1. 1. Presenter: Dr. Durga Department of Pathology, RIMS, Imphal.
2. 2. Anatomy & Histology
3. 3. Roof of nasal cavity contains olfactory mucosa. In infants extends to the mid portion of nasal septum and onto superior turbinate. In adults its replaced by respi epithelium. Olfactory mucosa has 3 types of cells- 1.Olfactory nerve cells(bipolar) 2. sustentacular cells or supporting cells 3. Basal cells.
4. 4. Classification of nasal cavity and PNS malignancies Benign Malignant 1.Epithelial Schnederian papilloma Squamous papilloma Minor salivary gland tumors 2.Neuroectodermal Ectopic pitutary adenoma Paragangliomas Meningioma 3. Mesenchymal Lobular Capillary Hemangioma Solitary fibrous tumor Fibrous histiocytoma Fibromatosis Osteoma Lipoma, Ameloblastoma Inderminant for malignancy/low grade malignant potential Sinonasal type hemangiopericytoma Epitheloid haemangioendothelioma 1.Epithelial Squamous cell carcinoma Keratininsing Non keratinising Variants of SCC Sinonasal undifferentiated carcinoma Adenocarcinoma Intestinal type Non intestinal type Minor salivary gland neoplasms. 2. Mesenchymal Angiosarcoma Mucosal malignant melanoma Olfactory neuroblastoma NHL Extra osseous Ewings MFH chondrosarcoma 3. Secondarytumors.
5. 5. Classification of nasopharyngeal carcinoma Benign Malignant 1. Epithelial: Squamous papilloma Minor salivary gland tumors 2. Mesenchymal: Angiofibroma Granular cell tumor Lymphangioma Hemangiomas Neurofibroma Paraganglioma Fibrous histiocytoma Lipoma 1. Epithelial: Nasopharyngeal carcinoma Keratinising Nonkeratinising Differentiated Undifferentiated Basaloid Low grade papillary adeno carcinoma Minor salivary gland tumors 2. Mesenchymal: Mucosal malignant melanoma Lymphoma Rhabdomyosarcoma Angiosarcoma Liposarcoma Kaposis sarcoma 3. Secondary tumors.
6. 6. Schneiderian papilloma (sinonasal papilloma) Schneiderian membrane; ectodermally derived lining of sinonasal tract. Represent less than 5 % of all sinonasal tumors. Affects most commonly 5th -8th decade and rare before 40 years Usually unilateral. Association with HPV 6 & 11. Symptoms: airway obstruction, epistaxis, asymptomatic mass and pain 3 morphologically distinct benign papillomas 1. Fungiform/exophytic/septal papilloma 2. Inverted papilloma 3. Oncocytic/cylindrical/columnar
7. 7. Exophytic variant Papillomatous proliferation of epithelial cells along with mucocytes seen along delicate fibrovascular core. Bland looking epithelial cells with retention of polarity, scattered mucocytes seen along the surface.
8. 8. Endophytic variant
9. 9. Exophytic squamous epithelial proliferation with readily apparent eosinophilic appearance Oncocytic variant
10. 10. Squamous papilloma Most common benign neoplasm of UADT-oral cavity & larynx. Less often involves nasopharynx & nasal vestibule. Gross: Exophytic warty or cauliflower like tumors ranging in size from few mm to 3 cm M/E: Benign squamous epithelium in multiple finger like projection with prominent fibro vascular core. Lacks dysplasia Treatment: Surgical excision is cuartive with no risk of malignant transformation.
11. 11. Sinonasal Squamous cell carcinoma
12. 12. SCC is the most common type of malignant epithelial neoplasm of sinonasal tract. Constitute app 3% of all head and neck malignant neoplasms. Men> Women in 6th -7th decade. Risk factors: Nickel exposure, textile dust, smoking , preexisting schederian papilloma. Site(order) Maxillary antrum, nasal cavity, ethmoid sinus, sphenoid and frontal sinuses. Clinical presentation: Facial asymmetry, unilateral nasal obstruction epistaxis, pain with persitent purulent rhinorrhea non healing ulcer.
13. 13. Variants: 1.Exophytic or papillary 2.Verrucous 3. Spindle cell squamous carcinoma 4. Basaloid squamous cell carcinoma 5.Adenosquamous carcinoma Gross: Growth varies acc to variants & is well circumscribed, with an expansile growth.
14. 14. Histologically keratising(MC) and non keratinising subtypes. Keratinising: Keratinising variant characterised by presence of keratinization and intercellular bridges. Graded as well, moderate and poorly differentiated . Desmoplastic response is typically found in stroma. Pic 4A.18
15. 15. Non keratinising SCC Exophytic or endophytic growth pattern. M/E: Nest of squamous epithelium with broad interconnections having smooth borders.
16. 16. Papillary Uncommon but distinct subtype showing solitary lesion with an exophtyic growth pattern (2mm- 4cm) Hpe:filiform growth with finger like projections & identifiable fibrovascular core. Squamous epithelium cytologically malignant d/f it from papillomas.
17. 17. Verrucous Highly differentiated variant of SCC with locally destructive but not distantly metastatic. Mc affecting oral cavity larynx. SNT is least coomon Dyson et al- protein product of HPV can bind the retinoblastoma gene product, removing the regulatory block of cell cycle. Gross: tan or white, warty, fungating or exophytic, firm to hard mass measuring upto 10 cm.
18. 18. Histologically bland squamous cell proliferation with uniform cells lacking dysplastic features. Retention of polarity with no atypia. Mitotic figures can be seen only in basal layer not elsewhere. Marked surface keratinisation and broad or bulbous rete pegs pushing downwards into stroma. Viral associated Kolicytic changes are seen.
19. 19. Spindle cell squamous carcinoma/ sarcomatoid carcinoma Occurs in sinonasal tract & nasopharynx. Appears as fungating ulcerated masses. More aggressive and radiorestitant tumors.
20. 20. IHC markers: 1.Cytokeratin (+) 2. P63 (+) 3.Viamentin & smooth muscle actin(+)
21. 21. Basaloid squamous cell carcinoma High grade SCC affecting hypopharynx less frequently sinonasal tract. Etiology: Excessive alcohol &/or tobacco use. Presents as a uni nasal mass lesion . Gross: firm to hard tan white masses often with central necrosis measuring upto 6cm Histologically: Infiltrating tumor showing varied patterns solid ,trabecular, gland like or cystic. Foci of squamous differentiation along with the presence of basaloid cell component which are small closely apposed cells with hyperchromatic nuclei, scanty cytoplasm & marked mitosis. Prone to have early metastasis to regional lymphnode even to visceral locations.
22. 22. WHO defined a carcinoma arising in the nasopharyngeal mucosa that shows light microscopic or ultrastructural evidence of squamous differentiation MC in southeast asia and north africa. Etiological factors: multifactorial 1. strong association with EBV nonkeratinising and un differentiated variant. 2. Diet (salted fish high in nitrosamines) 3. poor hygeine and environmental pollutants. 4.HLA A2, HLA B17, HLA Bw46, HLA BW 58 marker for genetic susceptibility. Non random deletions and rearragment of chromosome 3
23. 23. Genomic wide studies have shown multiple chromosomal abnormalities with mutation in oncogenes and tumor supressor genes. Inactivation of p16 TSG- most common alteration. Ras associated domain family1A. Clinical presentation: Asymptomatic cervical neck mass(Post cervical triangle) Nasal obstruction, discharge epistaxis with pain serous otitis media, otalgia . Site of occurrence: Fossa of rosenmuller on the Lateral wall of nasopharynx is the most common superior posterior wall.
24. 24. Gross appearance Varies from a mucosal bulge with an intact epithelium to clearly demonstrable infiltrative mass M/E: +/- evidence keratinization Most common
25. 25. Keratinising SCC of Nasopharynx
26. 26. Non keratinising: (12%) shows little to no evidence of keratinising Tumor growth pattern- stratified or pavemented arrangment showing sharp delination from surrounding stroma
27. 27. Undifferentiated This type represents around 60% NPC; can be seen in pediatric age group also. 2 patterns of growth are seen 1. Regaud type characterised by well defined aggregates of tumor cells surrounded by fibrous tissue and lymphoid cells 2. Schminkee type-Neoplastic epithelial cells grow diffusely & are closely intermingled with inflammatory cells. Misnomer- Lymphoepithelioma Tumor cells characteristically show large & vesicular nuclei with a smooth outline & a single eosinophilic nucleoli
28. 28. Regaud type Schminkee
29. 29. Imunohistochemical markers: Keratin CK5,6,8,13 & 19 (+) CK 4, 7, 10, 14(-) P53(+) Epithelial membrane antigen(+) CEA(+) S100 dendritic cells(+) Leucocyte common antigen & HER(-)
30. 30. Prognosis Radiotherapy is the treatment of choice. Stage at presentation is the most important prognostic factor 5 yr survival rate if presented stage I- 98% stage II-95% stage III-86% stage IV-73% Worse prognosis is seen with 1. Marked anaplasia 2. High cell proliferation rate 3. Lack of lymphocyte infiltrate. 4. High dendritic S 100 positivity 5. Her2neu expression. Other Important factors: Age Gender Presence of keratinisation Lymphnode status.
31. 31. 10-20% of all primaries SNT 2 types : Intestinal type & Non intestinal type Intestinal: they are malignant epithelial glandular tumors of SNT histologically resembling intestinal adenocarcinoma or an adenoma. Males>females of age 50-70 years Etiology: Occupational wood workers Gross: Exophytic growth with readily identifiable mucinous qualty.
32. 32. Low grade nasopharyngeal papillary adenocarcinoma Low grade tumors arising from naspharyngeal surface epithelium showing glandular differentiaion Indolent biologic behaviour. No gender prediliction occuring in age group ranging over 20-70 years Site: posterior nasopharyngeal wall. Gross: Exophytic, papillary, nodular or cauliflower like with a soft to gritty consistency measuring upto 4 cm
33. 33. Histologically: Unencapsulated and have papillary and glandular growth pattern. Cells vary from pseudostratified columnar to cuboidal with eosinophilic cytoplasm Nuclei round to oval with vesicular to optically clear chromatin
34. 34. Sinonasal undifferentiated carcinoma Original defintion by Freirson et al as a high grade malignant epithelial neoplasm of the nasal cavity and PNS of uncertain histiogenesis with or without neuroendocrine differentiation BUT with out evidence of squamous or glandular differentiation Rare tumor less than 100 cases Male predominance over a wide range of group 30-60 years. At presentation SNUC are extensive & involves multiple sites nasal cavity or PNS
35. 35. Presents clinically most commonly as unilateral mass, epistaxis, proptosis, diplopia, facial pain & cranial nerve involvement Typically pt presents with multiple symptoms of short duration. Histologically: Hypercellular proliferation with varied growth pattern- trabecular, sheet like, ribbons, solid, lobular.
36. 36. Cellular infiltrates composed of polygonal cells composed of medium to large sized , round to oval, hyperchromatic to vesicular nuclei with varying amount of eosinophilic cytoplasm
37. 37. IHC is non contributory to diagnosis: Epithelial mucin () P63 (v) Cytokeratin (v) Synaptophysin chromogranin S100 (r) Viamentin & smooth muscle markers (-)
38. 38. Hemangiomas Lobular capillary hemangiomas formerly known as Pyogenic granuloma Benign vascular tumors primarly affecting skin and mucous membrane. Affects both the genders equally. Age group: 40-50 years Location: Nasal septum over Littles area, Turbinates. Presents clinically as epistaxis, painless obstructive mass. Pathogenesis unclear but an association noted with pregnancy and OCP usage. They regress after parturition
39. 39. Gross: smooth lobulated, polypoid red mass measuring upto 1.5 cms Microscopically: submucosal vascular proliferation arranged in lobules and clusters composed of central capillaries and tributaries. Staghorn appearance Prominent endothelial cell lining and show endothelial tufting. Surrounded by granulation tissue & mixed chronic inflammatory cells.
40. 40. Pic 4A.7
41. 41. Nasopharyngeal angiofibroma Rare Benign mesenchymal tumor accounting less than 1% of all head and neck tumors Tumor exclusively affects male thought to be hormonally driven. Age group second decade and also older ages. Site: Roof of nasal cavity nasopalatine foramen. Symptoms: Nasal obstruction, epistaxis Late- facial swelling and deformity, nasal dicharge headache diplopia hearing defect Patients with FAP are 25 times more susceptible to have angiofibroma- APC B catenin mutations are noted . Radiography Holman miller sign. Gross: Sessile lobulated masses occasionally polypoid or pedunculated.
42. 42. Microscopic: unencapsulated & characterised by fibrocollagenous stromal proliferation with admixture of variable sized vascular spaces. Vascular component varies from small to large sized, staghorn to inconspicuos due to marked compression by the stromal fibrous tissue. Stroma- fibrous tissue with fine or coarse collagen fibres & may be focally myxoid. Mitotic figures are rare. Nuclear pleomorphism and MNGC can be seen. Tumors of longer duration tend to be more fibrous & less vascular. IHC: Smooth muscle actin; viamentin(+) Testosterone receptor (+) ER PR (-)
43. 43. pic4A.8
44. 44. The major complication with angiofibroma is excessive bleeding, recurrence, extension beyond nasopharynx. Nasal Biopsies of such young male with facial deformities should be performed with extreme caution because of the risk of excessive bleeding. Recurrence rate varies 6 to 24%.more with the one tumor showing intracranial extension. Good prognosis no risk of malignant transformation.
45. 45. Olfactory Neuroblastoma Malignant neuroectodermal neoplasm arising from olfactory membrane of sinonasal tract. Olfactory placode tumor, esthesioneuroblastoma, esthesioneuroepithelioma. Basal cells are mitotically active proposed to be putative cell of origin. Uncommon -2% SNT tumors Wide age range from 3 years to 9th decade Clinical: anosmia headache along with nasal obstruction. Site: cribriform plate Radiographically opacification of SNT with calcification(speckeled pattern)
46. 46. Gross: Glistening, mucosa covered, soft, polypoid mass varying from a small nodule
47. 47. 4A.31 Neuron specific enolase S-100 synaptophysin chromogranin. High proliferation index
48. 48. Histologically:
49. 49. Complete surgical excision Craniofacial resectio involving removal of cribriform plate Followed by full course radiotherapy Prognosis depends on clinical staging defined by kadish Stage Extent of tumor 5 year survival A Confined to nasal cavity 75-91% B Involving nasal cavity + 1/more PNS 68-71% C Extension tumor beyond sinonasal cavities. 41-47%
50. 50. Mucosal Malignant melanoma Neural crest derived neoplasm originating from melanocytes & show melanocytic differentiation. 15-20% of all MM arise in head n neck out of which 80 % are of cutaneous origin Of the non cutaneous head n neck melanomas most often have occular origin & few in SNT Men>women of age group 60-80 occuring MC on nasal septum Symptoms: airway obstruction, epistaxis Gross: polypoid or sessile, brown , black, pink or white friable mass. ulceration is most common
51. 51. Histologically: Pleomorphic epitheloid or spindled cells arranged in either solid, organoid, nested patterns cells are round to oval with high N C ratio having vesicular to hyperchromatic nuclei
52. 52. Diagnosis usually confirmed by IHC: HMB 45(+) and S 100(+) EMA (-) cytokeratin (-)
53. 53. Pseudoneoplastic lesions 1. Sinonasal polyp 2. Sinonasal & nasopharyngeal infectious disease 3. Human immunodefeciency virus infection 4. Heterotopic CNS tissue 5. Wegeners granulomatosis 6. Rosai dorfman disease/ extranodal sinus histiocytosis 7. Lymphangiomatous polyp of the tonsil
54. 54. Sinonasal polyp Non neoplastic inflammatory swelling of sinonasal mucosa Commonly seen in adults over 2o years age and less common in children less than 5 years.(except the child with CF) Location lateral wall of nose or ethmoid recess. Symptoms nasal obstruction rhinorrhea headaches. Antrochoanal polyp: 3-6% of all polyps. More common in men than in women usually single unilateral lesions with associated nasal obstruction. Gross: Soft, fleshy polypoid lesions with a mucoid appearance.
55. 55. Microscopically polyps are composed of loose edematous stroma with large number of eosinophils in allergic polyps. Basement membrane is thickened and stroma is edematous AND there is an absence of seromucinous glands. Mixed chronic inflammatory cell infiltrate.
56. 56. Sinonasal & nasopharyngeal infectious disease. Clinically simulate neoplasia Fungal disease aspergillosis &rhinosporidiosis bacterial rhinoscleroma mycobacterial disease ICP- viral disease HSV CMV Produce ulcerative mass over nasal cavity and nasopharynx
57. 57. Rhinosporidiosis Large globular cystic spaces surronding fibro vascular stroma PAS sporangia
58. 58. HIV infection of waldeyers tonsillar tissue Presents clinically as enlargment of lymphoid tissue of waldeyers ring including tonsils and adenoids Clinically presents as unilateral swelling. Histomorphology vary with progression of disease Early lesion: Florid follicular hyperplasia with follicular fragmentation & follicle lysis with areas of follicular involution Presence of monocytoid B cell hyperplasia Paracortical & interfollicular zone expansion with immunoblasts plasma cells Intrafollicular hemorrhage Multi nucleated gaint cells clusters adjacent to tonsillar crypt.
59. 59. In advanced stages there is effacement of nodal architecture, loss of normal lymphoid cell population with replacement by benign plasma cell and presence of increased vascularity. Less Multinucleated gaint cell in advanced stages.
60. 60. Heterotopic CNS tissue Glial heterotopia or nasal glioma Considered to be a variant of encephalocele in which communication to CNS has closed. Usually present at birth or with in first year Site: around nasal cavity; ethmoid sinus, nasopharynx Subcutaneous lesion over bridge of nose appears blue or red mass Clinical symptoms: Nasal obstruction, respiratory distress epistaxis with DNS Histologically: Astrocytes and neuroglial fibres ass with a fibrous vascularized connective tissue. On long standing fibrous stroma obscure the astrocytes Surgery is the treatment of choice & curable.
61. 61. References: 1. Fletcher Diagnostic Histopathology; 3 rd edition 2. Rosai & Ackerman Surgical pathology 10th edition 3. Robbins & cotran pathologic basis of disease; 8th edition 4. David J Dabbs Diagnostic immunohistochemistry;3rd edition. 5. Wheaters functional histology;6th edition.