Fine-Needle Aspiration Cytology of Cellular Basaloid Neoplasms of the Salivary Gland.

CONTEXT.­: Cellular basaloid neoplasms of the salivary gland represent a diverse group of benign and malignant neoplasms with significant cytomorphologic overlap on fine-needle aspiration cytology. All are marked by the presence of monotonous and usually bland basaloid epithelium. Distinction between basaloid neoplasms on fine-needle aspiration cytology is based on the presence or absence of additional features, including a second cell population (eg, myoepithelial cells), an acellular stromal component, and/or cytologic atypia within the basaloid epithelium. This review highlights the cytomorphologic features of the most common cellular basaloid neoplasms of the salivary gland, with an emphasis on classification and subclassification within the Milan System. OBJECTIVE.­: To provide a comprehensive review of the cytologic features of basaloid epithelial neoplasms of the salivary gland, with an emphasis on classification within the Milan System for Reporting Salivary Gland Cytopathology. DATA SOURCES.­: Peer-reviewed literature, recent textbooks, and personal experiences of the author. CONCLUSIONS.­: Some basaloid neoplasms, in particular pleomorphic adenomas and adenoid cystic carcinomas, may have characteristic findings on fine-needle aspiration that allow for definitive diagnosis. In other cases, however, fine-needle aspiration can confirm a neoplastic basaloid process, but specific classification of a benign or malignant neoplasm cannot be rendered. The Milan System for Reporting Salivary Gland Cytopathology acknowledges this difficulty, and recommends benign or malignant classification only when definitive diagnostic features of a specific neoplasm are present. For indeterminate cases, the subcategorization of salivary neoplasm of uncertain malignant potential is recommended.

MYB Translocation Status in Salivary Gland Epithelial-Myoepithelial Carcinoma: Evaluation of Classic, Variant, and Hybrid Forms.

Epithelial-myoepithelial carcinoma (EMC) is a malignant salivary gland neoplasm comprised of a biphasic arrangement of inner luminal ductal cells and outer myoepithelial cells. Adenoid cystic carcinoma (AdCC) is also a biphasic tumor comprised of ductal and myoepithelial cells, but these components tend to be arranged in a more cribriform pattern. The occurrence of "hybrid carcinomas" that show mixed patterns of EMC and AdCC raises questions about the relationship of these morphologically overlapping but clinically distinct tumors. AdCCs frequently harbor MYB-NFIB gene fusions. Mapping of EMCs (including hybrid forms with an AdCC component) for this fusion could help clarify the true nature of EMC as a distinct entity or simply as some variant form of AdCC. Twenty-nine cases of EMC were evaluated including 15 classic low-grade EMCs, 7 intermediate-grade EMCs, 2 EMCs with myoepithelial anaplasia, 1 EMC with high-grade transformation, and 4 hybrid EMCs with an AdCC component. Break apart fluorescence in situ hybridization for MYB was performed, as was MYB immunohistochemistry. For the hybrid carcinomas and those with high-grade transformation, the divergent tumor components were separately analyzed. A MYB translocation was identified in 5 of 28 (18%) tumors including 3 of 4 (75%) hybrid carcinomas and 2 of 7 (29%) intermediate-grade EMCs. For the positive hybrid carcinomas, the fusion was detected in both the EMC and AdCC components. The MYB fusion was not detected in any of the classic EMCs (0/15) or in any of the EMCs with myoepithelial anaplasia (0/2) or high-grade transformation (0/1). The fluorescence in situ hybridization assay was unsuccessful in 1 case. MYB immunostaining was seen in 5 of 5 fusion-positive cases, and also 9 of 23 fusion-negative tumors. Classic low-grade EMCs are genetically distinct from AdCCs in that they do not harbor MYB fusions. The presence of a MYB fusion in EMCs showing hybrid features of AdCC or exhibiting highly infiltrative growth points to a subset of these tumors that may well be true AdCCs masquerading as EMCs.

Human papillomavirus-related carcinoma with adenoid cystic-like features: a series of five cases expanding the pathological spectrum.

AIMS: Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). METHODS AND RESULTS: We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. CONCLUSIONS: This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs.

MYB expression: Potential role in separating adenoid cystic carcinoma (ACC) from pleomorphic adenoma (PA).

BACKGROUND: Basaloid tumors of the salivary gland both benign and malignant comprise ACC, cellular PA, basal cell adenoma (BCA), and basal cell adenocarcinoma. Rendering a diagnosis given a limited biopsy or fine needle aspiration (FNA) sample proves challenging. Activation of MYB by gene fusion has been found in salivary gland ACCs; therefore we investigated the utility of MYB immunohistochemistry (IHC) as a tool for distinguishing ACCs from other basaloid neoplasms. METHODS: We selected 48 cases of ACC (11 FNA blocks [CB]), 37 histologic resections [HR]), 74 PA (36 CB, 38 HR), and 18 BCA (7 CB, 11 HR). FNA CB showed 82% of ACCs (N = 9 of 11) as positive for MYB nuclear staining whereas 68% of ACCs (N = 25 of 37) were positive in HR. RESULTS: All PA were negative for MYB nuclear staining in both CB (N = 0 of 36) and HR (N = 0 of 38). CB showed 29% of BCA (N = 2 of 7) as positive for MYB nuclear staining and 55% (N = 6 of 11) positive in HR. Both ACC and BCA showed significantly higher mean staining intensity than PA in both CB and HR (P < 0.0001). When comparing ACC and BCA, significantly higher mean staining intensity was observed in CB (P = 0.02382) but not in HR (P = 0.42952). CONCLUSION: MYB nuclear staining may prove useful in separating ACC from PA and BCA, especially in limited cellular samples. Diagn. Cytopathol. 2016;44:799-804. © 2016 Wiley Periodicals, Inc.

[Salivary gland-type lung tumor: An update]. / Tumeurs de type glandes salivaires du poumon.

"Salivary gland-type" tumors arising from the bronchi and lung are rare but not exceptional entities. They are mostly represented by malignant entities such as cystic adenoid carcinoma, mucoepidermoid carcinoma and epithelial/myoepithelial carcinoma. Benign tumors are rare, mainly encompassing pleomorphic adenomas, which are to differentiate from mucous gland adenomas, another entity arising specifically from the peri-bronchial glands. These tumours develop in the proximal bronchi and are not associated with smoke abuse. Their main treatment is surgery. It is important to differentiate them from other broncho-pulmonary tumours as they do not share the same prognosis and therapeutic. This article will review the WHO 2015 classification of these tumours as well as recent updates from the literature to help define diagnosis criteria for these uncommon entities.

Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than mammary analogue secretory carcinoma.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that has morphologic features similar to secretory carcinoma of the breast and that also harbors the same ETV6 translocation. Diffuse mammaglobin and S-100 immunoreactivity are used to differentiate MASC from its morphologic mimics, especially acinic cell carcinoma and adenocarcinoma, not otherwise specified. However, the combination of mammaglobin and S-100 immunoreactivity has not been well studied in other types of salivary gland carcinomas that may have focal areas reminiscent of MASC. Here we evaluated mammaglobin and S-100 immunoreactivity in 15 cases each of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and mucoepidermoid carcinoma, and also in 2 cases of adenocarcinoma, not otherwise specified, and 1 mucinous adenocarcinoma. Cases with significant co-expression of mammaglobin and S-100 (moderate or strong immunoreactivity in >25% of tumor cells) were further analyzed by fluorescence in situ hybridization using the ETV6 (12p13) break-apart probe. Nine cases (60%) of polymorphous low-grade adenocarcinoma and two (13.3%) of adenoid cystic carcinoma met the criteria for significant co-expression of mammaglobin and S-100. All were negative for the ETV6 translocation by fluorescence in situ hybridization. Although mammaglobin and S-100 positivity was seen in the majority of polymorphous low-grade adenocarcinomas and a minority of adenoid cystic carcinomas, none were positive for the ETV6 translocation characteristic of MASC. This indicates a need for caution in the use of immunohistochemistry for diagnosing MASC, especially in the absence of cytogenetic confirmation.

Breast cancer pathology: the impact of molecular taxonomy on morphological taxonomy.

The concept of having an 'intrinsic subtype,' or a molecular taxonomy, lets us clearly recognize that breast cancers have characteristically different patterns of gene expression, thus giving newfound significance to morphological taxonomy. In this review, the concept of the 'intrinsic subtype' is discussed, research questions are introduced to refine the significance of morphological taxonomy, and a corresponding example is presented between microarray analysis and 'immunohistochemical subtype,' or histological taxonomy.

Genetic profiling reveals cross-contamination and misidentification of 6 adenoid cystic carcinoma cell lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2.

Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm of the salivary glands. Most patients survive more than 5 years after surgery and postoperative radiation therapy. The 10 year survival rate, however, drops to 40%, due to locoregional recurrences and distant metastases. Improving long-term survival in ACC requires the development of more effective systemic therapies based on a better understanding of the biologic behavior of ACC. Much preclinical research in this field involves the use of cultured cells and, to date, several ACC cell lines have been established. Authentication of these cell lines, however, has not been reported. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations and found that all six cell lines had been contaminated with other cells. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. ACCNS and CAC2 cells were contaminated with cells derived from non-human mammalian species: the cells labeled ACCNS were mouse cells and the CAC2 cells were rat cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or non-human cells.

American Joint Committee on Cancer classification predicts outcome of patients with lacrimal gland adenoid cystic carcinoma.

PURPOSE: To investigate whether American Joint Committee on Cancer (AJCC) classification at initial diagnosis of lacrimal gland adenoid cystic carcinoma predicts outcome of treatment on local recurrence. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with adenoid cystic carcinoma of the lacrimal gland treated at 8 institutions between January 1986 and December 2007. METHODS: Clinical records, including pathology reports and imaging studies, were reviewed. MAIN OUTCOME MEASURES: AJCC classification, histologic subtype, local recurrence rate, and survival. RESULTS: AJCC classification at initial diagnosis was assessable for 53 patients and was as follows: T1N0M0, 7 patients; T2N0M0, 8 patients; T3aN0M0, 14 patients; T3aNxM0, 1 patient; T3aN0M1, 1 patient; T3bN0M0, 13 patients; T3bN0M1, 1 patient; T4aN0M0, 2 patients; T4bN0M0, 4 patients; T4bN0M1, 1 patient; and T4bNXM0, 1 patient. Thirty-eight (72%) of the 53 patients had >T3 tumors at presentation. Of the 38 patients with >T3 tumors, 20 were treated with orbital exenteration and postoperative adjuvant radiotherapy (RT), 6 were treated with orbital exenteration without RT, and 12 were treated with globe-preserving surgery (10 with RT and 2 without RT). Of the 15 patients with T3 tumors, the risk of local recurrence (in the orbit or skull base) was higher in patients treated with conservative surgery as opposed to orbital exenteration and RT. Only 4 (20%) of the 20 patients treated with orbital exenteration and RT had local recurrence, compared with 3 (50%) of the 6 patients treated with orbital exenteration without RT and 8 (67%) of the 12 patients treated with globe-preserving surgery. Overall, 17 (45%) of the 38 patients with >T3 tumors and only 1 (7%) of the 15 patients with T3 disease at initial diagnosis correlates with worse outcomes than does AJCC

Stromal differences in salivary gland tumors of a common histopathogenesis but with different biological behavior: a study with picrosirius red and polarizing microscopy.

Salivary gland neoplasms - pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma - share a common histogenetic trait, but differ markedly in their biological properties. The objective of the study was to assess the polarization colors of picrosirius red-stained stromal collagen fibers in these salivary gland neoplasms to evaluate their possible role in the histopathogenesis of the tumors and to evaluate the potential usefulness of this approach as a diagnostic tool. Ten cases of each tumor type and 10 cases of mucous extravasation phenomenon (control) were examined using picrosirius red staining and polarizing microscopy. In each case, at least 50 thin ( approximately 0.8 microm) and 50 thick (1.6-2.4 microm) collagen fibers were counted and classified as green-yellow or yellow-orange, the mean percentage was calculated and statistical differences analyzed by one-way ANOVA. Results showed a similar thin fiber distribution in all tumor types and controls (82-88% green-yellow, 12-18% yellow-orange, p>0.05). Thick fibers showed a different distribution in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (approximately 50% green-yellow) compared to pleomorphic adenoma and mucous extravasation phenomenon (approximately 13% green-yellow) (p=0.001). Thick fiber distribution was similar in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (p>0.05). We conclude that with picrosirius red staining and polarizing microscopy, stromal collagen fibers differ significantly in pleomorphic adenoma from those in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma, but not from mucous extravasation phenomenon. Similarity between polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma may indicate that these tumor types represent a single entity with a broad spectrum of biological behavior.

Craniofacial resection for malignant tumours involving the anterior skull base.

Ethmoid malignant tumours are rare, but nearly all at least approach or involve the lamina cribrosa. An anterior craniofacial resection is almost always mandatory for a radical resection. While almost everything has been written about technical details, few studies reported meaningful analysis about prognostic factors and long-term results, for a series of reasons: the infrequency of these tumours, the variety of histologies, small patients cohorts presented by each author, a medley of untreated and pre-treated patients, the lack of a universally accepted classification. We perform a review of the literature in the light of our experience of 330 anterior craniofacial resections for ethmoid malignant tumours. We present our classification of ethmoid malignant tumours (called INT, Istituto Nazionale Tumori). It turned out to be more prognostic than AJCC-UICC classification.

New proposal for T classification of gingival carcinomas arising in the maxilla.

When the current T classification of the UICC (1987 and 1997) is used to stage carcinomas arising the upper alveolus and gingival and hard palate, most cases are classified as T4 because of their anatomic characteristics, similar to carcinomas arising in the lower alveolus and gingiva. This study compared the following two methods for classifying the T stage of maxillary carcinomas: (1) the original T classification criteria proposed by the UICC (1987 and 1997), and (2) a new T classification criteria, called the sinus and nasal floor (SNF) criteria. We found that the SNF criteria were more closely related to tumor control and survival than were the UICC criteria in patients with carcinomas arising in the upper alveolus and gingival and hard palate. Increased use of the SNF criteria is expected to improve staging of gingival tumors arising in the maxilla and increase the accuracy of diagnosis, especially of T4 tumors.

[Salivary gland tumors--tumor typing and grading]. / Speicheldrüsentumoren-Tumortypisierung und Grading.

In addition to staging, histological typing and grading provide important information for prognosis and adequate treatment of salivary gland cancers. Current classification and grading systems for mucoepidermoid carcinoma, adenoid cystic carcinoma, and malignant mixed tumor (carcinoma ex pleomorphic adenoma) are discussed.

Adenoid cystic carcinoma of salivary and lacrimal gland origin: localization, classification, clinical pathological correlation, treatment results and long-term follow-up control in 84 patients.

AIM: Adenoid cystic carcinoma (ACC) is a malignant tumor arising from glands. In the maxillofacial region, the salivary glands are particularly affected by ACC and, less frequently, the lacrimal glands. The aim of this study was to determine the outcome of patients with ACC in the maxillofacial region classified according to an internationally accepted staging system. MATERIALS AND METHODS: Over a period of more than 31 years, 84 patients with ACC underwent surgical treatment or a combined treatment in a University Hospital (primaries: 70; local recurrence: 13; distant metastasis: 1). RESULTS: In salivary glands the major glands were affected in 20 individuals, the minor glands in 50, while the glands of the maxillary sinus gave rise to ACC in 8. The lacrimal glands were affected in 6 patients [45 females (53.6%), 39 males (46.4%); age: 13 to 93 years, mean 55.9 years]. Reclassified TNM-stage (UICC, 1987) at the time of diagnosis varied (T0:1, T1:14, T2:13, T3:12, T4:30, NX:1, N0:53, N1:10, N2:5, N3:0, MX:5, M0:59, M1:5). The history of symptoms ranged from 1.82 to 7.3 years, depending on the localization, without any specificity of features. However, swelling and pain were the most frequently recorded findings (> 73%). The therapy of choice has to be the resection of the primary tumor with safety margins. The resection status is important for determining the local control. The resection of the related efferent lymphatics has to be included in the therapeutic concept in patients suspected of having metastasis of the regional lymph nodes. However, hematogenic spread was frequently recorded in our patients, even after several years. An excellent prognosis is only in ACC which is detected early and radically resected. Neither localisation nor the histological subtypes, but tumor stage, had statistically significant impact on prognosis. The differences in survival between surgically-treated patients and those who received radiotherapy as an adjunct were not significant. CONCLUSION: The TNM classification and the analysis of histopathological subtypes provide some information on the tumor biology. The prognosis is uncertain in ACC. Improvement of the current diagnostics and therapy hopefully will come from the development of tumor markers and future molecular genetic investigations.

Salivary gland tumours.

Salivary gland tumours are a relatively rare and morphologically diverse group of lesions. Although most clinicians and pathologists will have encountered the more common benign neoplasms, few have experience of the full range of salivary cancers, which are best managed in specialist centres. This review considers some current areas of difficulty and controversy in the diagnosis and management of these neoplasms. The classification of these lesions is complex, encompassing nearly 40 different entities, but precise classification and terminology is essential for an accurate diagnosis and for the allocation of tumours to prognostic groups. For many salivary tumours diagnosis is straightforward but the wide range of morphological diversity between and within tumour types means that a diagnosis may not be possible on small incisional biopsies and careful consideration of the clinical and pathological features together is essential. Although tumour grading is important and helpful, it is not an independent prognostic indicator and must be considered in the context of stage. Large malignancies tend to have a poor prognosis regardless of grade and even high-grade neoplasms may do well when they are small. A helpful guide to management of salivary cancers is the '4 cm rule'.

[Treatment results of patients with adenoid cystic carcinoma in the Otolaryngology Department at the University School of Medical Sciences in Poznan between 1958-1999]. / Wyniki lecznia chorych na raka gruczolowato--torbielowatego w Klinice Otolaryngologii AM w Poznaniu w latach 1958-1999.

In the years 1958-1999 the ENT Department at the University School of Medical Sciences in Poznan treated 125 patients suffering from adenoid cystic carcinoma located in the head and neck area. The aim of this study was to assess treatment results over a span of 41 years. The cases treated included 68 women and 57 men. The highest incidence of the disease was observed in men in their 70's--16 cases and women in their 50's--19 cases. In a majority of cases, the cancer started in major salivary glands, specifically parotid--51, submandibular--11, sublingual--4. Other places included minor salivary glands located in the palate--15, cheek--8, oral cavity--5 and tongue--4. Other glands affected by the tumor were those in the ethmoidomaxillary area--23. The treatment of choice was surgery with subsequent radiation. All patients were subjected to surgical treatment, 89 of them being subsequently radiated. Local recidivation was observed in 12 patients (i.e. 10%), metastases to neighbouring lymph nodes in 9 patients (i.e. 7%). Distant metastases affected the lungs--4 cases, liver--1 and bone--1.