Sinonasal intestinal-type adenocarcinomas comprise a distinct clinicopathologic entity.¹ The tumors most frequently involve the ethmoid sinuses and nasal cavity; however, they may be found within the other sinuses as well.²,³,⁴ They arise mostly in adult men over a wide age range, although most are diagnosed in the fifth and sixth decades of life. Occasional series that have attempted to report only cases not secondary to environmental exposures have shown no sex predilection, however.¹ The tumors are noteworthy for their increased prevalence in persons exposed to hardwood and other dusts, although the risks for such exposure do not appear to be the same throughout the world.²,³,⁴,⁵,⁶,⁷ Sinonasal intestinal-type adenocarcinomas have much higher recurrent rates than lower grade adenocarcinomas and accordingly worse prognoses; between 50% and 83% of patients survive 5 years after their diagnoses.⁸ Most tumors do not show the abnormalities typical of colorectal adenocarcinomas such as BRAF or RAS mutations, abnormalities of wnt-signaling pathway or mismatch repair protein loss,
and resultant microsatellite instability.⁹,¹⁰,¹¹,¹² Comparative genomic hybridization studies have consistently shown gains at 7q, 8q, and 20q with losses at 5q, 17p, and 18q.¹³,¹⁴

Grossly, sinonasal intestinal-type adenocarcinomas have been described as papillary and friable and range in color from white-tan to red-purple.¹,¹⁵ Microscopically, the tumors show an intestinal phenotype that can vary greatly with some tumors appearing akin to normal small intestinal epithelium (authors have even described an apparent muscularis mucosae), while others can be poorly differentiated and have a signet ring phenotype (Table 7.2; Figs. 7.1, 7.2, 7.3, eFigs. 7.1 and 7.2).¹⁵,¹⁶,¹⁷ Most tumors (70%-80%) have a papillary-tubular cylinder cell pattern akin to that seen with most colorectal adenocarcinomas. These usually show papillae or villi that spread across the surface and fold into the stroma. Numerous tubular structures can then be seen on cut surface that infiltrate the underlying stroma, some of which will have intratubular papillary growths. These tumors can produce a variable amount of mucus, and solid and cribriform areas can be seen. The neoplastic cells are tall and columnar with oval, hyperchromatic nuclei that appear stratified. A variable number of goblet cells, Paneth cells, and enterochromaffin cells can also be seen. These tumors can be graded as well-differentiated, moderately differentiated, and
poorly differentiated much like colorectal adenocarcinomas are graded. Another histologic pattern that may be seen has been termed the alveolar goblet cell pattern. This pattern is characterized by numerous mucus-filled cavities. These cavities are separated by thin septa of fibrous tissue and
have mucinous epithelial cells either lining the spaces or floating within the cavities. Finally, less than 5% of these tumors will show a signet-ring morphology akin to that seen throughout the enteric tract.

The subclassification of sinonasal intestinal-type adenocarcinomas and the grading of the most common pattern, the papillary-tubular type, have been shown to be predictive of overall survival with the lower grade papillary tubular variants showing the longest survival and highest survival rate at 5 years.¹⁶,¹⁸,¹⁹ Because the tumors are so rare, and because a limited number of therapeutic options are available, subtyping and grading are often not performed. It is unlikely that either is necessary with small biopsies.

Immunohistochemically, sinonasal intestinal-type adenocarcinomas show a marked resemblance to true colorectal adenocarcinomas and most tumors will react with antibodies to CK20, CDX2, SATB2, and MUC2 (Fig. 7.4, eFigs. 7.3-7.5).¹²,²⁰,²¹,²²,²³ This allows them to be distinguished from other sinonasal adenocarcinomas. Unlike true colorectal adenocarcinomas, sinonasal intestinal-type adenocarcinomas show greater immunoreactivity with antibodies to neuroendocrine antigens such as NSE and chromogranin, whereas they are less likely to show immunoreactivity with antibodies to carcinoembryonic antigen.²⁴

The WHO currently classifies nonintestinal-type adenocarcinomas of the sinonasal tract as low grade and high grade. Most are of lower grade cytologically and carry with their diagnosis a much better prognosis than the
intestinal-type adenocarcinomas.²⁵,²⁶ A low-grade papillary adenocarcinoma of the nasopharynx is also discussed here.

Low-grade adenocarcinomas have been described involving the nasal cavity and/or paranasal sinuses (i.e., low-grade sinonasal adenocarcinoma [SNAC]).²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹,³²,³³,³⁴ Patient ages have varied greatly, with median ages ranging from 37 to 54 years. The tumors occur equally in both sexes and present with nonspecific symptoms such as obstruction or epistaxis. The tumors generally behave in a benign fashion, only occasionally recurring.³⁰