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.

[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.

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.

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

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.

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.

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.

Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern.

The authors reviewed 74 adenoid cystic carcinomas of the lacrimal gland, 54 of which had sufficient follow-up data for analysis of survival. Patients with a basaloid pattern in their tumor had a five-year survival rate of 21 per cent and a median survival of three years, whereas patients whose tumor contained no trace of a basaloid component had a five-year survival rate of 71 per cent and a median survival rate of eight years. Nonparametric statistical analysis revealed that this difference in survival was significant at the 0.0005 level. The authors propose that, in the future, pathologists label all adenoid cystic carcinomas as either "basaloid" or "nonbasaloid" and code each case accordingly.

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.

WHO International Histological Classification of Tumours. Tentative Histological Classification of Salivary Gland Tumours.

The principles of the proposed modified WHO Histological Typing of Salivary Gland Tumours are based on the following: 1) The classification of tumours is oriented to the routine work of the practicing surgical pathologists, those who do not see tumours of the salivary glands very often. The inclusion of rare, but clearly defined tumour entities should be helpful to surgical pathologists consulting with clinical specialists. 2) The different types of carcinomas must be distinguished not only by precise histopathological definitions, but also considering differences in prognosis and treatment. For example, the polymorphous low-grade adenocarcinoma and the epithelial-myoepithelial carcinoma are characterized by a relatively good prognosis in contrast to the salivary duct carcinoma. 3) Special points of discussion are: subclassification and grading of carcinomas (e.g. acinic cell carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma), the classification of basal cell tumours (basal cell adenoma, basal cell carcinoma, solid type of adenoid cystic carcinoma), malignant tumours in pleomorphic adenomas and the differential diagnosis between primary tumours and metastases.

Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base.

Neural cell adhesion molecules (N-CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular-trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N-CAM and Ki-67, a proliferation marker, with the avidin-biotin-peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N-CAM. Proliferation, measured by the presence of nuclear Ki-67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N-CAM is expressed in adenoid cystic carcinoma. The role of N-CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study.

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.

Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands.

Ninety-one cases of adenoid cystic carcinoma (ACC) of the salivary glands with more than ten years' follow up were studied to investigate factors influencing the survival rate of patients, which vary according to site, histological type, clinical stage and nature of therapy. The data were statistically analysed for survival curves. Log rank tests were employed to assess the statistical significance of various groups. As a result, it may be concluded that tumour site, clinical stage and histological type are the important factors influencing the prognosis. ACC of the palate and parotid, early clinical stage, glandular/tubular histological type, and tumour without nerve involvement had the best prognosis. ACC in the submandibular gland, maxillary antrum and tongue, advanced clinical stage (stage III and IV), solid histological type, and tumour with nerve involvement had a poor prognosis.

[Silver-stained nucleolar organizer regions in adenoid cystic carcinoma].

The histological features of adenoid cystic carcinoma are varied. In general, the tumors are classified into 4 histological patterns: tubular, cribriform, trabecular and solid. Numerous previous reports have indicated that the tubular pattern usually represents a favorable prognosis, the solid pattern a poor prognosis and the cribriform pattern an intermediate prognosis. Therefore, the present study was undertaken to determine precisely the proliferative potential of each histological pattern of adenoid cystic carcinomas. A silver colloid technique to identify nucleolar organizer region associated protein (AgNORs) was applied to paraffin sections in a total of 16 adenoid cystic carcinomas. A morphometric analysis of highly magnified photographic images of AgNORs in light microscopic preparations was performed. Of the 16 tumors, 8 showed a mixture of different histological patterns in the same section. In comparing the AgNOR number among different histological patterns in the same section, the value was highest for the solid pattern, lowest for the cribriform pattern and intermediate for the trabecular pattern. Moreover, the mean AgNOR number also showed a stepwise increase from the cribriform pattern (2.3 +/- 0.3) through the trabecular pattern (2.9 +/- 0.2) to the solid pattern (3.3 +/- 0.6). There was a significant difference in AgNOR numbers between cribriform and trabecular and between cribriform and solid patterns. Our results indicate that the proliferative potential of histological patterns of adenoid cystic carcinoma is lowest in the cribriform, highest in the solid, and intermediate in the trabecular pattern area. The AgNOR staining technique appears to be of value in estimating the proliferative activity of adenoid cystic carcinomas.

[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.

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.