Challenging Differential Diagnoses in Small Biopsies from the Sinonasal Tract

Available online 14 April 2023

Author links open overlay panel, , ABSTRACT

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

Section snippetsINTRODUCTION

Sinonasal tumors are rare with an expanding catalog of genetically defined entities. They are typically mass-forming with non-specific symptoms including obstruction, pain, rhinorrhea, and epistaxis. Morphologic and immunophenotypic overlap between some entities makes definitive diagnosis challenging even in resection specimens. When faced with small biopsy samples of sinonasal tumors, these challenges are compounded by limited sampling of key diagnostic features seen in some entities.

Sinonasal Papillomas

Sinonasal (Schneiderian) papillomas are benign with three distinct types – inverted (ISP), oncocytic (OSP) and exophytic (ESP). ISP account for 40-70% of all sinonasal papillomas and are more common in older Caucasians adults with a male predilection. ISP typically involve the lateral nasal wall and/or paranasal sinuses.5 The majority demonstrate EGFR mutations with a smaller, mutually exclusive subset associated with low-risk human papillomavirus (HPV).6,7 High-risk HPV is rare in ISP.8 ISP

Hamartomas

Respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH) are benign glandular proliferations of the sinonasal tract that can be challenging to distinguishing from true glandular neoplasm.

REAH can be bilateral and most commonly affects posterior nasal septum and olfactory clefts.18 REAH is characterized by a polypoid proliferation of branching glands lined by respiratory epithelial cells with intermixed mucocytes. REAH extend deep into lamina propria and are surrounded

HIGH-GRADE CARCINOMAS

Keratinizing and non-keratinizing SqCC predominate in the sinonasal tract, with other carcinomas and SqCC variants being rare. Table 1 summarizes the comparison of the entities below.

LOW-GRADE SPINDLE CELL NEOPLASMS

There is considerable morphologic overlap between some of these entities and immunostains are often needed for definitive diagnosis. Table 2 compares important features of the entities discussed below.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

None

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

REFERENCES (83)O Savari et al.First Report of Thoracic Carcinoma With DEK::AFF2 Rearrangement: A Case Report

J Thorac Oncol

(2022)

AM Udager et al.Human papillomavirus (HPV) and somatic EGFR mutations are essential, mutually exclusive oncogenic mechanisms for inverted sinonasal papillomas and associated sinonasal squamous cell carcinomas

Ann Oncol Off J Eur Soc Med Oncol

(2018)

M Mehrad et al.Diagnostic Discrepancies in Mandatory Slide Review of Extradepartmental Head and Neck Cases: Experience at a Large Academic Center

Arch Pathol Lab Med

(2015)

WH Westra et al.The impact of second opinion surgical pathology on the practice of head and neck surgery: a decade experience at a large referral hospital

Head Neck

(2002)

A Schreiber et al.Diagnostic reliability of pretreatment biopsy in malignant nasoethmoidal tumors: A retrospective study of 77 cases

Laryngoscope

(2018)

KY Choi et al.Clinical Implication of Diagnostic and Histopathologic Discrepancies in Sinonasal Malignancies

Laryngoscope

(2021)

Oh My! An Update on Sinonasal (Schneiderian) Papillomas

Head Neck Pathol

(2017)

M Mehrad et al.Transcriptionally Active HPV and Targetable EGFR Mutations in Sinonasal Inverted Papilloma: An Association Between Low-risk HPV, Condylomatous Morphology, and Cancer Risk?

Am J Surg Pathol

(2020)

LM Rooper et al.Transcriptionally Active High-Risk Human Papillomavirus is Not a Common Etiologic Agent in the Malignant Transformation of Inverted Schneiderian Papillomas

Head Neck Pathol

(2017)

CY Fan et al.Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma: an immunohistochemical analysis of 13 cases and review of the literature

Am J Surg Pathol

(2000)

AM Udager et al.Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma

J Pathol

(2016)

S Maisch et al.Sinonasal papillomas: A single centre experience on 137 cases with emphasis on malignant transformation and EGFR/KRAS status in “carcinoma ex papilloma

Ann Diagn Pathol

(2020)

W Yang et al.Immunogenic neoantigens derived from gene fusions stimulate T cell responses

Nat Med

(2019)

E Todorovic et al.Middle Ear and Temporal Bone Nonkeratinizing Squamous Cell Carcinomas With DEK-AFF2 Fusion: An Emerging Entity

Am J Surg Pathol

(2020)

LM Rooper et al.DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity

Am J Surg Pathol

(2021)

M Goto et al.Respiratory epithelial adenomatoid hamartomas of the sinonasal tract: A histopathological analysis of 50 patients

Pathol Int

(2022)

BM Wenig et al.Respiratory epithelial adenomatoid hamartomas of the sinonasal tract and nasopharynx: a clinicopathologic study of 31 cases

Ann Otol Rhinol Laryngol

(1995)

JT Lee et al.Sinonasal respiratory epithelial adenomatoid hamartomas: series of 51 cases and literature review

Am J Rhinol Allergy

(2013)

I Weinreb et al.Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells

Histopathology

(2009)

A Ambrosini-Spaltro et al.Nasal seromucinous hamartoma (microglandular adenosis of the nose): a morphological and molecular study of five cases

Virchows Arch

(2010)

B Purgina et al.A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall

Head Neck Pathol

(2015)

A Skalova et al.The Role of SATB2 as a Diagnostic Marker of Sinonasal Intestinal-type Adenocarcinoma

Appl Immunohistochem Mol Morphol AIMM

(2018)

MT Kennedy et al.Expression pattern of CK7, CK20, CDX-2, and villin in intestinal-type sinonasal adenocarcinoma

J Clin Pathol

(2004)

VA Resto et al.Immunohistochemical distinction of intestinal-type sinonasal adenocarcinoma from metastatic adenocarcinoma of intestinal origin

Ann Otol Rhinol Laryngol

(2006)

EP Mathew et al.Metatypical Adenoid Cystic Carcinoma: A Variant Showing Prominent Squamous Differentiation With a Predilection for the Sinonasal Tract and Skull Base

Am J Surg Pathol

(2022)

B Xu et al.Sinonasal Secretory Carcinoma of Salivary Gland with High Grade Transformation: A Case Report of this Under-Recognized Diagnostic Entity with Prognostic and Therapeutic Implications

Head Neck Pathol

(2018)

S Andreasen et al.ETV6 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

Am J Surg Pathol

(2017)

JS. LewisSinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

Head Neck Pathol

(2016)

JA Bishop et al.Human papillomavirus-related carcinomas of the sinonasal tract

Am J Surg Pathol

(2013)

K Elgart et al.Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

Curr Otorhinolaryngol Rep

(2020)

JA Bishop et al.HPV-related Multiphenotypic Sinonasal Carcinoma HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features