Figure - available from: Virchows Archiv
This content is subject to copyright. Terms and conditions apply.
Morphologic features of case 2. A The tumor consisted of a papillomatous component as well as a deep glandular component. B The papillomatous component is thickened transitional type epithelium and shows an endophytic growth pattern reminiscent of sinonasal inverted papilloma. C The glandular component at the base shows a bilayered oncocytic papillary proliferation with scattered mucous cells similar to those of case 1
Source publication
Sinonasal non-intestinal type adenocarcinoma (non-ITAC) is a heterogeneous category that may benefit from improved taxonomy. With the recognition that most non-ITAC are phenotypically seromucinous, stratification may be improved by applying salivary type morphologic criteria and molecular findings. We report two cases of papillary seromucinous aden...
Citations
... 49 Despite showing similar seromucinous features, the molecular profile of these tumors is diverse, including mutations in b-catenin (CTNNB1) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), as well as a DnaJ homolog subfamily B member 1/protein kinase CAMP-activated catalytic subunit a (DNAJB1::PRKACA) fusion. 50,51 One emerging entity with 11 cases reported in the literature includes sinonasal adenocarcinoma with ETS variant transcription factor 6/neurotrophic tyrosine receptor kinase 3/rearranged during transfection (ETV6::NTRK3/RET) fusions. These tumors are typically low grade, 52 but the characteristic molecular finding can be a useful therapeutic target for this patient population. ...
Context.—:
Sinonasal tract malignancies are rare cancers with frequent morphologic overlap. Given the similar histologic profiles seen in many of these entities, they often present a diagnostic challenge to the practicing pathologist.
Objective.—:
To provide a streamlined algorithm using histologic clues, immunohistochemical profiles, and molecular assays to aid in diagnosis of these lesions.
Data sources.—:
Sources were the World Health Organization Tumor Classification, literature review, and institutional experience.
Conclusions.—:
Although many sinonasal tract malignancies show similar histology, distinct immunohistochemical and molecular profiles can help parse out differences, thereby facilitating diagnosis for the pathologist.
... One slight surprise was the sinonasal class, specifically non-intestinal type adenocarcinomas. The understanding now is that a significant proportion (if not most) of these are in fact seromucinous type adenocarcinomas whose classification is slowly evolving [23][24][25]. While only 8 cases were queried here, over a third shows NKX3.1 expression, with one case (shown in Fig. 3B) showing staining equivalent to that of the mucous acinar class of salivary gland lesions. ...
Background
Secretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland tumors have now been molecularly characterized, key drivers in SMCA have yet to be elucidated. Recently, NKX3.1, a homeodomain transcription factor implicated in salivary mucous acinar development was also shown in a subset of salivary mucinous neoplasms, salivary intraductal papillary mucinous neoplasms (SG-IPMN). To date, NKX3.1 expression has not been characterized in other mucinous salivary lesions. Here, we report molecular and extended immunophenotypic findings in SMCA and NKX3.1 expression in the context of other head and neck lesions.
Methods
We retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66).
Results
NKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4.
Conclusion
Despite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.
... 3 The study by Chen et al. also identified BRAF V600E mutation in 5 cases of SP. 4 A recent study has suggested that papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface component (PSASP-like surface) is the sinonasal analog to SP due to the shared morphologic and molecular features. 13 The 2 cases of PSASP-like surface in the study were found to harbor the BRAF V600E mutation. 13 In this current study, all 7 cases of classic SP were positive for BRAF V600E IHC in a moderate to weak intensity, while the oncocytic case was negative for BRAF V600E IHC. ...
... 13 The 2 cases of PSASP-like surface in the study were found to harbor the BRAF V600E mutation. 13 In this current study, all 7 cases of classic SP were positive for BRAF V600E IHC in a moderate to weak intensity, while the oncocytic case was negative for BRAF V600E IHC. ...
Introduction. Sialadenoma papilliferum (SP) is a rare benign neoplasm that usually arises in the minor salivary glands. Recently, it was demonstrated that SP shares similar molecular genetic alterations (BRAF V600E or HRAS mutations) with its morphologic analog, syringocystadenoma papilliferum. Methods. We sought to perform clinicopathologic and immunophenotypic (BRAF V600E and SOX10) analyses on 8 new cases of SP. Results. The cases were from 4 males and 4 females, with ages ranging from 28 to 81 years (average: 64 years). The common locations were the hard palate (n = 3) and buccal mucosa (n = 3). Histopathologically, 7 cases were classic and 1 case was oncocytic. BRAF V600E immunohistochemistry (IHC) was positive in all classic SP, involving both the exophytic and endophytic components, but negative in the oncocytic SP. SOX10 was positive in the endophytic ductal cells of the evaluated classic SP but was negative in the oncocytic SP. Conclusions. We report 8 new cases of this rare salivary gland neoplasm, using BRAF V600E and SOX10 IHC to further support the following points: (1) the functional role of BRAF V600E mutation, RAS/mitogen-activated protein kinase signaling pathway in the pathogenesis of classic SP of salivary glands by IHC; (2) the analogous relationship between SP, syringocystadenoma papilliferum, and papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface component (PSASP-like surface); (3) endophytic ductal component in classic SP arises from the intercalated ducts and not the excretory ducts; and (4) oncocytic SP is distinct from classic SP.
Aims
Low‐grade non‐intestinal‐type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal‐ and salivary‐type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.
Methods and results
Clinical, histological and molecular characterisation of four cases of biphasic, low‐grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo‐glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in‐situ /precursor lesions adjacent to the tumour. Follow‐up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.
Conclusion
This study further corroborates a distinct biphasic low‐grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial–myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.
