Challenging Differential Diagnosis Frontal Sinus In Sinonasal … · 2011-06-14 · Challenging Differential Diagnosis In Sinonasal Lesions Jennifer L. Hunt, M.D., ... French CA,

5/27/2011

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HARVARDMEDICAL SCHOOL

Challenging Differential DiagnosisIn Sinonasal Lesions

Jennifer L. Hunt, M.D., M.Ed.Associate Chief of PathologyDirector of Quality and SafetyMassachusetts General HospitalHarvard Medical School

Frontal Sinus

Ethmoid Sinus

Maxillary Sinus


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Challenging Sinonasal Lesions

• Inverted papilloma• Hamartomas

• Low grade sinonasal adenocarcinoma• Challenging high grade tumors


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Schneiderian Papilloma

• Incidence• Men > women• Adult age

• Clinical• Mass lesion, nasal obstruction

• Three types• Inverted, Exophytic, Oncocytic

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Inverted Papilloma


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Location of Inverted Papillomas

Location Number (%)

Nasal cavity/lateral wall 91 (60%)

Maxillary sinus 26 (17%)

Ethmoid sinus 16 (10%)

Sphenoid sinus 7 (5%)

Unspecified 13 (8%)

Allende D, In preparation


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Inverted Papilloma

• Location: Lateral nasal wall• Histology

• Epithelium >10 cell layers thick• Epithelial morphology

• Transitional• Squamous, respiratory, mucinous

• Transmigrating neutrophils• Decreased minor salivary glands

Inverted papilloma

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Inverted papilloma Inverted papilloma


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Inverted papilloma HARVARDMEDICAL SCHOOL

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Exophytic (fungiform) Papilloma

• Location: Septum• Histology

• Similar to squamous papilloma• Epithelium

• Squamous & transitional

• Residual goblet cells (100%)

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Exophytic Papilloma

Exophytic papilloma


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Oncocytic Schneiderian Papilloma


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Oncocytic Schneiderian Papilloma

• Location: Lateral nasal wall (or anywhere)• Histology

• Oncocytic epithelium• Microcysts in epithelium

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Oncocytic schneiderian papilloma Oncocytic schneiderian papilloma


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Challenges You Might Face

• Early changes of inverted papilloma• Frozen section diagnosis

• Identifying malignant transformation• Differentiating from hamartomas (topic 2)

Schneiderian Papilloma

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Schneiderian Papilloma HARVARDMEDICAL SCHOOL

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Malignant Transformation

• Clinical course• Synchronous tumors (61%)• Asynchronous tumors (29%)

• Classification• Dysplasia (5-20%)• Invasive carcinoma (2-27%)

• Tumor types: squamous cell carcinoma, schneiderian carcinoma, other

Inverted Papilloma with Dysplasia Schneiderian Carcinoma

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Schneiderian Carcinoma HARVARDMEDICAL SCHOOL

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Sinonasal Hamartomas

• Respiratory epithelial adenomatoid hamartoma

• Seromucinous hamartoma


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Respiratory Epithelial Adenomatoid Hamartoma

• Incidence• Unusual• Often posterior nasal septum

• Histology• Hyperplastic glands in the stroma• Lined by respiratory epithelium• Peri-glandular hyalinization

• IHC• CK7 positive• p63: + basal/myoepithelial cells

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Case 2 30REAH


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Sinonasal Serous Hamartomas

• Polypoid lesions• Posterior nasal septum

• Histologic features• Stroma (edematous to fibrous)• Invaginated respiratory epithelium• Small serous glands, ducts and tubules• Variable inflammation and basement

membrane thickening

Weinreb I. Histopathology, 54(2), 2009 32Sinonasal serous hamartomas

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Sinonasal serous hamartomasSinonasal serous hamartomas p63 stain


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Challenges You Might Face

• Differentiating hamartomas from low grade sinonasal adenocarcinoma


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Low Grade Non-ITAC

• Incidence• Rare

• Clinical• Generally good prognosis

Site %

Nasal 40%

Ethmoid 30%

Maxillary 13%

Multiple 18%0

10

20

30

40

50

Salivary ITAC Non-ITAC


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Low Grade Non-ITAC: Behavior

0%

10%

20%

30%

40%

50%

Recurrence Metastasis Died of disease

JO VY. AJSP. 33(3):401, 2009


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Low Grade Non-ITAC: Histology• Architecture

• Papillary, cystadenomatous, tubular• Single layer of epithelial lining• Back-to-back tubules

• Cytology• Bland nuclei• Few mitoses

• Usually no angiolymphatic or perineural invasion

• IHC: CK7 (+), no myoepithelia/basal cells

40Low grade Adenocarcinoma, non-ITAC (Papillary)

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Low grade Adenocarcinoma, non-ITAC (Tubular) Low grade Adenocarcinoma, non-ITAC (cystadenomatous)


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• Sinonasal undifferentiated carcinoma• Intestinal type adenocarcinoma• Olfactory neuroblastoma


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Sinonasal Undifferentiated Carcinoma

• Incidence: Rare• Clinical

• Present with large invasive tumors• Metastases frequently present at presentation

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Sinonasal Undifferentiated Carcinoma

• Histopathology• Undifferentiated tumor cells• Mitoses and necrosis• Vascular invasion and adjacent structures

• Immunohistochemistry• Positive for Cytokeratin• Rarely positive for NSE

SNUC, H&E

SNUC, H&E


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SNUC Molecular

• Midline carcinomas in young people• NUT-BRD4 translocation in 11 of 98

carcinomas• Average age 17 years • Keratinization in 82%• Highly lethal carcinomas

French CA, JCO, 22(20):4135, 2004

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SNUC Molecular

• Undifferentiated carcinomas of UADT• NUT rearrangement in 5/28 cases• NUT IHC positive in 3/5 cases

• Histology counterparts• 2/5 with focal abrupt keratinization• 4/5 with intense diffuse p63 staining

Stelow E, et al. AJSP, 32(6), 2008HARVARD

MEDICAL SCHOOL

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Sinonasal Adenocarcinoma

• Classification• Intestinal type adenocarcinoma (ITAC)• Non-intestinal type adenocarcinoma (non-ITAC)

0

10

20

30

40

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Salivary ITAC Non-ITAC


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Intestinal Type Adenocarcinoma

• Incidence• Rare• Men>Women• Ethmoid sinus in >80%

• Clinical• Sinonasal symptoms• Occupational exposure

• Wood and leather dust• Formaldehyde


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Sinonasal Adenocarcinoma--ITAC

• Histopathology: Resembles GI tumors• IHC

• CDX2 positive• CK20 positive• CK 7 positive (most cases)

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ITAC, H&E

ITAC, CDX2 ITAC, CK20


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Olfactory Neuroblastoma

• Incidence• Broad age range

• Histology• Small to medium sized cells with minimal

pleomorphism• Small to medium sized nests• Rosettes

• Homer Wright in ~50%• Flexner-Wintersteiner are rare

• Neuropil

Olfactory neuroblastoma

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Rosettes

Homer Wright Flexner-WintersteinerHARVARD

MEDICAL SCHOOL

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• Immunohistochemistry• Synpatophysin, chromogranin positive• S100 with sustentacular pattern• CAM5.2 occasionally focally positive

Olfactory neuroblastoma, S100 stain Olfactory neuroblastoma, Synaptophysin

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• Divergent Differentiation• Often high grade tumors• Other components present

• Often epithelial: “Olfactory Carcinoma”• Glandular (Adenocarcinoma)• ? Relationship to neuroendocrine carcinoma

• Rhabdomyosarcoma• Ganglion cells

“Olfactory carcinoma”, H&E and S100 stain

“Olfactory carcinoma”, synaptophysin and cytokeratin HARVARDMEDICAL SCHOOL

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Differential Diagnosis: High Grade Tumors

• Sinonasal undifferentiated carcinoma• Sinonasal neuroendocrine carcinoma• Sinonasal adenocarcinoma (ITAC vs. non-ITAC)• Olfactory neuroblastoma (“carcinoma”)• Schneiderian carcinoma• Lymphoepithelial carcinoma• Ewing’s/PNET• Melanoma• Rhabdomyosarcoma• Lymphoma

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Challenging Differential Diagnosis Frontal Sinus In Sinonasal … · 2011-06-14 · Challenging Differential Diagnosis In Sinonasal Lesions Jennifer L. Hunt, M.D., ... French CA,

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