma, secretory carcinoma and acinic cell carcinoma. Of the non-neoplastic conditions, necrotising 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.     

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.     

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.     

Polymorphous low-grade adenocarcinoma of seromucous glands of the nasopharynx. A report of a case and a discussion of the morphologic and immunohistochemical features

Polymorphous low-grade adenocarcinoma (PLGA) is a minor salivary gland neoplasm that is characterized by morphologic variability, cytologic uniformity, and an infiltrating growth pattern. To date, this entity has been identified either within the confines of the oral cavity or, rarely, in the nasal cavity. The authors report a case of PLGA that arose in the nasopharynx of a 44-year-old female, representing the first documented occurrence of this tumor outside the oral cavity or the sinonasal tract. The histopathologic and immunohistochemical differentiation from pleomorphic adenoma and adenoid cystic carcinoma is discussed.     

Nucleolar organizer regions in malignant salivary gland tumors.

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.     

Primary polymorphous low-grade adenocarcinoma of lung treated by sleeve bronchial resection: a case report

We report a surgical case of primary polymorphous low-grade adenocarcinoma (PLGA) of the minor salivary gland-type of the lung. A PLGA originating from the right upper lobar bronchial inlet was successfully treated by sleeve right upper lobectomy. PLGAs are thought to be indolent tumors that are preferentially localized to the palate, and they affect the minor salivary glands almost exclusively. Until now, two cases of distant metastases to the lung have been reported in the English literature. To the best of our knowledge, only one case of PLGA of minor salivary gland-type of the lung without evidence of a previous oropharyngeal primary tumor has been reported in the English literature. But the case was not a single lesion; it was bilateral tumors accompanied by tumors of the cervical lymph nodes. We report here the first case of a single primary PLGA of the minor salivary gland-type of the lung, which was successfully treated by sleeve bronchial resection of right upper lobe.     

Polymorphous adenocarcinoma of the breast. Report of three cases

We report three cases of polymorphous adenocarcinoma (PLA) of the breast in 37-, 55- and 74-year-old women, respectively. The patients have no evidence of previous malignancy. The tumours consist of monotonous cells showing a wide spectrum of growth patterns: solid nests, trabeculae, tubules, cribriform structures, strands and fascicles reminiscent of polymorphous low-grade adenocarcinoma of salivary glands. To our knowledge, PLA has never been reported in the breast; therefore, this tumour should be added to the list of neoplastic lesions of the breasts that have the same features as those of the salivary glands.     

Nucleolar Organizer Regions in Malignant Salivary Gland Tumors

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: muco-epidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoep-idermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior. Acta Pathol Jpn 42: 727–733, 1992.     

Polymorphous low grade adenocarcinoma with distant metastases and deletions on chromosome 6q23-qter and 11q23-qter: a case report

Polymorphous low grade adenocarcinomas (PLGAs) are thought to be indolent tumours that are localised preferentially to the palate and affect the minor salivary glands almost exclusively. Metastases to locoregional lymph nodes occur in only 6-10% of cases. Recently, two cases of PLGA with microscopically confirmed distant metastases have been reported. This study reports a third case of PLGA with histologically and immunohistochemically confirmed distant metastases. It is the first case with multiple pleural, as well as pulmonary parenchymal, metastases and metastases in cervical and paraoesophageal lymph nodes. In most cases, PLGAs are salivary gland tumours with limited potential to metastasis and a good prognosis after local treatment. However, the recently reported cases reveal that the tumour can give rise to widely spread metastases. To obtain more information about the incidence of distant metastases, periodic chest x ray examination during follow up is desirable.     

Metastatic carcinoma of the prostate presenting as parotid tumour

Two patients are described in each of whom metastatic prostatic carcinoma presented as a tumour of the parotid gland. In one, primary prostate cancer had been diagnosed three years prior to the appearance of what was believed clinically to be an unrelated salivary lesion. In the other a neck swelling was the first indication of disease, although subsequent investigation revealed widespread metastases. Biopsy of each tumour showed an adenocarcinoma with immunohistochemical expression of prostate markers. These cases, and the six previous reports, illustrate the need to consider metastatic carcinoma from the prostate in the assessment of any malignant tumour of the salivary glands in men of advancing years.     

Quality Standards for Diagnostic Electron Microscopy

A case of polymorphous low-grade adenocarcinoma arising in the right nasal cavity of a male patient with previous history of kidney transplantation is reported. The tumor contained extensive areas of undifferentiated carcinoma, probably arising from the low-grade component. This combination of findings has not been previously reported in this variety of salivary gland tumor.