Pathology of the Larynx

1
Pathology of the Larynx

• Nikolay Popnikolov M.D., Ph.D.
• Fellow, UTMB Dept. of Pathology
• January 2002

2
Normal Anatomy and Histology
3
Normal Anatomy and Histology
4
Normal Anatomy and Histology
5
Normal Anatomy and Histology
6
Normal Anatomy and Histology
7
Normal Anatomy and Histology
8
Laryngeal Epithelium
9
Goblet Cells and Columnar Mucinous Cells
10
Squamous Epithelium
11
Seromucinous Glands
12
Duct from Seromucinous Glands
13
Seromucinous Glands
14
Oncocytic Transformation of Seromucinous
Epithelium
15
Vocal Process of the Arythenoid Cartilage
16
Chondroid Metaplasia
17
Non-neoplastic Lesions of the Larynx
18
Tuberculosis
19
Granulomatous Inflammation
20
Fungal Infections

• Histolplasmosis
• Coccidiomycosis
• Cryptococcosis
• Blastomycosis
• Aspergilosis
• Candidiasis

21
Other Granulomatous Diseases

• Leprosy
• Tertiary Syphilis
• Sarcoidosis
• Crohns disease
• Wegeners granulomatosis

22
Acute Epiglottitis

• Haemophylus influenzae type B
• Reddened, markedly edematous supraglottic
  structures
• Edema with marked infiltrate of neutrophyls with
  or without microabscess formation

23
Diphtheria
24
Diphtheria
25
Vocal Cord Nodules

• Usually bilateral
• Anterior or middle third of true vocal cord
• Any age group
• Related to chronic voice abuse
• Hoarseness or voice changes

26
Vocal Cord Polyps

• Usually single
• Middle third of true vocal cord, but may
  originate from the ventricular area
• Any age group
• Sessile, raspberry-like, pedunculated
• Related to chronic voice abuse, infection, ETOH,
  smoking, hypothyroidism
• Hoarseness or voice changes

27
Vocal Cord Polyp
28
Edematous-Myxoid Type

• Submucosal accumulation of pale blue to pink
  material admixed with sparsely cellular and
  variably vascularized stroma

29
Vascular-Hyaline Type

• Dilated submucosal vascular spaces and deposition
  of dense eosinophilic fibrin-like material

30
Vocal Cord Polyp Fibrous Type

• Moderately cellular submucosal proliferation of
  uniform oval to spindle-shaped cells with varying
  amount of fibrous tissue deposition

31
Laryngocele

• Abnormal dilatation of the saccule (appendix of
  the ventricle) containing air and maintaining an
  open communication with laryngeal lumen
• Men gtwomen
• Bilateral - 25
• Hoarseness, lateral neck mass, dyspnea,
  dysphagia, laryngopyocele (pain)

32
Laryngocele Types

• Internal laryngocele confined to
  the intrinsic larynx
• External dilated sac
  projects upward and laterally
• Combined

33
Laryngocele Etiology

• Acquired increased intralaryngeal
  pressure (glassblowers, musicians, weight
  lifters)
• Congenital
• SCC in 15 of cases

34
Laryngocele

• Smooth -surfaced, sac-like structure usually
  filled with air

35
Laryngocele

• Respiratory epithelial-lined (ciliated, columnar)
  cyst with a fibrous wall
• Squamous metaplasia
• Oncocytic metaplasia

36
Laryngocele Differential Diagnosis

• Branchial cleft cyst
• Oncocytic papillary cystadenoma
• Laryngeal cysts

37
Contact Ulcers of the Larynx (Pyogenic Granuloma
of the Larynx)

• Benign, tumor-like condition, occurring most
  commonly along the posterior aspect of one or
  both vocal cords
• MengtWomen, usually adults
• Hoarseness, dysphagia, sore throat, dysphonia,
  difficulty breathing, choking, pain
• Etiology vocal abuse, acid regurgitation,
  postintubation trauma

38
Contact Ulcers of the Larynx (Pyogenic Granuloma
of the Larynx)

• Ulcerated, polypoid, nodular, or fungating mass
  with a beefy red to tan-white appearance, up to 3
  cm in diameter

39
Contact Ulcers of the Larynx (Pyogenic Granuloma
of the Larynx)

• Ulcerated lesion with associated fibrinoid
  necrosis, granulation tissue, acute and chronic
  inflammation

40
Contact Ulcers of the Larynx (Pyogenic Granuloma
of the Larynx)

• Giant cells, vascular proliferation, and spindle
  cells

41
Contact Ulcers of the Larynx Differential
Diagnosis

• Infectious diseases
• SCC
• Spindle cell carcinoma
• Vascular neoplasms lobular capillary hemangioma,
  angiosarcoma, Kaposis sarcoma

42
Laryngeal Amyloidosis

• Extracellular accumulation of fibrillar proteins
• Systemic or localized
• Primary or secondary
• Men gt women, in the 5th and 6th decades
• Polypoid mass (glottis and supraglottis) or
  diffuse mucosal swelling (subglottis)
• Hoarseness

43
Laryngeal Amyloidosis

• Extracellular, eosinophilic, amorphous material
  deposited randomly throughout submucosa
  depositions around or within the walls
• Disappearance of the seromucous glands,
• Mixed chronic inflammatory infiltrate

44
Laryngeal Amyloidosis

• Congo red apple-green birefringence under
  polarized light

45
Subglottic Stenosis

• Congenital or acquired
• Rare acquired gt congenital
• Progressive respiratory difficulty, stridor,
  dyspnea, air hunger, hoarseness, abnormal cry,
  aphonia, dysphagia
• Etiology trauma, neoplasms, infectious or
  autoimmune diseases, idiopathic

46
Subglottic Stenosis

• Narrowing of the endolaryngeal diameter with
  mucosal or submucosal mass or bulging
• Histologic picture depends on the cause
• Idiopathic stenosis submucosal fibrous
  proliferation with associated non-specific
  chronic inflammation
• Differential diagnosis infectious diseases,
  Wegeners granulomatosis, collagen vascular
  diseases, neoplasms

47
Idiopathic Subglottic Stenosis
48
Terminology of Epithelial Changes

• Leukoplakia white lesion on a mucosal
  membrane (clinical)
• Erythroplakia red lesion on a mucosal
  membrane (clinical)
• Hyperplasia thickening of epithelial
  surface as a result of an absolute increase in
  the number of cells.
• Pseudoepitheliomatous hyperplasia exuberant
  reactive or reparative overgrowth of squamous
  epithelium with no cytologic evidence of
  malignancy.

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Terminology of Epithelial Changes

• Keratosis presence of keratin on an
  epithelial surface
• Parakeratosis presence of nuclei in the
  keratin layer
• Dyskeratosis abnormal keratinization
  of epithelial cells
• Ulceration erosion or loss of
  surface epithelium
• Metaplasia change from one
  histologic tissue type to another

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Terminology of Epithelial Changes

• Koilocytosis cytoplasmic
  vacuolization suggestive of viral (HPV) effect
• Dysplasia or atypia abnormal
  maturation and cellular aberrations
• Carcinoma in situ full thickness
  epithelial dysplastic change with an intact
  basement membrane.
• Superficially (microscopically) invasive SCC SCC
  in which there is violation of the basement
  membrane with invasion into the underlying stroma.

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Hyperplastic Epithelial Changes

• Reactive or reparative benign process, reflecting
  the epithelial response to a stimulus or an
  injury
• Men gt women
• Occurs anywhere, but mainly along the true vocal
  cords
• Hoarseness
• Etiology smoking, ETOH, voice abuse, chronic
  inflammation

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Hyperplastic Epithelial Changes

• Flat, papillary, or verrucoid lesion with a white
  (leukoplakic) or red (erythroplakic) appearance
• Small or diffuse
• Thickening of epithelial surface as a result of
  an absolute increase in the number of cells
• Presence of superficial keratin layer (keratosis)
  or nuclei in the superficial keratin layer
  (parakeratosis)

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Hyperplastic Epithelial Changes

• Presence of keratohyaline granules in the
  granulosa cell layer
• Presence of koilocytosis
• Presence of cytologic atypia
• Presence of dyskeratosis
• Differential diagnosis contact ulcer,
  verruca vulgaris, verrucous carcinoma,
  well-differentiated conventional SCC

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Keratosis with Epithelial Hyperplasia w/o
Dysplasia
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Laryngeal Leukoplakia with a Papillary or
Verrucoid Appearance
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Laryngeal Leukoplakia with a Papillary or
Verrucoid Appearance
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Dysplastic Epithelial Changes

• Men gt women
• Occurs anywhere, but mainly along the anterior
  portion of the true vocal cords, 25 bilateral
• Hoarseness
• Etiology smoking, ETOH, chronic
  inflammation, voice abuse, Vit A deficiency,
  environmental exposure

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Dysplastic Epithelial Changes

• Localized, circumscribed flat or papillary area
  with white, red or gray appearance
• Cytologic alterations
  hyperchromasia, increase of nuclear/cytoplasmic
  ratio, mitoses, crowding of cells with loss of
  cellular polarity
• Begins in basal or parabasal areas

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Dysplastic Epithelial Changes Grading

• Mild lower 1/3 of the thickness of
  epithelium
• Moderate lower 2/3 of the
  thickness of epithelium
• Severe from 2/3 to almost
  complete thickness

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Dysplastic Epithelial Changes

• Normal maturation of the superficial layers of
  the epithelium
• Intact basement membrane
• May be associated with keratosis or dyskeratosis,
  or other hyperplastic changes
• Full-thickness dysplasia (carcinoma in situ) is
  not a prerequisite prior to the development of an
  invasive CA
• Differential diagnosis reactive epithelial
  changes, infectious disease, SCC

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Flat Keratosis with Epithelial Hyperplasia and
Mild Dysplasia
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Keratosis with Moderate Dysplasia
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Severe Dysplasia without Keratosis
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Benign Neoplasms of the Larynx
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Laryngeal Papilloma

• Benign, exophytic neoplastic growth composed of
  branching fronds of squamous epithelium with
  fibrovascular cores
• The most common benign laryngeal neoplasm
• No sex predilection
• Changes in phonation, dyspnea, cough, dysphagia,
  stridor
• HPV types 6 and 11

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Laryngeal Papilloma

• Juvenile type multiple lesions with
  extensive growth and rapid recurrence, may remit
  spontaneously or persist into old age
• Adult type more often single, recurs
  less often, less likely to spread

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• Exophytic, warty, friable, tan-white to red
  growths

68

• Papillary fronds of multilayered benign squamous
  epithelium containing fibrovascular cores
• Little or no keratin production

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Laryngeal Papilloma

• Absence of stromal invasion
• Certain degree of cellular atypia
• Koilocytic changes

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Laryngeal Granular Cell Tumor

• Men gt women
• Hoarseness
• Along the posterior aspect of true vocal cord (
  but also in supraglotic and infraglotic areas)

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Granular Cell Tumor

• Solitary, polypoid, sessile, papillary, or cystic
  lesion, measuring up to 3.0 cm in diameter

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Granular Cell Tumor

• Poorly circumscribed subepithelial lesion with
  syncytial, trabecular, or nested growth pattern
• Round to polygonal cells with round to vesicular
  nuclei and coarsely granular cytoplasm. Poorly
  defined cell borders.
• Variable degree of cellular pleomorphism
• Absence of mitoses or necroses

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S-100 Protein Immunostain
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Pseudoepitheliomatous hyperplasia
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Granular Cell Tumor

• Cytoplasmic granules PAS/d , Alcian
  blue pH 2.5 , trichrome (red)
• Angulate bodies needle shaped,
  PAS bodies in the interstitial cells
• Tumor cells S-100, NSE
• Interstitial cells with angulate bodies
  S-100 - and myelin protein
• EM membrane bound
  autophagic vacuoles containing mitochondria, RER,
  myelin, axon-like structures

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Malignant Granular Cell Tumor

• Rare ( 1 of all GCT)
• Do not occur in newborns
• Size gt 4 cm
• Increased cellularity, pleomorphism, necrosis,
  prominent nucleoli, spindle shaped cells and gt 2
  mitoses/10 HPF
• Metastasize via lymphatics and blood vessels

77
Chordoma

• Uncommon
• Males gt females
• Dyspnea, strydor, and hoarseness
• May originates from epiglottis, cricoid,
  arytenoid, or thyroid cartilages
• May arise in Reinkes space
• Lobulated, firm to hard, blue-gray, submucosal
  mass, usually lt 1 cm

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Chordoma

• Lobulated, normally looking chondrocytes
• Absence of pleomorphism, binucleated
  chondrocytes, or mitotic activity

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Rhabdomyoma

• Benign tumor of striated muscle
• Adult type
• less common
• Males gt females gt 40 y/o
• Hoarseness, dyspnea
• Well-defined, lobulated, red-brown mass, up to 5
  cm in diameter

80
Rhabdomyoma Adult Type

• Large polygonal to round cells with abundant
  deeply eosinophylic cyroplasm and one or two
  periphery placed vesicular nuclei
• Nucleoli, cytoplasmic vacuolization
• Cross-striation
• Absent mitoses
• Abundant cytoplasmic glycogen (diastase sensitive
  PAS positive)
• Desmin , Myoglobin

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Rhabdomyoma Fetal Type

• Very rare
• Male children lt 3 y/o
• Posterior auricular subcutaneous tissue gt
  nasopharynx, parotis, neck
• Solitary, well to moderately circumscribed
  nodule, 1-8 cm in size, gray to pink mucoid
  appearance

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Rhabdomyoma Fetal Type

• Spindle cells and immature muscle fibers with in
  a myxoid stroma
• Cross-striation rarely discernible. Mature muscle
  fibers can be seen in the periphery
• Absence of mitoses, necrosis, and significant
  pleomorphism

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Malignant Laryngeal Neoplasms
84
In Situ Squamous Cell Carcinoma

• Males gt females
• 6th 7th decades
• Most often involves anterior portion of true
  vocal cord
• Hoarseness
• May coexist with invasive SCC
• May be isolated or multifocal
• Circumscribed or diffuse lesion with a white,
  red, or gray color and smooth or granular
  appearance

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In Situ Squamous Cell Carcinoma

• Dysplastic process involves the entire thickness
  of the epithelium
• Loss of cellular maturation and polarity
• Increase of nuclear/cytoplaslic ratio
• Normal and abnormal mitoses
• Keratosis and dyskeratosis
• Extension into adjacent seromucinous glands

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Microinvasive or Superficially Invasive Squamous
Cell Carcinoma

• Nests of malignant cells that have penetrated the
  basement membrane and invaded superficially into
  the submucosa
• Capable of metastasizing
• Development from carcinoma in situ or from
  epithelium with no evidence of CIS

87
Invasive Squamous Cell Carcinoma

• 2.5 of all cancers in men
• 0.5 of all cancers in women
• 95 of all laryngeal carcinomas
• Etiology ETOH (supraglottic), tobacco (glottic),
  asbestos, nickel, wood, isopropyl alcohol,
  radiation
• DD reactive epithelial changes,
  pseudoepitheliomatous hyperplasia

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Invasive Squamous Cell Carcinoma
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Supraglottic Squamous Cell Carcinoma

• 2540 of laryngeal SCC
• Epiglottis (base), false vocal cords
• Changes in the quality of voice, dysphagia,
  odonophagia, hoarseness, hemoptisis, dyspnea
• Marginal carcinomas (suprahyoid epiglottis,
  aryepiglottic folds) remain quiescent for longer
  period and present at more advanced stage

90
Supraglottic Squamous Cell Carcinoma

• Ulcerated, flat, exophytic, or papillary
• Tend to be nonkeratinizing
• In situ component
• Mitoses and necrosis

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Supraglottic Squamous Cell Carcinoma

• Large, tan-white neoplasm in the right
  supraglottis, extending upward toward epiglottis

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Supraglottic Squamous Cell Carcinoma
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Glottic SCC

• Early irregular area of mucosal thickening
• Advanced exophytic, fungatic, endophytic,
  ulcerated mass
• More commonly keratinizing, well to moderately
  differentiated
• In situ component
• Invasive component predominantly infiltrative

94
Glottic SCC
95
Glottic SCC
96
Glottic SCC
97
Subglottic Squamous Cell Carcinoma

• 5 of all laryngeal tumors
• Tend to remain clinically quiescent, presenting
  with advanced stage
• Airway obstruction (dyspnea, stridor) and vocal
  cord fixation (voice changes)
• Large exophytic, fungating, ulcerating, or
  endophytic
• Tend to be keratinizing moderately to poorly
  differentiated
• In situ component is less common
• Invasive pattern is predominantly infiltrative

98
Subglottic SCC
99
Subglottic Squamous Cell Carcinoma

• Overall 5-year survival rate lt 40
• Spread
• Into thyroarytenoid muscle (vocal cord fixation)
• Anteriorly through cricothyroid membrane into
  thyroid gland superiorly glottis and
  supraglottis
• inferiorly trachea posteriorly below the
  cricoid cartilage and into the esophagus
• Lymphatic drainage upper and lower jugular
  chains, perlaryngeal and paratracheal nodes
• Stomal recurrent tumor

100
Transglottic SCC

• Involves both glottic and supraglottic structures
• Represents advanced tumor
• Nodal metastases and extranodal spread
• Overall 5-year survival rate lt 40

101
Transglottic SCC
102
Spindle Cell (Squamous) Carcinoma (SCSC)

• Foci of conventional SCC associated with
  malignant spindle cell stromal component
• Synonyms carcinosarcoma, pleomorphic carcinoma,
  metaplastic carcinoma, collision tumor,
  pseudosarcoma, Lane tumor
• Men (85), 6th 8th decades
• True vocal cords gt false vocal cords and
  supraglottis gt oral cavity gt skin gt tonsil and
  pharynx
• Symptoms vary according to site
• No specific etiology

103
Spindle Cell (Squamous) Carcinoma (SCSC)
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Spindle Cell (Squamous) Carcinoma (SCSC)

• Spindle cell component with variable degree of
  pleomorphism, mitoses
• Fascicular, storiform, or palisading patterns
  may be associated with myxomatous stroma

105
Spindle Cell (Squamous) Carcinoma (SCSC)

• Spindle cells are cytokeratin-positive, but
  negativity does not exclude the diagnosis

106
Heterologous Elements
107
Spindle Cell (Squamous) Carcinoma (SCSC)

• Differential diagnosis
• Reactive (fibroblastic) proliferation
• Malignant fibrous histiocytoma
• Fibrosarcoma
• Malignant melanoma

108
Spindle Cell (Squamous) Carcinoma (SCSC)

• Controversial histogenesis. Epithelial derivation
  is support by
• Association with conventional SCC
• ICH cytokeratin
• Cartilage or bone component have not been
  reported in metastases
• Metastases may include conventional or/and
  spindle cell component
• Poor prognosis (metastases in lymph nodes and
  lungs)

109
Verrucous Carcinoma

• Highly differentiated variant of SCC with focally
  destructive, but not metastatic capabilities
• 1-3 of all laryngeal carcinomas
• Men gt women, 6th 7th decades
• Oral cavity gt nasal fossa gt sinonasal tract,
  nasopharynx
• Larynx hoarseness
• In the larynx most common in the glottic area
• Potential etiologic factors tobacco, viruses

110
Verrucous Carcinoma

• Tan or white, warty, fungating, or exophytic,
  firm to hard mass, attached by a broad base
• Squamous cell proliferation
• uniform cells without dysplastic features and
  mitoses
• marked surface keratinization
• broad or bulbous rete pegs with pushing, NOT
  infiltrative margin
• Dysplastic features limited and confined to basal
  sone
• Mixed chronic immflammarory cell infiltrate

111
Verrucous Carcinoma

• Tan or white, warty, fungating, or exophytic,
  firm to hard mass, attached by a broad base

112
Verrucous Carcinoma
113
Verrucous Carcinoma

• Squamous cell proliferation
• uniform cells without dysplastic features and
  mitoses
• marked surface keratinization
• broad or bulbous rete pegs with pushing, NOT
  infiltrative margin
• Dysplastic features limited and confined to basal
  zone
• Mixed chronic inflammatory cell infiltrate

114
Verrucous Carcinoma

• Differential diagnosis
• Keratotic squamous papilloma
• Reactive keratosis and epithelial hyperplasia
• Pseudoepitheliomatous hyperplasia
• Verruca vulgaris
• Keratoacantoma
• Conventional SCC

115
Verrucous Carcinoma

• Metastasis in regional lymph nodes are rare, and
  distant metastases do not occur
• Excellent prognosis after complete surgical
  removal
• Anaplastic transformation may result in distant
  metastases
• Adequate biopsy material with a good
  epithelial-stromal interface is critical for the
  interpretation
• Cervical adenopathy- reactive changes

116
Basaloid Squamous Cell Carcinoma

• An invasive neoplasm, composed of basaloid cells
• Uncommon
• Men gt women, 6th 7th decades
• Hypopharynx (pyriform sinus), larynx
  (supraglottis), and tongue
• Hoarseness, dysphagia, pain, neck mass
• Etiology ETOH, tabacco
• Cell of origin unclear

117
Basaloid Squamous Cell Carcinoma

• Firm to hard, tan-white mass, often with
  associated central necrosis
• Patterns solid, lobular, cell nests, cribriform,
  cords, trabeculae, gland-like, or cystic
• Comedonecrosis
• Intercellular deposition of a hyaline or
  mucohyalin material
• Focal squamous differentiation or association
  with SCC, SCCIS, squamous dysplasia, or spindle
  cell component

118
Basaloid Squamous Cell Carcinoma

• Infiltrating tumor originating from the surface
  epithelium with solid growth pattern and
  comedonecrosis

119
Basaloid Squamous Cell Carcinoma

• Small, closely apposed cells with hyperchromatic
  nuclei, scanty cytoplasm, marked mitotic
  activity, large cells or pleomorphism can be seen

120
Basaloid SCC with Focal Keratinization
121
Basaloid Squamous Cell Carcinoma

• Histochemistry PAS and Alcian
  blue material in the cystic spaces
• IHC cytokeratin (), EMA (), CEA (),
  S-100 () chromogranin (-), synaptophysin (-),
  muscle-specific actin (-)
• EM
• basaloid component desmosomes, rare
  tonofilaments
• cystic spaces stellate granules or replicated
  basal lamina

122
Basaloid SCC Differential Diagnosis

• Adenoid cystic carcinoma
• Neuroendocrine carcinoma
• Adenosquamous carcinoma
• Spindle cell carcinoma

123
Basaloid Squamous Cell Carcinoma

• Multifocal, deeply invasive, metastatic
• Metastases lymph nodes, lung, bone, skin, brain
• Metastases include both basaloid and squamous
  components
• Rapidly fatal

124
Adenosquamous Carcinoma

• Malignant high grade epithelial neoplasm with
  histologic features of adenocarcinoma and SCC
• Uncommon
• Men gt women, 6th 7th decades
• Larynx, hypopharynx, oral cavity, sinonasal
  cavity
• Hoarseness, dysphagia, pain, neck mass, nasal
  obstruction
• Etiology not clear (ETOH, tobacco)
• Cell of origin unclear possible a single
  totipotential cell from surface epithelium or
  seromucous glands

125
Adenosquamous Carcinoma

• Exophytic or submucosal, friable, edematous or
  granular mass with or without surface ulcerations
• SCC component
• Well to poorly differentiated, associated in situ
  carcinoma or invasive SCC
• Individual cell keratinization, intercellular
  bridges, keratin pearl formation, dyskeratosis
• Adenocarcinoma component
• In the submucosa, glandular differentiation,
• Both components can be admixed
• Cellular pleomorphism, mitoses, necrosis,
  perineural invasion

126
Adenosquamous Carcinoma
127
Adenosquamous Carcinoma

• Histochemistry PAS/d () and mucicarnine ()
  intraluminal material
• IHC cytokeratin ()
• Behaves very aggressively, irrespective of the
  size of neoplasm
• Early lymph node metastases, lung, liver
• Poor prognosis 5-year survival rate of

128
Neuroendocrine Carcinoma Classification

• Carcinoid (well differentiated)
• Atypical carcinoid (moderately differentiated)
• Small (oat) cell carcinoma (poorly
  differentiated)

129
Neuroendocrine Carcinoma

• Submucosal nodular or polypoid mass with
  tan-white appearance and up to 4 cm in diameter
• Surface ulceration may present in moderately or
  well-differentiated neuroendocrine carcinoma

130
Carcinoid

• Organoid or trabecular growth pattern with
  fibtovascular stroma
• Glands or squamous differentiation can be seen
• Absence of surface ulceration

131
Carcinoid

• Uniform cells with centrally located round
  nuclei, vesicular chromatin, and eosinophilic
  cytoplasm
• Absence of pleomorphism, mitoses, necroses
• Low nuclearcytoplasmic ratio

132
Carcinoid

• Histochemistry PAS/d mucin, argyrophilia
• IHC Cytokeratin ,
  Chromogranin , NSE , synaptophysin
• EM neurosecretory granules,
  cellular junctional complexes

133
Atypical Carcinoid

• Organoid, trabecular, cribriform, or solid gowth
  pattern
• Mild to marked cellular pleomorphism
• Nucleoli may be prominent
• Mitoses and focal necrosis
• Variable nuclearcytoplasmic ratio
• Surface ulceration and lymphovascular and
  perineural invasion

134
Small Cell Carcinoma

• Solid nests, sheets, or ribbons, with absence of
  fibrovascular stroma
• Surface ulceration
• Lymphovascular and perineural invasion
• Glandular or squamous differentiation is rarely
  seen

135
Small Cell Carcinoma

• Marked cellular pleomorphism, crush artifacts,
  necrosis, hyperchromatic oval to spindle nuclei,
  abundant mitoses
• High nuclearcytoplasmic ratio
• IHC cytokeratin, chromogranin, synaptophysin,
  NSE positive
• EM rare neurosecretory granules

136
Chondrosarcoma

• Rare
• Males gtFemales, 4th - 7th decades
• Cricoid gt thyroid cartilage gt arytenoid
• Smooth, lobulated, hard submucosal mass larger
  than 2 cm

137
Chondrosarcoma (high grade)

• Lobulated hypercellular tumor with
  hyperchromatic, pleomorphic nuclei and prominent
  nucleoli
• Binucleate or multinucleated cells
• Mitoses usually uncommon

138
Synovial Sarcoma
139
Synovial Sarcoma
140
Synovial Sarcoma