Mesenchymal tumors of the salivary glands are rare and mostly localized to the parotid gland. We report on the clinico-pathological features of a distinct parotid tumor occurred in a newborn, showing glandular structures admixed with mature lipocytes and blood vessels in variable proportions. This was a well-circumscribed and slowly growing nodule of the superficial parotid lobe, mostly reddish in color with white-yellowish striations. Microscopically, a distinct lobular architecture was evident, along with normal-appearing acinar and ductal structures with interposed loose fibrous stroma. The latter contained aggregates of mature lipocytes and variably sized blood vessels. The morphological features of the lesion reported herein recapitulate those of sialolipoma but also include the presence of a prominent vascular component intimately admixed with both the glandular and the adipose tissues. At variance with salivary lipoadenoma, the glandular component in the current case distinctly showed all the cellular components of normal salivary (serous) glands. In consideration of the young age of the patient, the minimal growth rate and the histological features of the lesion, we hypothesize a hamartomatous origin for this lesion and propose the designation of sialoangiolipoma.

Sialolipoma is a new variant of salivary gland lipoma, which was first described in 2001. We report a rare case of sialolipoma of the palate, and review another 10 cases affecting the minor salivary gland and 13 affecting the major salivary gland, together with details of the clinical and histopathological findings.

BACKGROUND Oncocytic lipoadenoma is an uncommon benign salivary gland tumor. There are only rare case reports of this distinct entity in which only the histopathologic aspects are discussed. Fine needle aspiration cytologic (FNAC) findings of oncocytic lipoadenoma have not yet been documented. CASE A 50-year-old woman presented with a slow-growing swelling in the left parotid region that was clinically interpreted as a soft tissue tumor, with a differential of neurofibroma/lipoma. FNAC showed moderate cellularity, with oncocytic cells arranged predominantly as microacini in a prominent lipoid background. The adipose tissue background of the cytologic smears was ignored as material derived from the normal fat tissue; based on the oncocytic population of cells, a diagnosis of oncocytoma was considered. A remote possibility of acinic cell carcinoma with oncocytic features was also suggested. However, histopathologic examination showed it to be an oncocytic lipoadenoma, a tumor we were unaware of at the time of cytodiagnosis. CONCLUSION Both cytopathologists and histopathologists need to be aware of oncocytic lipoadenoma of the salivary gland in order to diagnose it precisely. The clinicocytopathologic correlation highlighted in our case will be useful for cytopathologists in preoperative interpretation and diagnosis.

CASE REPORT We report the case of an oncocytic sialolipoma of the submandibular gland with sebaceous differentiation in a 73-year-old man. The initial symptom was a right submandibular painless mass. Ultrasonography showed a hypoechoic oval mass posterior to the submandibular gland. The tumorectomy was performed with preservation of the salivary gland. The tumor was composed of mature adipose tissue surrounded by a thin fibrous capsule, multiple nodules of oncocytes, normal ductal-acinar units with focal ductal sebaceous differentiation. DISCUSSION We reviewed literature of the reported cases of mixed tumors of the salivary glands composed of mature adipose tissue with oncocytosis, salivary ducts, and acini with sebaceous differentiation. CONCLUSIONS Sialolipoma and lipoadenoma with or without oncocytosis and/or sebaceous differentiation should be considered organ-specific tumors with a distinct histological appearance and specific terminology.

Salivary gland oncocytic lipoadenoma is an exceptional benign tumor composed of mature adipose tissue associated with a mixture of oncocytes. We report a case of oncocytic lipoadenoma showing sebaceous differentiation, and provide a cytogenetic analysis, which has not yet been described. A 64-year-old male developed a left parotid gland, well-encapsulated tumor measuring 3.5x3cm(2), showing mature fat cells associated with oncocytic changes of epithelial components. Immunohistochemistry showed a dual epithelial population with ductal (positivity for AE1/AE3, CK19, CK7 antibodies) and basal-cell (positivity for p63, CK14, CK5,6 antibodies) differentiation in oncocytic areas. Moreover, oncocytic cells were stained with anti-alpha-1 antichymotrypsin antibody and phosphotungstic acid-hematoxylin staining. Molecular cytogenetic analysis showed a translocation t(12;14), resulting in structural rearrangement of the region framing the HMGA2 gene at 12q14.3. Such alterations in HMGA2 have been described in both lipomas and pleomorphic adenomas of the salivary glands.

Although uncommon, many variants of lipomatous lesions in or around salivary glands have been reported in the literature. We report a series of three such cases in the minor salivary gland region. The first case (oral floor) is a well-circumscribed lipocytic lesion admixed with glandular components (mucous acini, serous demilunes and ducts). The second case (alveolar mucosa) is a diffuse lipomatous proliferation with entrapped salivary glandular elements, muscles and blood vessels. The third case (palate) is similar to the first case but the gland is located at the periphery of the lesion. The purpose of the article was to report these three lesions and discuss in relation to other pertaining lipomatous lesions (sialolipoma, lipoadenoma, lipomatosis, lipometaplasia in pleomorphic adenoma and infiltrating lipoma).

This review summarizes the new findings on salivary gland pathology under the following categories: immunohistochemistry; molecular genetics; newly recognized tumour types; known tumour entities with new findings; and progression of salivary gland tumours. In the application of immunohistochemistry, CD117 can aid in highlighting the luminal cell component of various salivary gland tumours, whereas p63 or maspin can aid in highlighting the abluminal cell component. A high Ki67 index remains the most useful marker to predict adverse outcome in salivary gland carcinoma. Specific chromosomal translocations are recognized in pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and mucoepidermoid carcinoma (with MECT1-MAML2 gene fusion). Newly recognized entities include: sclerosing polycystic adenosis (with recent molecular evidence supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with eosinophilia, keratocystoma, adenoma with additional stromal component (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour entities with new findings include: salivary duct carcinoma (with newly recognized mucinous, micropapillary and sarcomatoid variants), intraductal carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with newly proposed grading parameters and oncocytic variant), epithelial-myoepithelial carcinoma (with newly recognized morphological variants), small cell carcinoma (with most cases being related to Merkel cell carcinoma), extranodal marginal zone B-cell lymphoma (with specific chromosomal translocation) and chronic sclerosing sialadenitis (being a component of IgG4-related sclerosing disease). Progression of salivary gland tumours can take the form of malignant transformation of a benign tumour, progression from low-grade to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ carcinoma.

Sialolipoma is a new variant of salivary gland lipoma first described in 2001. We present 2 cases of sialolipoma involving the soft palate and buccal mucosa of 2 female patients. A review of the English language literature revealed 16 cases of sialolipoma reported thus far. We have reviewed the clinicopathologic features of the literature cases and are adding the present 2 cases for a total of 18 cases. To the best of our knowledge, this is the first report of sialolipoma involving the buccal mucosa and the second case in the soft palate. The purpose of this publication is to increase awareness of this recently described variant of lipoma and to address the diagnostic challenges posed both clinically and histopathologically.

Adenolipomas are rare benign neoplasms composed of mature adipose tissue and glandular elements. We report 6 patients with adenolipomas of the head and neck region: 3 in the parathyroid, 2 in the thyroid, and 1 in the parotid gland. The patients were 4 women and 2 men, ranging in age from 21 to 70 years (mean, 62.5 years). The patients with parathyroid adenolipomas manifested signs and symptoms of hyperparathyroidism, whereas the others complained of a mass in the neck. Computed tomography and magnetic resonance imaging are useful tools for the preoperative diagnosis of adenolipomas of the head and neck. The findings of adipose tissue and benign glandular elements by fine-needle aspiration biopsy should prompt consideration of adenolipoma in the differential diagnosis. Complete surgical excision is curative.

We report a series of three cases of pleomorphic adenoma with extensive lipometaplasia, a recently described subtype of pleomorphic adenoma of salivary gland origin. Two patients were female and one male, ranging in age from 30 to 45 years. Two occurred in the minor salivary glands of the lip and palate, respectively, and one in the parotid. Typical histologic findings are presented. In addition, one case consists of a proliferation of spindle cells with an interesting combination of mature adipose tissue, hyaline cartilage, and bone in the absence of ductal structures. The differential diagnosis, as it pertains to other fat-containing tumors (such as lipoadenoma, spindle cell lipoma, interstitial lipomatosis, and benign mesenchymoma), is discussed. It is likely that the ability of myoepithelial cells to undergo various metaplasias is the cause of the unusual histologic appearances of this tumor.

Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated.(1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively.(2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks.(3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case.(4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Cytokeratin 20 (CK20) is a low-molecular-weight cytokeratin (CK) that shows restricted expression in the gastrointestinal epithelium, urothelium, and Merkel cell. Recent studies have suggested that since Merkel cell (primary cutaneous neuroendocrine) carcinomas are consistently CK20-positive, this feature may help to distinguish it from pulmonary small cell carcinomas. However, only limited numbers of these tumors have been studied, and the pattern of CK20 expression in other small cell carcinomas has not been established. Therefore, we studied CK20 expression in small cell carcinomas from a wide variety of sites. Immunohistochemical study was performed on paraffin sections using CK20 antibody, coupled with antigen retrieval by pressure cooking in citrate buffer. The cases included 34 Merkel cell carcinomas and 89 small cell carcinomas from various sites (pulmonary, 37; gastrointestinal tract, nine; pharynx and tongue, two; sinonasal tract, three; salivary gland, five; larynx, nine; breast, two; thymus, three; uterine cervix and corpus, 12, prostate, three; urinary bladder, two; kidney, one; pancreas, one). In addition, all cases were immunostained with pan-CK (MNF-116) and low-molecular-weight CK (CAM5.2) antibodies to ascertain their epithelial nature. With the exception of one case, all Merkel cell carcinomas were CK20-positive; and 30 of the 33 cases showed a punctate pattern. Almost 100% of tumor cells were positive, except for two cases that showed staining of 10% and 30% of tumor cells, respectively. Among the other small cell carcinomas, only five cases were CK20-positive, including one of 37 pulmonary (40% cells positive in punctate pattern), one of 11 cervical (10% cells positive), and three of five salivary gland (100% cells positive). We conclude that CK20-positivity in a small cell carcinoma of uncertain origin strongly predicts a diagnosis of Merkel cell carcinoma, especially if the majority of tumor cells are positive. A negative CK20 reaction can practically rule out Merkel cell carcinoma, provided that an effective antigen retrieval technique is used and appropriate staining is obtained with other cytokeratin antibodies. The frequent CK20 positivity observed in salivary gland small cell carcinomas in this series suggests that at least some of them may be more closely related biologically to Merkel cell carcinoma than to pulmonary-type small cell carcinoma. This may explain why they are far less clinically aggressive than other small cell carcinomas.

Primary salivary gland lymphomas are almost always of B lineage, with most being represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue. This study characterizes the rare non-B-cell lymphomas of the salivary gland based on an analysis of six cases. All patients were men, with a mean age of 53.5 years. They presented with submandibular or parotid mass, which on histological examination showed extensive interstitial infiltration by small, medium-sized, or large lymphoid cells. There was prominent invasion and expansion of the ducts and acini in five cases. Angioinvasion was evident in two cases. Three cases were of T lineage and were CD56 negative; one of these cases expressed CD30. Three cases showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative cases by polymerase chain reaction on paraffin sections using primers for the T-cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died within 3 years, and two were disease free at 4 and 1.5 years, respectively. This study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably distinguished from B-cell lymphomas on morphological grounds alone, because both can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas, which are often extranodal in localization and strongly associated with Epstein-Barr virus (EBV), show a predilection to involve the salivary glands as well.

Endocrine ductal carcinoma in situ (E-DCIS), first characterized by Cross et al. in 1985, is an uncommon entity, and there is little information on its pathobiologic features and natural history in the literature. This report describes the largest series of 34 cases: 14 cases were pure in situ (group A), and 20 were accompanied by an invasive component (group B). All except three patients were over the age of 60 years, with the mean being 69.5 years for group A and 72.6 years for group B. Except for six patients in group A who had nipple discharge, all had a breast mass. On follow-up, one of five group A patients developed local recurrence 5 years after mastectomy, and two of seven group B patients developed another invasive primary in the contralateral breast. Histologically, E-DCIS showed expansile intraductal growths forming solid sheets and festoons traversed by delicate fibrovascular septa. Accumulation of basophilic mucin might be found within the growth and the fibrovascular septa. There were variable degrees of stromal sclerosis. In some cases, the solid intraductal cellular proliferations were focally punctuated by microglandular spaces and rosettes. Comedo necrosis was absent. Intraductal papillomas were found in the immediate vicinity of the tumors in 18 cases and invariably showed pagetoid involvement by E-DCIS. Pagetoid spread into the adjacent ducts and ductules was also a common feature (17 cases). The tumor cells were polygonal, oval, or spindly, often with eccentrically placed, bland-looking, ovoid nuclei and abundant eosinophilic granular cytoplasm. Intracellular mucin was commonly demonstrable. Immunostaining for myoepithelium using muscle-specific actin antibody confirmed the in situ nature of the E-DCIS component. The majority of tumor cells showed strong staining with the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase (monoclonal). Immunostaining also dramatically highlighted the pagetoid spread into the papillomas and ductules by outlining the tumor cells between the negatively stained residual ductal epithelium and myoepithelium. All cases were immunoreactive for estrogen and progesterone receptor, but not p53 and c-erbB2. The Ki-67 index was < 5%. Ultrastructural studies on four cases showed many dense-core neurosecretory granules and larger mucigen granules. In group B cases, the invasive component, which comprised 5-95% of the tumor, included colloid carcinoma, 12;"carcinoid" tumor, 3; mixed "carcinoid"/colloid carcinoma, 4; and small cell neuroendocrine carcinoma, 1. Neuroendocrine markers were also consistently demonstrable in the invasive component. In conclusion, E-DCIS is predominantly a disease of older women that is frequently accompanied by papillomas in the vicinity and may present as nipple discharge (an uncommon presentation in the usual forms of DCIS). It can mimic epitheliosis histologically, but the pagetoid spread is a helpful clue to its neoplastic nature. The bland nuclear morphology, lack of necrosis, and biologic marker profile suggest that E-DCIS is a form of low-grade DCIS despite its solid growth pattern. The invasive carcinomas associated with E-DCIS are also neuroendocrine programmed rather than the usual types of ductal carcinomas, suggesting that E-DCIS represents a biologically distinctive category of DCIS.

BACKGROUND Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein-Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. METHODS Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. RESULTS The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Antiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3 epsilon+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. CONCLUSIONS This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ.

BACKGROUND. Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, and skin. Primary LELC of the lung is very rare, with only limited information in the literature. METHODS. The clinicopathologic features of 11 patients with pulmonary LELC collected from two regional hospitals in Hong Kong are described. RESULTS. The patients, all Chinese, were aged 38 to 73 years (median, 54 years), with equal sex incidence. Two of the 8 patients were smokers. Four presented with coin lesions incidentally discovered on chest X-ray, five with cough and blood-stained sputum, and two with pleural effusion. The tumor formed a discrete (9 patients) or an ill-defined (1 patient) nodule in the lung, or, rarely, showed extensive bilateral pulmonary involvement (1 patient). The major bronchi were not involved except in 1 patient. Three patients had lymph node metastasis at presentation; two of them had bone metastasis, one at presentation and one after 9 months. The tumors had pushing margins, and grew in the form of anastomosing islands and sheets, comprising syncytial-appearing large cells with vesicular nuclei and prominent nucleoli. They were infiltrated by an appreciable number of small lymphocytes and plasma cells. Intratumoral amyloid globules were found in one tumor. In five patients, the tumor showed intraepithelial growth within the small bronchi; this could represent either the in-situ phase of the tumor or pagetoid spread into the bronchial epithelium. The neoplastic cells of all patients harbored Epstein-Barr virus (EBV) as demonstrated by in situ hybridization for EBV-encoded small nuclear RNAs. All eight Asian patients with pulmonary LELC previously reported in the literature similarly have been EBV-positive, whereas the four reported Caucasian patients all have been EBV-negative. CONCLUSION. Lymphoepithelioma-like carcinoma of lung occurring in Asians is an EBV-associated neoplasm; it also appears to occur at a higher frequency in Asians than Caucasians. It usually presents as a solitary subpleural nodule, and there is no strong association with cigarette smoking. Most patients have early stage disease at presentation. From the limited available data, the behavior of LELC of lung is highly variable, ranging from apparent curability by excision (particularly for localized disease) to highly aggressive, extensive disease at presentation.

Although expression of CD56 (neural cell adhesion molecule, a natural killer cell marker) is uncommon among lymphomas, this feature has defined a distinctive and important category of lymphoma: the putative natural killer (NK) cell lymphoma, which shows a predilection for the upper aerodigestive tract, skin, skeletal muscle, and other extranodal sites and pursues an aggressive clinical course. Thus far, CD56 expression can be reliably analyzed only on fresh or frozen tissues. In this study, we evaluated the sensitivity and specificity of a CD56 antibody, 123C3, when applied on routine formalin-fixed, paraffin-embedded tissues for analysis of lymphomas, by comparing the staining results with those obtained on frozen tissues using the CD56 antibody NKH1. The 123C3 antibody worked on paraffin sections only with prior antigen retrieval using a pressure cooker or a microwave oven. Among 32 CD56+ T/NK cell lymphomas and one CD56+ B-lymphoblastic lymphoma, the neoplastic cells showed crisp membrane staining with 123C3 in all cases. None of the 24 CD56- T-cell lymphomas and 50 CD56-B-cell lymphomas stained with 123C3. In normal or reactive lymphoid tissues from a variety of sites, there were few small lymphocytes (< 0.1%) that showed cell membrane staining with 123C3, although occasional plasma cells might show cytoplasmic staining. We conclude that with suitable antigen retrieval procedures, 123C3 can be reliably applied on routine paraffin sections for detection of CD56 expression in lymphomas. Furthermore, this antibody can be used to support a diagnosis of lymphoma or to detect residual disease for cases of CD56+ T/NK cell lymphoma in which the neoplastic lymphoid cells are small and show minimal atypia, especially in small biopsies.

Our study included a number of 24 cases with Warthin tumor, diagnosed between 2007-2011, which were analyzed in terms of clinical, histopathological and immunohistochemistry point of view, using CK7, CK5÷6, CK19, and p63 antibodies. Warthin tumor is most often a tumor with a slow evolution, painless, usually affecting males (M÷F 3.2÷1) in the seventh decade of life. Histopathologically, it is distinguished the predominance of the typical forms of the tumor, with a balanced ratio epithelium÷stroma. The immunostaining for CK7 showed positivity in all the investigated cases both in the columnar luminal cells and basal cells. The immunostaining for CK5÷6 was positive in all the investigated cases in bilayer epithelial basal cells, both in the structure of the cysts and the papillae. In the case of the immunostaining for p63 we noticed limited nuclear positivity in the basal cells, while the columnar cells' nucleus were negative. The immunohistochemical study of the bilayer epithelial component of Warthin tumor showed different immunstaining of the two types of epithelia, the oncocytary columnar and the basal on, similar to those found in the salivary gland ducts.

The secretory units and duct system of the echidna sublingual glands exhibit subtle architectural modifications to accommodate the viscous secretion produced by these glands. The glands are compound tubular glands, the secretory units of which are elongate with open lumina and consist only of mucous cells. Closely packed spindle-shaped myoepithelial cells invest the secretory units, but are absent around the ducts. The branched secretory tubules open into an abbreviated duct system characterized by wide lumina. Striated ducts normally associated with the second portion of the intralobular duct system are absent. The duct system shows the most obvious modification of general salivary gland architecture presumably to accommodate the viscous secretion propelled from the secretory units by surrounding myoepithelial cells.

AIMS Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland neoplasm that most commonly occurs in the parotid gland, but can also arise in the minor salivary glands. Three cases are reported of epithelial-myoepithelial carcinoma of the minor salivary glands, with the goal of better defining this entity. PATIENTS AND METHODS All three cases showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. All parts of each tumor were surrounded by a myoepithelial cell rim and there was evidence of invasion. RESULTS Immunohistochemical analysis showed the tumor cells to be weakly positive for S100, cytokeratin (CK) CK5/6, CK7, CKAE-1/AE-3 and strongly positive for epithelial membrane antigen (EMA) and p63; they were focally positive for calponin and acute lymphoblastic leukemia antigen (CD10). The tumor cells were negative for vimentin, alpha-smooth muscle actin (SMA)(except one case), glial fibrillar acid protein (GFAP) and MIB1. The tumors were resected completely with wide margins and no recurrence or metastasis had occurred from 6 to 15 months after surgery. CONCLUSION Three cases of minor salivary gland tumors are described and the differential diagnosis underlined in relation to benign myoepithelioma. The characteristic morphological and immunohistochemical features aided diagnosis of these biphasic tumors.

Carcinomas arising in or from the epithelial component of preexisting parotid Warthin tumors (WTs) are rare; the other histologic types of carcinoma found to arise from WTs are adenocarcinoma not otherwise specified, undifferentiated, mucoepidermoid, squamous cell, and oncocytic. The aim of this study is to describe the clinicopathologic features of a distinct salivary gland neoplasm, previously undescribed, with a striated duct phenotype arising from WT. We have designated this neoplasm "Warthin adenocarcinoma"(WA). In this retrospective study, we searched the surgical pathology files of the Department of Pathology at The University of Texas M.D. Anderson Cancer Center for cases of malignant WT and salivary adenocarcinoma not otherwise specified diagnosed from January 1, 1985, through December 31, 2006, and evaluated patients' medical records and pathologic material. We obtained tissue sections and immunohistochemically stained them with antibodies against p63; Bcl-2; cytokeratin (CK)903, CK7, CK14, and CK18; antimitochondrial antibody (AMA); smooth muscle actin; calponin; S-100; and Ki-67. We identified 2 cases of WA; both patients were women, 44 and 60 years of age, with 4.0- and 4.5-cm tumors in the left parotid gland. Histologically, the tumors were composed of bilayered duct-like structures: The inner layer was formed by a single row of columnar oxyphilic cells expressing CK7, CK14, CK18, and AMA. The outer layer was composed of multiple layers of small round dark cells with scanty cytoplasm that expressed p63, Bcl-2, and CK903 and were focally positive for AMA and negative for myoepithelial markers. The Ki-67 proliferative indices were 20%; and 25%. A residual WT with transition to carcinoma was identified in both cases. Treatment had consisted of total parotidectomy with postoperative irradiation. Patients were free of disease 1 and 3 years after treatment. Warthin adenocarcinoma is a unique salivary gland carcinoma representing the malignant epithelial counterpart of WT. The identification of additional cases would help to better elucidate the line of differentiation of the tumor and further define its natural history.

We herein report an unusual case of a low-grade myxoid renal epithelial neoplasm, with peculiar and previously unreported morphologic and immunohistochemical features. The lesion was characterized by noninfiltrative borders, myxoid stroma and elongated tubular and cordlike epithelial structures. These were lined by 2 different epithelial cell types, flat and elongated basal cells and cuboidal to spindle shaped eosinophilic luminal cells, with low-grade nuclear features and a few small nucleoli. The lesion morphologically resembled a pleomorphic adenoma of the salivary gland. The immunohistochemical profile interestingly confirmed the myoepithelial differentiation of the basal epithelial layer, as demonstrated by the coexpression of several myoepithelial markers such as p63, caldesmon, calponin, smooth muscle actin, and S-100, together with epithelial markers such as low and high-molecular weight cytokeratins. The tumor proved benign at follow-up. A definitive classification and histogenetic interpretation of this previously unreported tumor type awaits description of further cases showing similar features which, perhaps, as it may happen, went so far unnoticed.

Canalicular adenoma is an uncommon benign salivary gland neoplasm that has a marked predilection for occurrence in the upper lip. It is composed of columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. This tumor has an excellent prognosis after conservative surgical treatment in all locations. In the present report we describe, using immunohistochemistry, the expression of cytokeratins (CK), S-100 protein and EMA in a canalicular adenoma that arose in the upper lip of a 55-year-old female. Cells of the canalicular adenoma showed an immunohistochemical profile that indicates an excretory duct origin: most of these cells positively expressed AE1/AE3 cytokeratins and S100 protein. A comparison of the immunohistochemical features of canalicular adenoma with other salivary gland neoplasms that share similar histological features is discussed.

Sex steroid hormone [ie, estrogen (ER), progesterone (PgR), and androgen (AR)] receptors have been identified previously in normal salivary glands and, more variably, in salivary gland and salivary gland-type tumors. No data are available, however, on their expression in pulmonary hamartoma, a benign biphasic tumor consisting of reactive epithelial cells and neoplastic fibromyxoid stroma, cartilage and fat, which shares some morphologic, immunophenotypic, and genotypic features to pleomorphic adenoma of major salivary glands. Thirty pulmonary hamartomas (15 in male patients and 15 in age-matched female patients), were evaluated for ER, PgR, and AR immunoreactivity, and also for mesenchymal, epithelial, and myoepithelial markers, in the fibromyxoid, epithelial, and chondroid components. ER immunoreactivity was encountered in 90% of hamartomas, PgRs in 90%, and ARs in 53%(P<0.001), but not in normal lung tissues. ARs were confined to males (P<0.001), with a marginal prevalence in the fibromyxoid component (P=0.067). PgRs and ERs were instead present in both sex, with the former being restricted to the fibromyxoid stromal component (P<0.001) and the latter preferentially located in epithelial cells (P=0.107). In most cases, fibromyxoid stroma and spindle cells surrounding the chondroid foci displayed simultaneous immunoreactivity for ERs, PgRs, and ARs, along with immunoreactivity for vimentin, S-100 protein, glial fibrillary acid protein, smooth muscle actin, and calponin but lack of staining for cytokeratins. This profile is consistent with an incomplete myoepithelial differentiation of the receptor-expressing mesenchymal cells. In conclusion, sex steroid hormone receptor expression is a nonrandom event in pulmonary hamartoma, and may be related to the development and growth of this tumor.

Basal cell adenocarcinomas (BCACs) of the oral minor salivary gland are very rare neoplasms. We report on an 86-year-old woman with BCAC arising from the minor salivary gland in the soft palate. Histologically, the tumor was located in the submucosa and showed microinvasion into the adjacent soft tissue without encapsulation. It contained tiny tumor islands with solid and tubular patterns, as well as myxoid stroma. The neoplastic cells were basaloid cells and were composed of large pale cells and small dark cells. They were positive for alpha-smooth muscle actin, cytokeratin 14, and vimentin in the periphery of the tumor island, showing a myoepithelial differentiation. The myxoid stroma was positive for alcian blue and colloidal iron. Apical membranes of the neoplastic cells were positive for MUC1 and CEA. The present case is the 14th documented case of oral BCAC (the fifth case of palatal BCAC).

OBJECTIVE To analyze the clinical features, morphology and biologic behavior of primary malignant myoepithelioma (MME) of salivary glands. METHODS The H&E sections of 16 MME cases were reviewed. Immunohistochemical study using EnVision method for cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, S-100 protein, desmin, muscle-specific actin (MSA), smooth muscle actin (SMA), Myo, proliferation cell nuclear antigen (PCNA), leukocyte common antigen (LCA) and glial fibrillary acidic protein (GFAP) was carried out. RESULTS Of the 16 patients studied, 6 were males and 10 were females. Their ages ranged from 12 to 65 years (with an average age of 44 years). The tumor occurred predominantly in the parotid gland and minor salivary gland of the palate. Common clinical features included sudden and rapid tumor growth, superficial ulceration, bony destruction and nerve infiltration. Seven of the 16 patients developed local recurrences, while 2 patients had metastasis in the lymph nodes of submandibular or other cervical regions. Most tumors infiltrated adjacent normal salivary gland, adipose, muscular and bony tissues. The extent of local invasion however varied. Histologically, MME showed a wide range of morphologic appearance, with various combinations of clear, spindle, epithelioid or plasmacytoid cells. The tumor cells were atypical and demonstrated high mitotic activity. In this study, 9 cases were composed predominantly of clear tumor cells. Immunohistochemically the tumor cells were positive for CK, EMA, MSA, desmin and S-100 protein. CONCLUSIONS In general, MME is a rare and low-grade malignant salivary gland tumor. It carries a low potential for lymph node or distant metastasis but relatively high tendency for local recurrences, resulting in destruction of adjacent soft and bony tissues. The biologic behavior also varies, depending on the site of involvement. Morphologic diagnosis of MME can be difficult in view of the wide spectrum of histologic changes. A definitive diagnosis however is possible with the application of immunohistochemistry.

Dedifferentiated salivary gland tumor is a rare, recently recognized tumor type. A case of dedifferentiated malignant myoepithelioma in a 59-year-old man who presented with a painful mass in the left preauricular region is reported. Histologically, two distinct neoplastic cell populations were observed in the same tumor mass. The first population was composed of solid nests of polygonal eosinophilic or glycogen-rich clear cells showing neoplastic myoepithelial immunocytological features, such as positivity for cytokeratins, vimentin, S-100 protein (S-100), alpha-smooth muscle actin (SMA) and glial fibrillary acidic protein (GFAP). A multinodular growth pattern, necrosis and occasional mitotic figures suggested malignancy. This population was diagnosed as low-grade malignant myoepithelioma. The second population infiltrated diffusely into the parotid gland and facial nerves. It consisted of polygonal or short spindle cells with obvious pleomorphism and atypical mitoses. The tumor cells were positive for vimentin and cytokeratins, and showed an accumulation of p53 and cyclin D1. S-100 protein, SMA and GFAP were negative. This population was regarded as undifferentiated carcinoma. A final diagnosis of dedifferentiated malignant myoepithelioma was made. This seems to be the first published case of dedifferentiation in malignant myoepithelioma. Because any tumor type can undergo dedifferentiation with accumulation of additional genetic changes, complete sampling should be the standard approach to all salivary gland tumors in order to avoid missing a dedifferentiation component.