Cribriform Adenocarcinoma Of Minor Salivary Gland Research Articles

CRIBRIFORM ADENOCARCINOMA OF MINOR SALIVARY GLANDS: A CASE REPORT WITH FOCUS ON RADIOGRAPHIC APPERANCE

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is currently classified as a subtype of polymorphous adenocarcinoma. CAMSG differs from polymorphous adenocarcinoma in that it has a distinct histopathologic appearance and clinically CAMSG has higher rate of lymph node metastasis at initial presentation. Panoramic radiograph shows an ill-defined radiolucent lesion in the right maxilla that extends from the distal of maxillary right canine to the mesial of maxillary second molar. The lesion has invasive borders and causes destruction and loss of the lamina dura and periodontal ligament space in the mesial of the second molar and distal of the canine. The lesion has also invaded into the right maxillary sinus destroying the floor of sinus. CBCT images show a low attenuation lesion involving the right maxillary alveolar bone at the premolars and first molar area. This report describes the radiographic appearance of a case of CAMSG on panoramic radiograph, cone-beam computed tomography (CBCT), multi-detector computed tomography (MDCT) and on magnetic resonance imaging (MRI).

Fine needle aspiration cytology of cribriform adenocarcinoma of minor salivary gland, a recently defined entity

Cribriform Adenocarcinoma of Minor Salivary Glands (CAMSG) is a recently recognized, distinct neoplasm of minor salivary gland origin. Its histological and cytological features show considerable overlap with other head and neck cancers like papillary thyroid carcinoma (PTC). Presence of cribriform and glomeruloid structures, metachromatically staining matrix, and a lack of colloid can help distinguish CAMSG from PTC.

Polymorphous adenocarcinoma of the salivary glands: reappraisal and update.

Although relatively rare, polymorphous adenocarcinoma (PAC) is likely the second most common malignancyof the minor salivary glands (MiSG). The diagnosis is mainly based on an incisional biopsy. The optimal treatment comprises wide surgical excision, often with adjuvant radiotherapy. In general, PAC has a good prognosis. Previously, PAC was referred to as polymorphous low-grade adenocarcinoma (PLGA), but the new WHO classification of salivary gland tumourshas also included under the PAC subheading, the so-called cribriform adenocarcinoma of minor salivary glands (CAMSG). This approach raised controversy,predominantlybecauseof possible differences in clinical behaviour. For example, PLGA (PAC, classical variant) only rarely metastasizes, whereas CAMSG often shows metastases to the neck lymph nodes. Given the controversy, this review reappraises the definition, epidemiology, clinical presentation, diagnostic work-up, genetics, treatment modalities, and prognosis of PAC of the salivary glands with a particular focus on contrasting differences with CAMSG.

Newly Described Entities in Salivary Gland Pathology.

Salivary glands may give rise to a wide spectrum of different tumors. This review concentrates on 4 salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma, cribriform adenocarcinoma of minor salivary glands (CASG), sclerosing polycystic adenosis/adenoma (SPA), and the mucinous/secretory variant of myoepithelioma. Mammary analog secretory carcinoma is a distinctive low-grade malignant salivary cancer that harbors a characteristic chromosomal translocation, t(12;15) (p13;q25), resulting in an ETV6-NTRK3 fusion. Cribriform adenocarcinoma (CASG) is a distinct tumor entity that differs from polymorphous low-grade adenocarcinoma by location (ie, most often arising on the tongue), by prominent nuclear clearing, differing alterations of the PRKD gene family, and clinical behavior with frequent metastases at the time of presentation of the primary tumor. Early nodal metastatic disease is seen in most cases of CASG; yet, they are still associated with indolent clinical behavior, making it a unique neoplasm among all low-grade salivary gland tumors. SPA is a rare sclerosing tumor of the salivary glands characterized by the combination of cystic ductal structures with variable cell lining including vacuolated, apocrine, mucinous, squamous, and foamy cells, by prominent large acinar cells with coarse eosinophilic cytoplasmic zymogen-like granules, and by closely packed ductal structures, surrounded by a peripheral myoepithelial layer and stromal fibrosis with focal inflammatory infiltrates. SPA frequently harbors intraductal epithelial dysplastic proliferations ranging from mild dysplasia to severe dysplasia/carcinoma in situ. Moreover, SPA has been proven to be a clonal process by HUMARA assay and is associated with considerable risk of recurrence. Therefore, on the basis of all these newly recognized findings, we believe that SPA is likely a neoplasm, and we suggest the name "sclerosing polycystic adenoma." The mucinous variant of myoepithelioma is a myoepithelial tumor with foci of prominent cytoplasmic clearing frequently containing intracellular mucin material and having signet-ring morphology.

Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin.

Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with "mixed/indeterminate" features. The RNAseq of 2 CAMSGs showed ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from "classic" PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types.

Cribriform adenocarcinoma of minor salivary gland: A report of two cases with an emphasis on cytology

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is a recently characterized low grade salivary gland malignancy that most commonly presents as a mass in the base of the tongue, frequently with regional lymph node metastasis. Given its relative rarity and overlapping cytomorphology, CAMSG may be confused with polymorphous low grade adenocarcinoma (PLGA) in minor salivary gland sites and papillary thyroid carcinoma (PTC) in cervical metastasis, in both fine-needle aspiration and excisional specimens. As there are no cytology reports in the literature, we present two new cases of CAMSG and describe the aspiration cytology of the tumor taken from bench top aspirates, compare it with the histomorphology, and discuss the features that may help one avoid misdiagnosis of PTC in the setting of cervical lymph node metastasis. We found that like PTC, aspirates of CAMSG contain polymorphic fragments of epithelial cells arranged in monolayer sheets, papillary fronds and tips, and occasional cribriform configurations, and metachromatic stromal fragments, which may be misinterpreted as colloid. A background of myxoid/mucoid material also reminiscent of colloid was prominent. Differentiation from PLGA is more difficult based strictly on cytology. A review of the most current literature in relation to the molecular and immunohistochemical profiles, therapeutic options, and prognosis is also presented. It is critical for pathologists and clinicians to be aware of this tumor when presented with patients having a cervical lymph node mass in the absence of a primary tumor.

Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes

The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.