Sinonasal adenocarcinomas

2025-04-08   Paola Dal Cin, PhD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Keywords
include intestinal-type adenocarcinoma (ITAC), non-intestinal-type adenocarcinomas (non-ITACs), sinonasal salivary-type carcinomas, occupation-related cancer

Classification

Definition

Sinonasal adenocarcinomas arise from the respiratory epithelium or the underlying seromucinous glands, and include intestinal-type adenocarcinoma (ITAC) and  non-intestinal-type adenocarcinomas (non-ITACs). While ITAC has a relatively well-characterized epidemiologic, clinical, and pathologic profile, non-ITACs are still not well understood and are diagnosed by exclusion. SATB2 immunohistochemistry in combination with CDX2 and CK20 differentiates sinonasal ITAC from non-ITAC. 1 The non- ITACs can be further distinguished in low-grade (LG) and high-grade (HG) non-ITAC based on the cytoarchitectural features. Virtually all  salivary-type carcinomas can arise in the sinonasal tract. 2
Occurrence of ITAC is strongly associated with exposure to hardwood dusts and distinct mutational characteristics were identified in ITAC and non-ITAC, suggesting that mutational signature analysis may eventually become useful for documentation of occupation-related cancer. 3
Emerging molecular studies suggest that these LG-adenocarcinomas have distinctive mutations e,g., CTNNB1, BRAF, AKT1  or many different  fusions, with ETV6::NTRK3 been, so far, the most frequent one .  A categorization of LG non-ITAC based on their histologic, immunophenotypic, and molecular feature have been proposed. 4,5


Sinonasal adenocarcinomasGenetic marker(s)
Intestinal-type sinonasal adenocarcinoma (ITAC) ITAC is strongly related to occupational exposure to wood and leather dust making it a disease more commonly seen in carpenters and furniture makers. ITAC also shares phenotypical features with colorectal carcinoma (CRC). 2,6 Several genetic similarities between ITAC and CRC were identifies : TP53, KMT2C, and APC were observed frequently in both groups, CHD2 mutations were seen more frequently in ITACs and mutations in LRP1B and KRAS more frequently in the CRC group.7 Metastases from CRCs to the sinonasal tract have been reported , and CSDE1 immunostaining represents a potential marker to use in distinguishing ITAC from a metastasis of colorectal origin. 8 A distinct mutational characteristics were identifid only in ITAC, and may eventually become useful for documentation of occupation-related cancer. 3
Chromosomal imbalances in wood dust-related ITAC have been reported in details. 3,8,9 However, the papillary subtype seems to consistently possess relatively few copy number alterations as compared to other subtypes,10 and notably, is often associated with more favorable clinical outcomes. 11
Non-intestinal-type sinonasal adenocarcinoma (non-ITAC)Non-ITACs represent a diagnosis of exclusion lacking a proper histopathological definition. They can be further distinguished in low-grade (LG) and high-grade (HG) cytoarchitectural features.2 A subset of low-grade (LG) with tubulo-papillary morphology harbors ETV6::NTRK3 fusion, with nonaggressive behavior compared with salivary type secretory carcinoma. 12 A ETV6::RET fusion was also reported in a single case, so far. 13 Several other molecular alterations have been reported in LG non-ITAC group including mutations of BRAF, CTNNB1 and AKT1 as as well as single cases with PRKAR1A::MET, FN1::NRG1 and DNAJB1::PRKACA fusions. 4 Based on their histologic, immunophenotypic, and molecular features CTNNB1 mutations are mainly seen in tubulo-lobular predominant tumors, BRAF mutations, including those with concurrenr AKT1 mutations , mostly seen in those papillary architecture. and some biphasic seromucinous differentiation cases harbor concurrent HRAS/AKT1 mutations 4,5,14
A group of high grade (HG) non-ITACs showed completely loss of SMARCB1.15 A ETV6::NTRK3 fusion was reported in 2 cases. 16
Salivary-type adenocarcinomasVirtually all salivary-type carcinomas can arise in the sinonasal tract with identical histopathological and molecular features of salivary gland counterparts. The adenoid cystic carcinoma (ACC) is the most frequent sinonasal salivary-type carcinoma. 2

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1272585602018The Role of SATB2 as a Diagnostic Marker of Sinonasal Intestinal-type Adenocarcinoma.Skalova A et al
2394895552024Sinonasal Adenocarcinomas: An Update.Arcovito G et al
3387110962024Genome-wide somatic mutation analysis of sinonasal adenocarcinoma with and without wood dust exposure.Sipilä LJ et al
4353221952022Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity.Rooper LM et al
5357155302022Sinonasal mixed transitional epithelial-seromucinous papillary glandular neoplasms with BRAF p.V600E mutations - sinonasal analogues to the sialadenoma papilliferum family tumors.Patel S et al
6272246552016Intestinal-type sinonasal adenocarcinomas: The road to molecular diagnosis and personalized treatment.Hoeben A et al
7330517252021Major driver mutations are shared between sinonasal intestinal-type adenocarcinoma and the morphologically identical colorectal adenocarcinoma.Sjöstedt S et al
8356622592022Differences in gene expression despite identical histomorphology in sinonasal intestinal-type adenocarcinoma and metastases from colorectal adenocarcinoma.Sjöstedt S et al
9160416932005Chromosomal imbalances in wood dust-related adenocarcinomas of the inner nose and their associations with pathological parameters.Korinth D et al
10289638202018Genomic profiling of intestinal-type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes.López-Hernández A et al
11185608622009Genetic and clinical aspects of wood dust related intestinal-type sinonasal adenocarcinoma: a review.Llorente JL et al
12287194682017ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non-intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract.Andreasen S et al
13296838172018The ETV6-RET Gene Fusion Is Found in ETV6-rearranged Low-grade Sinonasal Adenocarcinoma Without NTRK3 Involvement.Andreasen S et al
14389230262024Expanding the spectrum of low-grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations.Hadnagy VS et al
15380853332024SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma.Skálová A et al
16374150522023High-grade non-intestinal type sinonasal adenocarcinoma with ETV6::NTRK3 fusion, distinct from secretory carcinoma by immunoprofile and morphology.Klubíčková N et al

Citation

Paola Dal Cin, PhD

Sinonasal adenocarcinomas

Atlas Genet Cytogenet Oncol Haematol. 2025-04-08

Online version: http://atlasgeneticsoncology.org/solid-tumor/209318/sinonasal-adenocarcinomas