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RESPIRATROY TRACT (NASAL CAVITY, PARANASAL SINUSES AND NASOPHARYNX)

DR HANIA NAVEED

NORMAL ANATOMY

CONTD

NORMAL HISTOLOGY

CASE NO 1

1yr child Nasal polyp

Contd

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DIAGNOSIS

NASAL GLIOMA Malformed tumor like condition affecting infants Sub-cutaneous masses at the base of nose or intranasal polyps GFAP +ve Other causes: Encephaloceles (associated bony defects) Chondromesenchymal hamartoma

CASE NO 2

40 Yr, male Unilateral nasal polyp

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SINONASAL PAPILLOMA

Types: exophytic, inverted, oncocytic M/E: squamous/transitional/respiratory type epithelium. Intraepithelial neutrophils, microcysts, thin basement membrane HPV 6 AND 11 association

Type Exophytic

Location Nasal septum

Pathology Exophytic fronds of epithelium

Behavior Local recurrence; no risk of invasive carcinoma

Inverted

Lateral nasal wall;paranasal sinuses

Endophytic nests (more than a few inverted nests qualify for inverted)

Local recurrence; 10% risk of invasive carcinoma

Oncocytic/ cylindrical

Lateral nasal wall; paranasal sinus

Exophytic and endophytic nests of cells, oncocytic cells in less than 6-8 layers

Local recurrence; 5-10% risk of invasive carcinoma

NASAL POLYPS

Infants and children


Chondromesenchymal

hamartoma, Nasal glioma, encephalocele, rhabdomyosarcoma, lymphoma, lymphoepithelioma


angiofibroma

<20yrs
Neuroblastoma,

>20 yrs
Neuroblastoma,

inflammatory polyps, sinonasal papilloma, malignant melanoma

Others: allergic fungal sinusitis, rhinosporidiosis

CASE NO 3

50-year-old man with a nasal mass arising from the lateral nasal wall

MICROSCOPY

Contd

DIAGNOSIS

ONCOCYTIC PAPILLOMA

GRANULOMATOUS DISEASE OF NOSE AND PARANASAL SINUSES

Infectious
Spirochetes

(syphilis, yaws) Mycobacteria (tuberculosis, leprosy) Bacteria (rhinoscleroma) Fungus (aspergillus)

Inflammatory
Wegener

granulomatosis Sarcoidosis Churg-Strauss syndrome cocaine induced midline destructive lesions

Sarcoidosis

Wegener's granulomatosis

WEGENERS GRANULOMATOSIS

Diagnostic
Leukocytoclastic

vasculitis, granulomas, necrosis + involvement of lung OR kidney 2/3 microscopic features + involvement of lung AND kidney

Probable
2/3

microscopic features+ clinical involvement of lung OR kidney

Contd

Suggestive
1/3

microscopic features+ lung and kidney involvement microscopic features + lung or kidney involvement microscopic features + kidney and lung involvement

Suspicious
1/3

Non specific
No

Rhinoscleroma

Contd..

D/D:
LEPROSY

(acid fast bacilli) ROSAI-DORFMAN DISEASE

Mucormycosis

Aspergillus

CASE NO 3

23yrs old male with a nasal mass SLIDE

DIAGNOSIS

SINONASAL CARCINOMA

SINONASAL CARCINOMA

within nose - usually vestibule and lateral wall; rarely septum; sinus - usually ethmoid, rare in frontal sinus Risk factors: nickel refiners, woodworkers Usually HPV and EBV negative

Contd

Squamous cell carcinoma, conventional


Keratinizing Nonkeratinizing (formerly cylindrical cell, transitional cell)

Variants of Squamous Cell Carcinoma


Acantholytic squamous cell carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell squamous cell carcinoma Verrucous carcinoma

Contd

To label a tumor as keratinizing squamous cell carcinoma there should be histologic evidence of squamous differentiation
Keratin

(extracellular/intracellular) Intercellular bridges

Keratin profile of sinonasal carcinoma also relates to their microscopic sub-types


P53:

SCC (K) P16: cylindrical cell carcinoma

Contd

Subtypes of squamous carcinoma should be recognized and listed. Basaloid squamous cell carcinomas tend to present with more extensive disease but are also more radiosensitive than conventional squamous cell carcinomas. In this histologic grading scheme, 3 histologic grades are suggested, as follows: Grade 1 Well differentiated = Low-grade Grade 2 Moderately differentiated = Intermediategrade Grade 3 Poorly differentiated = High-grade Grade X Cannot be assessed

Contd

When a tumor manifests more than 1 grade of differentiation, the surgical report must designate both the highest and the most prevalent tumor grades.

CASE NO 4

Unilateral nasal mass causing nasal obstruction

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GLANDULAR HAMARTOMA

CASE NO 5

51yrs old female, swelling lateral wall of nose SLIDE

DIAGNOSIS

MUCINOUS ADENOCARCINOMA

ADENOCARCINOMA

10% of sinonasal malignancies Usually middle turbinate or ethmoid sinus Divided into:
Intestinal-type

adenocarcinoma Non-intestinal-type adenocarcinoma


low-grade high-grade

Salivary

gland type

Contd

Adenocarcinoma, Non-Salivary Gland Type Intestinal type


Papillary-type* Colonic-type* Solid type Mucinous type Mixed type

Contd

Intestinal type adenocarcinoma Strong association with woodworking industry Spectrum of appearance Well differentiated tumors: resembles the normal intestinal mucosa (goblet,paneth,argentaffin,well formed villi and muscularis mucosa) Less differentiated tumors: solid sheets of neoplastic cells having only scattered glandular lumen CK20, CDX-2, MUC2 +ve Molecular genetic studies indicate frequent mutations in K-RAS and TP53

Contd

Non-intestinal adenocarcinoma Not immunoreactive for colonic markers Usually low grade and can be misdiagnosed as adenoma or papilloma Grading into low and high grade is based on:
marked

cytological atypia a high mitotic rate necrosis

Contd

Low grade adenocarcinoma should be distinguished from the intestinal type adenocarcinoma because of the aggressive clinical course of the latter. The distinction is based on
Nuclear

stratification Colonic appearance

CASE NO 6

59 year-old woman with nose bleed and a nasal mass.

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NON-INTESTINAL TYPE ADENOCARCINOMA (LOW GRADE)

CASE NO 7

61yrs old woman presented with long standing bilateral nasal polyps SLIDE

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ADENOCARCINOMA ARISING IN A LONG STANDING PAPILLOMA

CASE NO 8

40 yrs old male with a nasal mass

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Transitional (cylindrical) cell carcinoma

ADENOCARCINOMA (SALIVARY TYPE)

For the majority of salivary gland carcinomas there is only a single histologic grade and classification alone determines the histologic grade (eg, acinic cell carcinoma is a histologically low-grade carcinoma; salivary duct carcinoma is a histologically high-grade carcinoma). In some carcinomas, histologic grading may be based on growth pattern, such as in adenoid cystic carcinoma, for which a histologic high-grade variant has been recognized based on the percentage of solid growth. Those adenoid cystic carcinomas showing 30% or greater of solid growth pattern are considered to be histologically high-grade carcinomas

CASE NO 9

52yrs female, mass right nasal cavity SLIDE

SINONASAL UNDIFFERENTIATED CARCINOMA

Highly aggressive epithelial malignancies composed of nests, lobules or sheets of atypical cells with a high mitotic rate, necrosis and apoptosis. Minimal or no evidence of:
neuroendocrine

differentiation (i.e. no Homer Wright rosettes, no fibrillary background, no ganglion-like cells) no squamous or glandular differentiation no dense lymphoplasmacytic infiltrate

Contd

Immunohistochemistry: Positive stains: CK7, CK8, CK19,Ki-67, NSE, EMA Negative stains: CK 5/6, CK13, EBV, PLAP, CEA, S100, EBER1, chromogranin, Synaptophysin D/D:

Olfactory neuroblastoma Nasopharyngeal undifferentiated carcinoma (syncytial growth of cells with uniform nuclei with vesicular chromatin in inflammatory stroma) Small cell carcinoma Lymphoma Melanoma Rhabdomyosarcoma

Contd

In children and young adults particularly, SNUC should be distinguished from NUT midline carcinomas which are characterized by translocations that involve the nuclear protein in testis (NUT).

CASE NO 10

A 65 year old male with a nasal mass.

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SALIVARY TYPE ADENOCARCINOMA (ADENOID CYTIC CARCINOMA)

CASE NO 11

60 year-old man with enlarging nasal mass

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PLASMABLASTIC LYMPHOMA

CASE NO 12

A 61 year old male with a left nasal mass

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HMB45

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MUCOSAL MALIGNANT MELANOMA

CASE NO 13

40 year-old man with nasal mass

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MENINGIOMA

CASE NO 14

50 year-old man with a nasal mass

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GLOMANGIOPERICYTOMA

CASE NO 15

The patient is a 16 year old male with a nasal mass

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DIAGNOSIS

Alveolar rhabdomyosarcoma

CASE NO 16

10 year-old girl with nasal polyps

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NASAL CHONDROMESENCHYMAL HEMARTOMA

CASE NO 17

A 40 year woman with nasal sinus congestion had a CT scan, which showed a mass. Endoscopy showed friable nasal tissue. A biopsy was obtained.

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Keratin

CD20

CD3

CD56

EBV

TIA

DIAGNOSIS

NK/T cell lymphoma

LETHAL MIDLINE GRANULOMA


A clinical syndrome characterized by slowly progressive ulceration and destruction of the nose and paranasal cavity with frequent erosion of the soft tissues, bone and cartilage of this region NK/T CELL LYMPHOMA WEGENERS GRANULOMATOSIS COCAINE ABUSE IDIOPATHIC

NK/T CELL LYMPHOMA

Highly associated with EBV Characterized by small to medium sized to large transformed cells showing angioinvasion Necrosis is nearly always present. EBER positive (imp to differentiate with reactive lymphoid infiltrate and other CD56+ve lymphoma)

OLFACTORY NEUROBLASTOMA

Also called esthesioneuroblastoma Rare, malignant neuroectodermal tumor thought to arise from olfactory membrane Gross: red-gray, highly vascular, polypoid mass of soft tissue Micro: nests or sheets of uniform small cells with scant cytoplasm, round nuclei with indistinct nuclear membrane and punctuate chromatin, no/indistinct nucleoli; mild to moderate nuclear pleomorphism; prominent fibrillary or reticular background, variable mitotic figures; variable Homer Wright rosettes, ganglion cells and tumor cell melanin; necrosis is poor prognostic factor

Contd

Positive stains: neuron-specific enolase (strong), synaptophysin (strong), chromogranin, occasional GFAP and keratin Negative stains: EWS-FL1, CD99, EMA, desmin

Contd

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DD:
Lymphoma
Ewing/PNET Plasmacytoma

Rhabdomyosarcoma
Small

cell carcinoma

NASOPHARYNGAL CARCINOMA

78-90% of malignant neoplasm in this region are non-glandular. Strongly associated with EBV infection for undifferentiated and nonkeratinizing subtypes Micro:
keratinizing

squamous cell carcinoma Nonkeratinizing carcinoma


Differentiated
Undifferentiated

Contd

SQUAMOUS CELL CARCINOMA (K) Squamous differentiation Adenoid or acantholytic forms NON-KERATINIZING CARCINOMA Lacks the microscopic evidence of squamous differentiation Pavement stone pattern and well defined cell margins Variable number of inflammatory cells in stroma

Contd

UNDIFFERENTIATED CARCINOMA (LYMPHOEPITHELIOMA) Syncytial pattern Uniform cells with ovoid, vesicular nuclei, indistinct cell borders Inflammatory cells rich in lymphocytes REGAUD PATTERN: well defined cells nests and cords separated by inflammation SCHMINKE PATTERN: diffuse inflammatory cells permeate cell nests causing isolation of carcinoma cells within lymphoid background D/D: EMA, CK and LCA (lymphoma)

Contd

In the revised W.H.O. the distinction between undifferentiated and differentiated nonkeratinizing nasopharyngeal carcinomas is no longer necessary since sub-classification is of no prognostic or therapeutic significance.

CASE NO

A 40-year old patient with a history of epistaxis.

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NUT MIDLINE CARCINOMA NMC is defined by translocations involving the NUT gene at 15q14 The most common (75%) translocation is t(15;19) Consistent reactivity to cytokeratins and p63 Surprisingly, CD34 expression, rare in carcinomas, is seen in about half of cases. Melanoma markers, neuroendocrine markers, muscle markers) are consistently negative. The gold standard for the diagnosis of NMC is FISH

THANKU

CASE NO

49 y.o. male with a 2.5 cm nasal mass NON K SCC Sections show an ulcerated polypoid tumor that is composed of basaloid appearing tumor cells with a predominantly inverted growth pattern. Focal keratinization is also noted. Immunostains for cytokeratin, p16 and p63 are strongly and diffusely positive.

CASE NO

67 y.o. female patient with a right nasopharyngeal mass The biopsy shows a malignant neoplasm composed of tumor cells that have scant cytoplasm, round to oval nuclei with open chromatin and small inconspicuous nucleoli that are infiltrated by small lymphocytes. The mitotic rate is high. Immunostains demonstrate that the tumor cells are cytokeratin positive (AE1/AE3), while chromogranin and p16 are negative.

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UNDIFFERENTIATED NASOPHARYNGEAL CARCINOMA

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