bromochloroacetic-acid and Parotid-Neoplasms

Keratocystoma is a rare benign tumour of the salivary glands. We report a patient who presented with a mass in the left parotid gland that was treated by subtotal parotidectomy and he was free of recurrence seven years later. After histological and immunohistochemical examinations we identified a keratocystoma.

Topics: Adult; Epithelial Cells; Fibrosis; Humans; Keratins; Ki-67 Antigen; Male; Metaplasia; Parotid Neoplasms; Transcription Factors; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

The authors investigated the clinicopathological characteristics of keratocystoma of the parotid gland. Two cases of parotid gland keratocystoma in the files of Nanjing Stomatological Hospital were analysed. These slowly growing parotid gland tumours occurred in two women aged 29 and 49 years. The cut surface showed multilocular cystic lesions filled with keratin materials. Histologically, there were multi-cystic spaces and solid epithelium islands, containing keratinized lamellae. Without cytological atypia, the lining stratified squamous epithelium showed apparent keratinization through an orthokeratotic or parakeratotic pathway. No skin appendage formation was observed. Both cases immunoreactively stained positively for AE1/AE3 and CK5/6 but negatively for CK8/18, S-100 and Calponin. There was no evidence of recurrence 3 or 4 years after superficial parotidectomy. The data from these two cases and cases previously published suggest that keratocystoma of the parotid gland is a benign cystic neoplasm. Surgical resection is apparently sufficient for cure.

Topics: Adult; Calcium-Binding Proteins; Calponins; Diagnosis, Differential; Epithelium; Female; Follow-Up Studies; Humans; Keratin-18; Keratin-5; Keratin-6; Keratin-8; Keratins; Microfilament Proteins; Middle Aged; Muscle Proteins; Parotid Neoplasms; Retrospective Studies; S100 Proteins

Primary sebaceous neoplasms of the salivary glands are extremely rare occurrences; furthermore, sebaceous lymphadenocarcinoma has only been reported in three patients. We report a case of sebaceous lymphadenocarcinoma arising in a lymphadenoma of the parotid gland. The patient was a 55-year-old man who presented with a parotid mass of 3 years' duration. Histologically, the lesion consisted of a sebaceous lymphadenoma with transition to a sebaceous carcinoma. The cytologic touch-preparation at the time of frozen section showed clusters of benign sebaceous cells in a rich lymphocytic background together with tridimensional clusters of malignant epithelial cells, strongly raising the suspicion of a malignant neoplasm arising in a benign sebaceous lesion. Malignant transformation of the sebaceous lymphadenoma, although rare, should be considered in enlarging, locally invasive parotid lesions, considering that clinical behavior and prognosis will be determined by the nature of the malignant component.

Topics: Adenocarcinoma; Adenolymphoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms; Radiotherapy, Adjuvant; Sebaceous Gland Neoplasms; Sebaceous Glands; Treatment Outcome

True malignant mixed tumor (carcinosarcoma) of the salivary gland is an extremely rare tumor. By definition, it is composed of both malignant epithelial and malignant mesenchymal elements. The most common type of the former is squamous cell carcinoma or adenocarcinoma and the most common type of the latter is chondrosarcoma, followed in frequency by fibrosarcoma, leiomyosarcoma, osteosarcoma, and in rare instances liposarcoma. We report a case of true malignant mixed tumor of the parotid gland in association with a pleomorphic adenoma in a 47-year-old man that contained a very unusual type of malignant mesenchymal component, rhabdomyosarcoma. Cytologic and histologic features and immunohistochemical results are presented. In addition, the literature is reviewed, and the possible histogenesis and pathogenesis of malignant mixed tumor of the salivary gland are briefly discussed.

Topics: Actins; Carcinosarcoma; Humans; Immunohistochemistry; Keratins; Male; Mesoderm; Middle Aged; Parotid Neoplasms; Rhabdomyosarcoma

We describe a case of a myoepithelial carcinoma of the superficial parotid gland in a 46-year-old male harboring a novel CTCF::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in myoepithelial carcinoma. A 46-year-old male patient presented with a mass involving the superficial left parotid gland with extension into the external auditory canal (EAC) and erosion of the conchal cartilage. Histologically, the neoplasm was composed of uniform spindled, epithelioid/ovoid cells arranged in cords and nests within hyalinized to myxoid stroma. On immunohistochemistry (IHC), the tumor cells demonstrated patchy and variable staining for low molecular weight cytokeratin (CAM5.2), pan-cytokeratin (OSCAR), and S-100. Overall, the morphological and immunohistochemical attributes supported a locally aggressive tumor of myoepithelial differentiation consistent with myoepithelial carcinoma. Molecular analysis using a custom 115-gene gene panel by targeted RNA sequencing, showed an in-frame CTCF::NCOA2 fusion. In addition to reporting this novel fusion in myoepithelial carcinoma, we also discuss relevant differential diagnosis, and provide a brief review of NCOA2 gene function in both normal and neoplastic contexts.

Topics: Carcinoma; Humans; Keratins; Male; Middle Aged; Myoepithelioma; Nuclear Receptor Coactivator 2; Parotid Gland; Parotid Neoplasms

The nature of the lymphoid stromal component in Warthin tumor and lymphadenoma of the parotid gland has been a controversial topic in salivary gland pathology for decades. Two theories exist: first, that these tumors arise from salivary gland inclusions within intraparotid lymph nodes; and second, that they arise within salivary gland parenchyma and induce tumor-associated lymphoid proliferation (TALP). A recent study demonstrated that low molecular weight cytokeratin is effective in distinguishing salivary gland tumors within lymph nodes from those inducing TALP via identification of extrafollicular reticulum cells, which are only found in true lymph nodes. Twenty-one Warthin tumors and 4 lymphadenomas were retrieved from the archives of the Department of Pathology at University of Texas Southwestern Medical Center. Cam5.2 immunohistochemistry was performed on each case and independently evaluated by two pathologists. Extrafollicular reticulum cells were identified by Cam5.2 immunostaining in 21 of 21 Warthin tumors (100%), and 3 of 4 lymphadenomas (75%). Extrafollicular reticulum cells were consistently localized to the perisinusoidal and paracortical areas of the lesions studied. Extrafollicular reticulum cells were identified via low molecular weight cytokeratin Cam5.2 immunohistochemistry in all of the Warthin tumors and most of the lymphadenomas evaluated. This finding strongly supports the notion that these most if not all of these tumors arise within intraparotid lymph nodes, presumably from salivary gland inclusions entrapped during embryonic development.

Topics: Adenolymphoma; Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Parotid Neoplasms; Salivary Gland Neoplasms

Secretory carcinoma of the salivary glands is a relatively new disease concept, and is characterized by "morphological resemblance to mammary secretory carcinoma and ETV6-NTRK3 gene fusion." Herein we describe a confusing case and briefly discuss practical diagnostic problems. The patient was a 71-year-old Japanese man who had a tumor consistent with secretory carcinoma at the microscopic and immunohistochemical levels. Immunohistochemically, EMA and S100 protein were noted to be positive along with various cytokeratins as well as mammaglobin and pSTAT5. Moreover, vimentin was focally positive. Smooth muscle actin, p63, p40, and androgen receptor were negative. However, a search using fluorescence in situ hybridization did not reveal a definite split signal for the ETV6 gene. It is presumed that confirming the diagnosis of secretory carcinoma without genetic retrieval will be accepted as a diagnostic method, and we hope that worldwide general recognition may earlier reach "gradual acceptance."

Topics: Aged; Biomarkers, Tumor; ETS Translocation Variant 6 Protein; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Mammary Analogue Secretory Carcinoma; Parotid Neoplasms; Proto-Oncogene Proteins c-ets; Repressor Proteins; S100 Proteins; STAT5 Transcription Factor

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651-654. © 2017 Wiley Periodicals, Inc.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Aged; Biomarkers; Biomarkers, Tumor; Biopsy, Fine-Needle; Carrier Proteins; Diagnosis, Differential; Epithelial Cells; Gene Expression; Glycoproteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Membrane Transport Proteins; Parotid Gland; Parotid Neoplasms; Salivary Gland Neoplasms

Although Warthin's tumor is one of the common tumors of the salivary glands, Warthin's tumors with a prominent component of nodular oncocytic hyperplasia reminiscent of oncocytoma are rare. Here we report such a tumor, measuring 3 cm in diameter, found in the parotid gland of an 81-year-old man. Histologically, approximately 70% of the mass was a component of nodular oncocytic proliferation, and the remaining portion was a component of conventional Warthin's tumor. We performed immunohistochemical analysis to explore what factors determined the morphogenesis of the two components in the single mass. Cytokeratin (CK) 5÷6-positive tumor cells, which represent basal cells, were aligned in a layer in the conventional Warthin's tumor component, whereas they were localized around blood vessels in the nodular oncocytic hyperplasia component. Immunostaining for CD34 showed that capillaries were sparsely present beneath the bilayered epithelia in the former component, while blood vessels resembling sinusoids separated the trabeculae of the tumor cells in the latter component. Ki-67 labeling index was slightly higher in the latter component. Double immunostaining for CK5÷6 and Ki-67 revealed that most of Ki-67-positive proliferating tumor cells were CK5÷6-positive, suggesting that CK5÷6-positive population contained proliferative progenitor cells of the tumor. These findings imply that the regional difference in the distribution pattern and proliferative activity of CK5÷6-positive putative progenitor cells along with the difference in the pattern of vascular network occurred during the tumorigenic process of the tumor and determined one region to become conventional Warthin's tumor morphology and the other to become nodular oncocytic hyperplasia.

Topics: Adenolymphoma; Adenoma, Oxyphilic; Aged, 80 and over; Humans; Hyperplasia; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Parotid Neoplasms; Stromal Cells

A case of recurrent hyalinizing clear cell carcinoma (HCCC) of the parotid gland in a 46-year-old female is here introduced. The patient had undergone a left superficial parotidectomy 6 months ago in another institution for an alleged benign, circumscribed mass 2.4 cm in diameter of the left parotid gland. Histopathological examination revealed a poorly differentiated HCCC bearing a EWSR-1 translocation on FISH examination. Fine Needle Cytology (FNC) was performed on three separate soft tissue masses in the pre-masseterine area and a cytological diagnosis of recurrent, poorly differentiated, possibly aggressive variant of HCCC, was rendered. FISH performed on a destained Diff Quik stained smear demonstrated an ESWR-1 translocation, which supported the cytopathological diagnosis. The cytomorphologic features and the differential diagnosis of this aggressive variant of HCCC are briefly discussed.

Topics: Adenocarcinoma, Clear Cell; Biomarkers, Tumor; Biopsy, Fine-Needle; Female; Humans; Keratins; Middle Aged; Neoplasm Recurrence, Local; Parotid Neoplasms; Rare Diseases; Ultrasonography

Topics: Aged; Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Parotid Neoplasms; Skin Neoplasms

Mammary analogue secretory carcinoma (MASC) is a newly described rare salivary gland tumor, which shares morphologic features with acinic cell carcinoma, low-grade cystadenocarcinoma, and secretory carcinoma of the breast. This is the first reported case of MASC of an accessory parotid gland detected by aspiration biopsy with radiologic and histologic correlation in a 34-year-old patient. Sonographically-guided aspiration biopsy showed cytologic features mimicking those of low-grade mucoepidermoid carcinoma, including sheets of bland epithelial cells, dissociated histiocytoid cells with intracytoplasmic mucinous material, and spindle cells lying in a web-like matrix. Histologic sections showed a circumscribed tumor with microcystic spaces lined by bland uniform epithelial cells and containing secretory material. The tumor cells expressed mammaglobin and BRST-2. The cytologic features, differential diagnosis, and pitfalls are discussed. The pathologic stage was pT1N0. The patient showed no evidence of disease at 1 year follow-up.

Topics: Adult; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma; Carcinoma, Mucoepidermoid; Diagnosis, Differential; Female; Humans; Image-Guided Biopsy; Keratins; Mammaglobin A; Neoplasm Staging; Parotid Neoplasms; Ultrasonography; Vimentin

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Biomarkers; Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Membrane Proteins; Middle Aged; Mucin-1; Myoepithelioma; Neoplasm Recurrence, Local; Parotid Gland; Parotid Neoplasms; S100 Proteins

Epithelioid angiosarcoma of the parotid gland is rare, and may pose a great diagnostic challenge. We report a case of primary epithelioid angiosarcoma in a 64-year-old male without history of radiation. The histopathological findings demonstrated a high grade epithelioid neoplasm. Immunostaining showed that the tumor was positive for the pan-cytokeratin, p63, cytokeratin18, Vimentin and vascular markers CD31, and was negative for CD34, cytokeratin5/6, cytokeratin7, cytokeratin20, CD68, CD30, S-100, HMB45, desmin, α-SMA and CD45. The tumor was diagnosed as an epithelioid angiosarcoma. To our knowledge, this is the first reported case of angiosarcoma which showed common positivity for cytokeratin and p63. In addition to cytokeratin, p63 is considered a useful marker for carcinoma. The co-expression of cytokeratin and p63 in epithelioid angiosarcoma represents a diagnostic pitfall. Thus, using a panel of antibodies is essential for distinguishing this tumor from poorly differentiated carcinoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6548916707504750.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms; Predictive Value of Tests; Transcription Factors; Tumor Suppressor Proteins

A 6-year-old Girolando dairy cow was presented for evaluation of a large subcutaneous facial mass. Fine-needle aspirates of the mass contained many neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and loosely cohesive clusters with streaming erythrocytes and neutrophils in the background. Neoplastic cells were 13-25 μm in diameter and were round to cuboidal with variably distinct borders. Based on the signalment, anatomic location, and cytologic findings, differential diagnoses included salivary adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow was euthanized and a necropsy was performed. The primary neoplasm arose from the left parotid salivary gland and meastatic tumor was found in the regional lymph nodes and lung. Histologically, the tumor was composed of anastomosing and irregular solid islets surrounded by scant stroma. Cells were negative for periodic acid-Schiff (PAS), PAS-diastase, and Alcian blue pH 2.5 stains, used to detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland cells expressed cytokeratin, but not S100, α-smooth muscle actin, or vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.

Topics: Adenocarcinoma; Animals; Biopsy, Fine-Needle; Cattle; Cattle Diseases; Diagnosis, Differential; Face; Fatal Outcome; Female; Keratins; Lung; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Parotid Gland; Parotid Neoplasms

A 29-year-old woman presented from another hospital with a 10-month history of an enlarging left-sided facial mass. Computed tomographic scan revealed a mass in the superficial lobe of the left parotid gland with left-sided cervical lymphadenopathy. The patient received a total left parotidectomy and a selective neck dissection. Histopathologic slides revealed lymphoepithelial carcinoma (LEC) that stained positive for cytokeratin, as well as Epstein-Barr virus (EBV). An LEC of the parotid is a rare salivary gland tumor accounting for less than 1% of all salivary gland tumors. As reaffirmed in our case, LEC is more common in women, occurs primarily in the parotid gland, and has an ethnic predilection. Histologic analysis reveals an infiltrative, poorly differentiated tumor nestled in a lymphoid stroma, with near 100% positivity for EBV in endemic areas. Complete resection of this poorly differentiated carcinoma followed by postoperative radiation is essential for local control.

Topics: Adult; Carcinoma, Squamous Cell; Female; Herpesvirus 4, Human; Humans; Keratins; Lymphoproliferative Disorders; Neck Dissection; Parotid Gland; Parotid Neoplasms

Topics: Carcinosarcoma; Follow-Up Studies; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin-1; Parotid Gland; Parotid Neoplasms; Radiotherapy, Adjuvant; Vimentin

Nonsebaceous lymphadenoma (NSL) is an unusual benign salivary gland tumor characterized by a predominant lymphoid background, dense lymphoid infiltrate, and absence of sebaceous differentiation. To our knowledge, only 10 previous cases have been reported in the literature. We report an additional case of NSL arising in the parotid gland in 58-year-old female patient. The extensive immunohistochemical investigation of the tumor revealed the presence of both luminal and myoepithelial cells. DNA analysis for flow cytometry was performed. The histogram presented a single peak in the G0-G1 area. The tumor was considered as being DNA diploid.

Topics: Adenolymphoma; Diploidy; Female; Flow Cytometry; Humans; Immunophenotyping; Interphase; Keratins; Middle Aged; Parotid Neoplasms

Myoepitheliomas of salivary glands are generally encapsulated, slowly growing asymptomic solid masses in which more than 50% are seen in the parotid gland. Cystic myoepitheliomas are very rare.. We present an 80-year-old man with a cystic mass in the right parotid gland that had undergone superficial parotidectomy. In gross examination, a mass containing a large cyst was observed. Microscopically, tumor consisted of clear cells and small cuboidal cells, forming tubules in a hyalinized stroma. Immunohistochemically, clear cells were immunoreactive for S100 and smooth muscle actin. Cuboidal cells were positive for cytokeratin. Diagnostic and differential diagnostic criteria were discussed under the light of the current literature.

Topics: Actins; Aged, 80 and over; Biomarkers, Tumor; Humans; Keratins; Male; Myoepithelioma; Parotid Gland; Parotid Neoplasms; S100 Proteins

Non-sebaceous lymphadenoma (NSL) is a rare, recently described, benign salivary gland tumor characterized by a dense lymphoid infiltrate and absence of sebaceous differentiation. To our knowledge, only seven previous cases have been reported. In this paper, we describe an additional example of NSL along with an extensive analysis of its keratin (CK) profile. The patient was a 50-year-old woman presenting with a slowly growing painless mass in the right parotid gland. The tumor was encapsulated and measured 3 x 2 x 2 cm. Microscopically, the tumor comprised islands of epithelial cells with centrally located duct-like structures within a dense lymphoid stroma. Immunohistochemically, the tumor regularly expressed CKs 7, 8/18, and 19, which are typical for columnar differentiation and CKs 17 and 5/6, which are most typically expressed in basal cells of complex epithelia. CK14 was only expressed in rare scattered cells and eventually in groups of cells. The expression of CK10/13, which correlates with squamous differentiation, was negative. Additionally, immunostaining for smooth muscle actin, vimentin, and S-100 was also performed. The immunohistochemical findings in the neoplastic epithelial component of our case suggest a differentiation of "intercalated duct phenotype" without myoepithelial cell participation.

Topics: Biomarkers, Tumor; Female; Humans; Keratins; Lymphoma; Middle Aged; Parotid Gland; Parotid Neoplasms; Treatment Outcome

Oncocytic lipoadenomas of salivary gland are extremely rare tumors with only two previously reported cases. In this paper, we describe an additional example of oncocytic lipoadenoma showing sebaceous differentiation, a hitherto unreported occurrence. The tumor was encapsulated and measured 3 x 2.5 x 2 cm. Microscopically, the tumor comprised a mixture of oncocytes with "light" and "dark" cells intimately associated with mature adipose tissue. The oncocytes were positive for low molecular keratin, epithelial membrane antigen (EMA), and keratin 7, with only a small subgroup of cells expressing high-molecular-weight keratin, keratin 5/6, keratin 19, and p63. Terminally differentiated sebaceous cells were positive for EMA and keratin 14 only. Calponin and actins were negative, indicating a lack of myoepithelial cells in the tumor. The keratin profile and p63 expression of this oncocytic lipoadenoma suggest the presence of a dual cell population somewhat similar to the dual cell population described in some ultrastructural studies of pure salivary gland oncocytomas and may represent partial basal-cell differentiation. The presence and nature of a dual cell population in oncocytic neoplasms of salivary glands merit further investigation to confirm these observations.

Topics: Adenoma; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Middle Aged; Parotid Neoplasms

This case report discusses the clinical presentation, imaging, surgery and further treatment and course of a primary angiosarcoma of a non-irradiated parotid gland.

Topics: Aged; Aged, 80 and over; Hemangiosarcoma; Humans; Keratins; Leukocyte Common Antigens; Magnetic Resonance Imaging; Male; Neoplasm Staging; Neoplasms, Second Primary; Parotid Neoplasms; Skin Neoplasms; Tomography, X-Ray Computed

Myoepithelioma is a rare but well-characterized group of tumours, among which myoepithelioma of the salivary glands is the best known. We report two patients with myoepithelioma of parotid gland presenting as infra-auricular subcutaneous mass. The lesions were clinically suspected to be epidermal cyst. The biopsies revealed that most of the tumour cells showed epithelioid features with oval or spindle eosinophilic cytoplasm. No ductal or syringomatous epithelial structures were observed. The tumour cells showed cytoplasmic immunoexpressions of vimentin, cytokeratin (AE1/AE3), S-100 protein and smooth muscle actin (SMA). In one patient, a strong calponin positivity was observed. Maguetic resonance imaging (MRI) of both patients revealed exophytic, well-defined, strongly enhancing mass in superficial lobe of parotid gland, confirming the parotid gland origin. Myoepithelioma of parotid gland can be presented as a slowly growing tumour of pre- or infra-auricular area. In dermatologic department, it can be misdiagnosed as various dermal or subcutaneous tumours.

Topics: Actins; Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Myoepithelioma; Parotid Neoplasms; S100 Proteins; Soft Tissue Neoplasms; Subcutaneous Tissue; Vimentin

Topics: Adenolymphoma; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Ki-67 Antigen; Male; Metaplasia; Middle Aged; Parotid Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Cytoplasmic Granules; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Parotid Neoplasms

Topics: Carcinoma, Squamous Cell; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms

Epithelial-myoepithelial carcinoma of the salivary gland is a rare, low-grade, neoplasm, composed of ductal and myoepithelial cells. We present two novel cell lines, which have been characterised by immunofluorescence, derived from an epithelial-myoepithelial carcinoma of the parotid gland. A resected mass of the parotid gland was diagnosed as an epithelial-myoepithelial carcinoma by routine histological examination. Part of the specimen was labelled with a panel of antibodies confirming the tumour type. The other part was finely minced and the explants were incubated in DMEM supplemented with penicillin and streptomycin, at 37 degrees C in a humidified 5% CO(2) atmosphere. Two cell types were identified by immunofluorescence-a small cobblestone cell, positive for AE1/AE3 and p53, and a polyhedral cell, positive for vimentin, smooth muscle markers and S-100. Herein two cell lines are presented in order to open up possibilities of new studies and a discussion of the events that culminate in this bimodal neoplasm is also performed.

Topics: Adult; Carcinoma; Cell Culture Techniques; Female; Humans; Keratins; Neoplasm Proteins; Nuclear Proteins; Parotid Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Tumor Cells, Cultured; Tumor Suppressor Protein p53

The correct diagnosis of high-grade mucoepidermoid (MEC), which is composed of solid islands of intermediate and squamous cells, may be challenging, due to its similarity to other tumours, mainly with squamous cell carcinoma (SCC). The present report employed immunohistochemical technique against different cytokeratins (CKs), in order to differentiate these two entities. : Six high-grade MEC and six SCC of the parotid region, retrieved from the files of both Oral Pathology Department of the School of Dentistry of University of São Paulo and Pathology Department of A.C. Camargo Hospital, were submitted immunohistochemical technique against Cks 7,8, 10, 13, 14 and 19. : High-grade MEC was positive for Cks 7, 8, 13, 14 and 19. The cases of SCC showed strong positivity for CK14, and CK10 was present only in focal areas. Our results highlight the use of CKs (especially CK14) to differentiate high-grade MEC and SCC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Proteins; Parotid Neoplasms

The aim of this study was to determine the immunoprofile of salivary duct carcinoma and to differentiate intraductal growth from invasive growth.. We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19, vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma. This panel is currently used for identification of different components of salivary gland tumours in our laboratory. All tumour cells were positive for cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells surrounding tumour islands.. The finding of cytokeratin 14 was important to confirm the in-situ intraductal growth, which probably characterizes this low-grade neoplasm.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms

Benign salivary gland tumors composed of purely squamous cells are quite unusual and are not included in the World Health Organization classification. We have seen two benign parotid gland tumors characterized by multicystic spaces with stratified squamous linings and focal solid epithelial nests. Seifert et al. recently described such a case as a choristoma; we, however, herein propose a new designation, keratocystoma, for this unique tumor group, because of its distinctive histological features. These tumors occurred in men aged 18 and 38 years with enlarging parotid gland tumors. Both had largely similar gross and histological features, with some variations. The epithelium lining of the cysts showed apparent keratinization through a parakeratotic or orthokeratotic pathway without forming a granular cell layer. Stratification of the epithelium was always regularly oriented from the outer basal to the inner keratotic cell layer. Focally, the outer layer had bud-like protrusions. In some areas, solid squamous cell islands surrounded by basement membrane were enclosed within the collagenous stroma. These cystic and solid structures were randomly distributed, showing no definite lobular architecture. All of the tumor cells had uniform, bland nuclei and abundant eosinophilic cytoplasm. Scattered mitotic figures were observed, limited to the outer epithelial layer, and showed no abnormal patterns. Transformation from the parotid ductal epithelium to the tumor cells is evident. Foci of foreign-body reactions against keratin materials were present. Immunoreactivities for cytokeratins reconfirmed the nature of squamous differentiation of the tumor cells. Ki-67-positive cells were confined along the outer basal layer of the tumor epithelium. Tests for alpha-smooth muscle actin and S-100 protein were completely negative. Both patients had no evidence of recurrence 3 and 2 years after subtotal parotidectomy, respectively, without any additional therapy. We believe that this lesion represents a benign cystic neoplasm rather than a malignant tumor or pseudoneoplastic metaplastic condition. It is important to recognize that this peculiar benign tumor does originate from the salivary gland.

Topics: Adult; Epithelium; Humans; Keratins; Male; Parotid Neoplasms; Tomography, X-Ray Computed

We report a case of acinic cell adenocarcinoma of the parotid in a 18-year-old young man. Clinical examination showed a firm mobile mass of the gland. Light microscopy revealed the tumor composed of two distinct cell populations: a main one with large, polyhedrical or round cells with eosinophilic cytoplasm and a smaller proportion of granular cytoplasm clear cells. These tumor cells were periodic acid Schiff reaction (PAS) and mucicarmine staining negative. Immunohistochemically tumor main cells exhibited diffuse positive reactivity for cytokeratin and focal for S-100 protein. Both reactions were negative in smaller cell population. Was formulated a diagnosis of "non-specific glandular cell-type of acinic cell adenocarcinoma.

Topics: Adenocarcinoma; Adolescent; Humans; Keratins; Male; Parotid Gland; Parotid Neoplasms; S100 Proteins

Topics: Actins; Adenoma, Pleomorphic; Adipose Tissue; Aged; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Muscle, Smooth; Parotid Neoplasms; S100 Proteins

A case of epithelial-myoepithelial carcinoma of the parotid gland harboring p53 mutation is reported. The tumor removed from a 67-year-old Japanese female was composed of an organoid biphasic population of cells: inner dark epithelial cells were surrounded by clear myoepithelial cells. The cells were immunopositive for EMA and smooth muscle actin, respectively. Some of the epithelial cells formed solid nests. Immunostaining for proliferating cell nuclear antigen (PCNA) resulted in a higher percentage of labeled cells in the solid epithelial region than in the region with the more general biphasic pattern. Genetic analysis, including polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and nucleotide sequencing, revealed a mutation in codon 207 (aspartic acid to glycine) of the p53 tumor-suppressor gene. To our knowledge, this is the first report of a mutation in the p53 gene in an epithelial-myoepithelial carcinoma of the salivary gland.

Topics: Actins; Aged; Base Sequence; Carcinoma; DNA Mutational Analysis; DNA, Neoplasm; Female; Genes, p53; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms; Point Mutation; Proliferating Cell Nuclear Antigen

Warthin's tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin's tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin's tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin's tumour and its metaplastic variant.. Twenty-six cases of Warthin's tumour, among them eight metaplastic Warthin's tumours, were investigated employing immunohistochemistry. Both Warthin's tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin's tumour, but involved basal as well as surface cells in metaplastic Warthin's tumour.. Warthin's tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin's tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin's tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin's tumour, but is expressed also in surface cells in metaplastic Warthin's tumour.

Topics: Adenolymphoma; Aged; Aged, 80 and over; Cell Differentiation; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Middle Aged; Parotid Neoplasms

A 69-year-old japanese female with epithelial myoepithelial carcinoma (EMC) in the parotid gland is reported. The tumor, 3.5 x 4.0 x 1.5 cm in size, was located in the left parotid gland. Histopathological examination of the surgically removed tumor revealed that it was composed of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well as solid clear cell nests. The unique histological finding of this tumor was that it had a cribriform-like arrangement of myoepithelial cells resembling an adenoid cystic carcinoma. On the other hand, the typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of low molecular weight cytokeratins, CAM 5.2 and EMA in the ductal part, and smooth muscle actin, S-100 protein, and vimentin in the myoepithelial component.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Parotid Neoplasms

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast. We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months. Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma. We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."

Topics: Aged; Biomarkers; Desmin; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucin-1; Parotid Neoplasms; Salivary Ducts; Sarcoma; Vimentin

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.

Topics: Aged; Base Sequence; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; Cyclin D1; Diagnosis, Differential; DNA Mutational Analysis; DNA, Neoplasm; ErbB Receptors; Humans; Keratins; Ki-67 Antigen; Loss of Heterozygosity; Lung Neoplasms; Male; Microscopy, Electron; Parotid Neoplasms; Point Mutation; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

A peculiar case of papillary carcinoma arising in the parotid gland is reported. A 68-year-old woman presented with a right, painless, parotid mass, measuring approximately 3 cm in greatest diameter. A conservative parotidectomy was performed. Histologically, the neoplasm showed exophytic papillary projections into a cavity. The cells were focally suggestive of epidermoidal differentiation, whereas a transitional differentiation was noted in other portions, as in bladder papilloma. Immunohistochemical studies showed strong positivity of the neoplastic cells for cytokeratin and weak positivity for PCNA and Mib-1. We classified this neoplasm among the papillary tumors with a low-grade of malignancy.

Topics: Aged; Antigens, Nuclear; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Nuclear Proteins; Parotid Neoplasms; Proliferating Cell Nuclear Antigen

Salivary duct carcinoma is a highly malignant adenocarcinoma of salivary origin. Its pathologic features are distinct from the other salivary gland tumors and bear a remarkable histologic resemblance to ductal breast carcinoma. The clinical course is rapid and the prognosis is dismal. Aggressive therapy is warranted, including primary tumor resection, cervical neck dissection, and radiotherapy. We present a case of salivary duct carcinoma of parotid origin with a very long-term evolution in clear contrast to its supposed aggressiveness. Tumor cells expressed low- and high-molecular-weight cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, and c-erbB-2 but not estrogen and progesterone receptors, actin, and S-100.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Male; Mucin-1; Neck Dissection; Neoplasm Invasiveness; Parotid Neoplasms; Radiotherapy, Adjuvant; Receptor, ErbB-2; Salivary Ducts

A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75-year-old man is presented. The tumor was a relatively well-defined, hard, subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek. Microscopic examination of an excisional biopsy specimen revealed tumor cells showing squamous differentiation, a papillary growth pattern, and ductal structures with comedo necrosis. Immunohistochemical studies showed positive reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought to be the accessory parotid gland duct epithelium.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleolus; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Epithelium; Humans; Keratins; Male; Mucin-1; Necrosis; Parotid Gland; Parotid Neoplasms; Salivary Ducts

True malignant mixed tumors (carcinosarcomas) of salivary gland origin are exceedingly rare and demonstrate malignant epithelial and stromal components. We report a case of parotid gland carcinosarcoma that showed squamous cell carcinoma and malignant fibrous hystiocytoma without clinical or histologic evidence of a preexisting pleomorphic adenoma. This tumor consisted of 2 histologically different populations of cells without evidence of a common origin from the myoepithelial cell, which is the putative precursor cell of pleomorphic adenoma and its derived carcinosarcoma. In addition to supplementing the literature, this case report includes cytohistologic and immunohistochemical analyses that provide further insights into the variable histogenesis of this neoplasm and the distinction between de novo carcinosarcoma and carcinosarcoma originating from pleomorphic adenoma.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinosarcoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Parotid Neoplasms; Tomography, X-Ray Computed

A case of distinctive benign cystadenoma of the parotid gland composed of several different morphological components is presented. The most conspicuous morphological component and the largest part of the neoplasm was represented by solid sheets of oncocytic cells surrounded by myoepithelial cell layer. Most oncocytic cells possessed large intracytoplasmic vacuoles with the nuclei displaced towards the periphery, imparting them with a striking signet-ring cell appearance. The size of the intracytoplasmic vacuoles ranged from 4 to 50 microm. Immunohistochemically these signet-ring cells lacked immunoreactivity for S-100 protein and cytokeratin but they strongly stained for antimitochondrial antibody 113-1. The present case illustrates an unusual, hitherto undescribed, morphological feature of benign oncocytic cystadenoma of the parotid gland.

Topics: Actins; Adenoma, Oxyphilic; Aged; Carcinoma, Signet Ring Cell; Cystadenoma; Female; Humans; Immunoenzyme Techniques; Keratins; Mitochondria; Parotid Neoplasms; S100 Proteins; Vacuoles

Juvenile pleomorphic adenoma of the parotid gland represents an extremely rare tumour entity and is comparable to congenital tumours of the salivary glands concerning its embryonal structure. The clinical detection of the tumour in a 7-year-old girl does not exclude that the tumour had developed either earlier or immediately after the birth. The high cellularity and the evidence of primitive epithelial and myoepithelial cellular structures do not justify its classification as a malignant tumour. However the presence of embryonal tissue structures associated with the end of the third month of embryogenesis is characterized by more solid cell formations in partly verticulate arrangement. The absence of further differentiation into lobular structures and differentiated duct or acinic cell formations may be due to cell arrest. Differential diagnosis of juvenile pleomorphic adenoma must distinguished it from other congenital salivary gland tumours (e.g. congenital basal cell adenoma, hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma, salivary gland anlage tumour.

Topics: Adenoma, Pleomorphic; Biomarkers, Tumor; Cell Transformation, Neoplastic; Child; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Parotid Gland; Parotid Neoplasms

Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully.. Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison.. The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics.. MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.

Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Microfilament Proteins; Middle Aged; Myoepithelioma; Myosins; Parotid Neoplasms; S100 Proteins; Salivary Gland Neoplasms; Submandibular Gland Neoplasms; Tumor Suppressor Protein p53; Vimentin

A 27-year-old woman with a Malignant Triton Tumor (MTT), or malignant schwannoma with rhabdomyoblastic differentiation, located in the parotid cell and infiltrating the nasal sinuses and the left orbit is described. The initially resected tumor showed three recurrences within a 2 years follow-up period. During successive recurrences an increase in cellular density, number of mitoses and necrosis was noticed. Immunohistochemical analysis showed that the tumor was composed of a mixed population of cells. Some of them showed positivity for actin, desmin and myoglobin, while others were positive for S-100 protein, glial fibrillary acid protein, and IV-collagen. Cytokeratin stainings were negative. Up to now, 8 benign triton tumors and another 45 cases of MTT have been described. None of them was primarily located in the parotid gland, and infiltration to the orbital cavity has not been previously described.

Topics: Actins; Adult; Collagen; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Myoglobin; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neurilemmoma; Orbital Neoplasms; Parotid Neoplasms; S100 Proteins

Clinical, histological and immunohistochemical data on 71 parotid gland tumors were analyzed. Benign neoplasms accounted for 71.8% of the case material and malignant tumors 22.6%. Chronic parotitis occurred in 5.6% of the total case number. Pleomorphic adenomas and mucoepidermoid carcinomas were the most frequently occurring benign and malignant neoplasms. Pleomorphic adenomas stained positive for S-100 protein, tenascin, smooth muscle actin, synaptophysin and chromogranin A. This immunohistochemical, histological and clinical analysis was believed to be of potential assistance in the diagnosis, treatment and prognosis of parotid gland tumors.

Topics: Actins; Adenoma, Pleomorphic; Antigens, Neoplasm; Carcinoma, Mucoepidermoid; Chromogranin A; Chromogranins; Chronic Disease; Desmin; Glycoproteins; Humans; Immunoglobulin A, Secretory; Immunohistochemistry; Keratins; Parotid Neoplasms; Parotitis; Prognosis; S100 Proteins; Secretory Component; Synaptophysin; Tenascin; Tumor Suppressor Protein p53

We report an example of lipoadenoma of the parotid gland, a previously undescribed tumor of the salivary gland. It is a well-circumscribed tumor comprising an intimate admixture of mature fat cells and branching narrow tubules. The tubules were elongated and had small or absent lumina, resulting in a remarkable Sertoliform pattern. They were lined by columnar cells, which were supported by a basal cell layer. The latter cells lacked evidence of myoepithelial differentiation but were best highlighted by immunostaining for high molecular-weight cytokeratin (34 beta E12). Comparison with the normal salivary gland components showed the greatest homology of the neoplastic tubules with the striated duct, which normally has an incomplete basal cell layer. The latter phenomenon is under-recognized, with some current textbooks still describing the presence of a single cell type only in the striated duct of the salivary gland.

Topics: Adenoma; Adult; Humans; Immunohistochemistry; Keratins; Male; Parotid Neoplasms

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Topics: Adenoma; Carcinoma; Diagnosis, Differential; Female; Hamartoma; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Microscopy, Electron; Parotid Neoplasms; Periodic Acid-Schiff Reaction; Submandibular Gland Neoplasms; Teratoma; Vimentin

The pathobiology of salivary neoplasms can best be studied in a model system that reflects the native state of the tumor. The present study describes the use of a three-dimensional collagen gel (organoid) system in which pleomorphic adenomas of the parotid gland were propagated in vitro. Five pleomorphic adenoma cultures were established as organoid gels and compared with touch-preparations or cryopreserved specimens of native tumor. The organoid cultures demonstrated normal DNA content, the expression of myoepithelial cell proteins, and the production of sulfated acid mucins; these cellular and secretory features mimicked those found in the archival specimens. Further, organoid cultures of pleomorphic adenoma could be initiated after monolayer culture, demonstrating that culture on a plastic support does not alter the nature of the cells. Development of an in vitro culture system that maintains the native state of pleomorphic adenoma is an important tool for studying the pathobiology of these tumors.

Topics: Actins; Adenoma; Adult; Aged; Biomarkers, Tumor; Chondroitin Sulfates; DNA, Neoplasm; Glycosaminoglycans; Humans; Immunohistochemistry; Keratins; Middle Aged; Organoids; Parotid Neoplasms; Tumor Cells, Cultured

Topics: Aged; Biomarkers, Tumor; Carcinoma, Small Cell; Humans; Keratins; Male; Microscopy, Electron; Neck Dissection; Parotid Gland; Parotid Neoplasms; Tomography, X-Ray Computed

Myoepitheliomas of the salivary glands remain a controversial entity. To contribute to the knowledge of this entity, 16 myoepithelial tumors of the salivary glands were studied: 12 benign myoepitheliomas (BME) and 4 malignant myoepitheliomas (MME). The clinical and the histologic findings of each case were studied Immunohistochemistry and flow-cytometry analysis were performed from the paraffin-embedded material in 15 cases. An electron-microscopy study was performed in 8 cases. The myoepithelial tumors affected patients of both sexes equally. The mean age of the patients with BME was 54 years, and the mean age of patients with MME was 62 years. Eight cases of BME originated in the parotid gland and 4 cases originated in the minor salivary glands. All the MME developed from a benign preexistent tumor: two developed from a pleomorphic adenoma in the parotid gland, and the other two MME developed in the minor salivary gland from a BME. The myoepithelial tumors were composed of epithelioid, plasmacytoid, spindle, or clear cell types, and they showed a solid or a myxoid pattern of growth. Immunohistochemical studies revealed marked and diffuse positivity to cytokeratins, vimentin, and S-100 protein in all cases. Glial fibrillary acidic protein was positive in 8 cases (53%), and muscle-specific actin and smooth-muscle actin were positive in only 3 cases (20%); they were all cases of BME. Desmin was negative in all tumors. Ultrastructural studies showed the presence of basal membrane, tight junctions, intermediate filaments, and microvilli as well as actin-like filaments lacking focal densities in all cases. But actin-like filaments with focal densities were not identified. Flow cytometry determined that all BME were diploid with a mean proliferative index of 7.73%. Two of the MME were diploid and the other two MME were aneuploid. The mean proliferative index of MME was 11.93%. In conclusion, BME and MME originated in major and minor salivary glands can display different histologic patterns and cellular features. Some immunohistochemical and ultrastructural characteristics have been found in all these neoplasms, which supports the idea that myoepitheliomas are composed by neoplastic modified myoepithelial cells, not fully differentiated. These techniques can be useful for the diagnosis of these tumors.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Desmin; DNA, Neoplasm; Female; Flow Cytometry; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Maxillary Neoplasms; Microscopy, Electron; Middle Aged; Myoepithelioma; Parotid Neoplasms; Ploidies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Vimentin

Salivary duct carcinoma (SDC) has been established as a morphologically distinct and highly aggressive (HG) malignancy of the major salivary glands. However, a low grade (LG) or intermediate grade salivary duct neoplasm has not been described.. We report the clinicopathologic findings of 10 cases believed to represent the (LG) counterpart of SDC. Immunoperoxidase stains were performed on five cases, and electron microscopy on three.. All of the tumors occurred in adult patients with no sex predilection, and presented as slow growing parotid gland lesions. Four cases involved the superficial lobe, one the deep lobe, and one arose within an intraparotid lymph node. The exact location of the tumor within the parotid gland was not stated in four cases. The size of the tumors ranged from 0.7 to 4 cm in greatest dimension, with most measuring between 1 and 2 cm. The gross appearance was focally to predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillary, tufted, and plaque-like intraluminal projections; (2) ducts distended by a solid or pseudocribriform (fenestrated) cellular proliferation, with varied cystic dilatation; and (3) ducts exhibiting architectural atypia. The three patterns coexisted and merged in most tumors, in varying proportions. All tumors shared bland to LG cytologic features, with the exception of one that had focal high-grade cytologic ductal atypia. Despite gross circumscription, there was microscopic multifocality, and in one case, stromal invasion. By immunohistochemistry, the neoplastic cells expressed the conventional ductal and glandular epithelial cell markers in addition to strong positivity for S-100 with coexpression for CK-903. Electron microscopy confirmed the ductal phenotype of the tumors and supported an in situ process evidenced by the presence of native myoepithelial cells. Nine patients underwent total parotidectomy and one superficial parotidectomy. One patient received radiation therapy following total parotidectomy. Follow-up for 6 cases ranged from 2 to 12 years and revealed no evidence of disease.. LG-SDC represents the LG end of the spectrum of salivary duct malignant neoplasms and exhibits differentiation towards an intercalated duct-like cell phenotype. Its relationship to HG-SDC should be further explored.

Topics: Adult; Aged; Carcinoma; Cell Membrane; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microvilli; Middle Aged; Organelles; Parotid Neoplasms; S100 Proteins; Salivary Ducts

Previous morphologic and histochemical studies have documented extracellular elastin and elastic fibers within the matrix of pleomorphic adenomas of the salivary glands. By morphologic criteria, the elastin appeared to be synthesized by the tumor rather than being a consequence of stroma produced in response to the tumor cells. To examine this issue, nine pleomorphic adenomas were studied by immunohistochemistry and in situ hybridization with tropoelastin-specific antibodies and complementary DNAs. Corroborating the previous morphologic studies, immunohistochemistry demonstrated abundant extracellular elastin within the matrix of pleomorphic adenomas. Additionally, both immunohistochemistry and in situ hybridization demonstrated continued synthesis of tropoelastin by the neoplastic cells. Tropoelastin production was seen in neoplastic cells with all morphologies.

Topics: Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Antibodies; DNA, Complementary; Elastin; Extracellular Matrix; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Middle Aged; Parotid Neoplasms; S100 Proteins; Tropoelastin

This study evaluated the distribution of cytokeratins detected by monoclonal antibodies directed against individual keratin proteins in normal human salivary glands and epithelial tumour cells of Warthin's tumour arising in parotid glands to determine a more precise mapping of their cellular distribution. The normal salivary ducts showed the presence of cytokeratin 7, 8, 18 and 19 in the intercalated, striated and excretory ducts, the primary keratins of stratified and simple epithelia with a profile very similar to the non-cornified epithelium of the oral mucosa. The basally located cells of salivary gland ducts other than myoepithelial cells were reactive for keratins 7 and 19 suggesting a close similarity in profile of keratin in the basal cells of the oral epithelium. In Warthin's tumour, keratins 7, 8, 18 and 19 were consistently detected in the epithelial cells of the tumour, a profile with a tendency to mimic the same in normal ductal epithelium. The distribution, however, was diverse and a heterogeneity was observed in the basal and luminal cells of Warthin's tumour which differed even in different areas of the same tumour specimen.

Topics: Adenolymphoma; Antibodies, Monoclonal; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Parotid Gland; Parotid Neoplasms; Submandibular Gland

Concerning the hypothesis that distinct types of salivary gland cysts may be the starting point of a salivary gland tumour, a histological examination of 1,661 salivary gland cysts was performed in order to analyse the cell types and their proliferative activity. Epithelial alterations were found especially in salivary duct cysts of parotid gland and in mucous retention cysts of minor salivary glands. Characteristic cellular changes were epithelial metaplasias (goblet cells, clear cells, squamous cells) and focal epithelial proliferations with plump or papillary plaques projecting into the cyst lumen. Only in one case had a mucoepidermoid carcinoma developed in the wall of a parotid duct cyst. The epithelial metaplasia and focal proliferative activity in salivary duct cysts is comparable to similar alterations in odontogenic cysts as possible early manifestation of a tumour, especially of an ameloblastoma or mucoepidermoid carcinoma. The differential diagnosis of salivary duct cysts must take primarily cystadenomas and cystic mucoepidermoid carcinomas of well-differentiated type into account.

Topics: Carcinoma, Mucoepidermoid; Cell Division; Cystadenoma, Mucinous; Cystadenoma, Papillary; Cysts; Epithelium; Histocytochemistry; Humans; Keratins; Parotid Neoplasms; Retrospective Studies; Salivary Ducts; Salivary Gland Diseases

Markers for normal salivary gland myoepithelium were used to determine the extent of their expression in the neoplastic myoepithelial (nonluminal) cells of pleomorphic adenomas and then in the tumor cells in myoepitheliomas and to gather information necessary to establish diagnostic criteria, especially muscle actin expression, for myoepitheliomas.. Methanol/acetic acid-fixed and paraffin-embedded tissue was used to immunohistochemically study expression of intermediate and smooth-muscle actin filaments in nonluminal cells in 14 pleomorphic adenomas and to compare this to their expression in five myoepitheliomas.. In routine histologic sections, the morphologic variants of nonluminal tumor cells--spindle, stellate, polygonal, angular, and plasmacytoid--in pleomorphic adenoma mirror the spectrum of tumor cells in myoepitheliomas. Immunocytochemical similarities are also apparent. Two specific markers for myoepithelial cells in the normal salivary gland, muscle-specific actin and cytokeratin 14, were both variably, independently, and never uniformly expressed in nonluminal cells of pleomorphic adenoma and tumor cells in myoepitheliomas regardless of their morphology. Cytokeratin 14 in addition labels basal cells of excretory ducts. Both muscle-specific actin and cytokeratin 14 preferentially localized to single layers of periductal cells in pleomorphic adenomas, angular, polygonal, and plasmacytoid cells preferentially expressed cytokeratin 14. Similar patterns were noted in the three myoepitheliomas with reasonable expression of the two markers. Only isolated single cells or small groups of plasmacytoid cells in four pleomorphic adenomas with a significant component of these cells and the two plasmacytoid myoepitheliomas immunostained for muscle-specific actin and cytokeratin 14. In both tumor types, vimentin was nearly uniformly expressed in nonluminal tumor cells of all morphologic types, including plasmacytoid cells.. The range and transition of morphology of nonluminal cells in pleomorphic adenomas is reflected in myoepitheliomas. Incomplete or absent expression of the myoepithelial/basal cell markers, muscle-specific actin, and cytokeratin 14, and the general expression of vimentin is common to both tumors. Because these findings apply to the majority of plasmacytoid cells in pleomorphic adenomas, tumor cells with a similar morphology and immunoprofile are to be expected in myoepitheliomas; the term plasmacytoid myoepitheliomas is thus appropriate regardless of the presence or absence of muscle-specific actin.

Topics: Actins; Adenoma, Pleomorphic; Biomarkers, Tumor; Cytoskeletal Proteins; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Myoepithelioma; Neoplasm Proteins; Parotid Gland; Parotid Neoplasms; Salivary Gland Neoplasms; Vimentin

Spindle cell carcinomas of the salivary gland are extremely rare, with only a few cases having been previously reported. We present a 55-year-old man with a rapidly enlarging mass in the left parotid gland. Despite radical surgery, the tumour recurred, and led to death 11 months later. Histopathologically, the tumour was composed of two components, a squamous cell carcinoma component and a spindle cell sarcomatoid component. A diagnosis of primary spindle cell carcinoma of the parotid gland was made. Immunohistochemical studies revealed keratin positivity and vimentin negativity in the squamous cell carcinoma component: the spindle cell sarcomatoid component was positive for vimentin and negative for keratin, but showed focal positivity for epithelial membrane antigen. The origin of the sarcomatoid component and the differential diagnosis from malignant mixed tumours are discussed.

Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms

Malignant lymphoepithelial lesions (MLEL) are rare tumors of the salivary glands that show high incidence in Inuit Canadians, Alaskans, and Greenland Eskimos. The tumors are usually anaplastic or poorly differentiated squamous cell carcinomas. Focal spindle cell elements have been rarely reported. The tumors have been epidemiologically linked to Epstein-Barr virus infection. We present a case of malignant lymphoepithelial lesion showing exclusive spindle cell morphology. The patient is a 44-year-old male Inuit Canadian who presented with a long-standing history of a left parotid mass. The mass did not show evidence of rapid growth or facial nerve involvement. Parotidectomy was performed. The tumor was histologically composed of spindle cells nodules in a background of lymphocytes. The spindle cells showed no evidence of cytologic atypia but were mitotically active. Immunohistochemical staining for low-molecular-weight cytokeratin was only focally positive. The differential diagnosis included a mesenchymal neoplasm and malignant lymphoepithelial lesion. Electron microscopic examination confirmed the squamous nature of the neoplasm. Intracytoplasmic viral particles were also identified ultrastructurally. In situ hybridization for Epstein-Barr virus mRNA using a 30-base oligonucleotide probe specific for the EBER-1 gene showed very high level of expression in the tumor cells. No expression was noted in the adjacent parotid gland tissue. Our findings confirm the squamous nature of malignant lymphoepithelial lesions despite the spindle cell morphology occasionally seen in these neoplasms. They also confirm the strong role of Epstein-Barr virus infection in the pathogenesis of these tumors. This may have further diagnostic and therapeutic implications.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Base Sequence; Carcinoma, Squamous Cell; Genes, Viral; Herpesvirus 4, Human; Humans; In Situ Hybridization; Inclusion Bodies; Keratins; Male; Molecular Sequence Data; Parotid Neoplasms; RNA, Messenger; RNA, Viral

We report a case of epithelial-myoepithelial carcinoma of the parotid gland arised in a 72 years-old woman, in which the diagnosis was suspected on fine-needle aspiration and confirmed on surgical specimen. Immunohistochemical evidence for the dual differentiation (glandular and myoepithelial) of the tumour was obtained both on surgical specimen and cytological inclusion. Morphological features and proliferating index (MIB1) analysis suggest that this case is an intermediate grade malignant neoplasm. Main differential diagnosis of the epithelial-myoepithelial carcinoma with predominantly clear cell tumours of the salivary glands were discussed.

Topics: Adenocarcinoma, Clear Cell; Aged; Biomarkers, Tumor; Carcinoma; Coloring Agents; Diagnosis, Differential; Female; Humans; Keratins; Mitotic Index; Mucin-1; Neoplasm Proteins; Nerve Tissue Proteins; Parotid Neoplasms

Topics: Actins; Carcinosarcoma; Cytoskeletal Proteins; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Parotid Neoplasms; S100 Proteins; Vimentin

Basal cell adenocarcinoma is a recently defined category of salivary gland neoplasms. As the terminology implies, this group of tumors has many histopathologic features that are similar to the more well-known basal cell adenomas. To better characterize these tumors, 23 basal cell adenocarcinomas were reviewed and compared with 11 basal cell adenomas with the use of light microscopic and immunohistochemical methods. Evaluation of cytokeratin, S-100 protein, glial fibrillary acidic protein, carcinoembryonic antigen, epithelial membrane antigen, smooth muscle actin, vimentin, B72.3, Ber-EP4, and milk fat globulin immunoreactivity was performed. Parallel to the morphologic similarity, the immunoprofiles of the basal cell adenocarcinoma and basal cell adenoma were quite similar. Both tumors showed reactivity patterns indicative of ductal epithelial and myoepithelial differentiation. In addition, reactivity to some polymorphic epithelial mucins was observed, which suggested glandular differentiation. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential salivary gland epithelial cells. The comparable immunohistochemical profiles imply evolvement from similar cell lines and lead us to conclude that distinction between the two is not possible on the basis of these findings.

Topics: Actins; Adenocarcinoma; Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Parotid Neoplasms; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

A unique extraskeletal chondroma is reported which occupied the entire right parotid gland of a 32-year old man. The midsized tumour was hard and well circumscribed. Its histological pattern was typical of a chondroma with lobules of hyaline cartilage and several areas of calcification. The chondrocytes were positive for S-100 protein and negative for smooth muscle and myoepithelial markers. Epithelial neoplastic elements, as found in pleomorphic adenomas, were not detected in the present case, neither morphologically nor immunohistochemically.

Topics: Adult; Biomarkers, Tumor; Chondroma; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mucin-1; Parotid Neoplasms; S100 Proteins

Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high-grade malignancy in the current classification of salivary gland neoplasms.. In an effort to identify clinically relevant prognostic features, we studied the clinicopathologic and immunohistochemical findings in 15 SDC, with ultrastructural evaluation of three tumors.. Thirteen SDC occurred in the parotid gland, one in the Stensens duct, and one in the palate. Twelve patients were men (ratio of men to women = 4:1). Patients ranged in age from 39 to 81 years (mean = 59 years). Tumor size varied from 1.2 to 6.5 cm (mean = 3.1 cm). An intraductal component was identified in 10 of 14 primary SDC that made up 10% to 95% of the tumor. In three SDC a preexisting pleomorphic adenoma was identified. Immunohistochemical and electron microscopic evaluation showed the SDC to be composed entirely of ductal cells, and one tumor exhibited features of striated duct differentiation.. SDC show a broader clinicopathologic spectrum than previously described. The tumor may arise in a pleomorphic adenoma. The proportion of intraductal and extraductal growth is variable and of prognostic significance. Although the majority of SDC behave in a high-grade fashion, those with a predominant intraductal component of greater than 90% (PID-SDC) and minimally invasive (< 8 mm) SDC in pleomorphic adenoma appear to have a more favorable prognosis.

Topics: Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Carcinoma, Intraductal, Noninfiltrating; Cell Membrane; Cell Nucleus; Cytoplasm; Epithelium; Female; Humans; Hyalin; Hyperplasia; Keratins; Male; Middle Aged; Mitochondria; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Palatal Neoplasms; Parotid Neoplasms

Immunohistological expressions of the cytokeratin (CK) subclass, vimentin, glial fibral antigen protein (GFAP), alpha-smooth muscle actin, and S-100 protein were investigated in pleomorphic adenoma of the parotid gland. In addition, the correlation between immunohistological findings in the normal parotid gland and those in pleomorphic adenoma was examined. Vimentin, S-100 protein, and GFAP, which were not detected in the normal parotid gland, were observed in pleomorphic adenoma. Only CK-1, which was not detected in the normal parotid gland, was expressed intensely in squamous metaplastic lesions of pleomorphic adenoma. All other CK detected in pleomorphic adenoma were also expressed in the normal parotid gland. Therefore, the expression of vimentin, S-100 protein, GFAP, and CK-1 in pleomorphic adenoma is related to oncogenesis. Since most types of CK expression were observed in solid pleomorphic adenoma lesions and all types of CK expression detected in other lesions were included, cellular differentiation between solid and nonsolid lesions was elucidated. According to the pattern of CK subclass expression, the following sequence of differentiation was suggested; solid lesion-->myxoid lesion-->chondroid lesion, solid lesion-->tubular lesion, solid lesion-->myoepithelioid lesion, and solid lesion-->squamous metaplastic lesion. In normal parotid glands, satellite cells around the ductal cells showed all types of CK subclass expression detected in myoepithelial cells, acinus cells, and ductal cells. Since the types and patterns of CK expression in solid lesions of pleomorphic adenoma are the same as those in satellite cells in the normal parotid gland, pleomorphic adenoma seems to originate from satellite cells. If satellite cells in the normal parotid gland are considered to be so-called reserve cells in the bicellular theory, the origin and cellular differentiation of pleomorphic adenoma can be explained in relation to CK subclass expression.

Topics: Actins; Adenoma, Pleomorphic; Cell Differentiation; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Parotid Gland; Parotid Neoplasms; S100 Proteins; Vimentin

In order to develop a more objective method of evaluating the origin of adenolymphoma, we immunohistochemically investigated the expression of cytokeratins, vimentin, S-100 protein, and alpha-smooth-muscle actin using the avidin-biotin-peroxidase (ABC) method in ethanol-fixed paraffin-embedded specimens from 8 adenolymphomas. Several kinds of monoclonal antibodies which react monospecifically with each subclass of cytokeratins were used. Results were compared with specimens of 8 normal parotid glands by radical neck dissection in patients with other diseases who had not undergone radiotherapy. In the adenolymphoma specimens, basal cells were strongly positive for CK-6, but reactivity of columnar cells was apparently reduced. In contrast, columnar cells were strongly positive for CK-7, but reactivity of basal cells was reduced. In normal parotid gland specimens, CK-7 was also detected in all columnar cells in the ductal system, although some duct cells around the columnar cells, which showed strong CK-6 expression, showed poor CK-7 expression. alpha-smooth-muscle actin was present in myoepithelial cells in normal parotid gland specimens, but not in basal cells of adenolymphoma or of the normal ductal system, which were CK-6-positive. As these characteristic findings were consistently observed in all specimens, the demonstration of CK-6, CK-7, and alpha-smooth-muscle actin may be useful in the recognition and classification of columnar and basal cells. CK-8 was present in both columnar and basal cells of adenolymphoma and of the normal duct, but in the normal parotid gland, acinus cells were also strongly positive for CK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actins; Adenolymphoma; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Parotid Gland; Parotid Neoplasms; S100 Proteins; Vimentin

The distribution of immunostaining in normal major salivary gland and in 12 pleomorphic adenomas was studied using monospecific monoclonal antibodies to a number of cytokeratins, including cytokeratin 14, to smooth muscle actin and vimentin. A number of these antibodies enabled a distinction to be made between structural components of the normal gland, and to relate this to the different structures of pleomorphic adenomas. In the normal gland, the luminal duct cells expressed cytokeratins 7, 8, 18 and 19. Three antibodies were of particular value for the characterization of normal myoepithelial and basal cells; while the antibody to smooth muscle actin and the cytokeratin antibody Ks8.12 mutually exclusively stained the myoepithelial (basket) cells and the basal duct (light) cells, respectively, the recently established monospecific antibodies to cytokeratin 14 showed specific immunostaining with both cell types. These three antibodies left luminal cells virtually unstained. Ck 13 was found occasionally in single luminal excretory duct cells. Antibodies to cytokeratins 1/2, 10 and 10/11 did not show any staining in the normal gland. In the pleomorphic adenomas, the staining pattern of the two-layered tubular formation resembled that of the normal gland ducts: tumour luminal cells showed the characteristic, although more irregular, expression of cytokeratins 7, 8, 18 and 19; the outer cells resembled normal ductal basal cells with their anti-cytokeratin 14/Ks8.12-epitope staining and in that they virtually lacked staining for smooth muscle actin. Trabecular formations and cells in myxoid areas were reactive with Ks8.12 and for cytokeratin 14, occasionally also for cytokeratins 7, 18 and 19. Epidermoid cell islets expressed mainly cytokeratin 14 and inconsistently the squamous epithelial cytokeratin 13 and the epidermal cytokeratin 10/11. Vimentin was found in cells of myxoid areas. The results support the postulate that some of the normal duct basal cells act as reserve cells and can give rise to tumour formation with a primitive myxoid or trabecular pattern and a more differentiated tubular or epidermoid configuration.

Topics: Actins; Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Epithelial Cells; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Parotid Gland; Parotid Neoplasms; Reference Values; Salivary Gland Neoplasms; Submandibular Gland; Vimentin

Topics: Adenocarcinoma; Antigens, Neoplasm; Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Parotid Neoplasms; Vimentin

Salivary duct carcinoma (cribriform salivary carcinoma of the excretory ducts [CSCED]) is an uncommon malignant tumor which occurs predominantly in men (83% in this series; mean age, 61 years) and most often in the parotid gland (92% in this series). The outcome is unfavorable for most patients; of 11 of 12 patients with follow-up, 45% had local recurrence, 54% had distant metastasis, and 45% were dead of disease within 10 years of diagnosis (mean, 3 years). Metastases to lymph nodes were common (72%). Immunohistochemical studies on paraffin-embedded tissue revealed that most tumors reacted with antibodies known to mark adenocarcinoma: B72.3 (11 of 11) and Lewis Y (ten of ten). High and low molecular weight cytokeratins were present in most tumors (nine of ten and seven of nine cases, respectively), supporting the concept that these adenocarcinomas were of ductal origin. Parotid ducts adjacent to CSCED expressed B72.3 in six of nine cases studied, but parotid ducts from normal tissue (adjacent to benign mixed tumors or enlarged periparotid lymph nodes) rarely expressed this marker (one of 17 cases). The detection of B72.3 diffusely in parotid ducts, especially those with atypia, may imply the presence of malignant tumor nearby, which could be useful in evaluating limited tissue from the parotid. However, further studies are necessary to confirm the significance of this finding.

Topics: Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Molecular Weight; Neoplasm Recurrence, Local; Parotid Neoplasms; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

In order to gain insight into the origin of Warthin's tumor, 10 cases of Warthin's tumor were compared immunohistologically with macroscopically and microscopically normal areas of the same glands, using 6 types of functional markers; carcinoembryonic antigen, secretory component, lactoferrin, keratin, S-100 protein and glial fibrillary acidic protein. It was shown that in normal parotid glands, the cells of acini, the intercalated ducts, the striated ducts, and the excretory ducts, as well as myoepithelial cells differed from each other in intensity and distribution of reaction products with antisera against those markers. Although the differences were rather subtle, the results suggested that those markers could differentiate the cell types of the salivary glands. In Warthin's tumors with double-layered tumor epithelia, the staining characteristics of the luminal and basal epithelia differed from each other. Epithelial cells on the luminal side showed immunological characteristics similar to striated duct cells of the parotid gland, while those of the basal side had characteristics similar to those of basal cells of the excretory duct. It is therefore suggested that the epithelia of Warthin's tumor may show differentiation into 2 different cell types.

Topics: Adenolymphoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Epithelium; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Lactoferrin; Male; Middle Aged; Parotid Gland; Parotid Neoplasms; S100 Proteins; Secretory Component

The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was widespread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonal-shaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.

Topics: Actins; Adult; Aged; Cell Nucleus; Female; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Middle Aged; Myoepithelioma; Organelles; Parotid Neoplasms; Vimentin

The purpose of this immunohistochemical study was to know the degree and direction of differentiation, the mechanism of mesenchymal appearance, and histogenesis in pleomorphic adenomas which were obtained from surgical removed specimens. All specimens were fixed in 10% neutral phosphoate buffered formalin, and embedded in paraffin. Sections were steined with the avidin-biotin peroxidase complex method for keratin, vimentin, desmin and S-100 protein, the peroxidase-antiperoxidase method for lysozyme, and the direct immunoperoxidase method for IgA and secretory component. Normal salivary glands were employed as controls. 1. Solid portion of pleomorphic adenomas were consisted of the focal hypline cells and scattered the duct cell-like cells. The hyaline cells were positive for vimentin and S-100 protein, and the duct cell-like cells were positive for keratin. But one case was found the bundles of spindle-shaped cells which was similar to myoepithelial cells were positive for actin and another case was consisted of the focal duct cell-like cells were observed. 2. In the tubular portion, the duct-like structures were classified into three types. One type was mono-layered structure, another type was double-layered structure and the other type is duct-like structure in the solid portion. Any inner layer of the duct-like structure were positive for keratin. 3. Double-layered duct-like structures were most common type. Among the double-layered structures, hyaline cells mostly made up the outer layered structures. At times, the spindleshaped cells of the outer layer were found. This structures were similar to intercalated portion of normal salivary glands. In one case, inner and outer layer was consisted of keratin positive cells, but outer layer was steined for keratin stronger than inner. This structure was similar to excretory duct of normal salivary glands. 4. IgA and sc were seen at inner cells and in luminal accumulation of the duct-like structures. 5. In the myxoid regions, stellate cells or spindle cells were positive for vimentin, S-100 protein and partial positive for desmin. In the chondroid regions, chondrocyte-like cells were positive for vimentin and S-100 protein. These results seemed to suggest that pleomorphic adenomas were composed of duct cell-like cells and hyaline cells. Duct cell-like cells consisted of the duct-like structure in order to transport secretion which was similar to the duct of normal salivary glands.(ABSTRACT TRUNCATED AT 250 WO

Topics: Adenoma, Pleomorphic; Desmin; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; S100 Proteins; Vimentin

A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +/- 1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.

Topics: Adenoma; Cytoskeleton; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filaments; Keratins; Parotid Gland; Parotid Neoplasms

The epithelial, vascular and lymphoid components present in two cases of adenolymphoma (Warthin's tumour) were characterized by immunohistochemistry on frozen sections. Epithelial cells were positive for cytokeratin and keratin and were in close contact with numerous factor VIII related antigen-positive capillary vessels, running parallel to the epithelial basement membrane. The capillary vessels were in communication with high endothelial post-capillary venules which were often lined by HLA-DR-positive endothelial cells. The lymphoid tissue was organized in B-cell and T-cell areas. The B-cell areas consisted of B4+/To15+ B-lymphocytes admixed with DRC-1-positive follicular dendritic reticulum cells. The T-cell areas were mainly populated by T11+/T3+/T4+ lymphocytes admixed with some S-100+/HLA-DR+ interdigitating reticulum cells. Plasma cells and T8+ lymphocytes were more numerous in the proximity of the epithelium. Leu-M3+/PAM-1+ macrophages were scattered singly in the T-cell areas or were arranged in sinus-like structures around the epithelial cysts. The epithelial basement membrane, the vascular membrane and the fibrillar reticular stroma of the lymphoid tissue were immunoreactive for laminin and type IV collagen. The possibility is discussed that the accumulation of lymphoid tissue in Warthin's tumour is modulated by the epithelial cells, perhaps through their ability to organize a peculiar pattern of vascularization.

Topics: Adenolymphoma; B-Lymphocytes; Collagen; Endothelium; Epithelium; Histocytochemistry; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Laminin; Parotid Neoplasms; T-Lymphocytes

Topics: Adenoma; Dendritic Cells; Epithelial Cells; HLA-D Antigens; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Parotid Neoplasms; S100 Proteins; Salivary Glands

Oncocytomas and Warthin's tumors were studied ultrastructurally and with immunofluorescence microscopic techniques against cytokeratins, desmin, vimentin, and actin, the latter characterizing myoepithelial cells. The cell types were found within oncocytomas, one type packed with mitochondria and virtually without filaments, the other contained fewer mitochondria but large amounts of cytokeratins. In Warthin's tumors, all cells contained cytokeratins, the basal cell to a much higher degree. No tumor cells contained vimentin or desmin. Actin was found only close to the apical cell surface in the cylindrical cells in the Warthin's tumors and around the few acinar lumina found in the oncocytomas; thus, a myoepithelial origin of oncocytic tumors of salivary glands seems less plausible. The similarity in staining pattern, namely the pronounced dimorphism of both tumor types, indicates a common progenitor of oncocytomas and the epithelial component in adenolymphomas.

Topics: Actins; Adenolymphoma; Adenoma; Deoxyribonuclease I; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Microscopy, Electron; Parotid Neoplasms; Vimentin

Twenty-two benign pleomorphic adenomas of the major salivary glands were studied by transmission electron microscopy and immunohistochemical techniques (three cases) in order to characterize the cell types comprising the epithelial and so-called mesenchymal regions of the tumors. Light- and electron-microscopic studies showed the tumors to consist of variable mixtures of neoplastic ductular epithelial cells, rare acinar cells, and metaplastic myoepithelial cells. Many of the loosely organized "stromal cells" contained structures indicative of their myoepithelial origin, e.g., perinuclear tonofilaments, ectoplasmic actin microfilaments, and remnants of basement membrane. Polyclonal antikeratin antisera strongly stained ductular epithelial and myoepithelial cells, squamoid cell nests, and periductular myoepithelial cells, whereas myxoid and chondroid cells were less intensely stained. Monoclonal cytokeratin antibody AE1 stained only the ductular epithelial cells in both the normal glands and tumors. In contrast, S-100 protein, which is present only in scattered acinar cells and myoepithelial cells in the normal parotid gland, was found in the ductular and periductular myoepithelial cells, isolated myxoid cells, and chondroid and cartilagenous cells in the tumors. Actin was found in all the cell types of the tumor but staining was strongest in the ducts. Double immunofluorescence staining for cytokeratin and vimentin revealed coexpression of both types of intermediate filaments in occasional normal acinar and intercalated duct myoepithelial cells, and in some cells in the myxoid and chondroid regions of the tumors. In the tumors, vimentin was present in occasional periductular myoepithelial cells, stellate myxoid cells, and especially in chondroid cells and chondrocytes. Our findings indicate that benign pleomorphic adenomas of the major salivary glands are pure epithelial cell tumors. The histologic complexity of these neoplasms is due to the ability of the neoplastic ductular myoepithelial cell to modulate its morphologic appearance and intermediate filament composition, and to produce large amounts of matrix substances. We further postulate that these tumors arise from neoplastically transformed intercalated ducts.

Topics: Actins; Adenoma, Pleomorphic; Adult; Aged; Antibodies, Monoclonal; Epithelium; Female; Humans; Immunoenzyme Techniques; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Parotid Gland; Parotid Neoplasms; Protein Precursors; S100 Proteins; Salivary Gland Neoplasms; Submandibular Gland; Submandibular Gland Neoplasms; Vimentin

A 76-year-old man underwent a subtotal parotidectomy for removal of a 3 cm. multicystic mass. The tumor was a salivary gland carcinoma, with both infiltrating and intraductal/intra-acinar components, exhibiting three histologic patterns: cribriform, papillary, and comedo-like. Immunohistochemical stain for keratin by the immunoperoxidase technique was strongly reactive in the vast majority of the tumor cells, indicating ductal differentiation of the tumor. Ultrastructural studies indicated primarily ductal differentiation of the tumor cells, with additional areas of acinous and myoepithelial differentiation.

Topics: Animals; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Chick Embryo; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Parotid Neoplasms

The fourth recorded squamous cell carcinoma arising in a pre-existing Warthin's tumor is reported. A gradual transition was noted from the mitochondria-rich epithelium of benign portions of the tumor to organelle-poor cells forming the areas of squamous metaplasia and carcinoma. Bundles of intermediate filaments corresponding to immunoreactive keratin were demonstrated in all epithelial parts of the tumor and also in the epithelium of a benign Warthin's tumor that was studied in parallel.

Topics: Adenolymphoma; Aged; Carcinoma, Squamous Cell; Fluorescent Antibody Technique; Humans; Keratins; Male; Microscopy, Electron; Parotid Neoplasms

Topics: Adenoma; Fluorescent Antibody Technique; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Muscle Proteins; Parotid Neoplasms; Vimentin

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Topics: Adenoma; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cytoskeleton; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; Salivary Gland Neoplasms

The aim of this study was to analyze the filament distribution in the parotid gland and their tumors. A correlation to the histogenetic implications and histological properties was attempted. Normal rat and human parotid glands as well as pleomorphic adenomas and squamous cell carcinomas of this gland were examined by the indirect immunoperoxidase technique using antibodies to the keratin polypeptide of 67,000 dalton, and 55,000 dalton and anti-actin auto-antibodies. Both keratin and actin antigens were demonstrated in the duct system and in the myoepithelial cells of the normal salivary glands. The acinar cells remained negative. In pleomorphic adenomas, there were numerous keratin-positive spindle-shaped cells which represented the so-called myoepithelial cells. These cells were demonstrated to contain actin, too. The tubular duct-like structures were labeled by keratin antiserum and by anti-actin auto-antibodies. In squamous cell carcinomas, the majority of the tumor cells were strongly labeled by keratin antibodies. Actin was detected in these malignant cells, too. Our results show important differences in the cellular elements of the normal salivary glands with regard to their filament distribution. In normal and tumoral conditions, our findings support the hypothesis of the epithelial nature of the myoepithelial cells. Our preliminary results encourage the research of filamentous structures for scientific and diagnostic purposes.

Topics: Actins; Adenoma; Animals; Carcinoma, Squamous Cell; Cytoskeleton; Histocytochemistry; Keratins; Male; Parotid Gland; Parotid Neoplasms; Rats

Topics: Actins; Adenoma, Pleomorphic; Cytoskeleton; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Parotid Neoplasms