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Fig. 5.38. Cribriform adenocarcinoma of the tongue (CAT). A vaguely nodular growth pattern is composed of solid nests with tubular structures

Fig. 5.39. Epithelial myoepithelial carcinoma (EMCa): characteristic biphasic appearance with an inner layer of ductal cells and outer layer of clear myoepithelial cells. Basal membrane-like material surrounds the outer cells vours PA, but it is sometimes not possible to distinguish these tumours, particularly on a small biopsy. Papillary structures form part of the spectrum of growth patterns seen in PLGA [206], but when extensive, there is evidence that these tumours are slightly but significantly more aggressive [63, 64], although they do not seem to affect long-term survival. Genuine high-grade malignancy can occur rarely, as either a poorly differentiated PLGA or as a salivary duct carcinoma [191].

ICD-O:8525/3

A newly described tumour [134] found so far only in the tongue, shares some histological features with PLGA, to which it is probably related. Cribriform adenocarci-noma of the tongue (CAT) usually arises in adults with a mean age of 50 years and equal sex incidence in the root of the tongue. Generally, at the time of diagnosis there are metastases in the neck lymph nodes, either unilaterally or bilaterally, but distant spread has not been described.

Microscopic examination shows lobules divided by fibrous septa, composed of areas with solid and micro-cystic growth patterns. In the solid areas, tumour nests often display a well-developed hyperchromatic outer layer with a perpendicular arrangement of cells. This layer is frequently detached, forming papillae or glomer-uloid structures surrounded by apparent clefts. The mi-crocystic growth pattern is composed of lobules of neoplastic cells with a cribriform and/or tubular architecture, the two patterns often intermingling. Typically, the tubules are approximately of the same size and consist of one cell layer. Cytologically, there is one cell type; characteristically, the nuclei, which often overlap one another, are pale and vesicular with a "ground glass" quality, thus resembling those of papillary thyroid carcinoma (Fig. 5.38).

Each nucleus can contain up to three nucleoli of varying conspicuousness. Immunohistochemically, a strong or patchy reaction is seen with cytokeratins and S-100 protein. Actin, calponin and smooth muscle myosin heavy chain react with only a few areas. They are completely negative for thyroglobulin.

Patients treated with surgical excision and subsequent irradiation have a good chance of prolonged survival without recurrence or further metastatic spread [134].

5.9.5 Epithelial-Myoepithelial Carcinoma

ICD-O:8562/3

The mean age at diagnosis of epithelial-myoepithelial carcinoma (EMCa) is 60 years (range 8-103), with a small majority in females [62]. It occurs predominantly in the parotid gland, less often in the submandibular gland, occasionally in minor salivary glands and rarely in the bronchus [234]. The microscopic appearance is characterised by small ductular lumina lined with two layers of cells (Fig. 5.39). The inner comprises cy-tokeratin-positive epithelial cells, and it is surrounded by an outer mantle of often clear myoepithelial cells, which express aSMA, smooth muscle myosin heavy chain and calponin. S-100 protein also stains the outer cells strongly, but is less specific and sometimes reacts with the inner layer [114] - CK 14 appears to be un-

5.9.4.1 Cribriform Adenocarcinoma of the Tongue helpful. The outer cells are in turn surrounded by a rim of PAS-positive basement membrane material of variable thickness. This pattern is reproduced throughout most of the tumour, though each element may vary in prominence both between and within each lesion. Grossly, the tumours often appear to be well circumscribed, but microscopy usually reveals some invasion of surrounding structures. Cytological pleomorphism is infrequent, but mitotic figures may be numerous. The stroma is usually scanty, but on occasions it consists of plentiful hyaline basement membrane material with relatively inconspicuous bilayered ducts; the tumour can then be mistaken for a pleomorphic adenoma [186]. Other differential diagnoses encompass a wide range of salivary neoplasms, mainly those composed of clear cells, both primary and metastatic. Many salivary tumours can be diagnosed purely on H&E morphology, but clear cell lesions are an exception, and most require immunohistochemistry and sometimes electron microscopy. EMCa can occasionally dedifferentiate as a high-grade adenocarcinoma [2] or a sarcomatoid spindle cell neoplasm of myoepithelial type [186]. That they originate from intercalated ducts is supported by an unusual case of a typical EMCa in a parotid gland, which also contained multiple nodules of intercalated duct hyperplasia (Figs. 5.40-5.42) [48].

This appearance may explain why EMCa is not infrequent in hybrid tumours [31, 37]. The behaviour of EMCa is generally considered to be low grade, and in a literature review of 67 cases, recurrences were noted in 31%, cervical lymph node metastasis in 18%, distant metastasis in 7% and death due to tumour in 7% [13]. In contrast, the series of Fonseca and Soares [71] found that 50% of neoplasms recurred and 40% of patients died of cancer. The only morphological feature found to correlate with a poor prognosis was nuclear atypia in more than 20% of tumour cells. In another study DNA analysis has shown that aneuploidy is associated with an increased chance of recurrence [34].

5.9.6 Hyalinising Clear Cell Carcinoma

ICD-0:8310/3

Monomorphic clear cell carcinomas are either epithelial or myoepithelial (clear cell malignant myoepithe-lioma). The former, now known as hyalinising clear cell carcinoma was first described by Skorpil in Czech and German [205] and was rediscovered recently [138, 193], but was not included in the revised WHO classification [171]. It usually arises in the minor glands and is of low-grade malignancy. Microscopically, it is characterised by groups and trabeculae of polygonal glycogen-rich cells separated by dense collagen bands. At times, particularly in the deeper parts of the tumours, the cells may lose their clarity when their cytoplasm appears weakly

Figs. 5.40-5.42. Intercalated duct hyperplasia of the parotid gland. Top: Hyperplastic foci are composed of an inner layer of epithelial cells surrounded by myoepithelial cells with ample and clear cytoplasm. The former stain for CAM5.2 (lower) and the latter for smooth muscle actin (middle)

eosinophilic. Immunohistochemistry reveals positivity with epithelial markers (e.g. cytokeratin), but myoepithelial markers (e.g. S-100 protein and aSMA) are negative [138].

5.9.7 Basal Cell Adenocarcinoma

This tumour has the architecture and cytology of basal cell adenoma, but displays infiltration. Most cases arise

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