Sino Nasal
Sino Nasal
Sino Nasal
Kurt Schaberg
Inflammatory
Rhinosinusitis
In adults, allergies are the most common cause of rhinosinusitis
(in kids, it’s viral URIs).
Submucosal chronic inflammatory infiltrate, generally composed
of lymphocytes, plasma cells, macrophages, and eosinophils
Thickened, hyalinized basement membrane
Stromal edema→ can develop into inflammatory polyps (see later)
Allergic Sinusitis
Exposure to allergen (pollen, dander, etc.)→ IgE-mediated reaction
Eosinophils predominate histologically. Can see Charcot Leyden crystals.
If lots of Eos→ stain for fungi (GMS) to evaluate for Allergic fungal sinusitis.
Bacterial Sinusitis
Mucopurulent discharge, headache, fever. Neutrophils predominate.
Mucormycosis
Zygomycetes fungus that classically infects those with diabetic ketoacidosis
and/or immunocompromised. Rapidly progressive invasive infection with
necrosis that often requires urgent surgical debridement.
Large/broad in diameter (10 to 20 µm), ribbon-like, non-septated hyphae with
branching at haphazard angles. See well on H&E (highlighted by PAS/GMS, but
special stains often unnecessary)
Rhinosporidiosis
Polypoid masses caused by the sporulating organism Rhinosporidium seeberi.
Rare in US (more common in India and Brazil). Cysts (sporangia) ranging in size
from 10 to 300 µm in diameter, containing innumerable sporangiospores
(endospores) seen on H&E.
Mucocele
Sinus outlet obstruction → build up of mucus → fills and distends sinus walls. Clinical/radiographic Dx.
Histologic findings nonspecific: flattened epithelium and squamous metaplasia, inflammation, bone
remodeling, and other reactive changes.
Necrotizing sialometaplasia
Squamous metaplasia of minor salivary glands
(just a fancy name for it! ;-)
Classic Mimic of SCC!
Lobular architecture is maintained
Smooth, rounded contours
Often associated inflammation and reactive changes
Acinar coagulative necrosis
(vs SCC, which does not have lobular architecture,
has infiltrative, irregular contours, and is more
atypical and less inflamed)
Benign Tumors
Sinonasal Papilloma aka “Schneiderian papilloma”
Type Morphology Location Risk of Molecular
transformation
Exophytic Exophytic and papillary growth; Nasal Very low risk Low-risk HPV
immature squamous epithelium septum subtypes
Seromucinous hamartoma
Monotonous proliferation of small pink tubules with
lobular architecture (resembles microglandular adenosis in
the breast); absent/rare myoepithelial/basal cells; discernible
basal lamina; no infiltrative pattern; no papillary architecture
or gland fusion. Can have eosinophilic secretions.
CNS Lesions
Heterotopic CNS tissue
aka Glial heterotopia
Congenital developmental, displacement of neuroglial tissue
in extracranial sites without connection to the cranial cavity.
Astrocytes and neuroglial fibers associated with a fibrous,
vascularized connective tissue. Neurons are usually rare/few.
May resemble plump fibroblasts (Does NOT really look like
normal brain). IHC: (+) GFAP and S100.
DDX: Encephalocele→ Herniation of brain outside of cranium
(connected to the brain). Closely resembles normal brain
tissue with neurons. Must exclude “surgical misadventure.”
Pituitary Adenoma
Benign anterior pituitary tumor
Although usually primary to sphenoid bone, can erode into
nasopharynx or be ectopic.
Can result in endocrine disorders, such as Cushing’s disease
or acromegaly.
Solid, nested, or trabecular growth of epithelioid cells with
round nuclei and speckled chromatin and eosinophilic,
granular chromatin.
IHC: (+)CK, and neuroendocrine markers.
(-) No S100 sustentacular pattern.
Can stain with hormone-specific markers (e.g., prolactin).
Can recur.
Meningioma
Dural-based. Oval nuclei, pseudoinclusions. Syncytial tumor
cells with whorls and psammoma bodies.
IHC: (+)SSTR2A, EMA, PR.
Adamantinomatous craniopharyngioma
Epithelial tumor derived from embryonic remnants of Rathke’s
pouch. Basal palisading. Stellate retinaculum. “Wet Keratin.”
IHC: nuclear β-catenin
Hairy Polyp
1
Polypoid structure with 1) ectodermal outer layer
resembling skin (keratinizing squamous epithelium with
adnexal structures, including hair), covering 2) mesodermal
tissue (always fibroadipose tissue, with bone, cartilage,
and/or skeletal muscle); no endodermal tissue should be
present. 2
Developmental abnormality→ mostly diagnosed in kids.
Malignant
Small Round Blue Cell: MR SLEEP ‘N
The most common malignancy in the
sinonasal region is squamous cell M: Melanoma, Mesenchymal chondrosarcoma
carcinoma. R: Rhabdomyosarcoma
S: SNUC, SCC, SWI/SNF-deficient sinonasal carcinoma
However, there are a lot of other
tumors that can arise there— L: Lymphoma
including some unique ones—many E: Esthesio(olfactory)neuroblastoma
of which have relatively “small round E: Ewing sarcoma
blue cell” morphology. To help with P: Pituitary adenoma, Plasmacytoma
these cases, I use this mnemonic. N: NUT Carcinoma, Nasopharyngeal Carcinoma, NEC,
Squamous cell carcinoma
Most common sinonasal malignancy!
Can be Keratinizing or Non-keratinizing
Like elsewhere: malignant infiltrative epithelial cells
with squamous differentiation.
NUT Carcinoma
Poorly-differentiated carcinoma (often small-round
blue cells), classically with “abrupt keratinization”
(1/3 of cases) or squamous differentiation.
Vesicular chromatin with prominent nucleoli
Often younger patients, in the midline, often in the
head and neck.
Molecular: NUTM1 fusions (most often with BRD4)
IHC: (+)NUT, CK (usually), (+/-)PRAME, p63, CD34
Need positive NUT IHC or molecular to make Dx
Aggressive high-grade malignancy→ poor outcome
SWI/SNF complex-deficient sinonasal carcinoma
Poorly-differentiated carcinoma with high N:C ratios
May show basaloid, plasmacytoid, or rhabdoid features
Required to show loss of SWI/SNF complex subunit
IHC: Loss of INI-1 or BIRG1 protein expression
Molecular: inactivation of SMARCB1 or SMARCA4
Aggressive→ Poor long-term outcomes
Teratocarcinosarcoma 2
Malignant tumor with:
1) Immature teratoma: Primitive neuroepithelial
3
elements with fibrillary matrix and rosettes
2) Carcinoma: Squamous or glandular, often with
fetal clear cell appearance
3) Sarcoma: usually fibroblastic, but can show
1
heterologous differentiation
Many have SMARCA4 (BIRG1) loss and/or nuclear β-
catenin.
Usually older men.
Neuroendocrine Carcinoma
Like Poorly-differentiated neuroendocrine
carcinomas of the lung.
Divided into:
1) Small cell neuroendocrine carcinoma
2) Large cell neuroendocrine carcinoma
Strong staining with a neuroendocrine stain
(e.g.., synaptophysin or chromogranin). Often
perinuclear “dot-like” keratin expression.
Mucosal Melanoma
Epithelioid to spindled cells with pleomorphic nuclei
and often prominent nucleoli.
Distinct from cutaneous melanomas biologically
(but must exclude metastatic melanoma clinically!)
Intracytoplasmic melanin
Melanoma markers: (+) S100, SOX10, HMB45, MelanA,
MITF, Tyrosinase. Do many (as can be loss)!
Molecular: Frequent RAS mutations
Poor prognosis: Staging starts at T3-4.
No need for Clark/Breslow depth.
Adenocarcinoma
Salivary gland adenocarcinomas are the most common!!
(particularly adenoid cystic→ see separate notes)
Sinonasal Adenocarcinomas
Intestinal type
Causal relationship with wood dust and leather dust (so, mostly men)
Morphology and IHC identical to colonic adenocarcinoma
(CK7-, CK20+, CDX2+)
Non-intestinal type
(CK7+, CK20-, CDX2-)
Low-grade:
Very bland cytologically (to the point where you wonder if it is
malignant!). Excellent prognosis.
High-grade:
Cytologically malignant. Diagnosis of exclusion (must exclude
metastasis, etc…). Poor prognosis.
Alveolar Rhabdo:
Larger, more rounded undifferentiated cells with only occasional
Rhabdomyoblasts.
Often arranged in an alveolar (nested) pattern
Distinctively strong and diffuse Myogenin positivity
Characteristic FOXO1 translocations
Lymphoma Always consider a hematologic malignancy and throw on heme stain or two
(particularly if it’s not staining with other stains ;-)!
Extranodal NK/T-cell lymphoma Plasmacytoma
IHC: CD3, CD56, EBER + IHC: CD138+ with light chain restriction
Most common in Asians May or may not be associated with multiple myeloma
Unique (Low-grade) Mesenchymal Tumors
Note: Spindle cell tumors may not be Mesenchymal!
Consider salivary gland tumors, melanoma, spindle cell SCC, etc..!
Glomangiopericytoma
Patternless proliferation of regular, syncytial ovoid to
spindled myoid-type cells within a richly vascularized
stroma and ovoid nuclei.
Prominent vascularity with perivascular hyalinization.
Can see “staghorn” vessels (“hemangiopericytoma-like”)
Extravasated erythrocytes, mast cells, and eosinophils.
IHC: SMA+, Nuclear ẞ-catenin (CTNNB1 mutations)
(-) STAT6, S100, CK
Relatively indolent with good survival.
SMARCB1(INI-1)–deficient sinonasal
Lymphoepithelial/Nasopharyngeal
Neuroendocrine Carcinoma
Squamous cell carcinoma
Olfactory Neuroblastoma
Rhabdomyosarcoma
Mucosal melanoma
NUT carcinoma
Ewing Sarcoma
Lymphoma
carcinoma
carcinoma
carcinoma
(SNUC)
CK
(AE1/AE3) + + + + + + + - - - - ±
CK5/6
+ - ± + + + - - - - - ±
P63 and
p40 + - ± + + + - - - - - ±
Synapto/
Chromo - - - - - - + - ± - + ±
CD56
- - - - - - + - ± ± + ±
CD99
- - - - - - - - - ± - +
P16
± ± - - + - - - - - -
S100
SOX10 - - - - + - - + - - + -
CD45
- - - - - - - - - + - -
Myogenin
- - - - - - - - + - - -
NUT
- - - + - - - - - - - -
INI-1
+ + - + + + + + + + + +
EBER
- - - - - + - - - ± - -
Note: Weak staining with synaptophysin, CD56, and CK can be seen with many tumors and
should be taken in context. Look for strong, diffuse staining (think Christmas tree).
Algorithm for Nasal Small Round Blue Cell Tumors
Starting IHC Panel: 1) AE1/AE3, 2) p40, 3) synaptophysin, 4) SOX10, 5) CD45, 6) CD99, and 7) Desmin
CK
- or F ++
INI-1 and
BIRG1 intact
Desmin/myogenin
lost p40
- or F ++ SWI/SNF complex- ++
CD99/NKX2.2
Alveolar
deficient sinonasal
carcinoma
- or F
Rhabdomyosarcoma
NUT
++
- or F Synaptophysin/Chromogranin
+
Ewing + -
Sarcoma NUT
Melanoma Pituitary
markers hormones/ carcinoma
+ sphenoid location EBER
- + +
Melanoma
Pituitary
- Lymphoepithelial -
- or F adenoma Carcinoma
Lymphoid
+ markers Multilineage
Myoepithelial
markers
Lymphoma Differentiation Neuroendocrine
+
- - carcinoma
+ - HPV ish
-
Synaptophysin/
Chromogranin
SNUC
Solid adenoid cystic carcinoma
+ CD99/NKX2.2
+ HPV-related multiphenotypic
Olfactory
sinonasal carcinoma - ++
neuroblastoma Non-keratinizing
Teratocarcinosarcoma squamous cell
carcinoma Adamantinoma-
like Ewing
sarcoma
Potential Pitfalls:
Many non-neuroendocrine tumors can show some
staining with synaptophysin (e.g., rhabdomyosarcoma)
Many of these lesions can stain with PRAME!
Adapted from a presentation from Justin A. Bishop, MD Chief of Anatomic Pathology UT Southwestern Medical Center