Primary Warthin's-like adenocarcinoma of the lung: A clinicopathological, immunohistochemical, and molecular analysis of three cases.

Three cases of primary pulmonary adenocarcinoma with prominent lymphoid stroma and papillary features mimicking Warthin's tumor are presented. The patients are two women and one man ages 52, 62, and 74 years respectively. Clinically, the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging showed the presence of an intrapulmonary mass in the right lower, right upper and left lower lobe. All patients underwent lobectomy. Histologically, the tumors were characterized by the presence of and oncocytic papillary growth pattern embedded in a lymphoid rich background. Immunohistochemical stains for TTF-1, keratin 7, and beta-catenin were positive in the epithelial component, while CD20 showed strong positive staining in the lymphoid component. In addition, CD4 and CD8 also showed positive staining in a ratio of 3-4:1, EBER was negative. Kras mutations with wild type EGFR were identified in one case. Clinical follow-up ranging from 8 to 24 months was obtained showing that all patients are alive without recurrence. The cases herein presented represent an unusual histological variant of primary lung adenocarcinoma, which closely mimics Warthin's tumor.

Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg-like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3+, CD4+, FoxP3+ T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.

Sebaceous lymphadenoma of the thymus: A clinicopathologic and immunohistochemical study of 2 cases.

Two cases of primary sebaceous lymphadenoma of the thymus are presented. The patients were a man and a woman 58 and 77 years old, respectively. The female patient had a history of breast carcinoma and on follow-up was identified to have an anterior mediastinal mass; the male patient did not have any history of malignancy, and the tumor was discovered during a chest radiographic evaluation when the patient presented with symptoms of fatigue, chest pain, and dyspnea. Histologically, both lesions were characterized by the presence of solid-cystic epithelial islands in a prominent lymphocytic background. The epithelial islands were haphazardly distributed in the form of small tubular structures with focal keratinization and groups of epithelial cells with clear cytoplasm, round nuclei and lack of mitotic activity in keeping with sebaceous cells. The presence of germinal centers in the lymphoid background was seen in both cases. Immunohistochemically, the epithelial component was positive for cytokeratin 8 (CAM5.2), cytokeratin 5/6, and for adipophilin in the sebaceous component. B- and T-cell markers were positive in the lymphoid component. Clinical follow-up in both patients showed that the 2 patients were well and alive 3 years after diagnosis. The cases herein presented expand the spectrum of salivary gland-type tumors in the mediastinum and raise awareness of lesions which are easily confused with other more common thymic tumors that have different prognosis and treatment implications.

Expression of SOX10 in Salivary Gland Oncocytic Neoplasms: A Review and a Comparative Analysis with Other Immunohistochemical Markers.

OBJECTIVES: We evaluated SOX10 (SRY-related HMG-box 10) in differentiating acinic cell carcinoma (AciCC) from other salivary gland neoplasms with oncocytic features on fine-needle aspiration cell blocks (FNA CB) and compared its performance to DOG1 (discovered on gastrointestinal stromal tumor 1). MATERIAL AND METHODS: 35 FNA CB of oncocytic salivary gland neoplasms, i.e. 13 cases of AciCC, 16 of Warthin tumor (WT), 3 of mucoepidermoid carcinoma (MEC) and 3 of oncocytoma (ONC), and 75 salivary gland resections, i.e. 26 AciCC, 7 WT, 36 MEC, 3 ONC, 2 mammary analog secretory carcinomas (MASC) and 1 papillary cystadenoma were stained for SOX10 and DOG1. RESULTS: None of the benign oncocytic neoplasms were immunoreactive for SOX10 on CB or resection, similar to DOG1. On CB, 61.5 and 77% of AciCC were positive for SOX10 and DOG1, respectively. All surgically resected AciCC cases were positive for SOX10 and DOG1; other malignant oncocytic lesions such as MEC and MASC demonstrated variable SOX10 and DOG1 staining. CONCLUSION: The use of SOX10 may increase the diagnostic accuracy of oncocytic lesions on FNA. In this context, SOX10 is equivalent to DOG1 in ruling out benign lesions such as WT and ONC; however, negative results for SOX10 as well as DOG1 do not favor a benign diagnosis since MEC is often negative for both markers.

Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of Warthin tumor.

Warthin tumor (War-T), the second most common benign salivary gland tumor, consists mainly of neoplastic epithelium and lymphoid stroma. Some proteins and genes thought to be involved in War-T were evaluated by molecular biology and immunology. However, lipids as an important component of many tumor cells have not been well studied in War-T. To elucidate the molecular biology and pathogenesis of War-T, we investigated the visualized distribution of phosphatidylcholines (PCs) by imaging mass spectrometry (IMS). In our IMS analysis of a typical case, 10 signals were significantly different in intensity (p < 0.01) between the War-T and non-tumor (Non-T) regions. Five specific PCs were frequently found in the War-T regions of all of the samples: [PC (16:0/16:0) + K](+) (m/z 772.5), [PC (16:0/20:4) + K](+) (m/z 820.5), [PC (16:0/20:3) + K](+) (m/z 822.5), [PC (18:2/20:4) + K](+) (m/z 844.5), and [PC (18:0/20:5) + K](+) (m/z 846.5). PC (16:0/16:0) was increased specifically in the folliculus lymphaticus of War-T lymphoid stroma, suggesting a different metabolism. Localization of PC (16:0/16:0) might reflect inflammation activity participating in the pathogenesis of War-T. Thus, our IMS analysis revealed the profile of PCs specific to the War-T region. The molecules identified in our study provide important information for further studies of War-T pathogenesis.

Detection of claudin-4 in salivary gland neoplasms (a study utilizing RT-PCR and immunohistochemistry).

BACKGROUND: Claudins are transmembrane proteins of tight junctions emerging as targets for diagnosis, prediction of prognosis, disease recurrence, and metastasis. Our goal was to evaluate expression of claudin-4 in the most common benign and malignant salivary gland neoplasms. METHODS: Claudin-4 gene levels and protein expression were determined by real-time polymerase chain reaction (PCR), and immunohistochemistry in a total of 30 specimens containing normal salivary tissue, pleomorphic adenoma, Warthin's tumor, mucoepidermoid carcinoma, and adenoid cystic carcinoma. RESULTS: We identified down-regulation of claudin-4 gene levels and protein expression from normal control to benign salivary gland neoplasms and reached their lowest values in the malignant salivary gland neoplasms. CONCLUSIONS: Low claudin-4 expression could be considered as a sign of increasing cellular disorientation and invasion of salivary gland tumors.

Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors.

Lymphadenomas (LADs) are rare salivary gland tumors. Their clinicopathologic characteristics and etiopathogenesis are poorly understood. We examined 33 LADs in 31 patients (17 women and 14 men) aged 11-79 years (median 65 years). There were 22 sebaceous LADs in 21 patients (9 women and 12 men) and 11 non-sebaceous LADs in 10 patients (8 women and 2 men). Two patients had synchronous double tumors. Twenty-six tumors (79%) arose in parotid, three in the neck, and two each in submandibular gland and oral cavity. Extraparotid tumors were seen in 2 of 21 (10%) patients with sebaceous and 4 of 10 (40%) patients with non-sebaceous LADs. Seven of twenty-three (30%) patients had immunosuppressive therapy for unrelated diseases. The tumors were well circumscribed, encapsulated (n=28, 84%) painless masses, varying in size from 0.6 to 6 cm (median 2.2). The cut surfaces were gray-tan to yellow, homogeneous and multicystic (n=24, 72%). The epithelial cells were basaloid, squamous and glandular, forming solid nests, cords, tubules, and cysts. Sebaceous differentiation was restricted to sebaceous lymphadenoma. The epithelial cells expressed basal cell markers (p63, 34BE12, and/or CK5/6, 18/18, 100%) and the luminal glandular cells expressed CK7 (12/12, 100%). Myoepithelial cells were absent (n=10/16, 63%) or focal. The lymphoid stroma was reactive, with germinal centers in 28 (84%). There was no evidence of HPV (0/11), EBV (0/7), and HHV-8 (0/8). Malignant transformation to sebaceous and basal cell adenocarcinoma was seen in one patient each. None of the 11 patients with follow-up (1-8 years) recurred. In summary, sebaceous and non-sebaceous LADs are benign, encapsulated, solid and cystic tumors affecting older adults. Non-sebaceous LADs affect women and extraparotid sites more frequently than sebaceous LADs. Altered immune status may have a role in their etiopathogenesis. Multiple synchronous tumors, origin in buccal mucosa, and malignant transformation may rarely occur.

Gamma-aminobutyric acid concentrations in benign parotid tumours and unstimulated parotid saliva.

OBJECTIVE: Apart from its role as an inhibitory neurotransmitter, γ-aminobutyric acid is also thought to regulate various stages of cell proliferation and differentiation in the brain and periphery. The present study aimed to assess the levels of γ-aminobutyric acid and its biochemical precursor glutamic acid (glutamate) in benign parotid tumours and in unstimulated parotid saliva. METHOD: Unstimulated parotid saliva was collected bilaterally, using the swab method, in 20 patients with unilateral pleomorphic adenoma or Warthin's tumour. Samples of tumour and adjacent salivary tissue were collected during tumour resection. RESULTS: Concentrations of γ-aminobutyric acid and glutamate, but not aspartate, were significantly higher in the tumour tissue than in the non-tumour tissue. There was no significant difference in salivary concentrations of γ-aminobutyric acid, glutamate or aspartate, comparing the involved and non-involved side. CONCLUSION: The present results provide preliminary evidence that γ-aminobutyric acid may be involved in the growth of benign parotid tumours.

Bax, cytochrome c, and caspase-8 staining in parotid cancer patients: markers of susceptibility in radiotherapy?

OBJECTIVE: Negative bcl-2 and HLA-DR protein expression have been associated with responsiveness to adjuvant radiotherapy in surgically treated parotid cancer patients. The aim of this study was to investigate the prognostic significance of bax, cytochrome c, and caspase-8 protein expression in a group of surgically treated patients to determine whether they also suggest markers of responsiveness to adjuvant radiotherapy. STUDY DESIGN: Historical cohort study. SETTING: Otolaryngology department in a university hospital. SUBJECTS AND METHODS: The immunohistochemical expression of bax, cytochrome c, and caspase-8 were studied in paraffin-embedded tissue specimens originating from 27 surgically treated parotid cancer patients and nine patients with Warthin parotid tumors (control group) and correlated with the patients' clinicopathological characteristics and clinical outcome. RESULTS: Caspase-8 negative staining was more frequently observed in higher TNM stages and in tumors measuring more than 4 cm (P = 0.009 and P = 0.018, respectively). Caspase-8 (-)/cytochrome c (-) patients carried low-grade lesions without nodal involvement (P = 0.01 and P = 0.05, respectively). Caspase-8 (-) patients who received postoperative radiotherapy presented a significantly increased disease-free survival compared to those who did not (P = 0.04). Patients bearing bax (-) tumors who received postoperative radiotherapy presented an improved four-year disease-free survival compared to bax (-) patients who did not receive any type of adjuvant radiotherapy (P = 0.017). CONCLUSION: Bax, cytochrome c, and caspase-8 protein expression failed to independently predict survival in parotid cancer patients. However, patients with bax (-) or caspase-8 (-) tumors should be considered as candidates for adjuvant radiotherapy in order to achieve better local disease control.

Immunophenotypical profiles of salivary gland tumours: a new evidence for their histogenetic origin.

The histogenetic origin of salivary gland tumours is not clear. In normal tissues smooth muscle actin (SMA) is expressed in myoepithelial cells, CK14 immunoreactivity is seen in myoepithelial and basal cells and CK10 in keratinized squamous epithelium. In this study, we examine the immunophenotypic properties of salivary gland tumours in order to obtain further insight into their histogenesis. 30 cases of salivary gland tumours (18 pleomorphic adenomas, 8 Warthin's tumours, 2 basal cell adenomas, 2 acinic cell carcinomas) were included in our study. Cytokeratin (CK) 10, CKI4, CKI7, CK18, CK 19, and smooth muscle actin (SMA) immunostains were applied to the sections. Immunoreactivities were detected and the statistical significance was evaluated by chi square test. SMA was not detected in Warthin's tumour (p < 0.0001). CK14 was found in all tumours except acinic cell carcinomas (p < 0.0001). CK10 immunoreactivity was observed in 5 Warthin's tumour. In conclusion, pleomorphic adenomas and basal cells adenomas originate from stem cells. Immunophenotypic profile of Warthin's tumour is suggestive of an embryological remnant origin.

Immunohistochemical detection of E-cadherin in certain types of salivary gland tumours.

OBJECTIVES: To investigate the topography of E-cadherin and its possible correlation with the histological phenotype of salivary gland tumours. MATERIAL AND METHODS: Archival formalin-fixed, paraffin-embedded sections of 54 benign and 56 malignant tumours and 24 samples of normal and inflamed salivary gland tissue were studied immunohistochemically using an Envision/horseraddish peroxidase (HRP) technique. RESULTS: In normal and inflamed salivary gland samples, E-cadherin was expressed at the membrane of acinar, myoepithelial and ductal cells located at cell-cell contact points. Reduction and/or absence of E-cadherin was only observed in pleomorphic adenoma at the peripheral cells of the duct-like or island structures, or in the cells exhibiting plasmacytoid or stromal differentiation. Neoplastic epithelium in Warthin's tumours and in myoepithelial and oncocytic adenomas was strongly positive. Furthermore, a weak to moderate loss of expression which was related to tissue tumour subtype was seen in malignant tumours such as: adenoid cystic carcinomas; polymorphous low-grade adenocarcinomas; acinic cell carcinomas; and mucoepidermoid low-grade, epithelial-myoepithelial, lymphoepithelial and squamous low-grade carcinomas. Moderate to extreme loss or alternative cytoplasmic non-functional expression were observed in cases of salivary ductal carcinoma, carcinosarcoma, myoepithelial carcinoma, oncocytic adenocarcinoma, unspecified adenocarcinoma and squamous high-grade carcinomas. CONCLUSION: This study suggests a direct association of E-cadherin expression with neoplastic histologic phenotype, which is lost in the more undifferentiated and invasive epithelial salivary gland tumours.

Warthin tumors do not have microsatellite instability and express normal DNA mismatch repair proteins.

CONTEXT: Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. OBJECTIVE: To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. DESIGN: Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute-recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. PATIENTS: Twelve patients with Warthin tumors were included. RESULTS: The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. CONCLUSIONS: These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.

Warthin tumor-like variant of papillary thyroid carcinoma: a case with dedifferentiation (anaplastic changes) and aggressive biological behavior.

Warthin tumor-like variant of papillary thyroid carcinoma is uncommon and approx 80 cases have been reported in the literature. This tumor is often associated with a favorable prognosis. In this report, a Warthin tumor-like variant of the papillary thyroid carcinoma, 5-cm in maximum dimension, underwent anaplastic changes in a 74-yr-old woman. The tumor was positive for CD15 and EMA, and a high proliferative index was noted in the anaplastic area. The patient developed distant metastases after operation and died of the disease 18 mo after the operation. The present case is the first reported case of Warthin tumor-like variant of papillary thyroid carcinoma with anaplastic changes.

Growth factors, extracellular matrix components and cell adhesion molecules Warthin's tumor.

We studied expressions of various growth factors, their receptors, cell adhesion molecules and extracellular matrix components in Warthin's tumor of the salivary gland with immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Various growth factors and their receptors, such as transforming growth factor-alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HB-EGF), TGF-beta2, TG-beta3, insulin-like growth factor (IGF)-I and -II, vascular endothelial growth factor (VEGF), EGF receptor (EGFR), erb-B4, TGF-betaRI and II, Flt and Flk-1 and IGF receptor Ibeta, were found in epithelial cells and/or in some lymphoid cells. Fibronectin, laminin, collagen type IV and tenascin were found in stroma of the lymphoid tissue. Integrins such as alpha3beta1 and beta3, Thy-1, CD44 and VCAM-1 were also expressed in epithelial and/or lymphoid cells. These various proteins may interact and regulate the proliferation and cell attachment of both epithelial and lymphoid components in this unique tumor.

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin's tumor (adenolymphoma) of the parotid glands.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the presence and extent of apoptosis in 36 cases of Warthin's tumor (WT) of the parotid glands. The distribution of CK18 in WT was also determined and compared with that of the product detected by MAb M30. In WT, CK18 was observed mainly in the tumor cells of duct-like structures, but not in the cells of lymphatic tissues. Positive MAb M30 reaction products were found in luminal contents, duct-like structures and the cytoplasm of some macrophages in lymphatic areas near the duct-like structures in WT. These findings indicated that apoptotic cells are phagocytosed and eliminated as waste by macrophages. It is suggested that a mechanism which regulates the balance of proliferative activity and apoptosis may be closely linked to the growth of WT.

Follicle center lymphoma and Warthin tumor involving the same anatomic site. Report of two cases and review of the literature.

We report 2 cases of follicle center non-Hodgkin lymphoma (NHL) and Warthin tumor involving the same site. Case 1 is a 68-year-old woman with Warthin tumor and grade 1 follicular NHL involving a periparotid lymph node. She had localized NHL and was treated with radiation therapy; dissemination developed 54 months later. Case 2 is a 55-year-old man with a 17-year history of a parotid mass with gradual enlargement during the last 5 years. Surgical excision revealed Warthin tumor and grade 1 follicular NHL involving the right parotid gland and surrounding lymph nodes. Immunohistochemical studies supported the diagnosis of NHL in both cases; the neoplasms were positive for CD20 and BCL-2 and negative for CD3. Polymerase chain reaction analysis done on paraffinembedded tissue of case 1 revealed monoclonal immunoglobulin heavy chain gene rearrangement and bcl-2/JH fusion DNA sequences diagnostic of the t(14;18)(q32;q21). The small size of the Warthin tumor in case 1, clearly arising in lymph node, supports the hypothesis that Warthin tumor arises from heterotopic salivary gland ducts within lymph nodes. The localized NHL in both patients suggests that the NHL initially arose in the lymph node involved by Warthin tumor, and, thus, the Warthin tumor may have provided a source of long-term antigenic stimulation from which a monoclonal B-cell population subsequently arose.

Metaplastic (infarcted) Warthin's tumour of the parotid gland: a possible consequence of fine needle aspiration biopsy.

AIMS: The metaplastic (or infarcted) variant of Warthin's tumour is characterized by replacement of much of the original oncocytic epithelium by metaplastic squamous cells, along with areas of extensive necrosis, fibrosis and inflammatory change. The pathogenesis is unknown, but it is most likely to be vascular in origin. An association with a previous fine needle aspiration (FNA) has been suggested, and this is explored further. METHODS AND RESULTS: Nine metaplastic Warthin's tumours were collected from several centres: all arose in the parotid gland, and all showed the characteristic histological features. Eight had previously undergone FNA some 1-4 months before surgery; the other case had had an incisional biopsy. CONCLUSIONS: It is important to recognize metaplastic Warthin's tumour, because the differential diagnoses of this benign neoplasm include mucoepidermoid and squamous carcinoma, both primary and metastatic. The tumours in this study followed FNA or biopsy, and we believe this association is unlikely to be coincidental. Although many metaplastic Warthin's tumours clearly arise spontaneously, we conclude that the balance of probabilities favours the view that FNA is capable of causing metaplastic change in a Warthin's tumour, and may have done so in these cases. If so, this previously unusual subtype will become increasingly common, as FNA becomes more widely used (and its value appreciated) in the investigation of patients with a mass in the neck.

Proliferative activity as detected by immunostaining with Ki-67 and proliferating cell nuclear antigen in benign and malignant epithelial lesions of the human parotid gland.

OBJECTIVE: A retrospective immunohistochemical study of parotid gland lesions was designed to evaluate the diagnostic and prognostic value of the proliferating cell nuclear antigen (PCNA) and Ki-67 with monoclonal antibodies PC 10 and MIB-1, respectively. STUDY DESIGN: Tissue samples comprised normal parotid gland (N, n = 10), chronic sialadenitis (CS, n = 8), Warthin's tumor (W, n = 10), benign pleomorphic adenoma (BPA, n = 8), mucoepidermoid carcinoma (MEC, n = 13), carcinoma in pleomorphic adenoma (CPA, n = 8) and adenoid cystic carcinoma (ACC, n = 12). The morphometric parameters for PCNA and MIB-1 comprised the PI and MI labelling indices (the numerical percentage of positive nuclei), NAP and NAM (the numerical density of positive nuclei), and NPI and NMI (volume corrected index). RESULTS: The values of MIB-1 parameters increased progressively in benign lesions in comparison with the N group and in malignant neoplasms in comparison with nonneoplastic groups and benign lesions. Values for all parameters in BPA were significantly lower than those in malignant groups. Spearman rank correlation analysis showed a highly positive correlation between the morphometric parameters and severity of the lesions. The mean values of MI and NMI were significantly higher in patients who died of the malignant tumors than in those who survived. The same quantitative parameters for PCNA did not differ significantly from those obtained for MIB-1 and showed similar trends. CONCLUSION: PCNA and MIB-1 indices are reliable markers for discriminating between benign and malignant tumors of the parotid gland, and the parameters PI, MI, NPI and NMI may have prognostic applications.

Oncocytic and oncocytoid tumors of the salivary glands.

Primary pink cell tumors of the salivary glands constitute a heterogeneous group of benign and malignant lesions characterized by tumor cells with abundant eosinophilic cytoplasm. These tumors are composed predominantly of oncocytic, epidermoid, or myoepithelial cells. Tumors with a significant oncocytic component include Warthin's tumor, oncocytoma, and oncocytic carcinoma. An epidermoid component can be seen as a metaplastic change or as a true cellular constituent of a mucoepidermoid carcinoma. Myoepithelial cells may have an epithelioid character and as a consequence may impart a pink cell appearance in pleomorphic adenoma, myoepithelioma, and myoepithelial carcinoma. Usually most of these tumors are fairly distinct morphologically and do not present diagnostic dilemmas. In select circumstances, especially when dealing with a limited tissue sample, a systematic approach with an appropriate immunohistochemical panel should be used in order to arrive at a correct diagnosis. Accurate assessment is the key in the subsequent management and follow-up of these patients.